Rationale, Aims, and Objectives: It is generally believed that evidence from low quality of evidence generate inaccurate estimates about treatment effects more often than evidence from high (certainty) quality evidence (CoE). As a result, we would expect that (a) estimates of effects of health interventions initially based on high CoE change less frequently than the effects estimated by lower CoE (b) the estimates of magnitude of effect size differ between high and low CoE. Empirical assessment of these foundational principles of evidence-based medicine has been lacking. Methods: We reviewed the Cochrane Database of Systematic Reviews from January 2016 through May 2021 for pairs of original and updated reviews for change in CoE assessments based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We assessed the difference in effect sizes between the original versus updated reviews as a function of change in CoE, which we report as a ratio of odds ratio (ROR). We compared ROR generated in the studies in which CoE changed from very low/low (VL/L) to moderate/high (M/H) versus M/H to VL/L. Heterogeneity and inconsistency were assessed using the tau and I2 statistic. We also assessed the change in precision of effect estimates (by calculating the ratio of standard errors) (seR), and the absolute deviation in estimates of treatment effects (aROR). Results: Four hundred and nineteen pairs of reviews were included of which 414 (207 \u00d7 2) informed the CoE appraisal and 384 (192 \u00d7 2) the assessment of effect size. We found that CoE originally appraised as VL/L had 2.1 [95% confidence interval (CI): 1.19\u20134.12; p = 0.0091] times higher odds to be changed in the future studies than M/H CoE. However, the effect size was not different (p = 1) when CoE changed from VL/L \u2192 M/H [ROR = 1.02 (95% CI: 0.74\u20131.39)] compared with M/H \u2192 VL/L (ROR = 1.02 [95% CI: 0.44\u20132.37]). Similar overlap in aROR between the VL/L \u2192 M/H versus M/H \u2192 VL/L subgroups was observed [median (IQR): 1.12 (1.07\u20131.57) vs. 1.21 (1.12\u20132.43)]. We observed large inconsistency across ROR estimates (I2 = 99%). There was larger imprecision in treatment effects when CoE changed from VL/L \u2192 M/H (seR = 1.46) than when it changed from M/H \u2192 VL/L (seR = 0.72). Conclusions: We found that low-quality evidence changes more often than high CoE. However, the effect size did not systematically differ between the studies with low versus high CoE. The finding that the effect size did not differ between low and high CoE indicate urgent need to refine current EBM critical appraisal methods.
\n \n\n \n \nBACKGROUND/AIMS: The European Union Clinical Trials Register is a public facing portal containing information on trials of medicinal products conducted under the purview of the European Union regulatory system. As of September 2021, the registry holds information on over 40,000 trials. Given its distinct regulatory purpose, and results reporting requirements, the European Union Clinical Trials Register should be a valuable open-source hub for trial information. Past work examining the European Union Clinical Trials Register has suggested that data quality on the registry may be lacking. We therefore set out to examine the quality and availability of trial data on the registry with a focus on areas that fall under the authority of regulators in each European Union/European Economic Area country. METHODS: Using data scraped from the full European Union Clinical Trials Register public dataset, we examined the extent of issues with three areas of trial data availability linked to European Union regulations. We examined whether there is evidence for missing registration of protocols in the public database, whether information on the completion of clinical trials is being made available and how often the results of trials are posted to the registry. We assessed each area overall, and examined variation between national regulators and over time. RESULTS: Major issues with the availability of expected protocols and information on trial completion were focused in a few countries. Overall, when comparing enrolment countries from tabular results to available registrations, 26,932 of 31,118 (86.5%) expected protocols were available and 22 of 30 (73%) countries had over 90% of expected protocols available. The majority of missing protocols, totalling 2764 (66%), were from just three countries: France, Norway and Poland. Evidence for this issue is further supported by data on trends in new registrations by country over time. Low availability of data on trial completion is also most pronounced in a minority of countries, like Spain and the Netherlands, with consistent trends for missingness over time. Finally, overall results availability is substantially worse among the 23,623 trials with a single registered European Union protocol (n = 6259, 26.5%) compared to 13,897 of those taking place in multiple countries (n = 8423, 60.6%). Reporting for single-protocol trials was consistently low across both time and location. CONCLUSION: Deficiencies in the public availability of trial protocols, trial completion information and summary results complicate the utility of the European Union Clinical Trials Register for research, transparency and accountability efforts. Users of the registry would benefit from a more complete and accurate accounting of the European research environment via the official European Union registry. We recommend regulators at the national and pan-national level undertake routine audits of approved trials to ensure national-level issues are proactively and transparently identified, documented and addressed.
