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Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes
BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo.
Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes
BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events.
Implementing the NIHR Oxford Health BRC's Equality, Diversity and Inclusion Strategy
The National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre (BRC) published its first equality, diversity and inclusion (EDI) strategy in 2023. This 5-year strategy aims to establish and enhance the evidence base for EDI, including data collection processes to enhance the diversity of research participants and the workforce. The NIHR has started to collect protected characteristics from applicants for research funding. Although the collection of the data is optional, it could become mandatory in the future. At the Public Mental Health Implementation Centre (PMHIC), of the Royal College of Psychiatry, we undertook a mapping and scoping project to provide Oxford Health BRC partners with insights into data collection for EDI purposes at the local level and identify any challenges and opportunities. This report also proposes solutions to overcoming possible ethical dilemmas, as well as enablers and barriers to implementing the BRC’s EDI strategy.
Physical, cognitive, and social triggers of symptom fluctuations in people living with long COVID: an intensive longitudinal cohort study
Background: Symptom fluctuations within and between individuals with long COVID are widely reported, but the extent to which severity varies following different types of activity and levels of exertion, and the timing of symptoms and recovery, have not previously been quantified. We aimed to characterise timing, severity, and nature of symptom fluctuations in response to effortful physical, social and cognitive activities, using Ecological Momentary Assessments. Methods: We recorded activity, effort, and severity of 8 core symptoms every 3 h for up to 24 days, in cohorts from both clinic and community settings. Symptom severities were jointly modelled using autoregressive and moving average processes. Findings: Consent was received from 376 participants providing ≥1 week's measurements (273 clinic-based, 103 community-based). Severity of all symptoms was elevated 30 min after all categories of activity. Increased effort was associated with increased symptom severity. Fatigue severity scores increased by 1.8/10 (95% CI: 1.6–1.9) following the highest physical exertions and by 1.5 (1.4–1.7) following cognitive efforts. There was evidence of only mild delayed fatigue 3 h (0.3, 0.2–0.5) or one day later (0.2, 0.0– 0.5). Fatigue severity increased as the day progressed (1.4, 1.0–1.7), and cognitive dysfunction was 0.2 lower at weekends (0.1–0.3). Interpretation: Cognitive, social, self-care and physical activities all triggered increased severity across every symptom, consistent with associated common pathways as potential therapeutic targets. Clear patterns of symptom fluctuations emerged that support more targeted self-management. Funding: National Institute for Health and Care Research.
Recommendation to update the British Society for Cutaneous Allergy corticosteroid series
Background Patch testing is an important investigation when dermatitis is unresponsive to, or worsened by, topical corticosteroid treatment. There is a balance to be struck between testing too many allergens, which is expensive, time consuming and risks causing sensitization, and testing too few, which risks missing the diagnosis. The current British Society for Cutaneous Allergy (BSCA) corticosteroid series comprises eight allergens and was last updated in February 2007. Aim To review and update the BSCA corticosteroid series. Methods We retrospectively analysed data from 16 patch test centres in the UK and Ireland for all patients who were patch tested to a corticosteroid series between August 2017 and July 2019. We recorded the allergens tested, the number and percentage tested to a corticosteroid series and the number of positive results for each allergen. We identified the allergens that test positive in≥0.1% of selectively tested patients. Results Overall, 3531 patients were tested to a corticosteroid series in the 16 centres. The number of allergens tested ranged from 7 to 18 (mean 10). The proportion of patch test patients who were tested to a corticosteroid series ranged from 1% to 99%. Six allergens in the 2017 BSCA series tested positive in≥0.1% of patients. Nine allergens not in the BSCA corticosteroid series tested positive in≥0.1% of patients. Conclusion This audit demonstrates the importance of regular review of recommended series and the significant variations in practice. The new BSCA corticosteroid series that we recommend contains 13 haptens, with the addition of the patient’s own steroid creams as appropriate.
