Vaccine Effectiveness Studies in the Field Evans, Stephen J.W; Jewell, Nicholas P
New England journal of medicine/The New England journal of medicine,
08/2021, Volume:
385, Issue:
7
Journal Article
Peer reviewed
Open access
The original trials of vaccines against infection with severe acute respiratory disease coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have clearly shown ...vaccine efficacy. However, questions crucial to vaccination policy remain, at best, only partially answered. These include the effect of new virus variants, the timing between vaccine doses, the effect of vaccines on asymptomatic infection in contrast to severe disease, the waning of vaccine immunity, and the potentially enhanced effectiveness of mix-and-match strategies that might be used with booster shots. Wherever possible, vaccine efficacy should be assessed by means of randomized trials. Valid comparison is . . .
The CONSORT (Consolidated Standards of Reporting Trials) Statement, which includes a checklist and a flow diagram, is a guideline developed to help authors improve the reporting of the findings from ...randomized controlled trials. It was updated most recently in 2010. Its primary focus is on individually randomized trials with 2 parallel groups that assess the possible superiority of one treatment compared with another. The CONSORT Statement has been extended to other trial designs such as cluster randomization, and recommendations for noninferiority and equivalence trials were made in 2006. In this article, we present an updated extension of the CONSORT checklist for reporting noninferiority and equivalence trials, based on the 2010 version of the CONSORT Statement and the 2008 CONSORT Statement for the reporting of abstracts, and provide illustrative examples and explanations for those items that differ from the main 2010 CONSORT checklist. The intent is to improve reporting of noninferiority and equivalence trials, enabling readers to assess the reliability of their results and conclusions.
Coronavirus disease 2019 (COVID-19) has rapidly affected mortality worldwide
. There is unprecedented urgency to understand who is most at risk of severe outcomes, and this requires new approaches ...for the timely analysis of large datasets. Working on behalf of NHS England, we created OpenSAFELY-a secure health analytics platform that covers 40% of all patients in England and holds patient data within the existing data centre of a major vendor of primary care electronic health records. Here we used OpenSAFELY to examine factors associated with COVID-19-related death. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with: being male (hazard ratio (HR) 1.59 (95% confidence interval 1.53-1.65)); greater age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people of white ethnicity, Black and South Asian people were at higher risk, even after adjustment for other factors (HR 1.48 (1.29-1.69) and 1.45 (1.32-1.58), respectively). We have quantified a range of clinical factors associated with COVID-19-related death in one of the largest cohort studies on this topic so far. More patient records are rapidly being added to OpenSAFELY, we will update and extend our results regularly.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Dementia and obesity are increasingly important public health issues. Obesity in middle age has been proposed to lead to dementia in old age. We investigated the association between BMI and risk of ...dementia.
For this retrospective cohort study, we used a cohort of 1,958,191 individuals derived from the United Kingdom Clinical Practice Research Datalink (CPRD) which included people aged 40 years or older in whom BMI was recorded between 1992 and 2007. Follow-up was until the practice's final data collection date, patient death or transfer out of practice, or first record of dementia (whichever occurred first). People with a previous record of dementia were excluded. We used Poisson regression to calculate incidence rates of dementia for each BMI category.
Our cohort of 1,958,191 people from UK general practices had a median age at baseline of 55 years (IQR 45-66) and a median follow-up of 9·1 years (IQR 6·3-12·6). Dementia occurred in 45,507 people, at a rate of 2·4 cases per 1000 person-years. Compared with people of a healthy weight, underweight people (BMI <20 kg/m(2)) had a 34% higher (95% CI 29-38) risk of dementia. Furthermore, the incidence of dementia continued to fall for every increasing BMI category, with very obese people (BMI >40 kg/m(2)) having a 29% lower (95% CI 22-36) dementia risk than people of a healthy weight. These patterns persisted throughout two decades of follow-up, after adjustment for potential confounders and allowance for the J-shape association of BMI with mortality.
Being underweight in middle age and old age carries an increased risk of dementia over two decades. Our results contradict the hypothesis that obesity in middle age could increase the risk of dementia in old age. The reasons for and public health consequences of these findings need further investigation.
None.
COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second ...waves of the COVID-19 pandemic in England.
We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 wave 1, and Sept 1 to Dec 31, 2020 wave 2). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region.
Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 95% CI 1·07–1·09), Black group (1·08 1·06–1·09), and mixed ethnicity group (1·04 1·02–1·05) and was decreased in the other ethnicity group (0·77 0·76–0·78) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 1·94–2·04), Black group (1·69 1·62–1·77), mixed ethnicity group (1·49 1·39–1·59), and other ethnicity group (1·20 1·14–1·28). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 1·41–1·55, Black group 1·78 1·67–1·90, mixed ethnicity group 1·63 1·45–1·83, other ethnicity group 1·54 1·41–1·69), COVID-19-related ICU admission (2·18 1·92–2·48, 3·12 2·65–3·67, 2·96 2·26–3·87, 3·18 2·58–3·93), and death (1·26 1·15–1·37, 1·51 1·31–1·71, 1·41 1·11–1·81, 1·22 1·00–1·48). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories.
Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.
Medical Research Council.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
AbstractObjectiveTo evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital ...with coronavirus disease 2019 (covid-19) in the United States.DesignObservational cohort study.SettingNationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system.ParticipantsAll 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation.Main outcome measuresThe main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion.ResultsOf 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses.ConclusionsEarly initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.
The CONSORT (Consolidated Standards of Reporting Trials) Statement, including a checklist and a flow diagram, was developed to help authors improve their reporting of randomized controlled trials. ...Its primary focus was on individually randomized trials with 2 parallel groups that assess the possible superiority of one treatment compared with another but is now being extended to other trial designs. Noninferiority and equivalence trials have methodological features that differ from superiority trials and present particular difficulties in design, conduct, analysis, and interpretation. Although the rationale for such trials occurs frequently, those designed and described specifically as noninferiority or equivalence trials appear less commonly in the medical literature. The quality of reporting of those that are published is often inadequate. In this article, we present an adapted CONSORT checklist for reporting noninferiority and equivalence trials and provide illustrative examples and explanations for those items amended from the original CONSORT checklist. The intent is to improve reporting of noninferiority and equivalence trials, enabling readers to assess the validity of their results and conclusions.
The prevalence of Huntington's disease (HD) in the UK is uncertain. Recently, it has been suggested that the prevalence may be substantially greater than previously reported. This study was ...undertaken to estimate the overall UK prevalence in adults diagnosed with HD, using data from primary care.
The electronic medical records of patients aged 21 years or more, with recorded diagnoses of HD, were retrieved from the UK's General Practice Research Database. Prevalence was estimated from the number of persons with recorded diagnoses of HD, on 1 July each year, between 1990 and 2010. This number was divided by the total number of persons registered with participating general practices on that same date. These data were also used to estimate both age specific prevalence and prevalence in various regions of the UK.
A total of 1136 patients diagnosed with HD, aged 21 years or more, were identified from the database. The estimated prevalence (expressed per 100 000 population) rose from 5.4 (95% CI 3.8 to 7.5) in 1990 to 12.3 (95% CI 11.2 to 13.5) in 2010. Although an increased prevalence was observed within every age group, the most dramatic was in older patients. Age specific prevalence was highest in the 51-60 year age range (15.8 95% CI 9.0 to 22.3). The prevalence of adult HD was lowest in the London region (5.4 (95% CI 3.0 to 8.9)) and highest in the North East of England (18.3 (95% CI 8.6 to 34.6)) and Scotland (16.1 (95% CI 10.8 to 22.9)).
The prevalence of diagnosed HD is clearly substantially higher in the UK than suggested from previous studies. By extrapolation to the UK as a whole, it is estimated that there are more than 5700 people, aged 21 years or more, with HD. There has also been a surprising doubling of the HD population between 1990 and 2010. Many factors may have caused this increase, including more accurate diagnoses, better and more available therapies and an improved life expectancy, even with HD. There also appears to be a greater willingness to register a diagnosis of HD in patients' electronic medical records. Such a high prevalence of HD requires more ingenuity and responsiveness in its care. How to appropriately care for, and respond to, so many individuals and families coping with the exigencies of HD demands our greatest resolve and imagination.
The Prevalence of Huntington's Disease Rawlins, Michael D; Wexler, Nancy S; Wexler, Alice R ...
Neuroepidemiology,
01/2016, Volume:
46, Issue:
2
Journal Article
Peer reviewed
Open access
Reviews of the epidemiology of Huntington's disease (HD) suggest that its worldwide prevalence varies widely. This review was undertaken to confirm these observations, to assess the extent to which ...differences in case-ascertainment and/or diagnosis might be responsible, and to investigate whether the prevalence pattern has changed over the past 50 years.
Eighty two relevant studies were identified from Medline and Embase, previous reviews, scrutiny of references from included and excluded studies and enquiry among those interested in the field.
The lowest rates were among the Asians and the highest among the Caucasians. The differences are not fully explained by varying approaches to case-ascertainment or diagnosis. There was evidence of an increasing prevalence of between 15 and 20% per decade in studies from Australia, North America and Western Europe.
The prevalence of HD varies more than tenfold between different geographical regions. This variation can in part be attributed to differences in case-ascertainment and/or diagnostic criteria, but there is consistent evidence of a lower incidence in Asian populations. There is also evidence that in Australia, North America and in Western Europe (including the United Kingdom), prevalence has increased over the past 50 plus years.
Abstract
Background
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant ...variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death.
Methods
With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021.
Results
Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio aHR: 1.73; 95% confidence interval CI: 1.41–2.13; P < .0001) and 62% higher hazards of hospital admission (1.62; 1.48–1.78; P < .0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74–1.95; P = .45).
Conclusions
The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.
The SARS-CoV-2 alpha variant is associated with a 62% increased risk of hospitalization and a 73% increased risk of death, compared with the originally circulating wild-type virus in England between 16 November 2020 and 21 April 2021.
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