Journal: BMJ

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Abstract

Risk prediction of covid-19 related death and hospital admission in adults after covid-19 vaccination: national prospective cohort study.

Hippisley-Cox J, Coupland CA, Mehta N, Keogh RH, ... Hayward A, Nguyen-Van-Tam JS
Objectives
To derive and validate risk prediction algorithms to estimate the risk of covid-19 related mortality and hospital admission in UK adults after one or two doses of covid-19 vaccination.
Design
Prospective, population based cohort study using the QResearch database linked to data on covid-19 vaccination, SARS-CoV-2 results, hospital admissions, systemic anticancer treatment, radiotherapy, and the national death and cancer registries.
Settings
Adults aged 19-100 years with one or two doses of covid-19 vaccination between 8 December 2020 and 15 June 2021.
Main outcome measures
Primary outcome was covid-19 related death. Secondary outcome was covid-19 related hospital admission. Outcomes were assessed from 14 days after each vaccination dose. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance was evaluated in a separate validation cohort of general practices.
Results
Of 6 952 440 vaccinated patients in the derivation cohort, 5 150 310 (74.1%) had two vaccine doses. Of 2031 covid-19 deaths and 1929 covid-19 hospital admissions, 81 deaths (4.0%) and 71 admissions (3.7%) occurred 14 days or more after the second vaccine dose. The risk algorithms included age, sex, ethnic origin, deprivation, body mass index, a range of comorbidities, and SARS-CoV-2 infection rate. Incidence of covid-19 mortality increased with age and deprivation, male sex, and Indian and Pakistani ethnic origin. Cause specific hazard ratios were highest for patients with Down\'s syndrome (12.7-fold increase), kidney transplantation (8.1-fold), sickle cell disease (7.7-fold), care home residency (4.1-fold), chemotherapy (4.3-fold), HIV/AIDS (3.3-fold), liver cirrhosis (3.0-fold), neurological conditions (2.6-fold), recent bone marrow transplantation or a solid organ transplantation ever (2.5-fold), dementia (2.2-fold), and Parkinson\'s disease (2.2-fold). Other conditions with increased risk (ranging from 1.2-fold to 2.0-fold increases) included chronic kidney disease, blood cancer, epilepsy, chronic obstructive pulmonary disease, coronary heart disease, stroke, atrial fibrillation, heart failure, thromboembolism, peripheral vascular disease, and type 2 diabetes. A similar pattern of associations was seen for covid-19 related hospital admissions. No evidence indicated that associations differed after the second dose, although absolute risks were reduced. The risk algorithm explained 74.1% (95% confidence interval 71.1% to 77.0%) of the variation in time to covid-19 death in the validation cohort. Discrimination was high, with a D statistic of 3.46 (95% confidence interval 3.19 to 3.73) and C statistic of 92.5. Performance was similar after each vaccine dose. In the top 5% of patients with the highest predicted covid-19 mortality risk, sensitivity for identifying covid-19 deaths within 70 days was 78.7%.
Conclusion
This population based risk algorithm performed well showing high levels of discrimination for identifying those patients at highest risk of covid-19 related death and hospital admission after vaccination.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.

BMJ: 16 Sep 2021; 374:n2244
Hippisley-Cox J, Coupland CA, Mehta N, Keogh RH, ... Hayward A, Nguyen-Van-Tam JS
BMJ: 16 Sep 2021; 374:n2244 | PMID: 34535466
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Abstract

Screening and prevention of colorectal cancer.

Kanth P, Inadomi JM
Mortality from colorectal cancer is reduced through screening and early detection; moreover, removal of neoplastic lesions can reduce cancer incidence. While understanding of the risk factors, pathogenesis, and precursor lesions of colorectal cancer has advanced, the cause of the recent increase in cancer among young adults is largely unknown. Multiple invasive, semi- and non-invasive screening modalities have emerged over the past decade. The current emphasis on quality of colonoscopy has improved the effectiveness of screening and prevention, and the role of new technologies in detection of neoplasia, such as artificial intelligence, is rapidly emerging. The overall screening rates in the US, however, are suboptimal, and few interventions have been shown to increase screening uptake. This review provides an overview of colorectal cancer, the current status of screening efforts, and the tools available to reduce mortality from colorectal cancer.

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.

BMJ: 14 Sep 2021; 374:n1855
Kanth P, Inadomi JM
BMJ: 14 Sep 2021; 374:n1855 | PMID: 34526356
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Abstract

Evaluating agreement between bodies of evidence from randomised controlled trials and cohort studies in nutrition research: meta-epidemiological study.

Schwingshackl L, Balduzzi S, Beyerbach J, Bröckelmann N, ... Nagavci B, Meerpohl JJ
Objective
To evaluate the agreement between diet-disease effect estimates of bodies of evidence from randomised controlled trials and those from cohort studies in nutrition research, and to investigate potential factors for disagreement.
Design
Meta-epidemiological study.
Data sources
Cochrane Database of Systematic Reviews, and Medline.
Review methods
Population, intervention or exposure, comparator, outcome (PI/ECO) elements from a body of evidence from cohort studies (BoE(CS)) were matched with corresponding elements of a body of evidence from randomised controlled trials (BoE(RCT)). Pooled ratio of risk ratios or difference of mean differences across all diet-disease outcome pairs were calculated. Subgroup analyses were conducted to explore factors for disagreement. Heterogeneity was assessed through I2 and τ2. Prediction intervals were calculated to assess the range of possible values for the difference in the results between evidence from randomised controlled trials and evidence from cohort studies in future comparisons.
Results
97 diet-disease outcome pairs (that is, matched BoE(RCT) and BoE(CS)) were identified overall. For binary outcomes, the pooled ratio of risk ratios comparing estimates from BoE(RCT) with BoE(CS) was 1.09 (95% confidence interval 1.04 to 1.14; I2=68%; τ2=0.021; 95% prediction interval 0.81 to 1.46). The prediction interval indicated that the difference could be much more substantial, in either direction. We further explored heterogeneity and found that PI/ECO dissimilarities, especially for the comparisons of dietary supplements in randomised controlled trials and nutrient status in cohort studies, explained most of the differences. When the type of intake or exposure between both types of evidence was identical, the estimates were similar. For continuous outcomes, small differences were observed between randomised controlled trials and cohort studies.
Conclusion
On average, the difference in pooled results between estimates from BoE(RCT) and BoE(CS) was small. But wide prediction intervals and some substantial statistical heterogeneity in cohort studies indicate that important differences or potential bias in individual comparisons or studies cannot be excluded. Observed differences were mainly driven by dissimilarities in population, intervention or exposure, comparator, and outcome. These findings could help researchers further understand the integration of such evidence into prospective nutrition evidence syntheses and improve evidence based dietary guidelines.

