Conrad Kabali

Urinary Sodium and Potassium Excretion, Mortality, and Cardiovascular Events

BACKGROUND The optimal range of sodium intake for cardiovascular health is controversial. METHODS We obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events. RESULTS The mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥ 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high estimated sodium excretion and the composite outcome was strongest among participants with hypertension (P=0.02 for interaction), with an increased risk at an estimated sodium excretion of 6.00 g or more per day. As compared with the reference range, an estimated sodium excretion that was below 3.00 g per day was also associated with an increased risk of the composite outcome (odds ratio, 1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a reduced risk of the composite outcome. CONCLUSIONS In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. (Funded by the Population Health Research Institute and others.).

Variation in Warfarin Dose Adjustment Practice Is Responsible for Differences in the Quality of Anticoagulation Control Between Centers and Countries An Analysis of Patients Receiving Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Trial

Background— The outcome of atrial fibrillation patients on warfarin partially depends on maintaining adequate time in therapeutic International Normalized Ratio range (TTR). Large differences in TTR have been reported between centers and countries. The association between warfarin dosing practice, TTR, and clinical outcomes was evaluated in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial patients receiving warfarin. Methods and Results— RE-LY provided an algorithm for warfarin dosing, recommending no change for in-range, and 10% to 15% weekly dose changes for out-of-range International Normalized Ratio values. We determined whether dose adjustments were consistent with algorithm recommendations but could not verify whether providers used the algorithm. Using multilevel regression models to adjust for patient, center, and country characteristics, we assessed whether algorithm-consistent warfarin dosing could predict patient TTR and the composite outcome of stroke, systemic embolism, or major hemorrhage. We included 6022 nonvalvular atrial fibrillation patients from 912 centers in 44 countries. We found a strong association between the proportion of algorithm-consistent warfarin doses and mean country TTR ( R 2=0.65). The degree of algorithm-consistency accounted for 87% of the between-center and 55% of the between-country TTR variation. Each 10% increase in center algorithm-consistent dosing independently predicted a 6.12% increase in TTR (95% confidence interval, 5.65–6.59) and an 8% decrease in rate of the composite clinical outcome (hazard ratio, 0.92; 95% confidence interval, 0.85–1.00). Conclusions— Adherence, intentional or not, to a simple warfarin dosing algorithm predicts improved TTR and accounts for considerable TTR variation between centers and countries. Systems facilitating algorithm-based warfarin dosing could optimize anticoagulation quality and improve clinical outcomes in atrial fibrillation on a global scale. Clinical Trial Registration— URL: . Unique identifier: [NCT00262600][1]. # Clinical Perspective {#article-title-22} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00262600&atom=%2Fcirculationaha%2F126%2F19%2F2309.atomBackground— The outcome of atrial fibrillation patients on warfarin partially depends on maintaining adequate time in therapeutic International Normalized Ratio range (TTR). Large differences in TTR have been reported between centers and countries. The association between warfarin dosing practice, TTR, and clinical outcomes was evaluated in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial patients receiving warfarin. Methods and Results— RE-LY provided an algorithm for warfarin dosing, recommending no change for in-range, and 10% to 15% weekly dose changes for out-of-range International Normalized Ratio values. We determined whether dose adjustments were consistent with algorithm recommendations but could not verify whether providers used the algorithm. Using multilevel regression models to adjust for patient, center, and country characteristics, we assessed whether algorithm-consistent warfarin dosing could predict patient TTR and the composite outcome of stroke, systemic embolism, or major hemorrhage. We included 6022 nonvalvular atrial fibrillation patients from 912 centers in 44 countries. We found a strong association between the proportion of algorithm-consistent warfarin doses and mean country TTR (R2=0.65). The degree of algorithm-consistency accounted for 87% of the between-center and 55% of the between-country TTR variation. Each 10% increase in center algorithm-consistent dosing independently predicted a 6.12% increase in TTR (95% confidence interval, 5.65–6.59) and an 8% decrease in rate of the composite clinical outcome (hazard ratio, 0.92; 95% confidence interval, 0.85–1.00). Conclusions— Adherence, intentional or not, to a simple warfarin dosing algorithm predicts improved TTR and accounts for considerable TTR variation between centers and countries. Systems facilitating algorithm-based warfarin dosing could optimize anticoagulation quality and improve clinical outcomes in atrial fibrillation on a global scale. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Comparative effectiveness of transitional care services in patients discharged from the hospital with heart failure: a systematic review and network meta‐analysis

