Antibiotics and oral contraceptive failure - a case-crossover study

Background: Evidence on the association between antibiotic use and combined oral contraceptive (COC) failure is controversial. We examined the effect of concomitant antibiotic treatment on the risk of breakthrough pregnancy among COC users. Study Designs: We performed a case-crossover study of 1330 COC failure cases among 17,721 women from the Slone Epidemiology Center Birth Defects Study (1997-2008) and among 25,941 women from the National Birth Defects Prevention Study (NBDPS, 1997-2005). Self-matched odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by comparing antibiotic use between the 4 weeks before conception ("case period") and the 4-8 weeks before conception ("control period") using conditional logistic regression. A case time-control analysis was conducted using nonusers of COCs with unplanned pregnancies as controls. Results: For the combined data, the self-matched OR was 1.08 (95% CI: 0.63-1.84) and the case time-control OR was 1.12 (0.63-1.98) for antibiotics overall. The results did not appreciably differ when adjusted for characteristics that might vary between the case and control period. However, among COC failure cases from the NBDPS, allowing a 1-month gap between the case and control period resulted in a self-matched OR of 1.45 (0.85-2.50) and a case time-control OR of 1.55 (0.86-2.79) for antibiotics overall. Conclusions: We did not find an association between concomitant antibiotic use and the risk of breakthrough pregnancy among COC users. However, due to limited power and potential carryover effects, findings from this study cannot rule out an elevated risk of COC failure among antibiotic users. (C) 2011 Elsevier Inc. All rights reserved

Risk of Ischemic Cerebrovascular and Coronary Events in Adult Users of Anticonvulsant Medications in Routine Care Settings

Background: Older‐generation anticonvulsants that highly induce cytochrome P450 enzyme system activity produce metabolic abnormalities that may increase cardiovascular risk. The objective of this study was to evaluate the risk of ischemic cerebrovascular and coronary events in adult new users of anticonvulsants that highly induce cytochrome P450 activity compared with other anticonvulsant agents, as observed in a routine care setting. Methods and Results: This was a cohort study of patients 40 to 64 years old from the HealthCore Integrated Research Database who had initiated an anticonvulsant medication between 2001 and 2006 and had no recorded major coronary or cerebrovascular condition in the 6 months before treatment initiation. Propensity score (PS) matching was used to evaluate ischemic cerebrovascular and coronary risk among anticonvulsant new users. High‐dimensional propensity score (hdPS)–matched analyses were used to confirm adjusted findings. The study identified 913 events in 166 031 unmatched new treatment episodes with anticonvulsant drugs. In a PS‐matched population of 22 864 treatment episodes, the rate ratio (RR) for ischemic coronary or cerebrovascular events associated with highly inducing agents versus other agents was 1.22 (95% CI, 0.90‐1.65). The RR moved to 0.99 (95% CI, 0.73‐1.33) with adjustment for hdPS matching (RR, 1.47; 95% CI, 0.95‐2.28 for cerebrovascular events; RR, 0.70; 95% CI, 0.47‐1.05 for coronary events). Conclusions: In this exploratory analysis, there was no evidence of a consistent and statistically significant effect of initiating anticonvulsants that highly induce cytochrome P450 activity on ischemic coronary or cerebrovascular outcomes compared with other agents, given routine care utilization patterns

Association of prenatal exposure to benzodiazepines and child internalizing problems: A sibling-controlled cohort study

Background: During pregnancy, many women experience sleep problems and anxiety that require treatment. The long-term safety for the child of maternal benzodiazepine (BZD) and z-hypnotic use during pregnancy remains controversial. Method We conducted a cohort and a sibling control study using data from the Norwegian Mother and Child Cohort Study. Data on use of BZD and z-hypnotics, internalizing and externalizing outcomes, and covariates were collected from mothers at gestational weeks 17 and 30 and when children were 0.5, 1.5, and 3 years of age. The total sample consisted of 71,996 children (19,297 siblings) at 1.5 years and 55,081 children (13,779 siblings) at 3 years. Short-term use was defined as use in one pregnancy period only. Long-term use was defined as use in two or more pregnancy periods. Linear full cohort random-effect and sibling-matched fixed-effect regression models were used to compare internalizing and externalizing behavior in children prenatally exposed compared to those unexposed in the full cohort of pregnancies accounting for family clusters, as well as within sibling clusters comparing pregnancies with discordant exposures. Propensity score (PS) adjustment included variables on indication for use (sleep problems, symptoms of anxiety and depression) and other potential confounding factors. Results: Long-term prenatal exposure to BZD or z-hypnotics was associated with increased internalizing behavior in crude cohort analyses and at age 1.5 years after PS adjustment in sibling-matched fixed-effect models [β 0.60, 95% confidence interval 0.17–0.95]. Analyses on specific drug groups showed that prenatal exposure to BZD-anxiolytics was associated with increased internalizing problems at both 1.5 years [β 0.25, 0.01–0.49] and 3 years [β 0.26, 0.002–0.52] while exposure to z-hypnotics was not associated with any adverse outcomes after adjustment. Conclusion: The findings suggest a moderate association between BZD-anxiolytic exposure and child internalizing problems that is not likely due to stable familial confounding factors

Risk of spontaneous abortion and other pregnancy outcomes in 15–25 year old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom

