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 > 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.

Comparative Safety of Sleeve Gastrectomy and Roux-en-Y: A Propensity Score Analysis.

BACKGROUND: Use of bariatric surgery has increased dramatically in the USA. However, there are growing concerns regarding the safety outcomes of different bariatric procedures. We aim to compare the safety of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), which includes hospital readmissions, emergency room (ER) visits, gastrointestinal bleeding, and revisional surgery. METHODS: A retrospective cohort analysis was conducted for adults (≥ 18 years) who received SG and RYGB in the USA. We used Truven MarketScan Commercial and Medicare supplemental claims databases from January 1, 2005, to October 1, 2015. To adjust for baseline demographic and clinical characteristics, we used stabilized inverse probability of treatment weighting using propensity score. Cox proportional hazard models was used to compare safety outcomes between SG and RYGB after bariatric surgery. RESULTS: A total of 194,248 patients met inclusion criteria; 79,813 patients (41%) received SG and 114,435 patients (59%) received RYGB. The use of SG was associated with a significantly lower 30-day hospital readmission rate [adjusted hazard ratios (aHRs) 0.77; 95% confidence interval (CI), 0.74-0.81] and ER visits [aHR, 0.82; 95% CI, 0.80-0.83], and decreased risk of gastrointestinal bleeding [aHR, 0.87; 95% CI, 0.78-0.98] compared to RYGB. However, SG was associated with an increased risk of revisional surgery, compared to RYGB [aHR,1.21; 95% CI, 1.08-1.35]. CONCLUSIONS: Among patients receiving bariatric surgery in a real-world setting, SG was associated with lower complication rate but a higher risk of revisional surgery compared to RYGB. Further longitudinal studies are needed to assess long-term findings.

Drug absorption in bariatric surgery patients: A narrative review.

Background: Despite the increase in the number of bariatric surgeries performed, little is known about the impact of the surgery on drug absorption. Unpredictability is assumed with drugs, given the anatomical changes after surgery. Objective: To evaluate the impact of bariatric surgery on drug absorption based on the type of procedure performed. Methods: We conducted a comprehensive literature review searching PubMed/Medline for published studies (from inception to December 2017) that evaluate the use of drugs and the assessment of drug absorption after bariatric surgery. Pharmacokinetic/pharmacodynamic studies, case reports, and observational studies were included in our review. Results: We found 60 studies addressing drug use after bariatric surgery. Twenty-eight studies reported a decrease in drug absorption after bariatric surgery while only four studies showed an increase in drug absorption. Unchanged absorption of drugs was seen in 23 studies after the surgery. Conclusion: The available information shows variations in drug absorption after bariatric surgery. The unpredictability may result from factors related to the patient, drug, and/or type of surgery. Therefore, pharmacists' involvement and close monitoring of patients after bariatric surgery could be effective to avoid sub-/supratherapeutic responses.

US national trends in bariatric surgery: A decade of study.

BACKGROUND: Since the 1990s, the number of bariatric surgeries has dramatically increased, including the number of bariatric centers in the United States; no recent studies have yet assessed trends of bariatric surgery. This study aims to assess the trends of bariatric surgery and the change in utilization by the type of surgery, from 2006 to 2015, using real-world data. METHODS: A cross-sectional analysis of MarketScan databases of privately insured beneficiaries aged equal to or more than 18 years, to assess the annual incidence rate of bariatric surgery type of surgery from 2006 to 2015. Linear regression analysis was used to assess the significance of bariatric surgery changes over time. RESULTS: A gradual increase in overall bariatric surgery was observed from 43.5 per 100,000 in 2006 to 70.6 per 100,000 in 2009. This increasing trend plateaued from 2010 to 2015. Among all bariatric surgeries performed, the sleeve gastrectomy showed a significant increase from (n = 596) 11% in 2006 to (n = 15,425) 70% in 2015 (P < .001), whereas there was a decrease in Roux-en-Y from (n = 10,129) 45% in 2010 to (n = 5074) 24% in 2015 (P < .001). CONCLUSION: Utilization of bariatric surgery showed a gradual increase in the first 5 years, with steady rates in the last 5 years of the study period. Sleeve gastrectomy and Roux-en-Y remain the most performed bariatric procedures. Laparoscopic surgery continues to dominate bariatric surgery compared with open surgery.

Challenges facing drug utilization research in the Latin American region.

