Pharmacoepidemiology and the Elderly

Summary: Pharmacoepidemiology employs the methods of epidemiology to study the frequency, determinants, and outcomes of drug therapy. Pharmacoepidemiology is becoming increasingly important with the aging of Western populations, due to the increased prevalence of medication use among older persons

Use of Antidiabetic drugs during pregnancy among U.S. women with Livebirth deliveries in the Mini-Sentinel system

BACKGROUND: As the prevalence of diabetes mellitus increases in the population, the exposure to antidiabetic drugs (ADDs) during pregnancies is expected to grow, as has been seen over the last decade. The objective of this study was to estimate the prevalence of ADD use during pregnancy among women in the Mini-Sentinel Distributed Database (MSDD) who delivered a liveborn infant. METHODS: We identified qualifying livebirth pregnancies among women aged 10 to 54 years in the MSDD from 2001 to 2013. ADD use was estimated using outpatient pharmacy dispensing claims and days-supplied among three cohorts: all livebirth pregnancies, pregnancies among women with pre-existing diabetes, and pregnancies among women without prior ADD use. RESULTS: Among the 1.9 million pregnancies in the MSDD that resulted in a livebirth from 2001 to 2013, 4.4% were exposed to an ADD. Of the 15,606 pregnancies (0.8%) with pre-existing diabetes, 92.8% were also exposed during the pregnancy period. The most commonly used product in these pregnancies was insulin (75.6% of pregnancies). In contrast, in pregnancies of women without prior ADD use, the most commonly used products were glyburide and insulin, and most of these users were diagnosed with gestational diabetes. CONCLUSIONS: Patterns of ADD use during pregnancy described here, along with changes in disease incidence and management, highlight the importance of continuing surveillance of ADD utilization patterns and examining the safety and effectiveness of these products in pregnancy

Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study

OBJECTIVE: To examine a reported association between use of angiotensin converting enzyme (ACE) inhibitors during the first trimester and risk of malformations in offspring. DESIGN: A population based, retrospective cohort study linking automated clinical and pharmacy databases including comprehensive electronic medical records. PARTICIPANTS: Pregnant women and their live born offspring (465,754 mother-infant pairs) in the Kaiser Permanente Northern California region from 1995 to 2008. MAIN OUTCOME MEASURE: Congenital malformation in live births. RESULTS: The prevalence of ACE inhibitor use in the first trimester only was 0.9/1000, and the use of other antihypertensive medications was 2.4/1000. After adjustment for maternal age, ethnicity, parity, and obesity, use of ACE inhibitors during the first trimester only seemed to be associated with increased risk of congenital heart defects in offspring compared with normal controls (those with neither hypertension nor use of any antihypertensives during pregnancy) (15/381 (3.9%) v 6232/400,021 (1.6%) cases, odds ratio 1.54 (95% confidence interval 0.90 to 2.62)). A similar association was observed for use of other antihypertensives (28/1090 (2.6%) cases of congenital heart defects, odds ratio 1.52 (1.04 to 2.21)). However, compared with hypertension controls (those with a diagnosis of hypertension but without use of antihypertensives) (708/29,735 (2.4%) cases of congenital heart defects), neither use of ACE inhibitors or of other antihypertensives in the first trimester was associated with increased congenital heart defects risk (odds ratios 1.14 (0.65 to 1.98) and 1.12 (0.76 to 1.64) respectively). CONCLUSIONS: Maternal use of ACE inhibitors in the first trimester has a risk profile similar to the use of other antihypertensives regarding malformations in live born offspring. The apparent increased risk of malformations associated with use of ACE inhibitors (and other antihypertensives) in the first trimester is likely due to the underlying hypertension rather than the medications

