Safety-net hospitals versus non-safety centers and clinical outcomes after trans-catheter aortic valve replacement.

OBJECTIVE: To compare post-procedural outcomes of trans-catheter valve replacement (TAVR) among safety-net (SNH) and non-safety net hospitals (non-SNH). BACKGROUND: SNH treat a large population of un-insured and low income patients; prior studies report worse outcome at these centers. Results of TAVR at these centers is limited. METHODS: Adults undergoing TAVR at hospitals in the US participating in the National In-patient sample (NIS) database from January 2014 to December 2015 were included. A 1:1 propensity-matched cohort of patients operated at SNH and non-SNH institutions was analyzed, on the basis of 16 demographic and clinical co-variates. Main outcome was all-cause post-procedural mortality. Secondary outcomes included stroke, acute kidney injury and length of post-operative stay. RESULTS: Between 2014 and 2015, 41,410 patients (mean age 80 ± 0.11 years, 46% female) underwent TAVR at 731 centers; 6,996 (16.80%) procedures were performed at SNH comprising 135/731 (18.4%) of all centers performing TAVR. SNH patients were more likely to be female (49% vs. 46%, p < .001); admitted emergently (31% vs. 21%; p < .001; at the lowest quartile for household income (25% % vs. 20%; p < .001) and from minorities (Blacks 5.9% vs. 3.9%; Hispanic 7.2% vs. 3.2%).Adjusted logistic regression was performed on 6,995 propensity-matched patient pairs. Post-procedural mortality [OR 0.99(0.98-1.007); p = .43], stroke [OR 1.009(0.99-1.02); p = .08], acute kidney injury [OR 0.99(0.96-1.01); p = .5] and overall length of stay (6.9 ± 0.1 vs. 7.1 ± 0.2 days; p = .57) were comparable in both cohorts. CONCLUSION: Post-procedural outcomes after TAVR at SNH are comparable to national outcomes and wider adoption of TAVR at SNH may not adversely influence outcomes.

Contribution of individual components to composite end points in contemporary cardiovascular randomized controlled trials.

Cardiovascular randomized controlled trials (RCTs) typically set composite end points as the primary outcome to enhance statistical power. However, influence of individual component end points on overall composite outcomes remains understudied. METHODS: We searched MEDLINE for RCTs published in 6 high-impact journals (The Lancet, the New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and the European Heart Journal) from 2011 to 2017. Two-armed, parallel-design cardiovascular RCTs which reported composite outcomes were included. All-cause or cardiovascular mortality, myocardial infarction, heart failure, and stroke were deemed "hard" end points, whereas hospitalization, angina, and revascularization were identified as "soft" end points. Type of outcome (primary or secondary), event rates in treatment and control groups for the composite outcome and of its components according to predefined criteria. RESULTS: Of the 45.8% (316/689) cardiovascular RCTs which used a composite outcome, 79.4% set the composite as the primary outcome. Death was the most common component (89.8%) followed by myocardial infarction (66.1%). About 80% of the trials reported complete data for each component. One hundred forty-seven trials (46.5%) incorporated a "soft" end point as part of their composite. Death contributed the least to the estimate of effects (R2 change = 0.005) of the composite, whereas revascularization contributed the most (R2 change = 0.423). CONCLUSIONS: Cardiovascular RCTs frequently use composite end points, which include "soft" end points, as components in nearly 50% of studies. Higher event rates in composite end points may create a misleading interpretation of treatment impact due to large contributions from end points with less clinical significance.

Effects of Nutritional Supplements and Dietary Interventions on Cardiovascular Outcomes: An Umbrella Review and Evidence Map.

Background: The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. Purpose: To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. Data Sources: PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. Study Selection: English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Data Extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Data Synthesis: Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence). Limitations: Suboptimal quality and certainty of evidence. Conclusion: Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke. Primary Funding Source: None.

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.

Transcatheter closure of patent foramen ovale following cryptogenic stroke: An updated meta-analysis of randomized controlled trials.