PURPOSE: The International Society of Pharmacoepidemiology (ISPE) in collaboration with the Latin America Drug Utilization Research Group (LatAm DURG), the Medicines Utilization Research in Africa (MURIA) group, and the Uppsala Monitoring Center, is leading an initiative to understand challenges to drug utilization research (DUR) in the Latin American (LatAm) and African regions with the goal of communicating results and proposing solutions to these challenges in four scientific publications. The purpose of this first manuscript is to identify the main challenges associated with DUR in the LatAm region. METHODS: Drug utilization (DU) researchers in the LatAm region voluntarily participated in multiple discussions, contributed with local data and reviewed successive drafts and the final manuscript. Additionally, we carried out a literature review to identify the most relevant publications related to DU studies from the LatAm region. RESULTS: Multiple challenges were identified in the LatAm region for DUR including socioeconomic inequality, access to medical care, complexity of the healthcare system, limited investment in research and development, limited institutional and organization resources, language barriers, limited health education and literacy. Further, there is limited use of local DUR data by decision makers particularly in the identification of emerging health needs coming from social and demographic transitions. CONCLUSIONS: The LatAm region faces challenges to DUR which are inherent in the healthcare and political systems, and potential solutions should target changes to the system.

Increased Risk of Acute Pancreatitis with Codeine Use in Patients with a History of Cholecystectomy.

BACKGROUND: Codeine has a spasmodic effect on sphincter of Oddi and is suspected to cause acute pancreatitis in patients with a history of cholecystectomy. AIMS: To assess the association between codeine use and acute pancreatitis in patients with a previous cholecystectomy. METHODS: We conducted a retrospective nested case-control study using the 2005-2015 MarketScan® Commercial Claims and Encounters Database. The cohort included patients aged 18-64; cohort entry began 365 days after cholecystectomy. Odds ratios (ORs) and 95% CIs for acute pancreatitis hospitalization were estimated comparing use of codeine with non-use of codeine. In a secondary analysis, use of codeine was compared with an active comparator: use of non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS: Of the 664,083 patients included in the cohort, 1707 patients were hospitalized for acute pancreatitis (incidence 1.1 per 1000 person-years) and were matched to 17,063 controls. Compared with non-use of codeine, use of codeine was associated with an increased risk of acute pancreatitis (OR 2.67; 95% CI 1.63, 4.36), particularly elevated in the first 15 days of codeine use (OR 5.37; 95% CI 2.70, 10.68). Compared with use of NSAIDs, use of codeine was also associated with an increased risk of acute pancreatitis (OR 2.64; 95% CI 1.54, 4.52). CONCLUSION: Codeine is associated with an increased risk of acute pancreatitis in patients who have previously undergone cholecystectomy; greater clinician awareness of this association is needed.

Metabolic syndrome and metabolically healthy status in adults with overweight or obesity, expressing no desire to lose weight.

AIM: To examine the prevalence of metabolic syndrome (MetS) and metabolically healthy status (MHS) in adults with excess weight, who express no desire to lose weight (DLW). METHODS: We used the National Health and Nutrition Examination Survey (2011-2016) to conduct a cross-sectional analysis of 4509 adults with excess weight. The prevalence of MetS and MHS was estimated by a DLW status. The prevalence ratios (PRs) were estimated, adjusting for demographic characteristics, to compare the prevalence of MetS and MHS between those with and without a DLW. RESULTS: Among adults who were overweight, the crude prevalence of MetS was 28.9% (95% CI 23.7, 34.1) in the no-DLW group and 36.0% (95% CI 31.9, 40.0) in the DLW group (adjusted PR 0.88; 95% CI 0.70, 1.11). Among adults with obesity, the crude prevalence of MetS was 60.0% (95% CI 52.3, 67.6) in the no-DLW group and 63.2% (95% CI 60.0, 66.4) in the DLW group (adjusted PR 1.00; 95% CI 0.88, 1.14). Among adults who were overweight, the prevalence of MHS was 17.5% (95% CI 13.4, 22.2) in the no-DLW group, and 9.5% (95% CI 7.6, 11.6) in the DLW group (adjusted PR 1.27; 95% CI 0.96, 1.69). Nearly all adults with obesity had at least one component of MetS regardless of DSW status. CONCLUSIONS: One in four overweight adults and three in five obese adults without a DLW had MetS in the U.S. A majority of adults who were overweight or obese without a DSW had at least one component of MetS.