Total hip replacement and surface replacement for the treatment of pain and disability resulting from end-stage arthritis of the hip (review of technology appraisal guidance 2 and 44): systematic review and economic evaluation
BACKGROUND: Total hip replacement (THR) involves the replacement of a damaged hip joint with an artificial hip prosthesis. Resurfacing arthroplasty (RS) involves replacement of the joint surface of the femoral head with a metal surface covering.
Aspirin in primary prevention of cardiovascular disease and cancer: A systematic review of the balance of evidence from reviews of randomized trials
Background: Aspirin has been recommended for primary prevention of cardiovascular disease (CVD) and cancer, but overall benefits are unclear. We aimed to use novel methods to re-evaluate the balance of benefits and harms of aspirin using evidence from randomised controlled trials, systematic reviews and meta-analyses. Methods and Findings: Data sources included ten electronic bibliographic databases, contact with experts, and scrutiny of reference lists of included studies. Searches were undertaken in September 2012 and restricted to publications since 2008. Of 2,572 potentially relevant papers 27 met the inclusion criteria. Meta-analysis of control arms to estimate event rates, modelling of all-cause mortality and L'Abbé plots to estimate heterogeneity were undertaken. Absolute benefits and harms were low: 60-84 major CVD events and 34-36 colorectal cancer deaths per 100,000 person-years were averted, whereas 46-49 major bleeds and 68-117 gastrointestinal bleeds were incurred. Reductions in all-cause mortality were minor and uncertain (Hazard Ratio 0.96; 95% CI: 0.90-1.02 at 20 years, Relative Risk [RR] 0.94, 95% CI: 0.88-1.00 at 8 years); there was a non-significant change in total CVD (RR 0.85, 95% CI: 0.69-1.06) and change in total cancer mortality ranged from 0.76 (95% CI: 0.66-0.88) to 0.93 (95% CI: 0.84-1.03) depending on follow-up time and studies included. Risks were increased by 37% for gastrointestinal bleeds (RR 1.37, 95% CI: 1.15-1.62), 54%-66% for major bleeds (Rate Ratio from IPD analysis 1.54, 95% CI: 1.30-1.82, and RR 1.62, 95% CI: 1.31-2.00), and 32%-38% for haemorrhagic stroke (Rate Ratio from IPD analysis 1.32; 95% CI: 1.00-1.74; RR 1.38; 95% CI: 1.01-1.82). Conclusions: Findings indicate small absolute effects of aspirin relative to the burden of these diseases. When aspirin is used for primary prevention of CVD the absolute harms exceed the benefits. Estimates of cancer benefit rely on selective retrospective re-analysis of RCTs and more information is needed. Copyright © 2013 Sutcliffe et al.
Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: A systematic review and overview of reviews
Background: Prophylactic aspirin has been considered to be beneficial in reducing the risks of heart disease and cancer. However, potential benefits must be balanced against the possible harm from side effects, such as bleeding and gastrointestinal (GI) symptoms. It is particularly important to know the risk of side effects when aspirin is used as primary prevention - that is when used by people as yet free of, but at risk of developing, cardiovascular disease (CVD) or cancer. In this report we aim to identify and re-analyse randomised controlled trials (RCTs), systematic reviews and meta-analyses to summarise the current scientific evidence with a focus on possible harms of prophylactic aspirin in primary prevention of CVD and cancer. Objectives: To identify RCTs, systematic reviews and meta-analyses of RCTs of the prophylactic use of aspirin in primary prevention of CVD or cancer. To undertake a quality assessment of identified systematic reviews and meta-analyses using meta-analysis to investigate study-level effects on estimates of benefits and risks of adverse events; cumulative meta-analysis; exploratory multivariable meta-regression; and to quantify relative and absolute risks and benefits. Methods: We identified RCTs, meta-analyses and systematic