\n \n\n \n \nBACKGROUND: The impact of the COVID-19 pandemic on patients' and clinicians' perceptions of healthcare-seeking behaviour and delivery of care is unclear. The pandemic accelerated the use of remote care and understanding its benefits and drawbacks may inform its implementation during this and future healthcare emergencies. AIM: To explore patients' and primary care professionals' (PCPs) experiences of primary care delivery in the first wave of the pandemic. DESIGN & SETTING: Qualitative study using semi-structured interviews in primary care in eight European countries RESULTS: We conducted 146 interviews with 80 PCPs and 66 patients consulting for respiratory tract infection (RTI) symptoms, in eight European countries (England, Ireland, Belgium, the Netherlands, Greece, Poland, Sweden and Germany). Data was collected between April and July 2020 and analysed using thematic analysis. We found that patients accepted telemedicine when PCPs spent time to understand and address their concerns, but a minority preferred in-person consultations. PCPs felt that remote consultations created emotional distance between themselves and patients, and they reported having to manage diverse COVID-19-related medical and social concerns. CONCLUSION: Remote consultations for RTI symptoms may be acceptable long-term if both groups are happy to use this format but it is important that PCPs take time to address patients' concerns and provide safety-netting advice.
\n \n\n \n \nBackground: Health worker training on disability is a recognized component of achieving high standards of health for people with disabilities, given that health worker's lack of knowledge, stigma, and negative attitudes towards people with disabilities act as barriers to high quality health care. Objective: To understand the published literature on training health workers about disability. Methods: We searched five databases for relevant peer-reviewed articles published between January 2012 and January 2021. Studies that focused on training health care workers to improve knowledge, confidence, self-efficacy, and competence to support people with physical, sensory, or intellectual impairments were included. Data about the details of the intervention (setting, participants, format, impact assessments, etc.) and its effects were extracted. Results: There is an array of highly local tools to train health workers across stages of their training and careers (preservice, in-service, and continuing professional development). Studies involving people with disabilities in the training, community placements, simulations, or interactive sessions were found to be most effective in improving knowledge, confidence, competency, and self-efficacy. Conclusions: As part of initiatives to build inclusive health systems and improve health outcomes for people with disabilities, health workers around the world need to receive appropriate and evidence-based training that combines multiple methods and involves people with disabilities. To monitor progress on the impact of training, there should also be a standardized measure of impact on core outcomes.
\n \n\n \n \nOBJECTIVES: The aim was to investigate the impact of a group-based weight management programme on symptoms of depression and anxiety compared with self-help in a randomised controlled trial (RCT). METHOD: People with overweight (Body Mass Index [BMI]\u226528kg/m2) were randomly allocated self-help (n = 211) or a group-based weight management programme for 12 weeks (n = 528) or 52 weeks (n = 528) between 18/10/2012 and 10/02/2014. Symptoms were assessed using the Hospital Anxiety and Depression Scale, at baseline, 3, 12 and 24 months. Linear regression modelling examined changes in Hospital Anxiety and Depression Scale between trial arms. RESULTS: At 3 months, there was a -0.6 point difference (95% confidence interval [CI], -1.1, -0.1) in depression score and -0.1 difference (95% CI, -0.7, 0.4) in anxiety score between group-based weight management programme and self-help. At subsequent time points there was no consistent evidence of a difference in depression or anxiety scores between trial arms. There was no evidence that depression or anxiety worsened at any time point. CONCLUSIONS: There was no evidence of harm to depression or anxiety symptoms as a result of attending a group-based weight loss programme. There was a transient reduction in symptoms of depression, but not anxiety, compared to self-help. This effect equates to less than 1 point out of 21 on the Hospital Anxiety and Depression Scale and is not clinically significant.
