We present the open-source software package DADA2 for modeling and correcting Illumina-sequenced amplicon errors (https://github.com/benjjneb/dada2). DADA2 infers sample sequences exactly and ...resolves differences of as little as 1 nucleotide. In several mock communities, DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.
Summary Background We report the 5-year results of the SYNTAX trial, which compared coronary artery bypass graft surgery (CABG) with percutaneous coronary intervention (PCI) for the treatment of ...patients with left main coronary disease or three-vessel disease, to confirm findings at 1 and 3 years. Methods The randomised, clinical SYNTAX trial with nested registries took place in 85 centres in the USA and Europe. A cardiac surgeon and interventional cardiologist at each centre assessed consecutive patients with de-novo three-vessel disease or left main coronary disease to determine suitability for study treatments. Eligible patients suitable for either treatment were randomly assigned (1:1) by an interactive voice response system to either PCI with a first-generation paclitaxel-eluting stent or to CABG. Patients suitable for only one treatment option were entered into either the PCI-only or CABG-only registries. We analysed a composite rate of major adverse cardiac and cerebrovascular events (MACCE) at 5-year follow-up by Kaplan-Meier analysis on an intention-to-treat basis. This study is registered with ClinicalTrials.gov , number NCT00114972. Findings 1800 patients were randomly assigned to CABG (n=897) or PCI (n=903). More patients who were assigned to CABG withdrew consent than did those assigned to PCI (50 vs 11). After 5 years’ follow-up, Kaplan-Meier estimates of MACCE were 26·9% in the CABG group and 37·3% in the PCI group (p<0·0001). Estimates of myocardial infarction (3·8% in the CABG group vs 9·7% in the PCI group; p<0·0001) and repeat revascularisation (13·7% vs 25·9%; p<0·0001) were significantly increased with PCI versus CABG. All-cause death (11·4% in the CABG group vs 13·9% in the PCI group; p=0·10) and stroke (3·7% vs 2·4%; p=0·09) were not significantly different between groups. 28·6% of patients in the CABG group with low SYNTAX scores had MACCE versus 32·1% of patients in the PCI group (p=0·43) and 31·0% in the CABG group with left main coronary disease had MACCE versus 36·9% in the PCI group (p=0·12); however, in patients with intermediate or high SYNTAX scores, MACCE was significantly increased with PCI (intermediate score, 25·8% of the CABG group vs 36·0% of the PCI group; p=0·008; high score, 26·8% vs 44·0%; p<0·0001). Interpretation CABG should remain the standard of care for patients with complex lesions (high or intermediate SYNTAX scores). For patients with less complex disease (low SYNTAX scores) or left main coronary disease (low or intermediate SYNTAX scores), PCI is an acceptable alternative. All patients with complex multivessel coronary artery disease should be reviewed and discussed by both a cardiac surgeon and interventional cardiologist to reach consensus on optimum treatment. Funding Boston Scientific.
Introducing new medical devices into routine practice raises concerns because patients and outcomes may differ from those in randomized trials.
To update the previous report of 30-day outcomes and ...present 1-year outcomes following transcatheter aortic valve replacement (TAVR) in the United States.
Data from the Society of Thoracic Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve Therapies Registry were linked with patient-specific Centers for Medicare & Medicaid Services (CMS) administrative claims data. At 299 US hospitals, 12 182 patients linked with CMS data underwent TAVR procedures performed from November 2011 through June 30, 2013, and the end of the follow-up period was June 30, 2014.
Transcatheter aortic valve replacement.
One-year outcomes including mortality, stroke, and rehospitalization were evaluated using multivariate modeling.
