Journal: BMJ

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<div><h4>Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study.</h4><i>Jia J, Zhao T, Liu Z, Liang Y, ... Gauthier S, Cummings J</i><br /><b>Objective</b><br />To identify an optimal lifestyle profile to protect against memory loss in older individuals.<br /><b>Design</b><br />Population based, prospective cohort study.<br /><b>Setting</b><br />Participants from areas representative of the north, south, and west of China.<br /><b>Participants</b><br />Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009.<br /><b>Main outcome measures</b><br />Participants were followed up until death, discontinuation, or 26 December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or previously smoked, and never drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample.<br /><b>Results</b><br />29 072 participants were included (mean age of 72.23 years; 48.54% (n=14 113) were women; and 20.43% (n=5939) were APOE ε4 carriers). Over the 10 year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95% confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95% confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95% confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52).<br /><b>Conclusion</b><br />A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline.<br /><b>Trial registration</b><br />ClinicalTrials.gov NCT03653156.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 25 Jan 2023; 380:e072691</small></div>
Jia J, Zhao T, Liu Z, Liang Y, ... Gauthier S, Cummings J
BMJ: 25 Jan 2023; 380:e072691 | PMID: 36696990
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<div><h4>Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): multicentre randomised phase 3 clinical trial.</h4><i>Pichler G, Goeral K, Hammerl M, Perme T, ... Schmölzer GM, COSGOD III study group</i><br /><b>Objective</b><br />To investigate whether monitoring of cerebral tissue oxygen saturation using near infrared spectroscopy in addition to routine monitoring combined with defined treatment guidelines during immediate transition and resuscitation increases survival without cerebral injury of premature infants compared with standard care alone.<br /><b>Design</b><br />Multicentre, multinational, randomised controlled phase 3 trial.<br /><b>Setting</b><br />11 tertiary neonatal intensive care units in six countries in Europe and in Canada.<br /><b>Participants</b><br />1121 pregnant women (<32 weeks\' gestation) were screened prenatally. The primary outcome was analysed in 607 of 655 randomised preterm neonates: 304 neonates in the near infrared spectroscopy group and 303 in the control group.<br /><b>Intervention</b><br />Preterm neonates were randomly assigned to either standard care (control group) or standard care plus monitoring of cerebral oxygen saturation with a dedicated treatment guideline (near infrared spectroscopy group) during immediate transition (first 15 minutes after birth) and resuscitation.<br /><b>Main outcome measure</b><br />The primary outcome, assessed using all cause mortality and serial cerebral ultrasonography, was a composite of survival without cerebral injury. Cerebral injury was defined as any intraventricular haemorrhage or cystic periventricular leukomalacia, or both, at term equivalent age or before discharge.<br /><b>Results</b><br />Cerebral tissue oxygen saturation was similar in both groups. 252 (82.9%) out of 304 neonates (median gestational age 28.9 (interquartile range 26.9-30.6) weeks) in the near infrared spectroscopy group survived without cerebral injury compared with 238 (78.5%) out of 303 neonates (28.6 (26.6-30.6) weeks) in the control group (relative risk 1.06, 95% confidence interval 0.98 to 1.14). 28 neonates died (near infrared spectroscopy group 12 (4.0%) <i>v</i> control group 16 (5.3%): relative risk 0.75 (0.33 to 1.70).<br /><b>Conclusion</b><br />Monitoring of cerebral tissue oxygen saturation in combination with dedicated interventions in preterm neonates (<32 weeks\' gestation) during immediate transition and resuscitation after birth did not result in substantially higher survival without cerebral injury compared with standard care alone. Survival without cerebral injury increased by 4.3% but was not statistically significant.<br /><b>Trial registration</b><br />ClinicalTrials.gov NCT03166722.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 24 Jan 2023; 380:e072313</small></div>
Pichler G, Goeral K, Hammerl M, Perme T, ... Schmölzer GM, COSGOD III study group
BMJ: 24 Jan 2023; 380:e072313 | PMID: 36693654
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<div><h4>Gestational age at birth and cognitive outcomes in adolescence: population based full sibling cohort study.</h4><i>Husby A, Wohlfahrt J, Melbye M</i><br /><b>Objective</b><br />To investigate the association between gestational age at birth and cognitive outcomes in adolescence.<br /><b>Design</b><br />Nationwide population based full sibling cohort study.<br /><b>Setting</b><br />Denmark.<br /><b>Participants</b><br />1.2 million children born between 1 January 1986 and 31 December 2003, of whom 792 724 had one or more full siblings born in the same period.<br /><b>Main outcome measures</b><br />Scores in written language (Danish) and mathematics examinations as graded by masked assessors at the end of compulsory schooling (ninth grade, ages 15-16 years), in addition to intelligence test score at military conscription (predominantly at age 18 years) for a nested sub-cohort of male adolescents. School grades were standardised as z scores according to year of examination, and intelligence test scores were standardised as z scores according to year of birth.<br /><b>Results</b><br />Among 792 724 full siblings in the cohort, 44 322 (5.6%) were born before 37+0 weeks of gestation. After adjusting for multiple confounders (sex, birth weight, malformations, parental age at birth, parental educational level, and number of older siblings) and shared family factors between siblings, only children born at <34 gestational weeks showed reduced mean grades in written language (z score difference -0.10 (95% confidence interval -0.20 to -0.01) for ≤27 gestational weeks) and mathematics (-0.05 (-0.08 to -0.01) for 32-33 gestational weeks, -0.13 (-0.17 to -0.09) for 28-31 gestational weeks, and -0.23 (-0.32 to -0.15) for ≤27 gestational weeks), compared with children born at 40 gestational weeks. In a nested sub-cohort of full brothers with intelligence test scores, those born at 32-33, 28-31, and ≤27 gestational weeks showed a reduction in IQ points of 2.4 (95% confidence interval 1.1 to 3.6), 3.8 (2.3 to 5.3), and 4.2 (0.8 to 7.5), respectively, whereas children born at 34-39 gestational weeks showed a reduction in intelligence of <1 IQ point, compared with children born at 40 gestational weeks.<br /><b>Conclusions</b><br />Cognitive outcomes in adolescence did not differ between those born at 34-39 gestational weeks and those born at 40 gestational weeks, whereas those with a gestational age of <34 weeks showed substantial deficits in multiple cognitive domains.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 18 Jan 2023; 380:e072779</small></div>
Husby A, Wohlfahrt J, Melbye M
BMJ: 18 Jan 2023; 380:e072779 | PMID: 36653028
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<div><h4>Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.</h4><i>Ong KL, Marklund M, Huang L, Rye KA, ... Mozaffarian D, Wu JH</i><br /><b>Objective</b><br />To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).<br /><b>Design</b><br />Pooled analysis.<br /><b>Data sources</b><br />A consortium of 19 studies from 12 countries identified up to May 2020.<br /><b>Study selection</b><br />Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.<br /><b>Data extraction and synthesis</b><br />Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis.<br /><b>Main outcome measures</b><br />Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m<sup>2</sup>. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m<sup>2</sup> and <75% of baseline rate.<br /><b>Results</b><br />25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I<sup>2</sup>=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I<sup>2</sup>=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I<sup>2</sup>=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 <i>v</i> <60 years), estimated glomerular filtration rate (60-89 <i>v</i> ≥90 mL/min/1.73 m<sup>2</sup>), hypertension, diabetes, and coronary heart disease at baseline.<br /><b>Conclusions</b><br />Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 18 Jan 2023; 380:e072909</small></div>
Ong KL, Marklund M, Huang L, Rye KA, ... Mozaffarian D, Wu JH
BMJ: 18 Jan 2023; 380:e072909 | PMID: 36653033
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<div><h4>Methenamine is as effective as antibiotics at preventing urinary tract infections.</h4><i>Saul H, Deeney B, Cassidy S, Kwint J, Harding C</i><br /><AbstractText>The studyHarding C, Mossop H, Homer T, et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial. <i>BMJ</i> 2022;376:e068229.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/methenamine-as-good-as-antibiotics-preventing-urinary-tract-infections/.</AbstractText><br /><br />Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.<br /><br /><small>BMJ: 17 Jan 2023; 380:p72</small></div>
Saul H, Deeney B, Cassidy S, Kwint J, Harding C
BMJ: 17 Jan 2023; 380:p72 | PMID: 36649970
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<div><h4>Telemental health for clinical assessment and treatment.</h4><i>Sugarman DE, Busch AB</i><br /><AbstractText>Telemental health-the use of videoconferencing or audio only (telephone) in mental health care-has accelerated tremendously since the start of the covid-19 pandemic. Meta-analyses have examined the reliability (ie, concordance) of assessment and the efficacy/effectiveness of telemental health compared with in-person care. Results indicate that telemental health assessment and clinical outcomes are similar compared with in-person care but there is much unexplained variability, as well as evidence that patient clinical and demographic characteristics can influence these findings. Further, gaps exist in the literature regarding specific patient populations (eg, psychotic disorders, children/adolescents), treatment modalities (eg, group therapy), audio only telemedicine, and hybrid care that mixes in-person with telemental health care. These gaps provide important directions for the next generation of telemental health research. Comprehensive clinical guidelines from mental health organizations are available to telemental health practitioners and focus on five content themes: legal and regulatory issues, clinical considerations, standard operating procedures and protocols, technical requirements, and considerations of specific populations and settings.</AbstractText><br /><br />Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.<br /><br /><small>BMJ: 16 Jan 2023; 380:e072398</small></div>
Sugarman DE, Busch AB
BMJ: 16 Jan 2023; 380:e072398 | PMID: 36646462
