•Willingness to be vaccinated was generally high across the UK population.•Vaccine hesitancy exists in population subgroups.•Black and Pakistani/Bangladeshi ethnic groups had higher levels of vaccine ...hesitancy.•Vaccine hesitancy levels are higher in people with lower education levels.•Focus on ethnic minority and socioeconomic groups is needed during vaccine delivery.
Vaccine hesitancy could undermine efforts to control COVID-19. We investigated the prevalence of COVID-19 vaccine hesitancy in the UK and identified vaccine hesitant subgroups. The ‘Understanding Society’ COVID-19 survey asked participants (n = 12,035) their likelihood of vaccine uptake and reason for hesitancy. Cross-sectional analysis assessed vaccine hesitancy prevalence and logistic regression calculated odds ratios. Overall vaccine hesitancy was low (18% unlikely/very unlikely). Vaccine hesitancy was higher in women (21.0% vs 14.7%), younger age groups (26.5% in 16–24 year olds vs 4.5% in 75 + ) and those with lower education levels (18.6% no qualifications vs 13.2% degree qualified). Vaccine hesitancy was high in Black (71.8%) and Pakistani/Bangladeshi (42.3%) ethnic groups. Odds ratios for vaccine hesitancy were 13.42 (95% CI:6.86, 26.24) in Black and 2.54 (95% CI:1.19, 5.44) in Pakistani/Bangladeshi groups (compared to White British/Irish) and 3.54 (95% CI:2.06, 6.09) for people with no qualifications versus degree. Urgent action to address hesitancy is needed for some but not all ethnic minority groups.
AbstractObjectiveTo review and appraise the validity and usefulness of published and preprint reports of prediction models for prognosis of patients with covid-19, and for detecting people in the ...general population at increased risk of covid-19 infection or being admitted to hospital or dying with the disease.DesignLiving systematic review and critical appraisal by the covid-PRECISE (Precise Risk Estimation to optimise covid-19 Care for Infected or Suspected patients in diverse sEttings) group.Data sourcesPubMed and Embase through Ovid, up to 17 February 2021, supplemented with arXiv, medRxiv, and bioRxiv up to 5 May 2020.Study selectionStudies that developed or validated a multivariable covid-19 related prediction model.Data extractionAt least two authors independently extracted data using the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist; risk of bias was assessed using PROBAST (prediction model risk of bias assessment tool).Results126 978 titles were screened, and 412 studies describing 731 new prediction models or validations were included. Of these 731, 125 were diagnostic models (including 75 based on medical imaging) and the remaining 606 were prognostic models for either identifying those at risk of covid-19 in the general population (13 models) or predicting diverse outcomes in those individuals with confirmed covid-19 (593 models). Owing to the widespread availability of diagnostic testing capacity after the summer of 2020, this living review has now focused on the prognostic models. Of these, 29 had low risk of bias, 32 had unclear risk of bias, and 545 had high risk of bias. The most common causes for high risk of bias were inadequate sample sizes (n=408, 67%) and inappropriate or incomplete evaluation of model performance (n=338, 56%). 381 models were newly developed, and 225 were external validations of existing models. The reported C indexes varied between 0.77 and 0.93 in development studies with low risk of bias, and between 0.56 and 0.78 in external validations with low risk of bias. The Qcovid models, the PRIEST score, Carr’s model, the ISARIC4C Deterioration model, and the Xie model showed adequate predictive performance in studies at low risk of bias. Details on all reviewed models are publicly available at https://www.covprecise.org/.ConclusionPrediction models for covid-19 entered the academic literature to support medical decision making at unprecedented speed and in large numbers. Most published prediction model studies were poorly reported and at high risk of bias such that their reported predictive performances are probably optimistic. Models with low risk of bias should be validated before clinical implementation, preferably through collaborative efforts to also allow an investigation of the heterogeneity in their performance across various populations and settings. Methodological guidance, as provided in this paper, should be followed because unreliable predictions could cause more harm than benefit in guiding clinical decisions. Finally, prediction modellers should adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guideline.Systematic review registrationProtocol https://osf.io/ehc47/, registration https://osf.io/wy245.Readers’ noteThis article is the final version of a living systematic review that has been updated over the past two years to reflect emerging evidence. This version is update 4 of the original article published on 7 April 2020 (BMJ 2020;369:m1328). Previous updates can be found as data supplements (https://www.bmj.com/content/369/bmj.m1328/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.