To compare the effectiveness of transitional care services in decreasing all‐cause death and all‐cause readmissions following hospitalization for heart failure (HF).

Efficacy of Hospital at Home in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Background Heart failure (HF) is the commonest cause of hospitalization in older adults. Compared to routine hospitalization (RH), hospital at home (HaH)—substitutive hospital-level care in the patient’s home—improves outcomes and reduces costs in patients with general medical conditions. The efficacy of HaH in HF is unknown. Methods and Results We searched MEDLINE, Embase, CINAHL, and CENTRAL, for publications from January 1990 to October 2014. We included prospective studies comparing substitutive models of hospitalization to RH in HF. At least 2 reviewers independently selected studies, abstracted data, and assessed quality. We meta-analyzed results from 3 RCTs (n = 203) and narratively synthesized results from 3 observational studies (n = 329). Study quality was modest. In RCTs, HaH increased time to first readmission (mean difference (MD) 14.13 days [95% CI 10.36 to 17.91]), and improved health-related quality of life (HrQOL) at both, 6 months (standardized MD (SMD) -0.31 [-0.45 to -0.18]) and 12 months (SMD -0.17 [-0.31 to -0.02]). In RCTs, HaH demonstrated a trend to decreased readmissions (risk ratio (RR) 0.68 [0.42 to 1.09]), and had no effect on all-cause mortality (RR 0.94 [0.67 to 1.32]). HaH decreased costs of index hospitalization in all RCTs. HaH reduced readmissions and emergency department visits per patient in all 3 observational studies. Conclusions In the context of a limited number of modest-quality studies, HaH appears to increase time to readmission, reduce index costs, and improve HrQOL among patients requiring hospital-level care for HF. Larger RCTs are necessary to assess the effect of HaH on readmissions, mortality, and long-term costs.

Micro-economic impact of congenital heart surgery: results of a prospective study from a limited-resource setting.

Introduction The microeconomic impact of surgery for congenital heart disease is unexplored, particularly in resource limited environments. We sought to understand the direct and indirect costs related to congenital heart surgery and its impact on Indian households from a family perspective. Methods Baseline and first follow-up data of 644 consecutive children admitted for surgery for congenital heart disease (March 2013 – July 2014) in a tertiary referral hospital in Central Kerala, South India was collected prospectivelyfrom parents through questionnaires using a semi-structured interview schedule. Results The median age was 8.2 months (IQR: 3.0– 36.0 months). Most families belonged to upper middle (43.0%) and lower middle (35.7%) socioeconomic class. Only 3.9% of families had some form of health insurance. The median expense for the admission and surgery was INR 201898 (IQR: 163287–266139) [I

The value of electrocardiography in prognosticating clinical deterioration and mortality in acute pulmonary embolism: A systematic review and meta‐analysis

11989 (IQR: 9696–15804)], which was 0.93 (IQR: 0.52–1.49) times the annual family income of affected patients. Median loss of man-days was 35 (IQR: 24–50) and job-days was 15 (IQR: 11–24). Surgical risk category and hospital stay duration significantly predicted higher costs. One in two families reported overwhelming to high financial stress during admission period for surgery. Approximately half of the families borrowed money during the follow up period after surgery. Conclusion Surgery for congenital heart disease results in significant financial burden for majority of families studied. Efforts should be directed at further reductions in treatment costs without compromising the quality of care together with generating financial support for affected families.

