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Context: Fluoroquinolones are commonly prescribed classes of antibiotics. Despite numerous case reports of ocular toxicity, a pharmacoepidemiological study of their ocular safety, particularly retinal detachment, has not been performed.Objective: To examine the association between use of oral fluoroquinolones and the risk of developing a retinal detachment.Design, Setting, and Patients: Nested case-control study of a cohort of patients in British Columbia, Canada, who had visited an ophthalmologist between January 2000 and December 2007. Retinal detachment cases were defined as a procedure code for retinal repair surgery within 14 days of a physician service code. Ten controls were selected for each case using risk-set sampling, matching on age and the month and year of cohort entry.Main Outcome Measure: The association between retinal detachment and current, recent, or past use of an oral fluoroquinolone.Results: From a cohort of 989,591 patients, 4384 cases of retinal detachment and 43,840 controls were identified. Current use of fluoroquinolones was associated with a higher risk of developing a retinal detachment (3.3% of cases vs 0.6% of controls; adjusted rate ratio [ARR], 4.50 [95% CI, 3.56-5.70]). Neither recent use (0.3% of cases vs 0.2% of controls; ARR, 0.92 [95% CI, 0.45-1.87]) nor past use (6.6% of cases vs 6.1% of controls; ARR, 1.03 [95% CI, 0.89-1.19]) was associated with a retinal detachment. The absolute increase in the risk of a retinal detachment was 4 per 10,000 person-years (number needed to harm = 2500 computed for any use of fluoroquinolones). There was no evidence of an association between development of a retinal detachment and β-lactam antibiotics (ARR, 0.74 [95% CI, 0.35-1.57]) or short-acting β-agonists (ARR, 0.95 [95% CI, 0.68-1.33]).Conclusion: Patients taking oral fluoroquinolones were at a higher risk of developing a retinal detachment compared with nonusers, although the absolute risk for this condition was small. [ABSTRACT FROM AUTHOR]

Because of the importance of relationship power and cultural norms on women's ability to protect themselves from HIV/STDs, effective interventions must address power differentials among men and women. These programs need to be informed by and adapted to the cultural values of the target population. Accordingly, we conducted exploratory interviews with 22 young African American women at risk of HIV/ STDs and unintended pregnancy and their male partners regarding the meaning of power in heterosexual relationships, what makes a woman feel powerful in a relationship with a man, and who makes sexual and reproductive decisions in their relationships. Content analyses suggested that relationship power was linked to control and decision-making for most participants; yet, others appeared to associate power with positive relationship qualities such as respect and security. In addition, most participants reported that they shared decision-making about sexual and reproductive matters with their partners. Subsequently, interviews were conducted with another 40 women to explore and identify cultural beliefs regarding what makes women feel powerful in their relationships with their husbands or partners. Cultural consensus analysis was performed and results indicated that the participants comprise a cultural group with shared beliefs about what makes women feel powerful in their relationships. Participants believed that women's sense of power in their relationships came from (1) knowing what they want and having autonomy and control; (2) the quality of their relationships; (3) having resources to provide for their families; and (4) physical attractiveness and sexual factors. [ABSTRACT FROM AUTHOR]

Background: Most studies of sexual behavior and risk are based on self-reports of individuals.Goal: The goal of this study was to assess interpartner concordance on self-reported sexual behavior, condom use, and relationship characteristics; and agreement between individuals' perceptions of their partners' sexual risks and the partners' actual reports.Study Design: Interviews were conducted separately but concurrently with 112 heterosexual couples at increased risk for HIV/sexually transmitted infections recruited through women at clinics and community locations.Results: Couples were concordant on reports of relationship characteristics (kappa > or = 0.84), sexual behavior, and condom use (r > or = 0.62), but disagreed on who has more power and sexual decision-making dominance (kappa < or = 0.26). We found substantial agreement between men's perceptions and their partners' reported risky behavior (kappa = 0.62), but only fair agreement between women's perceptions and their partners' reports (kappa = 0.30).Conclusion: Individual self-reports could be reliable measures of sexual behavior. Additionally, prevention interventions need to address women's misperceptions about their partners' risky behaviors. [ABSTRACT FROM AUTHOR]

This study examines the associations among relationship power, sexual decision-making dominance, and condom use within a sample of women at risk of HIV/STDs. Data from face-to-face interviews with 112 women were analyzed to (a) describe who women perceive as more powerful and who makes sexual decisions within their heterosexual relationships, (b) explore the association between relationship power and sexual decision-making dominance, and (c) examine the relationship of power and decision making regarding condom use to condom use behavior. Women were recruited from clinics and community locations in Atlanta, Los Angeles, Oklahoma City and Portland, OR. Participants were 18-25 years of age and were primarily Hispanic and African American. Over half (58.2%) reported that they share power with their partner, 25.5% said they have more power, and 16.4% reported that their partner has more power in their relationship. For the five domains of sexual decision-making examined, over half (50.5%-75.7%) of the women reported that they and their partners make decisions together. A higher percentage of women who perceived that they have more power or share power, as compared to those who perceived that their partners have more power, reported that 'I/We' make decisions about birth control use, condom use, whether to have sex, and type of sexual activity. Relationship power was not associated with condom use. Condom use was, however, significantly higher among women who reported that they make decisions about using condoms alone or with their partner as compared to those who reported that their partner makes those decisions. [ABSTRACT FROM AUTHOR]

As part of a needs and assets assessment for teen pregnancy prevention, university researchers and practitioners from community-based organizations collaborated to conduct focus groups with 102 young teens of diverse racial/ethnic backgrounds. Understanding ethnic and gender similarities and differences in teen views of adolescent pregnancy helped neighborhood-based planning groups tailor their interventions to specific populations. There were many more similarities in themes than differences across both gender and racial/ethnic groups. Common themes included wanting a baby because of loneliness or a desire to be loved, wanting a baby to maintain a relationship, and viewing teen pregnancy as an unintended consequence of having sex. Differences tended to be gender based, with males viewing teen pregnancy as less of a problem than females. Implications for teen pregnancy prevention are discussed, with examples of how the information was used in a teen pregnancy prevention project in Oklahoma City. [ABSTRACT FROM AUTHOR]

Abstract Background Physical activity has been shown to reduce depression in people with coronary heart disease (CHD), however many people with CHD do not engage in sufficient levels of physical activity to reap its positive effects. People with depression and CHD are at particular risk of non-adherence to physical activity. Little is known about the barriers to and facilitators of physical activity for people with CHD and depressive symptoms. Using qualitative interviews, the aim of this study was to explore the barriers to and facilitators of physical activity for cardiac patients with depressive symptoms. Methods Fifteen participants with CHD and depressive symptoms (assessed using the Cardiac Depression Scale) participated in in-depth semi-structured interviews. The interviews were focussed on investigating participants’ experiences of physical activity since their cardiac event. Interviews were content analysed to determine major themes. Results Participants identified a number of barriers to and facilitators of physical activity. Barriers included having negative perceptions towards health and life changes as a result of the cardiac event, having low mood and low motivation to exercise, feeling physically restricted towards or fearful of exercise, lacking knowledge regarding exercise and perceiving external barriers. Facilitators included having a reason for exercising, being able to identify the psychological benefits of exercise, having positive social support and using psychological strategies. ‘Inactive’ participants reported more barriers and fewer facilitators than did ‘active’ participants. Conclusions The barriers reported in this study were highly salient for a number of participants. Health professionals and researchers can use this information to assist people with CHD and depressive symptoms to identify and possibly overcome barriers to physical activity. Relevant barriers and facilitators could be taken into account to increase their effectiveness when designing interventions to encourage physical activity maintenance in this population.

