Waqas Qureshi

Public Availability of Published Research Data in High-Impact Journals

Background There is increasing interest to make primary data from published research publicly available. We aimed to assess the current status of making research data available in highly-cited journals across the scientific literature. Methods and Results We reviewed the first 10 original research papers of 2009 published in the 50 original research journals with the highest impact factor. For each journal we documented the policies related to public availability and sharing of data. Of the 50 journals, 44 (88%) had a statement in their instructions to authors related to public availability and sharing of data. However, there was wide variation in journal requirements, ranging from requiring the sharing of all primary data related to the research to just including a statement in the published manuscript that data can be available on request. Of the 500 assessed papers, 149 (30%) were not subject to any data availability policy. Of the remaining 351 papers that were covered by some data availability policy, 208 papers (59%) did not fully adhere to the data availability instructions of the journals they were published in, most commonly (73%) by not publicly depositing microarray data. The other 143 papers that adhered to the data availability instructions did so by publicly depositing only the specific data type as required, making a statement of willingness to share, or actually sharing all the primary data. Overall, only 47 papers (9%) deposited full primary raw data online. None of the 149 papers not subject to data availability policies made their full primary data publicly available. Conclusion A substantial proportion of original research papers published in high-impact journals are either not subject to any data availability policies, or do not adhere to the data availability instructions in their respective journals. This empiric evaluation highlights opportunities for improvement.

Does coronary CT angiography improve risk stratification over coronary calcium scoring in symptomatic patients with suspected coronary artery disease? Results from the prospective multicenter international CONFIRM registry

AIMS The prognostic value of coronary artery calcium (CAC) scoring is well established and has been suggested for use to exclude significant coronary artery disease (CAD) for symptomatic individuals with CAD. Contrast-enhanced coronary computed tomographic angiography (CCTA) is an alternative modality that enables direct visualization of coronary stenosis severity, extent, and distribution. Whether CCTA findings of CAD add an incremental prognostic value over CAC in symptomatic individuals has not been extensively studied. METHODS AND RESULTS We prospectively identified symptomatic patients with suspected but without known CAD who underwent both CAC and CCTA. Symptoms were defined by the presence of chest pain or dyspnoea, and pre-test likelihood of obstructive CAD was assessed by the method of Diamond and Forrester (D-F). CAC was measured by the method of Agatston. CCTAs were graded for obstructive CAD (>70% stenosis); and CAD plaque burden, distribution, and location. Plaque burden was determined by a segment stenosis score (SSS), which reflects the number of coronary segments with plaque, weighted for stenosis severity. Plaque distribution was established by a segment-involvement score (SIS), which reflects the number of segments with plaque irrespective of stenosis severity. Finally, a modified Duke prognostic index-accounting for stenosis severity, plaque distribution, and plaque location-was calculated. Nested Cox proportional hazard models for a composite endpoint of all-cause mortality and non-fatal myocardial infarction (D/MI) were employed to assess the incremental prognostic value of CCTA over CAC. A total of 8627 symptomatic patients (50% men, age 56 ± 12 years) followed for 25 months (interquartile range 17-40 months) comprised the study cohort. By CAC, 4860 (56%) and 713 (8.3%) patients had no evident calcium or a score of >400, respectively. By CCTA, 4294 (49.8%) and 749 (8.7%) had normal coronary arteries or obstructive CAD, respectively. At follow-up, 150 patients experienced D/MI. CAC improved discrimination beyond D-F and clinical variables (area under the receiver-operator characteristic curve 0.781 vs. 0.788, P = 0.004). When added sequentially to D-F, clinical variables, and CAC, all CCTA measures of CAD improved discrimination of patients at risk for D/MI: obstructive CAD (0.82, P < 0.001), SSS (0.81, P < 0.001), SIS (0.81, P = 0.003), and Duke CAD prognostic index (0.82, P < 0.0001). CONCLUSION In symptomatic patients with suspected CAD, CCTA adds incremental discriminatory power over CAC for discrimination of individuals at risk of death or MI.

