In February, the Swiss Medical Board recommended that no new systematic mammography screening programs be introduced, that time limits be put on current programs, that screening quality be evaluated, ...and that women be given clear information regarding benefits and harms.
In January 2013, the Swiss Medical Board, an independent health technology assessment initiative under the auspices of the Conference of Health Ministers of the Swiss Cantons, the Swiss Medical Association, and the Swiss Academy of Medical Sciences, was mandated to prepare a review of mammography screening. The two of us, a medical ethicist and a clinical epidemiologist, were members of the expert panel that appraised the evidence and its implications. The other members were a clinical pharmacologist, an oncologic surgeon, a nurse scientist, a lawyer, and a health economist. As we embarked on the project, we were aware of the . . .
In this trial, patients with patent foramen ovale and cryptogenic embolism were assigned to undergo closure with the use of a percutaneous device or to receive medical therapy. There was no ...significant difference in the rates of recurrent embolic events or death.
Paradoxical embolism by means of a patent foramen ovale has been blamed as a cause of stroke and other systemic ischemic events since the 19th century.
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The actual passage of a venous clot through a patent foramen ovale has been documented in a few cases and resulted in systemic embolic events such as ischemic stroke, transient ischemic attack (TIA),
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–
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or myocardial infarction.
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Catheter-based closure of patent foramen ovale was introduced in 1992.
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Observational long-term data suggest that closure of patent foramen ovale in patients with a history of ischemic stroke may reduce the risk of recurrent stroke as compared . . .
IMPORTANCE: Bayesian analysis of clinical trial data may provide useful information to aid in study interpretation, especially when trial evidence suggests that the benefits of an intervention are ...uncertain, such as in a trial that evaluated early extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). OBJECTIVE: To demonstrate the potential utility of Bayesian analyses by estimating the posterior probability, under various assumptions, that early ECMO was associated with reduced mortality in patients with very severe ARDS in a randomized clinical trial (RCT). DESIGN AND EVIDENCE: A post hoc Bayesian analysis of data from an RCT (ECMO to Rescue Lung Injury in Severe ARDS EOLIA) that included 249 patients with very severe ARDS who had been randomized to receive early ECMO (n = 124; mortality at 60 days, 35%) vs initial conventional lung-protective ventilation with the option for rescue ECMO (n = 125, mortality at 60 days, 46%). The trial was designed to detect an absolute risk reduction (ARR) of 20%, relative risk (RR) of 0.67. Statistical prior distributions were specified to represent varying levels of preexisting enthusiasm or skepticism for ECMO and by Bayesian meta-analysis of previously published studies (with downweighting to account for differences and quality between studies). The RR, credible interval (CrI), ARR, and probability of clinically important mortality benefit (varying from RR less than 1 to RR less than 0.67 and ARR from 2% or more to 20% or more) were estimated with Bayesian modeling. FINDINGS: Combining a minimally informative prior distribution with the findings of the EOLIA trial, the posterior probability of RR less than 1 for mortality at 60 days after randomization was 96% (RR, 0.78 95% CrI, 0.56-1.04); the posterior probability of RR less than 0.67 was 18%, the probability of ARR of 2% or more was 92%, and the probability of ARR of 20% or more was 2%. With a moderately enthusiastic prior, equivalent to information from a trial of 264 patients with an RR of 0.78, the estimated RR was 0.78 (95% CrI, 0.63-0.96), the probability of RR less than 1 was 99%, the probability of RR less than 0.67 was 8%, the probability of ARR of 2% or more was 97%, and the probability of ARR of 20% or more was 0%. With a strongly skeptical prior, equivalent to information from a trial of 264 patients with an RR of 1.0, the estimated RR was 0.88 (95% CrI, 0.71-1.09), the probability of RR less than 1 was 88%, the probability of RR less than 0.67 was 0%, the probability of ARR of 2% or more was 78%, and the probability of ARR of 20% or more was 0%. If the prior was informed by previous studies, the estimated RR was 0.71 (95% CrI, 0.55-0.94), the probability of RR less than 1 was 99%, the probability of RR less than 0.67 was 48%, the probability of ARR of 2% or more was 98%, and the probability of ARR of 20% or more was 4%. CONCLUSIONS AND RELEVANCE: Post hoc Bayesian analysis of data from a randomized clinical trial of early extracorporeal membrane oxygenation compared with conventional lung-protective ventilation with the option for rescue extracorporeal membrane oxygenation among patients with very severe acute respiratory distress syndrome provides information about the posterior probability of mortality benefit under a broad set of assumptions that may help inform interpretation of the study findings.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. We aimed to assess the effectiveness of different preparations and doses of NSAIDs on osteoarthritis ...pain in a network meta-analysis.