Abstract Background Cancer cachexia is a syndrome of progressive weight loss. Non-small cell lung cancer patients experience a high incidence of cachexia of 61%. Research into methods to combat cancer cachexia in various tumour sites has recently progressed to the combination of agents. The combination of the anti-cachectic agent Eicosapentaenoic acid (EPA) and the cyclo-oxygenase-2 (COX-2) inhibitor celecoxib has been tested in a small study with some benefit. The use of progressive resistance training (PRT) followed by the oral ingestion of essential amino acids (EAA), have shown to be anabolic on skeletal muscle and acceptable in older adults and other cancer groups. The aim of this feasibility study is to evaluate whether a multi-targeted approach encompassing a resistance training and nutritional supplementation element is acceptable for lung cancer patients experiencing cancer cachexia. Methods/Design Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) is an open label, prospective, randomised controlled feasibility study with two parallel arms. All patients will be treated with EPA and the COX-2 inhibitor celecoxib on an outpatient basis at the study site. In the experimental group patients will participate in PRT twice a week, followed by the ingestion of essential amino acids high in leucine. A total of 21 patients are planned to be enrolled. Patients will be randomised using 1:2 ratio with 7 patients enrolled into the control arm, and 14 patients into the treatment arm. The primary endpoint is the acceptability of the above multi-targeted approach, determined by an acceptability questionnaire. Discussion To our knowledge ACCeRT offers for the first time the opportunity to investigate the effect of stimulating the anabolic skeletal muscle pathway with the use of PRT along with EAA alongside the combination of EPA and celecoxib in this population. Trial registration Netherlands Trial Register (NTR): ACTRN12611000870954

Abstract Background Some patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels Results Both treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels Conclusions When assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels. Trial Registration (Registered at clinicaltrials.gov: Clinical trial # NCT00276484)

Abstract Background Personal Digital Assistants (PDAs) have been integrated into daily practice for many emergency physicians and house officers. Few objective data exist that quantify the effect of PDAs on documentation. The objective of this study was to determine whether use of a PDA would improve emergency medicine house officer documentation of procedures and patient resuscitations. Methods Twelve first-year Emergency Medicine (EM) residents were provided a Palm V (Palm, Inc., Santa Clara, California, USA) PDA. A customizable patient procedure and encounter program was constructed and loaded into each PDA. Residents were instructed to enter information on patients who had any of 20 procedures performed, were deemed clinically unstable, or on whom follow-up was obtained. These data were downloaded to the residency coordinator's desktop computer on a weekly basis for 36 months. The mean number of procedures and encounters performed per resident over a three year period were then compared with those of 12 historical controls from a previous residency class that had recorded the same information using a handwritten card system for 36 months. Means of both groups were compared a two-tailed Student's t test with a Bonferroni correction for multiple comparisons. One hundred randomly selected entries from both the PDA and handwritten groups were reviewed for completeness. Another group of 11 residents who had used both handwritten and PDA procedure logs for one year each were asked to complete a questionnaire regarding their satisfaction with the PDA system. Results Mean documentation of three procedures significantly increased in the PDA vs handwritten groups: conscious sedation 24.0 vs 0.03 (p = 0.001); thoracentesis 3.0 vs 0.0 (p = 0.001); and ED ultrasound 24.5 vs. 0.0 (p = 0.001). In the handwritten cohort, only the number of cardioversions/defibrillations (26.5 vs 11.5) was statistically increased (p = 0.001). Of the PDA entries, 100% were entered completely, compared to only 91% of the handwritten group, including 4% that were illegible. 10 of 11 questioned residents preferred the PDA procedure log to a handwritten log (mean ± SD Likert-scale score of 1.6 ± 0.9). Conclusion Overall use of a PDA did not significantly change EM resident procedure or patient resuscitation documentation when used over a three-year period. Statistically significant differences between the handwritten and PDA groups likely represent alterations in the standard of ED care over time. Residents overwhelmingly preferred the PDA procedure log to a handwritten log and more entries are complete using the PDA. These favorable comparisons and the numerous other uses of PDAs may make them an attractive alternative for resident documentation.

Background: There is a paucity of data on treatment of osteoporosis in patients with advanced chronic kidney disease (CKD)., Objective: To assess the risk for emergently treated hypocalcemia with denosumab by stage of CKD and presence of CKD-mineral and bone disorder (CKD-MBD)., Design: Target trial emulation., Setting: Medicare fee-for-service data with prescription drug coverage, 2012 to 2020., Participants: Female patients aged 65 years or older initiating denosumab, oral bisphosphonates, or intravenous (IV) bisphosphonates for osteoporosis., Measurements: Hospital and emergency department admissions (that is, emergent care) for hypocalcemia were assessed in the first 12 treatment weeks. Inverse probability of treatment weighted cumulative incidence and weighted risk differences (RDs) were calculated., Results: A total of 361 453 patients treated with denosumab, 829 044 treated with oral bisphosphonates, and 160 413 treated with IV bisphosphonates were identified. Risk for emergently treated hypocalcemia with denosumab versus oral bisphosphonates increased with worsening CKD stage ( P  < 0.001), with greatest risk among dialysis-dependent (DD) patients (3.01% vs. 0.00%; RD, 3.01% [95% CI, 2.27% to 3.77%]) and non-dialysis-dependent (NDD) patients with CKD stages 4 and 5 (0.57% vs. 0.03%; RD, 0.54% [CI, 0.41% to 0.68%]). Among patients with stages 4 and 5 CKD (NDD + DD), denosumab had a greater risk for emergently treated hypocalcemia versus oral bisphosphonates in those with CKD-MBD (1.53% vs. 0.02%; RD, 1.51% [CI, 1.21% to 1.78%]) than in those without CKD-MBD (0.22% vs. 0.03%; RD, 0.19% [CI, 0.08% to 0.31%]). Denosumab also showed increased risk compared with IV bisphosphonates., Limitation: Generalizability to men and non-Medicare populations., Conclusion: Risk for emergently treated hypocalcemia with denosumab increased with worsening CKD stage and was highest in DD patients and those with CKD-MBD., Primary Funding Source: U.S. Food and Drug Administration., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0013.

Importance: Dialysis-dependent patients experience high rates of morbidity from fractures, yet little evidence is available on optimal treatment strategies. Chronic kidney disease-mineral and bone disorder is nearly universal in dialysis-dependent patients, complicating diagnosis and treatment of skeletal fragility., Objective: To examine the incidence and comparative risk of severe hypocalcemia with denosumab compared with oral bisphosphonates among dialysis-dependent patients treated for osteoporosis., Design, Setting, and Participants: Retrospective cohort study of female dialysis-dependent Medicare patients aged 65 years or older who initiated treatment with denosumab or oral bisphosphonates from 2013 to 2020. Clinical performance measures including monthly serum calcium were obtained through linkage to the Consolidated Renal Operations in a Web-Enabled Network database., Exposures: Denosumab, 60 mg, or oral bisphosphonates., Main Outcomes and Measures: Severe hypocalcemia was defined as total albumin-corrected serum calcium below 7.5 mg/dL (1.88 mmol/L) or a primary hospital or emergency department hypocalcemia diagnosis (emergent care). Very severe hypocalcemia (serum calcium below 6.5 mg/dL [1.63 mmol/L] or emergent care) was also assessed. Inverse probability of treatment-weighted cumulative incidence, weighted risk differences, and weighted risk ratios were calculated during the first 12 treatment weeks., Results: In the unweighted cohorts, 607 of 1523 denosumab-treated patients and 23 of 1281 oral bisphosphonate-treated patients developed severe hypocalcemia. The 12-week weighted cumulative incidence of severe hypocalcemia was 41.1% with denosumab vs 2.0% with oral bisphosphonates (weighted risk difference, 39.1% [95% CI, 36.3%-41.9%]; weighted risk ratio, 20.7 [95% CI, 13.2-41.2]). The 12-week weighted cumulative incidence of very severe hypocalcemia was also increased with denosumab (10.9%) vs oral bisphosphonates (0.4%) (weighted risk difference, 10.5% [95% CI, 8.8%-12.0%]; weighted risk ratio, 26.4 [95% CI, 9.7-449.5])., Conclusions and Relevance: Denosumab was associated with a markedly higher incidence of severe and very severe hypocalcemia in female dialysis-dependent patients aged 65 years or older compared with oral bisphosphonates. Given the complexity of diagnosing the underlying bone pathophysiology in dialysis-dependent patients, the high risk posed by denosumab in this population, and the complex strategies required to monitor and treat severe hypocalcemia, denosumab should be administered after careful patient selection and with plans for frequent monitoring.