BACKGROUND: Transcatheter closure of patent foramen ovale (PFO) after cryptogenic stroke has long been a contentious issue. Herein, we pool aggregate data examining safety and efficacy of transcatheter closure of PFO compared with medical therapy following initial cryptogenic stroke. METHODS: We searched for randomized clinical trials (RCT) that compared device closure with medical management and reported on subsequent stroke and adverse events. Stroke was considered as the primary efficacy endpoint, whereas bleeding and atrial fibrillation were considered primary safety endpoints. Data were pooled by the random effects model and I2 was used to assess heterogeneity. RESULTS: A total of 5 RCT investigating 3630 patients met inclusion criteria. Pooled analysis revealed that device closure compared to medical management was associated with a significant reduction in stroke (RR=0.3, 95% CI=0.02-0.57). There was, however, a significant increase in atrial arrhythmias with device therapy (RR=4.8, 95% CI=2.2-10.7). We found no increase in bleeding (RR=0.80, 95% CI=0.5-1.4), death (RR=0.76, 95% CI=0.3-1.99) or "any adverse events" (RR=1.02, 95% CI=0.85-1.23) with device therapy. Sub-group analysis revealed that device closure significantly reduced the incidence of the composite primary endpoint among patients who had moderate to large shunt sizes (RR=0.22, 95% CI=0.02-0.42). CONCLUSIONS: Transcatheter closure is associated with a significant reduction in the risk of stroke compared to medical management at the expense of an increased risk of atrial arrhythmias.

Impact of total occlusion of culprit artery in acute non-ST elevation myocardial infarction: a systematic review and meta-analysis.

AIMS: Total occlusion (TO) of the culprit artery usually presents with ST-elevation myocardial infarction. A subset of patients with TO present as non-ST segment elevation myocardial infarction (NSTEMI) without classic ST-elevation on the electrocardiogram. This may lead to delay in identification of these patients and further management. We performed a meta-analysis to estimate the difference in outcomes between totally occluded and non-occluded culprit arteries in patients with NSTEMI. METHODS AND RESULTS: Our literature search yielded seven studies with 40 777 patients. The outcomes assessed were clinical presentation (Killip class), left ventricular ejection fraction, time to angiography, major cardiac adverse events (MACE) and all-cause mortality. The generic inverse or Mantel-Haenszel method was used to pool relevant outcomes and the mean difference (MD) or relative risk (RR) was calculated. A total of 10 415 (25.5%) patients had an occluded culprit artery with a predominant infero-lateral distribution (40% right coronary and 33% left circumflex artery). There was an increased risk of both MACE (short-term RR: 1.41; CI: 1.17, 1.70; P = 0.0003; I2 = 26%; medium- to long-term RR: 1.32; CI: 1.11, 1.56; P = 0.001; I2 = 25%) and all-cause mortality (short-term RR: 1.67; CI: 1.31, 2.13; P < 0.0001; I2 = 41%; medium to long-term RR: 1.42; CI: 1.08, 1.86; P = 0.01; I2 = 32%) with TO of the culprit artery. CONCLUSION: Our meta-analysis suggests that patients with NSTEMI who demonstrate a totally occluded culprit vessel on coronary angiography are at higher risk of mortality and major adverse cardiac events. Better risk stratification tools are needed to identify such high-risk acute coronary syndrome patients to facilitate earlier revascularization and potentially to improve outcomes.

Mortality Effect of ICD in Primary Prevention of Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Implantation of an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) is controversial in view of the recent DANISH trial which suggested no benefit with ICD for primary prevention in patients with non-ischemic cardiomyopathy (NICMP). METHODS: We conducted a meta-analysis of randomized control trials studying the role of ICD in primary prevention of SCD in patients with NICMP. Only six studies were identified after the application of inclusion/exclusion criteria. RESULTS: Pooling of these randomized trials showed a statistically significant benefit of using ICDs in patients with NICMP [OR 0.76 (0.64 - 0.91), I2 = 0%]. Sensitivity analysis did not show a statistically significant mortality benefit of ICD in NICMP in trials which had adequate beta blocker, ACE/ARB and aldosterone receptor blocker (ALD-RB) use [OR 0.70 (0.41, 1.19), I2 = 70%]. CONCLUSION: The DANISH trial's failure to show mortality benefit may be due to the significant number of patients who had CRT. Our meta-analysis studied the independent effect of ICDs and showed them to be associated with net mortality benefits in patients who are not on optimal guideline directed medical therapy; especially the patients not on ALD-RB.

