Comparison of Utilization and Clinical Outcomes for Belatacept- and Tacrolimus- Based Immunosuppression in Renal Transplant Recipients

The performance of belatacept in a real clinical setting has not been reported. A retrospective cohort study was conducted using registry data comparing 1-year clinical outcomes between belatacept- and tacrolimus-treated adult kidney transplant recipients (KTRs) from January 6, 2011, through January 12, 2014. Of 50 244 total patients, 417 received belatacept plus tacrolimus, 458 received belatacept alone, and 49 369 received tacrolimus alone at discharge. In the overall study cohort, belatacept alone was associated with a higher risk of 1-year acute rejection, with the highest rates associated with non–lymphocyte-depleting induction (adjusted hazard ratio 2.65, 95% confidence interval 1.90–3.70, p \u3c 0.0001). There was no significant difference in rejection rates between belatacept plus tacrolimus and tacrolimus alone. In KTRs who met inclusion criteria for the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial–Extended Criteria Donors (BENEFIT-EXT), 1-year kidney function was higher with belatacept plus tacrolimus and belatacept alone versus tacrolimus alone (mean estimated GFR 65.6, 60.4 and 54.3 mL/min per 1.73 m2, respectively; p \u3c 0.001). The incidence of new-onset diabetes after transplantation was significantly lower with belatacept plus tacrolimus and belatacept alone versus tacrolimus alone (1.7%, 2.2%, and 3.8%, respectively; p = 0.01). Despite improved graft function and metabolic complications with belatacept alone, it may be advisable to add short-term tacrolimus in the first year after transplant and to consider lymphocyte-depleting induction in patients with high rejection risk, as the risk–benefit ratio allows

Comparative Safety Analysis of Opioid Agonist Treatment in Pregnant Women with Opioid Use Disorder: A Population-Based Study

Introduction and Objective: Receipt of opioid agonist treatment during early and late pregnancy for opioid use disorder may relate to varying perinatal risks. We aimed to assess the effect of time-varying prenatal exposure to opioid agonist treatment using buprenorphine or methadone on adverse neonatal and pregnancy outcomes. Methods: We conducted a retrospective cohort study of pregnant women with opioid use disorder using Rhode Island Medicaid claims data and vital statistics during 2008–16. Time-varying exposure was evaluated in early (0–20 weeks) and late (≥ 21 weeks) pregnancy. Marginal structural models with inverse probability of treatment weighting were applied. Results: Of 400 eligible pregnancies, 85 and 137 individuals received buprenorphine and methadone, respectively, during early pregnancy. Compared with 152 untreated pregnancies with opioid use disorders, methadone exposure in both periods was associated with an increased risk of preterm birth (adjusted odds ratio [aOR]: 2.52; 95% confidence interval [CI] 1.07–5.95), low birth weight (aOR: 2.99; 95% CI 1.34–6.66), neonatal intensive care unit admission (aOR, 5.04; 95% CI 2.49–10.21), neonatal abstinence syndrome (aOR: 11.36; 95% CI 5.65–22.82), respiratory symptoms (aOR, 2.71; 95% CI 1.17–6.24), and maternal hospital stay \u3e 7 days (aOR, 14.51; 95% CI 7.23–29.12). Similar patterns emerged for buprenorphine regarding neonatal abstinence syndrome (aOR: 10.27; 95% CI 4.91–21.47) and extended maternal hospital stay (aOR: 3.84; 95% CI 1.83–8.07). However, differences were found favoring the use of buprenorphine for preterm birth versus untreated pregnancies (aOR: 0.17; 95% CI 0.04–0.77), and for several outcomes versus methadone. Conclusions: Methadone and buprenorphine prescribed for the treatment of opioid use disorder during pregnancy are associated with varying perinatal risks. However, buprenorphine may be preferred in the setting of pregnancy opioid agonist treatment. Further research is necessary to confirm our findings and minimize residual confounding

Combining Adverse Pregnancy and Perinatal Outcomes for Women Exposed to Antiepileptic Drugs During Pregnancy, Using a Latent Trait Model