Introduction: In administrative data, accurate timing of exposure relative to gestation is critical for determining the effect of potential teratogen exposure on pregnancy outcomes., Objective: To develop an algorithm for identifying stillbirth episodes in the ICD-9-CM era using national Medicaid claims data (1999-2014)., Methods: Unique stillbirth episodes were identified from clusters of medical claims using a hierarchy that identified the encounter with the highest potential of including the actual stillbirth delivery and that delineated subsequent pregnancy episodes. Each episode was validated using clinical detail on retrieved medical records as the gold standard., Results: Among 220 retrieved records, 197 were usable for validation of 1417 stillbirth episodes identified by the algorithm. The positive predictive value (PPV) was 64.0% (57.3-70.7%) overall, 80.4% (73.8-87.1%) for inpatient episodes, 28.2% (14.1-42.3%) for outpatient-only episodes, and 20.0% (2.5-37.5%) for outpatient episodes with overlapping hospitalizations. The absolute difference between the dates of the algorithm-specified stillbirth delivery and the medical record-based event was 4.2 ± 24.3 days overall, 1.7 ± 7.7 days for inpatient episodes, 14.3 ± 51.4 days for outpatient-only episodes, and 1.0 ± 2.0 days for outpatient episodes that overlapped with a hospitalization. Excluding all outpatient episodes, as well as pregnancies involving multiple births, the PPV increased to 82.7% (76.8-89.8%)., Conclusions: Our algorithm to identify stillbirths from administrative claims data had a moderately high PPV. Positive predictive value was substantially increased by restricting the setting to inpatient episodes and using only input diagnostic codes for singleton stillbirths., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Concerns have been raised about prenatal exposure to magnetic resonance imaging with gadolinium-based contrast agents because of nonclinical findings of gadolinium retention in fetal tissue and 1 population-based study reporting an association with adverse pregnancy outcomes., Objective: This study aimed to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death and neonatal intensive care unit admission., Study Design: We constructed a retrospective cohort of >11 million Medicaid-covered pregnancies between 1999 and 2014 to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death (primary endpoint) and neonatal intensive care unit admissions (secondary endpoint). Medicaid claims data were linked to medical records, Florida birth and fetal death records, and the National Death Index to validate the outcomes and gestational age estimates. Pregnancies with multiples, concurrent cancer, teratogenic drug exposure, magnetic resonance imaging focused on fetal or pelvic evaluation, undetermined gadolinium-based contrast agent use, or those preceded by or contemporaneous with congenital anomaly diagnoses were excluded. We adjusted for potential confounders with standardized mortality ratio weighting using propensity scores., Results: Among 5991 qualifying pregnancies, we found 11 fetal or neonatal deaths in the gadolinium-based contrast agent magnetic resonance imaging group (1.4%) and 73 in the non-gadolinium-based contrast agent magnetic resonance imaging group (1.4%) with an adjusted relative risk of 0.73 (95% confidence interval, 0.34-1.55); the neonatal intensive care unit admission adjusted relative risk was 1.03 (0.76-1.39). Sensitivity analyses investigating the timing of magnetic resonance imaging or repeat magnetic resonance imaging exposure during pregnancy and simulating the impact of exposure misclassification corroborated these results., Conclusion: This study addressed the safety concerns related to prenatal exposure to gadolinium-based contrast agents used in magnetic resonance imaging and the risk thereof on fetal and neonatal death or the need for neonatal intensive care unit admission. Although the results on fatal or severe acute effects are reassuring, the impact on subacute outcomes was not evaluated., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Current algorithms to evaluate gestational age (GA) during pregnancy rely on hospital coding at delivery and are not applicable to non-live births. We developed an algorithm using fertility procedures and fertility tests, without relying on delivery coding, to develop a novel GA algorithm in live-births and stillbirths., Methods: Three pregnancy cohorts were identified from 16 health-plans in the Sentinel System: 1) hospital admissions for live-birth, 2) hospital admissions for stillbirth, and 3) medical chart-confirmed stillbirths. Fertility procedures and prenatal tests, recommended within specific GA windows were evaluated for inclusion in our GA algorithm. Our GA algorithm was developed against a validated delivery-based GA algorithm in live-births, implemented within a sample of chart-confirmed stillbirths, and compared to national estimates of GA at stillbirth., Results: Our algorithm, including fertility procedures and 11 prenatal tests, assigned a GA at delivery to 97.9% of live-births and 92.6% of stillbirths. For live-births (n = 4 701 207), it estimated GA within 2 weeks of a reference delivery-based GA algorithm in 82.5% of pregnancies, with a mean difference of 3.7 days. In chart-confirmed stillbirths (n = 49), it estimated GA within 2 weeks of the clinically recorded GA at delivery for 80% of pregnancies, with a mean difference of 11.1 days. Implementation of the algorithm in a cohort of stillbirths (n = 40 484) had an increased percentage of deliveries after 36 weeks compared to national estimates., Conclusions: In a population of primarily commercially-insured pregnant women, fertility procedures and prenatal tests can estimate GA with sufficient sensitivity and accuracy for utility in pregnancy studies., (© 2022 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Purpose: To develop and validate an International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM)-based algorithm to identify cases of stillbirth using electronic healthcare data., Methods: We conducted a retrospective study using claims data from three Data Partners (healthcare systems and insurers) in the Sentinel Distributed Database. Algorithms were developed using ICD-10-CM diagnosis codes to identify potential stillbirths among females aged 12-55 years between July 2016 and June 2018. A random sample of medical charts (N = 169) was identified for chart abstraction and adjudication. Two physician adjudicators reviewed potential cases to determine whether a stillbirth event was definite/probable, the date of the event, and the gestational age at delivery. Positive predictive values (PPVs) were calculated for the algorithms. Among confirmed cases, agreement between the claims data and medical charts was determined for the outcome date and gestational age at stillbirth., Results: Of the 110 potential cases identified, adjudicators determined that 54 were stillbirth events. Criteria for the algorithm with the highest PPV (82.5%; 95% CI, 70.9%-91.0%) included the presence of a diagnosis code indicating gestational age ≥20 weeks and occurrence of either >1 stillbirth-related code or no other pregnancy outcome code (i.e., livebirth, spontaneous abortion, induced abortion) recorded on the index date. We found ≥90% agreement within 7 days between the claims data and medical charts for both the outcome date and gestational age at stillbirth., Conclusions: Our results suggest that electronic healthcare data may be useful for signal detection of medical product exposures potentially associated with stillbirth., (© 2021 John Wiley & Sons Ltd.)