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.

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.

Temporal Trends in Strut-Level Optical Coherence Tomography Evaluation of Coronary Stent Coverage: A Systematic Review and Meta-Analysis.

OBJECTIVES: We sought to pool data from all studies with reported strut-level data in human subjects evaluated by optical coherence tomography (OCT) surveillance and to compare the aggregate data of stent strut coverage on a longitudinal temporal timeline from initial implantation for different coronary stent subtypes. BACKGROUND: Delayed strut coverage following drug-eluting stent (DES) implantation is an important contributor to late stent thrombosis (LST). OCT can detect stent strut coverage. METHODS: We conducted a systematic search of published or presented studies reporting OCT stent strut coverage of bare-metal stents (BMS) and DES in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials to June 2014. Data from 3,515 patients with strut-level data on 731,761 struts were analyzed. RESULTS: The temporal kinetics of strut coverage differed according to stent type. The rate of strut coverage, reflected by the calculated regression coefficient, was found to be the highest in BMS, followed by early generation zotarolimus-eluting stent, everolimus-eluting stent, newer-generation zotarolimus-eluting stent, paclitaxel-eluting stent, and sirolimus-eluting stent (p < 0.0001). CONCLUSIONS: Aggregate rates of stent strut coverage assessed by OCT surveillance differed according to stent type. The clinical implications of these differences require further study but may underlie the differences in rates of stent thrombosis observed in clinical trials with different stent types. © 2015 Wiley Periodicals, Inc.

Trend over time; a structural review of articles published in Journal of Pakistan Medical Association from 1953-2009.

OBJECTIVE: To review the articles published in the Journal of Pakistan Medical Association from 1953 to 2009 and to assess the components of each article by a pretested proforma containing a checklist of items based on modified 'Strengthening the Reporting of Observational Studies in Epidemiology' statement. METHODS: The retrospective study was conducted at the office of the Journal of Pakistan Medical Association, Karachi, from February to November 2010. A checklist of items in the modified 'Strengthening the Reporting of Observational Studies in Epidemiology' statement was made after discussion among the authors of the study to finally include a revised checklist of 45 items instead of the checklist of 22 items of the statement. A total sample size of 370 was calculated. Simple randomisation was done for selection of articles from each year. For each article, major and minor items were documented. Data was fed into SPSS version 15. RESULTS: The scientific quality of reporting of most of the components of Introduction, Results and Discussion sections have improved progressively with time (p < 0.001) whereas most components of Methodology have remained consistent. CONCLUSION: A change in trend over time was observed over the study period in major and minor items of the articles in the Journal, showing improved reporting of various sub-components of articles.The modified 'Strengthening the Reporting of Observational Studies in Epidemiology' statement provides a checklist that may be used to improve the quality of articles.

The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature.

BACKGROUND: Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions. METHODS: We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients". RESULTS: Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary. CONCLUSION: Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

Role of vitamin K2 in preventing the recurrence of hepatocellular carcinoma after curative treatment: a meta-analysis of randomized controlled trials.

BACKGROUND: Hepatocellular cancer is notorious for recurrence even after curative therapy. High recurrence determines the long term prognosis of the patients. Vitamin K2 has been tested in trials for its effect on prevention of recurrence and improving survival. The results are inconclusive from individual trials and in our knowledge no systematic review which entirely focuses on Vitamin K2 as a chemo preventive agent is available to date. This review is an attempt to pool all the existing trials together and update the existing knowledge on the topic. METHODS: Medline, Embase and Cochrane Register of Controlled trials were searched for randomized controlled trials where vitamin K2 or its analogues, in any dosage were compared to placebo or No vitamin K2, for participants of any age or sex. Reference lists and abstracts of conference proceedings were searched by hand. Additional papers were identified by a manual search of the references from the key articles. Attempt was made to contact the authors of primary studies for missing data and with the experts in the field.Trials were assessed for inclusion by two independent reviewers. Primary outcomes were recurrence rates and survival rates. There were no secondary outcomes. Data was synthesized using a random effects model and results presented as relative risk with 95% Confidence Intervals. RESULT: For recurrence of hepatocellular cancer after hepatic resection or local ablative therapy, compared with controls, participants receiving Vitamin K2, pooled relative risks for hepatocellular cancer were 0.60; 95% CI: 0.28-1.28, p = 0.64) at 1 yr 0.66; 95% CI: 0.47-0.91), p = 0.01) at 2 yr; 0.71; 95% CI: 0.58-0.85, p = 0.004) at 3 yr respectively. The results were combined using the random analysis model. CONCLUSION: Five RCTs evaluated the preventive efficacy of menatetrenone on HCC recurrence after hepatic resection or local ablative therapy. The meta-analysis of all five studies, failed to confirm significantly better tumor recurrence- free survival at 1 year. Improved tumor recurrence at 2nd and 3rd year may be just due to insufficient data. There was no beneficial effect on the overall survival. However, to confirm the beneficial effect or lack of it, large, higher quality randomized controlled trials are still required.