© 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.

BMJ: 14 Sep 2021; 374:n1864
Schwingshackl L, Balduzzi S, Beyerbach J, Bröckelmann N, ... Nagavci B, Meerpohl JJ
BMJ: 14 Sep 2021; 374:n1864 | PMID: 34526355
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Abstract

Diagnostic accuracy of rapid antigen tests in asymptomatic and presymptomatic close contacts of individuals with confirmed SARS-CoV-2 infection: cross sectional study.

Schuit E, Veldhuijzen IK, Venekamp RP, van den Bijllaardt W, ... van den Hof S, Moons KGM
Objective
To assess the diagnostic test accuracy of two rapid antigen tests in asymptomatic and presymptomatic close contacts of people with SARS-CoV-2 infection on day 5 after exposure.
Design
Prospective cross sectional study.
Setting
Four public health service covid-19 test sites in the Netherlands.
Participants
4274 consecutively included close contacts (identified through test-and-trace programme or contact tracing app) aged 16 years or older and asymptomatic for covid-19 when requesting a test.
Main outcome measures
Sensitivity, specificity, and positive and negative predictive values of Veritor System (Beckton Dickinson) and Biosensor (Roche Diagnostics) rapid antigen tests, with reverse-transcriptase polymerase chain reaction (RT-PCR) testing as reference standard. The viral load cut-off above which 95% of people with a positive RT-PCR test result were virus culture positive was used as a proxy of infectiousness.
Results
Of 2678 participants tested with Veritor, 233 (8.7%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 149 were also detected by the rapid antigen test (sensitivity 63.9%, 95% confidence interval 57.4% to 70.1%). Of 1596 participants tested with Biosensor, 132 (8.3%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 83 were detected by the rapid antigen test (sensitivity 62.9%, 54.0% to 71.1%). In those who were still asymptomatic at the time of sampling, sensitivity was 58.7% (51.1% to 66.0%) for Veritor (n=2317) and 59.4% (49.2% to 69.1%) for Biosensor (n=1414), and in those who developed symptoms were 84.2% (68.7% to 94.0%; n=219) for Veritor and 73.3% (54.1% to 87.7%; n=158) for Biosensor. When a viral load cut-off was applied for infectiouness (≥5.2 log10 SARS-CoV-2 E gene copies/mL), the overall sensitivity was 90.1% (84.2% to 94.4%) for Veritor and 86.8% (78.1% to 93.0%) for Biosensor, and 88.1% (80.5% to 93.5%) for Veritor and 85.1% (74.3% to 92.6%) for Biosensor, among those who remained asymptomatic throughout. Specificities were >99%, and positive and negative predictive values were >90% and >95%, for both rapid antigen tests in all analyses.
Conclusions
The sensitivities of both rapid antigen tests in asymptomatic and presymptomatic close contacts tested on day 5 onwards after close contact with an index case were more than 60%, increasing to more than 85% after a viral load cut-off was applied as a proxy for infectiousness.

© 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.

BMJ: 26 Jul 2021; 374:n1676
Schuit E, Veldhuijzen IK, Venekamp RP, van den Bijllaardt W, ... van den Hof S, Moons KGM
BMJ: 26 Jul 2021; 374:n1676 | PMID: 34315770
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Abstract

Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial.

Ramsden CE, Zamora D, Faurot KR, MacIntosh B, ... Gaylord SA, Mann JD
Objective
To determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine.
Design
Three arm, parallel group, randomized, modified double blind, controlled trial.
Setting
Ambulatory, academic medical center in the United States over 16 weeks.
Participants
182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine).
Interventions
Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: H3 diet (n=61)-increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n=61)-increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n=60)-maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of energy. All participants received foods accounting for two thirds of daily food energy and continued usual care.
Main outcome measures
The primary endpoints (week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six item questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary.
Results
In intention-to-treat analyses (n=182), the H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (-1.6, -4.2 to 1.0, and -1.5, -4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (-1.7, -2.5 to -0.9, and -1.3, -2.1 to -0.5, respectively), moderate to severe headache hours per day (-0.8, -1.2 to -0.4, and -0.7, -1.1 to -0.3, respectively), and headache days per month (-4.0, -5.2 to -2.7, and -2.0, -3.3 to -0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (-2.0, -3.2 to -0.8), suggesting additional benefit from lowering dietary linoleic acid. The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2.
Conclusions
The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life.
Trial registration
ClinicalTrials.gov NCT02012790.

© 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.

BMJ: 29 Jun 2021; 374:n1448
Ramsden CE, Zamora D, Faurot KR, MacIntosh B, ... Gaylord SA, Mann JD
BMJ: 29 Jun 2021; 374:n1448 | PMID: 34526307
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Impact:

This program is still in alpha version.