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<div><h4>Prevalence, awareness, treatment, and control of hypertension in China, 2004-18: findings from six rounds of a national survey.</h4><i>Zhang M, Shi Y, Zhou B, Huang Z, ... Wang L, Li Y</i><br /><b>Objective</b><br />To assess the recent trends in prevalence and management of hypertension in China, nationally and by population subgroups.<br /><b>Design</b><br />Six rounds of a national survey, China.<br /><b>Setting</b><br />China Chronic Disease and Risk Factors Surveillance, 2004-18.<br /><b>Participants</b><br />642 523 community dwelling adults aged 18-69 years (30 501 in 2004, 47 353 in 2007, 90 491 in 2010, 156 836 in 2013, 162 293 in 2015, and 155 049 in 2018).<br /><b>Main outcome measures</b><br />Hypertension was defined as a blood pressure of ≥140/90 mm Hg or taking antihypertensive drugs. The main outcome measures were hypertension prevalence and proportion of people with hypertension who were aware of their hypertension, who were treated for hypertension, and whose blood pressure was controlled below 140/90 mm Hg.<br /><b>Results</b><br />The standardised prevalence of hypertension in adults aged 18-69 years in China increased from 20.8% (95% confidence interval 19.0% to 22.5%) in 2004 to 29.6% (27.8% to 31.3%) in 2010, then decreased to 24.7% (23.2% to 26.1%) in 2018. During 2010-18, the absolute annual decline in prevalence of hypertension among women was more than twice that among men (-0.83 percentage points (95% confidence interval -1.13 to -0.52) <i>v</i> -0.40 percentage points (-0.73 to -0.07)). Despite modest improvements in the awareness, treatment, and control of hypertension since 2004, rates remained low in 2018, at 38.3% (36.3% to 40.4%), 34.6% (32.6% to 36.7%), and 12.0% (10.6% to 13.4%). Of 274 million (95% confidence interval 238 to 311 million) adults aged 18-69 years with hypertension in 2018, control was inadequate in an estimated 240 million (215 to 264 million). Across all surveys, women with low educational attainment had higher prevalence of hypertension than those with higher education, but the finding was mixed for men. The gap in hypertension control between urban and rural areas persisted, despite larger improvements in diagnosis and control in rural than in urban areas.<br /><b>Conclusions</b><br />The prevalence of hypertension in China has slightly declined since 2010, but treatment and control remain low. The findings highlight the need for improving detection and treatment of hypertension through the strengthening of primary care in China, especially in rural areas.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 11 Jan 2023; 380:e071952</small></div>
Zhang M, Shi Y, Zhou B, Huang Z, ... Wang L, Li Y
BMJ: 11 Jan 2023; 380:e071952 | PMID: 36631148
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<div><h4>Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study.</h4><i>Mizrahi B, Sudry T, Flaks-Manov N, Yehezkelli Y, ... Bivas-Benita M, Greenfeld S</i><br /><b>Objectives</b><br />To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status.<br /><b>Design</b><br />Retrospective nationwide cohort study.<br /><b>Setting</b><br />Electronic medical records from an Israeli nationwide healthcare organisation.<br /><b>Population</b><br />1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021.<br /><b>Main outcome measures</b><br />Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection.<br /><b>Results</b><br />Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients.<br /><b>Conclusions</b><br />This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 11 Jan 2023; 380:e072529</small></div>
Mizrahi B, Sudry T, Flaks-Manov N, Yehezkelli Y, ... Bivas-Benita M, Greenfeld S
BMJ: 11 Jan 2023; 380:e072529 | PMID: 36631153
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<div><h4>When I use a word . . . . Medical anniversaries in 2023.</h4><i>Aronson JK</i><br /><AbstractText>My list of 66 medically related anniversaries for 2023 (events in years ending \'23 and\'73) includes:
● foundation of the Chelsea Physic Garden (1673);
● foundation of <i>The Lancet</i> by Thomas Wakley (October 1823);
● Roe v Wade (1973);
● Twenty five births include: Hans Berger, German neurologist; Aimé Bonpland, French physician and botanist; Alexis Carrel, French surgeon and Nobel prize winner; Lloyd Conover, American pharmaceutical chemist; Félix d\'Herelle, French-Canadian microbiologist; Théodore de Mayerne, Swiss physician; Carl Djerassi, American pharmaceutical chemist and novelist; Sigismund Elsholtz, German physician, botanist, and alchemist; Daniel Gajdusek, American virologist; Beatrix Hamburg, American psychiatrist; Richard Mead, English physician; Arthur Jensen, American educational psychologist; Otto Loewi, German pharmacologist; Georg Balthasar Metzger, German physician and scientist; William P Murphy Jr, American physician and inventor of medical devices; William Petty, English physician and political economist; Arnold S Relman, American physician and editor; Caspar Schamberger, German surgeon; Giovanni Antonio Scopoli, Italian physician and scientist; Ludwik Teichmann, Polish physician and anatomist; Alfred Russell Wallace, English naturalist; and Thomas Young, English scientist and polymath;
● Thirteen deaths include: Francis Anthony, English apothecary, physician, and alchemist; Matthew Baillie, Scottish physician and pathologist; John Caius, English physician; Regnier De Graaf, Dutch physician, physiologist, and anatomist; Walter Rudolf Hess, Swiss physiologist; Edward Jenner, English physician; Dickinson W Richards, American physician; Wilhelm Röntgen, German physicist; Antony van Leeuwenhoek, Dutch microscopist; Justus von Liebig, German chemist; and Selman Waksman, Ukrainian-American biochemist;
● Eleven biomedical texts published, written by Avicenna, Persian physician, astronomer, and philosopher; Gaspard Bauhin, Swiss botanist; William Budd, English physician; Aleixeu de Abreu, Portuguese physician and tropical pathologist; John Lelamour, English schoolmaster; Lucretius, Roman poet and philosopher; Marcello Malpighi, Italian physician; Girolamo Mercuriale, Italian physician; Raymond Pearl, American biologist; Costanzo Varolio, Italian anatomist and physician; Charles White, English physician; and Wilhelm Wundt, German physiologist;
● compilation of the <i>Lelamour Herbal</i> by John Lelamour, English schoolmaster (1373);
● anatomical, biochemical, haematological, microbiological, and physiological observations by Gasparus Aselli, Italian physician; Gerhard Henrik Armauer Hansen, Norwegian physician; William Prout, English chemist, physician, and theologian; Gaston Ramon, French biologist; Hilaire-Marin Rouelle, French chemist; and Antony van Leeuwenhoek, Dutch microscopist;
● Foundation of the pharmaceutical companies Novo Nordisk in Denmark (1923) and Sanofi in France (1973);
● Nobel prizes awarded to Banting and Macleod (1923) and to von Frisch, Lorenz, and Tinbergen (1973).</AbstractText><br /><br />Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.<br /><br /><small>BMJ: 06 Jan 2023; 380:p42</small></div>
Aronson JK
BMJ: 06 Jan 2023; 380:p42 | PMID: 36609556
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<div><h4>Labour market participation and retirement after stroke in Denmark: registry based cohort study.</h4><i>Skajaa N, Adelborg K, Horváth-Puhó E, Rothman KJ, ... Thygesen LC, Sørensen HT</i><br /><b>Objective</b><br />To examine labour market participation and retirement among patients with stroke and matched people in the general population according to stroke subtype.<br /><b>Design</b><br />Nationwide, population based, matched cohort study.<br /><b>Setting</b><br />Danish Stroke Registry, covering all Danish hospitals, and other nationwide registries (2005-18).<br /><b>Participants</b><br />Patients (aged 18-60 years and active in the labour market) with a first time diagnosis of ischaemic stroke (n=16 577), intracerebral haemorrhage (n=2025), or subarachnoid haemorrhage (n=4305), and individuals from the general population, matched on age, sex, and calendar year (n=134 428). The median Scandinavian stroke scale score was 55.<br /><b>Main outcome measures</b><br />Unweighted prevalences of labour market participation, receipt of sick leave benefits, receipt of disability pension, voluntary early retirement, state pension, and death were computed for each week and up to five years after stroke diagnosis. A log-linear Poisson model was used to obtain exact prevalence estimates as well as propensity score weighted prevalence differences and prevalence ratios at six months, one year, two years, and five years after stroke diagnosis.<br /><b>Results</b><br />Most patients (62% of those with ischaemic stroke, 69% of those with intracerebral haemorrhage, and 52% of those with subarachnoid haemorrhage) went on sick leave within three weeks of diagnosis. Prevalence of labour market participation among patients with ischaemic stroke compared with matched individuals from the general population was 56.6% versus 96.6% at six months, and 63.9% versus 91.6% at two years. Prevalence of sick leave was 39.8% versus 2.6% at six months, and 15.8% versus 3.8% at two years. Prevalence of receipt of a disability pension was 0.9% versus 0.2% at six months, and 12.2% versus 0.6% at two years. Adjusting for socioeconomic and comorbidity differences between patients and matched individuals from the general population using propensity score weighting methods had little impact on contrasts. Patients with intracerebral haemorrhage had higher prevalences of sick leave and receipt of a disability pension and thus a lower prevalence of labour market participation, while prevalences for patients with subarachnoid haemorrhage were similar in magnitude to those for patients with ischaemic stroke.<br /><b>Conclusions</b><br />In a highly resourced country, about two thirds of working age adults with ischaemic stroke of primarily mild severity participated in the labour market two years after diagnosis. Sick leave and receipt of a disability pension were the most common reasons for non-participation. Patients with intracerebral haemorrhage were less likely to return to the labour market than patients with ischaemic stroke and subarachnoid haemorrhage.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 03 Jan 2023; 380:e072308</small></div>
Skajaa N, Adelborg K, Horváth-Puhó E, Rothman KJ, ... Thygesen LC, Sørensen HT
BMJ: 03 Jan 2023; 380:e072308 | PMID: 36596583
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<div><h4>Quantifying the benefits of inefficient walking: Monty Python inspired laboratory based experimental study.</h4><i>Gaesser GA, Poole DC, Angadi SS</i><br /><b>Objective</b><br />To compare the rate of energy expenditure of low efficiency walking with high efficiency walking.<br /><b>Design</b><br />Laboratory based experimental study.<br /><b>Setting</b><br />United States.<br /><b>Participants</b><br />13 healthy adults (six women, seven men) with no known gait disorder, mean (±standard deviation) age 34.2±16.1 years, height 174.2±12.6 cm, weight 78.2±22.5 kg, and body mass index 25.6±6.0.<br /><b>Intervention</b><br />Participants performed three, five minute walking trials around an indoor 30 m course. The first trial consisted of walking at a freely chosen walking speed in the participant\'s usual style. The next two trials consisted of low efficiency walks in which participants were asked to duplicate the walks of Mr Teabag and Mr Putey (acted by John Cleese and Michael Palin, respectively) in the legendary Monty Python Ministry of Silly Walks (MoSW) skit that first aired in 1970. Distance covered during the five minute walks was used to calculate average speed. Ventilation and gas exchange were collected throughout to determine oxygen uptake (V̇O<sub>2</sub>; mL O<sub>2</sub>/kg/min) and energy expenditure (EE; kcal/kg/min; 1 kcal=4.18 kJ), reported as mean±standard deviation.<br /><b>Main outcome measures</b><br />V̇O<sub>2</sub> and EE.<br /><b>Results</b><br />V̇O<sub>2</sub> and EE were about 2.5 times higher (P<0.001) during the Teabag walk compared with participants\' usual walk (27.9±4.8 <i>v</i> 11.3±1.9 mL O<sub>2</sub>/kg/min; 0.14±0.03 <i>v</i> 0.06±0.01 kcal/kg/min), but were not different during the Putey walk (12.3±1.8 mL/kg/min; 0.06±0.01 kcal/kg/min). Each minute of Teabag walking increased EE over participants\' usual walking by an average of 8.0 kcal (range 5.5-12.0) in men and by 5.2 kcal (range 3.9-6.2) in women, and qualified as vigorous intensity physical activity (>6 resting metabolic equivalents).<br /><b>Conclusions</b><br />For adults with no known gait disorder who average approximately 5000 steps/day, exchanging about 22%-34% of their daily steps with higher energy, low efficiency walking in Teabag style-requiring around 12-19 min-could increase daily EE by 100 kcal. Adults could achieve 75 minutes of vigorous intensity physical activity per week by walking inefficiently for about 11 min/day. Had an initiative to promote inefficient movement been adopted in the early 1970s, we might now be living among a healthier society. Efforts to promote higher energy-and perhaps more joyful-walking should ensure inclusivity and inefficiency for all.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 21 Dec 2022; 379:e072833</small></div>