Methods of disposal of used syringes by hepatitis B and C patients at an urban and rural setting.

OBJECTIVE: To evaluate the methods of disposal of used syringes employed by patients with hepatitis B and hepatitis C. METHODS: This cross sectional study was conducted at a tertiary care hospital of Karachi and a clinic at Khairpur, Sindh. Diagnosed cases of Hepatitis B and C currently receiving treatment in the form of Interferon alpha injection were included by convenient sampling. The study instrument was a well structured questionnaire meant to ascertain the disposal methods of used syringes once they had been employed for treatment purpose. Open-epi sample size calculator (Multi-purpose statistical software for calculation of the sample size) and SPSS 15.0 was used for data entry and analysis. RESULTS: A total of 203 patients were interviewed, 147 from Karachi and 56 from interior. The majority i.e. 164 were suffering from Hepatitis C, 27 from Hepatitis B and 2 were co-infected with Hepatitis B and D. The mean age of patients was 35.8 +/- 11.5 years. Regarding disposal of injections, the most frequent mode was disposal of used syringes in house trash i.e. 71 (37.4%), patients 46 (24.2%) responded that they utilized a needle cutter, 37 (19.5%) safety box (disposal method in tertiary hospitals where the needle is disposed off safely in a box), 12 (6.3%) disposed in sewage, 3 (1.6%) disposal in water, 3 (1.6%) buried the used syringes, while 2 (1.1%) reused the syringe and needle once they had been used for therapeutic purposes. CONCLUSIONS: The study suggests that the injection practices by the majority of patients suffering from viral hepatitis were unsafe. Majority of the patients were disposing the used syringes and needles in the house trash.

Digital Health Applications in Heart Failure: a Critical Appraisal of Literature.

PURPOSE OF THE REVIEW: Despite advancements in the diagnostic and therapeutic armamentarium, heart failure (HF) remains a major public health concern in the USA and worldwide. Digital health applications hold promise to bridge this gap and improve HF care. This review will provide the reader with a concise overview of the current digital health applications in HF, the main challenges to its use, and discuss the future of digital health for promoting care for HF patients. RECENT FINDINGS: Emerging evidence continues to support the potential role of digital health across the continuum of HF disease process including primary prevention, early detection, disease management, and reducing associated morbidity. There is also increasing emphasis on the need to pursue rigorous investigations to validate these promising claims, with some successful stories that have changed clinical practices. SUMMARY: Digital health technologies have emerged as potentially useful tools to complement HF care in both research and clinical realms. As digital technologies continue to play an increasing role in transforming healthcare delivery, creating the framework for its effective use would be necessary to ensure that digital health applications consistently improve outcomes and enhance care for HF patients.

Gastroesophageal reflux disease (GERD) in students of a government medical college at Karachi.

OBJECTIVE: To assess the frequency of symptoms suggestive of Gastroesophageal reflux disease (GERD) in students of a government medical college at Karachi. METHODS: This is a cross sectional study conducted at Dow Medical College (from September to December 2008) through a well structured questionnaire meant to assess the typical and atypical manifestations of GERD in terms of frequency, consultation with physician and life style changes adopted to reduce the severity of symptoms. RESULTS: Out of 595 students interviewed, 444 (74.6%) were female. Majority of them were aged between 17-25 years. Abdominal discomfort ever developed in 288/595 (48.4%) students out of which 132/595 (22.18%) students complained of heartburn. Weekly episodes of heartburn were present in 35/444 (7.88%) female students and 10/151 (6.62%) male students. Dysphagia was present in 88/595 (14.8%) students, 9/88 (10.22%) of which also suffered weekly from heart burn. Overall 109/595 (18.3%) students, comprising of 82/444 (18.5%) female and 27/151 (17.9%) male, exhibited breathing problems. Weekly presentation of heartburn was also prevalent in 13/109 (11.92%) students who suffered from breathing problems. CONCLUSION: The study concludes that the percentage of students having weekly episodes of heart burn is significantly higher than that in general Asian population. The atypical symptoms of GERD are also found to be more prevalent among medical students.