\n \n\n \n \nBackground Physical health outcomes in severe mental illness are worse than in the general population. Routine physical health check completion in this group is poor. Aims To quantitatively and qualitatively evaluate the impact of point of care (POC) blood testing on physical health check completion in community mental health services. Method In a prospective cohort design, we equipped an early intervention service (EIS) and a community mental health team (CMHT) with a POC blood testing device for 6 months. We compared rates of blood test and full physical health check completion in the intervention teams with a matched EIS and CMHT, historically and during the intervention. We explored attitudes to POC testing using thematic analysis of semi-structured interviews with patients and clinicians. Results Although the CMHT scarcely used the POC device and saw no change in outcomes, direct comparison of testing rates in the intervention period showed increased physical health check completion in the EIS with the device (rate ratio RR = 5.18; 95% CI 2.54-12.44; P < 0.001) compared with usual care. The rate was consistent with the EIS's increasing rate of testing over time (RR = 0.45; 95% 0.09-2.08; P = 0.32). Similar trends were seen in blood test completion. POC testing was acceptable to patients but clinicians reported usability, provision and impact on the therapeutic relationship as barriers to uptake. Conclusions POC testing was beneficial and acceptable to patients and may increase physical health check uptake. Further research, accounting for clinician barriers, is needed to evaluate its clinical and cost-effectiveness.
\n \n\n \n \n\nBackground\nEvidence is required to guide the redesign of health care for older people who require hospital admission.\n\n\nObjectives\nWe assessed the clinical effectiveness and cost-effectiveness of geriatrician-led admission avoidance hospital at home with comprehensive geriatric assessment, the experiences of older people and their caregivers, and how the services differed.\n\n\nDesign\nA multisite, randomised, open trial of comprehensive geriatric assessment hospital at home, compared with admission to hospital, using a 2\u2009:\u20091 (hospital at home to hospital) ratio, and a parallel economic and process evaluation. Participants were randomised using a secure online system.\n\n\nSetting\nParticipants were recruited from primary care or acute hospital assessment units from nine sites across the UK.\n\n\nParticipants\nOlder people who required hospital admission because of an acute change in health.\n\n\nIntervention\nGeriatrician-led admission avoidance hospital at home with comprehensive geriatric assessment.\n\n\nMain outcome measures\nThe main outcome, \u2018living at home\u2019 (the inverse of death or living in a residential care setting), was measured at 6-month follow-up. Secondary outcomes at 6 months were the incidence of delirium, mortality, new long-term residential care, cognitive impairment, ability to perform activities of daily living, quality-adjusted survival, length of stay and transfer to hospital. Secondary outcomes at 12 months were living at home, new long-term residential care and mortality.\n\n\nResults\nParticipants were allocated to hospital at home (n\u2009=\u2009700) or to hospital (n\u2009=\u2009355). All reported relative risks (RRs) were adjusted and are reported for hospital at home compared with hospital. There were no significant differences between the groups in the proportions of patients \u2018living at home\u2019 at 6 months [528/672 (78.6%) vs. 247/328 (75.3%), RR 1.05, 95% confidence interval (CI) 0.95 to 1.15; p\u2009=\u20090.36] or at 12 months [443/670 (66.1%) vs. 219/325 (67.4%), RR 0.99, 95% CI 0.89 to 1.10; p\u2009=\u20090.80]; mortality at 6 months [114/673 (16.9%) vs. 58/328 (17.7%), RR 0.98, 95% CI 0.65 to 1.47; p\u2009=\u20090.92] or at 12 months [188/670 (28.1%) vs. 82/325 (25.2%), RR 1.14, 95% CI 0.80 to 1.62]; the proportion of patients with cognitive impairment [273/407 (67.1%) vs. 115/183 (62.8%), RR 1.06, 95% CI 0.93 to 1.21; p\u2009=\u20090.36]; or in ability to perform the activities of daily living as measured by the Barthel Index (mean difference 0.24, 95% CI \u20130.33 to 0.80; p\u2009=\u20090.411; hospital at home, n\u2009=\u2009521 patients contributed