The median age of patients was 84 years and 52% were women, with a median STS Predicted Risk of Operative Mortality (STS PROM) score of 7.1%. Following the TAVR procedure, 59.8% were discharged to home and the 30-day mortality was 7.0% (95% CI, 6.5%-7.4%) (n = 847 deaths). In the first year after TAVR, patients were alive and out of the hospital for a median of 353 days (interquartile range, 312-359 days); 24.4% (n = 2074) of survivors were rehospitalized once and 12.5% (n = 1525) were rehospitalized twice. By 1 year, the overall mortality rate was 23.7% (95% CI, 22.8%-24.5%) (n = 2450 deaths), the stroke rate was 4.1% (95% CI, 3.7%-4.5%) (n = 455 stroke events), and the rate of the composite outcome of mortality and stroke was 26.0% (25.1%-26.8%) (n = 2719 events). Characteristics significantly associated with 1-year mortality included advanced age (hazard ratio HR for ≥95 vs <75 years, 1.61 95% CI, 1.24-2.09; HR for 85-94 years vs <75 years, 1.35 95% CI, 1.18-1.55; and HR for 75-84 years vs <75 years, 1.23 95% CI, 1.08-1.41), male sex (HR, 1.21; 95% CI, 1.12-1.31), end-stage renal disease (HR, 1.66; 95% CI, 1.41-1.95), severe chronic obstructive pulmonary disease (HR, 1.39; 95% CI, 1.25-1.55), nontransfemoral access (HR, 1.37; 95% CI, 1.27-1.48), STS PROM score greater than 15% vs less than 8% (HR, 1.82; 95% CI, 1.60-2.06), and preoperative atrial fibrillation/flutter (HR, 1.37; 95% CI, 1.27-1.48). Compared with men, women had a higher risk of stroke (HR, 1.40; 95% CI, 1.15-1.71).
Among patients undergoing TAVR in US clinical practice, at 1-year follow-up, overall mortality was 23.7%, the stroke rate was 4.1%, and the rate of the composite outcome of death and stroke was 26.0%. These findings should be helpful in discussions with patients undergoing TAVR.
Eusociality has convergently evolved multiple times, but the genomic basis of caste-based division of labor and degree to which independent origins of eusociality have utilized common genes remain ...largely unknown. Here we characterize caste-specific transcriptomic profiles across development and adult body segments from pharaoh ants (Monomorium pharaonis) and honey bees (Apis mellifera), representing two independent origins of eusociality. We identify a substantial shared core of genes upregulated in the abdomens of queen ants and honey bees that also tends to be upregulated in mated female flies, suggesting that these genes are part of a conserved insect reproductive groundplan. Outside of this shared groundplan, few genes are differentially expressed in common. Instead, the majority of the thousands of caste-associated genes are plastically expressed, rapidly evolving, and relatively evolutionarily young. These results emphasize that the recruitment of both highly conserved and lineage-specific genes underlie the convergent evolution of novel traits such as eusociality.
Decision aids are interventions that support patients by making their decisions explicit, providing information about options and associated benefits/harms, and helping clarify congruence between ...decisions and personal values.
To assess the effects of decision aids in people facing treatment or screening decisions.
Updated search (2012 to April 2015) in CENTRAL; MEDLINE; Embase; PsycINFO; and grey literature; includes CINAHL to September 2008.
We included published randomized controlled trials comparing decision aids to usual care and/or alternative interventions. For this update, we excluded studies comparing detailed versus simple decision aids.
Two reviewers independently screened citations for inclusion, extracted data, and assessed risk of bias. Primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were attributes related to the choice made and the decision-making process.Secondary outcomes were behavioural, health, and health system effects.We pooled results using mean differences (MDs) and risk ratios (RRs), applying a random-effects model. We conducted a subgroup analysis of studies that used the patient decision aid to prepare for the consultation and of those that used it in the consultation. We used GRADE to assess the strength of the evidence.
