Journal: Lancet

Sorted by: date / impact
Abstract

Global estimates of the need for rehabilitation based on the Global Burden of Disease study 2019: a systematic analysis for the Global Burden of Disease Study 2019.

Cieza A, Causey K, Kamenov K, Hanson SW, Chatterji S, Vos T
Background
Rehabilitation has often been seen as a disability-specific service needed by only few of the population. Despite its individual and societal benefits, rehabilitation has not been prioritised in countries and is under-resourced. We present global, regional, and country data for the number of people who would benefit from rehabilitation at least once during the course of their disabling illness or injury.
Methods
To estimate the need for rehabilitation, data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were used to calculate the prevalence and years of life lived with disability (YLDs) of 25 diseases, impairments, or bespoke aggregations of sequelae that were selected as amenable to rehabilitation. All analyses were done at the country level and then aggregated to seven regions: World Bank high-income countries and the six WHO regions (ie, Africa, the Americas, Southeast Asia, Europe, Eastern Mediterranean, and Western Pacific).
Findings
Globally, in 2019, 2·41 billion (95% uncertainty interval 2·34-2·50) individuals had conditions that would benefit from rehabilitation, contributing to 310 million [235-392] YLDs. This number had increased by 63% from 1990 to 2019. Regionally, the Western Pacific had the highest need of rehabilitation services (610 million people [588-636] and 83 million YLDs [62-106]). The disease area that contributed most to prevalence was musculoskeletal disorders (1·71 billion people [1·68-1·80]), with low back pain being the most prevalent condition in 134 of the 204 countries analysed.
Interpretation
To our knowledge, this is the first study to produce a global estimate of the need for rehabilitation services and to show that at least one in every three people in the world needs rehabilitation at some point in the course of their illness or injury. This number counters the common view of rehabilitation as a service required by only few people. We argue that rehabilitation needs to be brought close to communities as an integral part of primary health care to reach more people in need.
Funding
Bill & Melinda Gates Foundation.

Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article\'s original URL.

Lancet: 18 Dec 2021; 396:2006-2017
Cieza A, Causey K, Kamenov K, Hanson SW, Chatterji S, Vos T
Lancet: 18 Dec 2021; 396:2006-2017 | PMID: 33275908
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Abstract

Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study.

Overton ET, Richmond G, Rizzardini G, Jaeger H, ... Vanveggel S, Spreen W
Background
Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing.
Methods
ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA ≥50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing.
Findings
Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34-50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI -0·6-2·2). There were eight (2%, every 8 weeks group) and two (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred.
Interpretation
The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1.
Funding
ViiV Healthcare and Janssen.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Lancet: 18 Dec 2021; 396:1994-2005
Overton ET, Richmond G, Rizzardini G, Jaeger H, ... Vanveggel S, Spreen W
Lancet: 18 Dec 2021; 396:1994-2005 | PMID: 33308425
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Abstract

Community-acquired bacterial meningitis.

van de Beek D, Brouwer MC, Koedel U, Wall EC
Progress has been made in the prevention and treatment of community-acquired bacterial meningitis during the past three decades but the burden of the disease remains high globally. Conjugate vaccines against the three most common causative pathogens (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae) have reduced the incidence of disease, but with the replacement by non-vaccine pneumococcal serotypes and the emergence of bacterial strains with reduced susceptibility to antimicrobial treatment, meningitis continues to pose a major health challenge worldwide. In patients presenting with bacterial meningitis, typical clinical characteristics (such as the classic triad of neck stiffness, fever, and an altered mental status) might be absent and cerebrospinal fluid examination for biochemistry, microscopy, culture, and PCR to identify bacterial DNA are essential for the diagnosis. Multiplex PCR point-of-care panels in cerebrospinal fluid show promise in accelerating the diagnosis, but diagnostic accuracy studies to justify routine implementation are scarce and randomised, controlled studies are absent. Early administration of antimicrobial treatment (within 1 hour of presentation) improves outcomes and needs to be adjusted according to local emergence of drug resistance. Adjunctive dexamethasone treatment has proven efficacy beyond the neonatal age but only in patients from high-income countries. Further progress can be expected from implementing preventive measures, especially the development of new vaccines, implementation of hospital protocols aimed at early treatment, and new treatments targeting checkpoints of the inflammatory cascade.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 21 Jul 2021; epub ahead of print
van de Beek D, Brouwer MC, Koedel U, Wall EC
Lancet: 21 Jul 2021; epub ahead of print | PMID: 34303412
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Abstract

Physical activity behaviours in adolescence: current evidence and opportunities for intervention.

van Sluijs EMF, Ekelund U, Crochemore-Silva I, Guthold R, ... Ding D, Katzmarzyk PT
Young people aged 10-24 years constitute 24% of the world\'s population; investing in their health could yield a triple benefit-eg, today, into adulthood, and for the next generation. However, in physical activity research, this life stage is poorly understood, with the evidence dominated by research in younger adolescents (aged 10-14 years), school settings, and high-income countries. Globally, 80% of adolescents are insufficiently active, and many adolescents engage in 2 h or more daily recreational screen time. In this Series paper, we present the most up-to-date global evidence on adolescent physical activity and discuss directions for identifying potential solutions to enhance physical activity in the adolescent population. Adolescent physical inactivity probably contributes to key global health problems, including cardiometabolic and mental health disorders, but the evidence is methodologically weak. Evidence-based solutions focus on three key components of the adolescent physical activity system: supportive schools, the social and digital environment, and multipurpose urban environments. Despite an increasing volume of research focused on adolescents, there are still important knowledge gaps, and efforts to improve adolescent physical activity surveillance, research, intervention implementation, and policy development are urgently needed.

Copyright © 2021 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.

Lancet: 20 Jul 2021; epub ahead of print
van Sluijs EMF, Ekelund U, Crochemore-Silva I, Guthold R, ... Ding D, Katzmarzyk PT
Lancet: 20 Jul 2021; epub ahead of print | PMID: 34302767
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Abstract

An evidence-based assessment of the impact of the Olympic Games on population levels of physical activity.

Bauman AE, Kamada M, Reis RS, Troiano RP, ... Murphy N, Hallal PC
Pre-Olympic Games predictions commonly include an increase in population-based physical activity in the host city, as often stated in the bid, but the post-Olympic Games effects on physical activity have not been summarised. In this Series paper, we aim to do the following: examine mentions of a physical activity legacy in pre-Olympic bid documentation; analyse existing physical activity surveillance data collected before, during, and after the Olympic Games in hosting areas around the world; and evaluate Google Trends data surrounding the London 2012 Olympic Games as a case study of community interest in the topic of exercise during the time of the Olympic Games. Before 2007, little mention of physical activity was made in pre-Olympic Games documentation, but, after that, most documents had targets for population physical activity or sports participation. The synthesis of available surveillance data indicates that there was no change in the prevalence of physical activity or sports participation, except for the 2008 Summer Olympics in Beijing and the 1998 Winter Olympics in Nagano; although, the increase in participation in Nagano might not be attributable to the Olympic Games since there was no change in participation in winter sports. The Google Trends data showed an acute spike in searches with the term \"Olympic\" immediately associated with the London Olympic Games period and showed a sustained peri-Olympic increase in searches with the term \"exercise\". By themselves, the Olympic Games have not improved population-wide physical activity but might be an important missed public health opportunity. Such a legacy will require strategic planning and partnerships across the International Olympic Committee and the Olympic, sport, and public health agencies and a thorough evaluation framework implemented throughout the pre-Olympic Games and post-Olympic Games period in the host country.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 20 Jul 2021; epub ahead of print
Bauman AE, Kamada M, Reis RS, Troiano RP, ... Murphy N, Hallal PC
Lancet: 20 Jul 2021; epub ahead of print | PMID: 34302766
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Abstract

Participation of people living with disabilities in physical activity: a global perspective.

Martin Ginis KA, van der Ploeg HP, Foster C, Lai B, ... Vásquez PM, Heath GW
Approximately 1·5 billion people worldwide live with a physical, mental, sensory, or intellectual disability, about 80% of which are in low-income and middle-income countries. This Series paper provides a global overview of the prevalence, benefits, and promotion policies for physical activity for people living with disabilities (PLWD). PLWD are 16-62% less likely to meet physical activity guidelines and are at higher risk of serious health problems related to inactivity than people without disabilities. Meta-analyses have shown that physical activity has beneficial effects on cardiovascular fitness (average standardised mean difference [SMD] 0·69 [95% CI 0·31-1·01]), musculoskeletal fitness (0·59 [0·31-0·87]), cardiometabolic risk factors (0·39 [0·04-0·75]), and brain and mental health outcomes (0·47 [0·21-0·73]). These meta-analyses also show that health benefits can be achieved even with less than 150 min of physical activity per week, and suggest that some physical activity is better than none. Meta-analyses of interventions to increase physical activity for PLWD have reported effect sizes ranging from SMD 0·29 (95% CI 0·17-0·41, k=10) to 1·00 (0·46-1·53, k=10). There is increasing awareness among policy makers of the needs of PLWD for full participation in physical activity. Physical activity action plans worldwide must be adequately resourced, monitored, and enforced to truly advance the fundamental rights of PLWD to fully participate in physical activity.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 20 Jul 2021; epub ahead of print
Martin Ginis KA, van der Ploeg HP, Foster C, Lai B, ... Vásquez PM, Heath GW
Lancet: 20 Jul 2021; epub ahead of print | PMID: 34302764
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Abstract

Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study.

Hillis SD, Unwin HJT, Chen Y, Cluver L, ... Nelson CA, Flaxman S
Background
The COVID-19 pandemic priorities have focused on prevention, detection, and response. Beyond morbidity and mortality, pandemics carry secondary impacts, such as children orphaned or bereft of their caregivers. Such children often face adverse consequences, including poverty, abuse, and institutionalisation. We provide estimates for the magnitude of this problem resulting from COVID-19 and describe the need for resource allocation.
Methods
We used mortality and fertility data to model minimum estimates and rates of COVID-19-associated deaths of primary or secondary caregivers for children younger than 18 years in 21 countries. We considered parents and custodial grandparents as primary caregivers, and co-residing grandparents or older kin (aged 60-84 years) as secondary caregivers. To avoid overcounting, we adjusted for possible clustering of deaths using an estimated secondary attack rate and age-specific infection-fatality ratios for SARS-CoV-2. We used these estimates to model global extrapolations for the number of children who have experienced COVID-19-associated deaths of primary and secondary caregivers.
Findings
Globally, from March 1, 2020, to April 30, 2021, we estimate 1 134 000 children (95% credible interval 884 000-1 185 000) experienced the death of primary caregivers, including at least one parent or custodial grandparent. 1 562 000 children (1 299 000-1 683 000) experienced the death of at least one primary or secondary caregiver. Countries in our study set with primary caregiver death rates of at least one per 1000 children included Peru (10·2 per 1000 children), South Africa (5·1), Mexico (3·5), Brazil (2·4), Colombia (2·3), Iran (1·7), the USA (1·5), Argentina (1·1), and Russia (1·0). Numbers of children orphaned exceeded numbers of deaths among those aged 15-50 years. Between two and five times more children had deceased fathers than deceased mothers.
Interpretation
Orphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families to nurture children bereft of caregivers and help to ensure that institutionalisation is avoided. These data show the need for an additional pillar of our response: prevent, detect, respond, and care for children.
Funding
UK Research and Innovation (Global Challenges Research Fund, Engineering and Physical Sciences Research Council, Medical Research Council), UK National Institute for Health Research, US National Institutes of Health, and Imperial College London.

© 2021 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted.

Lancet: 19 Jul 2021; epub ahead of print
Hillis SD, Unwin HJT, Chen Y, Cluver L, ... Nelson CA, Flaxman S
Lancet: 19 Jul 2021; epub ahead of print | PMID: 34298000
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Abstract

Central venous access devices for the delivery of systemic anticancer therapy (CAVA): a randomised controlled trial.

Moss JG, Wu O, Bodenham AR, Agarwal R, ... McCartney E, CAVA trial group
Background
Hickman-type tunnelled catheters (Hickman), peripherally inserted central catheters (PICCs), and totally implanted ports (PORTs) are used to deliver systemic anticancer treatment (SACT) via a central vein. We aimed to compare complication rates and costs of the three devices to establish acceptability, clinical effectiveness, and cost-effectiveness of the devices for patients receiving SACT.
Methods
We did an open-label, multicentre, randomised controlled trial (Cancer and Venous Access [CAVA]) of three central venous access devices: PICCs versus Hickman (non-inferiority; 10% margin); PORTs versus Hickman (superiority; 15% margin); and PORTs versus PICCs (superiority; 15% margin). Adults (aged ≥18 years) receiving SACT (≥12 weeks) for solid or haematological malignancy from 18 oncology units in the UK were included. Four randomisation options were available: Hickman versus PICCs versus PORTs (2:2:1), PICCs versus Hickman (1:1), PORTs versus Hickman (1:1), and PORTs versus PICCs (1:1). Randomisation was done using a minimisation algorithm stratifying by centre, body-mass index, type of cancer, device history, and treatment mode. The primary outcome was complication rate (composite of infection, venous thrombosis, pulmonary embolus, inability to aspirate blood, mechanical failure, and other) assessed until device removal, withdrawal from study, or 1-year follow-up. This study is registered with ISRCTN, ISRCTN44504648.
Findings
Between Nov 8, 2013, and Feb 28, 2018, of 2714 individuals screened for eligibility, 1061 were enrolled and randomly assigned, contributing to the relevant comparison or comparisons (PICC vs Hickman n=424, 212 [50%] on PICC and 212 [50%] on Hickman; PORT vs Hickman n=556, 253 [46%] on PORT and 303 [54%] on Hickman; and PORT vs PICC n=346, 147 [42%] on PORT and 199 [58%] on PICC). Similar complication rates were observed for PICCs (110 [52%] of 212) and Hickman (103 [49%] of 212). Although the observed difference was less than 10%, non-inferiority of PICCs was not confirmed (odds ratio [OR] 1·15 [95% CI 0·78-1·71]) potentially due to inadequate power. PORTs were superior to Hickman with a complication rate of 29% (73 of 253) versus 43% (131 of 303; OR 0·54 [95% CI 0·37-0·77]). PORTs were superior to PICCs with a complication rate of 32% (47 of 147) versus 47% (93 of 199; OR 0·52 [0·33-0·83]).
Interpretation
For most patients receiving SACT, PORTs are more effective and safer than both Hickman and PICCs. Our findings suggest that most patients receiving SACT for solid tumours should receive a PORT within the UK National Health Service.
Funding
UK National Institute for Health Research Health Technology Assessment Programme.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 19 Jul 2021; epub ahead of print
Moss JG, Wu O, Bodenham AR, Agarwal R, ... McCartney E, CAVA trial group
Lancet: 19 Jul 2021; epub ahead of print | PMID: 34297997
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Abstract

Lung cancer.

Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS
Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide with an estimated 2 million new cases and 1·76 million deaths per year. Substantial improvements in our understanding of disease biology, application of predictive biomarkers, and refinements in treatment have led to remarkable progress in the past two decades and transformed outcomes for many patients. This seminar provides an overview of advances in the screening, diagnosis, and treatment of non-small-cell lung cancer and small-cell lung cancer, with a particular focus on targeted therapies and immune checkpoint inhibitors.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 13 Jul 2021; epub ahead of print
Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS
Lancet: 13 Jul 2021; epub ahead of print | PMID: 34273294
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Abstract

Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: a modelling study.

Causey K, Fullman N, Sorensen RJD, Galles NC, ... Lim SS, Mosser JF
Background
The COVID-19 pandemic and efforts to reduce SARS-CoV-2 transmission substantially affected health services worldwide. To better understand the impact of the pandemic on childhood routine immunisation, we estimated disruptions in vaccine coverage associated with the pandemic in 2020, globally and by Global Burden of Disease (GBD) super-region.
Methods
For this analysis we used a two-step hierarchical random spline modelling approach to estimate global and regional disruptions to routine immunisation using administrative data and reports from electronic immunisation systems, with mobility data as a model input. Paired with estimates of vaccine coverage expected in the absence of COVID-19, which were derived from vaccine coverage models from GBD 2020, Release 1 (GBD 2020 R1), we estimated the number of children who missed routinely delivered doses of the third-dose diphtheria-tetanus-pertussis (DTP3) vaccine and first-dose measles-containing vaccine (MCV1) in 2020.
Findings
Globally, in 2020, estimated vaccine coverage was 76·7% (95% uncertainty interval 74·3-78·6) for DTP3 and 78·9% (74·8-81·9) for MCV1, representing relative reductions of 7·7% (6·0-10·1) for DTP3 and 7·9% (5·2-11·7) for MCV1, compared to expected doses delivered in the absence of the COVID-19 pandemic. From January to December, 2020, we estimated that 30·0 million (27·6-33·1) children missed doses of DTP3 and 27·2 million (23·4-32·5) children missed MCV1 doses. Compared to expected gaps in coverage for eligible children in 2020, these estimates represented an additional 8·5 million (6·5-11·6) children not routinely vaccinated with DTP3 and an additional 8·9 million (5·7-13·7) children not routinely vaccinated with MCV1 attributable to the COVID-19 pandemic. Globally, monthly disruptions were highest in April, 2020, across all GBD super-regions, with 4·6 million (4·0-5·4) children missing doses of DTP3 and 4·4 million (3·7-5·2) children missing doses of MCV1. Every GBD super-region saw reductions in vaccine coverage in March and April, with the most severe annual impacts in north Africa and the Middle East, south Asia, and Latin America and the Caribbean. We estimated the lowest annual reductions in vaccine delivery in sub-Saharan Africa, where disruptions remained minimal throughout the year. For some super-regions, including southeast Asia, east Asia, and Oceania for both DTP3 and MCV1, the high-income super-region for DTP3, and south Asia for MCV1, estimates suggest that monthly doses were delivered at or above expected levels during the second half of 2020.
Interpretation
Routine immunisation services faced stark challenges in 2020, with the COVID-19 pandemic causing the most widespread and largest global disruption in recent history. Although the latest coverage trajectories point towards recovery in some regions, a combination of lagging catch-up immunisation services, continued SARS-CoV-2 transmission, and persistent gaps in vaccine coverage before the pandemic still left millions of children under-vaccinated or unvaccinated against preventable diseases at the end of 2020, and these gaps are likely to extend throughout 2021. Strengthening routine immunisation data systems and efforts to target resources and outreach will be essential to minimise the risk of vaccine-preventable disease outbreaks, reach children who missed routine vaccine doses during the pandemic, and accelerate progress towards higher and more equitable vaccination coverage over the next decade.
Funding
Bill & Melinda Gates Foundation.

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article\'s original URL.

Lancet: 13 Jul 2021; epub ahead of print
Causey K, Fullman N, Sorensen RJD, Galles NC, ... Lim SS, Mosser JF
Lancet: 13 Jul 2021; epub ahead of print | PMID: 34273292
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Abstract

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019: a systematic analysis for the Global Burden of Disease Study 2020, Release 1.

GBD 2020, Release 1, Vaccine Coverage Collaborators
Background
Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time.
Methods
For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dose-specific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in country-reported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development.
Findings
By 2019, global coverage of third-dose DTP (DTP3; 81·6% [95% uncertainty interval 80·4-82·7]) more than doubled from levels estimated in 1980 (39·9% [37·5-42·1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38·5% [35·4-41·3] in 1980 to 83·6% [82·3-84·8] in 2019). Third-dose polio vaccine (Pol3) coverage also increased, from 42·6% (41·4-44·1) in 1980 to 79·8% (78·4-81·1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56·8 million (52·6-60·9) to 14·5 million (13·4-15·9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019.
Interpretation
After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines.
Funding
Bill & Melinda Gates Foundation.

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Lancet: 13 Jul 2021; epub ahead of print
GBD 2020, Release 1, Vaccine Coverage Collaborators
Lancet: 13 Jul 2021; epub ahead of print | PMID: 34273291
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Abstract

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study.

Global PaedSurg Research Collaboration
Background
Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality.
Methods
We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung\'s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis.
Findings
We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung\'s disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36-39) and median bodyweight at presentation was 2·8 kg (2·3-3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88-4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59-2·79], p<0·0001), sepsis at presentation (1·20 [1·04-1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4-5 vs ASA 1-2, 1·82 [1·40-2·35], p<0·0001; ASA 3 vs ASA 1-2, 1·58, [1·30-1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02-1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41-2·71], p=0·0001; parenteral nutrition 1·35, [1·05-1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47-0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50-0·86], p=0·0024) or percutaneous central line (0·69 [0·48-1·00], p=0·049) were associated with lower mortality.
Interpretation
Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030.
Funding
Wellcome Trust.

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Lancet: 12 Jul 2021; epub ahead of print
Global PaedSurg Research Collaboration
Lancet: 12 Jul 2021; epub ahead of print | PMID: 34270932
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Impact:
Abstract

Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of patients with rotator cuff disorders (GRASP): a multicentre, pragmatic, 2 × 2 factorial, randomised controlled trial.

Hopewell S, Keene DJ, Marian IR, Dritsaki M, ... Lamb SE, GRASP Trial Group
Background
Corticosteroid injections and physiotherapy exercise programmes are commonly used to treat rotator cuff disorders but the treatments\' effectiveness is uncertain. We aimed to compare the clinical effectiveness and cost-effectiveness of a progressive exercise programme with a single session of best practice physiotherapy advice, with or without corticosteroid injection, in adults with a rotator cuff disorder.
Methods
In this pragmatic, multicentre, superiority, randomised controlled trial (2 × 2 factorial), we recruited patients from 20 UK National Health Service trusts. We included patients aged 18 years or older with a rotator cuff disorder (new episode within the past 6 months). Patients were excluded if they had a history of significant shoulder trauma (eg, dislocation, fracture, or full-thickness tear requiring surgery), neurological disease affecting the shoulder, other shoulder conditions (eg, inflammatory arthritis, frozen shoulder, or glenohumeral joint instability), received corticosteroid injection or physiotherapy for shoulder pain in the past 6 months, or were being considered for surgery. Patients were randomly assigned (centralised computer-generated system, 1:1:1:1) to progressive exercise (≤6 sessions), best practice advice (one session), corticosteroid injection then progressive exercise, or corticosteroid injection then best practice advice. The primary outcome was the Shoulder Pain and Disability Index (SPADI) score over 12 months, analysed on an intention-to-treat basis (statistical significance set at 1%). The trial was registered with the International Standard Randomised Controlled Trial Register, ISRCTN16539266, and EuDRACT, 2016-002991-28.
Findings
Between March 10, 2017, and May 2, 2019, we screened 2287 patients. 708 patients were randomly assigned to progressive exercise (n=174), best practice advice (n=174), corticosteroid injection then progressive exercise (n=182), or corticosteroid injection then best practice advice (n=178). Over 12 months, SPADI data were available for 166 (95%) patients in the progressive exercise group, 164 (94%) in the best practice advice group, 177 (97%) in the corticosteroid injection then progressive exercise group, and 175 (98%) in the corticosteroid injection then best practice advice group. We found no evidence of a difference in SPADI score between progressive exercise and best practice advice when analysed over 12 months (adjusted mean difference -0·66 [99% CI -4·52 to 3·20]). We also found no evidence of a difference between corticosteroid injection compared with no injection when analysed over 12 months (-1·11 [-4·47 to 2·26]). No serious adverse events were reported.
Interpretation
Progressive exercise was not superior to a best practice advice session with a physiotherapist in improving shoulder pain and function. Subacromial corticosteroid injection provided no long-term benefit in patients with rotator cuff disorders.
Funding
UK National Institute for Health Research Technology Assessment Programme.

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Lancet: 11 Jul 2021; epub ahead of print
Hopewell S, Keene DJ, Marian IR, Dritsaki M, ... Lamb SE, GRASP Trial Group
Lancet: 11 Jul 2021; epub ahead of print | PMID: 34265255
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Impact:
Abstract

Histiocytosis.

Emile JF, Cohen-Aubart F, Collin M, Fraitag S, ... Donadieu J, Haroche J
Histiocytoses constitute a heterogeneous group of rare disorders, characterised by infiltration of almost any organ by myeloid cells with diverse macrophage or dendritic cell phenotypes. Histiocytoses can start at any age. Diagnosis is based on histology in combination with appropriate clinical and radiological findings. The low incidence and broad spectrum of clinical manifestations often leads to diagnostic delay, especially for adults. In most cases, biopsy specimens infiltrated by histiocytes have somatic mutations in genes activating the MAP kinase cell-signalling pathway. These mutations might also be present in blood cells and haematopoietic progenitors of patients with multisystem disease. A comprehensive range of investigations and molecular typing are essential to accurately predict prognosis, which can vary from spontaneous resolution to life-threatening disseminated disease. Targeted therapies with BRAF or MEK inhibitors have revolutionised salvage treatment. However, the type and duration of treatment are still debated, and the prevention of neurological sequelae remains a crucial issue.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 09 Jul 2021; 398:157-170
Emile JF, Cohen-Aubart F, Collin M, Fraitag S, ... Donadieu J, Haroche J
Lancet: 09 Jul 2021; 398:157-170 | PMID: 33901419
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Impact:
Abstract

Contemporary radiotherapy: present and future.

Chandra RA, Keane FK, Voncken FEM, Thomas CR
Oncology care is increasingly a multidisciplinary endeavour, and radiation therapy continues to have a key role across the disease spectrum in nearly every cancer. However, the field of radiation oncology is still one of the most poorly understood of the cancer disciplines. In this Review, we attempt to summarise and contextualise developments within the field of radiation oncology for the non-radiation oncologist. We discuss advancements in treatment technologies and imaging, followed by an overview of the interplay with advancements in systemic therapy and surgical techniques. Finally, we review new frontiers in radiation oncology, including advances within the metastatic disease continuum, reirradiation, and emerging types of radiation therapy.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 09 Jul 2021; 398:171-184
Chandra RA, Keane FK, Voncken FEM, Thomas CR
Lancet: 09 Jul 2021; 398:171-184 | PMID: 34166607
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Impact:
Abstract

Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial.