Adherence with urate-lowering therapies for the treatment of gout

INTRODUCTION: Adherence to urate-lowering drugs (ULDs) has not been well evaluated among those with gout. Our aim was to assess the level and determinants of non-adherence with ULDs prescribed for gout. METHODS: We identified persons using two integrated delivery systems aged 18 years or older with a diagnosis of gout who initiated use of allopurinol, probenecid or sulfinpyrazone from 1 January 2000 to 30 June 2006. Non-adherence was measured using the medication possession ratio (MPR) over the first year of therapy and defined as an MPR \u3c 0.8. Descriptive statistics were calculated and logistic regression was used to estimate the strength of the association between patient characteristics and non-adherence. RESULTS: A total of 4,166 gout patients initiated ULDs; 97% received allopurinol. Median MPR for any ULD use was 0.68 (interquartile range (IQR) 0.64). Over half of the patients (56%) were non-adherent (MPR \u3c 0.8). In adjusted analyses, predictors of poor adherence included younger age (odds ratio (OR) 2.43, 95% confidence interval (CI) 1.86 to 3.18 for ages \u3c45 and OR 1.44, 95% CI 1.08 to 1.93 for ages 45 to 49), fewer comorbid conditions (OR 1.46, 95% CI 1.20 to 1.77), no provider visits for gout prior to urate-lowering drug initiation (OR 1.28, 95% CI 1.05 to 1.55), and use of non-steroidal anti-inflammatory drugs in the year prior to urate-lowering drug initiation (OR 1.15, 95% CI 1.00 to 1.31). CONCLUSIONS: Non-adherence amongst gout patients initiating ULDs is exceedingly common, particularly in younger patients with less comorbidity and no provider visits for gout prior to ULD initiation. Providers should be aware of the magnitude of non-adherence with ULDs

Antiemetic use among pregnant women in the United States: the escalating use of ondansetron

PURPOSE: To examine ondansetron use in pregnancy in the context of other antiemetic use among a large insured United States population of women delivering live births. METHODS: We assessed ondansetron and other antiemetic use among pregnant women delivering live births between 2001 and 2015 in 15 data partners contributing data to the Mini-Sentinel Distributed Database. We identified live birth pregnancies using a validated algorithm, and all forms of ondansetron and other available antiemetics were identified using National Drug Codes or procedure codes. We assessed the prevalence of antiemetic use by trimester, calendar year, and formulation. RESULTS: In over 2.3 million pregnancies, the prevalence of ondansetron, promethazine, metoclopramide, or doxylamine/pyridoxine use anytime in pregnancy was 15.2, 10.3, 4.0, and 0.4%, respectively. Ondansetron use increased from \u3c1% of pregnancies in 2001 to 22.2% in 2014, with much of the increase attributable to oral ondansetron beginning in 2006. Promethazine and metoclopramide use increased modestly between 2001 (13.8%, 3.2%) and 2006 (16.0%, 6.0%) but decreased annually through 2014 (8.0%, 3.2%). Doxylamine/pyridoxine, approved for management of nausea and vomiting in pregnancy in 2013, was used in 1.8% of pregnancies in 2014. For all antiemetics, use was highest in the first trimester. CONCLUSIONS: We observed a marked increase in ondansetron use by study year, prescribed to nearly one-quarter of insured pregnant women in 2014, occurring in conjunction with decreased use of promethazine and metoclopramide. Given the widespread use of ondansetron in pregnancy, data establishing product efficacy and methodologically rigorous evaluation of post-marketing safety are needed

Methodological Challenges in Describing Medication Dosing Errors in Children

Summary: Although children are prescribed medications in 30 percent to 50 percent of clinic visits, little is known about medication errors in ambulatory pediatrics. In the process of completing a study to determine the prevalence of outpatient dosing errors, we identified a number of barriers to understanding the epidemiology of medication errors in children. These barriers include prescribing medication that is not labeled for use in children, discrepancies in published dosing recommendations for many medications, unclear guidelines on use of adult dosing recommendations for children of different ages and weights, and the lack of readily available documented weights to determine appropriate weight-based doses for children. In our study of pediatric medication errors, we found a wide range of doses prescribed to children for every medication we studied. Before we can truly understand medication errors in children and begin developing systems-based approaches to eliminating these errors, we need better national standards of medication doses that are appropriate for children and an improved ability to determine errors through databases that include children\u27s weights as well as prescription information

Neonatal Metabolomic Profiles Related to Prenatal Arsenic Exposure

Prenatal inorganic arsenic (iAs) exposure is associated with health effects evident at birth and later in life. An understanding of the relationship between prenatal iAs exposure and alterations in the neonatal metabolome could reveal critical molecular modifications, potentially underpinning disease etiologies. In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was used to identify metabolites in neonate cord serum associated with prenatal iAs exposure in participants from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort, in GoÌmez Palacio, Mexico. Through multivariable linear regression, ten cord serum metabolites were identified as significantly associated with total urinary iAs and/or iAs metabolites, measured as %iAs, %monomethylated arsenicals (MMAs), and %dimethylated arsenicals (DMAs). A total of 17 metabolites were identified as significantly associated with total iAs and/or iAs metabolites in cord serum. These metabolites are indicative of changes in important biochemical pathways such as vitamin metabolism, the citric acid (TCA) cycle, and amino acid metabolism. These data highlight that maternal biotransformation of iAs and neonatal levels of iAs and its metabolites are associated with differences in neonate cord metabolomic profiles. The results demonstrate the potential utility of metabolites as biomarkers/indicators of in utero environmental exposure

