Published evidence suggests that aspects of trial design lead to biased intervention effect estimates, but findings from different studies are inconsistent. This study combined data from 7 ...meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials. Outcome measures were classified as "mortality," "other objective," "or subjective," and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity. Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear (vs. adequate) random-sequence generation (ratio of odds ratios, 0.89 95% credible interval {CrI}, 0.82 to 0.96) and with inadequate or unclear (vs. adequate) allocation concealment (ratio of odds ratios, 0.93 CrI, 0.87 to 0.99). Lack of or unclear double-blinding (vs. double-blinding) was associated with an average of 13% exaggeration of intervention effects (ratio of odds ratios, 0.87 CrI, 0.79 to 0.96), and between-trial heterogeneity was increased for such studies (SD increase in heterogeneity, 0.14 CrI, 0.02 to 0.30). For each characteristic, average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes, with little evidence of bias in trials with objective and mortality outcomes. This study is limited by incomplete trial reporting, and findings may be confounded by other study design characteristics. Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes.
To evaluate the relation between diagnosis of covid-19 with SARS-CoV-2 variant B.1.1.7 (also known as variant of concern 202012/01) and the risk of hospital admission compared with diagnosis with ...wild-type SARS-CoV-2 variants.
Retrospective cohort analysis.
Community based SARS-CoV-2 testing in England, individually linked with hospital admission data.
839 278 patients with laboratory confirmed covid-19, of whom 36 233 had been admitted to hospital within 14 days, tested between 23 November 2020 and 31 January 2021 and analysed at a laboratory with an available TaqPath assay that enables assessment of S-gene target failure (SGTF), a proxy test for the B.1.1.7 variant. Patient data were stratified by age, sex, ethnicity, deprivation, region of residence, and date of positive test.
Hospital admission between one and 14 days after the first positive SARS-CoV-2 test.
27 710 (4.7%) of 592 409 patients with SGTF variants and 8523 (3.5%) of 246 869 patients without SGTF variants had been admitted to hospital within one to 14 days. The stratum adjusted hazard ratio of hospital admission was 1.52 (95% confidence interval 1.47 to 1.57) for patients with covid-19 infected with SGTF variants, compared with those infected with non-SGTF variants. The effect was modified by age (P<0.001), with hazard ratios of 0.93-1.21 in patients younger than 20 years with versus without SGTF variants, 1.29 in those aged 20-29, and 1.45-1.65 in those aged ≥30 years. The adjusted absolute risk of hospital admission within 14 days was 4.7% (95% confidence interval 4.6% to 4.7%) for patients with SGTF variants and 3.5% (3.4% to 3.5%) for those with non-SGTF variants.
The results suggest that the risk of hospital admission is higher for people infected with the B.1.1.7 variant compared with wild-type SARS-CoV-2, likely reflecting a more severe disease. The higher severity may be specific to adults older than 30 years.
Immersive technologies, like virtual and mixed reality, pose a novel challenge for our sensorimotor systems as they deliver simulated sensory inputs that may not match those of the natural ...environment. These include reduced fields of view, missing or inaccurate haptic information, and distortions of 3D space; differences that may impact the control of motor actions. For instance, reach-to-grasp movements without end-point haptic feedback are characterised by slower and more exaggerated movements. A general uncertainty about sensory input may also induce a more conscious form of movement control. We tested whether a more complex skill like golf putting was also characterized by more consciously controlled movement. In a repeated-measures design, kinematics of the putter swing and postural control were compared between (i) real-world putting, (ii) VR putting, and (iii) VR putting with haptic feedback from a real ball (i.e., mixed reality). Differences in putter swing were observed both between the real world and VR, and between VR conditions with and without haptic information. Further, clear differences in postural control emerged between real and virtual putting, with both VR conditions characterised by larger postural movements, which were more regular and less complex, suggesting a more conscious form of balance control. Conversely, participants actually reported less conscious awareness of their movements in VR. These findings highlight how fundamental movement differences may exist between virtual and natural environments, which may pose challenges for transfer of learning within applications to motor rehabilitation and sport.