Variation in Warfarin Dose Adjustment Practice Is Responsible for Differences in the Quality of Anticoagulation Control Between Centers and Countries

The role of electrocardiography (ECG) in prognosticating pulmonary embolism (PE) is increasingly recognized. ECG is quickly interpretable, noninvasive, inexpensive, and available in remote areas. We hypothesized that ECG can provide useful information about PE prognostication. We searched MEDLINE, EMBASE, Google Scholar, Web of Science, abstracts, conference proceedings, and reference lists through February 2017. Eligible studies used ECG to prognosticate for the main outcomes of death and clinical deterioration or escalation of therapy. Two authors independently selected studies; disagreement was resolved by consensus. Ad hoc piloted forms were used to extract data and assess risk of bias. We used a random‐effects model to pool relevant data in meta‐analysis with odds ratios (ORs) and 95% confidence intervals (CIs); all other data were synthesized qualitatively. Statistical heterogeneity was assessed using the I 2 value. We included 39 studies (9198 patients) in the systematic review. There was agreement in study selection (κ: 0.91, 95% CI: 0.86‐0.96). Most studies were retrospective; some did not appropriately control for confounders. ECG signs that were good predictors of a negative outcome included S1Q3T3 (OR: 3.38, 95% CI: 2.46‐4.66, P < 0.001), complete right bundle branch block (OR: 3.90, 95% CI: 2.46‐6.20, P < 0.001), T‐wave inversion (OR: 1.62, 95% CI: 1.19‐2.21, P = 0.002), right axis deviation (OR: 3.24, 95% CI: 1.86‐5.64, P < 0.001), and atrial fibrillation (OR: 1.96, 95% CI: 1.45‐2.67, P < 0.001) for in‐hospital mortality. Several ischemic patterns also were significantly predictive. Our conclusion is that ECG is potentially valuable in prognostication of acute PE.

Antithrombotic therapy in patients receiving saphenous vein coronary artery bypass grafts: a protocol for a systematic review and network meta-analysis

Background— The outcome of atrial fibrillation patients on warfarin partially depends on maintaining adequate time in therapeutic International Normalized Ratio range (TTR). Large differences in TTR have been reported between centers and countries. The association between warfarin dosing practice, TTR, and clinical outcomes was evaluated in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial patients receiving warfarin. Methods and Results— RE-LY provided an algorithm for warfarin dosing, recommending no change for in-range, and 10% to 15% weekly dose changes for out-of-range International Normalized Ratio values. We determined whether dose adjustments were consistent with algorithm recommendations but could not verify whether providers used the algorithm. Using multilevel regression models to adjust for patient, center, and country characteristics, we assessed whether algorithm-consistent warfarin dosing could predict patient TTR and the composite outcome of stroke, systemic embolism, or major hemorrhage. We included 6022 nonvalvular atrial fibrillation patients from 912 centers in 44 countries. We found a strong association between the proportion of algorithm-consistent warfarin doses and mean country TTR ( R 2=0.65). The degree of algorithm-consistency accounted for 87% of the between-center and 55% of the between-country TTR variation. Each 10% increase in center algorithm-consistent dosing independently predicted a 6.12% increase in TTR (95% confidence interval, 5.65–6.59) and an 8% decrease in rate of the composite clinical outcome (hazard ratio, 0.92; 95% confidence interval, 0.85–1.00). Conclusions— Adherence, intentional or not, to a simple warfarin dosing algorithm predicts improved TTR and accounts for considerable TTR variation between centers and countries. Systems facilitating algorithm-based warfarin dosing could optimize anticoagulation quality and improve clinical outcomes in atrial fibrillation on a global scale. Clinical Trial Registration— URL: . Unique identifier: [NCT00262600][1]. # Clinical Perspective {#article-title-22} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00262600&atom=%2Fcirculationaha%2F126%2F19%2F2309.atomBackground— The outcome of atrial fibrillation patients on warfarin partially depends on maintaining adequate time in therapeutic International Normalized Ratio range (TTR). Large differences in TTR have been reported between centers and countries. The association between warfarin dosing practice, TTR, and clinical outcomes was evaluated in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial patients receiving warfarin. Methods and Results— RE-LY provided an algorithm for warfarin dosing, recommending no change for in-range, and 10% to 15% weekly dose changes for out-of-range International Normalized Ratio values. We determined whether dose adjustments were consistent with algorithm recommendations but could not verify whether providers used the algorithm. Using multilevel regression models to adjust for patient, center, and country characteristics, we assessed whether algorithm-consistent warfarin dosing could predict patient TTR and the composite outcome of stroke, systemic embolism, or major hemorrhage. We included 6022 nonvalvular atrial fibrillation patients from 912 centers in 44 countries. We found a strong association between the proportion of algorithm-consistent warfarin doses and mean country TTR (R2=0.65). The degree of algorithm-consistency accounted for 87% of the between-center and 55% of the between-country TTR variation. Each 10% increase in center algorithm-consistent dosing independently predicted a 6.12% increase in TTR (95% confidence interval, 5.65–6.59) and an 8% decrease in rate of the composite clinical outcome (hazard ratio, 0.92; 95% confidence interval, 0.85–1.00). Conclusions— Adherence, intentional or not, to a simple warfarin dosing algorithm predicts improved TTR and accounts for considerable TTR variation between centers and countries. Systems facilitating algorithm-based warfarin dosing could optimize anticoagulation quality and improve clinical outcomes in atrial fibrillation on a global scale. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Use of fragmented QRS in prognosticating clinical deterioration and mortality in pulmonary embolism: A meta-analysis