Gaesser GA, Poole DC, Angadi SS
BMJ: 21 Dec 2022; 379:e072833 | PMID: 36543338
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<div><h4>Alcohol related disorders among elite male football players in Sweden: nationwide cohort study.</h4><i>Ueda P, Pasternak B, Svanström H, Lim CE, ... Ludvigsson JF, Kader M</i><br /><b>Objectives</b><br />To assess whether male elite football players are at increased risk of alcohol related disorders compared with men from the general population, and whether such an increased risk would vary on the basis of calendar year of the first playing season in the top tier of competition, age, career length, and goal scoring abilities.<br /><b>Design</b><br />Nationwide cohort study.<br /><b>Setting</b><br />Sweden, 1924-2020.<br /><b>Participants</b><br />6007 male football players who had played in the Swedish top division, Allsvenskan, from 1924 to 2019 and 56 168 men from the general population matched to players based on age and region of residence.<br /><b>Main outcome measures</b><br />Primary outcome was alcohol related disorders (diagnoses recorded in death certificates, during hospital admissions and outpatient visits, or use of prescription drugs for alcohol addiction); secondary outcome was disorders related to misuse of other drugs.<br /><b>Results</b><br />During follow-up up to 31 December 2020, 257 (4.3%) football players and 3528 (6.3%) men from the general population received diagnoses of alcohol related disorders. In analyses accounting for age, region of residence, and calendar time, risk of alcohol related disorders was lower among football players than among men from the general population (hazard ratio 0.71, 95% confidence interval 0.62 to 0.81). A reduced risk of alcohol related disorders was observed for football players who played their first season in the top tier in the early 1960s and later, while no significant difference versus men from the general population was seen in the risk for football players from earlier eras. The hazard ratio was lowest at around age 35 years, and then increased with age; at around age 75 years, football players had a higher risk of alcohol related disorders than men from the general population. No significant association was seen between goal scoring, number of games, and seasons played in the top tier and the risk of alcohol related disorders. Risk of disorders related to other drug misuse was significantly lower among football players than the general population (hazard ratio 0.22, 95% confidence interval 0.15 to 0.34).<br /><b>Conclusions</b><br />In this nationwide cohort study, male football players who had played in the Swedish top tier of competition had a significantly lower risk of alcohol related disorders than men from the general population.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 21 Dec 2022; 379:e074093</small></div>
Ueda P, Pasternak B, Svanström H, Lim CE, ... Ludvigsson JF, Kader M
BMJ: 21 Dec 2022; 379:e074093 | PMID: 36543350
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<div><h4>Everything causes cancer? Beliefs and attitudes towards cancer prevention among anti-vaxxers, flat earthers, and reptilian conspiracists: online cross sectional survey.</h4><i>Paytubi S, Benavente Y, Montoliu A, Binefa G, ... Alemany L, Costas L</i><br /><b>Objective</b><br />To evaluate, using an online non-probability sample, the beliefs about and attitudes towards cancer prevention of people professing vaccination scepticism or conspiracy theories.<br /><b>Design</b><br />Cross sectional survey.<br /><b>Setting</b><br />Data collected mainly from ForoCoches (a well known Spanish forum) and other platforms, including Reddit (English), 4Chan (English), HispaChan (Spanish), and a Spanish language website for cancer prevention (mejorsincancer.org) from January to March 2022.<br /><b>Participants</b><br />Among 1494 responders, 209 were unvaccinated against covid-19, 112 preferred alternative rather than conventional medicine, and 62 reported flat earth or reptilian beliefs.<br /><b>Main outcome measures</b><br />Cancer beliefs assessed using the Cancer Awareness Measure (CAM) and Cancer Awareness Measure Mythical Causes Scale (CAM-MYCS) (both validated tools).<br /><b>Results</b><br />Awareness of the actual causes of cancer was greater (median CAM score 63.6%) than that of mythical causes (41.7%). The most endorsed mythical causes of cancer were eating food containing additives or sweeteners, feeling stressed, and eating genetically modified food. Awareness of the actual and mythical causes of cancer among the unvaccinated, alternative medicine, and conspiracy groups was lower than among their counterparts. A median of 54.5% of the actual causes was accurately identified among each of the unvaccinated, alternative medicine, and conspiracy groups, and a median of 63.6% was identified in each of the three corresponding counterparts (P=0.13, 0.04, and 0.003, respectively). For mythical causes, medians of 25.0%, 16.7%, and 16.7% were accurately identified in the unvaccinated, alternative medicine, and conspiracy groups, respectively; a median of 41.7% was identified in each of the three corresponding counterparts (P<0.001 in adjusted models for all comparisons). In total, 673 (45.0%) participants agreed with the statement \"It seems like everything causes cancer.\" No significant differences were observed among the unvaccinated (44.0%), conspiracist (41.9%), or alternative medicine groups (35.7%), compared with their counterparts (45.2%, 45.7%, and 45.8%, respectively).<br /><b>Conclusions</b><br />Almost half of the participants agreed that \"It seems like everything causes cancer,\" which highlights the difficulty that society encounters in differentiating actual and mythical causes owing to mass information. People who believed in conspiracies, rejected the covid-19 vaccine, or preferred alternative medicine were more likely to endorse the mythical causes of cancer than their counterparts but were less likely to endorse the actual causes of cancer. These results suggest a direct connection between digital misinformation and consequent erroneous health decisions, which may represent a further preventable fraction of cancer.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 21 Dec 2022; 379:e072561</small></div>
Paytubi S, Benavente Y, Montoliu A, Binefa G, ... Alemany L, Costas L
BMJ: 21 Dec 2022; 379:e072561 | PMID: 36543351
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<div><h4>Can artificial intelligence pass the Fellowship of the Royal College of Radiologists examination? Multi-reader diagnostic accuracy study.</h4><i>Shelmerdine SC, Martin H, Shirodkar K, Shamshuddin S, Weir-McCall JR, FRCR-AI Study Collaborators</i><br /><b>Objective</b><br />To determine whether an artificial intelligence candidate could pass the rapid (radiographic) reporting component of the Fellowship of the Royal College of Radiologists (FRCR) examination.<br /><b>Design</b><br />Prospective multi-reader diagnostic accuracy study.<br /><b>Setting</b><br />United Kingdom.<br /><b>Participants</b><br />One artificial intelligence candidate (Smarturgences, Milvue) and 26 radiologists who had passed the FRCR examination in the preceding 12 months.<br /><b>Main outcome measures</b><br />Accuracy and pass rate of the artificial intelligence compared with radiologists across 10 mock FRCR rapid reporting examinations (each examination containing 30 radiographs, requiring 90% accuracy rate to pass).<br /><b>Results</b><br />When non-interpretable images were excluded from the analysis, the artificial intelligence candidate achieved an average overall accuracy of 79.5% (95% confidence interval 74.1% to 84.3%) and passed two of 10 mock FRCR examinations. The average radiologist achieved an average accuracy of 84.8% (76.1-91.9%) and passed four of 10 mock examinations. The sensitivity for the artificial intelligence was 83.6% (95% confidence interval 76.2% to 89.4%) and the specificity was 75.2% (66.7% to 82.5%), compared with summary estimates across all radiologists of 84.1% (81.0% to 87.0%) and 87.3% (85.0% to 89.3%). Across 148/300 radiographs that were correctly interpreted by >90% of radiologists, the artificial intelligence candidate was incorrect in 14/148 (9%). In 20/300 radiographs that most (>50%) radiologists interpreted incorrectly, the artificial intelligence candidate was correct in 10/20 (50%). Most imaging pitfalls related to interpretation of musculoskeletal rather than chest radiographs.<br /><b>Conclusions</b><br />When special dispensation for the artificial intelligence candidate was provided (that is, exclusion of non-interpretable images), the artificial intelligence candidate was able to pass two of 10 mock examinations. Potential exists for the artificial intelligence candidate to improve its radiographic interpretation skills by focusing on musculoskeletal cases and learning to interpret radiographs of the axial skeleton and abdomen that are currently considered \"non-interpretable.\"<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 21 Dec 2022; 379:e072826</small></div>
Shelmerdine SC, Martin H, Shirodkar K, Shamshuddin S, Weir-McCall JR, FRCR-AI Study Collaborators
BMJ: 21 Dec 2022; 379:e072826 | PMID: 36543352
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<div><h4>Global health nonsense.</h4><i>Stein F, Storeng KT, de Bengy Puyvallée A</i><br /><AbstractText>Global health discourse that either underinforms or misinforms its audience is “global health nonsense.” Such nonsense is widespread, and jeopardises improvement in global health governance, argue <b>Stein</b>, <b>Storeng</b>, and <b>de Bengy Puyvallée</b></AbstractText><br /><br /><br /><br /><small>BMJ: 19 Dec 2022; 379:o2932</small></div>
Stein F, Storeng KT, de Bengy Puyvallée A
BMJ: 19 Dec 2022; 379:o2932 | PMID: 36535671