Background Application of latent variable models in medical research are becoming increasingly popular. A latent trait model is developed to combine rare birth defect outcomes in an index of infant morbidity. Methods This study employed four statewide, retrospective 10-year data sources (1999 to 2009). The study cohort consisted of all female Florida Medicaid enrollees who delivered a live singleton infant during study period. Drug exposure was defined as any exposure to Antiepileptic drugs (AEDs) during pregnancy. Mothers with no AED exposure served as the AED unexposed group for comparison. Four adverse outcomes, birth defect (BD), abnormal condition of new born (ACNB), low birth weight (LBW), and pregnancy and obstetrical complication (PCOC), were examined and combined using a latent trait model to generate an overall severity index. Unidimentionality, local independence, internal homogeneity, and construct validity were evaluated for the combined outcome. Results The study cohort consisted of 3183 mother-infant pairs in total AED group, 226 in the valproate only subgroup, and 43,956 in the AED unexposed group. Compared to AED unexposed group, the rate of BD was higher in both the total AED group (12.8% vs. 10.5%, P \u3c .0001), and the valproate only subgroup (19.6% vs. 10.5%, P  \u3c .0001). The combined outcome was significantly correlated with the length of hospital stay during delivery in both the total AED group (Rho = 0.24, P \u3c .0001) and the valproate only subgroup (Rho = 0.16, P = .01). The mean score for the combined outcome in the total AED group was significantly higher (2.04 ± 0.02 vs. 1.88 ± 0.01, P \u3c .0001) than AED unexposed group, whereas the valproate only subgroup was not. Conclusions Latent trait modeling can be an effective tool for combining adverse pregnancy and perinatal outcomes to assess prenatal exposure to AED, but evaluation of the selected components is essential to ensure the validity of the combined outcome

Validation of a common data model for active safety surveillance research

Systematic analysis of observational medical databases for active safety surveillance is hindered by the variation in data models and coding systems. Data analysts often find robust clinical data models difficult to understand and ill suited to support their analytic approaches. Further, some models do not facilitate the computations required for systematic analysis across many interventions and outcomes for large datasets. Translating the data from these idiosyncratic data models to a common data model (CDM) could facilitate both the analysts' understanding and the suitability for large-scale systematic analysis. In addition to facilitating analysis, a suitable CDM has to faithfully represent the source observational database. Before beginning to use the Observational Medical Outcomes Partnership (OMOP) CDM and a related dictionary of standardized terminologies for a study of large-scale systematic active safety surveillance, the authors validated the model's suitability for this use by example

Written information about individual medicines for consumers.

Medicines are the most common intervention in most health services. As with all treatments, those taking medicines need sufficient information: to enable them to take and use the medicines effectively, to understand the potential harms and benefits, and to allow them to make an informed decision about taking them. Written medicines information, such as a leaflet or provided via the Internet, is an intervention that may meet these purposes

Net Efficacy Adjusted for Risk (NEAR): A Simple Procedure for Measuring Risk:Benefit Balance

BACKGROUND: Although several mathematical models have been proposed to assess the risk:benefit of drugs in one measure, their use in practice has been rather limited. Our objective was to design a simple, easily applicable model. In this respect, measuring the proportion of patients who respond favorably to treatment without being affected by adverse drug reactions (ADR) could be a suitable endpoint. However, remarkably few published clinical trials report the data required to calculate this proportion. As an approach to the problem, we calculated the expected proportion of this type of patients. METHODOLOGY/PRINCIPAL FINDINGS: Theoretically, responders without ADR may be obtained by multiplying the total number of responders by the total number of subjects that did not suffer ADR, and dividing the product by the total number of subjects studied. When two drugs are studied, the same calculation may be repeated for the second drug. Then, by constructing a 2 x 2 table with the expected frequencies of responders with and without ADR, and non-responders with and without ADR, the odds ratio and relative risk with their confidence intervals may be easily calculated and graphically represented on a logarithmic scale. Such measures represent "net efficacy adjusted for risk" (NEAR). We assayed the model with results extracted from several published clinical trials or meta-analyses. On comparing our results with those originally reported by the authors, marked differences were found in some cases, with ADR arising as a relevant factor to balance the clinical benefit obtained. The particular features of the adverse reaction that must be weighed against benefit is discussed in the paper. CONCLUSION: NEAR representing overall risk-benefit may contribute to improving knowledge of drug clinical usefulness. As most published clinical trials tend to overestimate benefits and underestimate toxicity, our measure represents an effort to change this trend

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