Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Comparison of revascularization strategies in patients with acute coronary syndrome and multivessel coronary disease: A systematic review and network meta-analysis.

BACKGROUND: Whether revascularization should be performed as multivessel intervention at the time of index procedure (MV-index), staged procedure (MV-staged), or culprit only intervention (COI) in patients with multivessel disease (MVD) presenting with acute coronary syndrome (ACS) is unclear. We performed a systematic review and network meta-analysis of randomized controlled trials to assess the optimal revascularization strategy in this patient population. METHODS: PubMed, Embase, and Cochrane Central databases were systematically searched to identify all relevant studies. The outcomes assessed were major cardiac adverse events (MACE), all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and revascularization. A Bayesian random-effects network meta-analysis was used to calculate odds ratio (OR) with credible interval (CrI). RESULTS: Thirteen studies with 8,066 patients were included in the analysis. There was a decreased risk of MACE (MV-index vs. COI: OR, 0.35; 95% CrI, 0.23-0.55; MV-staged vs COI: OR, 0.52; 95% CrI, 0.31-0.81) and revascularization (MV-index vs. COI: OR, 0.27; 95% CrI, 0.15-0.49; MV-staged vs. COI: OR, 0.38; 95% CrI, 0.19-0.70) with MV-index intervention and MV-staged intervention compared with COI. However, MV-index intervention and not MV-staged intervention was associated with a decreased risk of MI (MV-index vs. COI: OR, 0.35; 95% CrI, 0.12-0.93; MV-staged vs. COI: OR, 0.65; 95% CrI, 0.24-1.59) compared with COI. CONCLUSIONS: Our analysis suggests that multivessel intervention either at index procedure or as staged intervention may be more efficacious compared to COI in patients with MVD presenting with ACS.

Oxygen Administration Does Not Influence the Prognosis of Acute Myocardial Infarction: A Meta-Analysis.

BACKGROUND: The safety and efficacy of supplemental oxygen in acute myocardial infarction (AMI) remains unclear. STUDY QUESTION: To evaluate the safety and efficacy of supplemental oxygen in patients who present with AMI. DATA SOURCES: We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, ISI Web of Science, Scopus, and conference proceedings from inception through January 2016. STUDY DESIGN: Eligible studies were randomized trials that evaluated the role of oxygen compared with room air in AMI. The clinical outcome measured was 30-day mortality, and odds ratio (OR) was calculated for the measured outcome. The Mantel-Haenszel method was used to pool 30-day mortality in a random-effects model. Sensitivity analysis was carried out to evaluate the effect of revascularization of the culprit artery on the outcome. RESULTS: The pooled analysis suggested no difference in 30-day mortality [OR 1.09; 95% confidence interval (CI), 0.30-4.00; P = 0.89] between oxygen and room air. Metaregression demonstrated that all the between-study variance was because of coronary revascularization (P = 0.01, R = 1.0). A subgroup analysis suggested a trend toward increased mortality with oxygen (OR 3.26; 95% CI, 0.94-11.29; P = 0.06) when less than half of the patient population underwent revascularization. On the other hand, there was a nonsignificant numerical decrease in mortality with oxygen (OR 0.41; 95% CI, 0.14-1.19; P = 0.10) in the presence of coronary revascularization. Metaregression confirmed that all the between-study variance was because of coronary revascularization (P = 0.01, R = 1.0). CONCLUSIONS: In this meta-analysis, we found that the evidence on the safety and efficacy of oxygen was not only weak and inconsistent but also had modest statistical power. The variation in results was mainly because of the presence or absence of revascularization of the culprit artery. Adequately powered studies are needed to further delineate the role of oxygen in patients undergoing coronary revascularization.

Impact of Cell Therapy on Myocardial Perfusion and Cardiovascular Outcomes in Patients With Angina Refractory to Medical Therapy: A Systematic Review and Meta-Analysis.