Prevalence of Maternal-Risk Factors Related to Neonatal Abstinence Syndrome in a Commercial Claims Database: 2011-2015.

BACKGROUND: Despite the rising incidence of neonatal abstinence syndrome (NAS), data evaluating trends in maternal risk factors associated with NAS have not been available for recent years, a period characterized by declining opioid prescriptions. The objective of this study was to examine the prevalence of opioid- and non-opioid-related factors associated with NAS, and by mutually exclusive subgroups of deliveries without prescription-opioid use, with prescription-opioid use, and with opioid-use disorder (OUD). METHODS: A cohort of pregnancies resulting in live births in a commercial claims data base in 2011-2015 was identified. Examples of maternal risk factors of interest included antepartum prescription-drug use (e.g., opioids, selective serotonin reuptake inhibitors [SSRIs], antipsychotics) and nonprescription-related factors (e.g., smoking, OUD). RESULTS: A total of 659 cases of NAS among 621,940 deliveries was identified. Among NAS deliveries, prescription opioids were the most commonly used drug-class (39.0%). Adjusted relative risk (RR) for NAS was 5.43 (95% confidence interval [CI] 4.25-6.95), followed by SSRIs (20.9%; RR 3.16, CI 2.43-4.11); OUD was noted in 36.3% of the deliveries (RR 40.74, CI 22.64-73.32). In the subgroup of deliveries without a prescription opioid (33% of overall NAS deliveries), the absolute incidence of NAS was low (0.3 cases/1000 deliveries), and SSRIs were the most commonly used medication class (32.7%; RR 10.21, CI 7.28-14.31). In the subgroup of deliveries with an opioid prescription, the absolute incidence of NAS was 7.7/1000 (29% of all overall NAS deliveries), and 22.7% of these deliveries were exposed to one other psychotropic agent in addition to the opioid, most commonly an SSRI (18.0%). In the subgroup of deliveries with a diagnosis of OUD, the NAS incidence was high (214.3/1000 [36% of all NAS cases]). CONCLUSION: A third of NAS deliveries did not have evidence of prescription opioids. Other psychotropic medications, especially SSRIs, were strong predictors of NAS in this stratum but had no relevance among deliveries with OUD, suggesting varying etiologies and the need for tailored preventive approaches to reduce NAS effectively.

Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy.

BACKGROUND AND AIMS: Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD). METHODS: Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression. RESULTS: In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% in UC cohort). In the first year, adalimumab had the highest persistence and lowest switching rates for both CD (median survival time: 1.04 years) and UC (median survival time: 0.84 years). In subsequent years, infliximab users were more likely to persist in the use of biologic. Combination therapy with immunomodulators significantly decreased the risk of discontinuation, especially when immunomodulator therapy was started more than 30 days before the biologic (hazard ratio [HR], 0.22; CI, 0.16, 0.32). The major predictors for noncompliance included infection and hospitalization. CONCLUSION: Overall, the persistence profiles of biologics suggest a high rate of dissatisfaction or adverse disease outcomes resulting in discontinuation and switching to a different agent. Early initiation of immunomodulators will substantially increase the persistence of biologic treatment.

Decline in dopamine agonists prescribing and characteristics of drugs prescribed during ambulatory office visits for restless legs syndrome: the National Ambulatory Medical Care Survey 2007-2015.

OBJECTIVE: To examine prescribing of drugs treating or exacerbating restless legs syndrome (RLS) during U.S. physician office visits for RLS for the years 2007-2015; and to assess potential prescribing predictors of these drugs. METHODS: Using the National Ambulatory Medical Care Survey data, we conducted a retrospective cross-sectional study. We calculated weighted percentages of RLS-related office visits associated with RLS treatment drugs (alpha-2-delta ligands, dopamine agonists, and other drugs used for RLS) and exacerbating drugs. Using logistic regression, we examined the adjusted association between potential predictors and prescribing of major RLS treatment (dopamine agonists and alpha-2-delta ligands) and exacerbating drugs. RESULTS: A total of 456 RLS-related office visits were included for analysis, representing approximately 9.9 million visits. The weighted percentages of visits with dopamine agonists (excluding levodopa) decreased from 50% to 22% (RR 0.44; 95% CI 0.26, 0.77). A visit to a neurologist was associated with a 76% increase in prescribing of the major RLS treatment drugs compared with a visit to a family/general or internal medicine physician (RR 1.76; 95% CI 1.29, 2.42). RLS exacerbating drugs were listed in 28% (95% CI 21-36) of RLS-related visits, mostly for antidepressants (83%). Younger age groups (18-44 and 45-64) were predictors of RLS exacerbating drug prescribing, compared with the older age group (RR 2.46; RR 2.00, respectively). CONCLUSION: Prescribing of dopamine agonists during RLS-related visits decreased during 2007-2015, but prescribing of RLS exacerbating drugs remained high. More investigation is necessary concerning whether clinicians assess the appropriateness of RLS exacerbating drugs for RLS patients before newly prescribing or continuing those drugs. Also, future research would need to investigate what factors contribute to the difference in the RLS treatment prescribing patterns between neurologists and family/general or internal medicine physicians.

