Vitamin D plus calcium supplementation among postmenopausal women : effect on risk of heart failure in the Women\u27s Health Initiative.

This study evaluates the impact of vitamin D plus calcium supplementation as a primary intervention for heart failure (HF) prevention and examines whether preexisting conditions that are precursors of HF modify this relationship in a large cohort of postmenopausal women. Analysis included 35,113 postmenopausal women (17,595 intervention, 17,518 control) aged 50 to 81 years enrolled in the randomized trial of vitamin D plus calcium (CaD) in the Women’s Health Initiative (WHI) study. The women in this analysis cohort were free of HF at the time of randomization and during the first year of the trial. The intervention consisted of 1,000 mg/day of calcium and 400 IU/day of vitamin D3. Incident HF cases over an average follow-up period of 7.13 (standard deviation, 1.33) years were identified from hospital discharge records and adjudicated by a physician committee. An intention-to-treat (ITT) approach was used to estimate hazard ratios (HR) and 95% confidence (CI) intervals from multivariable Cox Proportional Hazards regression models. A formal test of interaction between the intervention and a composite of risk factors that predispose towards the development of HF (hypertension, cardiovascular diseases, coronary heart diseases/events, and diabetes) and define ‘Stage A’ HF was performed. CaD was associated with a non-significant 7% reduced risk of heart failure (HR = 0.92; 95% CI, 0.79 –1.06) in a multivariable model in the overall study cohort. However, CaD was associated with a clinically and statistically significantly lower risk (35%) of HF (HR = 0.65; 95% CI, 0.46 – 0.92; P = 0.01) among participants who were free of Stage A HF but neither a clinically nor a statistically significant effect among those with Stage A HF (HR = 1.02; 95% CI, 0.85 – 1.21; P = 0.87). Moreover, these effect estimates were not modified by baseline total (diet and supplements) vitamin D and calcium intake and persisted in a per-protocol and other sensitivity analyses. These findings suggest that a low cost daily supplementation with vitamin D plus calcium may be an effective primary prevention strategy in postmenopausal without major cardiovascular precursors of HF but of little value in those with these risk factors

Random control selection for conducting high-throughput adverse drug events screening using large-scale longitudinal health data

Case-control design based high-throughput pharmacoinformatics study using large-scale longitudinal health data is able to detect new adverse drug event (ADEs) signals. Existing control selection approaches for case-control design included the dynamic/super control selection approach. The dynamic/super control selection approach requires all individuals to be evaluated at all ADE case index dates, as the individuals' eligibilities as control depend on ADE/enrollment history. Thus, using large-scale longitudinal health data, the dynamic/super control selection approach requires extraordinarily high computational time. We proposed a random control selection approach in which ADE case index dates were matched by randomly generated control index dates. The random control selection approach does not depend on ADE/enrollment history. It is able to significantly reduce computational time to prepare case-control data sets, as it requires all individuals to be evaluated only once. We compared the performance metrics of all control selection approaches using two large-scale longitudinal health data and a drug-ADE gold standard including 399 drug-ADE pairs. The F-scores for the random control selection approach were between 0.586 and 0.600 compared to between 0.545 and 0.562 for dynamic/super control selection approaches. The random control selection approach was ~ 1000 times faster than dynamic/super control selection approach on preparing case-control data sets. With large-scale longitudinal health data, a case-control design-based pharmacoinformatics study using random control selection is able to generate comparable ADE signals than the existing control selection approaches. The random control selection approach also significantly reduces computational time to prepare the case-control data sets

Association Between Patient-Clinician Relationships and Adherence to Antihypertensive Medications Among Black Adults: An Observational Study Design

Background We assessed the associations between patient‐clinician relationships (communication and involvement in shared decision‐making [SDM]) and adherence to antihypertensive medications. Methods and Results The 2010 to 2017 Medical Expenditure Panel Survey (MEPS) data were analyzed. A retrospective cohort study design was used to create a cohort of prevalent and new users of antihypertensive medications. We defined constructs of patient‐clinician communication and involvement in SDM from patient responses to the standard questionnaires about satisfaction and access to care during the first year of surveys. Verified self‐reported medication refill information collected during the second year of surveys was used to calculate medication refill adherence; adherence was defined as medication refill adherence ≥80%. Survey‐weighted multivariable‐adjusted logistic regression models were used to measure the odds ratio (OR) and 95% CI for the association between both patient‐clinician constructs and adherence. Our analysis involved 2571 Black adult patients with hypertension (mean age of 58 years; SD, 14 years) who were either persistent (n=1788) or new users (n=783) of antihypertensive medications. Forty‐five percent (n=1145) and 43% (n=1016) of the sample reported having high levels of communication and involvement in SDM, respectively. High, versus low, patient‐clinician communication (OR, 1.38; 95% CI, 1.14–1.67) and involvement in SDM (OR, 1.32; 95% CI, 1.08–1.61) were both associated with adherence to antihypertensives after adjusting for multiple covariates. These associations persisted among a subgroup of new users of antihypertensive medications. Conclusions Patient‐clinician communication and involvement in SDM are important predictors of optimal adherence to antihypertensive medication and should be targeted for improving adherence among Black adults with hypertension