RATIONALE: The effect of stem/progenitor cells on myocardial perfusion and clinical outcomes in patients with refractory angina remains unclear because studies published to date have been small phase I-II trials. OBJECTIVE: We performed a meta-analysis of randomized controlled trials to evaluate the effect of cell-based therapy in patients with refractory angina who were ineligible for coronary revascularization. METHODS AND RESULTS: Several data sources were searched from inception to September 2015, which yielded 6 studies. The outcomes pooled were indices of angina (anginal episodes, Canadian Cardiovascular Society angina class, exercise tolerance, and antianginal medications), myocardial perfusion, and clinical end points. We combined the reported clinical outcomes (myocardial infarction, cardiac-related hospitalization, and mortality) into a composite end point (major adverse cardiac events). Mean difference (MD), standardized mean differences, or odds ratio were calculated to assess relevant outcomes. Our analysis shows an improvement in anginal episodes (MD, -7.81; 95% confidence interval [CI], -15.22 to -0.41), use of antianginal medications (standardized MD, -0.59; 95% CI, -1.03 to -0.14), Canadian Cardiovascular Society class (MD, -0.58; 95% CI, -1.00 to -0.16), exercise tolerance (standardized MD, 0.331; 95% CI, 0.08 to 0.55), and myocardial perfusion (standardized MD, -0.49; 95% CI, -0.76 to -0.21) and a decreased risk of major adverse cardiac events (odds ratio, 0.49; 95% CI, 0.25 to 0.98) and arrhythmias (odds ratio, 0.25; 95% CI, 0.06 to 0.98) in cell-treated patients when compared with patients on maximal medical therapy. CONCLUSIONS: The present meta-analysis indicates that cell-based therapies are not only safe but also lead to an improvement in indices of angina, relevant clinical outcomes, and myocardial perfusion in patients with refractory angina. These encouraging results suggest that larger, phase III randomized controlled trials are in order to conclusively determine the effect of stem/progenitor cells in refractory angina.

Single-Center Retrospective Study of Risk Factors and Predictive Value of Framingham Risk Score of Patients with ST Elevation Myocardial Infarction.

OBJECTIVES: The objective of this study was to identify risk factors and clinical profile of the patients presenting with ST elevation myocardial infarction (STEMI). We further evaluated the utility of the Framingham Risk Score (FRS) in the accurate identification of these patients if used before their coronary event. METHODS: We evaluated the demographic, clinical, and angiographic characteristics of patients admitted with STEMI. We also calculated cardiovascular event risk using the FRS in a subset of patients without prior known coronary artery disease and diabetes mellitus. RESULTS: A total of 44 patients, predominantly men (75%) and white (80%), with a mean age of 56 ± 10 years, were included in our analysis. Cigarette smoking was the predominant risk factor (83%) followed by hypertension (77%) and dyslipidemia (68%). The calculated FRS in a subset of patients without prior coronary artery disease or diabetes mellitus was 14.1% ± 5.8%. Based on the FRS, 8 (36%) patients had a 10-year risk >20% and 14 (63%) patients had a 10-year risk between 10% and 20%. CONCLUSIONS: In a series of consecutive patients with STEMI, we observed that high FRS was inadequate in correct identification and risk stratification of the majority of patients who had STEMI. Our study underlines the importance of being familiar with multiple risk scores and choosing the most applicable risk score based on the patient's individual characteristics. In addition, it is important to take into consideration the nontraditional risk factors or measurement of coronary artery calcium as a part of the risk assessment algorithm.

The State of US Health, 1990-2016: Burden of Diseases, Injuries, and Risk Factors Among US States.

Introduction: Several studies have measured health outcomes in the United States, but none have provided a comprehensive assessment of patterns of health by state. Objective: To use the results of the Global Burden of Disease Study (GBD) to report trends in the burden of diseases, injuries, and risk factors at the state level from 1990 to 2016. Design and Setting: A systematic analysis of published studies and available data sources estimates the burden of disease by age, sex, geography, and year. Main Outcomes and Measures: Prevalence, incidence, mortality, life expectancy, healthy life expectancy (HALE), years of life lost (YLLs) due to premature mortality, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 333 causes and 84 risk factors with 95% uncertainty intervals (UIs) were computed. Results: Between 1990 and 2016, overall death rates in the United States declined from 745.2 (95% UI, 740.6 to 749.8) per 100 000 persons to 578.0 (95% UI, 569.4 to 587.1) per 100 000 persons. The probability of death among adults aged 20 to 55 years declined in 31 states and Washington, DC from 1990 to 2016. In 2016, Hawaii had the highest life expectancy at birth (81.3 years) and Mississippi had the lowest (74.7 years), a 6.6-year difference. Minnesota had the highest HALE at birth (70.3 years), and West Virginia had the lowest (63.8 years), a 6.5-year difference. The leading causes of DALYs in the United States for 1990 and 2016 were ischemic heart disease and lung cancer, while the third leading cause in 1990 was low back pain, and the third leading cause in 2016 was chronic obstructive pulmonary disease. Opioid use disorders moved from the 11th leading cause of DALYs in 1990 to the 7th leading cause in 2016, representing a 74.5% (95% UI, 42.8% to 93.9%) change. In 2016, each of the following 6 risks individually accounted for more than 5% of risk-attributable DALYs: tobacco consumption, high body mass index (BMI), poor diet, alcohol and drug use, high fasting plasma glucose, and high blood pressure. Across all US states, the top risk factors in terms of attributable DALYs were due to 1 of the 3 following causes: tobacco consumption (32 states), high BMI (10 states), or alcohol and drug use (8 states). Conclusions and Relevance: There are wide differences in the burden of disease at the state level. Specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention. These data can be used to inform national health priorities for research, clinical care, and policy.