Treatment of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control, and this study updates a previous network meta-analysis of the best LTBI treatment options to ...inform public health action and programmatic management of LTBI.
To evaluate the comparative efficacy and harms of LTBI treatment regimens aimed at preventing active TB among adults and children.
PubMed, Embase, and Web of Science from indexing to 8 May 2017; clinical trial registries; and conference abstracts. No language restrictions were applied.
Randomized controlled trials that evaluated human LTBI treatments and recorded at least 1 of 2 prespecified end points (hepatotoxicity and prevention of active TB).
2 investigators independently extracted data from eligible studies and assessed study quality according to a standard protocol.
The network meta-analysis of 8 new and 53 previously included studies showed that isoniazid regimens of 6 months (odds ratio OR, 0.65 95% credible interval {CrI}, 0.50 to 0.83) or 12 to 72 months (OR, 0.50 CrI, 0.41 to 0.62), rifampicin-only regimens (OR, 0.41 CrI, 0.19 to 0.85), rifampicin-isoniazid regimens of 3 to 4 months (OR, 0.53 CrI, 0.36 to 0.78), rifampicin-isoniazid-pyrazinamide regimens (OR, 0.35 CrI, 0.19 to 0.61), and rifampicin-pyrazinamide regimens (OR, 0.53 CrI, 0.33 to 0.84) were efficacious compared with placebo. Evidence existed for efficacy of weekly rifapentine-isoniazid regimens compared with no treatment (OR, 0.36 CrI, 0.18 to 0.73). No conclusive evidence showed that HIV status altered treatment efficacy.
Evidence was sparse for many comparisons and hepatotoxicity outcomes, and risk of bias was high or unknown for many studies.
Evidence exists for the efficacy and safety of 6-month isoniazid monotherapy, rifampicin monotherapy, and combination therapies with 3 to 4 months of isoniazid and rifampicin.
U.K. National Institute for Health Research. (PROSPERO: CRD42016037871).
Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook ...prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.
Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression.
In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12–16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50–68%) Euroimmun, 41% (30–52%) RBD, 10% (8–14%) Roche (N) < 2% Roche (S).
Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.
Effective treatment of latent tuberculosis infection (LTBI) is an important component of TB elimination programs. Promising new regimens that may be more effective are being introduced. Because few ...regimens can be directly compared, network meta-analyses, which allow indirect comparisons to be made, strengthen conclusions.
To determine the most efficacious regimen for preventing active TB with the lowest likelihood of adverse events to inform LTBI treatment policies.
PubMed, EMBASE, and Web of Science up to 29 January 2014; clinical trial registries; and conference abstracts.
Randomized, controlled trials that evaluated LTBI treatment in humans and recorded at least 1 of 2 prespecified end points (preventing active TB or hepatotoxicity), without language or date restrictions.
Data from eligible studies were independently extracted by 2 investigators according to a standard protocol.
Of the 1516 articles identified, 53 studies met the inclusion criteria. Data on 15 regimens were available; of 105 possible comparisons, 42 (40%) were compared directly. Compared with placebo, isoniazid for 6 months (odds ratio OR, 0.64 95% credible interval {CrI}, 0.48 to 0.83) or 12 months or longer (OR, 0.52 CrI, 0.41 to 0.66), rifampicin for 3 to 4 months (OR, 0.41 CrI, 0.18 to 0.86), and rifampicin-isoniazid regimens for 3 to 4 months (OR, 0.52 CrI, 0.34 to 0.79) were efficacious within the network.
The risk of bias was unclear for many studies across various domains. Evidence was sparse for some comparisons, particularly hepatotoxicity.
Comparison of different LTBI treatment regimens showed that various therapies containing rifamycins for 3 months or more were efficacious at preventing active TB, potentially more so than isoniazid alone. Regimens containing rifamycins may be effective alternatives to isoniazid monotherapy.
None.