Residual inflammatory risk after contemporary lipid lowering therapy.

BACKGROUND: Recently, there has been an increasing interest in targeting inflammation to reduce major adverse cardiovascular events (MACE) in patients with cardiovascular risk. Statins, PCSK9 inhibitors, and ezetimibe have been shown to reduce MACE owing to reduction in low-density lipoproteins cholesterol (LDL-c). Herein, we investigate whether the intensity of these agents is associated with (i) discernible reduction in inflammation measured by the levels of high-sensitivity C-reactive protein (hsCRP); (ii) reduction in MACE; (iii) if there is an association between the baseline hsCRP and MACE. METHODS AND RESULTS: Electronic databases were searched for randomized controlled trials (RCTs) that compared statins, ezetimibe, PCSK9 inhibitors with placebos/active controls and reported MACEs and hsCRP (mg/L). Studies were stratified based on baseline hsCRP (<2, 2-3, >3) with subgroup analysis conducted across each stratum. Fourteen RCTs including 133 109 patients randomized into more intensive therapy (MIT) and less intensive therapy were selected. Meta-analysis did not demonstrate any significant differences between use of MIT and hsCRP levels (mean difference, -0.02; CI, -0.06, 0.02; P = 0.31). The MIT significantly reduced the risk of MACE (RR, 0.82; CI, 0.75, 0.91; P < 0.001). The relative risk and absolute risk remained consistent across the strata. However, there was a 0.5% statistically significant absolute risk reduction in all-cause mortality in patients with higher hsCRP (RD, -0.005; CI, -0.009, -0.001; P = 0.01). CONCLUSION: Overall, LDL-c lowering therapies reduce relative risk of MACEs particularly in patients with higher baseline hsCRP. However, there appears to be a residual inflammatory risk despite the use of contemporary lipid lowering agents.

Meta-analysis of the Relation of Body Mass Index to Cardiovascular Outcomes in Patients Receiving Intensive Low-Density Lipoprotein Cholesterol Lowering Therapy.

The impact of body mass index (BMI) on cardiovascular outcomes in patients receiving intensive low-density lipoprotein cholesterol (LDL-C) lowering therapy is uncertain. We performed meta-analysis of 29 randomized controlled trials using PubMed, Embase, and CENTRAL through April 2019. Therapies were grouped as more intensive LDL-C lowering therapy (statins, ezetimibe + statin or PCSK9 inhibitors) and less intensive LDL-C lowering therapy (less potent active control or placebo). Random effects meta-regressions and meta-analyses were performed to evaluate association of BMI with cardiovascular endpoints. In 265,766 patients, for every 1 kg/m2 increase in BMI, more intensive therapy compared with less intensive therapy was associated with hazard ratio (HR) of 1.07 for cardiovascular mortality (95% confidence interval 1.02 to 1.13); HR of 1.03 for all-cause mortality (0.99 to 1.06) HR of 1.06 for myocardial infarction (1.02 to 1.09), HR of 1.08 (1.03 to 1.12) for revascularization and HR of 1.04 for MACE (1.01 to 1.07). Meta-analysis showed that patients with BMI <25 kg/m2 had the highest risk reduction in mortality and cardiovascular outcomes compared with patients with BMI ≥30 kg/m2 (p-interaction ≤0.05). In conclusion, patients with normal BMI treated with intensive LDL-C lowering regimens may derive a larger clinical benefit compared with patients with larger BMI. The results could be due to the higher mortality rate of obese patients that may artificially lower the efficacy of therapy, or due to a true therapeutic limitation in these patients.

Participation of Women and Older Participants in Randomized Clinical Trials of Lipid-Lowering Therapies: A Systematic Review.