Intravascular ultrasound-guided vs angiography-guided drug-eluting stent implantation in complex coronary lesions: Meta-analysis of randomized trials.

The relative outcomes of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI with drug-eluting stent (DES) in complex lesions have not been established. We sought to compare the efficacy and safety of IVUS-guided PCI with angiography-guided PCI in patients with complex coronary lesions treated with DES. METHODS: Electronic databases were searched to identify all randomized trials comparing IVUS-guided vs angiography-guided DES implantation. We evaluated major adverse cardiac events (MACE), all-cause and cardiovascular death, myocardial infarction, target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis outcomes at the longest reported follow-up. Random-effects modeling was used to calculate pooled relative risk (RR) and 95% CIs. RESULTS: Eight trials comprising 3,276 patients (1,635 IVUS-guided and 1,641 angiography-guided) enrolling only patients with complex lesions were included. Mean follow-up was 1.4±0.5years. Compared with angiography-guided PCI, patients undergoing IVUS-guided PCI had significantly lower MACE (RR 0.64, 95% CI 0.51-0.80, P=.0001), TLR (RR 0.62, 95% CI 0.45-0.86, P=.004), and TVR (RR 0.60, 95% CI 0.42-0.87, P=.007). There were no significant differences for stent thrombosis, cardiovascular death, or all-cause death. In meta-regression analysis, IVUS-guided PCI was of greatest benefit in reducing MACE in patients with acute coronary syndromes, diabetes, and long lesions. CONCLUSIONS: The present meta-analysis demonstrates a significant reduction in MACE, TVR, and TLR with IVUS-guided DES implantation in complex coronary lesions.

Clinical outcomes associated with per-operative discontinuation of aspirin in patients with coronary artery disease: A systematic review and meta-analysis.

BACKGROUND: Postoperative state is characterized by increased thrombotic risk by virtue of platelet activation. Whether aspirin ameliorates this risk in patients with established coronary artery disease undergoing cardiac or noncardiac surgery is unknown. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiac events (MACE) and the risk of bleeding in patients with early (3-5 or more days before surgery) vs. late discontinuation(<3-5 days)/no discontinuation of aspirin. METHODS: Multiple databases were searched from inception of these databases until March 2015 to identify studies that reported discontinuation of aspirin in patients undergoing surgery. The outcomes measured were all cause mortality, nonfatal myocardial infarction and other relevant thrombotic events (MACE) which also may include, fatal and nonfatal MI, stent thrombosis and restenosis, stroke, perioperative cardiovascular complications (heart failure, MI, VTE, acute stroke) and perioperative bleeding during the perioperative period to up to 30 days after surgery. RESULTS: A total of 1,018 titles were screened, after which six observational studies met the inclusion criteria. Our analysis suggests that there is no difference in MACE with planned discontinuation of aspirin (OR = 1.17, 95% CI = 0.76-1.81; P = 0.05; I2 = 55%). Early discontinuation of aspirin showed a decreased risk of peri-operative bleeding (OR 0.82, 95% CI = 0.67-0.99; P = 0.04; I2 = 42%). CONCLUSION: Our analysis suggests that planned short-term discontinuation in the appropriate clinical setting appears to be safe in the correct clinical setting with no increased risk of thrombotic events and with a decreased risk of bleeding. © 2016 Wiley Periodicals, Inc.

Removal of arsenate and dichromate ions from different aqueous media by amine based p(TAEA-co-GDE) microgels.