Importance: Idelalisib (IDEL) is approved as monotherapy in relapsed follicular lymphoma (FL) and with rituximab (IDEL+R) for relapsed chronic lymphocytic leukemia (CLL). Toxic effects can be severe and treatment-limiting. Outcomes in a real-world population are not yet characterized., Objective: We compared IDEL treatment outcomes in the clinical setting with outcomes in clinical trial data., Design, Setting, and Participants: This cohort study compared clinical trial participants treated with IDEL, aged 65 years or older, in studies 101-09 and 312-0116 with Medicare beneficiaries treated with IDEL of the same disease state and treatment regimen. Study 101-09 was a phase 2, single-group, open-label trial supporting accelerated approval of IDEL for relapsed or refractory FL. Study 312-0116 was a phase 3, multicenter, randomized, double-blind trial supporting approval of IDEL+R for relapsed CLL. Analyses were conducted between February and December 2018., Main Outcomes and Measures: Treatment duration, on-treatment and overall mortality, and serious and fatal infections were compared between trial participants and Medicare beneficiaries. Cox proportional hazards models quantified differences by cohort., Results: We identified 26 trial participants (mean [SD] age, 73 [4.9] years; 12 [46.2%] women) and 305 Medicare beneficiaries (mean [SD] age, 76 [6.9] years; 103 [54.8%] women) receiving IDEL for FL and 89 trial participants (mean [SD] age, 74 [6.0] years; 30 [33.7%] women) and 294 Medicare beneficiaries (mean age, 76 [6.3] years; 111 [37.8%] women) receiving IDEL+R for CLL. Medicare beneficiaries were older with higher comorbidity; had a shorter median treatment duration for CLL (173 days vs 473 days, P < .001) but not FL (114, days vs 160 days, P = .38); a numerically higher mortality rate (CLL: HR, 1.40; 95% CI, 0.93-2.11; FL: HR, 1.39; 95% CI, 0.69-2.78); and a significantly higher fatal infection rate per 100 person-years for CLL (18.4 vs 9.8, P = .04) and a numerically higher rate for FL (27.6 vs 18.6, P = .54), compared with trial participants. Trial participants had approximately twice as many dose reductions (CLL: 32.6% vs 18.0%; P = .003; FL: 38.5% vs 16.1%; P = .02). Among Medicare beneficiaries, a hospitalized infection within 6 months prior to IDEL initiation was associated with a 2.11-fold increased risk for on-treatment fatal infections (95% CI, 1.44-3.10). Despite a March 2016 recommendation for Pneumocystis jirovecii pneumonia prophylaxis in patients treated with IDEL, prophylaxis rates were low after March 2016 (FL: 25%, CLL: 37%)., Conclusions and Relevance: We observed substantial imbalances in baseline comorbidities and treatment outcomes between Medicare beneficiaries and trial participants aged 65 years or older. Immunosuppression-related toxic effects, including infections, may have been somewhat reduced in trials by more frequent dose reductions and exclusion of patients with ongoing infections. Selective eligibility criteria and closer monitoring of trial patients may be responsible for limited generalizability of trial data to clinical practice.

Warfarin was selected as a case study to examine confounding when comparing a product across different manufacturers because it is a narrow therapeutic index drug with prevalent beliefs for brand-name superiority. Medicare beneficiaries aged ≥65 years with atrial fibrillation and an incident outpatient warfarin prescription from July 2006 through July 2015 were included in the study population (N = 746,098). Substantial imbalances were observed between brand-name warfarin and generics for (i) clinical comorbidity, (ii) socioeconomic status, (iii) prescriber specialty, (iv) recent ambulatory and emergent care, (v) drug adherence, (vi) pharmacy setting (e.g., retail, mail-order), and (vii) risk scores for bleeding and thrombosis. Patients receiving brand-name warfarin were healthier than patients receiving generic manufactured warfarin. Utilization of generic warfarin products also differed by geographic region and pharmacy setting. Manufacturer-level comparative-safety studies for causal inference should carefully consider the presence of these imbalances and their potential for introducing healthy user bias., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

BackgroundThe safety of gadolinium-based contrast agent (GBCA) exposure during pregnancy has not been established, and the use of GBCAs during pregnancy is not recommended unless it is essential to the health of the woman or fetus.PurposeTo examine the prevalence of GBCA exposure in a large sample of pregnancies resulting in a live birth.Materials and MethodsThe Sentinel Distributed Database was used to retrospectively identify U.S. pregnancies that resulted in live births between 2006 and 2017 from 16 data partners. The main outcome was the prevalence of MRI procedures with and without GBCAs, sorted by anatomic location and trimester, among pregnant and matched comparator women.ResultsAmong 4 692 744 pregnancies resulting in a live birth, we identified 6879 exposures to GBCAs in 5457 pregnancies, representing one contrast-enhanced MRI examination per 860 pregnancies (0.12% of all pregnancies). Most contrast-enhanced MRI examinations were performed in the head ( n = 3499), although pelvic and abdominal MRI constituted 22.3% ( n = 1536) of all contrast-enhanced MRI examinations during pregnancy. The majority (70.2%) of GBCA exposures occurred during the first trimester, with a 4.3-fold greater prevalence compared with that in the second trimester and a 5.1-fold greater prevalence compared with that in the third trimester.ConclusionThis study identified higher rates of gadolinium-based contrast agent (GBCA) exposure during the first few weeks of pregnancy compared with the later weeks of pregnancy, suggesting inadvertent exposure to GBCAs might occur before pregnancy is recognized.© RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kallmes and Watson in this issue.

Letrozole is an aromatase inhibitor that has an unapproved use for ovulation induction with infertility. Because of the proximity of this use to conception, we selected letrozole to study the effect of 3 different methods for identifying the pregnancy start date and their impact on exposure misclassification. Using electronic health data from the US Sentinel database (2001-2015), we identified live-birth pregnancies conceived through in-vitro fertilization or intrauterine insemination. The pregnancy start was calculated using 1) a validated algorithm to estimate the last menstrual period (LMP), 2) LMP + 14 days (i.e., conception estimate), and 3) the fertility-procedure date. We identified 47,628 live-births after intrauterine insemination (n = 24,962) and in-vitro fertilization (n = 22,666), in which 2,458 (5.3%) mothers received letrozole. The algorithm-based conception estimate occurred within 14 days of the fertility procedure for 78.3% of pregnancies. Defining pregnancy start as LMP (45.7/1,000 pregnancies) or LMP + 14 days (12.7/1,000 pregnancies) overestimated letrozole exposure during pregnancy by 8.4-fold and 2.3-fold, respectively, compared with defining it at the date of the fertility procedure (5.5/1,000 pregnancies). While most studies of drug utilization in pregnancy use LMP as the conventional pregnancy start, this introduced substantial exposure misclassification in the example of letrozole. LMP + 14 days was less biased. Researchers should carefully consider the impact of the method for identifying the pregnancy start date on the potential for exposure misclassification.