reviews, and searched electronic bibliographic databases (from 2008 September 2012) including MEDLINE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, NHS Centre for Reviews and Dissemination, and Science Citation Index. We limited searches to publications since 2008, based on timing of the most recent comprehensive systematic reviews. Results: In total, 2572 potentially relevant papers were identified and 27 met the inclusion criteria. Benefits of aspirin ranged from 6% reduction in relative risk (RR) for all-cause mortality [RR 0.94, 95% confidence interval (CI) 0.88 to 1.00] and 10% reduction in major cardiovascular events (MCEs) (RR 0.90, 95% CI 0.85 to 0.96) to a reduction in total coronary heart disease (CHD) of 15% (RR 0.85, 95% CI 0.69 to 1.06). Reported pooled odds ratios (ORs) for total cancer mortality ranged between 0.76 (95% CI 0.66 to 0.88) and 0.93 (95% CI 0.84 to 1.03). Inclusion of the Women's Health Study changed the estimated OR to 0.82 (95% CI 0.69 to 0.97). Aspirin reduced reported colorectal cancer (CRC) incidence (OR 0.66, 95% CI 0.90 to 1.02). However, including studies in which aspirin was given every other day raised the OR to 0.91 (95% CI 0.74 to 1.11). Reported cancer benefits appeared approximately 5 years from start of treatment. Calculation of absolute effects per 100,000 patient-years of follow-up showed reductions ranging from 33 to 46 deaths (all-cause mortality), 60-84 MCEs and 47-64 incidents of CHD and a possible avoidance of 34 deaths from CRC. Reported increased RRs of adverse events from aspirin use were 37% for GI bleeding (RR 1.37, 95% CI 1.15 to 1.62), between 54% (RR 1.54, 95% CI 1.30 to 1.82) and 62% (RR 1.62, 95% CI 1.31 to 2.00) for major bleeds, and between 32% (RR 1.32, 95% CI 1.00 to 1.74) and 38% (RR 1.38, 95% CI 1.01 to 1.82) for haemorrhagic stroke. Pooled estimates of increased RR for bleeding remained stable across trials conducted over several decades. Estimates of absolute rates of harm from aspirin use, per 100,000 patient-years of follow-up, were 99-178 for non-trivial bleeds, 46-49 for major bleeds, 68-117 for GI bleeds and 8-10 for haemorrhagic stroke. Meta-analyses aimed at judging risk of bleed according to sex and in individuals with diabetes were insufficiently powered for firm conclusions to be drawn. Limitations: Searches were date limited to 2008 because of the intense interest that this subject has generated and the cataloguing of all primary research in so many previous systematic reviews. A further limitation was our potential over-reliance on study-level systematic reviews in which the person-years of follow-up were not accurately ascertainable. However, estimates of number of events averted or incurred through aspirin use calculated from data in study-level meta-analyses did not differ substantially from estimates based on individual patient data-level meta-analyses, for which person-years of follow-up were more accurate (although based on less-than-complete assemblies of currently available primary studies). Conclusions: We have found that there is a fine balance between benefits and risks from regular aspirin use in primary prevention of CVD. Effects on cancer prevention have a long lead time and are at present reliant on post hoc analyses. All absolute effects are relatively small compared with the burden of these diseases. Several potentially relevant ongoing trials will be completed between 2013 and 2019, which may clarify the extent of benefit of aspirin in reducing cancer incidence and mortality. Future research considerations include expanding the use of IPD meta-analysis of RCTs by pooling data from available studies and investigating the impact of different dose regimens on cardiovascular and cancer outcomes. Funding: The National Institute for Health Research Health Technology Assessment programme. © Queen's Printer and Controller of HMSO 2013.
An international comparison of longitudinal health data collected on long COVID in nine high income countries: a qualitative data analysis.