Association Between Recombinant Human Bone Morphogenetic Proteins and Postoperative Opioid Use in Lumbar Fusion Procedure Patients: A Propensity Score-Matched Analysis.

BACKGROUND: Little is known about the effectiveness of recombinant human bone morphogenetic proteins (rhBMPs) in reducing the demand for opioids after surgery. We investigated the association between rhBMP use and the likelihood of achieving opioid independence and changes in opioid demand in the first postoperative year. METHODS: Using the Multi-Payer Claims Database from 2007 to 2010, patients aged >20 years who had undergone a degenerative disc disease-indicated lumbar fusion procedure and had had ≥1 opioid prescription in the 3 months before surgery were identified. Propensity score matching (1:1) of rhBMP-exposed and rhBMP-unexposed patients was used to mitigate confounding. The outcomes of interest were opioid independence and decreases in opioid doses in morphine equivalent units, assessed at 3-6 and 9-12 months after the procedure. Logistic regression and analysis of covariance models were used. RESULTS: The data from 318 patients were analyzed. Most patients were women (61%) and aged <65 years (68%). Few had achieved opioid independence at 3-6 (n = 71; 22.3%) or 9-12 (n = 115; 36.2%) months postoperatively. During the 3-6-month window, the rhBMP group reduced their opioid use rates (estimated mean difference. -28.4 vs. -19.5; P = 0.69) and achieved opioid independence (21.4% vs. 23.3%; odds ratio, 0.92; 95% confidence interval, 0.54-1.56; P = 0.74) at rates that were statistically comparable to their matched comparators. Similar patterns were observed during the 9-12-month window. CONCLUSION: We found no evidence to suggest that rhBMP use during spinal fusion procedures is associated with either the discontinuation or decrease of opioid analgesic therapy. The continued opioid use after surgery warrants further clinical and research attention.

Comparative risk of lipophilic and hydrophilic statins on incident depression: A retrospective cohort study.

OBJECTIVES: To evaluate the risk of new-onset depression in a cohort of US adult patients initiating lipophilic statin therapy compared to hydrophilic statin therapy. DESIGN: Retrospective cohort study. SETTING: Large US commercial claims database PARTICIPANTS: 1:1 propensity score matched cohort of lipophilic (atorvastatin, lovastatin and simvastatin) and hydrophilic (pravastatin and rosuvastatin) statin initiators between January 2009 to June 2015. OUTCOME: New onset of depression. RESULTS: In a propensity-score matched cohort of 299,298 statin initiators, the crude incidence of depression in the hydrophilic and lipophilic group was 136.6 and 142.8 per 10,000 person-years respectively. Compared to hydrophilic statin use, lipophilic statin use was not associated with a statistically significant increase in the risk of depression, adjusted HR 1.05 (95% CI, 1.00-1.10, p = 0.078) and excess incidence of 6.3 (95% CI, -0.7-13.7) per 10,000 person-years. Findings were consistent across the subgroups of patients with history of psychiatric conditions HR 1.05 (95% CI, 0.94-1.16, p = 0.41), and those initiating statins for primary or secondary prevention, HR 1.03 (95% CI, 0.97-1.10, p = 0.33) and 1.07 (95% CI, 0.99-1.16, p = 0.10) respectively. Within individual lipophilic statins, only simvastatin was associated with a moderate increase in the risk of depression HR 1.09 (95% CI, 1.02-1.16, p = 0.003), followed by lovastatin HR 1.07 (95% CI, 0.93-1.24, p = 0.34) and atorvastatin HR 1.05 (95% CI, 0.97-1.13, p = 0.27). LIMITATIONS: Findings are generalizable to patients with commercial insurance. CONCLUSIONS: Lipophilic statin use was not associated with a significant increase in the risk of incident depression.