Background: Serious and fatal deferasirox-induced kidney injury has been reported in paediatric patients. This study aimed to investigate the effects of deferasirox dose and serum ferritin concentrations on kidney function and the effect of impaired kidney function on dose-normalised deferasirox minimum plasma concentration (C min )., Methods: We did a case-control analysis using pooled data from ten clinical studies. We identified transfusion-dependent patients with thalassaemia, aged 2-15 years, who were receiving deferasirox and had available baseline and follow-up serum creatinine and ferritin measurements. Cases of acute kidney injury (AKI) were defined according to an estimated glomerular filtration rate (eGFR) threshold of 90 mL/min per 1·73 m 2 or less (if baseline eGFR was ≥100 mL/min per 1·73 m 2 ), an eGFR of 60 mL/min per 1·73 m 2 or less (if baseline eGFR was <100 mL/min per 1·73 m 2 ), or an eGFR decrease from baseline of at least 25%. Cases were matched to control visits (eGFR ≥120 mL/min per 1·73 m 2 ) on age, sex, study site, and time since drug initiation. We calculated rate ratios for AKI using conditional logistic regression, and evaluated the effect of eGFR changes on C min ., Findings: Among 1213 deferasirox-treated paediatric patients, 162 cases of AKI and 621 matched control visits were identified. Patients with AKI had a mean 50·2% (SD 15·5) decrease in eGFR from baseline, compared with a 6·9% (29·8) decrease in controls. A significantly increased risk for AKI (rate ratio 1·26, 95% CI 1·08-1·48, p=0·00418) was observed per 5 mg/kg per day increase in deferasirox dispersible tablet dose (equivalent to a 3·5 mg/kg per day dose of film-coated tablets or granules), above the typical starting dose (20 mg/kg per day). An increased risk (1·25, 1·01-1·56, p=0·0400) for AKI was also observed per 250 μg/L decrease in serum ferritin, starting from 1250 μg/L. High-dose deferasirox (dispersible tablet dose >30 mg/kg per day) resulted in an increased risk (4·47, 1·25-15·95, p=0·0209) for AKI when serum ferritin was less than 1000 μg/L. Decreases in eGFR were associated with increased C min ., Interpretation: Deferasirox can cause AKI in a dose-dependent manner. The increased AKI risk with high-dose deferasirox and lower serum ferritin concentration is consistent with overchelation as a causative factor. Small decreases in eGFR correlate with increased deferasirox C min , especially in younger patients. Physicians should closely monitor renal function and serum ferritin, use the lowest effective dose to maintain acceptable body iron burden, and interrupt deferasirox treatment when AKI or volume depletion are suspected., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S. ambulatory setting., Objective: To investigate whether entacapone is associated with prostate cancer and to assess whether the associations are correlated with advanced disease at the time of cancer diagnosis., Methods: Using data from the Department of Veterans Affairs healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014. Patients were followed on-treatment for occurrence of prostate cancer, identified via linkage to the VA cancer registry., Results: Mean follow-up time was 3.1 and 4.0 years in the entacapone and control cohort, respectively. There were 17,666 subjects meeting study criteria (mean age, 74 (SD 8.6) years); the entacapone-treated group comprised 5,257 subjects. Twenty-three prostate cancer cases occurred in the entacapone cohort and ninety-seven in the control cohort. The overall incidence of prostate cancer was 1.8 per 1,000 person-years of risk. There was no difference in risk of prostate cancer between the cohorts for increased duration of entacapone intake (adjusted HR: 1.08; 95% confidence interval: 0.46-2.51 for cumulative exposure of ≥2 years). Time since starting drug therapy and cumulative dose (mg) also do not suggest a difference in prostate cancer risk between cohorts., Conclusions: Prolonged therapy with entacapone was not associated with increased prostate cancer incidence; however, findings suggest a higher severity of prostate cancer., (Published by Elsevier Ltd.)

Purpose: To describe the utilization of drugs with pregnancy exposure registries by trimester during pregnancy, in comparison with matched nonpregnant episodes and a pre-pregnancy period., Methods: We identified live-born deliveries from women aged 10 to 54 years and matched the pregnancies 1:1 with nonpregnant episodes from a comparator cohort not delivering live-born infants, using data from 2001 to 2013 in the Sentinel Distributed Database. We evaluated the utilization of 34 drugs with pregnancy exposure registries, comparing utilization during pregnancy to the matched nonpregnant episodes, and to the 90 days before pregnancy., Results: We identified 1 895 597 pregnancies ending in live births in 1 598 697 women and 1 895 597 matched nonpregnant episodes in 1 582 581 women. We observed a lower prevalence of use for most drugs during pregnancy compared with the matched nonpregnant episodes, and the 90-day pre-pregnancy period. The median (interquartile range) prevalence ratio of use, at any time during pregnancy, for all products was 0.2 (0.1-0.3) comparing pregnant to nonpregnant episodes. Overall, there was a decrease in drug utilization by trimester; from 2.6% in the 90 days preceding pregnancy to 2.1% in the first trimester, 1.1% in the second trimester, and 0.9% in the third trimester., Conclusions: Among drugs with pregnancy exposure registries, use was less during pregnancy compared with before pregnancy and to the matched nonpregnant episodes. The lower utilization during pregnancy suggests that women may be avoiding these drugs to minimize potentially harmful exposure during pregnancy. This lower utilization may increase the challenges of further studying the safety of these drugs using pregnancy exposure registries., (Copyright © 2018 John Wiley & Sons, Ltd.)

Introduction: Pregnancy registries and spontaneous reports are essential pharmacovigilance tools to evaluate drug safety during pregnancy., Objectives: The aim of this study was to evaluate postmarket capture of exposed pregnancies., Methods: Pregnancy registries for drugs and biologics were identified in a systematic review. Through a standardized questionnaire, manufacturers provided information on (1) pregnancy registry enrollment and retention, and (2) worldwide receipt of spontaneous reports for exposed pregnancies. A validated algorithm for live-birth pregnancies allowed calculation of exposure rates per 100,000 live births using claims data., Results: Among 34 products with a pregnancy registry, median (interquartile range) registry enrollment was 36 pregnancies (5-258) and median spontaneous report capture was 450 pregnancies (89-1192). Products used in >20/100,000 live births had a median registry enrollment of 490 pregnancies and median capture of 1061 spontaneously reported exposed pregnancies. Lower median registry enrollment and spontaneous report capture was observed for products used in 0.5-20/100,000 live births (36 from registries, 541 spontaneous reports) and <0.5/100,000 live births (3 from registries, 41 spontaneous reports). Among 24 registries enrolling ≥10 pregnancies, median capture of pregnancy outcomes (e.g. live birth, spontaneous abortion) was 83.9%. For 19 registries enrolling ≥10 infants, the median proportion of infants achieving protocol-specified follow-up was 89.9% for up to 4 weeks post-birth, 75.0% for 1-5 months, and 57.1% for ≥6 months., Conclusions: Relatively higher product utilization among pregnant women predicted greater pregnancy registry enrollment. For products rarely used during pregnancy, registry enrollment was low and differences in registry enrollment compared with worldwide spontaneous report receipt were most pronounced. Products with very low utilization levels during pregnancy may require a combination of worldwide pharmacovigilance, pregnancy registries, and additional study methods to achieve adequate surveillance.