BACKGROUND: Long coronavirus disease (COVID) presents a significant health challenge. Long-term monitoring is critical to support understanding of the condition, service planning and evaluation. We sought to identify and examine longitudinal health data collected on long COVID to inform potential decisions in England regarding the rationale for data collection, the data collected, the sources from which data were collected and the methods used for collection. METHODS: We included datasets in high-income countries that experienced similar coronavirus disease 2019 (COVID-19) waves to England pre-vaccine rollout. Relevant datasets were identified through literature searches, the authors' networks and participants' recommendations. We undertook semi-structured interviews with individuals involved in the development and running of the datasets. We held a focus group discussion with representatives of three long COVID patient organisations to capture the perspective of those with long COVID. Emergent findings were tested in a workshop with country interviewees. RESULTS: We analysed 17 datasets from nine countries (Belgium, Canada, Germany, Italy, the Netherlands, New Zealand, Sweden, Switzerland and the United Kingdom). Datasets sampled different populations, used different data collection tools and measured different outcomes, reflecting different priorities. Most data collection was research (rather than health care system)-funded and time-limited. For datasets linked to specialist services, there was uncertainty surrounding how long these would continue. Definitions of long COVID varied. Patient representatives' favoured self-identification, given challenges in accessing care and receiving a diagnosis; New Zealand's long COVID registry was the only example identified using this approach. Post-exertion malaise, identified by patients as a critical outcome, was absent from all datasets. The lack of patient-reported outcome measures (PROMs) was highlighted as a limitation of datasets reliant on routine health data, although some had developed mechanisms to extend data collection using patient surveys. CONCLUSIONS: Addressing research questions related to the management of long COVID requires diverse data sources that capture different populations with long COVID over the long-term. No country examined has developed a comprehensive long-term data system for long COVID, and, in many settings, data collection is ending leaving a gap. There is no obvious model for England or other countries to follow, assuming there remains sufficient policy interest in establishing a long-term long COVID patient registry.
Protocol: A metabolomic analysis of convalescent inflammatory conditions
Background ‘The term ‘long covid’ describes persistent symptoms following infection with SARS-CoV-2 that are not explained by an alternative diagnosis. It embraces a number of globally used terms and reported prevalence is highly variable. In the United Kingdom (UK) in 2023, approximately 2.9% of the population were thought to be affected. The condition manifests in a constellation of fluctuant symptoms, which persist beyond the acute infection and frequently profoundly impact an individual’s functional and relational capacity. The underlying mechanisms remain imperfectly understood and there is great demand for diagnostic tools that distinguish long covid from other chronic conditions. This study aims to utilise metabolomics to develop such a test and identify potential pathophysiological mechanisms. Methods Blood and urine samples will be collected at two timepoints at least 9 months apart from non-hospitalised individuals with a previous confirmed COVID-19 infection. This population will be divided into those who recovered completely within six weeks and those who continue to experience persistent symptoms. Samples will be analysed using 1H NMR spectroscopy and the resultant metabolomic profiles will be subject to multivariate pattern recognition techniques. This will produce mathematical models capable of distinguishing these long covid and control groups. Symptoms, potential confounders, and qualitative narrative data will be collected alongside this process to add deeper richness to the subsequent analysis. Primary Outcome The creation of a diagnostic test for long covid using 1H NMR metabolomics. Secondary Outcomes The development of algorithms that predict the severity and chronicity of long covid, identification of subgroup differences in metabolomic and immune profiles, and triangulation with symptom and narrative data to produce a deeper understanding of the patient experience. Conclusion This study seeks to advance the understanding of long covid using advanced multi-omic and narrative techniques, which may offer potential diagnostic and therapeutic avenues.
Study protocol: Comparison of different risk prediction modelling approaches for COVID-19 related death using the OpenSAFELY platform.
On March 11th 2020, the World Health Organization characterised COVID-19 as a pandemic. Responses to containing the spread of the virus have relied heavily on policies involving restricting contact between people. Evolving policies regarding shielding and individual choices about restricting social contact will rely heavily on perceived risk of poor outcomes from COVID-19. In order to make informed decisions, both individual and collective, good predictive models are required. For outcomes related to an infectious disease, the performance of any risk prediction model will depend heavily on the underlying prevalence of infection in the population of interest. Incorporating measures of how this changes over time may result in important improvements in prediction model performance. This protocol reports details of a planned study to explore the extent to which incorporating time-varying measures of infection burden over time improves the quality of risk prediction models for COVID-19 death in a large population of adult patients in England. To achieve this aim, we will compare the performance of different modelling approaches to risk prediction, including static cohort approaches typically used in chronic disease settings and landmarking approaches incorporating time-varying measures of infection prevalence and policy change, using COVID-19 related deaths data linked to longitudinal primary care electronic health records data within the OpenSAFELY secure analytics platform.