Rosenstock J, Wysham C, Frías JP, Kaneko S, ... Karanikas CA, Thieu VT
Background
Despite advancements in care, many people with type 2 diabetes do not meet treatment goals; thus, development of new therapies is needed. We aimed to assess efficacy, safety, and tolerability of novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide monotherapy versus placebo in people with type 2 diabetes inadequately controlled by diet and exercise alone.
Methods
We did a 40-week, double-blind, randomised, placebo-controlled, phase 3 trial (SURPASS-1), at 52 medical research centres and hospitals in India, Japan, Mexico, and the USA. Adult participants (≥18 years) were included if they had type 2 diabetes inadequately controlled by diet and exercise alone and if they were naive to injectable diabetes therapy. Participants were randomly assigned (1:1:1:1) via computer-generated random sequence to once a week tirzepatide (5, 10, or 15 mg), or placebo. All participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) from baseline at 40 weeks. This study is registered with ClinicalTrials.gov, NCT03954834.
Findings
From June 3, 2019, to Oct 28, 2020, of 705 individuals assessed for eligibility, 478 (mean baseline HbA1c 7·9% [63 mmol/mol], age 54·1 years [SD 11·9], 231 [48%] women, diabetes duration 4·7 years, and body-mass index 31·9 kg/m2) were randomly assigned to tirzepatide 5 mg (n=121 [25%]), tirzepatide 10 mg (n=121 [25%]), tirzepatide 15 mg (n=121 [25%]), or placebo (n=115 [24%]). 66 (14%) participants discontinued the study drug and 50 (10%) discontinued the study prematurely. At 40 weeks, all tirzepatide doses were superior to placebo for changes from baseline in HbA1c, fasting serum glucose, bodyweight, and HbA1c targets of less than 7·0% (<53 mmol/mol) and less than 5·7% (<39 mmol/mol). Mean HbA1c decreased from baseline by 1·87% (20 mmol/mol) with tirzepatide 5 mg, 1·89% (21 mmol/mol) with tirzepatide 10 mg, and 2·07% (23 mmol/mol) with tirzepatide 15 mg versus +0·04% with placebo (+0·4 mmol/mol), resulting in estimated treatment differences versus placebo of -1·91% (-21 mmol/mol) with tirzepatide 5 mg, -1·93% (-21 mmol/mol) with tirzepatide 10 mg, and -2·11% (-23 mmol/mol) with tirzepatide 15 mg (all p<0·0001). More participants on tirzepatide than on placebo met HbA1c targets of less than 7·0% (<53 mmol/mol; 87-92% vs 20%) and 6·5% or less (≤48 mmol/mol; 81-86% vs 10%) and 31-52% of patients on tirzepatide versus 1% on placebo reached an HbA1c of less than 5·7% (<39 mmol/mol). Tirzepatide induced a dose-dependent bodyweight loss ranging from 7·0 to 9·5 kg. The most frequent adverse events with tirzepatide were mild to moderate and transient gastrointestinal events, including nausea (12-18% vs 6%), diarrhoea (12-14% vs 8%), and vomiting (2-6% vs 2%). No clinically significant (<54 mg/dL [<3 mmol/L]) or severe hypoglycaemia were reported with tirzepatide. One death occurred in the placebo group.
Interpretation
Tirzepatide showed robust improvements in glycaemic control and bodyweight, without increased risk of hypoglycaemia. The safety profile was consistent with GLP-1 receptor agonists, indicating a potential monotherapy use of tirzepatide for type 2 diabetes treatment.
Funding
Eli Lilly and Company.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 09 Jul 2021; 398:143-155
Rosenstock J, Wysham C, Frías JP, Kaneko S, ... Karanikas CA, Thieu VT
Lancet: 09 Jul 2021; 398:143-155 | PMID: 34186022
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Impact:
Abstract

Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial.

Sweeney C, Bracarda S, Sternberg CN, Chi KN, ... Garcia J, de Bono JS
Background
The PI3K/AKT and androgen-receptor pathways are dysregulated in metastatic castration-resistant prostate cancers (mCRPCs); tumours with functional PTEN-loss status have hyperactivated AKT signalling. Dual pathway inhibition with AKT inhibitor ipatasertib plus abiraterone might have greater benefit than abiraterone alone. We aimed to compare ipatasertib plus abiraterone with placebo plus abiraterone in patients with previously untreated mCRPC with or without tumour PTEN loss.
Methods
We did a randomised, double-blind, phase 3 trial at 200 sites across 26 countries or regions. Patients aged 18 years or older with previously untreated asymptomatic or mildly symptomatic mCRPC who had progressive disease and Eastern Collaborative Oncology Group performance status of 0 or 1 were randomly assigned (1:1; permuted block method) to receive ipatasertib (400 mg once daily orally) plus abiraterone (1000 mg once daily orally) and prednisolone (5 mg twice a day orally) or placebo plus abiraterone and prednisolone (with the same dosing schedule). Patients received study treatment until disease progression, intolerable toxicity, withdrawal from the study, or study completion. Stratification factors were previous taxane-based therapy for hormone-sensitive prostate cancer, type of progression, presence of visceral metastasis, and tumour PTEN-loss status by immunohistochemistry. Patients, investigators, and the study sponsor were masked to the treatment allocation. The coprimary endpoints were investigator-assessed radiographical progression-free survival in the PTEN-loss-by-immunohistochemistry population and in the intention-to-treat population. This study is ongoing and is registered with ClinicalTrials.gov, NCT03072238.
Findings
Between June 30, 2017, and Jan 17, 2019, 1611 patients were screened for eligibility and 1101 (68%) were enrolled; 554 (50%) were assigned to the placebo-abiraterone group and 547 (50%) to the ipatasertib-abiraterone group. At data cutoff (March 16, 2020), median follow-up duration was 19 months (range 0-33). In the 521 (47%) patients who had tumours with PTEN loss by immunohistochemistry (261 in the placebo-abiraterone group and 260 in the ipatasertib-abiraterone group), median radiographical progression-free survival was 16·5 months (95% CI 13·9-17·0) in the placebo-abiraterone group and 18·5 months (16·3-22·1) in the ipatasertib-abiraterone group (hazard ratio [HR] 0·77 [95% CI 0·61-0·98]; p=0·034; significant at α=0·04). In the intention-to-treat population, median progression-free survival was 16·6 months (95% CI 15·6-19·1) in the placebo-abiraterone group and 19·2 months (16·5-22·3) in the ipatasertib-abiraterone group (HR 0·84 [95% CI 0·71-0·99]; p=0·043; not significant at α=0·01). Grade 3 or higher adverse events occurred in 213 (39%) of 546 patients in the placebo-abiraterone group and in 386 (70%) of 551 patients in the ipatasertib-abiraterone group; adverse events leading to discontinuation of placebo or ipatasertib occurred in 28 (5%) in the placebo-abiraterone group and 116 (21%) in the ipatasertib-abiraterone group. Deaths due to adverse events deemed related to treatment occurred in two patients (<1%; acute myocardial infarction [n=1] and lower respiratory tract infection [n=1]) in the placebo-abiraterone group and in two patients (<1%; hyperglycaemia [n=1] and chemical pneumonitis [n=1]) in the ipastasertb-abiraterone group.
Interpretation
Ipatasertib plus abiraterone significantly improved radiographical progression-free survival compared with placebo plus abiraterone among patients with mCRPC with PTEN-loss tumours, but there was no significant difference between the groups in the intention-to-treat population. Adverse events were consistent with the known safety profiles of each agent. These data suggest that combined AKT and androgen-receptor signalling pathway inhibition with ipatasertib and abiraterone is a potential treatment for men with PTEN-loss mCRPC, a population with a poor prognosis.
Funding
F Hoffmann-La Roche and Genentech.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 09 Jul 2021; 398:131-142
Sweeney C, Bracarda S, Sternberg CN, Chi KN, ... Garcia J, de Bono JS
Lancet: 09 Jul 2021; 398:131-142 | PMID: 34246347
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Impact:
Abstract

Venous thromboembolism.

Khan F, Tritschler T, Kahn SR, Rodger MA
Venous thromboembolism, comprising both deep vein thrombosis and pulmonary embolism, is a chronic illness that affects nearly 10 million people every year worldwide. Strong provoking risk factors for venous thromboembolism include major surgery and active cancer, but most events are unprovoked. Diagnosis requires a sequential work-up that combines assessment of clinical pretest probability for venous thromboembolism using a clinical score (eg, Wells score), D-dimer testing, and imaging. Venous thromboembolism can be considered excluded in patients with both a non-high clinical pretest probability and normal D-dimer concentrations. When required, ultrasonography should be done for a suspected deep vein thrombosis and CT or ventilation-perfusion scintigraphy for a suspected pulmonary embolism. Direct oral anticoagulants (DOACs) are the first-line treatment for almost all patients with venous thromboembolism (including those with cancer). After completing 3-6 months of initial treatment, anticoagulation can be discontinued in patients with venous thromboembolism provoked by a major transient risk factor. Patients whose long-term risk of recurrent venous thromboembolism outweighs the long-term risk of major bleeding, such as those with active cancer or men with unprovoked venous thromboembolism, should receive indefinite anticoagulant treatment. Pharmacological venous thromboembolism prophylaxis is generally warranted in patients undergoing major orthopaedic or cancer surgery. Ongoing research is focused on improving diagnostic strategies for suspected deep vein thrombosis, comparing different DOACs, developing safer anticoagulants, and further individualising approaches for the prevention and management of venous thromboembolism.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 02 Jul 2021; 398:64-77
Khan F, Tritschler T, Kahn SR, Rodger MA
Lancet: 02 Jul 2021; 398:64-77 | PMID: 33984268
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Impact:
Abstract

First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.

Janjigian YY, Shitara K, Moehler M, Garrido M, ... Li M, Ajani JA
Background
First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone.
Methods
In this multicentre, randomised, open-label, phase 3 trial (CheckMate 649), we enrolled adults (≥18 years) with previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, regardless of PD-ligand 1 (PD-L1) expression from 175 hospitals and cancer centres in 29 countries. Patients were randomly assigned (1:1:1 while all three groups were open) via interactive web response technology (block sizes of six) to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks) plus chemotherapy (capecitabine and oxaliplatin every 3 weeks or leucovorin, fluorouracil, and oxaliplatin every 2 weeks), nivolumab plus ipilimumab, or chemotherapy alone. Primary endpoints for nivolumab plus chemotherapy versus chemotherapy alone were OS or progression-free survival (PFS) by blinded independent central review, in patients whose tumours had a PD-L1 combined positive score (CPS) of five or more. Safety was assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT02872116.
Findings
From March 27, 2017, to April 24, 2019, of 2687 patients assessed for eligibility, we concurrently randomly assigned 1581 patients to treatment (nivolumab plus chemotherapy [n=789, 50%] or chemotherapy alone [n=792, 50%]). The median follow-up for OS was 13·1 months (IQR 6·7-19·1) for nivolumab plus chemotherapy and 11·1 months (5·8-16·1) for chemotherapy alone. Nivolumab plus chemotherapy resulted in significant improvements in OS (hazard ratio [HR] 0·71 [98·4% CI 0·59-0·86]; p<0·0001) and PFS (HR 0·68 [98 % CI 0·56-0·81]; p<0·0001) versus chemotherapy alone in patients with a PD-L1 CPS of five or more (minimum follow-up 12·1 months). Additional results showed significant improvement in OS, along with PFS benefit, in patients with a PD-L1 CPS of one or more and all randomly assigned patients. Among all treated patients, 462 (59%) of 782 patients in the nivolumab plus chemotherapy group and 341 (44%) of 767 patients in the chemotherapy alone group had grade 3-4 treatment-related adverse events. The most common any-grade treatment-related adverse events (≥25%) were nausea, diarrhoea, and peripheral neuropathy across both groups. 16 (2%) deaths in the nivolumab plus chemotherapy group and four (1%) deaths in the chemotherapy alone group were considered to be treatment-related. No new safety signals were identified.
Interpretation
Nivolumab is the first PD-1 inhibitor to show superior OS, along with PFS benefit and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Nivolumab plus chemotherapy represents a new standard first-line treatment for these patients.
Funding
Bristol Myers Squibb, in collaboration with Ono Pharmaceutical.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 02 Jul 2021; 398:27-40
Janjigian YY, Shitara K, Moehler M, Garrido M, ... Li M, Ajani JA
Lancet: 02 Jul 2021; 398:27-40 | PMID: 34102137
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Impact:
Abstract

Low back pain.

Knezevic NN, Candido KD, Vlaeyen JWS, Van Zundert J, Cohen SP
Low back pain covers a spectrum of different types of pain (eg, nociceptive, neuropathic and nociplastic, or non-specific) that frequently overlap. The elements comprising the lumbar spine (eg, soft tissue, vertebrae, zygapophyseal and sacroiliac joints, intervertebral discs, and neurovascular structures) are prone to different stressors, and each of these, alone or in combination, can contribute to low back pain. Due to numerous factors related to low back pain, and the low specificity of imaging and diagnostic injections, diagnostic methods for this condition continue to be a subject of controversy. The biopsychosocial model posits low back pain to be a dynamic interaction between social, psychological, and biological factors that can both predispose to and result from injury, and should be considered when devising interdisciplinary treatment plans. Prevention of low back pain is recognised as a pivotal challenge in high-risk populations to help tackle high health-care costs related to therapy and rehabilitation. To a large extent, therapy depends on pain classification, and usually starts with self-care and pharmacotherapy in combination with non-pharmacological methods, such as physical therapies and psychological treatments in appropriate patients. For refractory low back pain, a wide range of non-surgical (eg, epidural steroid injections and spinal cord stimulation for neuropathic pain, and radiofrequency ablation and intra-articular steroid injections for mechanical pain) and surgical (eg, decompression for neuropathic pain, disc replacement, and fusion for mechanical causes) treatment options are available in carefully selected patients. Most treatment options address only single, solitary causes and given the complex nature of low back pain, a multimodal interdisciplinary approach is necessary. Although globally recognised as an important health and socioeconomic challenge with an expected increase in prevalence, low back pain continues to have tremendous potential for improvement in both diagnostic and therapeutic aspects. Future research on low back pain should focus on improving the accuracy and objectivity of diagnostic assessments, and devising treatment algorithms that consider unique biological, psychological, and social factors. High-quality comparative-effectiveness and randomised controlled trials with longer follow-up periods that aim to establish the efficacy and cost-effectiveness of low back pain management are warranted.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 02 Jul 2021; 398:78-92
Knezevic NN, Candido KD, Vlaeyen JWS, Van Zundert J, Cohen SP
Lancet: 02 Jul 2021; 398:78-92 | PMID: 34115979
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Impact:
Abstract

Body-mass index and obesity in urban and rural China: findings from consecutive nationally representative surveys during 2004-18.

Wang L, Zhou B, Zhao Z, Yang L, ... Ding G, Li X
Background
In China, mean body-mass index (BMI) and obesity in adults have increased steadily since the early 1980s. However, to our knowledge, there has been no reliable assessment of recent trends, nationally, regionally, or in certain population subgroups. To address this evidence gap, we present detailed analyses of relevant data from six consecutive nationally representative health surveys done between 2004 and 2018. We aimed to examine the long-term and recent trends in mean BMI and prevalence of obesity among Chinese adults, with specific emphasis on changes before and after 2010 (when various national non-communicable disease prevention programmes were initiated), assess how these trends might vary by sex, age, urban-rural locality, and socioeconomic status, and estimate the number of people who were obese in 2018 compared with 2004.
Methods
We used data from the China Chronic Disease and Risk Factors Surveillance programme, which was established in 2004 with the aim to provide periodic nationwide data on the prevalence of major chronic diseases and the associated behavioural and metabolic risk factors in the general population. Between 2004 and 2018 six nationally representative surveys were done. 776 571 individuals were invited and 746 020 (96·1%) participated, including 33 051 in 2004, 51 050 in 2007, 98 174 in 2010, 189 115 in 2013, 189 754 in 2015, and 184 876 in 2018. After exclusions, 645 223 participants aged 18-69 years remained for the present analyses. The mean BMI and prevalence of obesity (BMI ≥30 kg/m2) were calculated and time trends compared by sex, age, urban-rural locality, geographical region, and socioeconomic status.
Findings
Standardised mean BMI levels rose from 22·7 kg/m2 (95% CI 22·5-22·9) in 2004 to 24·4 kg/m2 (24·3-24·6) in 2018 and obesity prevalence from 3·1% (2·5-3·7) to 8·1% (7·6-8·7). Between 2010 and 2018, mean BMI rose by 0·09 kg/m2 annually (0·06-0·11), which was half of that reported during 2004-10 (0·17 kg/m2, 95% CI 0·12-0·22). Similarly, the annual increase in obesity prevalence was somewhat smaller after 2010 than before 2010 (6·0% annual relative increase, 95% CI 4·4-7·6 vs 8·7% annual relative increase, 4·9-12·8; p=0·13). Since 2010, the rise in mean BMI and obesity prevalence has slowed down substantially in urban men and women, and moderately in rural men, but continued steadily in rural women. By 2018, mean BMI was higher in rural than urban women (24·3 kg/m2vs 23·9 kg/m2; p=0·0045), but remained lower in rural than urban men (24·5 kg/m2vs 25·1 kg/m2; p=0·0007). Across all six surveys, mean BMI was persistently lower in women with higher levels of education compared with women with lower levels of education, but the inverse was true among men. Overall, an estimated 85 million adults (95% CI 70 million-100 million; 48 million men [95% CI 39 million-57 million] and 37 million women [31 million-43 million]) aged 18-69 years in China were obese in 2018, which was three times as many as in 2004.
Interpretation
In China, the rise in mean BMI among the adult population appears to have slowed down over the past decade. However, we found divergent trends by sex, geographical area, and socioeconomic status, highlighting the need for a more targeted approach to prevent further increases in obesity in the Chinese general population.
Funding
China National Key Research and Development Program, China National Key Project of Public Health Program, and Youth Scientific Research Foundation of the National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 02 Jul 2021; 398:53-63
Wang L, Zhou B, Zhao Z, Yang L, ... Ding G, Li X
Lancet: 02 Jul 2021; 398:53-63 | PMID: 34217401
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Impact:
Abstract

Acute respiratory distress syndrome.

Meyer NJ, Gattinoni L, Calfee CS
Acute respiratory distress syndrome (ARDS) is an acute respiratory illness characterised by bilateral chest radiographical opacities with severe hypoxaemia due to non-cardiogenic pulmonary oedema. The COVID-19 pandemic has caused an increase in ARDS and highlighted challenges associated with this syndrome, including its unacceptably high mortality and the lack of effective pharmacotherapy. In this Seminar, we summarise current knowledge regarding ARDS epidemiology and risk factors, differential diagnosis, and evidence-based clinical management of both mechanical ventilation and supportive care, and discuss areas of controversy and ongoing research. Although the Seminar focuses on ARDS due to any cause, we also consider commonalities and distinctions of COVID-19-associated ARDS compared with ARDS from other causes.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 30 Jun 2021; epub ahead of print
Meyer NJ, Gattinoni L, Calfee CS
Lancet: 30 Jun 2021; epub ahead of print | PMID: 34217425
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Impact:
Abstract

Prevalence of negative child disciplinary practices and its associated factors as reported by mothers in the West Bank: a cross-sectional study.

Al-Natsheh B, Al-Sharif R, Khdour R, Othman S, ... Nasr S, Giacaman R
Background
For parents, how to manage child discipline is a difficult question in the task of raising a socially, emotionally, and physically mature adult. Negative discipline can be physical or psychological, and can negatively affect child development, mental health, and wellbeing. This study aimed to assess the prevalence of negative disciplinary methods (NDMs) and their associated factors in the West Bank, occupied Palestinian territory, as reported by mothers.
Methods
The survey was conducted in November and December, 2014, to explore the disciplinary methods that mothers used for one of their children (aged 0-12 years) during the previous 12 months. 1195 Palestinian mothers were studied based on a stratified multistage cluster sampling method and using the International Society for Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse and Screening Tool for Parents (ICAST-P). A scale was built from mothers\' reports on the use of NDMs, with good internal consistency (Cronbach\'s α=0·75). The dataset was split according to whether the mother used 0-6 NDMs or 7-20 NDMs in the previous 12 months. Bivariate analyses were performed using the chi squared test to compare these two categories in terms of demographic and socioeconomic variables, and exposure to Israeli political violence. Binary logistic regression was performed to check for confounders. The Institute of Community and Public Health and Birzeit University approved the use of the data.
Findings
The mothers were aged between 15 and 55 years. 11·3% of mothers (135 of 1195) were 15-25 years old, 45·4% (541) were 26-35 years old, and 43·2% (515) were 36-55 years old. 52·5% of children (627 of 1195) were male, 34·0% (406) were 0-3 years old, and 66·0% (789) were 4-12 years old. 5·2% of children (62) were the only child, 4·4% of children (53) were the first child, 27·6% (330) were the middle child (a child that is not the first or the last child), and 62·8% (750) were the last child. 45·8% of the mothers and children (547) lived in the north of the West Bank, 23·3% (278) lived in the middle of the West Bank, and 31·0% (370) lived in the south of the West Bank. 5·3% of mothers (63) reported that their homes were bombed or shelled by the Israeli army. 83·8% of mothers (1002) reported using 0-6 NDMs and 16·2% (193) used 7-20 methods. Other demographic and socioeconomic variables collected were not significantly associated with NDMs. Binary logistic regression revealed that females were less likely to be exposed to NDMs than males (OR 0·63, 95% CI 0·45-0·88, p=0·0074), and that children aged 0-3 years were less likely to be exposed to NDMs than children aged 4-12 years (0·50, 0·33-0·76, p=0·0014). Compared with last children, first children (2·84, 1·46-5·51, p=0·0020) and middle children (1·49, 1·02-2·17, p=0·0375) were more likely to be exposed to NDMs. Compared with mothers aged 36-55 years, mothers aged 15-25 years (2·67, 1·47-4·85, p=0·0010) and 26-35 years (1·54, 1·05-2·26, p=0·0289) used more NDMs. Compared with children in the north of the West Bank, children in the south of the West Bank (2·46, 1·66-3·64, p<0·0001) and middle of the West Bank (1·90, 1·24-2·93, p=0·0034) were more likely to be exposed to NDMs. Compared with mothers whose houses were not bombed or shelled by the Israeli army, mothers whose houses were bombed or shelled were more likely to use a higher number of NDMs (2·71, 1·84-1·95, p=0·0012).
Interpretation
Negative child discipline is prevalent in Palestine and is associated with factors such as the child\'s gender, their age, their index in the family (whether they are the only child, first, middle, or last child), the mother\'s age, the district, and the political conditions in Palestine. Effort should be made to help families to understand alternative methods to address child discipline, through education, discussion, and parenting programmes.
Funding
This study is part of a larger study of child discipline in Qatar and the occupied Palestinian territory. The study was conceptualised and planned with the funding of Qatar National Research.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S9
Al-Natsheh B, Al-Sharif R, Khdour R, Othman S, ... Nasr S, Giacaman R
Lancet: 29 Jun 2021; 398:S9 | PMID: 34227991
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Impact:
Abstract

A cross-sectional survey of the prevalence and determinants of comorbid psychological distress in attendees at two general hospitals in Gaza.

Yaghi M, Chatterjee S, Alissawi F, Daher M, ... Abu Shawish M, Imad O
Background
There is an absence of mental health services within general hospitals in Gaza. As part of the Ministry of Health plan to develop mental health liaison services, a cross-sectional survey of the prevalence of and risk factors for psychological distress in attendees at two general hospitals was undertaken to estimate and highlight the need for establishing such services.
Methods
20 volunteers aged 24-30 years with a degree in psychological or social science from a university accredited by the Palestinian Ministry of Education and Higher Education, and with experience in field data collection for studies in mental health, were selected and trained in the use of the Arabic version of the 12-item General Health Questionnaire (GHQ-12), an internationally and well validated tool for measuring psychological distress in adults. The volunteers were supervised as they screened adult attendees at emergency rooms, inpatient wards and outpatient departments, and women attending the maternity units at two of the largest general hospitals in Gaza (Nasser and Indonesian) over seven consecutive days (March 18-23, 2018). Attendees at emergency and outpatient departments were included if they were on repeat visits with medically unexplained somatic complaints, if they attended with complaints resulting from any kind of social problem, physical or sexual violence, or had a history of any kind of chronic disease. All patients from the internal medicine and inpatient departments were included. The data from the questionnaires were collated and analysed with descriptive and inferential statistics.
Findings
1789 attendees (791 men and 998 women) were screened using the GHQ-12. Of these attendees, 23·8% (426 of 1789) had a GHQ-12 score of 6 or 7, indicating the presence of significant psychological distress with a high possibility of caseness (ie, meeting the diagnostic threshold for clinical depression). 36·2% (648 of 1789) scored 8 or above, indicating the presence of moderate to severe depression or anxiety disorders that require immediate clinical intervention. For all of the hospital departments surveyed, individuals with scores of 6 or greater made up a large proportion of the attendees (385 of 660 [58·3%] in emergency rooms, 197 of 306 [64·4%] in inpatient wards, 430 of 711 [60·5%] in outpatient departments, and 62 of 112 [55·4%] in maternity units), in both hospitals. In addition, a set of risk factors were found to be significantly associated with GHQ-12 scores of 6 or greater. These were being a woman (p=0·020), living in villages adjoining the most conflict prone areas (p<0·0001), no or low formal education (p<0·0001), being divorced (p<0·001) or widowed (p<0·0001), being unemployed (p<0·0001), and low family income (monthly income of <1000 ILS; p<0·0001). On further stepwise regression analysis, unemployment and low family income were found to be the most important risk factors associated with GHQ-12 scores of 6 or greater.
Interpretation
In general hospital attendees there was a very high rate of significant psychological distress. Given the absence of mental health services within general hospitals in Gaza, the findings indicate an urgent need to make mental health interventions routinely available through general hospital liaison units in Gaza. The risk factors that were identified indicate that psychosocial interventions and access to developmental support are key components of such clinical services, and will be required to reduce the very large, and mostly unmet, population burden of mental health problems in Gaza.
Funding
WHO, occupied Palestinian territory, as part of the EU project \"Building Palestinian resilience: improving psychosocial and mental health responses in emergency\".

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S52
Yaghi M, Chatterjee S, Alissawi F, Daher M, ... Abu Shawish M, Imad O
Lancet: 29 Jun 2021; 398:S52 | PMID: 34227987
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Abstract

Integration of mental health and psychosocial support services into primary health care in Gaza: a cross-sectional evaluation.