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<div><h4>Digital disparities among healthcare workers in typing speed between generations, genders, and medical specialties: cross sectional study.</h4><i>Schuurman AR, Baarsma ME, Wiersinga WJ, Hovius JW</i><br /><b>Objective</b><br />To investigate the typing skills of healthcare professionals.<br /><b>Design</b><br />Cross sectional study.<br /><b>Setting</b><br />Two large tertiary medical centres in Amsterdam, the Netherlands.<br /><b>Participants</b><br />2690 hospital employees working in patient care, research, or medical education.<br /><b>Main outcome measures</b><br />Participants completed a custom built, web based, Santa themed, typing test in 60 seconds and filled out an associated questionnaire. The primary outcome was corrected typing speed, defined as crude typing speed (words per minute) multiplied by accuracy (correct characters as a percentage of total characters in the final transcribed text). Feelings towards administrative tasks scored on the Visual Analogue Scale to Weigh Respondents\' Internalised Typing Enjoyment (VAS-WRITE), in which 0 represents the most negative and 100 the most positive feelings towards administration, were also recorded.<br /><b>Results</b><br />Between 18 and 21 May 2021, a representative cohort of 2690 study participants was recruited (1942 (72.2%) were younger than 40 years; 2065 (76.8%) were women). Respondents\' mean typing speed was 60.1 corrected words per minute (standard deviation 20.8; range 8.0-136.6) with substantial differences between professions and specialties, in which physicians in internal medicine were the fastest among the medical professionals. Typing speed decreased significantly with every age decade (rho -0.51, P<0.001), and people with a history of completing a typing course were more than 20% faster than those who had not (mean difference 12.1 words (standard error 0.8), (95% confidence interval 10.6 to 13.6), P<0.001). The corrected typing speed did not differ between genders (0.5 (0.9) words, (-1.4 to 2.4), P=0.61). Women were less negative towards administration than were men (mean difference VAS-WRITE score 7.68 (standard error 1.17), (95% confidence interval 5.33 to 10.03), P<0.001). Of all professional groups, medical staff reported the most negative feelings towards administration (mean VAS-WRITE score of 33.5 (standard deviation 22.9)).<br /><b>Conclusions</b><br />Important differences were reported in typing proficiency between age groups, professions, and medical specialties. Specific groups are at a disadvantage in an increasingly digitalised healthcare system, and these data could inform the implementation of training modules and alternative methods of data entry to level the playing field.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 19 Dec 2022; 379:e072784</small></div>
Schuurman AR, Baarsma ME, Wiersinga WJ, Hovius JW
BMJ: 19 Dec 2022; 379:e072784 | PMID: 36535672
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<div><h4>A Christmas themed physical activity intervention to increase participation in physical activity during Advent: pilot randomised controlled trial.</h4><i>Biddle GJH, Sanders JP, Gokal K, Madigan CD, ... CLiMB Active Advent Study Team, Daley AJ</i><br /><b>Objectives</b><br />To examine the recruitment, retention, and preliminary effects of a Christmas themed physical activity intervention designed to increase participation in physical activity and decrease sedentary behaviour in inactive adults.<br /><b>Design</b><br />Pilot randomised controlled trial.<br /><b>Setting</b><br />Recruitment from social medial platforms, workplaces, and community groups in the UK.<br /><b>Participants</b><br />107 inactive adults (who did not meet the UK guidelines for physical activity) aged 18-75 years.<br /><b>Interventions</b><br />The intervention consisted of an email sent to participants each day of Advent (1-24 December 2021), which contained a Christmas themed physical activity idea to be completed that day. Each physical activity idea was presented in three intensity formats, including Easy Elf (light intensity), Moderate Mrs Claus (moderate intensity), and Strenuous Santa (vigorous intensity). The comparator group received a leaflet about healthy living on the 1 December.<br /><b>Main outcome measures</b><br />Participants were randomly assigned (2:1) to either the intervention or control and were masked to group allocation before randomisation. Primary outcomes were recruitment rate, retention, and weekly minutes of participation in self-reported moderate-to-vigorous intensity physical activity by use of the exercise vital signs questionnaire. Primary analysis compared change in minutes of moderate-to-vigorous intensity physical activity from baseline to weeks one, two, and three during the Active Advent intervention. Secondary outcomes were participation in muscle strengthening based physical activity (days per week), accelerometer measured moderate-to-vigorous intensity physical activity, light intensity physical activity, total physical activity, and sedentary time (minutes per day), and enjoyment of and adherence to the intervention.<br /><b>Results</b><br />323 individuals expressed interest in participating in the trial and 107 were randomly assigned to the intervention (n=71) or the comparator (n=36) group. The recruitment target (n=105) was reached within 19 days of starting recruitment. 23 (21%) of 107 participants were lost to follow-up. On average, the groups reported participation in similar minutes of moderate-to-vigorous intensity physical activity in weeks one and two. At week three, the adjusted mean difference between groups was 20.6 minutes of participation in moderate-to-vigorous intensity physical activity per week (95% confidence interval -29.7 to 70.9) in favour of the intervention group. Accelerometer data showed that the intervention group spent fewer minutes sedentary per day than comparators (mean difference -58.6 (-113.5 to -3.8)). Overall, 42 (70%) of 60 participants in the intervention group reported that they liked the intervention and 41 (69%) of 59 reported that they completed the Active Advent intervention ideas each day.<br /><b>Conclusions</b><br />The public were interested to participate in a Christmas themed physical activity intervention during Advent, which might increase physical activity and reduce time sedentary. Enjoyment of, and adherence to the intervention shows the potential benefit that Christmas themed physical activity campaigns/initiatives might have for improving public health.<br /><b>Trial registration</b><br />ISRCTN12415556.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 19 Dec 2022; 379:e072807</small></div>
Biddle GJH, Sanders JP, Gokal K, Madigan CD, ... CLiMB Active Advent Study Team, Daley AJ
BMJ: 19 Dec 2022; 379:e072807 | PMID: 36535688
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<div><h4>Direct Uptake of Nutrition and Caffeine Study (DUNCS): biscuit based comparative study.</h4><i>Jones C, Francis J</i><br /><b>Objectives</b><br />To identify the time required to achieve optimal palatability of a cup of tea without risk of harm (oral scalding) using the resources available in a standard hospital staff room, and to identify the best accompanying biscuit for nutritional content, crunchiness, and integrity when dunking.<br /><b>Design</b><br />Prospective, non-masked, biscuit based, comparative study.<br /><b>Setting</b><br />Staff room in the surgery department of a UK hospital.<br /><b>Participants</b><br />Four different varieties of round, non-chocolate biscuit: oat, digestive, rich tea, and shortie. A standardised cup of tea was determined on the basis of the investigators\' preference for colour and palatability and pragmatic tea making methods.<br /><b>Main outcome measures</b><br />The main outcome was time to achieve a safe temperature for consumption of tea, and the best biscuit to pair with the tea on the basis of nutritional content, absorptive ability, crunchiness, and integrity after dunking. Biscuits were ranked first to last (according to scores 1-4), with penalty points given for adverse events such as scalds and breakability.<br /><b>Results</b><br />Baseline data suggested that after adding 240 mL of freshly boiled water to an unwarmed mug containing a tea bag, the median temperature of a standard cup of tea was 82ºC (range 81-84ºC). Optimal palatability and agreed universal drinking temperature of 61ºC was achieved at 400 (range 360-420) seconds with 30 mL of cow\'s milk and 370 (330-450) seconds with 40 mL of milk. The investigators considered tea colour preferable with 40 mL of milk.<br /><b>Conclusion</b><br />Healthcare workers can safely consume a cup of tea after less than 10 minutes, especially if enjoyed with a biscuit. Making time for a cup of tea may help healthcare workers avoid their break point.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 19 Dec 2022; 379:e072839</small></div>
Jones C, Francis J
BMJ: 19 Dec 2022; 379:e072839 | PMID: 36535701
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<div><h4>Human papillomavirus vaccination and cervical cancer risk.</h4><i>Rahangdale L, Mungo C, O\'Connor S, Chibwesha CJ, Brewer NT</i><br /><AbstractText>Persistent human papillomavirus infection is the central cause of cervical cancer, the leading cause of cancer death among women worldwide. Clear evidence from both randomized trials and population based studies shows that vaccination against human papillomavirus reduces the incidence of cervical pre-cancer. These data suggest that the vaccine reduces the incidence of cervical cancer. However, human papillomavirus vaccine coverage is inadequate in all countries, especially in low and middle income countries where disease burden is highest. Supply side strategies to improve coverage include increasing the availability of low cost vaccines, school located delivery, single dose vaccine schedules, and development of vaccines that do not need refrigeration. Demand side strategies include enhancing provider recommendations, correcting misinformation, and public awareness campaigns. The near elimination of cervical cancer is achievable through increased uptake of human papillomavirus vaccination and efforts to increase screening for cervical cancer, especially when enacted to reduce disparities in across the world.</AbstractText><br /><br />Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.<br /><br /><small>BMJ: 15 Dec 2022; 379:e070115</small></div>
Rahangdale L, Mungo C, O'Connor S, Chibwesha CJ, Brewer NT
BMJ: 15 Dec 2022; 379:e070115 | PMID: 36521855
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<div><h4>Evaluation of editors\' abilities to predict the citation potential of research manuscripts submitted to : a cohort study.</h4><i>Schroter S, Weber WEJ, Loder E, Wilkinson J, Kirkham JJ</i><br /><b>Objective</b><br />To evaluate the ability of <i>The BMJ</i> editors to predict the number of times submitted research manuscripts will be cited.<br /><b>Design</b><br />Cohort study.<br /><b>Setting</b><br />Manuscripts submitted to <i>The BMJ</i>, reviewed, and subsequently scheduled for discussion at a prepublication meeting between 27 August 2015 and 29 December 2016.<br /><b>Participants</b><br />10 <i>BMJ</i> research team editors.<br /><b>Main outcome measures</b><br />Reviewed manuscripts were rated independently by attending editors for citation potential in the year of first publication plus the next year: no citations, below average (<10 citations), average (10-17 citations), or high (>17 citations). Predicted citations were subsequently compared with actual citations extracted from Web of Science (WOS).<br /><b>Results</b><br />Of 534 manuscripts reviewed, 505 were published as full length articles (219 in <i>The BMJ)</i> by end of 2019 and indexed in WOS, 22 were unpublished, and one abstract was withdrawn. Among the 505 manuscripts, the median (IQR [range]) number of citations in the year of publication plus the following year was 9 (4-17 [0-150]); 277 (55%) manuscripts were cited <10 times, 105 (21%) were cited 10-17 times, and 123 (24%) cited >17 times. Manuscripts accepted by <i>The BMJ</i> were cited more highly (median 12 (IQR 7-24) citations) than those rejected (median 7 (3-12) citations). For all 10 editors, predicted ratings tended to increase in line with actual citations, but with considerable variation within categories; nine failed to identify the correct citation category for >50% (range 31%-52%) of manuscripts, and κ ranged between 0.01 to 0.19 for agreement between predicted and actual categories. Editors more often rated papers that achieved high actual citation counts as having low citation potential than the reverse. Collectively, the mean percentage of editors predicting the correct citation category was 43%, and for 160 (32%) manuscripts at least 50% of editors predicted the right category.<br /><b>Conclusions</b><br />Editors weren\'t good at estimating the citation potential of manuscripts individually or as a group; there is no wisdom of the crowd when it comes to <i>BMJ</i> editors.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 14 Dec 2022; 379:e073880</small></div>
