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It is unclear whether seasonal changes, school closures or other public health interventions will result in a slowdown of the current coronavirus disease 2019 (COVID-19) pandemic. We aimed to determine whether epidemic growth is globally associated with climate or public health interventions intended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed a prospective cohort study of all 144 geopolitical areas worldwide (375 609 cases) with at least 10 COVID-19 cases and local transmission by Mar. 20, 2020, excluding China, South Korea, Iran and Italy. Using weighted random-effects regression, we determined the association between epidemic growth (expressed as ratios of rate ratios [RRR] comparing cumulative counts of COVID-19 cases on Mar. 27, 2020, with cumulative counts on Mar. 20, 2020) and latitude, temperature, humidity, school closures, restrictions of mass gatherings, and measures of social distancing during an exposure period 14 days previously (Mar. 7 to 13, 2020). In univariate analyses, there were no associations of epidemic growth with latitude and temperature, but weak negative associations with relative humidity (RRR per 10% 0.91, 95% confidence interval [CI] 0.85–0.96) and absolute humidity (RRR per 5 g/m3 0.92, 95% CI 0.85–0.99). Strong associations were found for restrictions of mass gatherings (RRR 0.65, 95% CI 0.53–0.79), school closures (RRR 0.63, 95% CI 0.52–0.78) and measures of social distancing (RRR 0.62, 95% CI 0.45–0.85). In a multivariable model, there was a strong association with the number of implemented public health interventions (p for trend = 0.001), whereas the association with absolute humidity was no longer significant. Epidemic growth of COVID-19 was not associated with latitude and temperature, but may be associated weakly with relative or absolute humidity. Conversely, public health interventions were strongly associated with reduced epidemic growth.

PRECIS is a tool to help trialists make design decisions consistent with the intended purpose of their trial. This paper gives guidance on how to use an improved, validated version, PRECIS-2, which has been developed with the help of over 80 international trialists, clinicians, and policymakers. Keeping the original simple wheel format, PRECIS-2 has nine domains—eligibility criteria, recruitment, setting, organisation, flexibility (delivery), flexibility (adherence), follow-up, primary outcome, and primary analysis—scored from 1 (very explanatory) to 5 (very pragmatic) to facilitate domain discussion and consensus. It is hoped PRECIS-2 will be valuable in supporting the explicit matching of design decisions to how the trial results are intended to be used

National Medicines Policies use the National Essential Medicines Lists (NEML) to improve equitable access to medications. An effective list selection process should address a country's priority healthcare needs and be aligned with WHO guidelines. The purpose of this study was to develop and test an instrument to measure the effectiveness of NEML selection process design. An instrument consisting of 16 items, along with an associated rating scheme, was created through a literature review and consultation with subject matter experts. Reliability was assessed using intraclass correlation coefficients (ICCs) for absolute agreement and consistency. Validity was evaluated by comparing instrument scores with two proxy measures of NEML selection process effectiveness. The total score for NEML selection process design effectiveness, based on ratings from 5 raters across 4 countries, demonstrated an absolute agreement ICC of 0.98 (95% confidence interval 0.91 to 0.99) and a consistency ICC of 0.97 (95% confidence interval 0.88 to 0.99). Instrument scores varied correspondingly with two proxy measures of NEML selection process effectiveness, indicating good validity. The instrument developed in this study measures the construct of NEML selection process design effectiveness, which essentially evaluates the alignment of national policy content with policy intent. The instrument demonstrated good validity and excellent reliability.

In a randomized trial, 5243 patients undergoing cardiac surgery were assigned to a restrictive or a liberal red-cell transfusion threshold. The restrictive threshold was noninferior to the liberal one for the composite outcome of death, myocardial infarction, stroke, or renal failure.

Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression. In this randomised, multicentre, non-inferiority clinical trial, we recruited patients who were referred to specialty neurostimulation centres based at three Canadian university hospitals (Centre for Addiction and Mental Health and Toronto Western Hospital, Toronto, ON, and University of British Columbia Hospital, Vancouver, BC). Participants were aged 18–65 years, were diagnosed with a current treatment-resistant major depressive episode or could not tolerate at least two antidepressants in the current episode, were receiving stable antidepressant medication doses for at least 4 weeks before baseline, and had an HRSD-17 score of at least 18. Participants were randomly allocated (1:1) to treatment groups (10 Hz rTMS or iTBS) by use of a random permuted block method, with stratification by site and number of adequate trials in which the antidepressants were unsuccessful. Treatment was delivered open-label but investigators and outcome assessors were masked to treatment groups. Participants were treated with 10 Hz rTMS or iTBS to the left dorsolateral prefrontal cortex, administered on 5 days a week for 4–6 weeks. The primary outcome measure was change in 17-item Hamilton Rating Scale for Depression (HRSD-17) score, with a non-inferiority margin of 2·25 points. For the primary outcome measure, we did a per-protocol analysis of all participants who were randomly allocated to groups and who attained the primary completion point of 4 weeks. This trial is registered with ClinicalTrials.gov, number NCT01887782. Between Sept 3, 2013, and Oct 3, 2016, we randomly allocated 205 participants to receive 10 Hz rTMS and 209 participants to receive iTBS. 192 (94%) participants in the 10 Hz rTMS group and 193 (92%) in the iTBS group were assessed for the primary outcome after 4–6 weeks of treatment. HRSD-17 scores improved from 23·5 (SD 4·4) to 13·4 (7·8) in the 10 Hz rTMS group and from 23·6 (4·3) to 13·4 (7·9) in the iTBS group (adjusted difference 0·103, lower 95% CI −1·16; p=0·0011), which indicated non-inferiority of iTBS. Self-rated intensity of pain associated with treatment was greater in the iTBS group than in the 10 Hz rTMS group (mean score on verbal analogue scale 3·8 [SD 2·0] vs 3·4 [2·0] out of 10; p=0·011). Dropout rates did not differ between groups (10 Hz rTMS: 13 [6%] of 205 participants; iTBS: 16 [8%] of 209 participants); p=0·6004). The most common treatment-related adverse event was headache in both groups (10 Hz rTMS: 131 [64%] of 204; iTBS: 136 [65%] of 208). In patients with treatment-resistant depression, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression. Both treatments had low numbers of dropouts and similar side-effects, safety, and tolerability profiles. By use of iTBS, the number of patients treated per day with current rTMS devices can be increased several times without compromising clinical effectiveness. Canadian Institutes of Health Research.

Tuberculosis (TB) remains a significant public health challenge, particularly in rural areas of high-burden countries like China. Active case finding (ACF) and timely treatment have been proven effective in reducing TB prevalence, but the impact on the TB epidemic when employing new technologies in ACF is still unknown. This study aims to evaluate the effectiveness of a comprehensive ACF package utilizing mobile vans equipped with artificial intelligence (AI)-aided radiology and GeneXpert testing in reducing TB prevalence among high-risk populations in rural Guangxi, China. A pragmatic cluster randomized controlled trial will be conducted in two counties of Guangxi, China. The trial will randomize 23 townships to intervention or control groups at approximately 1:1 ratio. The intervention group will receive an ACF campaign in Year 1 among high-risk populations, incorporating visited by mobile vans equipped with AI-based digital X-ray screening, symptom assessment, and sputum collection for GeneXpert testing. Control group participants receive usual care. TB patients identified in Year 1 will complete their treatment in Year 2. The primary outcome is the prevalence rate of bacteriologically confirmed TB among high-risk populations in Year 3. Process evaluation will explore acceptability, feasibility and adaptation of the intervention. We will conduct incremental costing study to inform future scale-up of the intervention in other settings. This study will provide valuable insights into the effectiveness and feasibility of utilizing AI-equipped mobile vans and GeneXpert for TB ACF to reduce TB prevalence in rural settings. If successful, this model will contribute to possible solutions to achieve the WHO End TB Strategy by 2035. ClinicalTrials.gov NCT06702774.

The most effective timing for renal-replacement therapy in critically ill patients is unclear. In this randomized trial, patients with acute kidney injury who were assigned to an accelerated strategy did not have a lower risk of death at 90 days than those assigned to a standard strategy.

To propose a tool to assist trialists in making design decisions that are consistent with their trial's stated purpose. Randomized trials have been broadly categorized as either having a pragmatic or explanatory attitude. Pragmatic trials seek to answer the question, “Does this intervention work under usual conditions?,” whereas explanatory trials are focused on the question, “Can this intervention work under ideal conditions?” Design decisions make a trial more (or less) pragmatic or explanatory, but no tool currently exists to help researchers make the best decisions possible in accordance with their trial's primary goal. During the course of two international meetings, participants with experience in clinical care, research commissioning, health care financing, trial methodology, and reporting defined and refined aspects of trial design that distinguish pragmatic attitudes from explanatory. We have developed a tool (called PRECIS) with 10 key domains and which identifies criteria to help researchers determine how pragmatic or explanatory their trial is. The assessment is summarized graphically. We believe that PRECIS is a useful first step toward a tool that can help trialists to ensure that their design decisions are consistent with the stated purpose of the trial.

In this study, patients with cryptogenic stroke who were randomly assigned to undergo intensive ECG monitoring for 30 days had a higher incidence of detected atrial fibrillation (16%) than those assigned to receive standard 24-hour monitoring (3%). The prevention of stroke related to atrial fibrillation is a global public health priority. Strokes due to atrial fibrillation are common and frequently devastating (70 to 80% of patients die or become disabled 1 , 2 ), yet they are largely preventable with anticoagulant therapy (64% reduction in the risk of stroke and 25% reduction in mortality). 3 However, because atrial fibrillation is often intermittent and asymptomatic, it can be a silent risk factor that easily evades detection. 4 , 5 Since patients who have had a stroke or transient ischemic attack (TIA) due to atrial fibrillation face a high annual risk of stroke recurrence, . . .