Ubaid M, Jadba G, Mughari H, Tabash H, ... Aljaish A, Shahin U
Background
Integration of mental health and psychosocial support (MHPSS) into primary health care in the Gaza Strip involves the delivery of mental health services within the essential service package provided by UNRWA, as recommended by WHO to fill the treatment gap. In early 2016, a successful pilot demonstrated that the integration is achievable in limited resource settings, and resulted in the adoption of a stepped care model to screen, identify, support, and treat patients. This study aimed to evaluate the MHPSS integration process and outcomes at UNRWA health centres in the Gaza Strip.
Methods
We used a descriptive analytical study design, with quantitative and qualitative data collected from records, and individual feedback from patients and health care providers (HCPs). The study was performed in the 22 UNRWA health centres of the Gaza Strip and all participants agreed to participate either verbally or by written consent. Approval was also obtained from the UNRWA Health Program Gaza Field Office.
Findings
The integration process started with the comprehensive training of 460 medical and nursing HCPs, in accordance with the Mental Health Gap Action Programme (mhGAP) Intervention Guide. On completion of training, the HCPs put into practice their learning, under close supervision for the first month and with only technical support thereafter. During the period of technical support, MHPSS activities, referral pathways, and proper reporting were ensured and standardised in all health centres. Overall, the integration process achieved success in training, implementation, and supervision. The success of training was assessed with an evaluation form and participants\' feedback, the success of implementation by the numbers of people who benefitted, their response to the intervention, and their feedback, and the success of supervision by the standardisation of the process and the technical validity of the intervention. By the end of September, 2018, 80 857 high-risk patients were screened using the General Health Questionnaire 12 (GHQ-12) and 9·0% (7327) were identified as requiring intervention and support, and were assisted using the UNRWA stepped care approach. Of the individuals who were assisted, 30·2% (2212 of 7327) showed significant improvement and 38·9% (2849) were identified as having mental health issues according to the mhGAP. In the same period, 1020 patients benefited from 113 support groups, with excellent effects on their physical and mental health as assessed with qualitative data, patients\' testimonies and, in some cases, laboratory investigations. The challenges that were faced were due to manual documentation and reporting, sociopolitical uncertainty, an increase in the number and needs of patients, and the imposed burden on HCPs. In addition, during implementation many individuals who were screened and identified required an urgent response: individuals who were suicidal and individuals whose mental health had been affected by the Great March of Return.
Interpretation
The integration showed remarkable success in a short time as a result of the collective effort of all participants. However, there are challenges to overcome, and observation, further evaluation, and refinement of the process are needed to stabilise and sustain the integration of MHPSS services into primary health care for maximum benefit.
Funding
WHO, and UNRWA resources.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S51
Ubaid M, Jadba G, Mughari H, Tabash H, ... Aljaish A, Shahin U
Lancet: 29 Jun 2021; 398:S51 | PMID: 34227986
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Abstract

The effect of home-based care on housebound patients and their caregivers in two Palestinian refugee camps in Lebanon: a qualitative study.

Sunallah M, van den Boogaard W, Lakis C, Rinchey L, Saavedra L
Background
The incidence of non-communicable diseases (NCDs) increases annually by approximately 5% among older (age 50 years and older) Palestinian refugees in Lebanon, of whom around 10% are housebound. Care for housebound patients does not exist in the over-medicalised and highly privatised Lebanese health system or within the health system for Palestinian refugees in Lebanon. This has led to a neglected population. In 2016, Médecins Sans Frontières (MSF) started to provide home-based care (HBC) for housebound patients in two Palestinian camps: Bourj-el-Barajneh and Ain-al-Hilweh. HBC is carried out by a team comprising a doctor, nurse, and social worker, and includes basic medical monitoring, health literacy educational sessions, support for treatment adherence, as well as networking with relevant social service providers.
Methods
A qualitative study was carried out between January and October, 2018, nine patients, ten caregivers, and personnel from two main international non-governmental organisations providing health care for refugees were interviewed, and one focus group discussion was conducted with MSF HBC staff. Thematic content analysis was carried out manually, with investigators\' observations for triangulation. The study was approved by the MSF ethical review board.
Findings
The housebound patients described various ways in which they felt socially isolated, useless, and unproductive. These are underserved needs. Caregivers reported feeling burdened socially, mentally, and financially. They also reported that they assumed full responsibility for the housebound relative, as there was no alternative. HBC was appreciated by patients and caregivers for providing psychosocial and medical support; patients viewed MSF staff as a \"friend in care\", a temporary escape from isolation, and caregivers expressed appreciation for sharing the burden of caring for the housebound person. There was a decrease in anxiety expressed by caregivers and patients, as well as a declining sense of burden described by caregivers, during the provision of HBC by the MSF staff. To a lesser extent, patients and caregivers sensed improved self management as their disease literacy and treatment adherence increased, and as caregivers became more efficient in handling toilet care, bathing, and wound dressing. Missing components of HBC were perceived to be \"outdoor\" activities and mental health services.
Interpretation
HBC had an effect in reducing patients\' social isolation, decreasing caregivers\' burden and anxiety, and enhancing self management of disease for both. HBC should be considered for replication by all refugee health care providers as well as by the Lebanese Ministry of Public Health. This model of care needs to adopt a more holistic approach by including provision of mental health care and by increasing the focus on social isolation.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S50
Sunallah M, van den Boogaard W, Lakis C, Rinchey L, Saavedra L
Lancet: 29 Jun 2021; 398:S50 | PMID: 34227985
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Impact:
Abstract

Daily experiences and strategies for psychological survival during the 2014 assaults in Gaza: a retrospective analysis of chronological diaries.

Sousa C, Veronese G, Jaradah A, Hamdouna H
Background
Public health research suggests that multiple factors contribute to the mental health sequalae of political violence, but the daily experiences and ongoing strategies of psychological survival during active warfare are not clearly understood. We analysed retrospective chronological diaries from Palestinian women in Gaza, occupied Palestinian territory, to explore their lives during Operation Protective Edge in 2014, when a series of aerial bombardments killed over 2000 Palestinians and left around 500 000 displaced from their homes.
Methods
20 Palestinian female teachers in Gaza were recruited via an intervention for trauma recovery 1 month after the end of Operation Protective Edge, in September, 2014. Following the experience sampling method, women were asked to chronicle specific memories and affective responses associated with their experiences. Data were imported into qualitative data analysis software, coded line by line, and analysed using content analysis, with special attention to the causes of mental distress associated with political violence.
Findings
The women\'s narratives included memories of exposure to bombings, injuries, death, and destruction of vital infrastructure and systems. Their experiences of flight were described as exhausting and demoralising. Their temporary shelters lacked their basic needs for sanitation, food, and privacy. These experiences resulted in intense terror, grief, exhaustion, hopelessness, and isolation. Strategies of psychological survival included reframing; trying to appreciate \"being able to escape death\", a sense of solidarity within families and neighbourhoods, and pride and satisfaction found in a context of resistance and global attention to the suffering in Gaza.
Interpretation
Our results reveal the importance of tracing the events of warfare, its psychosocial consequences, and the distinct patterns of emotional and logistical survival in Gaza. This study was limited by the representativeness of our study population and the small sample size. Future studies should explore this topic in larger populations. Limitations notwithstanding, in drawing out the unique contribution of reflective narratives of women survivors of war, our study highlights the need to solicit and analyse reflective and chronologically grounded narratives within global mental health epidemiology.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S49
Sousa C, Veronese G, Jaradah A, Hamdouna H
Lancet: 29 Jun 2021; 398:S49 | PMID: 34227983
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Impact:
Abstract

Assessment of health-related quality of life in patients with inflammatory bowel disease in occupied Palestinian territory: a correlation cross-sectional study.

Smerat T, Khdour M, Abdoh Q, Hallak H
Background
Disease activity is suggested to be an important indicator for quality of life (QoL) in patients with inflammatory bowel disease (IBD). Few studies of the association between adherence to medication and QoL in patients with IBD are available, and their findings are conflicting. We examined associations between disease activity, medication adherence, and QoL in patients with IBD in occupied Palestinian territory.
Methods
This correlation cross-sectional study was done from July 1, 2017, to Feb 30, 2018. We used convenience sampling to recruit patients from three major hospitals in southern and northern regions of occupied Palestinian territory. The disease-specific inflammatory bowel disease questionnaire (IBDQ) was used to examine QoL. Medication adherence was measured with the modified Morisky adherence scale. Associations were assessed by regression analysis. Results were analysed with SPSS version 20. The study was approved by the Al-Quds University Research Ethics Committee. Informed verbal consent was obtained from the participants before the start of the study.
Interpretation
132 patients were enrolled. The mean age was 34 years (SD 13) and 77 (58%) patients were men. Active disease in the previous 6 months was reported in 81 participants (61%). Low adherence to medication (score <6) was reported in 52 (39%) of participants. The average IBDQ score was low (150·72 [SD 30·08]), with the emotional and bowel domains being most affected. Active disease was the most significant factor associated with patients\' QoL overall (p<0·001). No significant association was found between medication adherence and QoL. Regression analysis revealed significant independent associations between QoL and disease remission (p<0·001), high educational status (p=0·009), and using azathioprine (p=0·034).
Interpretation
Our results provides baseline data about Palestinian IBD patients\' QoL and medication use and adherence, and might help health-care providers to identify patients with IBD at risk of low QoL, especially those with relapse and active symptoms. Attention should be given by health-care providers and strategists to increasing knowledge about IBD. The importance of treatment adherence should be explored further. Some limitations were encountered during the study period; it was conducted in only three hospitals and the results might not be generalisable. The cross-sectional type of this study might prevent the identification of any cause-and-effect relationships, especially between medication and post-treatment improvements in QoL.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S48
Smerat T, Khdour M, Abdoh Q, Hallak H
Lancet: 29 Jun 2021; 398:S48 | PMID: 34227982
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Impact:
Abstract

A multidimensional measure of wellbeing among youth: a cross-sectional study of the Palestinian refugee youth in Lebanon.

Salti N, Chaaban J, Irani A, Al-Mokdad R
Background
Increasing refugee populations worldwide highlight the need for development indicators that cover refugees, especially as they tend to be excluded from national statistics. Refugee youth face double exclusion, as most wellbeing indices are not youth-specific. We developed a youth wellbeing index (YWI) for Palestinian refugees in Lebanon (PRL) and Palestinian refugees from Syria (PRS) living in Lebanon, with the aim of providing a snapshot of youth wellbeing to inform evidence-based youth-specific development strategies.
Methods
The YWI was developed and its data generated using information from the 2015 survey of PRL and PRS, which was approved by the American University of Beirut Institutional Review Board. The wellbeing of PRL (n=3940) and PRS (n=1581) aged 15-29 was measured using the YWI, which examines five wellbeing dimensions: educational attainment, health, housing, active education or employment, and access to information. Scores for each of the five dimensions are scaled to [0, 1], and YWI is their arithmetic mean. The data enable us to look at the YWI by gender, by camp residence, and by narrower age bands to detect any generational differences within youth. Findings are reported using sampling weights for representativeness.
Findings
4 years after displacement (2011-2015), PRS youth showed lower levels of wellbeing (YWI=0·56, 95% CI 0·55-0·57) than PRL youth (YWI=0·65, 95% CI 0·64-0·67). Although money-metric poverty was significantly higher inside than outside camps for both PRL youth (inside camps, 75·00%, 95% CI 71·55-78·15; outside camps, 61·98%, 55·26-68·27) and PRS youth (inside camps, 93·89%, 90·56-96·1; ; outside camps, 88·72%, 85·35-91·39), there was no such disparity in the YWI for PRL youth (inside camps, YWI=0·65, 95% CI 0·63-0·66; outside camps, 0·66, 0·62-0·69) or PRS youth (inside camps, 0·55, 0·54-0·56; outside camps, 0·57, 0·54-0·59). Young male refugees had significantly higher YWI (PRL, 0·66, 95% CI 0·65-0·68; PRS, 0·57, 0·56-0·59) than young female refugees (PRL, 0·64, 0·62-0·66; PRS, 0·55, 0·53-0·56). Young female PRL and PRS scored significantly higher for education (PRL, YWI=0·60; PRS, 0·61) than young male refugees from these populations (PRL, 0·48; PRS, 0·47), but significantly lower on active education or employment (PRL, 0·45; PRS, 0·18) than the young male refugees (PRL, 0·72; PRS, 0·47). Older PRS scored higher on the YWI education dimension (20-24 years age group, 0·61; 25-29 years age group, 0·50) than their PRL peers (20-24 years age group, 0·53; 25-29 years age group, 0·45), but the reverse was true for the 15-19 years age group (PRL, 0·60; PRS, 0·53).
Interpretation
Residence inside versus outside camps showed no significant differences in wellbeing based on the YWI, whereas money-metric poverty was higher inside camps, which suggests a need to move beyond assistance policies based on money-metric measures alone. The female edge in educational attainment is reversed when considering active education or employment, signalling the need for gender-specific strategies for the school-to-work transition for both PRL and PRS. The reversal of the educational edge of PRS over PRL in the 15-19 years age group is another concerning indicator of the cost of conflict for PRS that persists even four years after their displacement.
Funding
UNRWA funded the 2015 survey data collection and the Economic Research Forum funded the development of the YWI.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S47
Salti N, Chaaban J, Irani A, Al-Mokdad R
Lancet: 29 Jun 2021; 398:S47 | PMID: 34227981
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Impact:
Abstract

Prevalence of overweight, obesity, and associated factors among adolescents in the occupied Palestinian territory: a cross-sectional study.

Salah RO, Ghandour R, Husseini A
Background
Overweight and obesity are multifactorial conditions that are spreading fast in both developing and developed countries. They are emerging as a major public health threat among children and adolescents, and present a serious morbidity and mortality burden. Adolescence is a critical period in which lifestyle and dietary behaviours are shaped that persist into adulthood. Therefore, adolescents are an ideal study target in terms of estimating the magnitude of the problem, understanding its risk factors and investigating potential effective intervention programmes. This study assesses the prevalence of overweight, obesity, and associated factors among adolescents in Palestinian schools.
Methods
Weighted analysis was conducted on data from the Palestinian Micronutrient Survey, a national cross-sectional study carried out in 2013 by the Palestinian Ministry of Health in collaboration with UNICEF. For sample selection, stratified cluster random sampling was used. This school-based survey involved 2400 male and female adolescents aged 15-18 years in government schools in the West Bank and Gaza Strip. Data were analysed at univariate, bivariate, and multivariate levels, by the use of proportions, confidence intervals, and logistic regression. In the original survey, written informed consent was obtained from parents and guardians of the participants. A letter of approval to use the study data was obtained from the Ministry of Health (who own the data). The study was also approved by the Ethics Committee of the Institute of Community and Public Health.
Findings
The analysis indicates a prevalence of 23·6% (95% CI 20·6-26·5) for overweight and obesity, with a prevalence of 26·1% in the West Bank and 19·5% in the Gaza Strip. The multivariate analysis revealed that the likelihood of overweight and obesity was significantly higher for adolescents from the West Bank than from the Gaza Strip, for those eating two main meals or less than for those eating three meals, for those who reported a high frequency of vegetable intake, and those who observed a diet for weight loss.
Interpretation
The data suggest that one in every four adolescents is overweight or obese, which is an alarming statistic and calls for attention. The high prevalence can be attributed to different lifestyles, eating behaviours, and dietary intake, which affect energy balance. These factors should be investigated within social, political, and economic contexts, and addressed comprehensively, first at the level of individuals and family, and then at the level of schools and the community. It should be noted that the original study included students in the 10th grade and 11th grade only, whereas adolescence covers a wider age group (10-19 years).
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S46
Salah RO, Ghandour R, Husseini A
Lancet: 29 Jun 2021; 398:S46 | PMID: 34227980
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Impact:
Abstract

Knowledge and attitude of Palestinian women to contraceptives: a cross-sectional study.

Warasna B, Rajabi N, Mustafa B, Najjar A, ... Al-Atrash S, Amro A
Background
Contraceptives have documented efficiency, but outcomes are highly dependent on women\'s understanding of how they should be used. We assessed the knowledge and attitudes of married Palestinian women about contraceptives and understanding of use of the available methods and side-effects.
Methods
This cross-sectional study involved married Palestinian women of childbearing age (18-50 years), and was done between Jan 20, 2017, and Jan, 1, 2018. A stratified random sample of 900 women was selected from each Palestinian governorate in the West Bank and East Jerusalem, with the number selected based on population size. An interviewer-assisted questionnaire was completed by each participant.
Findings
833 women were selected to participate and 771 (93%) completed the questionnaire. 123 (16%) of women reported not using any method of contraception. Among those who used contraception, intrauterine devices were most commonly used (312 [41%] of 771), followed by oral contraceptives (162 [21%]). Progestagen-only pills were the most frequently used type of oral contraceptive (45 [28%] of 162). Female sterilisation was used as a birth control method by 19 (3%) of 771 women. Investigation of the reasons behind contraception use showed that organisation of pregnancies was most common (511 [79%] of 648), followed by having too many children (131 [20%]) and economic reasons (73 [11%]). Regarding attitudes and beliefs towards contraceptive use, of the 771 participants, 49 (6%) believed that religion forbids their use and 112 (14·5%) considered them socially unacceptable. The study revealed poor scores for knowledge about use and possible side effects of contraceptives (mean 8·2 [SD 2·9] correct answers to 14 questions).
Interpretation
Most Palestinian women have used contraceptives, but poor knowledge of how to use them and side-effects is apparent. The attitudes of Palestinian women and their partners towards contraceptives indicates general acceptance of their use. A strength of our study is that it included representative sample of Palestinian women and our results and conclusions reflect the knowledge and attitudes towards contraceptives in Palestinian society.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S45
Warasna B, Rajabi N, Mustafa B, Najjar A, ... Al-Atrash S, Amro A
Lancet: 29 Jun 2021; 398:S45 | PMID: 34227979
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Impact:
Abstract

Wellbeing, symptoms of trauma, and personal resources in Palestinian professional helpers: a cross-sectional quantitative survey.

Pepe A, Cavazzoni F, Addimando L, Jaradah A, Obaid H, Veronese G
Background
Professional helpers working in adverse circumstances are at risk of developing psychosocial stress and signs of primary and secondary trauma (eg, anxiety and hyperarousal). We used modelling to investigate whether and to what extent personal resources (ie, post-traumatic growth, sense of coherence, and wellbeing) of Palestinian helpers affected their experience of psychological distress and trauma symptoms.
Methods
Eligible participants were professional health-care providers working in Gaza and the West Bank, occupied Palestinian territory, between June and October, 2018. We used the following quantitative measures: WHO Well Being Index (WHO-5), General Health Questionnaire (GHQ-12), Impact of Event Scale (IES-13), Sense of Coherence Scale (SOC-3), and Post-traumatic Growth Index (PTGI-10). Data were analysed by multivariate structural equation modelling with latent and empirical indicators to test the fit of these constructs to the empirical data. The model was specified to evaluate whether and to what extent mental resources may be interpreted as a set of protective factors mitigating risk factors. The study was approved by the ethics board of the University of Milano-Bicocca, Milan, Italy. Written consent was obtained from participants.
Findings
181 participants were enrolled, ranging in age from 18 to 65 years (mean 31·1, SD 8·7). 135 (75%) were men. The mean GHQ-12 score was 17·7 (SD 7·5), revealing a medium to high degree of psychological trauma. 60 (33%) participants reported low mood (although not necessarily depression) on WHO-5. The structural model showed an excellent fit (χ2 [24] 31·8, p=0·132, root mean square error of approximation 0·043, 90% CI 0·019-0·077). Stronger personal resources were associated with lower levels of both psychological distress (β=-0·25, p<0·01) and trauma (β=-0·16, p<0·01). Personal resources were especially associated with reduced levels of anxiety (β=-0·23, p<0·01) and intrusion symptoms (β=-0·22, p<0·01).
Interpretation
Our integrated model showed that, despite heavy psychological burden, perceptions of post-traumatic growth, coherence, and wellbeing are associated with reduced psychological distress. Targeted training of health-care providers focused on self-awareness of their personal skills and survival resources could improve their psychological health. The study was limited by the cross-sectional research design, and the outcomes of the structural model should be read in terms of probabilistic associations rather than cause-effect relationships. A second limitation concerns the kind of data collected. All the research instruments yielded self-reported quantitative scores, meaning that the standardised β weights in the model could potentially be an artifact of common method variance (ie, attributable to the measurement method rather than to the constructs themselves.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S44
Pepe A, Cavazzoni F, Addimando L, Jaradah A, Obaid H, Veronese G
Lancet: 29 Jun 2021; 398:S44 | PMID: 34227978
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Impact:
Abstract

Morbidity patterns among hospitalised Palestine refugees from Syria in Jordan: a population-based study.

Kitamura A, Paolucci G, Abu-Zayed I, Seita A
Background
Palestine refugees from Syria (PRS) are among the most vulnerable refugee groups for adverse health outcomes and require assistance from humanitarian agencies. As the armed conflict in Syria has continued, most Palestinians have been displaced from that country to neighbouring countries, where they have experienced difficulties in accessing essential services. More than 17 000 PRS are in Jordan as of 2018 and have received assistance from the United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA), including free primary care and subsidised secondary and tertiary care through contracted governmental hospitals. In this study, we investigated the morbidity patterns among PRS in Jordan receiving UNRWA-supported hospital care.
Methods
We assessed cross-sectional data extracted from the UNRWA Hospitalization Database in Jordan on Oct 18, 2018, for PRS who used UNRWA hospitalisation support between May 31, 2012, and Dec 9, 2017. The database records demographic and medical characteristics of patients and financial information for the care sought. We used descriptive statistics to reveal morbidity patterns. Analyses were done with Microsoft Excel 2016 and Stata/IC (version 15). No ethics approval was required for this study as it was conducted as a part of routine internal monitoring by UNRWA.
Findings
889 PRS were included in analysis, among whom 637 (72%) were girls or women and 252 (28%) were boys or men. The age range was 1-78 years, with girls and women being younger than boys and men (28·1 years [SD 15·1] vs 31·0 years [SD 21·3], p=0·02). The most common reasons for seeking care were pregnancy, childbirth, and the puerperium (381 [60%] of 637 girls and women). Diseases of the circulatory system, digestive system, and musculoskeletal system and connective tissue were the most common diagnoses among boys and men (34 cases [14%] of 252 for each diagnosis). The mean length of stay for women (1·8 days [SD 2·0]) was slightly shorter than that for men (2·0 days [SD 2·2]) but the difference was not significant. The cost was significantly higher for boys and men (mean US$729·7 [SD 557·4] per person) than for girls and women ($326·0 [SD 1190·4], p<0·001). Of all, 886 (>99%) patients were discharged from hospital, two died, and one was transferred to another hospital.
Interpretation
More girls and women than boys and men sought care through the UNRWA support programme during the study period, mostly for pregnancy, childbirth, and the puerperium. However, the conditions seen in boys and men led to longer stays in hospitals and significantly higher costs. Diagnoses based on International Classification of Diseases standards should be investigated further, but this study highlights the demand for health-care services and types of care required by the PRS population. Future research should focus on identifying similarities and differences in hospital admissions for PRS compared with other Palestine refugees to inform future preventive public health efforts by UNRWA. The study examined PRS who accessed to UNRWA services only, thus the findings are not representative of PRS in general. However, this is to our knowledge the first study to present morbidity patters and differences in female and male PRS patients receiving care at UNRWA in Jordan.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S43
Kitamura A, Paolucci G, Abu-Zayed I, Seita A
Lancet: 29 Jun 2021; 398:S43 | PMID: 34227977
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Impact:
Abstract

The prevalence and risk factors of urinary incontinence among women with type 2 diabetes in the north West Bank: a cross-sectional study.

Nazzal Z, Khatib B, Al-Quqa B, Abu-Taha L, Jaradat A
Background
Diabetes is one of the most common chronic illnesses worldwide, and it is increasing in prevalence. Urinary incontinence is another worldwide health problem, with a reported prevalence that ranges from 9% to 67%. It decreases quality of life for men and women and has been associated with many poor outcomes, such as longer hospital stays, recurrent or persistent urinary tract infection, and a higher mortality rate. Previous studies have suggested that diabetes is an independent risk factor for urinary incontinence. In addition, the patients\' background and clinical characteristics such as age, obesity, and child-bearing history have been found to increase the risk. The aim of this study was to determine the prevalence of urinary incontinence in women with type 2 diabetes in the north West Bank and to assess the role of potential risk factors, including age, marital status, weight, and diabetes control.
Methods
Women with diabetes attending the six governmental primary health care centres in the north West Bank (Jenin, Tubas, Tulkarem, Nablus, Qalqilya, and Salfit) were interviewed using the CDC National Health and Nutrition Examination Survey (NHANES) standardised incontinence questionnaire. SPSS version 22 was used for data entry and analysis. The prevalence of urinary incontinence was estimated and differences between groups (variables of interest) were evaluated using the chi squared test. The study was approved by the Institutional Review Board of An-Najah National University, and permission to conduct the study was obtained from the Ministry of Health.
Findings
400 Palestinian women with diabetes were invited to participate in the study by convenience sampling, of whom 381 were recruited (a sample size that was chosen with a sample size formula, based on the population of the north West Bank). The participants were aged 30-83 years, and 44% (165 of 381; 95% CI 39-49) reported incontinence, regardless of the type. The prevalence of stress and urge incontinence were 34% (128) and 35% (133), respectively. 30% of women with urinary incontinence (49 of 165) reported that it did not affect their quality of life, and 34% (56 of 165) stated that it did not affect their daily activity. The presence or absence of urinary incontinence was studied in relation to the background and clinical variables by use of the chi squared test. The analysis showed a significant relationship between urinary incontinence status and age (p=0·0011), previous abdominal and genitourinary surgeries (p=0·0037), and caffeine consumption (p=0·041). There was no relationship between urinary incontinence and the duration, type of treatment, or complications of diabetes.
Interpretation
The prevalence of urinary incontinence (regardless of the type) is high among Palestinian women with diabetes. This is similar to reported prevalence in women with diabetes in neighbouring countries, such as Jordan (44%) and Qatar (21%). The majority of participants in this study (70%) reported that urinary incontinence did not affect their quality of life. This may suggest that patients consider the problem to be ordinary, that it does not require medical advice, or that the symptoms are mild. The findings highlight the importance of educating women with diabetes about urinary incontinence. The primary health care medical teams, general practitioners, and nurses who care for patients with diabetes should focus on this neglected problem, and physicians should be alert to urinary incontinence as it may often go unreported and therefore undertreated. To understand whether non-reporting of urinary incontinence reflects mild symptoms, investigating a potential association between non-reporting and the severity or frequency of urinary incontinence may be of interest for future study.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S42
Nazzal Z, Khatib B, Al-Quqa B, Abu-Taha L, Jaradat A
Lancet: 29 Jun 2021; 398:S42 | PMID: 34227976
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Abstract

Life conditions and quality of life of Palestinians living in the Biddu Enclave: a qualitative study.