Schroter S, Weber WEJ, Loder E, Wilkinson J, Kirkham JJ
BMJ: 14 Dec 2022; 379:e073880 | PMID: 36517041
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<div><h4>Hospital policies can create barriers to good management of opioid withdrawal.</h4><i>Saul H, Gursul D, Deeney B, Harris M, Holland A</i><br /><AbstractText>The studyHarris M, Holland A, Lewer D, et al. Barriers to management of opioid withdrawal in hospitals in England: a document analysis of hospital policies on the management of substance dependence. <i>BMC Med</i> 2022;20:151.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/many-hospital-policies-create-barriers-to-good-management-of-opioid-withdrawal/.</AbstractText><br /><br />Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.<br /><br /><small>BMJ: 02 Dec 2022; 379:o2860</small></div>
Saul H, Gursul D, Deeney B, Harris M, Holland A
BMJ: 02 Dec 2022; 379:o2860 | PMID: 36460314
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<div><h4>Correction for vol. 379, p.</h4><i></i><br /><AbstractText>Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM): cluster randomised controlled trial.</AbstractText><br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 01 Dec 2022; 379:o2859</small></div>
BMJ: 01 Dec 2022; 379:o2859 | PMID: 36455932
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<div><h4>Effectiveness of mRNA-1273, BNT162b2, and BBIBP-CorV vaccines against infection and mortality in children in Argentina, during predominance of delta and omicron covid-19 variants: test negative, case-control study.</h4><i>Castelli JM, Rearte A, Olszevicki S, Voto C, ... Giovacchini CM, Vizzotti C</i><br /><b>Objective</b><br />To estimate the effectiveness of a two dose vaccine schedule (mRNA-1273, BNT162b2, and BBIBP-CorV) against SARS-CoV-2 infection and covid-19 related death and short term waning of immunity in children (3-11 years old) and adolescents (12-17 years old) during periods of delta and omicron variant predominance in Argentina.<br /><b>Design</b><br />Test negative, case-control study.<br /><b>Setting</b><br />Database of the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina.<br /><b>Participants</b><br />844 460 <b>c</b>hildren and adolescents without previous SARS-CoV-2 infection eligible to receive primary vaccination schedule who were tested for SARS-CoV-2 by polymerase chain reaction or rapid antigen test from September 2021 to April 2022. After matching with their corresponding controls, 139 321 (60.3%) of 231 181 cases remained for analysis.<br /><b>Exposures</b><br />Two dose mRNA-1273, BNT162b2, and BBIBP-CorV vaccination schedule.<br /><b>Main outcome measures</b><br />SARS-CoV-2 infection and covid-19 related death. Conditional logistic regression was used to estimate the odds of SARS-CoV-2 infection among two dose vaccinated and unvaccinated participants. Vaccine effectiveness was estimated as (1-odds ratio)×100%.<br /><b>Results</b><br />Estimated vaccine effectiveness against SARS-CoV-2 infection was 61.2% (95% confidence interval 56.4% to 65.5%) in children and 66.8% (63.9% to 69.5%) in adolescents during the delta dominant period and 15.9% (13.2% to 18.6%) and 26.0% (23.2% to 28.8%), respectively, when omicron was dominant. Vaccine effectiveness declined over time, especially during the omicron period, from 37.6% (34.2% to 40.8%) at 15-30 days after vaccination to 2.0% (1.8% to 5.6%) after ≥60 days in children and from 55.8% (52.4% to 59.0%) to 12.4% (8.6% to 16.1%) in adolescents.Vaccine effectiveness against death related to SARS-CoV-2 infection during omicron predominance was 66.9% (6.4% to 89.8%) in children and 97.6% (81.0% to 99.7%) in adolescents.<br /><b>Conclusions</b><br />Vaccine effectiveness in preventing mortality remained high in children and adolescents regardless of the circulating variant. Vaccine effectiveness in preventing SARS-CoV-2 infection in the short term after vaccination was lower during omicron predominance and decreasing sharply over time.<br /><b>Trial registration</b><br />National Registry of Health Research IS003720.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 30 Nov 2022; 379:e073070</small></div>
Abstract
<div><h4>Oxygen administration during surgery and postoperative organ injury: observational cohort study.</h4><i>McIlroy DR, Shotwell MS, Lopez MG, Vaughn MT, ... Billings FT, Multicenter Perioperative Outcomes Group</i><br /><b>Objective</b><br />To examine whether supraphysiological oxygen administration during surgery is associated with lower or higher postoperative kidney, heart, and lung injury.<br /><b>Design</b><br />Observational cohort study.<br /><b>Setting</b><br />42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry.<br /><b>Participants</b><br />Adult patients undergoing surgical procedures ≥120 minutes\' duration with general anesthesia and endotracheal intubation who were admitted to hospital after surgery between January 2016 and November 2018.<br /><b>Intervention</b><br />Supraphysiological oxygen administration, defined as the area under the curve of the fraction of inspired oxygen above air (21%) during minutes when the hemoglobin oxygen saturation was greater than 92%.<br /><b>Main outcomes</b><br />Primary endpoints were acute kidney injury defined using Kidney Disease Improving Global Outcomes criteria, myocardial injury defined as serum troponin >0.04 ng/mL within 72 hours of surgery, and lung injury defined using international classification of diseases hospital discharge diagnosis codes.<br /><b>Results</b><br />The cohort comprised 350 647 patients with median age 59 years (interquartile range 46-69 years), 180 546 women (51.5%), and median duration of surgery 205 minutes (interquartile range 158-279 minutes). Acute kidney injury was diagnosed in 19 207 of 297 554 patients (6.5%), myocardial injury in 8972 of 320 527 (2.8%), and lung injury in 13 789 of 312 161 (4.4%). The median fraction of inspired oxygen was 54.0% (interquartile range 47.5%-60.0%), and the area under the curve of supraphysiological inspired oxygen was 7951% min (5870-11 107% min), equivalent to an 80% fraction of inspired oxygen throughout a 135 minute procedure, for example. After accounting for baseline covariates and other potential confounding variables, increased oxygen exposure was associated with a higher risk of acute kidney injury, myocardial injury, and lung injury. Patients at the 75th centile for the area under the curve of the fraction of inspired oxygen had 26% greater odds of acute kidney injury (95% confidence interval 22% to 30%), 12% greater odds of myocardial injury (7% to 17%), and 14% greater odds of lung injury (12% to 16%) compared with patients at the 25th centile. Sensitivity analyses evaluating alternative definitions of the exposure, restricting the cohort, and conducting an instrumental variable analysis confirmed these observations.<br /><b>Conclusions</b><br />Increased supraphysiological oxygen administration during surgery was associated with a higher incidence of kidney, myocardial, and lung injury. Residual confounding of these associations cannot be excluded.<br /><b>Trial registration</b><br />Open Science Framework osf.io/cfd2m.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 30 Nov 2022; 379:e070941</small></div>
McIlroy DR, Shotwell MS, Lopez MG, Vaughn MT, ... Billings FT, Multicenter Perioperative Outcomes Group
BMJ: 30 Nov 2022; 379:e070941 | PMID: 36450405
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<div><h4>Advances in diagnosis and treatment of testicular cancer.</h4><i>Chovanec M, Cheng L</i><br /><AbstractText>Testicular cancer is a curable cancer. The success of physicians in curing the disease is underpinned by multidisciplinary advances. Cisplatin-based combination chemotherapy and the refinement of post-chemotherapy surgical procedures and diagnostic strategies have greatly improved long term survival in most patients. Despite such excellent outcomes, several controversial dilemmas exist in the approaches to clinical stage I disease, salvage chemotherapy, post-chemotherapy surgical procedures, and implementing innovative imaging studies. Relapse after salvage chemotherapy has a poor prognosis and the optimal treatment is not apparent. Recent research has provided insight into the molecular mechanisms underlying cisplatin resistance. Phase 2 studies with targeted agents have failed to show adequate efficacy; however, our understanding of cisplatin resistant disease is rapidly expanding. This review summarizes recent advances and discusses relevant issues in the biology and management of testicular cancer.</AbstractText><br /><br />Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.<br /><br /><small>BMJ: 28 Nov 2022; 379:e070499</small></div>
Chovanec M, Cheng L
BMJ: 28 Nov 2022; 379:e070499 | PMID: 36442868
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<div><h4>Retracted papers originating from paper mills: cross sectional study.</h4><i>Candal-Pedreira C, Ross JS, Ruano-Ravina A, Egilman DS, Fernández E, Pérez-Ríos M</i><br /><b>Objectives</b><br />To describe retracted papers originating from paper mills, including their characteristics, visibility, and impact over time, and the journals in which they were published.<br /><b>Design</b><br />Cross sectional study.<br /><b>Setting</b><br />The Retraction Watch database was used for identification of retracted papers from paper mills, Web of Science was used for the total number of published papers, and data from Journal Citation Reports were collected to show characteristics of journals.<br /><b>Participants</b><br />All paper mill papers retracted from 1 January 2004 to 26 June 2022 were included in the study. Papers bearing an expression of concern were excluded.<br /><b>Main outcome measures</b><br />Descriptive statistics were used to characterise the sample and analyse the trend of retracted paper mill papers over time, and to analyse their impact and visibility by reference to the number of citations received.<br /><b>Results</b><br />1182 retracted paper mill papers were identified. The publication of the first paper mill paper was in 2004 and the first retraction was in 2016; by 2021, paper mill retractions accounted for 772 (21.8%) of the 3544 total retractions. Overall, retracted paper mill papers were mostly published in journals of the second highest Journal Citation Reports quartile for impact factor (n=529 (44.8%)) and listed four to six authors (n=602 (50.9%)). Of the 1182 papers, almost all listed authors of 1143 (96.8%) paper mill retractions came from Chinese institutions and 909 (76.9%) listed a hospital as a primary affiliation. 15 journals accounted for 812 (68.7%) of 1182 paper mill retractions, with one journal accounting for 166 (14.0%). Nearly all (n=1083, 93.8%) paper mill retractions had received at least one citation since publication, with a median of 11 (interquartile range 5-22) citations received.<br /><b>Conclusions</b><br />Papers retracted originating from paper mills are increasing in frequency, posing a problem for the research community. Retracted paper mill papers most commonly originated from China and were published in a small number of journals. Nevertheless, detected paper mill papers might be substantially different from those that are not detected. New mechanisms are needed to identify and avoid this relatively new type of misconduct.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 28 Nov 2022; 379:e071517</small></div>