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 <1% 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. Published 2017. This article is a U.S. Government work and is in the public domain in the USA., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

Purpose: Our study sought to systematically evaluate protocol-specified study methodology in prospective pregnancy exposure registries including pre-specified pregnancy outcomes, power calculations for sample size, and comparator group selection., Methods: U.S. pregnancy exposure registries designed to evaluate safety of drugs or biologics were identified from www.clinicaltrials.gov, the FDA's Office of Women's Health website, and the FDA's list of postmarketing studies. Protocols or similar documentation were obtained., Results: We identified 35 U.S. registries for drugs or biologic use during pregnancy. All registries assessed risk for overall major congenital malformations. Pre-specified target enrollment was stated for 18 (51%) registries, and ranged from 150 to 500 exposed pregnancies (median 300). Thirty-two (91%) registries identified at least one comparison group, but only nine (26%) planned to use an internal comparator. The most common external comparator group (n = 24, 69%) was the Metropolitan Atlanta Congenital Defects Program (MACDP)., Conclusions: No registries were designed to have sufficient power to assess specific malformations, despite the plausibility that most teratogens cause specific defects. Only half of the registries included a power analysis. Despite their common use, external comparators, including MACDP, have important limitations. In the absence of randomized controlled trial data in pregnant women, pregnancy registries remain an important tool as part of a comprehensive pregnancy surveillance program; however, pregnancy registries alone may not be sufficient to obtain adequate data regarding risks of specific malformations. Published 2016. This article is a U.S. Government work and is in the public domain in the USA., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: To characterize risk of hypotension requiring admission to hospital in middle aged and older men treated with tamsulosin for benign prostatic hyperplasia., Design: Population based retrospective cohort study (between patient methodology) and self controlled case series (within patient methodology)., Setting: Healthcare claims data from the IMS Lifelink database in the United States., Participants: Men aged 40-85 years with private US healthcare insurance entering the cohort at their first dispensing for tamsulosin or for a 5α reductase inhibitor (5ARI) between January 2001 and June 2011 after a minimum of six months' enrolment., Main Outcomes Measures: Hypotension requiring admission to hospital. Cox proportional hazards models estimated rate ratios at time varying intervals during follow-up: weeks 1-4, 5-8, and 9-12 after tamsulosin initiation; weeks 1-4, 5-8, and 9-12 after restarting tamsulosin (after a four week gap); and maintenance tamsulosin treatment (remaining exposed person time). Covariates included age, calendar year, demographics, antihypertensive use, healthcare use, and a Charlson comorbidity score. A self controlled case series, having implicit control for time invariant covariates, was additionally conducted., Results: Among 383,567 new users of study drugs (tamsulosin 297,596; 5ARI 85,971), 2562 admissions to hospital for severe hypotension were identified. The incidence for hypotension was higher for tamsulosin (42.4 events per 10,000 person years) than for 5ARIs (31.3 events per 10,000 person years) or all accrued person time (29.1 events per 10,000 person years). After tamsulosin initiation, the cohort analysis identified an increased rate of hypotension during weeks 1-4 (rate ratio 2.12 (95% confidence interval 1.29 to 3.04)) and 5-8 (1.51 (1.04 to 2.18)), and no significant increase at weeks 9-12. The rate ratio for hypotension also increased at weeks 1-4 (1.84 (1.46 to 2.33)) and 5-8 (1.85 (1.45 to 2.36)) after restarting tamsulosin, as did maintenance tamsulosin treatment (1.19 (1.07 to 1.32)). The self controlled case series gave similar results as the cohort analysis., Conclusions: We observed a temporal association between tamsulosin use for benign prostatic hyperplasia and severe hypotension during the first eight weeks after initiating treatment and the first eight weeks after restarting treatment. This association suggests that physicians should focus on improving counseling strategies to warn patients regarding the "first dose phenomenon" with tamsulosin.

Purpose: We examined the association between 5α-reductase inhibitors and male breast cancer., Materials and Methods: Study participants were men 40 to 85 years old, with prescription and medical coverage, enrolled in the United States IMS LifeLink™ Health Plan claims database between 2001 and 2009. Cases required a primary breast cancer diagnosis (ICD-9-CM 175.x) on 2 different dates and a procedural code for mastectomy or lumpectomy/partial mastectomy with evidence of continuous care (radiation/chemotherapy or diagnoses in 2 or more months). Eligible controls were within 5 years in age and had duration of prior health care enrollment within 6 weeks. Risk set sampling selected 20 controls per case. We assessed the rate ratio for male breast cancer with 5α-reductase inhibitor exposure using conditional logistic regression. Analyses were stratified by duration of health care enrollment before diagnosis (1 year or more, 2 years or more and 3 years or more), each incremental 180 and 365 days of cumulative 5α-reductase inhibitor exposure, and period specific time frames before diagnosis (years 1, 2 and 3)., Results: We identified 339 breast cancer cases matched to 6,780 controls. No statistically significant associations were observed between 5α-reductase inhibitors and breast cancer regardless of exposure assessment before the index date (1 year or more-RR 0.70, 95% CI 0.34-1.45; 2 years or more-RR 0.59, 95% CI 0.24-1.48; or 3 years or more-RR 0.75, 95% CI 0.27-2.10). Each subsequent 180 days (RR 1.02, 95% CI 0.67-1.53) and 365 days (RR 1.03, 95% CI 0.45-2.37) of cumulative 5α-reductase inhibitor therapy and period specific rate ratios also showed null associations., Conclusions: The lack of an association in our study suggests that the development of breast cancer should not influence the prescribing of 5α-reductase inhibitor therapy., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers., Methods: We formed a nested cohort of men aged 40-85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011. We defined cases as men admitted to hospital for acute kidney injury, and controls were admitted to hospital with a different presenting diagnosis. Using risk-set sampling, we matched 10 controls to each case based on hospital admission, calendar time (within 6 wk), cohort entrance (within 6 wk) and age (within 5 yr). We used conditional logistic regression to assess the rate ratio (RR) for acute kidney injury with current, recent and past use of fluoroquinolones, adjusted by potential confounding variables. We repeated this analysis with amoxicillin and azithromycin as controls. We used a case-time-control design for our secondary analysis., Results: We identified 1292 cases and 12 651 matched controls. Current fluoroquinolone use had a 2.18-fold (95% confidence interval [CI] 1.74-2.73) higher adjusted RR of acute kidney injury compared with no use. There was no association between acute kidney injury and recent (adjusted RR 0.87, 95% CI 0.66-1.16) or past (RR 0.86, 95% CI 0.66-1.12) use. The absolute increase in acute kidney injury was 6.5 events per 10 000 person-years. We observed 1 additional case per 1529 patients given fluoroquinolones or per 3287 prescriptions dispensed. The dual use of fluoroquinolones and renin-angiotensin-system blockers had an RR of 4.46 (95% CI 2.84-6.99) for acute kidney injury. Our case-time-control analysis confirmed an increased risk of acute kidney injury with fluoroquinolone use (RR 2.16, 95% CI 1.52-3.18). The use of amoxicillin or azithromycin was not associated with acute kidney injury., Interpretation: We found a small, but significant, increased risk of acute kidney injury among men with the use of oral fluoroquinolones, as well as a significant interaction between the concomitant use of fluoroquinolones and renin-angiotensin-system blockers.

Background: We aimed to determine how single and combination antihypertensive therapy alters risk for diabetes mellitus (DM).Thiazide diuretics (TD), β blockers (BB), and renin-angiotensin system blockers (RASB) impact DM risk while calcium channel blockers (CCB) are neutral. DM risk associated with combinations is unclear., Methods and Results: We enrolled nondiabetic patients from Kaiser Permanente Northwest with a fasting plasma glucose (FPG) <126 mg/dL between 1997 and 2010. DM cases were defined by a FPG ≥ 126 mg/dL, random plasma glucose ≥ 200 mg/dL, HbA1c ≥ 7.0%, or new DM prescription (index date). We used incidence density sampling to match 10 controls per case on the date of follow-up glucose test (to reduce detection bias), in addition to age and date of cohort entry. Exposure to antihypertensive class was assessed during the 30 days prior to index date. Our cohort contained 134 967 patients and had 412 604 glucose tests eligible for matching. A total of 9097 DM cases were matched to 90 495 controls (median age 51 years). Exposure to TD (OR 1.54, 95% CI 1.41 to 1.68) or BB (OR 1.19, 95% CI 1.11 to 1.28) was associated with an increased DM risk, while CCB and RASB exposure was not. TD+BB combination resulted in the fully combined diabetogenic risk of both agents (OR 1.99, 95% CI 1.80 to 2.20; interaction OR 1.09, 95% CI 0.97 to 1.22). In contrast, combination of RASB with either TD or BB showed significant negative interactions, resulting in a smaller DM risk than TD or BB monotherapy., Conclusions: Diabetogenic potential of combination therapy should be considered when prescribing antihypertensive therapy.