Nasr S, Heneiti A, Hammoudeh W
Background
Palestinians have been exposed to long-term violence, displacement, and conflict since the 1940s. Continued expropriation and fragmentation of the region has affected people\'s quality of life. The Biddu Enclave communities, located northwest of Jerusalem, are behind a barrier wall that detaches them from Jerusalem and the rest of the West Bank other than by access through a tunnel controlled by the Israeli authorities. The enclave is fully or partially under Israeli administration. We explored the effects of socioeconomic and geographical transformations and isolation on the quality of life of these communities, specifically on daily uncertainty, stress, and overall wellbeing of residents.
Methods
We included four communities-Beit Iksa, Qatanna, Biddu, and Beit A\'nan-that have varied characteristics and circumstances. Between early October, 2018, and the end of November, 2019, we did in-depth interviews with 20 key informants, such as mayors, village council members, municipality employees, and teachers, and 16 residents older than 20 years and from a range backgrounds, including activists, retirees, and housewives. We also did two focus groups involving young adults from all four communities. Questions were asked about living conditions and consequences of the socioeconomic and geographic transformations in the study area. We analysed the data by repeated readings to identify patterns and themes.
Findings
We found poor overall quality of life, characterised by chronic daily uncertainty, insecurity and heightened vulnerability, leading to stress and reduced wellbeing. The main negative determinants of quality of life were poor infrastructure, dependence on work in the Israeli labour market, a precarious permit system, increasing land expropriation and expansion of Israeli settlements, separation from Jerusalem, and marginalisation by the Palestinian National Authority. Community characteristics, such as social solidarity and active community organisations were important in mediating some of these effects. Other variations in the characteristics of the communities, such as topography, having relatives living in the USA, levels of education, unemployment rate, and proximity to Israeli settlements seemed to play a role in the abilities of residents to endure conditions.
Interpretation
Our findings highlight the importance of political and socioeconomic transformations in the wellbeing of residents in the Biddu Enclave. Sustained insecurity and uncertainty, marginalisation, and isolation of the communities have negative effects on quality of life. More research focusing on these communities is needed to better understand the mechanisms by which these factors affect health and how they may lead to ill health and disease in the long term.
Funding
Arab Council for Social Sciences.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S41
Nasr S, Heneiti A, Hammoudeh W
Lancet: 29 Jun 2021; 398:S41 | PMID: 34227975
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Impact:
Abstract

Self-perceived health among children with spina bifida in the West Bank: a cross-sectional study.

Sudki Nahal M, Axelsson ÅB, Imam A, Wigert H
Background
Children born with spina bifida endure constant physical disability, which is challenging for themselves and their families. To date, the impact of spina bifida on the health-related quality of life (HRQOL; eg, physical, psychological, and social wellbeing) of these children has been assessed mainly through parent proxy reports, and self-perceived health among these children is rarely measured. This study aimed to measure self-perceived health in children with spina bifida in the West Bank, to compare this with that in a healthy reference group also from the West Bank, and to assess the potential association between self-perceived health and the level of disability in children with spina bifida.
Methods
A cross-sectional study was conducted in the West Bank. The Paediatric Quality of Life Inventory (PedsQL) was administered to a convenience sample of 200 children aged 8-12 years, of whom 50 have spina bifida and 150 are healthy. For the children with spina bifida, their disability was categorised and ranked according to four aspects of impairment (mobility, bowel function, bladder function, and hydrocephaly). Data were analysed with SPSS version 24. Difference in PedsQL scores between the two groups of children was tested with the Mann-Whitney U-test. The Spearman\'s rank correlation coefficient was used to evaluate the association between the level of physical impairment in children with spina bifida and their self-perceived health. Written informed consent was obtained from the children\'s parents. The children\'s verbal assent was also obtained, and their right to withdraw from the study at any time was emphasised.
Findings
Children with spina bifida had lower overall PedsQL scores (mean 45·5, SD 14.5) than those reported by the reference group of healthy children (mean 80·0, SD 12·8). For children with spina bifida, social functioning had the lowest mean score (30·5, SD 20·8), followed by physical functioning (37·5, SD 16.6), emotional functioning (56·0, SD 17·2), and school functioning (62·6, SD 17.8), whereas the range for all of the PedsQL scores in the reference group was 71·7-84·5. The results demonstrate significant inverse associations between self-perceived health (overall PedsQL score) in children with spina bifida and both the level of mobility impairment (rs=-0·65, p<0·0001) and the presence of hydrocephalus (rs=-0·53, p<0·0001). A weak inverse association was found between self-perceived health and both bladder and bowel dysfunction. For both groups, no associations were found between demographic characteristics (age, gender, type of settlement of residence [city, village, camp]) and self-perceived health.
Interpretation
The findings provide insights into the importance of social support and rehabilitation services for children with spina bifida in the occupied Palestinian territory. In particular, community awareness, and education of health care providers and family members, may be important.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S39
Sudki Nahal M, Axelsson ÅB, Imam A, Wigert H
Lancet: 29 Jun 2021; 398:S39 | PMID: 34227972
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Abstract

Clinical and pathological characteristics and hormone receptor status of women with breast cancer in the European Gaza Hospital: a retrospective chart-based review.

Musallam R, Alnajjar M, Al-Shurafa A, Bottcher B
Background
Breast cancer is the most common cancer (accounting for 31·3% of all cancers) among women in the Gaza Strip. This audit examines clinical and pathological characteristics of women presenting with breast carcinoma to the European Gaza Hospital (EGH), a governmental hospital and oncological centre serving 600 000 people in the southern Gaza Strip.
Methods
Data were collected from the records of patients with breast cancer treated at the EGH from March, 2015, to Sept, 2017. 397 cases were identified, including 218 patients with full hormone receptor status (oestrogen, progesterone, and Her2/neu receptor status). Data were analysed using Student\'s t test.
Findings
The mean age was 54 years (SD 11·2). 64% of the women (139 of 218) were older than 50 years, and 16% (33 of 218) were younger than 40 years. Histological grade was assessed for 56% of the women (122 of 218), and 55% of these women (67 of 122) presented with grade II tumours. Tumour size was documented in 82% of the files (178 of 218), and tumours were 2-5 cm in 47% of the documented cases (83 of 178). Furthermore, 51% of women (112 of 218) tested positive for the presence of cancer cells in lymph nodes, and 6% (14 of 218) had distant metastasis at presentation. The clinical stage at diagnosis was recorded in 56% of cases (122 of 218), of whom 4% (five of 122) presented at stage I, 54% (66 of 122) presented at stage II, and 42% (51 of 122) presented at stage III/IV. Pre-operative histopathology was carried out for 120 women, of whom 85% (102 of 120) had intraductal carcinoma. Only 81% of women (177 of 218) had post-operative histopathology, of whom 79% (139 of 177) had intraductal carcinoma. The histopathological type was significantly different for pre-operative and post-operative specimens (p<0·0001). Oestrogen receptor status was positive in 58% of patients (127 of 218), progesterone receptor status was positive in 57% of patients (124), and HER2/neu receptor was overexpressed in 33% of patients (65). Triple-negative breast cancer (testing negative for oestrogen, progesterone, and HER2/neu) was found in 23% of the women (49) and double-negative breast cancer (testing negative for oestrogen and progesterone but positive for HER2) in 11% of the women (24).
Interpretation
Patients with breast cancer present with advanced disease in the Gaza Strip. HER2/neu overexpression was approximately 10% higher than the percentages reported in the literature for the USA. The significant difference between pre-operative and post-operative specimens\' histopathological type could be due to use of fine-needle aspiration. Guidance from the Royal College of Radiologists recommends pre-operative core biopsy. It should be noted that documentation in the patient medical files was incomplete, which is a common obstacle in Gaza that must be tackled for effective improvement in the quality of care.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S38
Musallam R, Alnajjar M, Al-Shurafa A, Bottcher B
Lancet: 29 Jun 2021; 398:S38 | PMID: 34227971
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Abstract

Perceptions of health-care professionals about quality of care and barriers to management of war injuries in Gaza Strip: a qualitative analysis.

Mosleh M, Al Jeesh Y, Dalal K, Carlerby H, Viitasara E
Background
War-related injury is a growing clinical and public health concern in occupied Palestinian territory, especially in the Gaza Strip. However, little research has been done into the quality of care and management of war injuries in public hospitals. We explored the perceptions of health-care workers about these factors in Palestinian health-care facilities in Gaza.
Methods
This was a qualitative descriptive study. Data were obtained in four focus group discussions attended at public health facilities by 30 purposively selected health-care providers, comprising 14 head surgeons, and 16 head nurses, aged 38-55 years. A semi-structured topic guide was developed by the authors for the study based on earliest literature, and was critically reviewed by a panel of experts to ensure the trustworthiness of the qualitative guide and to minimise complexity and enhance clarity of the questions for participants. Audio recordings of discussions were transcribed verbatim, translated, and analysed with a thematic analysis approach. The study was approved by the Palestinian Health Research Council and facilitated by the Ministry of Health.
Findings
A consensus was expressed that, despite some positive aspects in the system, fundamental changes and essential improvements were needed to advance the care and facilitation of war injury management. Some respondents had serious concerns about the health-care system, suggesting that it needs to be comprehensively rebuilt. Unanimous views were expressed about the important barriers to effective management and quality of care: shortages of resources, medicines, and funding; underuse or absence of specific and unified clinical practice guidelines; no official commitment by the Ministry of Health to adopt updated clinical guidelines; few incentives and poor motivation, poor communications; blockade and siege; division of health systems in the country; overcrowding of patients with war injuries in hospitals with limited capacity; spreading of infection due to poor cleanliness; shortages in fuel and power supply; and low wages, which negatively affected staff motivation. Respondents also reported inadequate sharing of care and cooperation between different health-care facilities.
Interpretation
The perceptions about barriers to management of war injuries and the quality of care provided were similar across Palestinian health-care facilities in the Gaza strip. Our findings suggest that fundamental changes and comprehensive reform of the health-care system are needed to make the care of patients with war injuries more effective and efficient. One of the important strengths of this study is that it addressed the perspective and opinions of different key health professionals, which made it possible gain deeper and better understanding of how war injuries are managed in the Palestinian health system. In addition, the outcomes of the study were based on diverse information. However, the analysis of the qualitative data may represent challenges, and be more complicated and time consuming than a quantitative approach.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S37
Mosleh M, Al Jeesh Y, Dalal K, Carlerby H, Viitasara E
Lancet: 29 Jun 2021; 398:S37 | PMID: 34227970
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Abstract

Pain management in adults during long-bone fracture reduction in the Gaza Strip: a clinical audit.

Lubbad M, Ahmad M, Adwan H, Al-Ra\'of Sammor A, Böttcher B
Background
Ongoing protests in Gaza have led to numerous injuries, including long-bone fractures. We investigated assessment of pain severity and strategies for pain management in the emergency department. As no local guidelines exist, delivered care was compared with the guidance of the UK National Institute for Health and Care Excellence (NICE).
Methods
A clinical audit was conducted at the emergency department in Dar Al Shifa Medical Complex, Gaza, among patients who attended the emergency department with acute long-bone fractures between April 15 and July 15, 2018. Data were collected on pain assessment methods and strategies for pain management and analgesia administration. Ethics approval was obtained from the Palestinian Ministry of Health. The purpose of the audit was explained to patients and their written consent was obtained before inclusion.
Findings
Of 79 patients invited to participate, 50 gave consent. 25 patients (50%) were aged 16-24 years, 20 (40%) 25-64 years, and five (10%) 65 years and older. Structured pain assessments were performed in only three patients (6%). No analgesia was administered to patients in the emergency department, except for two patients (4%) received infiltration of lidocaine as analgesia for haematoma.
Interpretation
No local guidelines for acute pain management in emergency departments exist in the Gaza Strip. Clinical practice showed no adherence to international standards, such as the NICE guidelines for pain management. Factors contributing to such poor management might be large numbers of patients presenting at the time during conflict and protests and that only one room was available in the Shifa\' Medical Complex emergency department for examining, assessment, prescribing, and cast application. A limitation of the study is the small sample size is relatively small, but strengths were the 3-month period and prospective enrolment in the emergency department.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S36
Lubbad M, Ahmad M, Adwan H, Al-Ra'of Sammor A, Böttcher B
Lancet: 29 Jun 2021; 398:S36 | PMID: 34227969
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Abstract

Food insecurity in the context of conflict: analysis of survey data in the occupied Palestinian territory.

Lin TK, Kafri R, Hammoudeh W, Mitwalli S, ... Giacaman R, Leone T
Background
Conflict impacts food security and decreases household dietary diversity. However, few studies have explored the routes by which prolonged conflict and social stressors affect food insecurity experience and food diversity. This study examines the influence of political, economic, and agricultural stressors on food insecurity and food diversity, and evaluates variations in food insecurity and food diversity with location of residence for households in the occupied Palestinian territory.
Methods
A secondary data analysis with structural equation modelling was carried out on data from the Socio-Economic & Food Security Survey 2014 of the Palestinian Central Bureau of Statistics. The survey was completed by a representative sample of the Palestinian population in the occupied Palestinian territory at governorate and locality levels, and consisted of 4215 households in the West Bank and 2916 households in the Gaza Strip. The primary outcomes were food diversity (measured with a food consumption score) and food insecurity (assessed with a composite experience-based measure of food security). We used structural equation models to examine the relationships between location of residence (in the West Bank, living in Area C versus not Area C; in the Gaza Strip, proximity of residence to the buffer zone), the number of political stressors, economic stressors, and agricultural stressors (eg, restricted access to land), and the primary outcomes. We controlled for demographic characteristics, including education, governorate, and wealth.
Findings
In the West Bank, there was no statistically significant direct association between living in Area C and food insecurity. Living in Area C is associated with a higher number of agricultural stressors than not Area C (p=0·032), and a higher number of agricultural stressors is in turn associated with lower food diversity (p=0·0080) and higher food insecurity (p=0·040). In the Gaza Strip, proximity to the buffer zone is directly associated with higher food insecurity (p=0.041) and lower food diversity (p=0·019) and a higher number of political stressors (p=0·057). A higher number of political stressors is associated with a higher number of economic stressors (p=0·026) and higher food insecurity (p=0·034).
Interpretation
The findings suggest that political, economic, and agricultural factors contribute to food insecurity and food diversity, and that their interactions are complex. Conflict and occupation affect food availability through both direct and indirect channels. In the Gaza Strip, living in close proximity to the buffer zone is associated with lower food diversity and higher food insecurity. In the West Bank, although residing in Area C may not directly increase food insecurity, the hardship generated by the conditions in Area C contributes to higher food insecurity.
Funding
The Emirates Foundation.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S35
Lin TK, Kafri R, Hammoudeh W, Mitwalli S, ... Giacaman R, Leone T
Lancet: 29 Jun 2021; 398:S35 | PMID: 34227968
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Abstract

Enhancing the quality of maternal and neonatal care by the Safe Childbirth Project in Al Shifa Hospital, Gaza occupied Palestinian territory (oPt): a descriptive retrospective study.

Abu Ward I, Jouda A, Balousha S, Egenberg S, Al Masri N, Blix E
Background
The Safe Childbirth Project is a campaign, launched by WHO in 2012, to improve the quality of care for women and babies during childbirth by promoting evidence-based practice and a midwifery-led approach to care. It was intended to contribute towards achieving UN Sustainable Development Goal 3: ensure healthy lives and promote wellbeing for all at all ages. In September, 2015, the project was launched in the maternity ward of Dar Al-Shifa Hospital, Gaza City, to promote midwifery-led care for low-risk deliveries, with de-medicalisation of normal birth, early initiation of breastfeeding, and early detection of complications during the postpartum period.
Methods
Dar Al-Shifa Hospital is the largest Ministry of Health hospital in the Gaza Strip, is the referral hospital for the whole area, and includes medical, surgical, and maternity departments. Most women who attend the maternity department (70%) have high-risk pregnancies. The caesarean section rate in 2016 was 27%. 88 midwives and 82 doctors are employed on the maternity wards. We did a descriptive retrospective analysis of all women admitted in labour to the maternity hospital from the start of the Safe Childbirth Project on Sept 1, 2015, to June 30, 2018. Data were extracted from patients\' files then aggregated and analysed. Six indicators of quality of care were assessed: risk assessment on admission to the labour ward; use of partograms; oxytocin augmentation of labour; babies delivered by a midwife; breastfeeding initiation within 1 h of birth; and the number of postnatal examinations. Ethics approval was obtained from the Helsinki Committee, at the Palestinian Health Research Council.
Findings
Of 16 400 births at Dar Al-Shifa Hospital during the study period, 11 480 (70%) were normal vaginal deliveries. The percentages of women risk assessed on admission increased from 65% at the start of the study to 100% at the end, but the proportions of pregnancies classified as being at low risk or high risk remained at roughly one-third to two-thirds (low risk 20% and high risk 45% at the start of the study vs 30% and 70%, respectively, at the end of the study). Partograms were used in all women throughout the study period. Use of oxytocin augmentation of labour decreased from 24% to 8%. Midwives delivered 53% of low-risk women at the beginning of the study and 100% at the end. The proportion of women who initiated breastfeeding within 1 h of birth increased from 45% to 81% and the percentage of women who had five or more postpartum examinations increased from 27% to 81%.
Interpretation
Implementation of the Safe Childbirth Project in Dar Al-Shifa Hospital improved most of our indicators of quality of care and was maintained along with regular clinical auditing. Management commitment and close clinical supervision have been the cornerstones of success.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S34
Abu Ward I, Jouda A, Balousha S, Egenberg S, Al Masri N, Blix E
Lancet: 29 Jun 2021; 398:S34 | PMID: 34227967
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Abstract

Associations between stressful working conditions and psychosomatic symptoms among Palestinian nurses: a cross-sectional survey.

Jaradat Y, Bjertness E, Birkeland Nielsen M, Bast-Pettersen R
Background
Stressful working conditions among nurses have adverse effects on their physical and mental health. We investigated associations between self-reported stressful working conditions and psychosomatic symptoms among nurses in the Hebron district, occupied Palestinian Territory, and whether there are differences the sexes in the perceptions of working conditions and psychosomatic symptoms.
Methods
We did a cross-sectional survey between Oct 7 and Dec 10, 2012, among registered nurses in all health sectors in Hebron district. A nine-point ordinal scale of working conditions was used to categorise perception of stress as low, medium, or high, and seven psychosomatic symptoms were recorded on a checklist coded as never (0), seldom (1), occasionally (2), or often (3), allowing for a total score between 0 and 21. All analyses were done with STATA (version 10). P values of less than 0·05 were significant. Participation in the study was voluntary, and written informed consent was obtained from each participant. The study was approved by the Regional Committee for Medical and Health Research Ethics, Norway. Permission to do the study was obtained from the Palestinian Ministry of Health.
Findings
Among 372 eligible nurses, ten were on extended leave from work, 16 declined to participate, and four had incomplete data, giving a final sample of 342 nurses (92% response rate). 212 (62%) were women and 130 (38%) were men. Low levels of stress were reported by 42 (12%) nurses, medium levels by 206 (60%), and high levels by 94 (28%). The mean score of psychosomatic symptoms for the group was 10·4 (SD 4·02, range 0-21). Scores did not differ significantly between men and women. Mean symptom scores differed between nurses with self-reported highly stressful working conditions and those with low levels of stress (12.6 vs 8.4, difference 4·1, 95% CI 2·7-5·5; p<0·001). Among male nurses, those with self-reported highly stressful working conditions had a mean psychosomatic symptom score of 13.0, compared with that was 7.7 among those working in low-stress conditions (difference 5·3 units, p<0·001). This effect remained significant after adjustment for the covariates age, education, number of children, work schedule, and years of experience (12·6 vs 7·7, difference 4·9 units, 95% CI 2·6-7·2). Among female nurses, the scores among those with high-stress working conditions was 12.4 and for those with low-stress working conditions was 9.0 (difference 3·4 units, p<0·001). After adjustment the difference remained similar (12·4 vs 9·0, difference 3·5 units, 95% CI 1·7-5·3, p<0·001).
Interpretation
We found that psychosomatic symptoms increased as self-reported perception of stressful working conditions increased, irrespective of sex. The study had a cross-sectional design and both exposure and outcomes were measured using self-report and, therefore, interpretation of the results should be made with caution. Longitudinal epidemiological studies are recommended. Future studies should investigate whether stressful working conditions affect the quality of patients\' care in health services.
Funding
Norwegian Programme for Development, Research and Education.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S33
Jaradat Y, Bjertness E, Birkeland Nielsen M, Bast-Pettersen R
Lancet: 29 Jun 2021; 398:S33 | PMID: 34227966
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Impact:
Abstract

Child deprivation among Palestinian refugees in Lebanon and Palestinian refugees from Syria living in Lebanon: a cross-sectional analysis of co-occurrence of deprivation indicators.

Jamaluddine Z, Irani A, Salti N, Abdulrahim S, ... El-Asmar K, Ghattas H
Background
Palestinian refugees in Lebanon (PRL) and Palestinian refugees from Syria (PRS) living in Lebanon have high poverty rates. As the social, economic, and physical environment in which a child develops is a strong determinant of health and wellbeing, a comprehensive approach that recognises the influence of multidimensional deprivation on child wellbeing is needed. This study investigates overlaps (co-occurrences) in deprivation indicators experienced by Palestinian children compared to those experienced by other vulnerable children living alongside them in Lebanon; children who are Syrian refugees (SYR) and children who are Lebanese nationals (LBN).
Methods
This analysis adopted a life-cycle approach using data from the UNICEF 2016 Lebanon Household Survey, and included data on children aged 2-17 years (PRL, n=7106; PRS, n=2768; LBN, n=10555; SYR n=5891). We report on indicators relating to early childhood (24-59 months) and school age (6-17 years), including child survival (nutrition, health, water, sanitation, and overcrowding), child development (education), and child protection (labour, exposure to violence, and early marriage), as well as the co-occurrence of these deprivation indicators. Socio-demographic and geographical correlates of child deprivation were explored using univariate and multivariable logistic regression analysis, a using sampling weights and clustering for children in the same households. Analyses were conducted using Stata 15.
Findings
Among children aged 24-59 months, 28·9% (347 of 1202) of PRL and 46·2% (260 of 563) of PRS children were deprived in at least two dimensions, compared with 13·2% (67 of 508) of LBN and 68·5% (915 of 1335) of SYR children. Co-occurring deprivations were highest across the protection and overcrowding dimensions in Palestinian refugee children aged 6-17 years (PRL, 14·2% [769 of 5421]; PRS, 26·7% [531 of 1985]). Across all ages, PRS children were more likely to be deprived in two dimensions than PRL children. However, indicators of health and education deprivation were lower in PRL and PRS children than in SYR children. Geographical disparities in deprivation existed within all four populations, with the highest disparity among those living in North Lebanon and the Bekaa. Higher maternal education (completed intermediate education) was consistently associated with lower odds of having at least two concurrent deprivations among children aged 6-17 years (LBN odds ratio [OR] 0·1, 95% CI 0·1-0·2, p<0·0001; PRL OR 0·3, 95% CI 0·3-0·5, p<0·0001; PRS OR 0·5, 95% CI 0·3-0·7, p=0·0002; SYR OR 0·4, 95% CI 0·2-0·7, p=0·0004).
Interpretation
The most common overlaps in deprivation indicators were in housing (overcrowding) and protection (exposure to violence) among PRL and PRS children, highlighting the need to focus simultaneously on housing improvements and protection programmes. Deprivation in health and education were relatively low as PRS children have been included in the well-established UNRWA health and education systems, largely protecting them from poor health and education outcomes.
Funding
UNICEF Lebanon. The findings, interpretations, and conclusions do not necessarily reflect the view of UNICEF.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S32
Jamaluddine Z, Irani A, Salti N, Abdulrahim S, ... El-Asmar K, Ghattas H
Lancet: 29 Jun 2021; 398:S32 | PMID: 34227965
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Impact:
Abstract

Gestational age recorded at delivery versus estimations using antenatal care data from the Electronic Maternal and Child Health Registry in the West Bank: a comparative analysis.

Isbeih M, Venkateswaran M, Abbas E, Abu-Khader K, ... White R, Frøen JF
Background
Estimated dates of delivery have important consequences for clinical decisions during pregnancy and labour. The Electronic Maternal and Child Health Registry (MCH eRegistry) in Palestine includes antenatal care data and birth data from hospitals. Our objective was to compare computed best estimates of gestational age in the MCH eRegistry with the gestational ages recorded by health-care providers in hospital delivery units.
Methods
We obtained data for pregnant women in the West Bank registered in the MCH eRegistry from Jan 1, 2017 to March 31, 2017. Best estimates of gestational age in the registry are automated and based on a standard pregnancy duration of 280 days and ultrasound-based pregnancy dating before 20 weeks\' gestation or the woman\'s last menstrual period date. Hospital recorded gestational ages are reported by care providers in delivery units and are rounded to the nearest week. We calculated proportions of gestational ages (with 95% CIs) from both sources that fell into the categories of term, very preterm (24-32 weeks\' gestation), preterm (33-37 weeks), or post-term (>42 weeks).
Findings
1924 women were included in the study. The median hospital recorded gestational age was 39 weeks (IQR 38-40 weeks) and according to MCH eRegistry estimates was 39 weeks and 5 days (IQR 38 weeks and 1 day to 40 weeks and 5 days). Proportions of very preterm, preterm, and post-term deliveries were higher based on MCH eRegistry estimates than on hospital recorded gestational ages (very preterm 3%, 95% CI 2-4 vs 2%, 1-2; preterm 6%, 5-7 vs 5%, 3-6 ; post-term 6%, 5-7 vs 1%, 1-2).
Interpretation
In addition to clinical care, the proportions of term, very preterm, preterm, and post-term births can have implications for public health monitoring. The proportion of deliveries within the normal range of term gestation was calculated to be higher by care providers in delivery units than by MCH eRegistry estimates. Extending the access of hospitals to information from antenatal care in the MCH e-Registry could improve continuity of data and better care for pregnant women.
Funding
European Research Council, Research Council of Norway.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S31
Isbeih M, Venkateswaran M, Abbas E, Abu-Khader K, ... White R, Frøen JF
Lancet: 29 Jun 2021; 398:S31 | PMID: 34227964
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Abstract

Long-term health effects after conflict-related traumatic amputation among patients in Gaza.

Heszlein-Lossius H, Ismail A, Al-Borno Y, Shaqqoura S, ... Matar M, Gilbert M
Background
In the past 10-15 years, thousands of civilians in Gaza have experienced conflict-related traumatic injuries. How injuries affect survivors\' risks of negative long-term health effects and serious illness is unclear. We report follow-up findings in a group of patients with traumatic amputations.
Methods
Eligible patients had traumatically amputated limbs and showed signs and symptoms of possible serious illness on standardised clinical examination. The patients were all receiving rehabilitation treatment at the Artificial Limbs and Polio Centre, Gaza, which is the main provider of rehabilitation and protheses. All patients had suffered from at least one amputation during Israeli military incursions between 2006 and 2016. All were offered referral to the Al-Shifa Hospital, Gaza, for further diagnostic clinical, radiological, and laboratory tests. Each patient was examined by CT of the abdomen (or ultrasonography if CT could not be performed) and chest and MRI of the amputation stump or stumps. Laboratory analyses included ESR, complete blood count, kidney and liver function tests, serum glucose, creatine kinase, lactate dehydrogenase, and hepatitis B and hepatitis C virus infections.
Findings
Of 254 traumatically amputated patients assessed, 105 had signs and symptoms of possible serious illness, among whom 94 accepted referrals. 88 (93%) of 94 were men and the median age was 31.5 years, mean age 34 years (SD 9·6). Of 90 patients who had imaging, 19 (21%) patients had fatty liver infiltration, three (<1%) had lung nodules, and ten had lung atelectasis. Shrapnel was found in the chest of 12 patients (13%), the abdomen of five patients (6%), the scrotum of one patient (<1%), in the amputation stumps of 26 patients (29%), and the non-amputated limbs of eight patients (1%). Three (<1%) of 90 patients had liver lesions. 32 (34%) of 94 patients had elevated ESR, 19 (20%) had elevated liver enzyme concentrations, and 12 (13%) were anaemic. Two patients tested positive for hepatitis C virus and three were positive for hepatitis B virus (one with fatty liver changes). Two of the 19 patients with fatty liver infiltration were diagnosed as having type 2 diabetes. A limitation of this study is that, owing to conflict-related supply-chain issues in Gaza, we were unable to collect complete data in four (5%) of patients.
Interpretation
As well as residual shrapnel in more than half of patients, a notable proportion of patients had fatty liver infiltration, for which we have no clear hypothesis. We recommend close medical follow-up for trauma patients in injured by explosives.
Funding
The Norwegian street-artist AFK provided €1,500 to this project, which was used to cover patients\' transportation costs.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S30
Heszlein-Lossius H, Ismail A, Al-Borno Y, Shaqqoura S, ... Matar M, Gilbert M
Lancet: 29 Jun 2021; 398:S30 | PMID: 34227963
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Impact:
Abstract

The psychological impact of deprivation in regions affected by conflict: a multilevel analysis of a cross-sectional survey in the occupied Palestinian territory.