Candal-Pedreira C, Ross JS, Ruano-Ravina A, Egilman DS, Fernández E, Pérez-Ríos M
BMJ: 28 Nov 2022; 379:e071517 | PMID: 36442874
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<div><h4>Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial.</h4><i>Ageno W, Bertù L, Bucherini E, Camporese G, ... Palareti G, RIDTS study group</i><br /><b>Objective</b><br />To compare two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis (DVT).<br /><b>Design</b><br />Randomised, double blind, placebo controlled clinical trial.<br /><b>Setting</b><br />28 outpatient clinics specialising in venous thromboembolism.<br /><b>Participants</b><br />402 adults (≥18 years) with symptomatic isolated distal DVT.<br /><b>Interventions</b><br />After receiving standard dose rivaroxaban for six weeks, participants were randomly assigned to receive rivaroxaban 20 mg or placebo once daily for an additional six weeks. Follow-up was for 24 months from study inclusion.<br /><b>Main outcomes measures</b><br />The primary efficacy outcome was recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety outcome was major bleeding after randomisation until two days from the last dose of rivaroxaban or placebo. An independent committee adjudicated the outcomes.<br /><b>Results</b><br />200 adults were randomised to receive additional rivaroxaban treatment and 202 to receive placebo. Isolated distal DVT was unprovoked in 81 (40%) and 86 (43%) patients, respectively. The primary efficacy outcome occurred in 23 (11%) patients in the rivaroxaban arm and 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03, number needed to treat 13, 95% confidence interval 7 to 126). Recurrent isolated distal DVT occurred in 16 (8%) patients in the rivaroxaban arm and 31 (15%) in the placebo arm (P=0.02). Proximal DVT or pulmonary embolism occurred in seven (3%) patients in the rivaroxaban arm and eight (4%) in the placebo arm (P=0.80). No major bleeding events occurred.<br /><b>Conclusions</b><br />Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage.<br /><b>Trial registration</b><br />EudraCT 2016-000958-36; ClinicalTrials.gov NCT02722447.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 23 Nov 2022; 379:e072623</small></div>
Ageno W, Bertù L, Bucherini E, Camporese G, ... Palareti G, RIDTS study group
BMJ: 23 Nov 2022; 379:e072623 | PMID: 36520715
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<div><h4>Impact of community asymptomatic rapid antigen testing on covid-19 related hospital admissions: synthetic control study.</h4><i>Zhang X, Barr B, Green M, Hughes D, ... García-Fiñana M, Buchan I</i><br /><b>Objective</b><br />To analyse the impact of voluntary rapid testing for SARS-CoV-2 antigen in Liverpool city on covid-19 related hospital admissions.<br /><b>Design</b><br />Synthetic control analysis comparing hospital admissions for small areas in the intervention population with a group of control areas weighted to be similar for past covid-19 related hospital admission rates and sociodemographic factors.<br /><b>Setting</b><br />Liverpool city, UK, 6 November 2020 to 2 January 2021, under the intervention of Covid-SMART (systematic meaningful asymptomatic repeated testing) voluntary, open access supervised self-testing with lateral flow devices, compared with control areas selected from the rest of England.<br /><b>Population</b><br />General population of Liverpool (n=498 042) and a synthetic control population from the rest of England.<br /><b>Main outcome measure</b><br />Weekly covid-19 related hospital admissions for neighbourhoods in England.<br /><b>Results</b><br />The introduction of community testing was associated with a 43% (95% confidence interval 29% to 57%) reduction (146 (96 to 192) in total) in covid-19 related hospital admissions in Liverpool compared with the synthetic control population (non-adjacent set of neighbourhoods with aggregate trends in covid-19 hospital admissions similar to Liverpool) for the initial period of intensive testing with military assistance in national lockdown from 6 November to 3 December 2020. A 25% (11% to 35%) reduction (239 (104 to 333) in total) was estimated across the overall intervention period (6 November 2020 to 2 January 2021), involving fewer testing centres, before England\'s national roll-out of community testing, after adjusting for regional differences in tiers of covid-19 restrictions from 3 December 2020 to 2 January 2021.<br /><b>Conclusions</b><br />The city-wide pilot of community based asymptomatic testing for SARS-CoV-2 was associated with substantially reduced covid-19 related hospital admissions. Large scale asymptomatic rapid testing for SARS-CoV-2 could help reduce transmission and prevent hospital admissions.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 23 Nov 2022; 379:e071374</small></div>
Zhang X, Barr B, Green M, Hughes D, ... García-Fiñana M, Buchan I
BMJ: 23 Nov 2022; 379:e071374 | PMID: 36418047
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<div><h4>Changing patterns in reporting and sharing of review data in systematic reviews with meta-analysis of the effects of interventions: cross sectional meta-research study.</h4><i>Nguyen PY, Kanukula R, McKenzie JE, Alqaidoom Z, ... Welch VA, Page MJ</i><br /><b>Objectives</b><br />To examine changes in completeness of reporting and frequency of sharing data, analytical code, and other review materials in systematic reviews over time; and factors associated with these changes.<br /><b>Design</b><br />Cross sectional meta-research study.<br /><b>Population</b><br />Random sample of 300 systematic reviews with meta-analysis of aggregate data on the effects of a health, social, behavioural, or educational intervention. Reviews were indexed in PubMed, Science Citation Index, Social Sciences Citation Index, Scopus, and Education Collection in November 2020.<br /><b>Main outcome measures</b><br />The extent of complete reporting and the frequency of sharing review materials in the systematic reviews indexed in 2020 were compared with 110 systematic reviews indexed in February 2014. Associations between completeness of reporting and various factors (eg, self-reported use of reporting guidelines, journal policies on data sharing) were examined by calculating risk ratios and 95% confidence intervals.<br /><b>Results</b><br />Several items were reported suboptimally among 300 systematic reviews from 2020, such as a registration record for the review (n=113; 38%), a full search strategy for at least one database (n=214; 71%), methods used to assess risk of bias (n=185; 62%), methods used to prepare data for meta-analysis (n=101; 34%), and source of funding for the review (n=215; 72%). Only a few items not already reported at a high frequency in 2014 were reported more frequently in 2020. No evidence indicated that reviews using a reporting guideline were more completely reported than reviews not using a guideline. Reviews published in 2020 in journals that mandated either data sharing or inclusion of data availability statements were more likely to share their review materials (eg, data, code files) than reviews in journals without such mandates (16/87 (18%) <i>v</i> 4/213 (2%)).<br /><b>Conclusion</b><br />Incomplete reporting of several recommended items for systematic reviews persists, even in reviews that claim to have followed a reporting guideline. Journal policies on data sharing might encourage sharing of review materials.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 22 Nov 2022; 379:e072428</small></div>
Nguyen PY, Kanukula R, McKenzie JE, Alqaidoom Z, ... Welch VA, Page MJ
BMJ: 22 Nov 2022; 379:e072428 | PMID: 36414269
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<div><h4>Little evidence supports gabapentinoid use in bipolar disorder or insomnia.</h4><i>Saul H, Gursul D, Cassidy S, Harrison P</i><br /><AbstractText>The studyHong JSW, Atkinson LZ, Al-Juffali N, et al. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: systematic review, meta-analysis, and rationale. <i>Mol Psychiatry</i> 2022;27:1339-49.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/review-finds-little-evidence-support-gabapentinoid-use-bipolar-disorder-or-insomnia/.</AbstractText><br /><br />Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.<br /><br /><small>BMJ: 18 Nov 2022; 379:o2576</small></div>
Saul H, Gursul D, Cassidy S, Harrison P
BMJ: 18 Nov 2022; 379:o2576 | PMID: 36400449
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<div><h4>Maternal mortality in eight European countries with enhanced surveillance systems: descriptive population based study.</h4><i>Diguisto C, Saucedo M, Kallianidis A, Bloemenkamp K, ... Nyflot LT, Deneux-Tharaux C</i><br /><b>Objective</b><br />To compare maternal mortality in eight countries with enhanced surveillance systems.<br /><b>Design</b><br />Descriptive multicountry population based study.<br /><b>Setting</b><br />Eight countries with permanent surveillance systems using enhanced methods to identify, document, and review maternal deaths. The most recent available aggregated maternal mortality data were collected for three year periods for France, Italy, and the UK and for five year periods for Denmark, Finland, the Netherlands, Norway, and Slovakia.<br /><b>Population</b><br />297 835 live births in Denmark (2013-17), 301 169 in Finland (2008-12), 2 435 583 in France (2013-15), 1 281 986 in Italy (2013-15), 856 572 in the Netherlands (2014-18), 292 315 in Norway (2014-18), 283 930 in Slovakia (2014-18), and 2 261 090 in the UK (2016-18).<br /><b>Outcome measures</b><br />Maternal mortality ratios from enhanced systems were calculated and compared with those obtained from each country\'s office of vital statistics. Age specific maternal mortality ratios; maternal mortality ratios according to women\'s origin, citizenship, or ethnicity; and cause specific maternal mortality ratios were also calculated.<br /><b>Results</b><br />Methods for identifying and classifying maternal deaths up to 42 days were very similar across countries (except for the Netherlands). Maternal mortality ratios up to 42 days after end of pregnancy varied by a multiplicative factor of four from 2.7 and 3.4 per 100 000 live births in Norway and Denmark to 9.6 in the UK and 10.9 in Slovakia. Vital statistics offices underestimated maternal mortality by 36% or more everywhere but Denmark. Age specific maternal mortality ratios were higher for the youngest and oldest mothers (pooled relative risk 2.17 (95% confidence interval 1.38 to 3.34) for women aged <20 years, 2.10 (1.54 to 2.86) for those aged 35-39, and 3.95 (3.01 to 5.19) for those aged ≥40, compared with women aged 20-29 years). Except in Norway, maternal mortality ratios were ≥50% higher in women born abroad or of minoritised ethnicity, defined variously in different countries. Cardiovascular diseases and suicides were leading causes of maternal deaths in each country. Some other conditions were also major contributors to maternal mortality in only one or two countries: venous thromboembolism in the UK and the Netherlands, hypertensive disorders in the Netherlands, amniotic fluid embolism in France, haemorrhage in Italy, and stroke in Slovakia. Only two countries, France and the UK, had enhanced methods for studying late maternal deaths, those occurring between 43 and 365 days after the end of pregnancy.<br /><b>Conclusions</b><br />Variations in maternal mortality ratios exist between high income European countries with enhanced surveillance systems. In-depth analyses of differences in the quality of care and health system performance at national levels are needed to reduce maternal mortality further by learning from best practices and each other. Cardiovascular diseases and mental health in women during and after pregnancy must be prioritised in all countries.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 16 Nov 2022; 379:e070621</small></div>
