Background Multimorbidity presents an increasing challenge in the global ageing population. Predicting its development is necessary to help design and deliver effective healthcare. Objective This scoping review aimed to collate and present the body of published evidence on biomarkers and multimorbidity, identifying what work has been done and what gaps remain. Methods We searched the electronic databases MEDLINE, Register of Controlled Trials (Cochrane CENTRAL), CINAHL, PsycINFO, EMBASE, Scopus, Web of Science and TRIP database up until 11 August 2020 and hand-searched the reference lists of included articles. Results We found 34 relevant studies including 12 reporting prospective data and 22 reporting cross-sectional data. These encompassed 14 studies on serum biomarkers, 2 on molecular biomarkers, 7 on physiological biomarkers, 8 on body size biomarkers and 3 on brain function biomarkers. Most studies were undertaken in European or North American populations. There was a broadly consistent finding that obesity was associated with increased multimorbidity. Other results were more varied, reflecting the diverse range of biomarkers investigated, and lack of standardisation of multimorbidity outcome definitions. Longitudinal studies have been set up that are maturing and further evidence can be expected over time. Conclusion There has been limited research on biomarkers to predict the development of multimorbidity, with minimal investigation of putative biomarkers identified in basic research. High quality research studies in this area are needed to progress the development of targeted interventions to prevent or delay the onset of multimorbidity.
\n \n\n \n \nBackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic in 2020, the UK government began a mass severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing program. This study aimed to determine the feasibility and acceptability of organized regular self-testing for SARS-CoV-2.MethodsThis was a mixed-methods observational cohort study in asymptomatic students and staff at University of Oxford, who performed SARS-CoV-2 antigen lateral flow self-testing. Data on uptake and adherence, acceptability, and test interpretation were collected via a smartphone app, an online survey, and qualitative interviews.ResultsAcross 3 main sites, 551 participants (25% of those invited) performed 2728 tests during a follow-up of 5.6 weeks; 447 participants (81%) completed at least 2 tests, and 340 (62%) completed at least 4. The survey, completed by 214 participants (39%), found that 98% of people were confident to self-test and believed self-testing to be beneficial. Acceptability of self-testing was high, with 91% of ratings being acceptable or very acceptable. A total of 2711 (99.4%) test results were negative, 9 were positive, and 8 were inconclusive. Results from 18 qualitative interviews with students and staff revealed that participants valued regular testing, but there were concerns about test accuracy that impacted uptake and adherence.ConclusionsThis is the first study to assess feasibility and acceptability of regular SARS-CoV-2 self-testing. It provides evidence to inform recruitment for, adherence to, and acceptability of regular SARS-CoV-2 self-testing programs for asymptomatic individuals using lateral flow tests. We found that self-testing is acceptable and people were able to interpret results accurately.
\n \n\n \n \nBACKGROUND: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. METHODS: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older-or aged 18 years or older with relevant comorbidities-and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs \u226550 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. FINDINGS: Between Dec 8, 2021, and April 27, 2022, 26\u2009411 participants were randomly assigned, 12\u2009821 to molnupiravir plus usual care, 12\u2009962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12\u2009529 participants from the molnupiravir plus usual care group, and 12\u2009525 from the usual care group were included in the primary analysis population. The mean age of the population was 56\u00b76 years (SD 12\u00b76), and 24\u2009290 (94%) of 25\u2009708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12\u2009529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12\u2009525 in the usual care group (adjusted odds ratio 1\u00b706 [95% Bayesian credible interval 0\u00b781-1\u00b741]; probability of superiority 0\u00b733). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0\u00b74%) of 12\u2009774 participants in the molnupiravir plus usual care group and for 45 (0\u00b73%) of 12\u2009934 in the usual care group. None of these events were judged to be related to molnupiravir. INTERPRETATION: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community. FUNDING: UK National Institute for Health and Care Research.
\n \n\n \n \nThe COVID-19 pandemic has led to the commercialization of many antigen-based rapid diagnostic tests (Ag-RDTs), requiring independent evaluations. This report describes the clinical evaluation of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom. The collected samples (446 nasal swabs from Brazil and 246 nasopharyngeal samples from the UK) were analyzed by the Ag-RDT and compared to reverse transcription-quantitative PCR (RT-qPCR). Analytical evaluation of the Ag-RDT was performed using direct culture supernatants of SARS-CoV-2 strains from the wild-type (B.1), Alpha (B.1.1.7), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529) lineages. An overall sensitivity and specificity of 88.2% (95% confidence interval [CI], 81.3 to 93.3) and 100.0% (95% CI, 99.1 to 100.0), respectively, were obtained for the Brazilian and UK cohorts. The analytical limit of detection was determined as 1.0 \u00d7 103 PFU/mL (Alpha), 2.5 \u00d7 102 PFU/mL (Delta), 2.5 \u00d7 103 PFU/mL (Gamma), and 1.0 \u00d7 103 PFU/mL (Omicron), giving a viral copy equivalent of approximately 2.1 \u00d7 104 copies/mL, 9.0 \u00d7 105 copies/mL, 1.7 \u00d7 106 copies/mL, and 1.8 \u00d7 105 copies/mL for the Ag-RDT, respectively. Overall, while a higher sensitivity was claimed by the manufacturers than that found in this study, this evaluation finds that the Ag-RDT meets the WHO minimum performance requirements for sensitivity and specificity of COVID-19 Ag-RDTs. This study illustrates the comparative performance of the Hotgen Ag-RDT across two global settings and considers the different approaches in evaluation methods.