Background: Previous studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage., Objectives: To assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20 μg (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30 μg (DRSP/EE30)., Methods: Our cohort included women aged 18-46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current)., Results: The study included 238 683 drospirenone and 193,495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10,000 women-years) vs. levonorgestrel (8.9 VTE/10,000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44-3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12-5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42-1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41)., Conclusions: We observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected., (Copyright © 2013 International Society on Thrombosis and Haemostasis.)

The October 2010 ESHRE/ASRM polycystic ovary syndrome (PCOS) workshop concluded: (1) all combined oral contraceptives (COC) appear to have equal efficacy for PCOS, (2) addition of antiandrogens (spironolactone) to COCs has little treatment benefit and (3) metformin does not improve the live-birth rate and should only be used with impaired glucose tolerance. We compared these guidelines to current practice in the United States IMS claims-database. Time-series analyses were conducted by calendar-year in women with PCOS to evaluate prescribing preferences for COCs, concomitant use of spironolactone, and utilization of metformin. Trends were analyzed with linear regression. Our cohort included 1.6 million women taking COCs, 46 780 with a PCOS claim. Drospirenone utilization increased by 1.52% (SE:0.48%, p = 0.007) per-year more in women with PCOS (4.16%, SE:0.45%, p < 0.001) than in women without PCOS (2.64%, SE:0.17%, p < 0.001)). Concomitant use of drospirenone and spironolactone was common (14.26%) and increased by 0.75% (SE:0.15%, p = 0.002) per-year. Although plasma glucose tests were unavailable, women with PCOS were more likely to take metformin than have a diabetes claim (45.8% versus 15.2%, p < 0.001), indicating some women likely receive metformin solely for PCOS. Our data suggests further attention is needed to medication management of PCOS to bridge the gap between guidelines and practice.

Background: There is an increased risk of venous thromboembolism among women taking oral contraceptives. However, whether there is an additional risk among women with polycystic ovary syndrome (PCOS) is unknown., Methods: We developed a population-based cohort from the IMS LifeLink Health Plan Claims Database, which includes managed care organizations in the United States. Women aged 18-46 years taking combined oral contraceptives and who had a claim for PCOS (n = 43 506) were matched, based on a propensity score, to control women (n = 43 506) taking oral contraceptives. Venous thromboembolism was defined using administrative coding and use of anticoagulation. We used Cox proportional hazards models to assess the relative risk (RR) of venous thromboembolism among users of combined oral contraceptives with and without PCOS., Results: The incidence of venous thromboembolism among women with PCOS was 23.7/10 000 person-years, while that for matched controls was 10.9/10 000 person-years. Women with PCOS taking combined oral contraceptives had an RR for venous thromboembolism of 2.14 (95% confidence interval [CI] 1.41-3.24) compared with other contraceptive users. The incidence of venous thromboembolism was 6.3/10 000 person-years among women with PCOS not taking oral contraceptives; the incidence was 4.1/10 000 person-years among matched controls. The RR of venous thromboembolism among women with PCOS not taking oral contraceptives was 1.55 (95% CI 1.10-2.19)., Interpretation: We found a 2-fold increased risk of venous thromboembolism among women with PCOS who were taking combined oral contraceptives and a 1.5-fold increased risk among women with PCOS not taking oral contraceptives. Physicians should consider the increased risk of venous thromboembolism when prescribing contraceptive therapy to women with PCOS.

Objective: To examine the association between isotretinoin and the risk for inflammatory bowel disease (IBD) among women of reproductive age., Design: Nested case-control study and meta-analysis., Setting: A US health claims database., Participants: We formed a cohort of women aged 18 to 46 years who had received at least 1 oral contraceptive prescription from May 1, 2001, through December 31, 2009. The IBD cases were required to have 3 health care contacts with documentation of IBD or a single health care contact followed by use of a drug to treat IBD. Twenty controls were selected for each case using incidence-density sampling, matched on age and date of diagnosis., Main Outcome Measures: Risk ratios (RRs) were formed for incident cases of IBD associated with the use of isotretinoin. A subgroup analysis examined the risk for IBD among those diagnosed as having Crohn disease (CD) and ulcerative colitis (UC). A meta-analysis of published and unpublished studies assessing isotretinoin and IBD used a random-effects model to estimate a pooled RR., Results: In the case-control study, we identified 2159 IBD cases (1056 with UC and 1103 with CD) and matched them with 43 180 controls. Only 10 cases (0.46%) and 191 controls (0.44%) were exposed to isotretinoin. The adjusted RR for IBD was 0.99 (95% CI, 0.52-1.90). The RRs for UC and CD were 1.10 (95% CI, 0.44-2.70) and 0.91 (0.37-2.25), respectively. For the meta-analysis, the pooled RR for IBD for the 5 studies was 0.94 (95% CI, 0.65-1.36)., Conclusions: The results of this study do not suggest an increase in the risk for IBD, including UC or CD, with use of isotretinoin. Because inflammatory acne in children and adolescents carries a high psychological burden, clinicians should not be discouraged from prescribing this drug owing to a putative association with IBD.

Background: Mineralocorticoids are thought to play a role in tissue repair, including fibrous tissue formation. The antimineralocorticoid activity of spironolactone has been linked to an increased risk of gastrointestinal bleeding. Drospirenone is a synthetic progestin approved in combination with ethinyl-estradiol as an oral contraceptive (OC). It is a spironolactone-derivative, and its antimineralocorticoid effects could irritate the gastrointestinal tract leading to symptoms of irritable bowel syndrome (IBS)., Methods: A retrospective cohort study was conducted evaluating women 18-46 years of age in the IMS claims-database. New-users of progestin-based OCs were identified between 1997-2009. Ninety days of OC therapy and one year of prior enrollment with no prior diagnosis of IBS were required for inclusion. Cases were identified using a previously validated method for the diagnosis of IBS. Cox proportional hazards models were used to estimate the hazard ratio (HR) for developing IBS with the different OC formulations using levonorgestrel as a reference., Results: The cohort included 939,281 women, averaging 29.1 years of age and 247 days of OC therapy. 3,050 incident cases of IBS were detected. The annualized incidence for IBS with drospirenone was 0.77% (1083 cases) while that for levonorgestrel was 0.46% (483 cases). The crude HR for development of IBS with drospirenone compared to levonorgestrel was 1.70 (95%CI 1.53-1.90), while the adjusted HR was 1.63 (95%CI 1.46-1.82). Multiple sensitivity analyses confirmed this association. Other OCs were unassociated with IBS., Conclusion: Our study found a positive association between drospirenone and a diagnosis of IBS that was not observed with other OCs.