We included 105 studies involving 31,043 participants. This update added 18 studies and removed 28 previously included studies comparing detailed versus simple decision aids. During the 'Risk of bias' assessment, we rated two items (selective reporting and blinding of participants/personnel) as mostly unclear due to inadequate reporting. Twelve of 105 studies were at high risk of bias.With regard to the attributes of the choice made, decision aids increased participants' knowledge (MD 13.27/100; 95% confidence interval (CI) 11.32 to 15.23; 52 studies; N = 13,316; high-quality evidence), accuracy of risk perceptions (RR 2.10; 95% CI 1.66 to 2.66; 17 studies; N = 5096; moderate-quality evidence), and congruency between informed values and care choices (RR 2.06; 95% CI 1.46 to 2.91; 10 studies; N = 4626; low-quality evidence) compared to usual care.Regarding attributes related to the decision-making process and compared to usual care, decision aids decreased decisional conflict related to feeling uninformed (MD -9.28/100; 95% CI -12.20 to -6.36; 27 studies; N = 5707; high-quality evidence), indecision about personal values (MD -8.81/100; 95% CI -11.99 to -5.63; 23 studies; N = 5068; high-quality evidence), and the proportion of people who were passive in decision making (RR 0.68; 95% CI 0.55 to 0.83; 16 studies; N = 3180; moderate-quality evidence).Decision aids reduced the proportion of undecided participants and appeared to have a positive effect on patient-clinician communication. Moreover, those exposed to a decision aid were either equally or more satisfied with their decision, the decision-making process, and/or the preparation for decision making compared to usual care.Decision aids also reduced the number of people choosing major elective invasive surgery in favour of more conservative options (RR 0.86; 95% CI 0.75 to 1.00; 18 studies; N = 3844), but this reduction reached statistical significance only after removing the study on prophylactic mastectomy for breast cancer gene carriers (RR 0.84; 95% CI 0.73 to 0.97; 17 studies; N = 3108). Compared to usual care, decision aids reduced the number of people choosing prostate-specific antigen screening (RR 0.88; 95% CI 0.80 to 0.98; 10 studies; N = 3996) and increased those choosing to start new medications for diabetes (RR 1.65; 95% CI 1.06 to 2.56; 4 studies; N = 447). For other testing and screening choices, mostly there were no differences between decision aids and usual care.The median effect of decision aids on length of consultation was 2.6 minutes longer (24 versus 21; 7.5% increase). The costs of the decision aid group were lower in two studies and similar to usual care in four studies. People receiving decision aids do not appear to differ from those receiving usual care in terms of anxiety, general health outcomes, and condition-specific health outcomes. Studies did not report adverse events associated with the use of decision aids.In subgroup analysis, we compared results for decision aids used in preparation for the consultation versus during the consultation, finding similar improvements in pooled analysis for knowledge and accurate risk perception. For other outcomes, we could not conduct formal subgroup analyses because there were too few studies in each subgroup.
Compared to usual care across a wide variety of decision contexts, people exposed to decision aids feel more knowledgeable, better informed, and clearer about their values, and they probably have a more active role in decision making and more accurate risk perceptions. There is growing evidence that decision aids may improve values-congruent choices. There are no adverse effects on health outcomes or satisfaction. New for this updated is evidence indicating improved knowledge and accurate risk perceptions when decision aids are used either within or in preparation for the consultation. Further research is needed on the effects on adherence with the chosen option, cost-effectiveness, and use with lower literacy populations.
Knowledge of the atmospheric chemistry of reactive greenhouse gases is needed to accurately quantify the relationship between human activities and climate, and to incorporate uncertainty in our ...projections of greenhouse gas abundances. We present a method for estimating the fraction of greenhouse gases attributable to human activities, both currently and for future scenarios. Key variables used to calculate the atmospheric chemistry and budgets of major non‐CO2greenhouse gases are codified along with their uncertainties, and then used to project budgets and abundances under the new climate‐change scenarios. This new approach uses our knowledge of changing abundances and lifetimes to estimate current total anthropogenic emissions, independently and possibly more accurately than inventory‐based scenarios. We derive a present‐day atmospheric lifetime for methane (CH4) of 9.1 ± 0.9 y and anthropogenic emissions of 352 ± 45 Tg/y (64% of total emissions). For N2O, corresponding values are 131 ± 10 y and 6.5 ± 1.3 TgN/y (41% of total); and for HFC‐134a, the lifetime is 14.2 ± 1.5 y.
Key Points
A new method proposed for projecting non‐CO2 GHG with uncertainty
Enables the community to evaluate the importance of different processes
Independent evaluation of natural and anthropogenic GHG emissions
Metal-catalyzed reductive coupling has emerged as an alternative to the use of stoichiometric organometallic reagents in an increasingly diverse range of carbonyl and imine additions. In this review, ...the use of diene, allene, and enyne pronucleophiles in intermolecular carbonyl and imine reductive couplings are surveyed, along with related hydrogen autotransfer processes.