SCORE studies on the impact of drug treatment on morbidity due to <i>Schistosoma mansoni</i> and <i>Schistosoma haematobium</i> infection

The Schistosomiasis Consortium for Operational Research (SCORE) was funded in 2008 to improve the evidence base for control and elimination of schistosomiasis-better understanding of the systemic morbidities experienced by children in schistosomiasis-endemic areas and the response of these morbidities to treatment, being essential for updating WHO guidelines for mass drug administration (MDA) in endemic areas. This article summarizes the SCORE studies that aimed to gauge the impact of MDA-based treatment on schistosomiasis-related morbidities. Morbidity cohort studies were embedded in the SCORE's larger field studies of gaining control of schistosomiasis in Kenya and Tanzania. Following MDA, cohort children had less undernutrition, less portal vein dilation, and increased quality of life in Year 5 compared with baseline. We also conducted a pilot study of the Behavioral Assessment System for Children (BASC-2) in conjunction with the Kenya gaining control study, which demonstrated beneficial effects of treatment on classroom behavior. In addition, the SCORE's Rapid Answers Project performed systematic reviews of previously available data, providing two meta-analyses related to morbidity. The first documented children's infection-related deficits in school attendance and achievement and in formal tests of learning and memory. The second showed that greater reductions in egg output following drug treatment correlates significantly with reduced odds of most morbidities. Overall, these SCORE morbidity studies provided convincing evidence to support the use of MDA to improve the health of school-aged children in endemic areas. However, study findings also support the need to use enhanced metrics to fully assess and better control schistosomiasis-associated morbidity

Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic

Background: Drug adverse event (AE) signal detection using the Gamma Poisson Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method—the tree-based scan statistic (TreeScan). Results: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. Conclusions: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds

Fatores de risco e possíveis complicações associadas à síndrome hipertensiva na gravidez: uma revisão integrativa

Os distúrbios hipertensivos são responsáveis por elevado número de mortes maternas no cenário mundial e também no Brasil. A hipertensão gestacional é dividida em hipertensão crônica, hipertensão gestacional transitória, hipertensão crônica sobreposta pela pré-eclâmpsia, pré-eclâmpsia e eclâmpsia. Este trabalho tem como objetivo avaliar a SHG no que se relaciona ao padrão de prevalência, perfis acometidos, fatores de risco, e impactos ao binômio mãe-feto. A pergunta norteadora deste trabalho foi: ‘’ Quais os fatores de risco e possíveis complicações da SHG para a gestante e para o recém-nascido?’’. É um estudo que tem como fundamento a revisão integrativa da literatura. Foram selecionados 20 artigos, estes escolhidos entre os meses de fevereiro a março de 2021 nas bases de dados Google Acadêmico, Scielo e PubMed. Os descritores utilizados foram: Hipertensão gestacional; Gravidez; Cardiovascular; Hipertensão; Hipertensão arterial e do booleano ‘’AND’’. Como critérios de exclusão foram retirados artigos de revisão bibliográfica, os que não estavam disponíveis para visualização na íntegra, os que abordaram o tema de forma superficial e os estudos de análises muito específicas. A literatura convergentemente mostra que a maioria das pacientes acometidas com a Síndrome Hipertensiva Gestacional está na faixa etária entre 18 e 35 anos. Dentre os fatores de risco, se destacam doença vascular, obesidade, AVC, sífilis, hipertireoidismo, cefaleia, gestação tardia, diabetes, antecedentes familiares de hipertensão e tabagismo. Nos países desenvolvidos, as Síndromes Hipertensivas Gestacionais acometem cerca de 6% das gestantes, outrora nos países subdesenvolvidos o acometimento é maior. Além disso, a hipertensão gestacional é responsável por alto número de partos prematuros, restrições no crescimento intrauterino, baixo peso ao nascer, sofrimento fetal e abortamento, esses fatores que geram diversas complicações para a mãe e para o feto. Logo, se conclui a importância do pré-natal para identificar os fatores de risco e diminuir as complicações ao binômio mãe-feto