In this work, microgels based on tris(2-aminoethyl) amine (TAEA) and glycerol diglycidyl ether (GDE) via simple microemulsion polymerization was prepared as p(TAEA-co-GDE) microgels were used as adsorbent for removal of dichromate (Cr (VI)) and arsenate (As (V)) ions from different aqueous environments. The p(TAEA-co-GDE) microgels were demonstrated very efficient adsorption capacity for Cr (VI), and As (V) that are 164.98 mg/g, and 123.64 mg/g from distilled (DI) water, respectively. The effect of the medium pH on the adsorption capacity of p(TAEA-co-GDE) microgels for Cr (VI) and As (V) ions were investigated. The maximum adsorption capacity was obtained at pH 4.0 for both ions with maximum adsorbed amounts of 160.62, and 98.72 mg/g, respectively. In addition, the microgels were also shown moderate adsorption capacity for Cr (VI) and As (V) from other water sources; tap water with 115.18 mg/g and 82.86 mg/g, sea water with 64.24 mg/g and 46.88 mg/g and creek water with 73.52 mg/g and 59.33 mg/g, respectively. Moreover, the increase in adsorbent dose from 0.025 to 0.125 g enhanced % adsorption of Cr (VI) from 54.13 to 98.03, and As (V) from % 26.72-98.70, respectively. For the adsorption process Langmuir and Freundlich adsorption isotherms were applied and found that Langmuir adsorption isotherm with R2 value of 0.99 for both the metal ions are suitable. Moreover, the experimental adsorption capacities of Cr (VI) and As (V) were found very close to the theoretical values calculated from Langmuir adsorption isotherm. More importantly, the microgels were made magnetic responsive to recover them easily from adsorption medium for reuse studies by applying external magnetic field with little decrease in adsorption capacity. Additionally, reusability of p(TAEA-co-GDE) microgels was also evaluated for adsorption of Cr (VI) and As (V) from DI water.

Efficacy and safety of transcatheter aortic valve replacement in intermediate surgical risk patients: A systematic review and meta-analysis.

BACKGROUND: The efficacy of transcatheter aortic valve replacement (TAVR) in aortic stenosis patients at high surgical risk has been established. The data on patients with intermediate risk is not conclusive. We performed a meta-analysis of studies which compared TAVR with surgical aortic valve replacement (SAVR) in patients at intermediate surgical risk. METHODS: Several databases searched from inception to February 2015 yielded 7 eligible studies with 2,173 participants. The measured outcome of efficacy was all-cause mortality. Data on safety included stroke, permanent pacemaker implantation (PPI), aortic regurgitation (AR), vascular access complications, and major bleeding. Outcomes were pooled and relative risk (RR) was calculated with the Mantel-Haenszel method. RESULTS: There was no difference in either short-term (RR, 1.02; 95% CI: 0.63-1.63; P = 0.94; I2 = 0%) or medium to long-term all-cause mortality (RR, 0.99; 95% CI: 0.81-1.21; P = 0.91; I2 = 0%). There was increased incidence of stroke (RR, 2.96; 95% CI: 0.87-10.09; P = 0.08; I2 = 0%), AR (RR, 3.59; 95% CI: 2.13-7.19; P < 0.00001; I2 = 2%), PPI (RR, 6.53; 95% CI: 1.91-22.32; P < 0.003; I2 = 0%) and vascular access complications (RR, 3.84; 95% CI: 0.65-22.76; P < 0.14; I2 = 48%) in patients with TAVR. There was a small, albeit increased risk of major or life threatening bleeding with SAVR as compared to TAVR (RR, 1.36; 95% CI: 1.04-1.80; P < 0.03; I2 = 0%). CONCLUSIONS: In this meta-analysis we found that TAVR may be an acceptable alternative to SAVR in patients with intermediate risk for surgery. However, we must await evidence from the current large randomized trials before widespread adoption of this procedure is undertaken. © 2016 Wiley Periodicals, Inc.

Fanconi Syndrome and Antiretrovirals: It Is Never Too Late.

Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure.

Efficient Photocatalytic Degradation of Norfloxacin in Aqueous Media by Hydrothermally Synthesized Immobilized TiO2/Ti Films with Exposed {001} Facets.