Thermoablative Treatments for Malignant Liver Lesions: 10-Year Experience of MRI Appearances of Treatment Response

OBJECTIVE The objective of our study was to describe our 10-year experience using MRI to evaluate response to local thermoablative interventions in the treatment of malignant liver lesions. MATERIALS AND METHODS This retrospective study was conducted from 1998 to 2008. MRI studies were performed at 1.5 and 3 T and were acquired < 4, 4-9, and > 9 months after radiofrequency ablation (RFA), cryoablation, and microwave ablation. MR features were evaluated on the basis of signal intensity on unenhanced T1-weighted images and the presence of ill-defined perilesional enhancement, well-defined lesional enhancement, or washout on contrast-enhanced images. Imaging features were evaluated with all interventional modalities together and separately. RESULTS The study population was composed of 135 men and 36 women (203 ablated lesions) with a mean age of 65 years (range, 39-78 years). When the data for all treatment methods were combined, well-defined lesional enhancement and washout were significant findings among the resolved and unresolved outcome groups regardless of follow-up time category. After RFA, ablated areas had a tendency to show high signal intensity on T1 images, whereas low signal was seen after cryoablation and a hyperintense rim was seen after microwave ablation. Washout was only depicted 9 months after cryoablation but was seen in 12% of lesions < 4 months after RFA. No difference was appreciated on ill-defined perilesional enhancement with all methods combined or separately. CONCLUSION MRI findings after ablation are dependent on the treatment modality and the length of time between the procedure and follow-up examination.

A critical review of the use of carvedilol in ischemic heart disease.

β-Adrenergic receptor antagonists (β-blockers) have been recognized for their cardioprotective properties, prompting use of these pharmacologic agents to become more mainstream in acute myocardial infarction (AMI) and congestive heart failure (CHF). Despite their popularity as a class, the ability to protect the myocardium varies significantly between different agents. Carvedilol is a non-selective β-blocker with α₁-adrenergic receptor antagonism properties. It is unique among β-blockers because in addition to improving exercise tolerance and its anti-ischemic properties secondary to a reduction in heart rate and myocardial contractility, carvedilol exerts other beneficial effects including: antioxidant effects; reduction in neutrophil infiltration; apoptosis inhibition; reduction of vascular smooth muscle migration; and improvement of myocardial remodeling post-AMI. These properties, documented in animal models and subsequent clinical trials, are consistent with established evidence demonstrating decreased morbidity and mortality in patients with CHF and post-AMI. This article reviews the role of carvedilol compared with other β-blockers in the treatment of CHF and post-AMI management.

Impact of restarting warfarin therapy in renal disease anticoagulated patients with gastrointestinal hemorrhage

Abstract Background: Atrial fibrillation (AF) is emerging as a major health problem. The prevalence is as high as 32% in patients with renal disease. Gastrointestinal bleeding (GIB) is a frequent complication. Objective: To investigate the hazards of resumption or discontinuation of anticoagulation in renal disease patients after an episode of GIB. Design, settings, participants and measurements: This is a multicenter retrospective cohort of patients with AF on warfarin that developed an episode of GIB. Chronic kidney disease (CKD) was defined by eGFR ≤60 mL/min and end stage renal disease (ESRD) was defined by being on hemodialysis for >3 months. Outcomes were 90-day recurrent gastrointestinal bleeding (GIB), mortality, and stroke/transient ischemic attack (TIA). Results: Out of 11,513 AF patients, index GIB occurred in 96 ESRD and 159 CKD patients. Outcomes of CKD patients did not differ when compared with patients with normal kidney function. CKD patients who resumed warfarin had decreased stroke/TIA rates (p < 0.0001). There were no significant differences between CKD patients who resumed warfarin versus that did not resume warfarin (p > 0.05). ESRD patients also did not have significant differences in outcomes when compared to patients with normal kidney function restarted on warfarin. However, there was an increase in recurrent GIB and decrease in mortality as well as stroke/TIA when patients with ESRD that restarted warfarin were compared with ESRD patients who did not restart warfarin. Conclusion: Study suggests resuming warfarin after an episode of GIB in CKD patients but recommends considering the increased risk of recurrent GIB in ESRD patients.