Diguisto C, Saucedo M, Kallianidis A, Bloemenkamp K, ... Nyflot LT, Deneux-Tharaux C
BMJ: 16 Nov 2022; 379:e070621 | PMID: 36384872
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<div><h4>Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform.</h4><i>Zheng B, Green ACA, Tazare J, Curtis HJ, ... Goldacre B, Tomlinson LA</i><br /><b>Objective</b><br />To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19.<br /><b>Design</b><br />Observational cohort study with the OpenSAFELY platform.<br /><b>Setting</b><br />With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings.<br /><b>Participants</b><br />Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.<br /><b>Interventions</b><br />Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units.<br /><b>Main outcome measures</b><br />Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment.<br /><b>Results</b><br />Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England.<br /><b>Conclusions</b><br />In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 16 Nov 2022; 379:e071932</small></div>
Abstract
<div><h4>Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial.</h4><i>Jardine MJ, Kotwal SS, Bassi A, Hockham C, ... Jha V, CLARITY trial investigators</i><br /><b>Objective</b><br />To determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19.<br /><b>Design</b><br />CLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial.<br /><b>Setting</b><br />17 hospital sites in India and Australia.<br /><b>Participants</b><br />Participants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19.<br /><b>Intervention</b><br />Oral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days.<br /><b>Main outcome measures</b><br />The primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population.<br /><b>Results</b><br />Between 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of >1 (Pr(OR>1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR>1)=0.53). The trial was stopped when a prespecified futility rule was met.<br /><b>Conclusions</b><br />In patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan.<br /><b>Trial registration</b><br />ClinicalTrials.gov NCT04394117.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 16 Nov 2022; 379:e072175</small></div>
Jardine MJ, Kotwal SS, Bassi A, Hockham C, ... Jha V, CLARITY trial investigators
BMJ: 16 Nov 2022; 379:e072175 | PMID: 36384746
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<div><h4>Pathophysiology, diagnosis, and management of endometriosis.</h4><i>Horne AW, Missmer SA</i><br /><AbstractText>Endometriosis affects approximately 190 million women and people assigned female at birth worldwide. It is a chronic, inflammatory, gynecologic disease marked by the presence of endometrial-like tissue outside the uterus, which in many patients is associated with debilitating painful symptoms. Patients with endometriosis are also at greater risk of infertility, emergence of fatigue, multisite pain, and other comorbidities. Thus, endometriosis is best understood as a condition with variable presentation and effects at multiple life stages. A long diagnostic delay after symptom onset is common, and persistence and recurrence of symptoms despite treatment is common. This review discusses the potential genetic, hormonal, and immunologic factors that lead to endometriosis, with a focus on current diagnostic and management strategies for gynecologists, general practitioners, and clinicians specializing in conditions for which patients with endometriosis are at higher risk. It examines evidence supporting the different surgical, pharmacologic, and non-pharmacologic approaches to treating patients with endometriosis and presents an easy to adopt step-by-step management strategy. As endometriosis is a multisystem disease, patients with the condition should ideally be offered a personalized, multimodal, interdisciplinary treatment approach. A priority for future discovery is determining clinically informative sub-classifications of endometriosis that predict prognosis and enhance treatment prioritization.</AbstractText><br /><br />Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.<br /><br /><small>BMJ: 14 Nov 2022; 379:e070750</small></div>
Horne AW, Missmer SA
BMJ: 14 Nov 2022; 379:e070750 | PMID: 36375827
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Abstract
<div><h4>More people survived a cardiac arrest when first aiders received an app alert.</h4><i>Saul H, Gursul D, Cassidy S, Smith C</i><br /><AbstractText>The studySmith CM, Lall R, Fothergill RT, Spaight R, Perkins GD. The effect of the GoodSAM volunteer first-responder app on survival to hospital discharge following out-of-hospital cardiac arrest. <i>Eur Heart J Acute Cardiovasc Care</i> 2022;11:20-31.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/more-people-survived-cardiac-arrest-first-aiders-goodsam-alert/.</AbstractText><br /><br />Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.<br /><br /><small>BMJ: 11 Nov 2022; 379:o2578</small></div>
Saul H, Gursul D, Cassidy S, Smith C
BMJ: 11 Nov 2022; 379:o2578 | PMID: 36368720
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<div><h4>Integrating genome-wide polygenic risk scores and non-genetic risk to predict colorectal cancer diagnosis using UK Biobank data: population based cohort study.</h4><i>Briggs SEW, Law P, East JE, Wordsworth S, ... Hippisley-Cox J, Tomlinson I</i><br /><b>Objective</b><br />To evaluate the benefit of combining polygenic risk scores with the QCancer-10 (colorectal cancer) prediction model for non-genetic risk to identify people at highest risk of colorectal cancer.<br /><b>Design</b><br />Population based cohort study.<br /><b>Setting</b><br />Data from the UK Biobank study, collected between March 2006 and July 2010.<br /><b>Participants</b><br />434 587 individuals with complete data for genetics and QCancer-10 predictions were included in the QCancer-10 plus polygenic risk score modelling and validation cohorts.<br /><b>Main outcome measures</b><br />Prediction of colorectal cancer diagnosis by genetic, non-genetic, and combined risk models. Using data from UK Biobank, six different polygenic risk scores for colorectal cancer were developed using LDpred2 polygenic risk score software, clumping, and thresholding approaches, and a model based on genome-wide significant polymorphisms. The top performing genome-wide polygenic risk score and the score containing genome-wide significant polymorphisms were combined with QCancer-10 and performance was compared with QCancer-10 alone. Case-control (logistic regression) and time-to-event (Cox proportional hazards) analyses were used to evaluate risk model performance in men and women.<br /><b>Results</b><br />Polygenic risk scores derived using the LDpred2 program performed best, with an odds ratio per standard deviation of 1.584 (95% confidence interval 1.536 to 1.633), and top age and sex adjusted C statistic of 0.733 (95% confidence interval 0.710 to 0.753) in logistic regression models in the validation cohort. Integrated QCancer-10 plus polygenic risk score models out-performed QCancer-10 alone. In men, the integrated LDpred2 model produced a C statistic of 0.730 (0.720 to 0.741) and explained variation of 28.2% (26.3 to 30.1), compared with 0.693 (0.682 to 0.704) and 21.0% (18.9 to 23.1) for QCancer-10 alone. In women, the C statistic for the integrated LDpred2 model was 0.687 (0.673 to 0.702) and explained variation was 21.0% (18.7 to 23.7), compared with 0.645 (0.631 to 0.659) and 12.4% (10.3 to 14.6) for QCancer-10 alone. In the top 20% of individuals at highest absolute risk, the sensitivity and specificity of the integrated LDpred2 models for predicting colorectal cancer diagnosis was 47.8% and 80.3% respectively in men, and 42.7% and 80.1% respectively in women, with increases in absolute risk in the top 5% of risk in men of 3.47-fold and in women of 2.77-fold compared with the median. Illustrative decision curve analysis indicated a small incremental improvement in net benefit with QCancer-10 plus polygenic risk score models compared with QCancer-10 alone.<br /><b>Conclusions</b><br />Integrating polygenic risk scores with QCancer-10 modestly improves risk prediction over use of QCancer-10 alone. Given that QCancer-10 data can be obtained relatively easily from health records, use of polygenic risk score in risk stratified population screening for colorectal cancer currently has no clear justification. The added benefit, cost effectiveness, and acceptability of polygenic risk scores should be carefully evaluated in a real life screening setting before implementation in the general population.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 09 Nov 2022; 379:e071707</small></div>
Briggs SEW, Law P, East JE, Wordsworth S, ... Hippisley-Cox J, Tomlinson I
BMJ: 09 Nov 2022; 379:e071707 | PMID: 36351667
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<div><h4>Development and external validation of a risk prediction model for falls in patients with an indication for antihypertensive treatment: retrospective cohort study.</h4><i>Archer L, Koshiaris C, Lay-Flurrie S, Snell KIE, ... Sheppard JP, STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY) investigators</i><br /><b>Objective</b><br />To develop and externally validate the STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY)-Falls clinical prediction model to identify the risk of hospital admission or death from a fall in patients with an indication for antihypertensive treatment.<br /><b>Design</b><br />Retrospective cohort study.<br /><b>Setting</b><br />Primary care data from electronic health records contained within the UK Clinical Practice Research Datalink (CPRD).<br /><b>Participants</b><br />Patients aged 40 years or older with at least one blood pressure measurement between 130 mm Hg and 179 mm Hg.<br /><b>Main outcome measure</b><br />First serious fall, defined as hospital admission or death with a primary diagnosis of a fall within 10 years of the index date (12 months after cohort entry). Model development was conducted using a Fine-Gray approach in data from CPRD GOLD, accounting for the competing risk of death from other causes, with subsequent recalibration at one, five, and 10 years using pseudo values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves and the observed to expected ratio, C statistic, and D statistic, pooled across general practices, and clinical utility using decision curve analysis at thresholds around 10%.<br /><b>Results</b><br />Analysis included 1 772 600 patients (experiencing 62 691 serious falls) from CPRD GOLD used in model development, and 3 805 366 (experiencing 206 956 serious falls) from CPRD Aurum in the external validation. The final model consisted of 24 predictors, including age, sex, ethnicity, alcohol consumption, living in an area of high social deprivation, a history of falls, multiple sclerosis, and prescriptions of antihypertensives, antidepressants, hypnotics, and anxiolytics. Upon external validation, the recalibrated model showed good discrimination, with pooled C statistics of 0.833 (95% confidence interval 0.831 to 0.835) and 0.843 (0.841 to 0.844) at five and 10 years, respectively. Original model calibration was poor on visual inspection and although this was improved with recalibration, under-prediction of risk remained (observed to expected ratio at 10 years 1.839, 95% confidence interval 1.811 to 1.865). Nevertheless, decision curve analysis suggests potential clinical utility, with net benefit larger than other strategies.<br /><b>Conclusions</b><br />This prediction model uses commonly recorded clinical characteristics and distinguishes well between patients at high and low risk of falls in the next 1-10 years. Although miscalibration was evident on external validation, the model still had potential clinical utility around risk thresholds of 10% and so could be useful in routine clinical practice to help identify those at high risk of falls who might benefit from closer monitoring or early intervention to prevent future falls. Further studies are needed to explore the appropriate thresholds that maximise the model\'s clinical utility and cost effectiveness.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 08 Nov 2022; 379:e070918</small></div>