Abstract Background The STS/ACC Transcatheter Valve Therapy (TVT) Registry captures all procedures with Food and Drug Administration (FDA) approved transcatheter valve devices performed in the United ...States and is mandated as a condition of reimbursement by a Centers for Medicaid and Medicare Services (CMS) Objectives This annual report focuses on patient characteristics, trends, and outcomes of transcatheter aortic and mitral valve catheter-based valve procedures in the United States. Methods Data for all patients receiving commercially approved devices from 2012 through December 31, 2015 are entered in the TVT Registry. Results The 54,782 TAVR patients demonstrated decreases in expected risk of 30-day operative mortality (STS PROM) 7% to 6% and TAVR PROM (TVT PROM) 4% to 3% (both p<.0001) from 2012 to 2015. Observed in-hospital mortality decreased from 5.7% to 2.9% and one-year mortality decreased from 25.8% to 21.6. However, 30-day post procedure pacemaker insertion increased from 8.8% in 2013 to 12.0% in 2015. The 2,556 patients who underwent TMC in 2015 were similar to 2013-14 patients with hospital mortality of 2% with mitral regurgitation reduced to gradient ≤ 2 in 87% of patients (p<.0001). The 349 patients who underwent MViV and MViR procedures were high risk with, an STS PROM for MVR of 11%. The observed hospital mortality was 7.2% and 30-day post procedure was 8.5%. Summary The TVT Registry is an innovative registry that that monitors quality, patient safety and trends for these rapidly evolving new technologies. Condensed Abstract The STS/ACC TVT Registry captures all Food and Drug Administration (FDA) approved transcatheter valve devices preformed in the United States and is mandated as a condition for reimbursement by the Centers for Medicare Services. TAVR patients’ expected risks of mortality and actual in-hospital mortality decreased. Transcatheter mitral clip procedures had a low mortality with reduced in mitral regurgitation to grade ≤ 2 in 87%. Mitral valve in valve or valve in ring patients were high risk for mortality, but actual hospital mortality was lower. The TVT Registry is an innovative registry that monitors quality, safety and trends of these evolving technologies
Coronary artery bypass grafting (CABG) has been considered the standard of care for patients with three-vessel disease (3VD), but long-term comparative results from randomized trials of CABG vs. ...percutaneous coronary intervention (PCI) using drug-eluting stents (DES) remain limited.
Patients with de novo 3VD or left main disease were randomly assigned to PCI with the paclitaxel-eluting first-generation stent or CABG in the SYNTAX trial. This pre-specified analysis presents the 5-year outcomes of patients with 3VD (n = 1095). The rate of major adverse cardiac and cerebrovascular events (MACCE) was significantly higher in patients with PCI compared with CABG (37.5 vs. 24.2%, respectively; P < 0.001). Percutaneous coronary intervention as opposed to CABG resulted in significantly higher rates of the composite of death/stroke/myocardial infarction (MI) (22.0 vs. 14.0%, respectively; P < 0.001), all-cause death (14.6 vs. 9.2%, respectively; P = 0.006), MI (9.2 vs. 4.0%, respectively; P = 0.001), and repeat revascularization (25.4 vs. 12.6%, respectively; P < 0.001); however, stroke was similar between groups at 5 years (3.0 vs. 3.5%, respectively; P = 0.66). Results were dependent on lesion complexity (P for interaction = 0.12); in patients with a low (0-22) SYNTAX score, PCI vs. CABG resulted in similar rates of MACCE (33.3% vs. 26.8%, respectively; P = 0.21) but significantly more repeat revascularization (25.4% vs. 12.6%, respectively; P = 0.038), while in intermediate (23-32) or high (≥ 33) SYNTAX score terciles, CABG demonstrated clear superiority in terms of MACCE, death, MI, and repeat revascularization. Differences in MACCE between PCI and CABG were larger in diabetics hazard ratio (HR) = 2.30 than non-diabetics (HR = 1.51), although the P for interaction failed to reach significance for MACCE (P for interaction = 0.095) or any of the other endpoints.
Five-year results of patients with 3VD treated with CABG or PCI using the first-generation paclitaxel-eluting DES suggest that CABG should remain the standard of care as it resulted in significantly lower rates of death, MI, and repeat revascularization, while stroke rates were similar. For patients with low SYNTAX scores, PCI is an acceptable revascularization strategy, although at a price of significantly higher rates of repeat revascularization.
NCT00114972.
Given vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2). Two critical issues arise: How timing of delivery of the second dose will affect infection dynamics and how it will affect prospects for the evolution of viral immune escape via a buildup of partially immune individuals. Both hinge on the robustness of the immune response elicited by a single dose as compared with natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short term, focusing on one dose generally decreases infections, but that longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection and find that a one-dose policy may increase the potential for antigenic evolution under certain conditions of partial population immunity. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose and to ramp up vaccination efforts globally.
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