Adherence and persistence to ropinirole, pramipexole, and gabapentin in patients with newly diagnosed restless legs syndrome.

STUDY OBJECTIVES: The objective of this study is to assess adherence and persistence of ropinirole, pramipexole, and gabapentin; to investigate factors associated with non-adherence and non-persistence in restless legs syndrome (RLS) patients. METHODS: We used the 2008-2014 Marketscan® Research Databases to conduct a retrospective data analysis. The study included newly diagnosed RLS patients who initiated ropinirole, pramipexole, or gabapentin therapy. During 365 days of follow-up, mean medication possession ratios (MPRs) for adherence and the proportion of adherent users were calculated. The mean persistence (time to discontinuation) and the proportion of persistent users were also assessed during the same follow-up period. Factors associated with non-adherence and non-persistence were analyzed using multivariate logistic regression. RESULTS: This study included 5163 ropinirole, 3380 pramipexole, and 1353 gabapentin users. The mean MPRs for ropinirole, pramipexole, and gabapentin were 0.52, 0.52, and 0.48, respectively. The proportions of adherent users were 33.2%, 34.6%, and 27.4%, respectively. Mean time to treatment discontinuation was 158 days, 158 days, and 145 days, respectively. The proportions of persistent users at 365 days were 25.0%, 25.8%, and 20.6%, respectively. Younger age, higher number of concomitant medications, and gabapentin use (vs. ropinirole or pramipexole use) were positively associated with non-adherence and non-persistence. Additionally, retail pharmacy use (vs. mail order pharmacy use) and use of benzodiazepines were positively associated with non-adherence. CONCLUSION: Adherence and persistence to ropinirole, pramipexole, and gabapentin were low in newly diagnosed RLS patients during 365 days of follow-up. Certain patient characteristics were predictors of non-adherence and non-persistence.

High Generic Drug Prices and Market Competition: A Retrospective Cohort Study.

BACKGROUND: Prices for some generic drugs have increased in recent years, adversely affecting patients who rely on them. OBJECTIVE: To determine the association between market competition levels and the change in generic drug prices in the United States. DESIGN: Retrospective cohort study. SETTING: Prescription claims from commercial health plans between 2008 and 2013. MEASUREMENTS: The 5.5 years of data were divided into 11 study periods of 6 months each. The Herfindahl-Hirschman Index (HHI)-calculated by summing the squares of individual manufacturers' market shares, with higher values indicating a less competitive market-and average drug prices were estimated for the generic drugs in each period. The HHI value estimated in the baseline period (first half of 2008) was modeled as a fixed covariate. Models estimated price changes over time by level of competition, adjusting for drug shortages, market size, and dosage forms. RESULTS: From 1.08 billion prescription claims, a cohort of 1120 generic drugs was identified. After adjustment, drugs with quadropoly (HHI value of 2500, indicating relatively high levels of competition), duopoly (HHI value of 5000), near-monopoly (HHI value of 8000), and monopoly (HHI value of 10 000) levels of baseline competition were associated with price changes of -31.7% (95% CI, -34.4% to -28.9%), -11.8% (CI, -18.6% to -4.4%), 20.1% (CI, 5.5% to 36.6%), and 47.4% (CI, 25.4% to 73.2%), respectively, over the study period. LIMITATION: Study findings may not be generalizable to drugs that became generic after 2008. CONCLUSION: Market competition levels were associated with a change in generic drug prices. Such measurements may be helpful in identifying older prescription drugs at higher risk for price change in the future. PRIMARY FUNDING SOURCE: None.

Trends in utilization of warfarin and direct oral anticoagulants in older adult patients with atrial fibrillation.