data; hospital, n\u2009=\u2009256 patients contributed data) or Comorbidity Index (adjusted mean difference 0.0002, 95% CI \u20130.15 to 0.15; p\u2009=\u20090.10; hospital at home, n\u2009=\u2009474 patients contributed data; hospital, n\u2009=\u2009227 patients contributed data) at 6 months. The varying denominator reflects the number of participants who contributed data to the different outcomes. There was a significant reduction in the RR of living in residential care at 6 months [37/646 (5.7%) vs. 27/311 (8.7%), RR 0.58, 95% CI 0.45 to 0.76; p\u2009<\u20090.001] and 12 months [39/646 (6.0%) vs. 27/311 (8.7%), RR 0.61, 95% CI 0.46 to 0.82; p\u2009<\u20090.001], a significant reduction in risk of delirium at 1 month [10/602 (1.7%) vs. 13/295 (4.4%), RR 0.38, 95% CI 0.19 to 0.76; p\u2009=\u20090.006] and an increased risk of transfer to hospital at 1 month [173/672 (25.7%) vs. 64/330 (19.4%), RR 1.32, 95% CI 1.06 to 1.64; p\u2009=\u20090.012], but not at 6 months [343/631 (54.40%) vs. 171/302 (56.6%), RR 0.95, 95% CI 0.86 to 1.06; p\u2009=\u20090.40]. Patient satisfaction was in favour of hospital at home. An unexpected adverse event that might have been related to the research was reported to the Research Ethics Committee. At 6 months, there was a mean difference in NHS, personal social care and informal care costs (mean difference \u2013\u00a33017, 95% CI \u2013\u00a35765 to \u2013\u00a3269), and no difference in quality-adjusted survival. Older people and caregivers played a crucial role in supporting the delivery of health care. In hospital at home this included monitoring a patient\u2019s health and managing transitional care arrangements.\n\n\nLimitations\nThe findings are most applicable to patients referred from an acute hospital assessment unit.\n\n\nConclusions\nComprehensive geriatric assessment hospital at home can provide a cost-effective alternative to hospitalisation for selected older people. Further research that includes a stronger element of carer support might generate evidence to improve health outcomes.\n\n\nTrial registration\nThis trial is registered as ISRCTN60477865.\n\n\nFunding\nThis project was funded by the National Institute for Health Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 2. See the NIHR Journals Library website for further project information.\n
\n \n\n \n \nBACKGROUND: Cerebral Palsy (CP) is the most common childhood physical disability in developed countries. Parents of children with CP experience difficulties which can result in reduced wellbeing. Health professionals supporting children with CP have been encouraged to focus on parental wellbeing as this forms part of the child's essential environment. There is a lack of evidence about interventions which holistically support the whole family by providing therapeutic input for the child and support for parents. This study aimed to explore parents' experiences of play-based groups for children with CP and their parents, with a focus on the groups' impact on parents' wellbeing. METHODS: Parents of children with CP who had attended play-based groups in the year prior were recruited for this qualitative study. Semi-structured interviews were conducted, audio-recorded and transcribed verbatim. Participants' demographic characteristics were collected as contextual information. Data was analysed using an inductive thematic approach. RESULTS: Ten mothers were interviewed. Overall, mothers had positive experiences of the groups and perceived them as an important influence on their wellbeing. Four themes described mothers' experiences of the groups and the subsequent impact on their wellbeing: (1) Practical Support, (2) Connecting with Others, (3) Transitioning Journeys, and (4) Different Motivators, Different Experiences. Numerous factors influenced mothers' experiences of attending the groups and the subsequent impact on their wellbeing. This included mothers' individual experiences of having a child with CP. CONCLUSIONS: Interventions combining practical and social support for the whole family can have a positive impact on the wellbeing of mothers of children with CP. Care should be taken to provide individualised support for each family. There is no 'one size fits all' approach and a package of care can provide multiple services which meet the varying needs of mothers and their children with CP.