Background & Aims Hepatitis C (HCV) related disease in England is predicted to rise, and it is unclear whether treatment at current levels will be able to avert this. The aim of this study was to ...estimate the number of people with chronic HCV infection in England that are treated and assess the impact and costs of increasing treatment uptake. Methods Numbers treated were estimated using national data sources for pegylated interferon supplied, dispensed, or purchased from 2006 to 2011. A back-calculation approach was used to project disease burden over the next 30 years and determine outcomes under various scenarios of treatment uptake. Results 5000 patients were estimated to have been treated in 2011 and 28,000 in total from 2006 to 2011; approximately 3.1% and 17% respectively of estimated chronic infections. Without treatment, incident cases of decompensated cirrhosis and hepatocellular carcinoma were predicted to increase until 2035 and reach 2290 cases per year. Treatment at current levels should reduce incidence by 600 cases per year, with a peak around 2030. Large increases in treatment are needed to halt the rise; and with more effective treatment the best case scenario predicts incidence of around 500 cases in 2030, although treatment uptake must still be increased considerably to achieve this. Conclusions If the infected population is left untreated, the number of patients with severe HCV-related disease will continue to increase and represent a substantial future burden on healthcare resources. This can be mitigated by increasing treatment uptake, which will have the greatest impact if implemented quickly.
•Athletes reported higher body appreciation than non-athletes.•Athletes reported higher functionality appreciation than non-athletes.•Female athletes reported lower levels of positive body image than ...male athletes.•Athletes’ positive body image was associated with sport confidence and flow state.•Athletes’ subjective sport performance was associated with functionality appreciation.
The primary purpose of the present study was to examine differences in positive body image, specifically body appreciation and functionality appreciation, between student athletes and non-athletes. A secondary purpose was to examine the relationships between positive body image and other sport-related variables. Seventy-nine National Collegiate Athletic Association (NCAA) Division I student athletes (Mage = 19.79, SD = 1.13) and 175 non-athletes (Mage = 19.38, SD = 1.81) completed measures of body appreciation and functionality appreciation. The athletes further completed measures of sport confidence, flow state, and subjective sport performance. Student athletes reported higher levels of both facets of positive body image. Significant relationships were also found between positive body image and the sport-related variables. The present results contribute novel findings to the positive body image literature and potential implications for coaches to encourage a culture that focuses less on body appearance and more on cultivating positive body image.
Summary
In England, 160 000 individuals were estimated to be chronically infected with hepatitis C virus (HCV) in 2005 and the burden of severe HCV‐related liver disease has increased steadily for ...the past 15 years. Direct‐acting antiviral treatments can clear infection in most patients, motivating HCV elimination targets. However, the current burden of HCV is unknown and new methods are required to monitor progress. We employed a Bayesian back‐calculation approach, combining data on severe HCV‐related liver disease and disease progression, to reconstruct historical HCV incidence and estimate current prevalence in England. We explicitly modelled infections occurring in people who inject drugs, the key risk group, allowing information on the size of this population and surveillance data on HCV prevalence to inform recent incidence. We estimated that there were 143 000 chronic infections in 2015 (95% credible interval 123 000‐161 000), with 34% and 54% in those with recent and past injecting drug use, respectively. Following the planned scale‐up of new treatments, chronic infections were predicted to fall to 113 400 (94 900‐132 400) by the end of 2018 and to 89 500 (71 300‐108 600) by the end of 2020. Numbers developing severe HCV‐related liver disease were predicted to fall by at least 24% from 2015 to 2020. Thus, we describe a coherent framework to monitor progress using routinely collected data, which can be extended to incorporate additional data sources. Planned treatment scale‐up is likely to achieve 2020 WHO targets for HCV morbidity, but substantial efforts will be required to ensure that HCV testing and patient engagement are sufficiently high.
People who inject drugs are at high risk of acquiring hepatitis C infection, many of whom will develop cirrhosis and severe liver disease. We use surveillance data to model this process, estimating the number of HCV‐infected people in England and predicted impact of new treatments. We estimate 143,000 people had chronic infection in 2015 and predict that this will fall to around 90,000 in 2020.
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