British Society of Gastroenterology National Evaluation of Colonoscopy Quality: Findings from the National Endoscopy Database.
BACKGROUND AND AIMS: Analysis of national colonoscopy quality using automatically uploaded data from a national database, including exploring performance variation. METHODS: Data on all colonoscopies performed in the UK 01/03/2019-29/02/2020 and recorded in the National Endoscopy Database were analysed. Unadjusted key performance indicators were calculated and proportions of endoscopists achieving national standards were determined. Regression models tested associations between case-mix (patient age, sex, indication) and colonoscopy quality. Endoscopist factors (specialty, annual procedure numbers, withdrawal times) were added to case-mix adjusted models, with results presented as adjusted odds ratios (aOR) with 95% confidence intervals. RESULTS: 592,764 colonoscopies were analysed. Rates of caecal intubation (93.5%, 95% CI 93.4-93.6), polyp detection (37.3%, 95% CI 37.2-37.4), and moderate/severe patient discomfort (4.8%, 95% CI 4.7-4.8) had all improved since the 2011 national audit (p<0.01 for all). 63.9% of endoscopists met all minimum standards for caecal intubation, polyp detection, and discomfort, but only 46.4% did so among those performing fewer than 100 colonoscopies annually. Overall, surgeons recorded lower caecal intubation and polyp detection rates than gastroenterologists (p<0.01); however, those performing over 100 annual colonoscopies achieved KPIs similar to gastroenterologists. Endoscopists with longer withdrawal times were almost twice as likely to identify polyps (aOR 1.9, 95% CI 1.7-2.2) and detected more large polyps (aOR 1.6, 95% CI 1.3-2.0). CONCLUSIONS: UK colonoscopy quality has improved, yet almost 40% of endoscopists still fell short of minimum standards. Variation in quality was strongly associated with endoscopist procedure volumes; mandating minimum annual procedures and emphasising longer withdrawal times could improve overall quality.
Echocardiography reporting in heart failure with preserved ejection fraction: Delphi consensus study
BackgroundHeart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome in which signs and symptoms of heart failure (HF) occur despite a normal left ventricular ejection fraction. Transthoracic echocardiography (TTE) is the first-line imaging modality but disparities in patient pathways across the UK can lead to delayed diagnosis and treatment. We aimed to develop and validate a consistent, clinically appropriate and practical approach for reporting the echocardiographic suspicion of HFpEF.MethodsUsing the Delphi method, a steering group of nine UK experts identified key domains for discussion and generated consensus statements relevant to the echocardiographic detection of HFpEF. Using a four-pointLikertscale, a survey including all statements was disseminated among a wider audience of healthcare professionals to determine agreement. A consensus threshold of 75% agreement was defined as ‘strong’ and ≥90% as ‘very strong’.ResultsA total of 34 consensus statements were generated in seven domains: (1) challenges in the system approach to HFpEF; (2) enhancing referral for specialist review including echocardiography; (3) confidence in using a summary statement in an echo report; (4) identifying HFpEF and its underlying aetiology; (5) HF awareness, training and education; (6) refining multidisciplinary team roles in decision-making; (7) optimising patient experience.135 UK specialists experienced in managing HF participated in the survey, including physiologists/clinical scientists (n=43), HF specialist nurses (n=35), cardiologists (n=34), general practitioners (n=12), pharmacists (n=4) and others (n=7). 20 of 34 (59%) statements achieved very strong agreement, 10 of 34 (29%) achieved strong agreement and 4 of 34 (12%) did not meet the consensus threshold.ConclusionsDiagnosis of HFpEF requires access to essential diagnostic tools. Establishing standardised pathways for specialist assessment and referral, including TTE reporting of HFpEF, may help eliminate diagnostic delays and geographical disparities. Further education and awareness are crucial for improving detection rates, prompt referral and patient experience.