In this study, a novel immobilized TiO2/Ti film with exposed {001} facets was prepared via a facile one-pot hydrothermal route for the degradation of norfloxacin from aqueous media. The effects of various hydrothermal conditions (i.e., solution pH, hydrothermal time (HT) and HF concentration) on the growth of {001} faceted TiO2/Ti film were investigated. The maximum photocatalytic performance of {001} faceted TiO2/Ti film was observed when prepared at pH 2.62, HT of 3 h and at HF concentration of 0.02 M. The as-prepared {001} faceted TiO2/Ti films were fully characterized by field-emission scanning electron microscope (FE-SEM), X-ray diffraction (XRD), high resolution transmission electron microscope (HR-TEM), and X-ray photoelectron spectroscopy (XPS). More importantly, the as-prepared {001} faceted TiO2/Ti film exhibited excellent photocatalytic performance toward degradation of norfloxacin in various water matrices (Milli-Q water, tap water, river water and synthetic wastewater). The individual influence of various anions (SO42-, HCO3-, NO3-, Cl-) and cations (K+, Ca2+, Mg2+, Cu2+, Na+, Fe3+) usually present in the real water samples on the photocatalytic performance of as-prepared TiO2/Ti film with exposed {001} facet was investigated. The mechanistic studies revealed that •OH is mainly involved in the photocatalytic degradation of norfloxacin by {001} faceted TiO2/Ti film. In addition, norfloxacin degradation byproducts were investigated, on the basis of which degradation schemes were proposed.

Cardioprotective role of ischemic postconditioning in acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Evidence suggests that ischemic postconditioning (IPoC) may reduce the extent of reperfusion injury. We performed a meta-analysis of randomized controlled trials, which compared the role of IPoC during primary percutaneous coronary intervention (PCI) to PCI alone (control group) in ST-segment elevation myocardial infarction. METHODS: Several databases were searched, which yielded 19 studies. The outcomes of interest were measures of myocardial damage (serum cardiac enzymes and infarct size by imaging) and left ventricular function (left ventricular ejection fraction and wall motion score index). Mean difference (MD) and standardized mean difference (SMD) were used to assess the treatment effect. An inverse variance method was used to pool data into a random-effects model. RESULTS: Ischemic postconditioning demonstrated a decrease in serum cardiac enzymes (SMD -0.48, 95% CI -0.92 to -0.05, I(2) = 92%), reduction in infarct size by imaging (SMD -0.30, 95% CI -0.58 to -0.01, I(2) = 80%), wall motion score index (MD -0.19, 95% CI -0.29 to -0.09, I(2) = 44%), and showed improvement in left ventricular ejection fraction (IPoC 52 ± 0.4, control 49.7 ± 0.4) (MD 2.78, 95% CI 0.66-4.91, I(2) = 69%). All included studies were limited by high risk of performance and publication bias. CONCLUSIONS: Ischemic postconditioning during PCI in ST-segment elevation myocardial infarction appears to be superior to PCI alone in reduction of both myocardial injury or damage and improvement in global and regional left ventricular function. The effect seems to be more pronounced when a greater myocardial area is at risk. Given the limitations of the current available evidence, additional data from large randomized controlled trials are warranted.

Safety and efficacy of interrupted dabigatran for peri-procedural anticoagulation in catheter ablation of atrial fibrillation: a systematic review and meta-analysis.

AIMS: To examine the safety (defined as bleeding risk) and efficacy (defined as prevention of thromboembolic events) of interrupted dabigatran for peri-procedural anticoagulation in catheter ablation (CA) of atrial fibrillation (AF) in comparison with warfarin. METHODS AND RESULTS: Reviewers independently searched literature databases from January 2010 through April 2013 for studies comparing the safety and efficacy of dabigatran and warfarin in CA of AF and extracted pre-defined data. The Mantel-Haenszel method was used to pool data of bleeding and thromboembolism outcomes into random and fixed effect model meta-analyses, respectively. Odds ratios (ORs), and risk difference (RD) analysis when studies reported no events in either arm, were used to generate an overall effect estimate of both outcomes. Publication bias and heterogeneity were assessed by contour funnel plot and the I(2) test, respectively. Nine citations, including 3036 patients (1073 dabigatran), met the inclusion criteria. There was no significant difference between interrupted dabigatran and warfarin therapy in CA of AF in occurrence of bleeding [dabigatran 58 (5.4%), warfarin 103 (5.2%); OR 0.92 (95% confidence interval (CI) 0.55-1.45); χ(2) = 13.03-P = 0.11; I(2) = 39%] or thromboembolism [dabigatran 5 (0.4%), warfarin 2 (0.1%); OR 2.15 (95% CI-0.58-7.98); χ(2) = 2.14, P = 0.54; I(2) = 0%; RD 0.00 (95% CI-0.00 to 0.01); χ(2) = 3.37, P = 0.81; I(2) = 0%]. Analysis of pre-defined subgroups (published articles vs. abstracts), sensitivity analyses (interrupted warfarin, USA studies, and Japanese studies) and fixed effect model analyses showed similar results. Heterogeneity was mild in the bleeding outcome analysis and zero in thromboembolism. There was no evidence of publication bias in either meta-analysis. CONCLUSION: Meta-analysis of currently available studies showed no significant difference in bleeding and thromboembolism between interrupted dabigatran and warfarin therapy in CA of AF. Dabigatran appears to be safe and effective for peri-procedural anticoagulation in CA of AF.