\n \n\n \n \nBACKGROUND: Biomedical scientists have become de facto leaders for their research teams. Theories of expert leadership suggest that the specialist knowledge and credibility these researcher-leaders bring to their roles can lead to improved performance. Formal leadership development for biomedical researchers remains uncommon, and it is unclear whether existing leadership development programmes achieve improved individual and organisational outcomes. Our study evaluates the effectiveness of a single centre leadership development programme for biomedical researchers using a mixed-methods approach. METHODS: 26 biomedical researchers participated in an 8 month single centre multidisciplinary leadership development programme. Participants completed prospective pre-test, retrospective then-test and traditional post-test self-assessments using the Primary Colours Questionnaire (PCQ) and Medical Leadership Competency Framework Self-Assessment Tool (MLCFQ). Pre-post pairs and then-post pairs were analysed for changes using Wilcoxon signed-rank tests and compared with a parallel mixed-methods evaluation organised by Kirkpatrick levels. RESULTS: There were significant increases in 3/7 domains and 1/5 tasks of leadership in the PCQ, in both pre-post and then-post paired assessments. There were statistically significant but small increases in 2/7 domains of the MLCFQ. The mixed-methods data showed positive outcomes at all Kirkpatrick levels.\u00a0Participants said the programme was relevant, interesting and well-organised, with 63% reporting increased confidence and motivation. Participants had a significant change in behaviour, spending 1-2 hours per week on group projects, which were successfully implemented locally. 42% of participants expected these projects to continue beyond the programme. DISCUSSION: This study demonstrates a local leadership programme can have positive impact within a biomedical research centre despite time and financial constraints. We encourage future studies to utilise a mixed-methods approach to evaluating the impact of leadership development programmes.
\n \n\n \n \n\n My list of 66 medically related anniversaries for 2023 (events in years ending \u201923 and\u201973) includes:\u2028\u25cf foundation of the Chelsea Physic Garden (1673);\u2028\u25cf foundation of\n The Lancet\n by Thomas Wakley (October 1823);\u2028\u25cf Roe v Wade (1973);\u2028\u25cf Twenty five births include: Hans Berger, German neurologist; Aim\u00e9 Bonpland, French physician and botanist; Alexis Carrel, French surgeon and Nobel prize winner; Lloyd Conover, American pharmaceutical chemist; F\u00e9lix d'Herelle, French-Canadian microbiologist; Th\u00e9odore 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;\u2028\u25cf 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 R\u00f6ntgen, German physicist; Antony van Leeuwenhoek, Dutch microscopist; Justus von Liebig, German chemist; and Selman Waksman, Ukrainian-American biochemist;\u2028\u25cf 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;\u2028\u25cf compilation of the\n Lelamour Herbal\n by John Lelamour, English schoolmaster (1373);\u2028\u25cf 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;\u2028\u25cf Foundation of the pharmaceutical companies Novo Nordisk in Denmark (1923) and Sanofi in France (1973);\u2028\u25cf Nobel prizes awarded to Banting and Macleod (1923) and to von Frisch, Lorenz, and Tinbergen (1973).\n
\n \n\n \n \nBackground. IgA nephropathy is the most common primary glomerulonephritis in the world. Up to 30% of patients can progress to end-stage renal disease (ESRD) in 10 years. Methods. We studied 168 Chinese patients with IgA nephropathy followed for an average of 7.4 years in our hospital and tried to identify the clinical and pathological data that were associated with the prognosis of the disease. Clinical features at the time of renal biopsy were reviewed. Severity of histological involvement was scored semi-quantitatively as grade 1-3. Results. There was a female preponderance in our cohort of patients (male:female ratio 1:1.5). The average age at biopsy was 32.9 \u00b1 10.0 years. Forty-seven of the 168 patients (28.0%) were hypertensive and 47 of 136 patients (34.6%) had a family history of hypertension. A high histological grade of IgA nephropathy was associated with hypertension at presentation, family history of hypertension, a higher serum creatinine, total cholesterol and 24-h urine protein excretion, and a lower serum albumin level. During the follow-up period, four patients died and another 24 progressed to ESRD. The renal survival was 92.0% at 1 year, 87.5% at 5 years and 81.8% at 10 years. With univariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation (plasma creatinine > 120 \u03bcmol/1), high cholesterol, proteinuria > 1 g day and high histological grading were associated with poor prognosis. With multivariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation, proteinuria > 1 g/day and histological grading were independent predictors of renal survival. The relative risks of renal failure for patients were 9.60 (95% confidence interval 4.02-22.92) with hypertension, 1.56 (1.16-2.02) with a family history of hypertension, 15.38 (6.40-36.93) with renal impairment and 5.93 (3.07-11.46) with every increase of one histological grade. Male patients did not show a more adverse outcome compared with females. Conclusions. Our results suggest that renal biopsy remains useful, even in clinically trivial disease, because of its distinct value in prognosis and risk stratification. The long-term prognosis of IgA nephropathy in Chinese patients is guarded. The prognostic importance of family history of hypertension has not been widely recognized and requires further study.