Hammoudeh W, Mitwalli S, Kafri R, Lin TK, Giacaman R, Leone T
Background
Deprivation is an important determinant of poor health. Locality can be key in understanding variation in deprivation across a population. This study aimed to analyse how different forms of deprivation affect mental health among Palestinians, and how they account for locality effects in the occupied Palestinian territory.
Methods
We used multilevel modelling to analyse data from the Socio-Economic & Food Security Survey 2014 conducted by the Palestinian Central Bureau of Statistics, which had a sample size of 7827 adults representing the same number of households. The main outcome is a General Health Questionnaire (GHQ) score, in which a higher score signifies worse mental health. Deprivation variables include subjective deprivation, material deprivation, food deprivation, and political deprivation (which was measured by use of the human insecurity scale). For the analysis, we included data on experience of different stressors (economic, political, health-related, and weather-related stress) reported at the household level in the 6 months preceding the survey, and we controlled for demographic characteristics, including age, gender, education, wealth, and region. We also conducted a two-level random effects multilevel regression, with locality as a proxy for neighbourhood.
Findings
The model indicates significant variance at the locality (neighbourhood) level. There is a significant association between poor mental health and subjective, economic, political, and food deprivation; health, economic, and political stressors; age, and being a woman. Education beyond secondary school level and wealth have a significant inverse association with poor mental health. Individuals who indicated that they felt somewhat or very deprived have significantly higher GHQ scores than individuals who indicated that they did not feel deprived (β=1·73 and 4·33 for those who felt deprived and who did not feel deprived, respectively, p<0·0001). Food consumption was inversely associated with GHQ score (β=-0·01, p<0·0001) and food insecurity was positively associated with GHQ score (β=0·19, p<0·0001). Political deprivation, and health-related, political, and economic stressors were significantly positively associated with GHQ scores (β=0·043, 0·23, 0·35, and 0·19 respectively, p<0·0001). Age (β=0·079, p<0·0001) and being a woman were positively associated with GHQ score (β=0·26, p=0·0040), whereas education beyond secondary school level was inversely associated with GHQ score (β=-0·54, p<0·0001).
Interpretation
The findings that the mental health of Palestinians is associated with various forms of deprivation and stressors, provide further evidence that political and social factors are determinants of health. Correlated factors include both subjective and objective measures, and suggest that although material conditions are important, people\'s subjective experiences are also important. Feeling deprived is an important correlate of mental health. The community effect suggests that services (or lack thereof), checkpoints and blockades, political situations, and other factors that vary across localities, may influence mental health issues at the neighbourhood level.
Funding
This project is part of the study \"Re-conceptualising health in wars and conflicts: a new focus on deprivation and suffering\" funded by the Middle East Centre at the London School of Economics and Political Science.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S29
Hammoudeh W, Mitwalli S, Kafri R, Lin TK, Giacaman R, Leone T
Lancet: 29 Jun 2021; 398:S29 | PMID: 34227961
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Abstract

Prevalence and characteristics of Palestine refugee mothers at risk of postpartum depression in Amman, Jordan: a cross-sectional study.

Yoneda K, Hababeh M, Kitamura A, Seita A, Kamiya Y
Background
Postpartum depression (PPD) is a major public health concern because it adversely affects maternal health and children\'s physical and mental development. The prevalence of PPD in Arab countries is higher than the worldwide prevalence. Additionally, refugee women are more likely to develop PPD than women in the general population, but little research of refugee women in Arab countries is available. The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) have provided primary health care to Palestine refugees since 1950 and began the Mental Health and Psychosocial (MHPSS) programme in Jordan in 2017 to enhance the psychosocial and social wellbeing of Palestine refugees. We assessed the prevalence of PPD and examined associated factors among Palestine refugee women living in Amman, Jordan.
Methods
This cross-sectional descriptive study was done between April 21 and May 21, 2018. Eligible participants were Palestine refugee mothers who had given birth 3-16 weeks previously and were attending any of five UNRWA health centres in Amman that were launching the MHPSS programme. Data were gathered in face-to-face structured interviews that included the Edinburgh Postpartum Depression Scale (EPDS) to assess PPD, the Maternal Social Support Scale to assess levels of perceived social support, and a structured questionnaire about sociodemographic, obstetric or paediatric, psychological, and social factors. Participants with scores greater than 12 in the EPDS were classified as having depressive symptoms. Logistic regression was used to identify factors associated with depressive symptoms. The study protocol was approved by the Department of Health, UNRWA Headquarters, Amman, Jordan, and Nagasaki University. Each participant provided written informed consent.
Findings
251 women participated in the study, with a mean age of 27·2 years (range 18-42, SD 5·43). 123 (49%) women were classified as having PPD. Logistic regression showed that factors associated with PPD were perceived low levels of social support (adjusted odds ratio 3·76, 95% CI 1·92-10·93) and experiencing stressful life events (one event 3·92, 1·51-9·91; two events 5·77, 2·33-14·27; and three or more events 14·8, 5·23-41·89).
Interpretation
The prevalence of PPD among Palestine refugee women in Amman was higher than that reported in a previous study of the general childbearing population (women aged 18-45 years) in Irbid in Jordan (22%, Mohammad et al. Midwifery 2011; 27: e238-45) but similar to findings in the West Bank (47%, Quandil et al. BMC Pregnancy Childbirth 2016; 16: 375) and in Syrian refugee women in Jordan (49·6%, Mohammad et al. Res Nurs Health 2011; 41: 519-245). Our findings highlight the need to address this disorder in Palestine refugee mothers. Periodical PPD screening, raising awareness about PPD, providing information to husbands and families, and building a support system for mothers could alleviate the risk of PPD. Future studies should examine whether factors of antenatal depression, which were not assessed in this study, correlate with having PPD to clarify the need for early intervention in mothers.
Funding
Nagasaki University.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S28
Yoneda K, Hababeh M, Kitamura A, Seita A, Kamiya Y
Lancet: 29 Jun 2021; 398:S28 | PMID: 34227960
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Abstract

Assessment of the surveillance system for adverse events following immunisation in the Gaza Strip: a cross-sectional study.

Awad JA, Dhair MI, Ghuneim NI, Abu Ali K, ... Abu Rabee\' M, Sarsour A
Background
In the occupied Palestinian territory, the expanded programme on immunisation (EPI) has successfully targeted 13 diseases through vaccination and achieved high population coverage. However, surveillance of adverse events following immunisation (AEFI) is inadequate in the Gaza Strip, as only post-BCG lymphadenitis is reported. This study assessed the adherence of health-care workers (HCWs) to the AEFI surveillance system in the Gaza Strip.
Methods
Data were collected by four methods: 105 HCWs answered a questionnaire; 24 health facilities completed a checklist enquiry; 17 medical health officers and information system managers from Ministry of Health (MOH) and UNRWA health centres and hospitals underwent in-depth interviews; and a focus group was held with 22 epidemiologists, stakeholders, consultants, and managers of the EPI. The 24 health facilities comprised seven MOH primary health-care centres (PHCs) providing vaccination, five MOH PHCs not providing vaccination, seven UNRWA PHCs, and the five hospitals of the Gaza Strip with paediatric departments. Data collected from June, 2015, to August, 2015, were analysed with SPSS version 19. Relationships among variables were assessed by independent t tests, chi squared tests and one-way ANOVA. Verbal informed consent was obtained from all participants, and written approval for the study was obtained from MOH and UNWRA directorates.
Findings
AEFI are reported infrequently; approximately half of the 105 HCWs (51%; 53) report AEFI, but there were conflicting views as to whom they should report. 65% (68) thought that they should report all AEFI. Participants\' educational background, participation in workshops, and number of years of employment affected AEFI recognition and reporting. The majority (74%; 78) participate in immunisation workshops. There is an ineffective structure in MOH centres, and the UNRWA has a well-established internal system for reporting AEFI but a poor system for external reporting to the MOH epidemiology department. A lack of HCW awareness of responsibilities may also have a role. The majority of HCWs (95%; 100) reported a need for further training, and all reported a lack of cooperation or coordination between hospitals and PHCs regarding AEFI notification. All individuals (17) who were interviewed knew that they must report AEFI. A majority (65%; 11) stated no difficulties, whereas some (35%; six) reported difficulties due to absence of guidelines, protocols, or notification forms, and to fear of punishment. Focus group participants felt that all AEFI should be reported. They agreed that HCWs face obstacles such as fear of consequences, lack of knowledge and training, high workloads, not considering AEFI as related to immunisation, and absence or shortage of notification forms, protocols, and guidelines. Some felt that certain AEFI should be reported only to treating doctors, but all agreed that there is no cooperation or coordination among PHCs and between hospitals and PHCs regarding AEFI reporting.
Interpretation
Common themes may explain poor adherence of HCWs to AEFI surveillance. The system is ineffective in MOH centres, and UNRWA PHCs have well-established internal but poor external reporting systems. Absence of monitoring may have a role, and a lack of guidelines, protocols, and forms for reporting were mentioned by HCWs, medical health officers and information system managers, and the focus group. Some HCWs may not know their responsibilities (eg, to whom AEFI should be reported). Many other obstacles face HCWs, including fear of punishment and accountability. Therefore, HCWs must be encouraged to report adverse events without fear of penalty. In addition, lack of education on AEFI and lack of experience in identifying AEFI may affect reporting. Training of HCWs, development of guidelines and protocols, database construction and design, and monitoring of the AEFI surveillance system are highly recommended.
Funding
WHO EMRO.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S27
Awad JA, Dhair MI, Ghuneim NI, Abu Ali K, ... Abu Rabee' M, Sarsour A
Lancet: 29 Jun 2021; 398:S27 | PMID: 34227959
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Abstract

Effect of hypertension on pregnancy outcomes at UNRWA health centres in Gaza governorates: a comparative study.

El-Qatrawi KJ
Background
Hypertensive disorders affect 10% of all pregnant women and increase the risk of adverse maternal and neonatal outcomes and the psychological wellbeing and quality of life of women. This study is to the best of my knowledge the first to investigate these issues in the Gaza Strip. I compared adverse effects in pregnancy between hypertensive and non-hypertensive women.
Methods
In this comparative study, eligible participants were hypertensive and non-hypertensive women attending health centres for postnatal care between August, 2016, and May, 2017. Six UNRWA health centres of 21 in Gaza Strip were selected randomly and quota sampling was applied after written informed consent was obtained. Data were collected by face-to-face interview and completion of the WHOQOL-BREF scale and SF-36 to assess quality of life. Additionally, data were extracted from patients\' electronic primary medical records. Differences were analysed with Student\'s t test and the χ2 test, using SPSS version 22.
Findings
430 mothers were enrolled, including 215 with hypertension and 215 without. Mean age was 28·0 years (SD 6·15). The mean gravidity and parity were 4·3 and 3·4, respectively, in the hypertensive group and 3·6 and 2·7 in the non-hypertensive group. Compared with the non-hypertensive group, the hypertensive group had a greater mean body-mass index (30·7 kg/m2vs 25·8 kg/m2), number of antenatal care visits (8·6 vs 6·6), and rate of pre-eclampsia (29%). 45 (21%) women in the hypertensive group had persistent hypertension after the postnatal period. Hypertensive mothers had higher rates of caesarean section (80 [37%] vs 35 [16%], p=0·001), delivery induction (58 [27%] vs 18 [8%], p=0·001). antepartum haemorrhage (30 [14%] vs six [3%], p=0·001), and postpartum haemorrhage (15 [7%] vs three [1·4%], p=0·003). Neonates born to women in the hypertensive group were at increased risk of having preterm birth (32 [15%] of 213 vs 16 [8%] of 215, p=0·013), low birthweight (21 [10%] vs 6 [3%], p=0·003), and neonatal admissions (26 [13%] vs 14 [7%], p=0·044) compared with those born to women in the non-hypertensive group. Hypertensive mothers had a lower mean quality of life score than women in the non-hypertensive group (64·2 vs 71·3, p=0·001).
Interpretation
Neonatal admission in the hypertensive group and the caesarean section rates were lower than expected given the rates of preterm birth and low birthweight. These findings might be attributed to inadequate specialised management due to limited resources, blockade, receiving specialist treatment outside Gaza Strip, and political context. However, higher number of antenatal care visits suggests that hypertensive women receive more antenatal care from health-care providers at UNRWA clinics than non-hypertensive women. Secondary and tertiary maternal care in Gaza Strip need to be improved. A limitation of this study was poor documentation of some secondary health care data in electronic primary medical records but was overcome by reviewing hospital records.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S26
El-Qatrawi KJ
Lancet: 29 Jun 2021; 398:S26 | PMID: 34227958
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Impact:
Abstract

Anti-D immunoglobulin versus immunoglobulin G for the treatment of acute immune thrombocytopenia in children: a 10-year retrospective study.

El-Habil MK
Background
Anti-D immunoglobulin (anti-D) therapy is cheaper and has a shorter infusion time than intravenous immunoglobulin G (IgG), but their comparative effects in the treatment of acute immune thrombocytopenia (ITP) have not been studied thoroughly. The aim of this study was to compare the effect of anti-D and intravenous IgG in the treatment of acute ITP in children.
Methods
The medical records of children diagnosed with acute ITP between January, 2008, and January, 2018, at Al-Rantisy Specialized Pediatric Hospital (a tertiary care centre) in Gaza were reviewed. Patients who received either intravenous anti-D (75 μg/kg, single dose) or intravenous IgG (2 g/kg, divided doses) as initial treatment for ITP were included in this retrospective study. Data on patient demographics, hospital stay period, and adverse drug reactions were collected for analysis. Laboratory results, including platelet counts and haemoglobin levels, were evaluated before treatment, and after 1, 3, 5, and 7 days of treatment. The therapy response was defined as the time taken to increase the platelet count to at least 20,000 platelets per μL.
Findings
Data from 134 patients (mean age, 5·8 years; range, 1·1-10·4 years) were included for analysis. 32% of patients (43 of 134) received anti-D and 68% of patients (91) received intravenous IgG. Mean pre-treatment platelet counts were 6420 platelets per μL and 8750 platelets per μL for anti-D and intravenous IgG groups, respectively. The platelet count increased significantly after 1, 3, 5, and 7 days of treatment in both groups (p<0·001). After 24 h of treatment, 58% of patients (25 of 43) in the anti-D group and 55% of patients (50 of 91) in the intravenous IgG group had platelet counts of over 20 000 platelets per μL. Moreover, all of the patients in both groups had more than 20 000 platelets per μL after 7 days of therapy. There were no significant differences in platelet count after treatment between the two groups. Haemoglobin levels decreased during the 72 h after treatment (anti-D group, mean 0·8 g/dL, range, 0·1-1·4 g/dL; intravenous IgG group, mean 0·5 g/dL, range, 0·2-1·2 g/dL; p=0·237), but increased on days 5 and 7 in both groups. The changes in haemoglobin after treatment were similar in both study groups. No patient developed severe anaemia requiring medical intervention. The average length of hospital stay was significantly shorter in the anti-D group than in the intravenous IgG group (1·8 days and 3·2 days, respectively; p<0·0001). Fewer adverse effects (headache, vomiting, chills) were reported in children who received anti-D therapy.
Interpretation
In this analysis, anti-D was as effective as intravenous IgG in the treatment of children with acute ITP. Given that patients in the anti-D group experienced fewer adverse effects and shorter hospitalisation times than patients in the intravenous IgG group, this suggests that anti-D is a good substitute for intravenous IgG in the treatment of children with acute ITP.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S25
El-Habil MK
Lancet: 29 Jun 2021; 398:S25 | PMID: 34227957
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Impact:
Abstract

Effect of nurse-supported care on pain management in women undergoing caesarean delivery: a comparative study.

El Hams S, El Najar N, Abu El-Aish K
Background
Pain management after caesarean delivery is important because acute pain in the postoperative period is associated with persistent pain, increased opioid use and postpartum depression, and delayed functional recovery. We investigated the role of nurse-supported care in acute pain management after caesarean delivery, which as far as we know has not previously been investigated in Gaza.
Methods
This was a comparative study done from March, 2018, to October, 2018, among women assigned to undergo caesarean delivery. Research nurses at the Al-Helal Al-Emirati Hospital, Rafah, Gaza Strip, occupied Palestinian territory, were trained to give supportive pain management care to women after caesarean delivery, including individualised care and educational sessions on pain, nutrition, exercise, and wound care. Women were randomly assigned to receive nurse-supported care or usual care. Pain assessment scales (range 1-5, where 1=no pain and 5=pain as bad as it could be) were used to record pain at 1, 6, 12, 18, and 24 h after caesarean delivery. The time from the end of the caesarean delivery to the first request for analgesia and the total amounts and types of analgesics (pethidine ampules, diclofenac ampules, or indometacin suppositories) used in the first 24 h were recorded as primary outcomes. Secondary outcomes were nausea and vomiting scores (0-3, where 0=no nausea or vomiting and 3=severe and unresponsive to antiemetic drugs), sedation scores (0-3, where 0=patient awake and 3=severe sedation and patient difficult to rouse), and pruritis scores (0-2, where 0=no pruritis and 2=severe pruritis needing treatment). Data were analysed with SPSS (version 22.0). Groups were compared by using the Student\'s t-test and χ2. P values less than 0·05 were significant. The study was approved by the Ministry of Health and Helsinki Committee, Gaza Strip. Women provided verbal informed consent for inclusion in the study when they were assigned to the caesarean delivery.
Findings
108 women participated, with a mean age of 29·2 years (SD 5·50). 49 women were randomly assigned to nurse-supported care and 59 to usual care. Pain was reduced in the nurse-supported care group compared with in the usual care group at 12 h (mean score 1·15 [SD 0·25] vs 1·60 [0·67], p=0·002) and at 18 h (1·08 [0·22] vs 1·26 [0·21], p=0·049) but did not differ significantly at other times. The time to first requesting analgesia was shorter in the nurse-supported care group than in the usual care group (mean 3·38 h [SD 1·01] vs 6·16 h [2·01], p=0·038). The proportions of women who asked for a first analgesic were similar in the two groups (30 [61%] and 36 [61%]), whereas seven (14%) women in the nurse-supported care group requested a second analgesic compared with 13 (22%) in the usual care group (p=0·045). There were no significant differences between the two groups for nausea and vomiting, sedation, or pruritis.
Interpretation
Nurse-supported care provided better analgesia than usual care in women who had undergone caesarean delivery. A multicentre study is needed to explore the types, duration, and repeatability of the effects of nurse supportive care on pain perception and duration of hospital stay after caesarean delivery.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S24
El Hams S, El Najar N, Abu El-Aish K
Lancet: 29 Jun 2021; 398:S24 | PMID: 34227956
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Impact:
Abstract

Effects of change in hospital treatment payment policy for Palestinian refugees in Lebanon: a health economics analysis.

de Almeida SV, Paolucci G, Seita A, Ghattas H
Background
In 2016, the United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) changed from covering the full cost of secondary care in contracted public and private hospitals in Lebanon, Jordan, to requesting that these hospitals pay 10% of the costs. Meanwhile, services at UNWRA-contracted Palestine Red Crescent Society (PRCS) hospitals remained fully covered. We did a health economics analysis to assess the effects this policy change on the demand for secondary care in UNRWA hospitals.
Methods
We assessed the difference in use of different types of hospital (demand) from January to May, 2016, and June, 2016, to October, 2017, before and after the payment policy change. Data were collected by UNWRA from each hospital\'s database, including individual-level inpatient information for 22 193 Palestinian refugees in Lebanon who were admitted to secondary care at UNRWA-contracted hospitals (public, private, and PRCS). We used regression analyses to estimate the effects on demand for the different hospital types, length of stay, and total costs of treatment to UNWRA and patients.
Findings
Around 64% of patients attended PRCS, 26% private, and 9% public hospitals. According to our econometric estimations, after June, 2016, patients were 16% more likely to choose a PRCS hospital over the other types of hospital. Mean length of stay in PRCS hospitals increased, leading to a 20% chance of patients staying 1 day longer in PRCS hospitals than in public or private hospitals. However, the length of stay in public and private hospitals decreased (by an average of 22% at public and 28% at private hospitals), giving an overall decrease in length of stay of 13%. In terms of bill value (ie, total costs to UNRWA and to patients), we found no difference between before and after the policy change.
Interpretation
The introduction of the UNWRA cost-sharing component for secondary care led patients to attend PRCS hospitals more often and for longer periods of time. The finding that no effect was seen on costs for UNRWA or patients suggests that the 10% cut in cover at public and private hospitals did not save any money for UNWRA because patients managed to accommodate the increase by changing their hospital preference The study is limited in that it cannot argue causality between the policy and the results found because there is no control group. Nevertheless, robustness testing, including assessing the year 2017, supports our results. This study contributes to the literature on the impacts of co-payments in health care in a very specific context of poverty and conflict that has rarely been subject to scrutiny and provides feedback to UNRWA on a health-care system measure, relevant for future policy designs.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S23
de Almeida SV, Paolucci G, Seita A, Ghattas H
Lancet: 29 Jun 2021; 398:S23 | PMID: 34227955
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Impact:
Abstract

Non-communicable diseases among Palestinian refugees from Syria: a cross-sectional study on prevalence, case management, access to and utilisation of UNRWA Health Services.

Chaaya M, Ghandour LA, Fouad FM, Germani A, ... Ismail S, Fahd S
Background
As of Feb 14, 2014, UNRWA had registered almost 53 000 Palestinian refugees from Syria (PRS) who had fled to Lebanon as the result of the conflict in Syria. Half of the PRS had gone to one of the 12 Palestinian camps, which are overcrowded and of poor infrastructure. Consequently, there is concern for the wellbeing of PRS; in particular, their health status and access to medical care. Little attention has been given to non-communicable diseases (NCDs) in the acute phases of emergencies. Therefore, an assessment of the prevalence of NCDs among PRS, as well as the patterns of use of available health care services by PRS, is warranted.
Methods
A cross-sectional study was conducted in April, 2018, with 1100 PRS residing inside and outside refugee camps across all governorates of Lebanon. A listing of all PRS families was the sampling frame. A random sample of families was selected and contacted, and then one adult randomly selected from each family was approached for data collection. Pregnant women and participants who were too ill to participate were excluded. After obtaining informed verbal consent, we did face-to-face interviews to collect data on household details (such as type of settlement, source of income) and sociodemographic information, major NCDs (for the household representative), lifestyle behaviours, and health-care use. We invited all participants to UNRWA clinics for physical and biochemical measurements. The study protocol was approved by the Institutional Review Board of the American University of Beirut.
Findings
We surveyed 959 PRS (59% male [465], 82% married [785], mean age 43 years [SD 12]). A quarter of those interviewed had at least one NCD; the most prevalent were hypertension (23%; 221 of 959), rheumatic diseases (17%; 166), cardiovascular diseases (CVDs, 13%; 126), diabetes (13%; 124), and chronic respiratory diseases (CRDs) (10%; 100). All these NCDs were more prevalent among PRS inside camps than in those residing outside camps, except for diabetes. Most participants who had been diagnosed with NCDs were adhering to their prescribed medications (90-98%). However, of those reporting CVDs, only 56% (71 of 126) had attended at least one follow-up appointment, and of those reporting rheumatic diseases, only 33% (55 of 166) had attended at least one follow-up appointment. About half of participants reported that they checked their blood pressure (55%; 528 of 959) or blood glucose (45%; 430). 111 of 221 (50%) participants with hypertension monitored their blood pressure, and 78 of 124 (63%) participants with diabetes monitored their blood glucose. 133 participants attended UNRWA clinics for measurements; 40% (54) had obesity (>30 kg/cm2), 10% (13) had elevated blood pressure, 12% (16) had stage 1 hypertension, and 8% (10) had stage 2 hypertension. Most participants had normal glucose (67%; 89 of 133), cholesterol (65%; 87), triglyceride (58%; 77), and glycosylated haemoglobin levels (64; 85). A substantial proportion of participants who were tested had undiagnosed diabetes (14%; 33 of 108 reporting no diabetes), undiagnosed hypertension (23%; 19 of 81), uncontrolled diabetes (79% of participants with diabetes; 19 of 24), or uncontrolled hypertension (64% of participants with hypertension; 29 of 45).
Interpretation
Further study is needed to understand why the prevalence of NCDs among PRS residing in Palestinian camps is higher than among those living outside, and to understand whether and why access to medicines is a problem, particularly outside camps. The burden of NCDs among PRS is high and their access to services is not optimal; therefore UNRWA should pay special attention to NCD services in this population. UNRWA should invest in efforts to increase awareness of free blood pressure and blood glucose monitoring services in its clinics, and could actively offer free testing in public areas inside camps. Doctors at UNRWA clinics should recommend that patients monitor their disease more frequently and educate them on how to do so. A limitation of the study was the low percentage of participants who attended UNRWA clinics for physical and biochemical measurements.
Funding
UNRWA.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S22
Chaaya M, Ghandour LA, Fouad FM, Germani A, ... Ismail S, Fahd S
Lancet: 29 Jun 2021; 398:S22 | PMID: 34227954
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Abstract

Spatial agency among children living in the Dheisheh refugee camp in the West Bank: a qualitative investigation of space and place as risk and protection factors from political and military violence.