The impact of the COVID-19 pandemic on antimicrobial usage: an international patient-level cohort study
Background: This study aimed to evaluate the trends in antimicrobial prescription during the first 1.5 years of COVID-19 pandemic. Methods: This was an observational, retrospective cohort study using patient-level data from Bangladesh, Brazil, India, Italy, Malawi, Nigeria, South Korea, Switzerland and Turkey from patients with pneumonia and/or acute respiratory distress syndrome and/or sepsis, regardless of COVID-19 positivity, who were admitted to critical care units or COVID-19 specialized wards. The changes of antimicrobial prescription between pre-pandemic and pandemic were estimated using logistic or linear regression. Pandemic effects on month-wise antimicrobial usage were evaluated using interrupted time series analyses (ITSAs). Results: Antimicrobials for which prescriptions significantly increased during the pandemic were as follows: meropenem in Bangladesh (95% CI: 1.94–4.07) with increased prescribed daily dose (PDD) (95% CI: 1.17–1.58) and Turkey (95% CI: 1.09–1.58), moxifloxacin in Bangladesh (95% CI: 4.11–11.87) with increased days of therapy (DOT) (95% CI: 1.14–2.56), piperacillin/tazobactam in Italy (95% CI: 1.07–1.48) with increased DOT (95% CI: 1.01–1.25) and PDD (95% CI: 1.05–1.21) and azithromycin in Bangladesh (95% CI: 3.36–21.77) and Brazil (95% CI: 2.33–8.42). ITSA showed a significant drop in azithromycin usage in India (95% CI: −8.38 to −3.49 g/100 patients) and South Korea (95% CI: −2.83 to −1.89 g/100 patients) after WHO guidelines v1 release and increased meropenem usage (95% CI: 93.40–126.48 g/100 patients) and moxifloxacin (95% CI: 5.40–13.98 g/100 patients) in Bangladesh and sulfamethoxazole/trimethoprim in India (95% CI: 0.92–9.32 g/100 patients) following the Delta variant emergence. Conclusions: This study reinforces the importance of developing antimicrobial stewardship in the clinical settings during inter-pandemic periods.
Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study
Orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (PoTS) and orthostatic hypotension (OH), are often reported in long covid, but published studies are small with inconsistent results. We sought to estimate the prevalence of objective OI in patients attending long covid clinics and healthy volunteers and associations with OI symptoms and comorbidities. Participants with a diagnosis of long covid were recruited from eight UK long covid clinics, and healthy volunteers from general population. All undertook standardized National Aeronautics and Space Administration Lean Test (NLT). Participants' history of typical OI symptoms (e.g., dizziness, palpitations) before and during the NLT were recorded. Two hundred seventy-seven long covid patients and 50 frequency-matched healthy volunteers were tested. Healthy volunteers had no history of OI symptoms or symptoms during NLT or PoTS, 10% had asymptomatic OH. One hundred thirty (47%) long covid patients had previous history of OI symptoms and 144 (52%) developed symptoms during the NLT. Forty-one (15%) had an abnormal NLT, 20 (7%) met criteria for PoTS, and 21 (8%) had OH. Of patients with an abnormal NLT, 45% had no prior symptoms of OI. Relaxing the diagnostic thresholds for PoTS from two consecutive abnormal readings to one abnormal reading during the NLT, resulted in 11% of long covid participants (an additional 4%) meeting criteria for PoTS, but not in healthy volunteers. More than half of long covid patients experienced OI symptoms during NLT and more than one in 10 patients met the criteria for either PoTS or OH, half of whom did not report previous typical OI symptoms. We therefore recommend all patients attending long covid clinics are offered an NLT and appropriate management commenced.