\n \n\n \n \nBackground: Morton\u2019s neuroma is a common condition that routinely presents in podiatric practice. The aim of this study was to systematically synthesize the evidence relating to the effectiveness of a corticosteroid injection for Morton\u2019s neuroma. Methods: Studies with a publication date of 1960 or later were eligible, and searches were performed within the Turning Research Into Practice database; the Cochrane Central Register of Controlled Trials; the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register; MEDLINE (Ovid); PubMed; Embase; Cumulative Index to Nursing and Allied Health Literature; and the gray literature. Study selection criteria included randomized and nonrandomized controlled trials where a single corticosteroid injection for Morton\u2019s neuroma pain was investigated. The primary outcome was Morton\u2019s neuroma pain as measured by any standard validated pain scale. Results: Ten studies involving 695 participants were included. The quality of the studies was considered low and subject to bias. Of the included studies, five compared corticosteroid injection to usual care, one compared corticosteroid injection to local anesthetic alone, one compared ultrasound-guided to non\u2013ultrasound-guided injections, three compared corticosteroid injections to surgery, one compared small to large neuromas, six assessed patient satisfaction, four measured adverse events, one studied return to work, and one examined failure of the corticosteroid injection to improve pain. Overall, these studies identified a moderate short-to medium-term benefit of corticosteroid injections on the primary outcome of pain and a low adverse event rate. Conclusions: A single corticosteroid injection appears to have a beneficial short-to medium-term effect on Morton\u2019s neuroma pain. It appears superior to usual care, but its superiority to local anaesthetic alone is questionable, and it is inferior to surgical excision. A very low adverse event rate was noted throughout the studies, indicating the intervention is safe when used for Morton\u2019s neuroma. However, the quality of the evidence is low, and these findings may change with further research.
\n \n\n \n \nIntroductionThe UK Medicines and Healthcare products Regulatory Agency (MHRA) has published frequent summaries of spontaneous reports of suspected adverse drug reactions (ADRs) (Yellow Cards) to vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The EudraVigilance database has provided similar data for the European Economic Area.ObjectiveOur objective was to characterize the evolution over time of spontaneous reports of suspected ADRs to coronavirus disease 2019 (COVID-19) vaccines and to observe the effect of a publicized reaction (cerebral venous and sinus thrombosis [CVST]) on reporting rates.MethodsWe used publicly available data on reports of suspected ADRs and doses of vaccine administered, published by the MHRA, EudraVigilance, and the European Centre for Disease Prevention and Control to calculate reporting rates.ResultsApproximately 4814 Yellow Card reports (23 fatal) per million doses of ChAdOx1 nCoV-19 (AstraZeneca) and 2890 (13 fatal) per million doses of tozinameran (Pfizer/BioNTech) have been lodged. Between 15 March and 31 October 2021, cumulative European reports of CVST rose from 0 to 443 (183 with thrombocytopenia, 72 fatal) with ChAdOx1 nCoV-19 and from 2 to 315 (9 with thrombocytopenia, 28 fatal) with tozinameran. European cases of retinal vein occlusion and thrombosis rose from 0 to 168 with ChAdOx1 nCoV-19 and from 1 to 220 with tozinameran; four of the ChAdOx1 nCoV-19 cases were associated with thrombocytopenia.ConclusionReports of fatal adverse reactions to coronavirus vaccines are very rare. Reports of CVST have been made in relation to both vaccines. Most were submitted after the reaction had been publicized. Thrombocytopenia occurred in a minority of cases. Reports linked both vaccines to cases of retinal vein thrombosis, just four\u00a0cases with thrombocytopenia. This suggests two different mechanisms of thrombosis associated with the vaccines.
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