\n \n\n \n \nFollowing publication of the original article [1], an error was identified between the primary outcome specified in the original protocol, the detailed SAP, and the endpoint forms and a later version of the protocol that this paper was based upon. The following paragraph in the \u201cOutcomes\u201d section should be changed as follows: Outcomes Primary endpoint Time from randomisation until the first occurring of death or hospitalisation for heart disease (coronary heart disease, arrhythmia, atrial fibrillation, sudden death, resuscitated sudden death), stroke, transient ischaemic attack, peripheral arterial disease or heart failure or first onset of any condition listed above not present at baseline. Primary endpoints will be adjudicated by an independent endpoints committee blinded to treatment arm. Existing Text: Outcomes Primary endpoint Time from randomisation until the first occurring death, first onset, or hospitalisation for heart disease (coronary heart disease, arrhythmia, new onset/first recorded atrial fibrillation, sudden death, failed sudden death), stroke, or heart failure. Primary endpoints will be adjudicated by an independent Endpoint Committee blinded to the treatment arm.
\n \n\n \n \nIntroduction: Primary cam morphology is highly prevalent in many athlete populations, causing debilitating hip osteoarthritis in some. Existing research is mired in confusion partly because stakeholders have not agreed on key primary cam morphology elements or a prioritised research agenda. We aimed to inform a more rigorous, inclusive and evidence-based approach to research on primary cam morphology and its natural history by working towards agreement on a set of research priorities for conditions affecting the young person's hip. Methods: An international expert panel - the Young Athlete's Hip Research (YAHiR) Collaborative - rated research priority statements through an online two-round Delphi exercise and met online to explore areas of tension and dissent. Panellists ranked the prioritised research statements according to the Essential National Health Research (ENHR) ranking strategy. Reporting of results followed REPRISE (REporting guideline for PRIority SEtting of health). Results: A diverse Delphi panel (n=65, Delphi rounds 1 and 2; three ENHR strategy surveys: n=49; n=44; n=42) from 18 countries representing six stakeholder groups, prioritised and ranked 18 of 38 research priority statements. The prioritised statements outlined seven research domains: (1) best practice physiotherapy, (2) rehabilitation progression and return to sport, (3) exercise intervention and load management, (4) primary cam morphology prognosis and aetiology, (5) femoroacetabular impingement syndrome prognosis and aetiology, (6) diagnostic criteria, and (7) screening. The panel recommended areas of tension and dissent for the research community to focus on immediately. Conclusion: While informing more rigorous, inclusive and evidence-based research, this consensus is a roadmap for researchers, policy-makers and funders to implement research dedicated to reducing the cost and burden of hip disease related to primary cam morphology.
\n \n\n \n \nIntroduction: Primary cam morphology is a mostly benign bony prominence that develops at the femoral head-neck junction of the hip, but it is highly prevalent in many athlete populations. In the small proportion of athletes for whom it is not benign, the resulting hip osteoarthritis can be debilitating. Clinicians, athletes, patients and researchers do not yet agree on important primary cam morphology elements. We aimed to ascertain and improve the level of agreement on primary cam morphology definitions, terminology, taxonomy and imaging outcome measures. Methods: To collect and aggregate informed opinions, an expert panel - the Young Athlete's Hip Research Collaborative - rated primary cam morphology definition, terminology, taxonomy and imaging outcome statements through an online Delphi exercise followed by an online meeting to explore areas of tension and dissent. Reporting followed Conducting and REporting DElphi Studies. Results: A diverse and inclusive Delphi panel (n=65 for rounds 1 and 2, representing 18 countries; 6 stakeholder groups; 40% women) agreed on 35 of 47 statements in 4 domains, while surfacing areas of tension and dissent. This Delphi panel agreed on four key issues essential to moving research and clinical care forward around primary cam morphology. They agreed on: (1) definition, confirming its conceptual attributes (tissue type, size, location, shape and ownership); (2) terminology - use 'morphology' and not terms with a negative connotation like 'lesion', 'abnormality' or 'deformity'; (3) taxonomy, distinguishing between primary and secondary cam morphology, and (4) imaging outcomes, a continuous bone/cartilage alpha angle on radial femoral head-neck MRI for primary cam morphology aetiology research. Conclusion: This consensus provides athletes, patients, clinicians and researchers with a strong foundation to guide more precise communication, better clinical decision-making and higher value research about primary cam morphology and its natural history.
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