Background: Drospirenone/ethinyl-estradiol is an oral contraceptive (OC) that possesses unique antimineralocorticoid activity. It is conjectured that drospirenone, taken alone or concomitantly with spironolactone, may be associated with an increased risk of hyperkalemia., Methods: A retrospective cohort study was conducted evaluating women between 18-46 years of age in the Lifelink™ Health Plan Claims Database. The study was restricted to new users of OCs between 1997-2009. Cox proportional hazards models were used to estimate the time to first occurrence of hyperkalemia diagnosis. The main analysis compared OCs containing drospirenone with OCs containing levonorgestrel, a second generation OC not known to impact potassium homeostasis. Logistic regression evaluated concomitant prescribing of drospirenone and spironolactone, Results: The cohort included 1,148,183 women, averaging 28.8 years of age and 280 days of OC therapy. 2325 cases of hyperkalemia were identified. The adjusted hazard ratio (HR) for hyperkalemia with drospirenone compared to levonorgestrel was 1.10 (95%CI 0.95-1.26). There was an increased risk of hyperkalemia with norethindrone HR 1.15 (95%CI: 1.00-1.33) and norgestimate HR 1.27 (95%CI: 1.11-1.46). Other OCs were unassociated with hyperkalemia. The odds of receiving spironolactone while taking drospirenone were 2.66 (95%CI 2.53-2.80) times higher than the odds of receiving spironolactone and levonorgestrel. Only 6.5% of patients taking drospirenone and spironolactone had a serum potassium assay within 180 days of starting concomitant therapy., Conclusions: A clinically significant signal for hyperkalemia with drospirenone was not demonstrated in the current study. Despite the bolded warning for hyperkalemia with joint drospirenone and spironolactone administration, physicians are actually using them together preferentially, and are not following the recommended potassium monitoring requirements in the package insert.

We developed and tested a multifaceted model of condom use intentions with cross-sectional data from 435 heterosexual women at risk for HIV/STIs. In addition to traditional intrapersonal variables drawn from established models of HIV prevention (e.g. attitudes, norms, self-efficacy), the present study examined the role of relationship factors and dynamics (i.e. relationship commitment, duration, condom use and pregnancy prevention decision-making) in shaping condom use intentions. In some cases, relationship variables were directly associated with condom use intentions. In other cases their effects on condom use intentions were mediated by intrapersonal constructs. The final model accounted for 66% of the variance in condom use intentions and confirmed the importance of integrating intrapersonal variables and relationship characteristics and dynamics in understanding women's intentions to use condoms. These results offer important insights for the design of interventions directed at promoting condom use among young women at risk for HIV/STIs and underscore the need to design prevention programs that address relationship characteristics and dynamics.

In this article, we examine the potential role that conspiracy beliefs regarding HIV/AIDS (e.g., "HIV is a manmade virus") and birth control (e.g., "The government is trying to limit the Black population by encouraging the use of condoms") play in the prevention of HIV, other STIs, and unintended pregnancies among African Americans in the United States. First, we review prior research indicating that substantial percentages of African Americans endorse conspiracy beliefs about HIV/AIDS and birth control. Next, we present a theoretical framework that suggests how conspiracy beliefs influence sexual behavior and attitudes. We then offer several recommendations for future research. Finally, we discuss the policy and programmatic implications of conspiracy beliefs for the prevention of HIV, other STIs, and unintended pregnancy.

Objective: The diaphragm, an internal barrier contraceptive device, is a candidate for a female-controlled method for preventing human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). This study's objective was to examine how women who use the diaphragm differ from women using the pill and/or condoms with respect to factors hypothesized to influence the acceptability of contraceptive methods. Our goal was to increase understanding of who finds the diaphragm acceptable and why., Methods: We conducted a cross-sectional telephone survey with selected female members of a managed care organization. For this analysis, we limited the sample to 585 women currently using the diaphragm (n = 196), pill (n = 200), condoms (n = 132), or pill and condoms (n = 57). We conducted bivariate analyses and multinomial logistic regression analyses to assess the associations between selected characteristics and diaphragm use., Results: Diaphragm use was significantly associated with several variables. Of particular interest, placing less importance on hormonal method characteristics was significantly associated with diaphragm use (versus use of the pill, condoms, or both). Placing more importance on barrier method attributes was significantly associated with diaphragm use (versus pill use, alone or with condoms). In addition, lower condom use self-efficacy was significantly associated with diaphragm use (versus condom use, alone or with pill). Lack of motivation to avoid HIV/STIs was significantly associated with using the diaphragm versus condoms (only)., Conclusion: These results have important implications for future research, interventions, counseling strategies for providers, and product development. Our findings suggest that if the diaphragm protects against HIV, it could be a desirable option for some women.

The present research consists of three studies examining the role of patients' stereotypes about health care providers in the health care decision process. Study 1 examined the association of stereotypes to health care satisfaction and help-seeking behavior among a low-income clinic sample; Study 2 examined the relationship of stereotypes to satisfaction and adherence to treatment among low-income individuals living with HIV; and Study 3 examined the association of stereotypes to satisfaction and help-seeking among a sample of homeless individuals. Overall findings indicate that individuals who held more negative stereotypes about physicians sought care less often when sick, were less satisfied with the care that they did obtain, and were less likely to adhere to physician recommendations for treatment. Moreover, African Americans, but not Whites, with more positive stereotypes reported better adherence in Study 2 and were more satisfied with their health care in Study 3. Our findings point to the need to better understand the role of patients' beliefs about health care in predicting health care satisfaction and health behaviors.

Context: Interest in the diaphragm has been growing, in part because it is a female-controlled method that might protect against HIV and other sexually transmitted diseases (STDs). A better understanding of diaphragm acceptability is needed., Methods: In 2001-2002, female members of a managed care organization were interviewed by telephone. The 215 participants, aged 19-49, who reported diaphragm use during the past three months were asked about their experience with the method and background characteristics. Characteristics associated with women's satisfaction with and consistent use of the diaphragm were identified through multiple logistic regression analysis., Results: Most participants had a low risk for HIV and other STDs. The mean duration of diaphragm use was 8.5 years. Although only 42% of participants reported consistent use in the past three months, most were satisfied with the method (79%) and planned to use it at next vaginal intercourse (85%). Satisfied users had significantly higher diaphragm use self-efficacy and more positive perceptions of the method than those not satisfied. Consistent use was significantly associated with older age and having had some college education rather than none. More than half of women cited dissatisfaction with previous methods (72%) and provider recommendation (61%) as moderately to extremely important in their decision to begin diaphragm use. When asked what they would change about the diaphragm, 32% mentioned concerns related to inserting or removing it., Conclusions: From an acceptability point of view, the diaphragm appears to be a viable candidate for a female-controlled method for prevention of HIV and other STDs. Our findings have important implications for the reintroduction of the traditional diaphragm and development of new diaphragm-like products.

Negative interactions with health care providers can have important implications for the health and health care of HIV-positive individuals. The purpose of this study was to examine perceptions of race-based and socioeconomic status (SES)-based discrimination during interactions with HIV treatment providers. We recruited 110 individuals (17% female, 51% white) living with HIV from an AIDS service organization in a midwestern city. Results indicated that the majority of participants had perceived discrimination in their interactions with providers when getting treatment for HIV. More specifically, 71% reported having experienced discrimination when receiving treatment for HIV based on their race or color, and 66% reported discrimination attributed to their socioeconomic status, position, or social class. However, participants indicated that they experienced discrimination infrequently. No significant racial/ethnic differences in reports of discrimination were observed. In addition, greater race-based and SES-based discrimination were each associated with greater levels of depression and posttraumatic stress symptoms, greater severity of AIDS-related symptoms, lower perceived general health, and less health care satisfaction. Greater SES-based discrimination was also related to lower adherence to antiretroviral medications. Our findings suggest that experiences with discrimination when getting treatment have important implications for the health and health care of HIV-positive individuals. It is important to note, however, that discrimination based on HIV status or sexual orientation was not assessed and may have affected the results. Studies that explore perceptions of discrimination based on other factors among HIV-positive individuals may improve understanding of the nature, extent, and consequences of discrimination in patient-provider interactions.