The reporting quality in medical research has recently been critically discussed. While reporting guidelines intend to maximize the value from funded research, and initiatives such as the EQUATOR ...network have been introduced to advance high quality reporting, the uptake of the guidelines by researchers could be improved. The aim of this study was to assess the contribution of a biostatistician to the reporting and methodological quality of health research, and to identify methodological knowledge gaps.
In a retrospective, single center, observational cohort study, two groups of publications were compared. The group of exposed publications had an academic biostatistician on the author list, whereas the group of non-exposed publications did not include a biostatistician of the evaluated group. Rating of reporting quality was done in blinded fashion and in duplicate. The primary outcome was a sum score based on six dimensions, ranging between 0 (worst) and 11 (best). The study protocol was reviewed and approved as a registered report.
There were 131 publications in the exposed group published between 2017 and 2018. Of these, 95 were either RCTs, observational, or prediction / prognostic studies. Corresponding matches in the group of non-exposed publications were identified in a reproducible manner. Comparison of reporting quality overall revealed a 1.60 (95%CI from 0.92 to 2.28, p <0.0001) units higher reporting quality for exposed publications. A subgroup analysis within study types showed higher reporting quality across all three study types.
Our study is the first to report an association of a higher reporting quality and methodological strength in health research publications with a biostatistician on the author list. The higher reporting quality persisted through subgroups of study types and dimensions. Methodological knowledge gaps were identified for prediction / prognostic studies, and for reporting on statistical methods in general and missing values, specifically.
Clinically significant, localized prostate cancer is currently treated with whole gland therapy. This approach is effective but associated with genitourinary and rectal side effects. Focal therapy of ...prostate cancer has been proposed as an alternative. The aim of this study was to determine the oncologic and functional outcomes of focal high intensity focused ultrasound therapy of prostate cancer.
In this single center, prospective study 75 men were treated between April 2014 and April 2018. Multiparametric magnetic resonance imaging and transperineal template saturation prostate biopsy were performed to localize prostate cancer, followed by focal ablation with high intensity focused ultrasound. The study primary end point was the detection of clinically significant prostate cancer, defined as Gleason score 7 or greater, at 6-month followup transperineal template saturation prostate biopsy. Genitourinary side effects were of secondary interest.
Median patient age was 67 years (IQR 60-71) and median prostate specific antigen was 5.87 ng/ml (IQR 4.65-7.44). There were 5 low risk (6.7%) and 70 intermediate risk (93.3%) cancers. Clinically significant prostate cancer was detected in 41% of the men (95% CI 30.3-53.0) who underwent biopsy at 6 months and the median number of sampled cores was 44 (IQR 36-44). Prostate specific antigen (OR 1.17, IQR 0.49-2.85, p=0.71) and multiparametric magnetic resonance imaging (14.3% sensitivity, IQR 6.7-31.5) performed poorly to predict positive biopsies. Pad-free continence and erection sufficient for penetration were preserved in 63 of 64 (98.4%) and 31 of 45 patients (68.9%), respectively.
Focal therapy with high intensity focused ultrasound leads to a low rate of genitourinary side effects. Followup biopsy of treated and untreated prostates remains the only modality to adequately select men in need of early salvage treatment.