Cavazzoni F, Kittaneh H, Veronese G
Background
In Palestine, the ongoing Israeli occupation shapes and endangers all spaces that are used by children in their everyday lives. In this study, Palestinian children were considered active agents in their lives, both affecting and being affected by the world around them. Our research aimed to explore the role of resources, competencies, and attitudes of spatial agency in the lives of children in the occupied Palestinian territory. Specifically, we investigated how children use domestic and social spaces to actively maintain positive function and wellbeing despite an environmental backdrop of military violence.
Methods
A convenience sample of 29 children aged 7-13 years (mean 9·66, SD 1·63) attending the primary school in Dheisheh refugee camp, West Bank, was selected. 17% (5 of 29) were boys and 83% (24) were girls. All children were asked to draw and describe a map of safe and unsafe places in the camp. Ten children were asked to continue the conversation outdoors using a \"walk-along\" technique, showing familiar places and narrating their experiences. Data were collected in April, 2018. All of the children\'s narratives were audiotaped, transcribed, and translated by a local bilingual researcher. Thematic content analysis was applied. Children who have been diagnosed with a physical or psychological disease were excluded from the sample. The study was approved by the ethical board of the University of Milano-Bicocca. Written informed consent was obtained from children and their families, who were informed of the scope of the research.
Findings
Five themes emerged: using the mosque and the school to access spiritual and educational resources for subjective wellbeing; internal spaces as a safe place for growth and development (including domestic spaces to experience a sense of protection and security); community spaces to have fun and play an active part in the social and political life of the camp; enjoying the outdoor spaces of the camp despite environmental dangers and the violence of the occupation. Some children perceived risks and lack of safety in their lives. Children\'s narratives made plain the ways in which their ability to mobilise functioning resources (such as playing and socialising) were constrained by military and community violence, and environmental degradation. Overall, social and external places as spaces to restore a sense of normality and happiness were valorised more by boys than by girls, and girls were more active in internal spaces than in external spaces.
Interpretation
Spatial agency is a key factor that potentiates wellbeing in children. Psychosocial interventions should aim to promote children\'s participation in transforming and reshaping spaces and places for their own protection and to improve the psychological wellbeing of the community.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S21
Cavazzoni F, Kittaneh H, Veronese G
Lancet: 29 Jun 2021; 398:S21 | PMID: 34227953
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Abstract

Survival analysis for patients with cancer in Gaza applying for Israeli permits to exit the Gaza Strip for health care: a retrospective cohort study of patients from 2008 to 2017.

Bouquet B, Barone-Adesi F, Lafi M, Quanstrom K, ... Rockenschaub G, Rashidian A
Background
Gaza has been under land, sea, and aerial blockade for more than 13 years, during which time Israel has continued its permit regime to control access for Palestinian patients from Gaza to health facilities in the West Bank (including East Jerusalem), Israel, and Jordan. Specific groups, such as patients with cancer, have a high need for permits owing to a lack of services in Gaza. The approval rate for patient permits to exit Gaza dropped from 94% in 2012 to 54% in 2017. We aimed to assess the effect of access restrictions due to permit denials or delays on all-cause mortality for patients with cancer from Gaza who were referred for chemotherapy, radiotherapy, or both.
Methods
This study matched 17 072 permit applications for 3816 patients referred for chemotherapy, radiotherapy, or both, from Jan 1, 2008, to Dec 31, 2017, with referral data for the same period and mortality data from Jan 1, 2008, to Jun 30, 2018. We stratified survival analysis by period of first application (2008-14, 2015-17), in light of varying access to Egypt during these times. Primary analysis compared survival of patients according to their first referral decision (approved versus denied or delayed) using Kaplan-Meier methods and Cox regression. Consent for the study was granted by the Palestinian Ministry of Health, and ethical approval was granted by the Helsinki Committee of the Palestinian Ministry of Health.
Findings
Mortality was significantly higher among patients who were initially unsuccessful in permit applications from 2015 to 2017 (141 events over 493 person-years, corresponding to a rate of 286 per 100 person-years) than among patients who were initially successful in the same period (375 events over 1923 person-years, corresponding to a rate of 195 per 100 person-years) with a hazard ratio of 1·45 (95% CI 1·19-1·78, p=0.0009) after adjusting for age, sex, type of procedure, and type of cancer. There was no significant difference in mortality risk between the two groups in the 2008-14 period, with a hazard ratio of 0·84 (95% CI 0·69-1·01, p=0·071).
Interpretation
Barriers to patient access to health care through denied or delayed permit applications had a significant impact on mortality for patients with cancer who applied for chemotherapy, radiotherapy, or both, in the period 2015-17. Relative ease of access through Rafah from 2008 to 2014 may have mitigated the health effects of access restrictions.
Funding
WHO received funding from the Swiss Agency for Development and Cooperation.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S20
Bouquet B, Barone-Adesi F, Lafi M, Quanstrom K, ... Rockenschaub G, Rashidian A
Lancet: 29 Jun 2021; 398:S20 | PMID: 34227952
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Abstract

Health attacks and protection strategies during Gaza\'s Great March of Return: a mixed methods study using data from WHO\'s Surveillance System for Attacks on Healthcare.

Shehada W, Bouquet B, Nassar J, Briody C, ... Pollock A, Kim HJ
Background
WHO defines an attack on health care as \"any act of verbal or physical violence or obstruction or threat of violence that interferes with the availability, access and delivery of curative and/or preventive health services during emergencies.\" Gaza\'s Great March of Return (GMR) began on Mar 30, 2018, with 322 Palestinians killed and 33 141 injured by December, 2019, and first-response health-care teams exposed to high levels of violence. The aims of this study were threefold: to explore the vulnerabilities of health workers to attacks during the GMR; to understand the effectiveness and comprehensiveness of systems for monitoring health attacks; and to identify potential strategies and interventions to improve protection.
Methods
WHO\'s Surveillance System for Attacks on Healthcare (SSA) verifies and records health attacks. We analysed SSA data for the Gaza Strip from Mar 30, 2018, to Dec 31, 2019, examining the number and type of attacks, the mechanisms of injury, and the distribution of attacks by gender, time, and location. We analysed the correlation of health worker injuries and deaths with total injuries and deaths of Palestinians during the GMR. We held interviews and focus groups with individuals working for organizations defined as partners contributing to the SSA in the Gaza Strip, to understand data comprehensiveness, the nature and impact of violence, and protection gaps and strategies.
Findings
During the study period, there were 567 confirmed incidents, in which three health workers were killed, 845 health workers were injured, and 129 ambulances and vehicles and 7 health facilities were damaged, including one hospital and three medical field stations. Of the total health personnel killed and injured, 166 of 848 (20%) were in the Gaza governorate, 274 (32%) were in the Khan Yunis governorate, 119 (14%) were in the middle governorate, 192 (22%) were in North governorate, and 96 (11%) were in the Rafah governorate. Of 845 injuries, 743 (88%) were in men, 45 (5%) were live ammunition injuries, 62 (7%) were rubber bullet injuries, 151 (18%) were gas canister injuries, 41 (5%) were shrapnel injuries, and 533 (64%) were gas inhalation injuries. Injuries and deaths among health workers correlated moderately (R2=0·54) with and accounted for 2% of the total. Qualitative findings highlighted the incidental and structural nature of violence, normalisation and under-reporting of attacks, the need for improved coordination of protection for health care, and gaps in the availability of protective equipment.
Interpretation
Health-care workers function at great personal risk. The correlation of attacks against health care with total injuries and deaths points to the need for alignment of efforts to protect health care with strategies to safeguard civilian populations, including protection of populations living under occupation and those engaged in civil demonstrations. Health-care workers identified the need for systemic measures to improve protection through training, monitoring, and coordination, and through linking of monitoring and documentation of health attacks with stronger accountability measures for prevention.
Funding
In 2017 and 2018, WHO\'s Right to Health Advocacy programme received funding from the Swiss Development Cooperation and the oPt Humanitarian Fund.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S19
Shehada W, Bouquet B, Nassar J, Briody C, ... Pollock A, Kim HJ
Lancet: 29 Jun 2021; 398:S19 | PMID: 34227950
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Impact:
Abstract

Development of a targeted client communication intervention for pregnant and post-partum women: a descriptive study.

Bogale B, Mørkrid K, O\'Donnell B, Ghanem B, ... Rabah Y, Frøen JF
Background
Targeted client communication using text messages can inform, motivate, and remind pregnant and postpartum women to use care in a timely way. The mixed results of previous studies of the effectiveness of targeted client communication highlight the importance of theory-based co-design with users. We planned, developed, and tested a theory-based intervention tailored to pregnant and postpartum women, to be automatically distributed via an electronic maternal and child health registry in occupied Palestinian territory.
Methods
We did 26 in-depth interviews with pregnant women and health-care providers in seven purposively selected public primary health-care clinics in the West Bank and Gaza to include clinics with different profiles. An interview guide was developed using the Health Belief Model to explore women\'s perceptions of high-risk conditions (anaemia, hypertension, diabetes, and fetal growth restriction) and timely attendance for antenatal care, as predefined by a national expert panel. We did thematic analyses of the interview data. Based on the results, we composed messages for a targeted client communication intervention, applying concepts from the Model of Actionable Feedback, social nudging, and enhanced active choice. We assessed the acceptability and understandability of the messages through unstructured interviews with local health promotion experts, health-care providers, and pregnant women.
Findings
The recurring themes indicated that most women were aware of the health consequences of anaemia, hypertension, and diabetes, but that they seldom associated these conditions with pregnancy. We identified knowledge gaps and low awareness of susceptibility to and severity of these complications and the benefits of timely antenatal care. The actionable messages were iteratively improved with stakeholder and end-user feedback after presenting the initial draft, and the messages deemed were understandable and acceptable based on reflections during unstructured assessment.
Interpretation
Following a stepwise iterative process by a theory-based approach and co-designing the intervention with users, we revealed elements critical to an efficacious targeted client communication intervention. A potential limitation of our study is that conducting in-depth interviews on several health conditions simultaneously might have reduced the depth of information we could have obtained. The strength of our study was that we assessed for, developed, and refined the intervention following recommended theoretical frameworks and best practices. The effectiveness of this intervention is under evaluation in a cluster-randomised trial (ISRCTN10520687).
Funding
European Research Council and Research Council of Norway.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S18
Bogale B, Mørkrid K, O'Donnell B, Ghanem B, ... Rabah Y, Frøen JF
Lancet: 29 Jun 2021; 398:S18 | PMID: 34227949
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Impact:
Abstract

The impact of e-health system implementation on UNWRA health services: an observational study.

Ballout G, Al-Shorbaji N, Zeidan W, Shahin Y, ... Albeik S, Seita A
Background
The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides primary-health-care services to more than 5 million Palestinian refugees in five operational fields (Jordan, Syria, Lebanon, West Bank, and Gaza) through 144 health centres. UNRWA developed its electronic health records (e-Health) system to improve monitoring and facilitation of health services provided to Palestinian refugees. By the end of 2017, the system had been deployed in 129 health centres, included the health files of 3 million patients, and managed more than 8 million visits per year. We assessed whether preventive-health-care services had improved following implementation of the system.
Methods
This observational study used three key performance indicators to assess preventive-health-care services reported in UNRWA\'s annual reports in 2012-17: the percentage of targeted people aged 40 years and older screened for diabetes; the percentage of pregnant women with a livebirth who attended at least four antenatal visits; and the prevalence of growth problems (underweight, stunting, wasting, and overweight or obesity) in children younger than 5 years. Simple descriptive analysis was conducted with Microsoft Excel 2010. Ethical approval was obtained from the UNRWA Headquarters Department of Health.
Findings
Screening for diabetes significantly increased from 13% in 2012 to 21% in 2017 (p<0·0001) since the e-Health system started sending alerts to clerks at health centres. The percentage of pregnant women with a livebirth who attended at least four antenatal visits, increased from 87% in 2012 to 92% in 2017, when the e-Health System allowed health-care providers to log all pregnant women who missed their appointments to enable follow-up. Additionally, an electronic maternal and child health mobile application, sends regular reminders to mothers about appointments for themselves and their children. The percentages of underweight, stunting, wasting, and overweight or obesity among children younger than 5 years increased respectively from 3%, 4%, 2%, and 2% in 2014 to 5%, 7%, 4%, and 5% in 2017, but this was due to the increased detection of growth problems through the e-Health system.
Interpretation
The e-Health system improved detection and monitoring by UNRWA health-care providers and access to health services for Palestinian refugees in all three indicator categories. This study has several limitations. It is an observational study based on assessing health records of children rather than a prospective study over time. The focus of the study was to assess the impact of the eHealth system on health-care delivery and not to assess the changes in health-care delivery itself. The electronic health records that were reviewed are for the Palestine refugees who are registered at UNRWA health clinics and not for other refugees or residents of the five countries. Strengths of the study are that it is based on electronic health records which contain data recorded by the treating staff; the e-health system used by UNRWA clinics staff is centralised and the data are aggregated agency wide; and the growth monitoring indicators used by UNRWA were derived from the WHO Multi-center Growth Reference Study to assess the growth of children from birth up to age 5 years.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S17
Ballout G, Al-Shorbaji N, Zeidan W, Shahin Y, ... Albeik S, Seita A
Lancet: 29 Jun 2021; 398:S17 | PMID: 34227948
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Impact:
Abstract

The experience of family carers of children with incurable cancer: a qualitative study from the occupied Palestinian territory.

Atout M, Alrimawi I, Abu Salameh E
Background
Treatments for childhood cancers have raised the survival rate, however different forms of malignancy continue to cause untimely deaths, and cancer remains a leading cause of death among children. Global research on paediatric cancer is limited for several reasons. Most research has focused on specific methodologies, including questionnaires with heterogeneous samples. In addition, many studies have covered a broad range of cancer diagnoses, and a wide range of children\'s ages and periods between diagnosis and treatment. These methods are unable to capture the essence of experiences and cultural differences. This study aimed to explore the experience of family carers of children with incurable cancer in occupied Palestinian territory.
Methods
The study was conducted in the Paediatric Cancer Department of Beit Jala Hospital, which is the first public cancer department for children in the West Bank. The family carers of children aged 1-18 years with any type of incurable cancer in this hospital were considered eligible for participation, and the individual most involved in the care of the child was selected. To recruit participants, head nurses of medical and surgical paediatric floors provided assistance in approaching the carers of eligible children. The main objectives of the study were then discussed with the family carers. Semi-structured interviews were conducted with participants, and an interpretative phenomenological analysis approach was used to analyse the collected information. Ethical approval was obtained from the Beit Jala Hospital ethical review board and written informed consent was obtained from all participants.
Findings
14 interviews were conducted. Participants were nine mothers, four grandmothers, and one father. Family carers discussed their caring experiences, including their experiences in administering special treatments, their suffering due to treating irritable children, and the information given to them about their children\'s illness. Family carers reported that they changed the focus of their care from an initial emphasis on normalising their children\'s lives to relieving their physical and psychological discomfort. This change of focus accompanied changes in carers\' understanding of their child\'s disease over time. As carers became more realistic regarding the future of their children, they attempted to make their lives as comfortable as possible. Finally, carers discussed the support system around them; they found several resources to support them in the care of their children, including the experiences of other parents of children with similar diseases, the hospital environment, and their religious beliefs. Nevertheless, they stated that they needed more support during this difficult time of their lives.
Interpretation
There is a need to support parents of children with incurable cancer in the occupied Palestinian territory. Suggestions to improve the quality of care provided for these parents include the education and recruitment of health care professionals, including social workers and psychologists, to provide emotional and spiritual support.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S16
Atout M, Alrimawi I, Abu Salameh E
Lancet: 29 Jun 2021; 398:S16 | PMID: 34227947
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Abstract

The prevalence of diabetic peripheral neuropathy among diabetic Palestinian refugees in the Nuzha area, Jordan: a cross-sectional study.

Atallah SM, Al-Jaghbir MT, Zayed AA
Background
Diabetic peripheral neuropathy (DPN) is the most common type of diabetic neuropathy. It accounts for significant morbidity, including lower extremity amputations. There are few studies on the prevalence of DPN among Palestinian refugees in Jordan. This study aimed to determine the prevalence of DPN and its associated factors among Palestinian refugees with diabetes in the Nuzha area of Jordan, using the Michigan Neuropathy Screening Instrument (MNSI).
Methods
A cross-sectional study was conducted at the UNRWA Nuzha Health Centre, Amman, Jordan, during the first quarter of 2016 (Jan 2-Mar 31, 2016). The Nuzha Health Centre was randomly chosen from the UNRWA clinics in Jordan. Study participants were selected by systematic random sampling. The number of participants was decided with Cochran\'s formula and adjusting the sample size by use of the finite population correction equation. 343 patients with diabetes were assessed for DPN using the history and physical assessment sections of the MNSI. We generated descriptive statistics, and tested for associations between variables using univariate and multivariate logistic regression analysis to identify the best subset of predictors for the presence of DPN. We used SPSS version 22 to input and analyse data. This study was approved by the UNRWA Jordan Field Office and the Institutional Review Board at the University of Jordan, and by the Michigan Diabetes Research Centre, which gave its permission to use the MNSI. Written informed consent was obtained from each participant.
Findings
Prevalence of DPN was 11% (37 of 343) based on the history section and 36% (122 of 343) based on the physical assessment section of the MNSI. Multivariate logistic regression revealed that significant predictors for DPN based on the history section of the MNSI were education level and duration of diabetes. Compared with participants with no education, the odds ratio (OR) for DPN was 0·13 (95% CI 0·04-0·49, p=0·0023) for participants with elementary education, 0·11 (0·03-0·49, p=0·0035) for those with high school education, and 0·04 (0·01-0·41, p=0·0070) for those with a diploma. Compared with participants who had diabetes for less than 10 years, the OR for DPN was 7·69 (1·99-30·30, p=0·0031) for those who had diabetes for 10-19 years and 32·26 (6·76-142·86, p<0·0001) for those who had diabetes for 20 years or longer. However, the predictors for DPN based on the physical assessment part of MNSI were age, duration of diabetes, and type of treatment for diabetes. Compared with participants aged 70 years or older, the OR for DPN was 0·18 (0·04-0·89, p=0·036) for those aged 40-49 years and 0·22 (0·06-0·82, p=0·024) for those aged 50-59 years. Compared with participants who had diabetes for less than 10 years, the OR for DPN was 32·26 (13·70-76·92, p<0·0001) for those who had diabetes for 10-19 years and 200 (34·48-1000, p<0·0001) for those who had diabetes for 20 years or longer. The OR for DPN was 0·23 (0·08-0·70, p=0·0094) for participants who were treated with oral hypoglycemic agents alone, compared those who were treated with insulin and oral hypoglycaemic agents.
Interpretation
The prevalence of DPN is high among Palestinian refugees with diabetes in the Nuzha area, Jordan, consistent with the results of other studies of DPN in individuals with diabetes. There is a need for early detection and regular screening for DPN in patients with diabetes, with special attention given to patients with risk factors for DPN.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S15
Atallah SM, Al-Jaghbir MT, Zayed AA
Lancet: 29 Jun 2021; 398:S15 | PMID: 34227946
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Impact:
Abstract

Visual outcomes associated with delay from trauma to surgery for open globe eye injury in Palestine: a retrospective chart review study.

Amro MY
Background
Open globe eye injuries have poor visual outcomes. In Palestine, no studies have completely described the impact of time delays to surgery on visual outcomes. This study examines the causal factors for open globe eye injuries, time to presentation, and the effects of delays to surgery on visual outcomes.
Methods
A retrospective review was carried out of 413 patients with monocular open globe eye injuries attending St John Eye Hospital, Jerusalem, occupied Palestine territory, from Jan 1, 2000, to Dec 31, 2005. Injury cause, time to presentation, visual acuity on arrival, and the final corrected visual outcomes were assessed.
Findings
Open globe eye injuries were caused by traumatic injury during the Intifada in 2002 (13%) and military actions throughout the study period (14%), but most injuries (38%) occurred in workplace or were related to domestic eye injuries (20%). The median time from open globe eye injury to arrival at hospital was 4 hours (IQR 11-3); 290 (70%) of 413 patients arrived within 8 h of injury. Visual acuity on arrival was normal only in five eyes (1·2%), functionally accepted vision in 42 eyes (10%), visually impaired in 77 eyes (18.6%), blindness in 229 (55%), and difficult to measure in 60 (15%). Surgical repair was performed in 366 eyes (89%) and 47 (11%) eyes were removed. After surgery, visual status was classified as visual acuity impaired in 85 (20·6%) of 336 repaired eyes, blindness in 87 (21%), normal vision restored in 58 eyes (14%), functionally acceptable vision restored in 116 eyes (28%), difficult to measure in 20 (4·8%). Among the 290 patients who presented within 8 h of injury, the final visual outcomes were impaired visual acuity in 72 (25%), blindness in 71 (24%), eye removed in 38 (13%), and visual acuity difficult to measure due to very young age or devastating injury remaining after surgery in 14 (4.8%) and vision was restored in 95 (33%).
Interpretation
Despite the devastating nature of open globe eye injury, minimum time from trauma to surgical intervention could save the injured eyes. Further studies should investigate whether delay in surgery affects outcomes in relation to the severity of injuries, as this study is cross-sectional and longitudinal epidemiological studies might yield better interpretations.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S14
Amro MY
Lancet: 29 Jun 2021; 398:S14 | PMID: 34227945
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Impact:
Abstract

Clinical audit as a quality improvement tool in the Gaza Strip: an audit of audits.

Alyacoubi S, Böttcher B, Albarqouni L, Elessi K
Background
Clinical audit plays a fundamental role in improving the quality of patient care and hence, is considered a cornerstone of clinical governance. This quality improvement tool is newly introduced in the health-care system of the Gaza Strip. Although the number of audits completed in Gaza has been increasing over the past few years, little evidence is available of subsequent quality improvements in practice.
Methods
An online survey was used to collect information on the audit team, location, applied methods, outcomes, presentation of data, and reaudit. Medical students and health-care professionals who had conducted audits between 2015 and 2018 were invited to complete the survey from Oct 12 to Nov 2, 2018.
Findings
Data on 62 audits were collected. Training in clinical governance was received by 55 auditors (89%) and a senior supervisor was available in 56 audits (90%). Audits were performed across different hospitals and specialties: 18 (29%) in obstetrics, 16 (26%) in medicine, and 11 (18%) in each of surgery and paediatrics, with six (10%) in other specialties. A clear trend of increasing numbers of audits was observed, with four (6%) having been done in 2015, 12 (19%) in 2016, 22 (35%) in 2017, and 24 audits (39%) in 2018. Students were involved in 46 audits (74%) whereas practising doctors were involved in only 29 audits (47%). 17 (27.4%) audits were done at more than one health-care facility and the remaining audits were done at one of 13 other main hospitals or community centres across the Gaza Strip. Clear standards were identified in 54 audits (90%) while eight audits (13%) reported not setting standards at all. Improvement of documentation was recommended in 44 audits (71%), development of national guidelines in 37 (60%), and staff training in 32 (52%). Only 32 audits (51.6%) were presented to the local staff. The audit cycle was completed in 13 projects (20.9%) with only seven of them reporting subsequent improvements in practice.
Interpretation
A rise in the numbers of audits reflects a growing awareness of their key role in health care and patients\' safety. However, completion of audit cycles and the actual implementation of recommendations are lagging. Therefore, more focused efforts supported by both clinical and administrative leaderships are needed to implement changes and ensure continuous evaluation of their effectiveness.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S13
Alyacoubi S, Böttcher B, Albarqouni L, Elessi K
Lancet: 29 Jun 2021; 398:S13 | PMID: 34227944
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Impact:
Abstract

Awareness and prevalence of needle stick injuries among cleaners and health-care providers in Gaza Strip hospitals: a cross-sectional study.

Alwali A, Shaheen A, Ahmed M, Mansour Z, ... Hamouda M, Böttcher B
Background
Needle stick injuries (NSIs) are preventable hazards that can be avoided with appropriate staff training and safety systems. We assessed the prevalence and awareness of NSIs among health-care workers and cleaners in hospitals in Gaza.
Methods
We did a cross-sectional study in four hospitals from July 14 to Oct 25, 2018. All cleaners and health-care workers were eligible to participate. Data were gathered via a survey tool designed for the study that covered sociodemographic data, NSI prevalence, and response to possible injuries. The primary outcomes were prevalence and staff awareness of NSIs.
Findings
538 staff participated in the survey, among whom the mean age was 28.9 (SD 7.71) years, 331 (62%) were men, 119 (22%) were doctors, 262 (49%) were nurses, 72 (13%) were medical students, and 85 (16%) were cleaners. 289 participants (54%) had had at least one NSI: 59 doctors (50% of all doctors), 142 nurses (54%), 32 students (44%), and 56 cleaners (66%). NSIs were obtained during various activities, including 168 incidents (40%) during drug administration, 82 (20%) while recapping needles, 78 (19%) during wound suturing, 63 (15%) while cleaning, and 27 (6%) during arterial blood gas sampling. Only 94 (33%) of 289 participants with NSIs reported their injuries. Among the 195 (67%) participants who did not report NSIs, 41 (21%) did not know that they should do so, 65 (33%) did not know how to report, 62 (32%) believed that reporting was useless, and 27 (14%) forgot to report.
Interpretation
More than half the participants had had NSIs, but reporting of injuries was low. The Ministry of Health should provide targeted interventions and training to improve risk awareness and understanding of the importance of reporting for health-care employees. The strengths of this study are the large sample size and recruitment from diverse professional backgrounds. The main limitation was the lack of validation of the study instrument.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S12
Alwali A, Shaheen A, Ahmed M, Mansour Z, ... Hamouda M, Böttcher B
Lancet: 29 Jun 2021; 398:S12 | PMID: 34227943
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Impact:
Abstract

Assessment of pain control among patients with cancer in hospitals of the Gaza Strip: a cross-sectional study.