Clinical predictors of post-liver transplant new-onset heart failure.

Objectives of this study were (1) to evaluate preoperative predictors of systolic and diastolic heart failure in patients undergoing liver transplantation (LT) and (2) to describe the prognostic implications of systolic and diastolic heart failure in these patients. The onset of heart failure after orthotopic LT remains poorly understood. Data were obtained for all LT recipients between January 2000 and December 2010. The primary outcome was post‐LT heart failure: systolic (ejection fraction ≤ 50%), diastolic, or mixed heart failure. Patients underwent echocardiographic evaluation before and after LT. Pretransplant variables were evaluated as predictors of heart failure with Cox proportional hazards model. 970 LT recipients were followed for 5.3 ± 3.4 years. Ninety‐eight patients (10.1%) developed heart failure in the posttransplant period. There were 67 systolic (6.9%), 24 diastolic (2.5%), and 7 mixed systolic/diastolic (0.7%) heart failures. Etiology was ischemic in 18 (18.4%), tachycardia‐induced in 8 (8.2%), valvular in 7 (7.1%), alcohol‐related in 4 (4.1%), hypertensive heart disease in 3 (3.1%), and nonischemic in majority of patients (59.2%). Pretransplant grade 3 diastolic dysfunction, diabetes, hypertension, mean arterial pressure ≤ 65 mm Hg, mean pulmonary artery pressure ≥ 30 mm Hg, mean pulmonary capillary wedge pressure ≥ 15 mm Hg, hemodialysis, brain natriuretic peptide level and QT interval > 450 ms were found to be predictive for the development of new‐onset systolic heart failure. However beta‐blocker use before LT and tacrolimus after LT were associated with reduced development of new‐onset systolic heart failure. In conclusion, pretransplant risk factors, hemodynamic variables, and echocardiographic variables are important predictors of post‐LT heart failure. In patients undergoing LT, postoperative onset of systolic or diastolic heart failure was found to be an independent predictor of mortality. Liver Transpl 19:701–710, 2013.

The role of minocycline in ischemia-reperfusion injury: a comprehensive review of an old drug with new implications.

Minocycline is a semi-synthetic tetracycline that inhibits bacterial protein synthesis and hence is used for the treatment of many infectious diseases. Over the years, many other interesting properties of minocycline have been identified and been used to make patents which include anti-inflammatory, anti-apoptotic, matrix metalloproteinase inhibitor and free oxygen radical scavenger activity. Ischemia-reperfusion injury is a concern for almost every clinical specialty and minocycline seems to be an attractive cytoprotective agent that can ameliorate the damage due to these properties. Ischemia-reperfusion injury is a complex process and involves various pathways that lead to cell death. This review focuses on the body of evidence describing various proposed mechanisms of action of minocycline and its current experimental use in various animal models of ischemia-reperfusion injury.

Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation.

BACKGROUND There is growing controversy regarding the association between digoxin and mortality in atrial fibrillation (AF). The aim of this analysis was to systematically review digoxin use and risk of mortality in patients with AF. METHODS MEDLINE, EMBASE, GoogleScholar, CINAHL, meeting abstracts, presentations, and Cochrane central databases were searched from inception through December 2014, without language restrictions. For a study to be selected, it had to report the risk of mortality associated with digoxin use in AF patients as an outcome measure. Data were extracted by 2 independent authors. Evidence tables were created. RESULTS A total of 16 studies (6 post hoc analyses of randomized controlled trials) with 111,978 digoxin users and 389,643 non-digoxin users were included. In a random effects model, patients treated with digoxin had a 27% increased risk of all-cause mortality (pooled HR 1.27; 95% CI 1.19-1.36) and 21% increased risk of cardiovascular mortality (pooled HR 1.21; 95% CI 1.12-1.30) compared with those who did not use digoxin. In a random effects model, the association of digoxin with all-cause mortality was stronger for AF patients without heart failure (pooled HR 1.47; 95% CI 1.25-1.73) than AF patients with heart failure (pooled HR 1.21; 95% CI 1.07-1.36, interaction p = 0.06). CONCLUSIONS Digoxin use in AF is associated with increased risk of all-cause and cardiovascular mortalities. The effect size was larger for AF patients without heart failure than AF patients with heart failure. The study suggests further directed analyses to study the effect that is suggested by this meta-analysis, especially in AF without heart failure.