The Concurrent Initiation of Medications Is Associated with Discontinuation of Buprenorphine Treatment for Opioid Use Disorder

Introduction Retention in buprenorphine treatment for opioid use disorder (OUD) yields better opioid abstinence and reduces all-cause mortality for patients with OUD. Despite significant efforts have been made to expand the availability and use of buprenorphine in the United States, its retention rates remain on a low level. The current study examines discontinuation of buprenorphine with respect to concurrent initiation of other medications using real-world evidence. Methods Case-crossover study was conducted to examine discontinuation of buprenorphine using a large-scale longitudinal health dataset including 148,306 commercially-insured individuals initiated on medications for opioid use disorder (MOUD). Odds ratios and Bonferroni adjusted p-values were calculated for medications and therapeutic classes of medications. Results Clonidine was associated with increased discontinuation risk of buprenorphine both using the buprenorphine dataset alone (OR = 1.583 and adjusted p-value = 1.22 × 10−6) and using naltrexone as a comparison drug (OR = 2.706 and adjusted p-value = 4.11 × 10−5). Opioid medications (oxycodone, morphine and fentanyl) and methocarbamol were associated with increased discontinuation risk of buprenorphine using the buprenorphine dataset alone (adjusted p-value < 0.05), but not significant using naltrexone as a comparison drug. 6 drug therapeutic classes were associated with increased discontinuation risk of buprenorphine both using the buprenorphine dataset alone and using naltrexone as a comparison drug (adjusted p-value < 0.05). Conclusion Concurrent initiation of medications is associated with increased discontinuation risk of buprenorphine. Opioid medications are prescribed among patients on MOUD and associated with increased discontinuation risk of buprenorphine. Analgesics is associated with increased discontinuation risk of buprenorphine for patients without previous exposure of pain medications

Preoperative Aspirin Use and Its Effect on Adverse Events in Patients Undergoing Cardiac Operations

BackgroundPreoperative aspirin use within 5 days of cardiac operations is controversial. Aspirin could reduce cardiovascular complications and yet might increase risk of bleeding. Recent reports showed conflicting results, and whether aspirin has variable effects for different cardiac surgical procedures is unclear.MethodsA single-center retrospective cohort analysis was performed. After propensity score matching (PSM) for identified confounders, the relationship between preoperative aspirin use and 30-day all-cause mortality, postoperative renal failure, major adverse cardiocerebral events (MACE), blood transfusion, reoperation for bleeding, and postoperative infection were estimated with separate logistic regression models.ResultsPreoperative aspirin therapy was associated with a 49% (p = 0.04) increased risk of reoperation for bleeding among 868 matched pairs of patients undergoing valve operations. Among 725 matched patients undergoing coronary artery bypass grafting (CABG), preoperative aspirin therapy was not associated with a statistically significant higher risk of reoperation for bleeding. However, preoperative aspirin use, compared with nonuse, was not associated with risks of MACE, 30-day mortality, postoperative renal failure, blood transfusion, or postoperative infection in the entire cohort, in patients undergoing valve operations only, and in patients undergoing CABG only after PSM.ConclusionsPreoperative aspirin use in all patients undergoing cardiac operations was not associated with risks of major cardiac, cerebral, or renal complications and infections and death; however, the risk of reoperation for bleeding was elevated among preoperative aspirin users compared with nonusers in a subpopulation of patients undergoing valve operations only

Challenges and issues in drug utilization research identified from the Latin American and African regions