Alswerki MN, Alwali A, Al-Aqad A, Hamouda M, ... Elshami M, Elessi K
Background
Poor control of cancer pain is a major public health problem worldwide. Many potential barriers can lead to suboptimal treatment of cancer pain. One such barrier is inadequate measurement and assessment of cancer-related pain control. This study aimed to assess current pain control and management for hospitalized adult patients with cancer in the Gaza Strip.
Methods
A cross-sectional study was conducted from Dec 10, 2017, to April 25, 2018, in the Gaza Strip. The validated Brief Pain Inventory (BPI) questionnaire was translated into Arabic for data collection. The first section of the questionnaire described the patients\' sociodemographic characteristics, the second evaluated the severity of cancer, and the third assessed the interference of pain with daily activities. A ten-point Likert scale was used to evaluate the magnitude of cancer pain and its impact on the patients\' lifestyle. Participants were 12 years of age and older, and were patients with cancer who had been admitted to Al-Rantisi Hospital or European Gaza Hospital (the two cancer institutes available in the Gaza Strip), and who had no mental illness or disorder affecting pain perception. Convenience sampling was used to recruit eligible patients for face-to-face interviews to complete the questionnaire. The primary outcome was the median score of cancer pain control. Ethical approval was obtained from the Palestinian Ministry of Health and informed verbal consent was obtained from patients. Data were analysed with SPSS version 22.
Findings
97 patients were assessed, of whom 75% (73 of 97) were eligible and were recruited. The sample size was decided based on the available cases in the included centres during study period. The median age was 49 years (IQR 37-60), 56% (41 of 73) were females, and 86% (63 of 73) were married. Most (81%; 59 of 73) had an educational level of high school or below, and 52% (38 of 73) were unemployed. 90% of patients (66 of 73) had cancer pain as a presenting symptom at diagnosis. 93% (68 of 73) had received painkillers (analgesics) within the past week, 74% (54 of 73) were using analgesics daily, and 43% (31 of 73) reported that they needed potent analgesics. 15% (11 of 73) reported concerns about analgesic addiction. The level of functional impairment owing to pain, as reported using the ten-point Likert scale, was highest for daily activities and routines (median 9·0, IQR 7·0-10·0) and least for social relationships (5·0, 0·0-9·0). There was no statistically significantly association between cancer-related pain and gender, educational level, or occupation.
Interpretation
Most patients were taking analgesics but a large proportion reported the need for more potent or frequent doses of painkillers. In addition, pain had a significant effect on the patients\' lifestyle. These findings indicate poor control of cancer pain. There is an urgent need to address the reasons for this, to alleviate pain and to improve quality of life.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S11
Alswerki MN, Alwali A, Al-Aqad A, Hamouda M, ... Elshami M, Elessi K
Lancet: 29 Jun 2021; 398:S11 | PMID: 34227942
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Impact:
Abstract

The motives, academic performance, and career prospects of Gazan medical students abroad: a cross-sectional study.

Alser M, Alkhatib M, Alnakhala A, Barhoom MI
Background
In Gaza, 2 million people have been affected by more than 13 years of strict land, air, and sea blockades and three wars, during which over 4000 people have been killed and many more have been injured. Additional severe effects have been seen on lives, aspirations, and prospects. Given the conditions, medical students have many competing reasons for and against studying medicine abroad. We investigated motives, academic situations, and future plans of the upcoming generation of doctors in Gaza, occupied Palestinian territory.
Methods
We did a questionnaire-based cross-sectional study involving Palestinian medical students originally from Gaza who were studying at the largest five medical schools in Egypt (Cairo, Ain Shams, Alexandria, Mansoura, and Zagazig Universities). We used a self-designed questionnaire developed from previous similar studies and created on Google Forms (Google, Menlo Park, CA, USA). A pilot study of 37 participants was done to test the comprehensibility of questions and the time needed to complete the questionnaire. After being updated, the questionnaire was distributed in August and September, 2018, to individuals who provided verbal informed decision to participate. Analysis of the results was performed with SPSS version 22.
Findings
Of 453 questionnaires given to students, 340 (75%) were returned completed. The mean age of respondents was 21·7 (SD 1·8) years; 225 (66%) were men and 115 (34%) were women. Excellence was achieved in secondary school examinations (result ≥90%) by 315 (93%) of students, but only 26 (8%) of students achieved excellence in their first year of medical school (examination results ≥85%). 317 students (93%) reported that they chose their medical schools independently without pressure from their families. Among the 115 women, 70 (61%) went to a third party to persuade their parents to allow them to study abroad. Of ten motives to study medicine given in the questionnaire, \"to relieve pains\" and \"childhood dream\" were the most frequently selected among the 340 respondents, chosen by 228 (67%) and 208 (61%), respectively. 104 (31%) reported they were seeking freedom more than to study medicine. 214 (63%) of students had at least one relative who had been physically injured in or killed during of one of the wars in Gaza. Most students (n=278 [82%]) were delayed from starting at their medical school due to border closures and 189 (56%) had been unable to attend for at least one semester. Since starting at medical school, 269 (79%) of 340 respondents had visited Gaza only once or not at all. 55 (16%) intended never return to Gaza and 209 (62%) reported that they wanted to specialise and work abroad for a period and then return to Gaza. Of the remainder, 64 (19%) wanted to specialise abroad then return to work in Gaza, and 12 (3%) wanted to specialise and work in Gaza.
Interpretation
The motives, academic performance, and career prospects of Gazan medical students studying in Egypt are influenced in many ways by the situation in Gaza, some of which could worsen the already bad condition of medical care in Gaza. Awareness and supportive programmes for Gazan medical students should be encouraged to improve the quality of health care providers in Gaza.
Funding
None.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 29 Jun 2021; 398:S10
Alser M, Alkhatib M, Alnakhala A, Barhoom MI
Lancet: 29 Jun 2021; 398:S10 | PMID: 34227941
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Impact:
Abstract

Physical punishment and child outcomes: a narrative review of prospective studies.

Heilmann A, Mehay A, Watt RG, Kelly Y, ... van Turnhout J, Gershoff ET
Physical punishment is increasingly viewed as a form of violence that harms children. This narrative review summarises the findings of 69 prospective longitudinal studies to inform practitioners and policy makers about physical punishment\'s outcomes. Our review identified seven key themes. First, physical punishment consistently predicts increases in child behaviour problems over time. Second, physical punishment is not associated with positive outcomes over time. Third, physical punishment increases the risk of involvement with child protective services. Fourth, the only evidence of children eliciting physical punishment is for externalising behaviour. Fifth, physical punishment predicts worsening behaviour over time in quasi-experimental studies. Sixth, associations between physical punishment and detrimental child outcomes are robust across child and parent characteristics. Finally, there is some evidence of a dose-response relationship. The consistency of these findings indicates that physical punishment is harmful to children and that policy remedies are warranted.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 27 Jun 2021; epub ahead of print
Heilmann A, Mehay A, Watt RG, Kelly Y, ... van Turnhout J, Gershoff ET
Lancet: 27 Jun 2021; epub ahead of print | PMID: 34197808
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Impact:
Abstract

Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.

Spertus JA, Fine JT, Elliott P, Ho CY, ... Sehnert AJ, Jacoby D
Background
Improving symptoms is a primary treatment goal in patients with obstructive hypertrophic cardiomyopathy. Currently available pharmacological options for hypertrophic cardiomyopathy are not disease-specific and are often inadequate or poorly tolerated. We aimed to assess the effect of mavacamten, a first-in-class cardiac myosin inhibitor, on patients\' health status-ie, symptoms, physical and social function, and quality of life.
Methods
We did a health status analysis of EXPLORER-HCM, a phase 3, double-blind, randomised, placebo-controlled trial. The study took place at 68 clinical cardiovascular centres in 13 countries. Adult patients (≥18 years) with symptomatic obstructive hypertrophic cardiomyopathy (gradient ≥50 mm Hg and New York Heart Association class II-III) were randomly assigned (1:1) to mavacamten or placebo for 30 weeks, followed by an 8-week washout period. Both patients and staff were masked to study treatment. The primary outcome for this secondary analysis was the Kansas City Cardiomyopathy Questionnaire (KCCQ), a well validated disease-specific measure of patients\' health status. It was administered at baseline and weeks 6, 12, 18, 30 (end of treatment), and 38 (end of study). Changes from baseline to week 30 in KCCQ overall summary (OS) score and all subscales were analysed using mixed model repeated measures. This study is registered with ClinicalTrials.gov, NCT03470545.
Findings
Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned. Of 123 patients randomly assigned to mavacamten, 92 (75%) completed the KCCQ at baseline and week 30 and of the 128 patients randomly assigned to placebo 88 (69%) completed the KCCQ at baseline and week 30. At 30 weeks, the change in KCCQ-OS score was greater with mavacamten than placebo (mean score 14·9 [SD 15·8] vs 5·4 [13·7]; difference +9·1 [95% CI 5·5-12·8]; p<0·0001), with similar benefits across all KCCQ subscales. The proportion of patients with a very large change (KCCQ-OS ≥20 points) was 36% (33 of 92) in the mavacamten group versus 15% (13 of 88) in the placebo group, with an estimated absolute difference of 21% (95% CI 8·8-33·4) and number needed to treat of five (95% CI 3-11). These gains returned to baseline after treatment was stopped.
Interpretation
Mavacamten markedly improved the health status of patients with symptomatic obstructive hypertrophic cardiomyopathy compared with placebo, with a low number needed to treat for marked improvement. Given that the primary goals of treatment are to improve symptoms, physical and social function, and quality of life, mavacamten represents a new potential strategy for achieving these goals.
Funding
MyoKardia, a Bristol Myers Squibb company.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 25 Jun 2021; 397:2467-2475
Spertus JA, Fine JT, Elliott P, Ho CY, ... Sehnert AJ, Jacoby D
Lancet: 25 Jun 2021; 397:2467-2475 | PMID: 34004177
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Impact:
Abstract

Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial.

Koo BK, Kang J, Park KW, Rhee TM, ... Kim HS, HOST-EXAM investigators
Background
Optimal antiplatelet monotherapy during the chronic maintenance period in patients who undergo coronary stenting is unknown. We aimed to compare head to head the efficacy and safety of aspirin and clopidogrel monotherapy in this population.
Methods
We did an investigator-initiated, prospective, randomised, open-label, multicentre trial at 37 study sites in South Korea. We enrolled patients aged at least 20 years who maintained dual antiplatelet therapy without clinical events for 6-18 months after percutaneous coronary intervention with drug-eluting stents (DES). We excluded patients with any ischaemic and major bleeding complications. Patients were randomly assigned (1:1) to receive a monotherapy agent of clopidogrel 75 mg once daily or aspirin 100 mg once daily for 24 months. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater, in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02044250.
Findings
Between March 26, 2014, and May 29, 2018, we enrolled 5530 patients. 5438 (98·3%) patients were randomly assigned to either the clopidogrel group (2710 [49·8%]) or to the aspirin group (2728 [50·2%]). Ascertainment of the primary endpoint was completed in 5338 (98·2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5·7%) patients in the clopidogrel group and 207 (7·7%) in the aspirin group (hazard ratio 0·73 [95% CI 0·59-0·90]; p=0·0035).
Interpretation
Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention with DES significantly reduced the risk of the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and BARC bleeding type 3 or greater. In patients requiring indefinite antiplatelet monotherapy after percutaneous coronary intervention, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events.
Funding
ChongKunDang, SamJin, HanMi, DaeWoong, and the South Korea Ministry of Health and Welfare.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 25 Jun 2021; 397:2487-2496
Koo BK, Kang J, Park KW, Rhee TM, ... Kim HS, HOST-EXAM investigators
Lancet: 25 Jun 2021; 397:2487-2496 | PMID: 34010616
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Impact:
Abstract

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial.

Azizi M, Sanghvi K, Saxena M, Gosse P, ... Kirtane AJ, RADIANCE-HTN investigators
Background
Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications.
Methods
In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426.
Findings
Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups.
Interpretation
Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension.
Funding
ReCor Medical.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 25 Jun 2021; 397:2476-2486
Azizi M, Sanghvi K, Saxena M, Gosse P, ... Kirtane AJ, RADIANCE-HTN investigators
Lancet: 25 Jun 2021; 397:2476-2486 | PMID: 34010611
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Impact:
Abstract

Chronic kidney disease.

Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V
Chronic kidney disease is a progressive disease with no cure and high morbidity and mortality that occurs commonly in the general adult population, especially in people with diabetes and hypertension. Preservation of kidney function can improve outcomes and can be achieved through non-pharmacological strategies (eg, dietary and lifestyle adjustments) and chronic kidney disease-targeted and kidney disease-specific pharmacological interventions. A plant-dominant, low-protein, and low-salt diet might help to mitigate glomerular hyperfiltration and preserve renal function for longer, possibly while also leading to favourable alterations in acid-base homoeostasis and in the gut microbiome. Pharmacotherapies that alter intrarenal haemodynamics (eg, renin-angiotensin-aldosterone pathway modulators and SGLT2 [SLC5A2] inhibitors) can preserve kidney function by reducing intraglomerular pressure independently of blood pressure and glucose control, whereas other novel agents (eg, non-steroidal mineralocorticoid receptor antagonists) might protect the kidney through anti-inflammatory or antifibrotic mechanisms. Some glomerular and cystic kidney diseases might benefit from disease-specific therapies. Managing chronic kidney disease-associated cardiovascular risk, minimising the risk of infection, and preventing acute kidney injury are crucial interventions for these patients, given the high burden of complications, associated morbidity and mortality, and the role of non-conventional risk factors in chronic kidney disease. When renal replacement therapy becomes inevitable, an incremental transition to dialysis can be considered and has been proposed to possibly preserve residual kidney function longer. There are similarities and distinctions between kidney-preserving care and supportive care. Additional studies of dietary and pharmacological interventions and development of innovative strategies are necessary to ensure optimal kidney-preserving care and to achieve greater longevity and better health-related quality of life for these patients.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 23 Jun 2021; epub ahead of print
Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL, Perkovic V
Lancet: 23 Jun 2021; epub ahead of print | PMID: 34175022
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Impact:
Abstract

Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.

Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, ... Martin T, Jagannath S
Background
CARTITUDE-1 aimed to assess the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma with poor prognosis.
Methods
This single-arm, open-label, phase 1b/2 study done at 16 centres in the USA enrolled patients aged 18 years or older with a diagnosis of multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0·75 × 106 CAR-positive viable T cells per kg) was administered 5-7 days after start of lymphodepletion. The primary endpoints were safety and confirmation of the recommended phase 2 dose (phase 1b), and overall response rate (phase 2) in all patients who received treatment. Key secondary endpoints were duration of response and progression-free survival. This trial is registered with ClinicalTrials.gov, NCT03548207.
Findings
Between July 16, 2018, and Oct 7, 2019, 113 patients were enrolled. 97 patients (29 in phase 1b and 68 in phase 2) received a cilta-cel infusion at the recommended phase 2 dose of 0·75 × 106 CAR-positive viable T cells per kg. As of the Sept 1, 2020 clinical cutoff, median follow-up was 12·4 months (IQR 10·6-15·2). 97 patients with a median of six previous therapies received cilta-cel. Overall response rate was 97% (95% CI 91·2-99·4; 94 of 97 patients); 65 (67%) achieved stringent complete response; time to first response was 1 month (IQR 0·9-1·0). Responses deepened over time. Median duration of response was not reached (95% CI 15·9-not estimable), neither was progression-free survival (16·8-not estimable). The 12-month progression-free rate was 77% (95% CI 66·0-84·3) and overall survival rate was 89% (80·2-93·5). Haematological adverse events were common; grade 3-4 haematological adverse events were neutropenia (92 [95%] of 97 patients), anaemia (66 [68%]), leukopenia (59 [61%]), thrombocytopenia (58 [60%]), and lymphopenia (48 [50%]). Cytokine release syndrome occurred in 92 (95%) of 97 patients (4% were grade 3 or 4); with median time to onset of 7·0 days (IQR 5-8) and median duration of 4·0 days (IQR 3-6). Cytokine release syndrome resolved in all except one with grade 5 cytokine release syndrome and haemophagocytic lymphohistiocytosis. CAR T-cell neurotoxicity occurred in 20 (21%) patients (9% were grade 3 or 4). 14 deaths occurred in the study; six due to treatment-related adverse events, five due to progressive disease, and three due to treatment-unrelated adverse events.
Interpretation
A single cilta-cel infusion at the target dose of 0·75 × 106 CAR-positive viable T cells per kg led to early, deep, and durable responses in heavily pretreated patients with multiple myeloma with a manageable safety profile. The data from this study formed the basis for recent regulatory submissions.
Funding
Janssen Research & Development and Legend Biotech.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 23 Jun 2021; epub ahead of print
Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, ... Martin T, Jagannath S
Lancet: 23 Jun 2021; epub ahead of print | PMID: 34175021
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Impact:
Abstract

Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions.

McGinley MP, Cohen JA
The sphingosine 1-phosphate (S1P) signalling pathways have important and diverse functions. S1P receptors (S1PRs) have been proposed as a therapeutic target for various diseases due to their involvement in regulation of lymphocyte trafficking, brain and cardiac function, vascular permeability, and vascular and bronchial tone. S1PR modulators were first developed to prevent rejection by the immune system following renal transplantation, but the only currently approved indication is multiple sclerosis. The primary mechanism of action of S1PR modulators in multiple sclerosis is through binding S1PR subtype 1 on lymphocytes resulting in internalisation of the receptor and loss of responsiveness to the S1P gradient that drives lymphocyte egress from lymph nodes. The reduction in circulating lymphocytes presumably limits inflammatory cell migration into the CNS. Four S1PR modulators (fingolimod, siponimod, ozanimod, and ponesimod) have regulatory approval for multiple sclerosis. Preclinical evidence and ongoing and completed clinical trials support development of S1PR modulators for other therapeutic indications.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 23 Jun 2021; epub ahead of print
McGinley MP, Cohen JA
Lancet: 23 Jun 2021; epub ahead of print | PMID: 34175020
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Impact:
Abstract

The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030.

Vogel B, Acevedo M, Appelman Y, Bairey Merz CN, ... Zühlke L, Mehran R
Cardiovascular disease is the leading cause of death in women. Decades of grassroots campaigns have helped to raise awareness about the impact of cardiovascular disease in women, and positive changes affecting women and their health have gained momentum. Despite these efforts, there has been stagnation in the overall reduction of cardiovascular disease burden for women in the past decade. Cardiovascular disease in women remains understudied, under-recognised, underdiagnosed, and undertreated. This Commission summarises existing evidence and identifies knowledge gaps in research, prevention, treatment, and access to care for women. Recommendations from an international team of experts and leaders in the field have been generated with a clear focus to reduce the global burden of cardiovascular disease in women by 2030. This Commission represents the first effort of its kind to connect stakeholders, to ignite global awareness of sex-related and gender-related disparities in cardiovascular disease, and to provide a springboard for future research.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 18 Jun 2021; 397:2385-2438
Vogel B, Acevedo M, Appelman Y, Bairey Merz CN, ... Zühlke L, Mehran R
Lancet: 18 Jun 2021; 397:2385-2438 | PMID: 34010613
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Impact:
Abstract

Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019.

GBD 2019 Tobacco Collaborators
Background
Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally.
Methods
We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available.
Findings
Globally in 2019, 1·14 billion (95% uncertainty interval 1·13-1·16) individuals were current smokers, who consumed 7·41 trillion (7·11-7·74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27·5% [26·5-28·5] reduction) and females (37·7% [35·4-39·9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0·99 billion (0·98-1·00) in 1990. Globally in 2019, smoking tobacco use accounted for 7·69 million (7·16-8·20) deaths and 200 million (185-214) disability-adjusted life-years, and was the leading risk factor for death among males (20·2% [19·3-21·1] of male deaths). 6·68 million [86·9%] of 7·69 million deaths attributable to smoking tobacco use were among current smokers.
Interpretation
In the absence of intervention, the annual toll of 7·69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a clear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens.
Funding
Bloomberg Philanthropies and the Bill & Melinda Gates Foundation.

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Lancet: 18 Jun 2021; 397:2337-2360
GBD 2019 Tobacco Collaborators
Lancet: 18 Jun 2021; 397:2337-2360 | PMID: 34051883
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Impact:
Abstract

Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.

Moreau P, Dimopoulos MA, Mikhael J, Yong K, ... Martin T, IKEMA study group
Background
Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone for relapsed or refractory multiple myeloma. This phase 3, open-label study compared the efficacy of isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma.
Methods
This was a prospective, randomised, open-label, parallel-group, phase 3 study done at 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients with relapsed or refractory multiple myeloma aged at least 18 years who had received one to three previous lines of therapy and had measurable serum or urine M-protein were eligible. Patients were randomly assigned (3:2) to isatuximab plus carfilzomib-dexamethasone (isatuximab group) or carfilzomib-dexamethasone (control group). Patients in the isatuximab group received isatuximab 10 mg/kg intravenously weekly for the first 4 weeks, then every 2 weeks. Both groups received the approved schedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatment continued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assigned treatment. Safety was assessed in all patients who received at least one dose according to treatment received. The study is registered at ClinicalTrials.gov, NCT03275285.
Findings
Between Nov 15, 2017, and March 21, 2019, 302 patients with a median of two previous lines of therapy were enrolled. 179 were randomly assigned to the isatuximab group and 123 to the control group. Median progression-free survival was not reached in the isatuximab group compared with 19·15 months (95% CI 15·77-not reached) in the control group, with a hazard ratio of 0·53 (99% CI 0·32-0·89; one-sided p=0·0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 136 (77%) of 177 patients in the isatuximab group versus 82 (67%) of 122 in the control group, serious TEAEs occurred in 105 (59%) versus 70 (57%) patients, and TEAEs led to discontinuation in 15 (8%) versus 17 (14%) patients. Fatal TEAEs during study treatment occurred in six (3%) versus four (3%) patients.
Interpretation
The addition of isatuximab to carfilzomib-dexamethasone significantly improves progression-free survival and depth of response in patients with relapsed multiple myeloma, representing a new standard of care for this patient population.
Funding
Sanofi. VIDEO ABSTRACT.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 18 Jun 2021; 397:2361-2371
Moreau P, Dimopoulos MA, Mikhael J, Yong K, ... Martin T, IKEMA study group
Lancet: 18 Jun 2021; 397:2361-2371 | PMID: 34097854
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Impact:
Abstract

Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial.

Feagan BG, Danese S, Loftus EV, Vermeire S, ... Hibi T, Peyrin-Biroulet L
Background
The global prevalence of ulcerative colitis is increasing, and induction and maintenance of remission is a crucial therapeutic goal. We assessed the efficacy and safety of filgotinib, a once-daily, oral Janus kinase 1 preferential inhibitor, for treatment of ulcerative colitis.
Methods
This phase 2b/3, double-blind, randomised, placebo-controlled trial including two induction studies and one maintenance study was done in 341 study centres in 40 countries. Eligible patients were aged 18-75 years with moderately to severely active ulcerative colitis for at least 6 months before enrolment (induction study A: inadequate clinical response, loss of response to or intolerance to corticosteroids or immunosuppressants, naive to tumour necrosis factor [TNF] antagonists and vedolizumab [biologic-naive]; induction study B: inadequate clinical response, loss of response to or intolerance to any TNF antagonist or vedolizumab, no TNF antagonist or vedolizumab use within 8 weeks before screening [biologic-experienced]). Patients were randomly assigned 2:2:1 to receive oral filgotinib 200 mg, filgotinib 100 mg, or placebo once per day for 11 weeks. Patients who had either clinical remission or a Mayo Clinic Score response at week 10 in either induction study entered the maintenance study. Patients who received induction filgotinib were rerandomised 2:1 to continue their induction filgotinib regimen or to placebo. Patients who received induction placebo continued receiving placebo. The primary endpoint was clinical remission by Mayo endoscopic, rectal bleeding, and stool frequency subscores at weeks 10 and 58. For the induction studies, efficacy was assessed in all randomised patients who received at least one dose of study drug or placebo within that study. For the maintenance study, efficacy was assessed in all patients randomised to any filgotinib treatment group in the induction studies who received at least one dose of study drug or placebo in the maintenance study. Patients who received placebo throughout the induction and maintenance study were not included in the full analysis set for the maintenance study. Safety was assessed in all patients who received at least one dose of the study drug or placebo within each study. This trial is registered with ClinicalTrials.gov, NCT02914522.
Findings
Between Nov 14, 2016, and March 31, 2020, we screened 2040 patients for eligibility. 659 patients enrolled in induction study A were randomly assigned to receive filgotinib 100 mg (n=277), filgotinib 200 mg (n=245), or placebo (n=137). 689 patients enrolled into induction study B were randomly assigned to receive filgotinib 100 mg (n=285), filgotinib 200 mg (n=262), or placebo (n=142). 34 patients in induction study A and 54 patients in induction study B discontinued the study drug before week 10. After efficacy assessment at week 10, 664 patients entered the maintenance study (391 from induction study A, 273 from induction study B). 93 patients continued to receive placebo. 270 patients who had received filgotinib 100 mg in the induction study were randomly assigned to receive filgotinib 100 mg (n=179) or placebo (n=91). 301 patients who had received filgotinib 200 mg in the induction study were randomly assigned to receive filgotinib 200 mg (n=202) or placebo (n=99). 263 patients discontinued treatment in the maintenance study. At week 10, a greater proportion of patients given filgotinib 200 mg had clinical remission than those given placebo (induction study A 26·1% vs 15·3%, difference 10·8%; 95% CI 2·1-19·5, p=0·0157; induction study B 11·5% vs 4·2%, 7·2%; 1·6-12·8, p=0·0103). At week 58, 37·2% of patients given filgotinib 200 mg had clinical remission versus 11·2% in the respective placebo group (difference 26·0%, 95% CI 16·0-35·9; p<0·0001). Clinical remission was not significantly different between filgotinib 100 mg and placebo at week 10, but was significant by week 58 (23·8% vs 13·5%, 10·4%; 0·0-20·7, p=0·0420). The incidence of serious adverse events and adverse events of interest was similar between treatment groups. In the induction studies, serious adverse events occurred in 28 (5·0%) of 562 patients given filgotinib 100 mg, 22 (4·3%) of 507 patients given filgotinib 200 mg, and 13 (4·7%) of 279 patients given placebo. In the maintenance study, serious adverse events were reported in eight (4·5%) of 179 patients given filgotinib 100 mg, seven (7·7%) of 91 patients in the respective placebo group, nine (4·5%) of 202 patients in the filgotinib 200 mg group, and no patients in the respective placebo group. No deaths were reported during either induction study. Two patients died during the maintenance study; neither was related to treatment.
Interpretation
Filgotinib 200 mg was well tolerated, and efficacious in inducing and maintaining clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis.
Funding
Gilead Sciences.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 18 Jun 2021; 397:2372-2384
Feagan BG, Danese S, Loftus EV, Vermeire S, ... Hibi T, Peyrin-Biroulet L
Lancet: 18 Jun 2021; 397:2372-2384 | PMID: 34090625
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Abstract

Parkinson\'s disease.

Bloem BR, Okun MS, Klein C
Parkinson\'s disease is a recognisable clinical syndrome with a range of causes and clinical presentations. Parkinson\'s disease represents a fast-growing neurodegenerative condition; the rising prevalence worldwide resembles the many characteristics typically observed during a pandemic, except for an infectious cause. In most populations, 3-5% of Parkinson\'s disease is explained by genetic causes linked to known Parkinson\'s disease genes, thus representing monogenic Parkinson\'s disease, whereas 90 genetic risk variants collectively explain 16-36% of the heritable risk of non-monogenic Parkinson\'s disease. Additional causal associations include having a relative with Parkinson\'s disease or tremor, constipation, and being a non-smoker, each at least doubling the risk of Parkinson\'s disease. The diagnosis is clinically based; ancillary testing is reserved for people with an atypical presentation. Current criteria define Parkinson\'s disease as the presence of bradykinesia combined with either rest tremor, rigidity, or both. However, the clinical presentation is multifaceted and includes many non-motor symptoms. Prognostic counselling is guided by awareness of disease subtypes. Clinically manifest Parkinson\'s disease is preceded by a potentially long prodromal period. Presently, establishment of prodromal symptoms has no clinical implications other than symptom suppression, although recognition of prodromal parkinsonism will probably have consequences when disease-modifying treatments become available. Treatment goals vary from person to person, emphasising the need for personalised management. There is no reason to postpone symptomatic treatment in people developing disability due to Parkinson\'s disease. Levodopa is the most common medication used as first-line therapy. Optimal management should start at diagnosis and requires a multidisciplinary team approach, including a growing repertoire of non-pharmacological interventions. At present, no therapy can slow down or arrest the progression of Parkinson\'s disease, but informed by new insights in genetic causes and mechanisms of neuronal death, several promising strategies are being tested for disease-modifying potential. With the perspective of people with Parkinson\'s disease as a so-called red thread throughout this Seminar, we will show how personalised management of Parkinson\'s disease can be optimised.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 11 Jun 2021; 397:2284-2303
Bloem BR, Okun MS, Klein C
Lancet: 11 Jun 2021; 397:2284-2303 | PMID: 33848468
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Abstract

Comparing real-time and intermittently scanned continuous glucose monitoring in adults with type 1 diabetes (ALERTT1): a 6-month, prospective, multicentre, randomised controlled trial.