Archer L, Koshiaris C, Lay-Flurrie S, Snell KIE, ... Sheppard JP, STRAtifying Treatments In the multi-morbid Frail elderlY (STRATIFY) investigators
BMJ: 08 Nov 2022; 379:e070918 | PMID: 36347531
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<div><h4>Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial.</h4><i>Futier E, Jaber S, Garot M, Vignaud M, ... Paugam-Burtz C, COMBINE study group</i><br /><b>Objective</b><br />To investigate whether oral antimicrobial prophylaxis as an adjunct to intravenous antibiotic prophylaxis reduces surgical site infections after elective colorectal surgery.<br /><b>Design</b><br />Multicentre, randomised, double blind, placebo controlled trial.<br /><b>Setting</b><br />11 university and non-university hospitals in France between 25 May 2016 and 8 August 2019.<br /><b>Participants</b><br />926 adults scheduled for elective colorectal surgery.<br /><b>Intervention</b><br />Patients were randomised to receive either a single 1 g dose of ornidazole (n=463) or placebo (n=463) orally 12 hours before surgery, in addition to intravenous antimicrobial prophylaxis before surgical incision.<br /><b>Main outcome measures</b><br />The primary outcome was the proportion of patients with surgical site infection within 30 days after surgery. Secondary outcomes included individual types of surgical site infections and major postoperative complications (Clavien-Dindo classification grade 3 or higher) within 30 days after surgery.<br /><b>Results</b><br />Of the 960 patients who were enrolled, 926 (96%) were included in the analysis. The mean age of participants was 63 years and 554 (60%) were men. Surgical site infection within 30 days after surgery occurred in 60 of 463 patients (13%) in the oral prophylaxis group and 100 of 463 (22%) in the placebo group (absolute difference -8.6%, 95% confidence interval -13.5% to -3.8%; relative risk 0.60, 95% confidence interval 0.45 to 0.80). The proportion of patients with deep infections was 4.8% in the oral prophylaxis group and 8.0% in the placebo group (absolute difference -3.2%, 95% confidence interval -6.4% to -0.1%). The proportion of patients with organ space infections was 5.0% in the oral prophylaxis group and 8.4% in the placebo group (absolute difference -3.4%, -6.7% to -0.2%). Major postoperative complications occurred in 9.1% patients in the oral prophylaxis group and 13.6% in the placebo group (absolute difference -4.5%, -8.6% to -0.5%).<br /><b>Conclusion</b><br />Among adults undergoing elective colorectal surgery, the addition of a single 1 g dose of ornidazole compared with placebo before surgery significantly reduced surgical site infections.<br /><b>Trial registration</b><br />ClinicalTrials.gov NCT02618720.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 03 Nov 2022; 379:e071476</small></div>
Futier E, Jaber S, Garot M, Vignaud M, ... Paugam-Burtz C, COMBINE study group
BMJ: 03 Nov 2022; 379:e071476 | PMID: 36328372
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<div><h4>Transmission dynamics of monkeypox in the United Kingdom: contact tracing study.</h4><i>Ward T, Christie R, Paton RS, Cumming F, Overton CE</i><br /><b>Objective</b><br />To analyse the transmission dynamics of the monkeypox outbreak in the UK, declared a Public Health Emergency of International Concern in July 2022.<br /><b>Design</b><br />Contact tracing study, linking data on case-contact pairs and on probable exposure dates.<br /><b>Setting</b><br />Case questionnaires from the UK Health Security Agency (UKHSA), United Kingdom.<br /><b>Participants</b><br />2746 people with polymerase chain reaction confirmed monkeypox virus in the UK between 6 May and 1 August 2022.<br /><b>Main outcome measures</b><br />The incubation period and serial interval of a monkeypox infection using two bayesian time delay models-one corrected for interval censoring (ICC-interval censoring corrected) and one corrected for interval censoring, right truncation, and epidemic phase bias (ICRTC-interval censoring right truncation corrected). Growth rates of cases by reporting date, when monkeypox virus was confirmed and reported to UKHSA, were estimated using generalised additive models.<br /><b>Results</b><br />The mean age of participants was 37.8 years and 95% reported being gay, bisexual, and other men who have sex with men (1160 out of 1213 reporting). The mean incubation period was estimated to be 7.6 days (95% credible interval 6.5 to 9.9) using the ICC model and 7.8 days (6.6 to 9.2) using the ICRTC model. The estimated mean serial interval was 8.0 days (95% credible interval 6.5 to 9.8) using the ICC model and 9.5 days (7.4 to 12.3) using the ICRTC model. Although the mean serial interval was longer than the incubation period for both models, short serial intervals were more common than short incubation periods, with the 25th centile and the median of the serial interval shorter than the incubation period. For the ICC and ICRTC models, the corresponding estimates ranged from 1.8 days (95% credible interval 1.5 to 1.8) to 1.6 days (1.4 to 1.6) shorter at the 25th centile and 1.6 days (1.5 to 1.7) to 0.8 days (0.3 to 1.2) shorter at the median. 10 out of 13 linked patients had documented pre-symptomatic transmission. Doubling times of cases declined from 9.07 days (95% confidence interval 12.63 to 7.08) on the 6 May, when the first case of monkeypox was reported in the UK, to a halving time of 29 days (95% confidence interval 38.02 to 23.44) on 1 August.<br /><b>Conclusions</b><br />Analysis of the instantaneous growth rate of monkeypox incidence indicates that the epidemic peaked in the UK as of 9 July and then started to decline. Short serial intervals were more common than short incubation periods suggesting considerable pre-symptomatic transmission, which was validated through linked patient level records. For patients who could be linked through personally identifiable data, four days was the maximum time that transmission was detected before symptoms manifested. An isolation period of 16 to 23 days would be required to detect 95% of people with a potential infection. The 95th centile of the serial interval was between 23 and 41 days, suggesting long infectious periods.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 02 Nov 2022; 379:e073153</small></div>
Ward T, Christie R, Paton RS, Cumming F, Overton CE
BMJ: 02 Nov 2022; 379:e073153 | PMID: 36323407
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<div><h4>Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study.</h4><i>Pradhan R, Lu S, Yin H, Yu OHY, ... Suissa S, Azoulay L</i><br /><b>Objective</b><br />To determine whether the use of glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, separately, is associated with a decreased risk of exacerbations of chronic obstructive pulmonary disease among patients with chronic obstructive pulmonary disease and type 2 diabetes.<br /><b>Design</b><br />Population based cohort study using an active comparator, new user design.<br /><b>Setting</b><br />The United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases.<br /><b>Participants</b><br />Three active comparator, new user cohorts of patients starting the study drugs (GLP-1 receptor agonists, DPP-4 inhibitors, or SGLT-2 inhibitors) or sulfonylureas with a history of chronic obstructive pulmonary disease. The first cohort included 1252 patients starting GLP-1 receptor agonists and 14 259 starting sulfonylureas, the second cohort included 8731 patients starting DPP-4 inhibitors and 18 204 starting sulfonylureas, and the third cohort included 2956 patients starting SGLT-2 inhibitors and 10 841 starting sulfonylureas.<br /><b>Main outcome measures</b><br />Cox proportional hazards models with propensity score fine stratification weighting were fitted to estimate hazard ratios and 95% confidence intervals of severe exacerbation of chronic obstructive pulmonary disease (defined as hospital admission for chronic obstructive pulmonary disease), separately for GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Whether these drugs were associated with a decreased risk of moderate exacerbation (defined as a co-prescription of an oral corticosteroid and an antibiotic along with an outpatient diagnosis of acute chronic obstructive pulmonary disease exacerbation on the same day) was also assessed.<br /><b>Results</b><br />Compared with sulfonylureas, GLP-1 receptor agonists were associated with a 30% decreased risk of severe exacerbation (3.5 <i>v</i> 5.0 events per 100 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and moderate exacerbation (0.63, 0.43 to 0.94). DPP-4 inhibitors were associated with a modestly decreased incidence of severe exacerbation (4.6 <i>v</i>. 5.1 events per 100 person years; hazard ratio 0.91, 0.82 to 1.02) and moderate exacerbation (0.93, 0.82 to 1.07), with confidence intervals including the null value. Finally, SGLT-2 inhibitors were associated with a 38% decreased risk of severe exacerbation (2.4 <i>v</i> 3.9 events per 100 person years; hazard ratio 0.62, 0.48 to 0.81) but not moderate exacerbation (1.02, 0.83 to 1.27).<br /><b>Conclusions</b><br />In this population based study, GLP-1 receptor agonists and SGLT-2 inhibitors were associated with a reduced risk of severe exacerbations compared with sulfonylureas in patients with chronic obstructive pulmonary disease and type 2 diabetes. DPP-4 inhibitors were not clearly associated with a decreased risk of chronic obstructive pulmonary disease exacerbations.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 01 Nov 2022; 379:e071380</small></div>
Abstract
<div><h4>Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial.</h4><i>Blom AW, Lenguerrand E, Strange S, Noble SM, ... Whitehouse MR, INFORM trial group</i><br /><b>Objectives</b><br />To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures.<br /><b>Design</b><br />Pragmatic, parallel group, open label, randomised controlled trial.<br /><b>Setting</b><br />High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018.<br /><b>Participants</b><br />140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision).<br /><b>Interventions</b><br />A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure.<br /><b>Main outcome measures</b><br />The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups.<br /><b>Results</b><br />The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval -8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of £11 167 (95% confidence interval £638 to £21 696) at a £20 000 per quality adjusted life years threshold (£1.0; $1.1; €1.4).<br /><b>Conclusions</b><br />At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery.<br /><b>Trial registration</b><br />ISRCTN registry ISRCTN10956306.<br /><br />© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.<br /><br /><small>BMJ: 31 Oct 2022; 379:e071281</small></div>
Blom AW, Lenguerrand E, Strange S, Noble SM, ... Whitehouse MR, INFORM trial group
BMJ: 31 Oct 2022; 379:e071281 | PMID: 36316046
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This program is still in alpha version.