For this network meta-analysis, we considered randomised trials comparing any of the following interventions: NSAIDs, paracetamol, or placebo, for the treatment of osteoarthritis pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the reference lists of relevant articles for trials published between Jan 1, 1980, and Feb 24, 2015, with at least 100 patients per group. The prespecified primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven timepoints after the start of treatment. We used an extension of multivariable Bayesian random effects models for mixed multiple treatment comparisons with a random effect at the level of trials. For the primary analysis, a random walk of first order was used to account for multiple follow-up outcome data within a trial. Preparations that used different total daily dose were considered separately in the analysis. To assess a potential dose–response relation, we used preparation-specific covariates assuming linearity on log relative dose.
We identified 8973 manuscripts from our search, of which 76 randomised trials with a total of 58 451 patients were included in this analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo were considered. All preparations, irrespective of dose, improved point estimates of pain symptoms when compared with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size ES −0·37) was at least 95%. Among maximally approved daily doses, diclofenac 150 mg/day (ES −0·57, 95% credibility interval CrI −0·69 to −0·45) and etoricoxib 60 mg/day (ES −0·58, −0·74 to −0·43) had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference. Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for naproxen (p=0·034). We found no evidence that treatment effects varied over the duration of treatment. Model fit was good, and between-trial heterogeneity and inconsistency were low in all analyses. All trials were deemed to have a low risk of bias for blinding of patients. Effect estimates did not change in sensitivity analyses with two additional statistical models and accounting for methodological quality criteria in meta-regression analysis.
On the basis of the available data, we see no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function. Nevertheless, in view of the safety profile of these drugs, physicians need to consider our results together with all known safety information when selecting the preparation and dose for individual patients.
Swiss National Science Foundation (grant number 405340-104762) and Arco Foundation, Switzerland.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Aims
Owing to new evidence from randomized controlled trials (RCTs) in low-risk patients with severe aortic stenosis, we compared the collective safety and efficacy of transcatheter aortic ...valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the entire spectrum of surgical risk patients.
Methods and results
The meta-analysis is registered with PROSPERO (CRD42016037273). We identified RCTs comparing TAVI with SAVR in patients with severe aortic stenosis reporting at different follow-up periods. We extracted trial, patient, intervention, and outcome characteristics following predefined criteria. The primary outcome was all-cause mortality up to 2 years for the main analysis. Seven trials that randomly assigned 8020 participants to TAVI (4014 patients) and SAVR (4006 patients) were included. The combined mean STS score in the TAVI arm was 9.4%, 5.1%, and 2.0% for high-, intermediate-, and low surgical risk trials, respectively. Transcatheter aortic valve implantation was associated with a significant reduction of all-cause mortality compared to SAVR {hazard ratio HR 0.88 95% confidence interval (CI) 0.78–0.99, P = 0.030}; an effect that was consistent across the entire spectrum of surgical risk (P-for-interaction = 0.410) and irrespective of type of transcatheter heart valve (THV) system (P-for-interaction = 0.674). Transcatheter aortic valve implantation resulted in lower risk of strokes HR 0.81 (95% CI 0.68–0.98), P = 0.028. Surgical aortic valve replacement was associated with a lower risk of major vascular complications HR 1.99 (95% CI 1.34–2.93), P = 0.001 and permanent pacemaker implantations HR 2.27 (95% CI 1.47–3.64), P < 0.001 compared to TAVI.
Conclusion
Compared with SAVR, TAVI is associated with reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of THV system.
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/m
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 (
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.
In view of the currently available evidence from randomized trials, we aimed to compare the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve ...replacement (SAVR) across the spectrum of risk and in important subgroups.