Introduction The current evidence for the prevention of saphenous vein graft failure (SVGF) after coronary artery bypass graft (CABG) surgery consists of direct head-to-head comparison of treatments (including placebo) in randomised-controlled trials (RCTs) and observational studies. However, summarising the evidence using traditional pairwise meta-analyses does not allow the inclusion of data from treatments that have not been compared head to head. Exclusion of such comparisons could impact the precision of pooled estimates in a meta-analysis. Hence, to address the challenge of whether aspirin alone or in addition to another antithrombotic agent is a more effective regimen to improve SVG patency, a network meta-analysis (NMA) is necessary. The objectives of this study are to synthesise the available evidence on antithrombotic agents (or their combination) and estimate the treatment effects among direct and indirect treatment comparisons on SVGF and major adverse cardiovascular events, and to generate a treatment ranking according to their efficacy and safety outcomes. Methods We will perform a systematic review of RCTs evaluating antithrombotic agents in patients undergoing CABG. A comprehensive English literature search will be conducted using electronic databases and grey literature resources to identify published and unpublished articles. Two individuals will independently and in duplicate screen potential studies, assess the eligibility of potential studies and extract data. Risk of bias and quality of evidence will also be evaluated independently and in duplicate. We will investigate the data to ensure its suitability for NMA, including adequacy of the outcome data and transitivity of treatment effects. We plan to estimate the pooled direct, indirect and the mixed effects for all antithrombotic agents using a NMA. Ethics and dissemination Due to the nature of the study, there are no ethical concerns nor informed consent required. We anticipate that this NMA will be the first to simultaneously assess the relative effects of multiple antithrombotic agents in patients undergoing CABG. The results of this NMA will inform clinicians, patients and guideline developers the best available evidence on comparative effects benefits of antithrombotic agents after CABG while considering the side effect profile to support future clinical decision-making. We will disseminate the results of our systematic review and NMA through a peer-reviewed journal. PROSPERO registration number CRD42017065678.

Variation in Warfarin Dose Adjustment Practice Is Responsible for Differences in the Quality of Anticoagulation Control Between Centers and CountriesClinical Perspective

Fragmented QRS (fQRS) on electrocardiography is potentially valuable in prognosticating acute pulmonary embolism (PE). ECG is one of the first tests performed in the emergency department, quickly interpretable, noninvasive, inexpensive, and available in remote areas. We aimed to review fQRSs role in PE prognostication.