Thrombosis in VonWillebrand disease.

OBJECTIVE To date, only a few case studies have reported occurrence of thrombosis in patients with VonWillebrand disease (VWD). No studies have looked at its incidence in this patient population. The aim of this study was to test our hypothesis that decreased VonWillebrand factor (VWF) levels confer a protective effect on arterial and venous thrombosis. METHODS This is a retrospective cohort study including patients (n=350) with the ICD-9 code of VWD who were identified from our hospital database over a period of 25 years, out of which 198 patients were included in the final sample. A parallel control sample without VWD matched for age, sex, hypertension, hyperlipidemia, atrial fibrillation and diabetes mellitus was also obtained from the hospital database. The primary outcomes were incidence of diagnosis of symptomatic arterial and venous thrombosis. The results were computed using multivariate conditional logistic regression analysis and proportions were compared using McNemers Chi - square test. RESULTS Out of 198 patients (mean age 44.2 ± 17.5, women 72%) with VWD, 170 (86%) were VWD type 1, 21 (10%) were type 2 and 7 (3%) were type 3. VWD was found to be an independent protective predictor from arterial thrombosis (OR 0.28, 95% CI 0.14-0.54, p<0.0001), more so in CAD (OR 0.28, 95% CI 0.12-0.64, p=0.002) than in CVD (OR 0.28, 95% CI 0.10-0.77, p=0.01). However this was not the case in venous thrombosis (p=0.42). CONCLUSION In a population of relatively younger individuals with VWD, our study suggests a reduced incidence of arterial thrombosis but not of venous thrombosis. This brings up the possibility that there could be other pathways or factors involved in arterial and venous thrombosis. To our knowledge, this is the first large observational study that has provided insight into the thrombotic disease in this group of patients.

Bidirectional association between atrial fibrillation and congestive heart failure in the elderly.

Aims The aim of this study was to examine the bidirectional association between atrial fibrillation and congestive heart failure (CHF) in older adults. Methods We studied the association of atrial fibrillation at entry with incident CHF (N = 5281; 85% white, 42% male) and the association of CHF at entry with incident atrial fibrillation (N = 5233; 85% white, 42% male) in the Cardiovascular Health Study (CHS). Baseline atrial fibrillation was identified during the study electrocardiogram and by self-reported history, and incident cases were identified during subsequent study electrocardiograms and hospitalization data. Baseline CHF was identified by self-reported history and adjudication of medical records, and incident cases were identified using hospitalization data. Cox regression was used to compute hazard ratios and 95% confidence intervals (CIs) for the association between atrial fibrillation and incident CHF, and CHF and incident atrial fibrillation, separately. Results Over a median follow-up of 12.6 years, 534 (10%) participants developed atrial fibrillation. CHF was associated with an increased risk of atrial fibrillation (hazard ratio 2.0, 95% CI 1.4, 3.0). A total of 1692 (32%) participants developed CHF over a median follow-up of 11.7 years and atrial fibrillation was associated with an increased risk of CHF (hazard ratio 1.9, 95% CI 1.5, 2.2). Conclusion Our results suggest that a bidirectional relationship exists between atrial fibrillation and CHF, with each condition influencing the development of the other.