PURPOSE: Results of a study to determine trends in oral anticoagulant (OAC) use and OAC switching in patients with atrial fibrillation (AF) or atrial flutter are presented. METHODS: Warfarin has been the most prescribed anticoagulant in patients with AF for decades. Since 2010, several direct OACs (DOACs) have gained U.S. marketing approval for stroke prevention in AF or atrial flutter. A cross-sectional longitudinal analysis was conducted using healthcare and prescription claims databases to characterize OAC use and rates of OAC and DOAC switching during the period 2008-14 in cohorts of Medicare beneficiaries 65 years of age or older with AF or atrial flutter. RESULTS: Overall, 66% of patients with AF or atrial flutter were receiving OACs during the study period. The prevalence of warfarin use decreased from 69.8% in 2008 to 42.2% in 2014. This decrease in warfarin use was paralleled by an increase in dabigatran use, which rose from 1.3% in 2010 to 12.1% in 2011 and then declined to 7.6% in 2014. The prevalence of rivaroxaban use increased from 0.13% in 2011 to 13.87% in 2014. Among anticoagulated patients, an average of 6% annually were switched from one OAC to another. CONCLUSION: Overall OAC utilization in patients with AF or atrial flutter remained steady over the study period. Beginning in 2010, a gradual decrease in use of warfarin was paralleled by an increase in use of DOACs.

Duration of Reproductive Years and the Risk of Cardiovascular and Cerebrovascular Events in Older Women: Insights from the National Health and Nutrition Examination Survey.

BACKGROUND: Studies have shown conflicting information regarding the association between the age at menarche and/or menopause and cardiovascular and cerebrovascular diseases in older women. This study aimed to determine whether a longer duration of reproductive years in older women in the U.S. population was associated with a lower risk of cardiovascular and cerebrovascular diseases. MATERIALS AND METHODS: Women ≥60 years who participated in the National Health and Nutrition Examination Survey from 2007 to 2012 were included. Subjects provided information about the age of menarche and menopause along with the presence/absence of cardiovascular and cerebrovascular diseases. Participants were categorized into either a longer reproductive duration group (>30 years) or shorter reproductive duration group (≤30 years). Subgroup analysis for each 5-year increment in the longer reproductive duration group was conducted. Relative risk (RR) regression was performed using a generalized linear model adjusting for several confounding factors. RESULTS: 3081 participants were included in the analysis. A longer duration of reproductive years was associated with a lower risk of cardiovascular and cerebrovascular diseases, compared with a shorter duration (RR 0.70, 95% confidence interval [CI] 0.53-0.92). This association was due to a reduction in the risk of stroke (RR 0.53, 95% CI 0.34-0.88) and angina (RR 0.57, 95% CI 0.34-0.97). A 1 year increase in the reproductive duration was associated with a 3% reduction in the risk of events (RR 0.97, 95% CI 0.95-0.99). CONCLUSION: Among women ≥60 years, a longer duration of reproductive years was associated with lower risk of cardiovascular and cerebrovascular diseases. This association was mainly due to a reduction in the risk of stroke and angina.

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 < .0001), and the valproate only subgroup (19.6% vs. 10.5%, P < .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 < .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 < .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.

Stimulant use following the publicity of cardiovascular safety and the introduction of patient medication guides.

PURPOSE: To explore changes in stimulant utilization and pre-treatment electrocardiography (ECG) screening in response to cardiovascular (CV) safety concerns. METHODS: Two source populations were established from Florida Medicaid Fee-for-service beneficiaries between 2001 and 2008: approximately 44 571 newly diagnosed attention deficit/hyperactivity disorder patients and 33 000 new stimulant users. Time-series design and Joinpoint analysis were used to describe monthly trend changes in stimulant initiation, persistence, dosing, and pre-treatment ECG screening. RESULTS: Initial and maintenance daily dose declined 6 mg (95% confidence interval [CI] -14 to -1.9) methylphenidate (MPH) equivalent dose from a steady 27 mg after Canada withdrew Adderall XR in February 2005; the trend rebounded to a daily dose of 23 mg, after the remarketing of Adderall XR and a debate in the US over issuing a boxed warning on stimulant CV safety in early 2006. Monthly initiation increased 3.9% (CI -1.0 to 9.1) after the boxed warning debate to 54 per 100 patients per month (CI 44 to 68), but declined 2.4% (CI -3.6 to -1.2) after requirement of medication guides in February 2007. Monthly ECG screening increased 3.2% (CI 2.3 to 4.2) after Adderall XR withdrawal and further increased 13% (CI 4 to 23) after the American Heart Association recommended pre-treatment ECG screening to 40 per 100 patients per month (CI 17 to 48). CONCLUSIONS: The first signal of stimulant CV safety concerns was followed by varying responses depending on the outcome measure used, suggesting that patients and physicians responded at different times after the publicity of safety concerns. Clinical consequences of the changes are uncertain. Copyright © 2015 John Wiley & Sons, Ltd.