IntroductionIt is known that only a limited proportion of developed clinical prediction models (CPMs) are implemented and/or used in clinical practice. This may result in a large amount of research ...waste, even when considering that some CPMs may demonstrate poor performance. Cross-sectional estimates of the numbers of CPMs that have been developed, validated, evaluated for impact or utilized in practice, have been made in specific medical fields, but studies across multiple fields and studies following up the fate of CPMs are lacking.Methods and analysisWe have conducted a systematic search for prediction model studies published between January 1995 and December 2020 using the Pubmed and Embase databases, applying a validated search strategy. Taking random samples for every calendar year, abstracts and articles were screened until a target of 100 CPM development studies were identified. Next, we will perform a forward citation search of the resulting CPM development article cohort to identify articles on external validation, impact assessment or implementation of those CPMs. We will also invite the authors of the development studies to complete an online survey to track implementation and clinical utilization of the CPMs.We will conduct a descriptive synthesis of the included studies, using data from the forward citation search and online survey to quantify the proportion of developed models that are validated, assessed for their impact, implemented and/or used in patient care. We will conduct time-to-event analysis using Kaplan-Meier plots.Ethics and disseminationNo patient data are involved in the research. Most information will be extracted from published articles. We request written informed consent from the survey respondents. Results will be disseminated through publication in a peer-reviewed journal and presented at international conferences.OSF registration(https://osf.io/nj8s9).
Introduction
This study aims at exploring biventricular remodelling and its implications for outcome in a representative patient cohort with severe aortic stenosis (AS) undergoing transcatheter ...aortic valve implantation (TAVI).
Methods and results
Pre-interventional echocardiographic examinations of 100 patients with severe AS undergoing TAVI were assessed by speckle tracking echocardiography of both ventricles. Association with mortality was determined for right ventricular global longitudinal strain (RVGLS), RV free wall strain (RVFWS) and left ventricular global longitudinal strain (LVGLS). During a median follow-up of 1,367 959–2,123 days, 33 patients (33%) died. RVGLS was lower in non-survivors −13.9% (−16.4 to −12.9) than survivors −17.1% (−20.2 to −15.2);
P
= 0.001. In contrast, LVGLS as well as the conventional parameters LV ejection fraction (LVEF) and RV fractional area change (RVFAC) did not differ (
P
= ns). Kaplan–Meier analyses indicated a reduced survival probability when RVGLS was below the −14.6% cutpoint (
P
< 0.001). Lower RVGLS was associated with higher mortality HR 1.13 (95% CI 1.04–1.23);
P
= 0.003 independent of LVGLS, LVEF, RVFAC, and EuroSCORE II. Addition of RVGLS clearly improved the fitness of bivariable and multivariable models including LVGLS, LVEF, RVFAC, and EuroSCORE II with potential incremental value for mortality prediction. In contrast, LVGLS, LVEF, and RVFAC were not associated with mortality.
Discussion
In patients with severe AS undergoing TAVI, RVGLS but not LVGLS was reduced in non-survivors compared to survivors, differentiated non-survivors from survivors, was independently associated with mortality, and exhibited potential incremental value for outcome prediction. RVGLS appears to be more suitable than LVGLS for risk stratification in AS and timely valve replacement.
Background
Researchers have in recent years begun to investigate ophthalmological manifestations of multiple sclerosis (MS) other than optic neuritis (ON), and it is now clear that changes to retinal ...function (measured using the electroretinogram, ERG) and structure (measured using optical coherence tomography, OCT) are found in MS patients irrespective of prior ON episodes. ERG results are consistent with dysfunctional bipolar cells, as in other autoimmune diseases. To date, studies have presented only cross-sectional data regarding ERG and OCT. We, therefore, studied the longitudinal course of ERG and OCT in patients with MS, as well as the effect of disability changes and non-ON clinical relapses on these functional and structural measures.
Methods
MS patients (
n
= 23) participating in an ongoing longitudinal observational study were invited to take part in a 3-year ophthalmological substudy. ERG and OCT were performed, and measures of MS-related disability and relapse history were obtained. Study visits were repeated annually. ERG peak times, rod b-wave amplitude, mixed rod/cone and cone b-/a-wave amplitude ratios, thickness of the peripapillary retinal nerve fibre layer, and volumes of the segmented retinal layers/complexes were analysed. Using generalised estimating equation models adjusted for age, ON, and MS treatment status, we assessed changes to ERG and OCT over the study duration, the effect of changes in disability and recent non-ON MS relapses on ERG and OCT, and the effect of selected OCT parameters on corresponding ERG parameters.
Results
At the group level, small fluctuations of several ERG peak times were recorded, with OCT values remaining stable. Increased disability between visits was associated with significant prolongation of mixed rod-cone ERG b-wave peak times. No evidence of associations between OCT and ERG parameters was observed.