Importance: Randomized clinical trials (RCTs) of lipid-lowering therapies form the evidence base for national and international guidelines. However, concerns exist that women and older patients are underrepresented in RCTs. Objective: To determine the trends of representation of women and older patients (≥65 years) in RCTs of lipid-lowering therapies from 1990 to 2018. Data Sources: The electronic databases of MEDLINE and ClinicalTrials.gov were searched from January 1990 through December 2018. Study Selection: RCTs of lipid-lowering therapies with sample sizes of at least 1000 patients and follow-up periods of at least 1 year were included. Data Extraction and Synthesis: Two independent investigators abstracted the data on a standard data collection form. Main Outcomes and Measures: Patterns of representation of women and older adults were examined overall in lipid-lowering RCTs and according to RCT-level specific characteristics. The participation-to-prevalence ratio (PPR) metric was used to estimate the representation of women compared with their share of disease burden. Results: A total of 60 RCTs with 485 409 participants were included. The median (interquartile range) number of participants per trial was 5264 (1062-27 564). Overall, representation of women was 28.5% (95% CI, 24.4%-32.4%). There was an increase in the enrollment of women from the period 1990 to 1994 (19.5%; 95% CI, 18.4%-20.5%) to the period 2015 to 2018 (33.6%; 95% CI, 33.4%-33.8%) (P for trend = .01). Among common limiting factors were inclusion of only postmenopausal women or surgically sterile women (28.3%; 95% CI, 18.5%-40.7%) or exclusion of pregnant (23.3%; 95% CI, 14.4%-35.4%) and lactating (16.6%; 95% CI, 9.3%-28.1%) women. Women were underrepresented compared with their disease burden in lipid RCTs of diabetes (PPR, 0.74), heart failure (PPR, 0.27), stable coronary heart disease (PPR, 0.48), and acute coronary syndrome (PPR, 0.51). Only 23 RCTs with 263 628 participants reported the proportion of older participants. Overall representation of older participants was 46.7% (95% CI, 46.5%-46.9%), which numerically increased from 31.6% (95% CI, 30.8%-32.3%) in the period 1995 to 1998 to 46.2% (95% CI, 46.0%-46.5%) in the period 2015 to 2018 (P for trend = .43). A total of 53.0% (95% CI, 41.8%-65.3%) and 36.6% (95% CI, 25.6% to 49.3%) trials reported outcomes according to sex and older participants, respectively, which did not improve over time. Conclusions and Relevance: In this systematic review of RCTs of lipid-lowering therapies, the enrollment of women and older participants increased over time, but women and older participants remained consistently underrepresented. This limits the evidence base for efficacy and safety in these subgroups.

Systematic review and meta-analysis of current risk models in predicting short-term mortality after transcatheter aortic valve replacement.

AIMS: The aim of this study was to evaluate the performance of risk stratification models (RSMs) in predicting short-term mortality after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: MEDLINE and Scopus were queried to identify studies which validated RSMs designed to assess 30-day or in-hospital mortality after TAVR. Discrimination and calibration were assessed using C-statistics and observed/expected ratios (OERs), respectively. C-statistics were pooled using a random-effects inverse-variance method, while OERs were pooled using the Peto odds ratio. A good RSM is defined as one with a C-statistic >0.7 and an OER close to 1.0. Twenty-four studies (n=68,215 patients) testing 11 different RSMs were identified. Discrimination of all RSMs was poor (C-statistic <0.7); however, certain TAVR-specific RSMs such as the in-hospital STS/ACC TVT (C-statistic=0.65) and STT (C-statistic=0.66) predicted individual mortality more reliably than surgical models (C-statistic range=0.59-0.61). A good calibration was demonstrated by the in-hospital STS/ACC TVT (OER=0.99), 30-day STS/ACC TVT (OER=1.08) and STS (OER=1.01) models. Baseline dialysis (OER: 2.64 [1.88, 3.70]; p<0.001) was the strongest predictor of mortality. CONCLUSIONS: This study demonstrates that the STS/ACC TVT model (in-hospital and 30-day) and the STS model have accurate calibration, making them useful for comparison of centre-level risk-adjusted mortality. In contrast, the discriminative ability of currently available models is limited.