Trials comparing TAVI vs. SAVR were identified through Medline, Embase, and Cochrane databases. The primary outcome was death from any cause at 2 years. We performed random-effects meta-analyses to combine the available evidence and to evaluate the effect in different subgroups. This systematic review and meta-analysis is registered with PROSPERO (CRD42016037273). We identified four eligible trials including 3806 participants, who were randomly assigned to undergo TAVI (n = 1898) or SAVR (n = 1908). For the primary outcome of death from any cause, TAVI when compared with SAVR was associated with a significant 13% relative risk reduction hazard ratio (95% CI): 0.87 (0.76-0.99); P = 0.038 with homogeneity across all trials irrespective of TAVI device (P
= 0.306) and baseline risk (P
= 0.610). In subgroup analyses, TAVI showed a robust survival benefit over SAVR for patients undergoing transfemoral access 0.80 (0.69-0.93); P = 0.004, but not transthoracic access 1.17 (0.88-1.56); P = 0.293 (P
= 0.024) and in female 0.68 (0.50-0.91); P = 0.010, but not male patients 0.99 (0.77-1.28); P = 0.952 (P
= 0.050). Secondary outcomes of kidney injury, new-onset atrial fibrillation, and major bleeding favoured TAVI, while major vascular complications, incidence of permanent pacemaker implantation, and paravalvular regurgitation favoured SAVR.
Compared with SAVR, TAVI is associated with a significant survival benefit throughout 2 years of follow-up. Importantly, this superiority is observed irrespective of the TAVI device across the spectrum of intermediate and high-risk patients, and is particularly pronounced among patients undergoing transfemoral TAVI and in females.
One month after the implantation of biodegradable-polymer sirolimus-eluting coronary stents, patients at high bleeding risk were randomly assigned to stop dual antiplatelet therapy or to continue it ...for at least 2 additional months. At 1 year, 1 month of DAPT was noninferior to the longer treatment for ischemic cardiovascular events and was superior for bleeding.
Curtailing the Spring 2020 COVID-19 surge required sweeping and stringent interventions by governments across the world. Wastewater-based COVID-19 epidemiology programs have been initiated in many ...countries to provide public health agencies with a complementary disease tracking metric and non-discriminating surveillance tool. However, their efficacy in prospectively capturing resurgences following a period of low prevalence is unclear. In this study, the SARS-CoV-2 viral signal was measured in primary clarified sludge harvested every two days at the City of Ottawa's water resource recovery facility during the summer of 2020, when clinical testing recorded daily percent positivity below 1%. In late July, increases of >400% in normalized SARS-CoV-2 RNA signal in wastewater were identified 48 h prior to reported >300% increases in positive cases that were retrospectively attributed to community-acquired infections. During this resurgence period, SARS-CoV-2 RNA signal in wastewater preceded the reported >160% increase in community hospitalizations by approximately 96 h. This study supports wastewater-based COVID-19 surveillance of populations in augmenting the efficacy of diagnostic testing, which can suffer from sampling biases or timely reporting as in the case of hospitalization census.
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•SARS-CoV-2 WW viral signal increases 48 h prior to increase in new COVID cases.•SARS-CoV-2 WW viral signal increases 96 h prior to increase in COVID hospitalisations.•Time-lagged correlations confirm WBE predates new COVID cases and hospitalisations.•WBE may be better than clinical testing at detecting surges in COVID cases.•RNA epidemiological metric may become a valuable public health metric.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background:
In some randomized clinical trials, transradial access (TRA) compared with transfemoral access (TFA) was associated with lower mortality in patients with coronary artery disease ...undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter randomized clinical trials and whether these associations are modified by patient or procedural characteristics.
Methods:
We performed an individual patient data meta-analysis of multicenter randomized clinical trials comparing TRA with TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention. The primary outcome was all-cause mortality and the co–primary outcome was major bleeding at 30 days. The primary analysis was conducted by 1-stage mixed-effects models on the basis of the intention-to-treat cohort. The effect of access site on mortality and major bleeding was assessed further by multivariable analysis. The relationship among access site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment.
Results:
A total of 21 600 patients (10 775 TRA, 10 825 TFA) from 7 randomized clinical trials were included. The median age was 63.9 years, 31.9% were women, 95% presented with acute coronary syndrome, and 75.2% underwent percutaneous coronary intervention. All-cause mortality (1.6% versus 2.1%; hazard ratio, 0.77 95% CI, 0.63–0.95;
P
=0.012) and major bleeding (1.5% versus 2.7%; odds ratio, 0.55 95% CI, 0.45–0.67;
P
<0.001) were lower with TRA. Subgroup analyses for mortality showed consistent results, except for baseline hemoglobin level (
P
interaction
=0.003), indicating that the benefit of TRA was substantial in patients with moderate or severe anemia, whereas it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding, respectively. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention and ancillary mechanisms are required to fully explain the causal association.
Conclusions:
TRA is associated with lower all-cause mortality and major bleeding at 30 days compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit.
Registration:
URL:
https://www.crd.york.ac.uk/prospero
; Unique identifier: CRD42018109664.
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