Background: Despite advancements in drug utilization research (DUR), these have not been universal. Some regions such as the Latin America (LatAm) and African regions are facing challenges that are impeding the development of DUR. Objectives: To identify the main challenges and issues for DUR in the LatAm and African regions Methods: A collaborative initiative by the International Society of Pharmacoepidemiology Global Development Committee in partnership with the Latin America Drug Utilization Group and the Medicines Utilization Research in Africa Group was undertaken. A comprehensive literature review was conducted to identify local and international DUR publications. A core group of investigators and experts in DUR reviewed the publications and identified the main methodological challenges and issues. Subsequently, the group exchanged materials, participated in WebEx discussions, and reviewed the draft document. Results: Main issues: 1) Socioeconomic: high unemployment rate with poor standard of living, socioeconomic inequalities, low literacy levels, urban segregation, high migration rates, high rates of violent crime including drug trafficking and possession. 2) Healthcare-related: Disparities of social determinants of health, differences in the quality of public and private health sectors; and epidemiologic transition from communicable diseases to non-communicable diseases. Most health care systems are fragmented with variable access to medical care and medicines, and substandard record keeping. 3) Drug utilization-related: Inappropriate use of medicines including the elderly; limited infrastructure to reliably collect DU data; over-prescription of antimicrobials; polypharmacy; high rates of self-medication; and poor patient adherence (e.g. HIV/AIDS, diabetes mellitus and hypertension). Planning for DUR is affected by the multiplicity of drug distribution channels; trading in sub-standard, counterfeit medicines and insufficient quality control centers. Some publications are generated by local investigators, often suffering of methodological issues such as lack of representativeness of the population, limited data validity, and small sample sizes. Conclusions: There are common challenges for DUR when working within the LatAm and African regions. Based on our findings, the group is developing Guidance on Good Practices of Drug Utilization Research in those regions to assist researchers with issues pertaining to the planning, conduct, and evaluation of DUR

Preoperative Aspirin Use and Its Effect on Adverse Events in Patients Undergoing Cardiac Operations.

BackgroundPreoperative aspirin use within 5 days of cardiac operations is controversial. Aspirin could reduce cardiovascular complications and yet might increase risk of bleeding. Recent reports showed conflicting results, and whether aspirin has variable effects for different cardiac surgical procedures is unclear.MethodsA single-center retrospective cohort analysis was performed. After propensity score matching (PSM) for identified confounders, the relationship between preoperative aspirin use and 30-day all-cause mortality, postoperative renal failure, major adverse cardiocerebral events (MACE), blood transfusion, reoperation for bleeding, and postoperative infection were estimated with separate logistic regression models.ResultsPreoperative aspirin therapy was associated with a 49% (p = 0.04) increased risk of reoperation for bleeding among 868 matched pairs of patients undergoing valve operations. Among 725 matched patients undergoing coronary artery bypass grafting (CABG), preoperative aspirin therapy was not associated with a statistically significant higher risk of reoperation for bleeding. However, preoperative aspirin use, compared with nonuse, was not associated with risks of MACE, 30-day mortality, postoperative renal failure, blood transfusion, or postoperative infection in the entire cohort, in patients undergoing valve operations only, and in patients undergoing CABG only after PSM.ConclusionsPreoperative aspirin use in all patients undergoing cardiac operations was not associated with risks of major cardiac, cerebral, or renal complications and infections and death; however, the risk of reoperation for bleeding was elevated among preoperative aspirin users compared with nonusers in a subpopulation of patients undergoing valve operations only

Preoperative Aspirin Use and Its Effect on Adverse Events in Patients Undergoing Cardiac Operations.

BackgroundPreoperative aspirin use within 5 days of cardiac operations is controversial. Aspirin could reduce cardiovascular complications and yet might increase risk of bleeding. Recent reports showed conflicting results, and whether aspirin has variable effects for different cardiac surgical procedures is unclear.MethodsA single-center retrospective cohort analysis was performed. After propensity score matching (PSM) for identified confounders, the relationship between preoperative aspirin use and 30-day all-cause mortality, postoperative renal failure, major adverse cardiocerebral events (MACE), blood transfusion, reoperation for bleeding, and postoperative infection were estimated with separate logistic regression models.ResultsPreoperative aspirin therapy was associated with a 49% (p = 0.04) increased risk of reoperation for bleeding among 868 matched pairs of patients undergoing valve operations. Among 725 matched patients undergoing coronary artery bypass grafting (CABG), preoperative aspirin therapy was not associated with a statistically significant higher risk of reoperation for bleeding. However, preoperative aspirin use, compared with nonuse, was not associated with risks of MACE, 30-day mortality, postoperative renal failure, blood transfusion, or postoperative infection in the entire cohort, in patients undergoing valve operations only, and in patients undergoing CABG only after PSM.ConclusionsPreoperative aspirin use in all patients undergoing cardiac operations was not associated with risks of major cardiac, cerebral, or renal complications and infections and death; however, the risk of reoperation for bleeding was elevated among preoperative aspirin users compared with nonusers in a subpopulation of patients undergoing valve operations only