Conclusions
Retinal bipolar cell function may be affected by changes in disability in patients with MS; however, recent non-ON MS clinical relapses appear not to affect ERG or OCT results. As ERG changes in MS patients over 3 years are likely to be small and of uncertain clinical relevance, longitudinal studies of retinal function in MS should be planned over an extended period.
Unpaid carers who look after another member of their household (home-carers) have poorer mental health than the general population. The first COVID-19 national lockdown led to an increasing reliance ...on home-carers and we investigate the short- and longer-term impacts of lockdown on their mental health.
Data from 9737 adult participants (aged 16+) from the UK Household Longitudinal Study (Understanding Society) were used to explore changes in 12-item General Health Questionnaire (GHQ-12) score between (a) pre-pandemic (2019) and early lockdowns (April 2020) and (b) early and later (July 2020) lockdowns.
GHQ-12 scores among home-carers were higher pre-lockdown and increased more than for non-carers from 2019 to April 2020 with further increases for home-carers compared with non-carers between April and July. Compared with respondents caring for a spouse/partner, those caring for a child under 18 had a particularly marked increase in GHQ-12 score between 2019 and April, as did those caring for someone with a learning disability. Home-carers of children under 18 improved from April to July while those caring for adult children saw a marked worsening of their mental health. Home-carers with greater care burden saw larger increases in GHQ-12 score from 2019 to April and from April to July, and increases through both periods were greater for home-carers who had formal help prior to lockdown but then lost it.
The mental health of home-carers deteriorated more during lockdown than non-carers. Policies that reinstate support for them and their care-recipients will benefit the health of both vulnerable groups.
Comparative simulation studies are workhorse tools for benchmarking statistical methods. As with other empirical studies, the success of simulation studies hinges on the quality of their design, ...execution, and reporting. If not conducted carefully and transparently, their conclusions may be misleading. In this paper, we discuss various questionable research practices, which may impact the validity of simulation studies, some of which cannot be detected or prevented by the current publication process in statistics journals. To illustrate our point, we invent a novel prediction method with no expected performance gain and benchmark it in a preregistered comparative simulation study. We show how easy it is to make the method appear superior over well‐established competitor methods if questionable research practices are employed. Finally, we provide concrete suggestions for researchers, reviewers, and other academic stakeholders for improving the methodological quality of comparative simulation studies, such as preregistering simulation protocols, incentivizing neutral simulation studies, and code and data sharing.
Abstract
Background
Postoperative delirium (POD) is a frequent complication in older adults, characterised by disturbances in attention, awareness and cognition, and associated with prolonged ...hospitalisation, poor functional recovery, cognitive decline, long-term dementia and increased mortality. Early identification of patients at risk of POD can considerably aid prevention.
Methods
We have developed a preoperative POD risk prediction algorithm using data from eight studies identified during a systematic review and providing individual-level data. Ten-fold cross-validation was used for predictor selection and internal validation of the final penalised logistic regression model. The external validation used data from university hospitals in Switzerland and Germany.
Results
Development included 2,250 surgical (excluding cardiac and intracranial) patients 60 years of age or older, 444 of whom developed POD. The final model included age, body mass index, American Society of Anaesthesiologists (ASA) score, history of delirium, cognitive impairment, medications, optional C-reactive protein (CRP), surgical risk and whether the operation is a laparotomy/thoracotomy. At internal validation, the algorithm had an AUC of 0.80 (95% CI: 0.77–0.82) with CRP and 0.79 (95% CI: 0.77–0.82) without CRP. The external validation consisted of 359 patients, 87 of whom developed POD. The external validation yielded an AUC of 0.74 (95% CI: 0.68–0.80).
Conclusions
The algorithm is named PIPRA (Pre-Interventional Preventive Risk Assessment), has European conformity (ce) certification, is available at http://pipra.ch/ and is accepted for clinical use. It can be used to optimise patient care and prioritise interventions for vulnerable patients and presents an effective way to implement POD prevention strategies in clinical practice.
Graphical abstract
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