Visser MM, Charleer S, Fieuws S, De Block C, ... Mathieu C, Gillard P
Background
People with type 1 diabetes can continuously monitor their glucose levels on demand (intermittently scanned continuous glucose monitoring [isCGM]), or in real time (real-time continuous glucose monitoring [rtCGM]). However, it is unclear whether switching from isCGM to rtCGM with alert functionality offers additional benefits. Therefore, we did a trial comparing rtCGM and isCGM in adults with type 1 diabetes (ALERTT1).
Methods
We did a prospective, double-arm, parallel-group, multicentre, randomised controlled trial in six hospitals in Belgium. Adults with type 1 diabetes who previously used isCGM were randomly assigned (1:1) to rtCGM (intervention) or isCGM (control). Randomisation was done centrally using minimisation dependent on study centre, age, gender, glycated haemoglobin (HbA1c), time in range (sensor glucose 3·9-10·0 mmol/L), insulin administration method, and hypoglycaemia awareness. Participants, investigators, and study teams were not masked to group allocation. Primary endpoint was mean between-group difference in time in range after 6 months assessed in the intention-to-treat sample. This trial is registered with ClinicalTrials.gov, NCT03772600.
Findings
Between Jan 29 and Jul 30, 2019, 269 participants were recruited, of whom 254 were randomly assigned to rtCGM (n=127) or isCGM (n=127); 124 and 122 participants completed the study, respectively. After 6 months, time in range was higher with rtCGM than with isCGM (59·6% vs 51·9%; mean difference 6·85 percentage points [95% CI 4·36-9·34]; p<0·0001). After 6 months HbA1c was lower (7·1% vs 7·4%; p<0·0001), as was time <3·0 mmol/L (0·47% vs 0·84%; p=0·0070), and Hypoglycaemia Fear Survey version II worry subscale score (15·4 vs 18·0; p=0·0071). Fewer participants on rtCGM experienced severe hypoglycaemia (n=3 vs n=13; p=0·0082). Skin reaction was more frequently observed with isCGM and bleeding after sensor insertion was more frequently reported by rtCGM users.
Interpretation
In an unselected adult type 1 diabetes population, switching from isCGM to rtCGM significantly improved time in range after 6 months of treatment, implying that clinicians should consider rtCGM instead of isCGM to improve the health and quality of life of people with type 1 diabetes.
Funding
Dexcom.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 11 Jun 2021; 397:2275-2283
Visser MM, Charleer S, Fieuws S, De Block C, ... Mathieu C, Gillard P
Lancet: 11 Jun 2021; 397:2275-2283 | PMID: 34089660
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Abstract

Cardiovascular risk prediction in type 2 diabetes before and after widespread screening: a derivation and validation study.

Pylypchuk R, Wells S, Kerr A, Poppe K, ... Zhao J, Jackson R
Background
Until recently, most patients with diabetes worldwide have been diagnosed when symptomatic and have high cardiovascular risk, meaning most should be prescribed cardiovascular preventive medications. However, in New Zealand, a world-first national programme led to approximately 90% of eligible adults being screened for diabetes by 2016, up from 50% in 2012, identifying many asymptomatic patients with recent-onset diabetes. We hypothesised that cardiovascular risk prediction equations derived before widespread screening would now significantly overestimate risk in screen-detected patients.
Methods
New Zealanders aged 30-74 years with type 2 diabetes and without known cardiovascular disease, heart failure, or substantial renal impairment were identified from the 400 000-person PREDICT primary care cohort study between Oct 27, 2004, and Dec 30, 2016, covering the period before and after widespread screening. Sex-specific equations estimating 5-year risk of cardiovascular disease were developed using Cox regression models, with 18 prespecified predictors, including diabetes-related and renal function measures. Equation performance was compared with an equivalent equation derived in the New Zealand Diabetes Cohort Study (NZDCS), which recruited between 2000 and 2006, before widespread screening.
Findings
46 652 participants were included in the PREDICT-1° Diabetes subcohort, of whom 4114 experienced first cardiovascular events during follow-up (median 5·2 years, IQR 3·3-7·4). 14 829 (31·8%) were not taking oral hypoglycaemic medications or insulin at baseline. Median 5-year cardiovascular risk estimated by the new equations was 4·0% (IQR 2·3-6·8) in women and 7·1% (4·5-11·2) in men. The older NZDCS equation overestimated median cardiovascular risk by three times in women (median 14·2% [9·7-20·0]) and two times in men (17·1% [4·5-20·0]). Model and discrimination performance measures for PREDICT-1° Diabetse equations were also significantly better than for the NZDCS equation (eg, for women: R2=32% [95% CI 29-34], Harrell\'s C=0·73 [0·72-0·74], Royston\'s D=1·410 [1·330-1·490] vs R2=24% [21-26], C=0·69 [0·67-0·70], and D=1·147 [1·107-1·187]).
Interpretation
International treatment guidelines still consider most people with diabetes to be at high cardiovascular risk; however, we show that recent widespread diabetes screening has radically changed the cardiovascular risk profile of people with diabetes in New Zealand. Many of these patients have normal renal function, are not dispensed glucose-lowering medications, and have low cardiovascular risk. These findings have clear international implications as increased diabetes screening is inevitable due to increasing obesity, simpler screening tests, and the introduction of new-generation glucose-lowering medications that prevent cardiovascular events. Cardiovascular risk prediction equations derived from contemporary diabetes populations, with multiple diabetes-related and renal function predictors, will be required to better differentiate between low-risk and high-risk patients in this increasingly heterogeneous population and to inform appropriate non-pharmacological management and cost-effective targeting of expensive new medications.
Funding
Health Research Council of New Zealand, Heart Foundation of New Zealand, and Healthier Lives National Science Challenge.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 11 Jun 2021; 397:2264-2274
Pylypchuk R, Wells S, Kerr A, Poppe K, ... Zhao J, Jackson R
Lancet: 11 Jun 2021; 397:2264-2274 | PMID: 34089656
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Impact:
Abstract

Parental education and inequalities in child mortality: a global systematic review and meta-analysis.

Balaj M, York HW, Sripada K, Besnier E, ... Gakidou E, Eikemo TA
Background
The educational attainment of parents, particularly mothers, has been associated with lower levels of child mortality, yet there is no consensus on the magnitude of this relationship globally. We aimed to estimate the total reductions in under-5 mortality that are associated with increased maternal and paternal education, during distinct age intervals.
Methods
This study is a comprehensive global systematic review and meta-analysis of all existing studies of the effects of parental education on neonatal, infant, and under-5 child mortality, combined with primary analyses of Demographic and Health Survey (DHS) data. The literature search of seven databases (CINAHL, Embase, MEDLINE, PsycINFO, PubMed, Scopus, and Web of Science) was done between Jan 23 and Feb 8, 2019, and updated on Jan 7, 2021, with no language or publication date restrictions. Teams of independent reviewers assessed each record for its inclusion of individual-level data on parental education and child mortality and excluded articles on the basis of study design and availability of relevant statistics. Full-text screening was done in 15 languages. Data extracted from these studies were combined with primary microdata from the DHS for meta-analyses relating maternal or paternal education with mortality at six age intervals: 0-27 days, 1-11 months, 1-4 years, 0-4 years, 0-11 months, and 1 month to 4 years. Novel mixed-effects meta-regression models were implemented to address heterogeneity in referent and exposure measures among the studies and to adjust for study-level covariates (wealth or income, partner\'s years of schooling, and sex of the child). This study was registered with PROSPERO (CRD42020141731).
Findings
The systematic review returned 5339 unique records, yielding 186 included studies after exclusions. DHS data were compiled from 114 unique surveys, capturing 3 112 474 livebirths. Data extracted from the systematic review were synthesized together with primary DHS data, for meta-analysis on a total of 300 studies from 92 countries. Both increased maternal and paternal education showed a dose-response relationship linked to reduced under-5 mortality, with maternal education emerging as a stronger predictor. We observed a reduction in under-5 mortality of 31·0% (95% CI 29·0-32·6) for children born to mothers with 12 years of education (ie, completed secondary education) and 17·3% (15·0-18·8) for children born to fathers with 12 years of education, compared with those born to a parent with no education. We also showed that a single additional year of schooling was, on average, associated with a reduction in under-5 mortality of 3·04% (2·82-3·23) for maternal education and 1·57% (1·35-1·72) for paternal education. The association between higher parental education and lower child mortality was significant for both parents at all ages studied and was largest after the first month of life. The meta-analysis framework incorporated uncertainty associated with each individual effect size into the model fitting process, in an effort to decrease the risk of bias introduced by study design and quality.
Interpretation
To our knowledge, this study is the first effort to systematically quantify the transgenerational importance of education for child survival at the global level. The results showed that lower maternal and paternal education are both risk factors for child mortality, even after controlling for other markers of family socioeconomic status. This study provides robust evidence for universal quality education as a mechanism to achieve the Sustainable Development Goal target 3.2 of reducing neonatal and child mortality.
Funding
Research Council of Norway, Bill & Melinda Gates Foundation, and Rockefeller Foundation-Boston University Commission on Social Determinants, Data, and Decision Making (3-D Commission).

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Lancet: 09 Jun 2021; epub ahead of print
Balaj M, York HW, Sripada K, Besnier E, ... Gakidou E, Eikemo TA
Lancet: 09 Jun 2021; epub ahead of print | PMID: 34119000
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Abstract

Non-alcoholic fatty liver disease.

Powell EE, Wong VW, Rinella M
Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of 25% and is a leading cause of cirrhosis and hepatocellular carcinoma. NAFLD encompasses a disease continuum from steatosis with or without mild inflammation (non-alcoholic fatty liver), to non-alcoholic steatohepatitis (NASH), which is characterised by necroinflammation and faster fibrosis progression than non-alcoholic fatty liver. NAFLD has a bidirectional association with components of the metabolic syndrome, and type 2 diabetes increases the risk of cirrhosis and related complications. Although the leading causes of death in people with NAFLD are cardiovascular disease and extrahepatic malignancy, advanced liver fibrosis is a key prognostic marker for liver-related outcomes and overall mortality, and can be assessed with combinations of non-invasive tests. Patients with cirrhosis should be screened for hepatocellular carcinoma and oesophageal varices. There is currently no approved therapy for NAFLD, although several drugs are in advanced stages of development. Because of the complex pathophysiology and substantial heterogeneity of disease phenotypes, combination treatment is likely to be required for many patients with NAFLD. Healthy lifestyle and weight reduction remain crucial to the prevention and treatment of NAFLD.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 04 Jun 2021; 397:2212-2224
Powell EE, Wong VW, Rinella M
Lancet: 04 Jun 2021; 397:2212-2224 | PMID: 33894145
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Impact:
Abstract

Cystic fibrosis.

Shteinberg M, Haq IJ, Polineni D, Davies JC
Cystic fibrosis is a monogenic disease considered to affect at least 100 000 people worldwide. Mutations in CFTR, the gene encoding the epithelial ion channel that normally transports chloride and bicarbonate, lead to impaired mucus hydration and clearance. Classical cystic fibrosis is thus characterised by chronic pulmonary infection and inflammation, pancreatic exocrine insufficiency, male infertility, and might include several comorbidities such as cystic fibrosis-related diabetes or cystic fibrosis liver disease. This autosomal recessive disease is diagnosed in many regions following newborn screening, whereas in other regions, diagnosis is based on a group of recognised multiorgan clinical manifestations, raised sweat chloride concentrations, or CFTR mutations. Disease that is less easily diagnosed, and in some cases affecting only one organ, can be seen in the context of gene variants leading to residual protein function. Management strategies, including augmenting mucociliary clearance and aggressively treating infections, have gradually improved life expectancy for people with cystic fibrosis. However, restoration of CFTR function via new small molecule modulator drugs is transforming the disease for many patients. Clinical trial pipelines are actively exploring many other approaches, which will be increasingly needed as survival improves and as the population of adults with cystic fibrosis increases. Here, we present the current understanding of CFTR mutations, protein function, and disease pathophysiology, consider strengths and limitations of current management strategies, and look to the future of multidisciplinary care for those with cystic fibrosis.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 04 Jun 2021; 397:2195-2211
Shteinberg M, Haq IJ, Polineni D, Davies JC
Lancet: 04 Jun 2021; 397:2195-2211 | PMID: 34090606
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Impact:
Abstract

Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

Chen YP, Liu X, Zhou Q, Yang KY, ... Sun Y, Ma J
Background
Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.
Methods
This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.
Findings
Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.
Interpretation
The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.
Funding
The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise
Introduction:
Project for Discipline Innovation.
Translation
For the Chinese translation of the abstract see Supplementary Materials section.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 03 Jun 2021; epub ahead of print
Chen YP, Liu X, Zhou Q, Yang KY, ... Sun Y, Ma J
Lancet: 03 Jun 2021; epub ahead of print | PMID: 34111416
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Impact:
Abstract

KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study.

Shah BD, Ghobadi A, Oluwole OO, Logan AC, ... Masouleh BK, Houot R
Background
Despite treatment with novel therapies and allogeneic stem-cell transplant (allo-SCT) consolidation, outcomes in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia remain poor, underlining the need for more effective therapies.
Methods
We report the pivotal phase 2 results of ZUMA-3, an international, multicentre, single-arm, open-label study evaluating the efficacy and safety of the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy KTE-X19 in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia. Patients were enrolled at 25 sites in the USA, Canada, and Europe. Eligible patients were aged 18 years or older, with Eastern Cooperative Oncology Group performance status of 0-1, and morphological disease in the bone marrow (>5% blasts). After leukapheresis and conditioning chemotherapy, patients received a single KTE-X19 infusion (1 × 106 CAR T cells per kg bodyweight). The primary endpoint was the rate of overall complete remission or complete remission with incomplete haematological recovery by central assessment. Duration of remission and relapse-free survival, overall survival, minimal residual disease (MRD) negativity rate, and allo-SCT rate were assessed as secondary endpoints. Efficacy and safety analyses were done in the treated population (all patients who received a dose of KTE-X19). This study is registered with ClinicalTrials.gov, NCT02614066.
Findings
Between Oct 1, 2018, and Oct 9, 2019, 71 patients were enrolled and underwent leukapheresis. KTE-X19 was successfully manufactured for 65 (92%) patients and administered to 55 (77%). The median age of treated patients was 40 years (IQR 28-52). At the median follow-up of 16·4 months (13·8-19·6), 39 patients (71%; 95% CI 57-82, p<0·0001) had complete remission or complete remission with incomplete haematological recovery, with 31 (56%) patients reaching complete remission. Median duration of remission was 12·8 months (95% CI 8·7-not estimable), median relapse-free survival was 11·6 months (2·7-15·5), and median overall survival was 18·2 months (15·9-not estimable). Among responders, the median overall survival was not reached, and 38 (97%) patients had MRD negativity. Ten (18%) patients received allo-SCT consolidation after KTE-X19 infusion. The most common adverse events of grade 3 or higher were anaemia (27 [49%] patients) and pyrexia (20 [36%] patients). 14 (25%) patients had infections of grade 3 or higher. Two grade 5 KTE-X19-related events occurred (brain herniation and septic shock). Cytokine release syndrome of grade 3 or higher occurred in 13 (24%) patients and neurological events of grade 3 or higher occurred in 14 (25%) patients.
Interpretation
KTE-X19 showed a high rate of complete remission or complete remission with incomplete haematological recovery in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia, with the median overall survival not reached in responding patients, and a manageable safety profile. These findings indicate that KTE-X19 has the potential to confer long-term clinical benefit to these patients.
Funding
Kite, a Gilead Company.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 02 Jun 2021; epub ahead of print
Shah BD, Ghobadi A, Oluwole OO, Logan AC, ... Masouleh BK, Houot R
Lancet: 02 Jun 2021; epub ahead of print | PMID: 34097852
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Impact:
Abstract

Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.

Rovin BH, Teng YKO, Ginzler EM, Arriens C, ... Solomons N, Huizinga RB
Background
Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis.
Methods
This multicentre, double-blind, randomised phase 3 trial was done in 142 hospitals and clinics across 27 countries. Patients with a diagnosis of systemic lupus erythematosus with lupus nephritis according to the American College of Rheumatology criteria, and a kidney biopsy within 2 years that showed class III, IV, or V (alone or in combination with class III or IV) were eligible. Patients were randomly assigned (1:1) to oral voclosporin (23·7 mg twice daily) or placebo, on a background of mycophenolate mofetil (1 g twice daily) and rapidly tapered low-dose oral steroids, by use of an interactive web response system. The primary endpoint was complete renal response at 52 weeks defined as a composite of urine protein creatinine ratio of 0·5 mg/mg or less, stable renal function (defined as estimated glomerular filtration rate [eGFR] ≥60 mL/min/1·73 m2 or no confirmed decrease from baseline in eGFR of >20%), no administration of rescue medication, and no more than 10 mg prednisone equivalent per day for 3 or more consecutive days or for 7 or more days during weeks 44 through 52, just before the primary endpoint assessment. Safety was also assessed. Efficacy analysis was by intention-to-treat and safety analysis by randomised patients receiving at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03021499.
Findings
Between April 13, 2017, and Oct 10, 2019, 179 patients were assigned to the voclosporin group and 178 to the placebo group. The primary endpoint of complete renal response at week 52 was achieved in significantly more patients in the voclosporin group than in the placebo group (73 [41%] of 179 patients vs 40 [23%] of 178 patients; odds ratio 2·65; 95% CI 1·64-4·27; p<0·0001). The adverse event profile was balanced between the two groups; serious adverse events occurred in 37 (21%) of 178 in the voclosporin group and 38 (21%) of 178 patients in the placebo group. The most frequent serious adverse event involving infection was pneumonia, occurring in 7 (4%) patients in the voclosporin group and in 8 (4%) patients in the placebo group. A total of six patients died during the study or study follow-up period (one [<1%] patient in the voclosporin group and five [3%] patients in the placebo group). None of the events leading to death were considered by the investigators to be related to the study treatments.
Interpretation
Voclosporin in combination with MMF and low-dose steroids led to a clinically and statistically superior complete renal response rate versus MMF and low-dose steroids alone, with a comparable safety profile. This finding is an important advancement in the treatment of patients with active lupus nephritis.
Funding
Aurinia Pharmaceuticals.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 28 May 2021; 397:2070-2080
Rovin BH, Teng YKO, Ginzler EM, Arriens C, ... Solomons N, Huizinga RB
Lancet: 28 May 2021; 397:2070-2080 | PMID: 33971155
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Abstract

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial.

RECOVERY Collaborative Group
Background
Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.
Methods
This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Findings
Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93-1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94-1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93-1·05; p=0·79).
Interpretation
In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.
Funding
UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Lancet: 28 May 2021; 397:2049-2059
RECOVERY Collaborative Group
Lancet: 28 May 2021; 397:2049-2059 | PMID: 34000257
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Abstract

IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial.

Ridker PM, Devalaraja M, Baeres FMM, Engelmann MDM, ... Davidson M, RESCUE Investigators
Background
IL-6 has emerged as a pivotal factor in atherothrombosis. Yet, the safety and efficacy of IL-6 inhibition among individuals at high atherosclerotic risk but without a systemic inflammatory disorder is unknown. We therefore addressed whether ziltivekimab, a fully human monoclonal antibody directed against the IL-6 ligand, safely and effectively reduces biomarkers of inflammation and thrombosis among patients with high cardiovascular risk. We focused on individuals with elevated high-sensitivity CRP and chronic kidney disease, a group with substantial unmet clinical need in whom previous studies in inflammation inhibition have shown efficacy for cardiovascular event reduction.
Methods
RESCUE is a randomised, double-blind, phase 2 trial done at 40 clinical sites in the USA. Inclusion criteria were age 18 years or older, moderate to severe chronic kidney disease, and high-sensitivity CRP of at least 2 mg/L. Participants were randomly allocated (1:1:1:1) to subcutaneous administration of placebo or ziltivekimab 7·5 mg, 15 mg, or 30 mg every 4 weeks up to 24 weeks. The primary outcome was percentage change from baseline in high-sensitivity CRP after 12 weeks of treatment with ziltivekimab compared with placebo, with additional biomarker and safety data collected over 24 weeks of treatment. Primary analyses were done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. The trial is registered with ClinicalTrials.gov, NCT03926117.
Findings
Between June 17, 2019, and Jan 14, 2020, 264 participants were enrolled into the trial, of whom 66 were randomly assigned to each of the four treatment groups. At 12 weeks after randomisation, median high-sensitivity CRP levels were reduced by 77% for the 7·5 mg group, 88% for the 15 mg group, and 92% for the 30 mg group compared with 4% for the placebo group. As such, the median pairwise differences in percentage change in high-sensitivity CRP between the ziltivekimab and placebo groups, after aligning for strata, were -66·2% for the 7·5 mg group, -77·7% for the 15 mg group, and -87·8% for the 30 mg group (all p<0·0001). Effects were stable over the 24-week treatment period. Dose-dependent reductions were also observed for fibrinogen, serum amyloid A, haptoglobin, secretory phospholipase A2, and lipoprotein(a). Ziltivekimab was well tolerated, did not affect the total cholesterol to HDL cholesterol ratio, and there were no serious injection-site reactions, sustained grade 3 or 4 neutropenia or thrombocytopenia.
Interpretation
Ziltivekimab markedly reduced biomarkers of inflammation and thrombosis relevant to atherosclerosis. On the basis of these data, a large-scale cardiovascular outcomes trial will investigate the effect of ziltivekimab in patients with chronic kidney disease, increased high-sensitivity CRP, and established cardiovascular disease.
Funding
Novo Nordisk.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 28 May 2021; 397:2060-2069
Ridker PM, Devalaraja M, Baeres FMM, Engelmann MDM, ... Davidson M, RESCUE Investigators
Lancet: 28 May 2021; 397:2060-2069 | PMID: 34015342
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Abstract

Chronic pain: an update on burden, best practices, and new advances.

Cohen SP, Vase L, Hooten WM
Chronic pain exerts an enormous personal and economic burden, affecting more than 30% of people worldwide according to some studies. Unlike acute pain, which carries survival value, chronic pain might be best considered to be a disease, with treatment (eg, to be active despite the pain) and psychological (eg, pain acceptance and optimism as goals) implications. Pain can be categorised as nociceptive (from tissue injury), neuropathic (from nerve injury), or nociplastic (from a sensitised nervous system), all of which affect work-up and treatment decisions at every level; however, in practice there is considerable overlap in the different types of pain mechanisms within and between patients, so many experts consider pain classification as a continuum. The biopsychosocial model of pain presents physical symptoms as the denouement of a dynamic interaction between biological, psychological, and social factors. Although it is widely known that pain can cause psychological distress and sleep problems, many medical practitioners do not realise that these associations are bidirectional. While predisposing factors and consequences of chronic pain are well known, the flipside is that factors promoting resilience, such as emotional support systems and good health, can promote healing and reduce pain chronification. Quality of life indicators and neuroplastic changes might also be reversible with adequate pain management. Clinical trials and guidelines typically recommend a personalised multimodal, interdisciplinary treatment approach, which might include pharmacotherapy, psychotherapy, integrative treatments, and invasive procedures.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 28 May 2021; 397:2082-2097
Cohen SP, Vase L, Hooten WM
Lancet: 28 May 2021; 397:2082-2097 | PMID: 34062143
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Abstract

Pre-eclampsia.

Chappell LC, Cluver CA, Kingdom J, Tong S
Pre-eclampsia is a multisystem pregnancy disorder characterised by variable degrees of placental malperfusion, with release of soluble factors into the circulation. These factors cause maternal vascular endothelial injury, which leads to hypertension and multi-organ injury. The placental disease can cause fetal growth restriction and stillbirth. Pre-eclampsia is a major cause of maternal and perinatal mortality and morbidity, especially in low-income and middle-income countries. Prophylactic low-dose aspirin can reduce the risk of preterm pre-eclampsia, but once pre-eclampsia has been diagnosed there are no curative treatments except for delivery, and no drugs have been shown to influence disease progression. Timing of delivery is planned to optimise fetal and maternal outcomes. Clinical trials have reported diagnostic and prognostic strategies that could improve fetal and maternal outcomes and have evaluated the optimal timing of birth in women with late preterm pre-eclampsia. Ongoing studies are evaluating the efficacy, dose, and timing of aspirin and calcium to prevent pre-eclampsia and are evaluating other drugs to control hypertension or ameliorate disease progression.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 26 May 2021; epub ahead of print
Chappell LC, Cluver CA, Kingdom J, Tong S
Lancet: 26 May 2021; epub ahead of print | PMID: 34051884
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Abstract

F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial.

Jani AB, Schreibmann E, Goyal S, Halkar R, ... Dhere VR, Schuster DM
Background
Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of 18F-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy.
Methods
In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov, NCT01666808 and is closed to new participants.
Findings
From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3·52 years (95% CI 2·98-3·95). PET findings resulted in four patients in the 18F-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35·2-not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached-not reached; 20% of 76 patients) in the 18F-fluciclovine-PET/CT group, and 3 year event-free survival was 63·0% (95% CI 49·2-74·0) in the conventional imaging group versus 75·5% (95% CI 62·5-84·6) for 18F-fluciclovine-PET/CT (difference 12·5; 95% CI 4·3-20·8; p=0·0028). In adjusted analyses, study group (hazard ratio 2·04 [95% CI 1·06-3·93], p=0·0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group).
Interpretation
Inclusion of 18F-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study.
Funding
National Institutes of Health/National Cancer Institute, Blue Earth Diagnostics, and Winship Cancer Institute of Emory University.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Lancet: 21 May 2021; 397:1895-1904
Jani AB, Schreibmann E, Goyal S, Halkar R, ... Dhere VR, Schuster DM
Lancet: 21 May 2021; 397:1895-1904 | PMID: 33971152
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