Cell therapy for nonischemic dilated cardiomyopathy: A systematic review and meta-analysis of randomized controlled trials.

Cell therapy involves transplantation of human cells to promote repair of diseased or injured tissues and/or cells. Only a limited number of mostly small-scale trials have studied cell therapy in nonischemic cardiomyopathy (NICM). We performed a meta-analysis of randomized clinical trials (RCTs) to assess the safety and efficacy of cell therapy in NICM. Electronic databases were searched for relevant RCTs from inception until August 2020. Outcomes assessed were left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter or volume (LVEDD), quality of life (QoL) indices, and major adverse cardiac events (MACEs). Weighted mean differences (MDs) and standardized mean differences (SMDs) were calculated using random-effects methods. Eleven RCTs with 574 participants were included in the analysis. There was a significant increase in mean LVEF (MD, 4.17%; 95% confidence interval [CI] = 1.66-6.69) and modest decrease in LVEDD (SMD, -0.50; 95% CI = -0.95 to -0.06) in patients treated with cell therapy compared with controls. Cell therapy was also associated with improvement in functional capacity, as assessed by the 6-minute walking distance (MD, 72.49 m; 95% CI = 3.44-141.53). No significant differences were seen in MACEs and QoL indices between treated and control groups. This meta-analysis suggests that cell therapy may improve LV systolic function and may be associated with improvement in LVEDD and functional capacity compared with maximal medical therapy. Cell therapy was safe, with no significant difference in MACEs between treatment and control groups. However, given the limitations of current studies, larger well-designed RCTs are needed to evaluate the efficacy of cell therapy in patients with NICM.

Quality and strength of evidence of the Infectious Diseases Society of America clinical practice guidelines.

OBJECTIVE: To describe the distribution and temporal trends of the quality and strength of evidence supporting recommendations in the Infectious Diseases Society of America (IDSA) clinical practice guidelines. METHODS: Guidelines either issued or endorsed by IDSA from March 1994 to July 2009 were evaluated using the IDSA-US Public Health Service Grading System. In this system, the letters A-E signify the strength of the recommendation, and numerals I-III indicate the quality of evidence supporting these recommendations. The distribution of the guideline recommendations among strength of recommendation and quality of evidence classes was quantified. Temporal changes between the first and current guideline version were evaluated. RESULTS: Approximately one-half (median, 50.0%; interquartile range [IQR], 38.1%-58.6%) of the recommendations in the current guidelines are supported by level III evidence (derived from expert opinion). Evidence from observational studies (level II) supports 31% of recommendations (median, 30.9%; IQR, 23.3%-43.2%), whereas evidence based on ≥ 1 randomized clinical trial (level I) constitutes 16% of the recommendations (median, 15.8%; IQR, 5.8%-28.3%). The strength of recommendation was mainly distributed among classes A (median, 41.5%; IQR, 28.7%-55.6%) and B (median, 40.3%; IQR, 27.1%-47.9%). Among guidelines with ≥ 1 revised version, the recommendations moved proportionately toward more level I evidence (+12.4%). Consequently, there was a proportional increase in class A recommendations (+11.1%) with a decrease in class C recommendations (-23.5%). CONCLUSIONS: The IDSA guideline recommendations are primarily based on low-quality evidence derived from nonrandomized studies or expert opinion. These findings highlight the limitations of current clinical infectious diseases research that can provide high-quality evidence. There is an urgent need to support high-quality research to strengthen the evidence available for the formulation of guidelines.