AbstractBackgroundWe assessed the risk of spontaneous abortion (SA) after inadvertent exposure to HPV-16/18-vaccine during pregnancy using an observational cohort design.MethodsThe study population included women aged 15–25 years registered with the Clinical Practice Research Datalink General Practice OnLine Database in the United Kingdom (UK), who received at least one HPV-16/18-vaccine dose between 1st September 2008 and 30th June 2011. Exposed women had the first day of gestation between 30 days before and 45 days (90 days for the extended exposure period) after any HPV-16/18-vaccine dose. Non-exposed women had the first day of gestation 120 days–18 months after the last dose. SA defined as foetal loss between weeks 1 and 23 of gestation (UK definition).ResultsThe frequency of SA was 11.6% (among 207 exposed) and 9.0% (632 non-exposed), women: hazard ratio (HR) adjusted for age at first day of gestation 1.30 (95% confidence interval: 0.79–2.12). Sensitivity analysis per number of doses administered (−30 to +45-day risk period) showed a HR for SA of 1.11 (0.64–1.91) for 18/178 women with one dose during the risk period versus 2.55 (1.09–5.93) in 6/29 women with two doses within a 4–5 weeks period. The proportion of pre-term/full-term/postterm deliveries, small/large for gestational age infants, and birth defects was not significantly different between exposed and non-exposed women. Results were consistent using a (United States) SA definition of foetal loss between weeks 1–19 and/or the extended risk period.ConclusionThere was no evidence of an increased risk of SA and other adverse pregnancy outcomes in young women inadvertently HPV-16/18-vaccinated around gestation. Nevertheless, women who are pregnant or trying to become pregnant are advised to postpone vaccination until completion of pregnancy

Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study

Objective: To provide absolute and relative risk estimates of neonatal abstinence syndrome (NAS) based on duration and timing of prescription opioid use during pregnancy in the presence or absence of additional NAS risk factors of history of opioid misuse or dependence, misuse of other substances, non-opioid psychotropic drug use, and smoking. Design: Observational cohort study. Setting: Medicaid data from 46 US states. Participants: Pregnant women filling at least one prescription for an opioid analgesic at any time during pregnancy for whom opioid exposure characteristics including duration of therapy: short term (<30 days) or long term (≥30 days); timing of use: early use (only in the first two trimesters) or late use (extending into the third trimester); and cumulative dose (in morphine equivalent milligrams) were assessed. Main outcome measure Diagnosis of NAS in liveborn infants. Results: 1705 cases of NAS were identified among 290 605 pregnant women filling opioid prescriptions, corresponding to an absolute risk of 5.9 per 1000 deliveries (95% confidence interval 5.6 to 6.2). Long term opioid use during pregnancy resulted in higher absolute risk of NAS per 1000 deliveries in the presence of additional risk factors of known opioid misuse (220.2 (200.8 to 241.0)), alcohol or other drug misuse (30.8 (26.1 to 36.0)), exposure to other psychotropic medications (13.1 (10.6 to 16.1)), and smoking (6.6 (4.3 to 9.6)) than in the absence of any of these risk factors (4.2 (3.3 to 5.4)). The corresponding risk estimates for short term use were 192.0 (175.8 to 209.3), 7.0 (6.0 to 8.2), 2.0 (1.5 to 2.6), 1.5 (1.0 to 2.0), and 0.7 (0.6 to 0.8) per 1000 deliveries, respectively. In propensity score matched analyses, long term prescription opioid use compared with short term use and late use compared with early use in pregnancy demonstrated greater risk of NAS (risk ratios 2.05 (95% confidence interval 1.81 to 2.33) and 1.24 (1.12 to 1.38), respectively). Conclusions: Use of prescription opioids during pregnancy is associated with a low absolute risk of NAS in the absence of additional risk factors. Long term use compared with short term use and late use compared with early use of prescription opioids are associated with increased NAS risk independent of additional risk factors

Lentiviral gene therapy reverts GPIX expression and phenotype in Bernard-Soulier syndrome type C

Bernard-Soulier syndrome (BSS) is a rare congenital disease characterized by macrothrombocytopenia and frequent bleeding. It is caused by pathogenic variants in three genes (GP1BA, GP1BB, or GP9) that encode for the GPIbα, GPIbβ, and GPIX subunits of the GPIb-V-IX complex, the main platelet surface receptor for von Willebrand factor, being essential for platelet adhesion and aggregation. According to the affected gene, we distinguish BSS type A1 (GP1BA), type B (GP1BB), or type C (GP9). Pathogenic variants in these genes cause absent, incomplete, or dysfunctional GPIb-V-IX receptor and, consequently, a hemorrhagic phenotype. Using gene-editing tools, we generated knockout (KO) human cellular models that helped us to better understand GPIb-V-IX complex assembly. Furthermore, we developed novel lentiviral vectors capable of correcting GPIX expression, localization, and functionality in human GP9-KO megakaryoblastic cell lines. Generated GP9-KO induced pluripotent stem cells produced platelets that recapitulated the BSS phenotype: absence of GPIX on the membrane surface and large size. Importantly, gene therapy tools reverted both characteristics. Finally, hematopoietic stem cells from two unrelated BSS type C patients were transduced with the gene therapy vectors and differentiated to produce GPIX-expressing megakaryocytes and platelets with a reduced size. These results demonstrate the potential of lentiviral-based gene therapy to rescue BSS type C

A family-based study of the association between labor induction and offspring attention-deficit hyperactivity disorder and low academic achievement

The current study examined associations between labor induction and both (1) offspring attention-deficit hyperactivity disorder (ADHD) diagnosis in a Swedish birth cohort born 1992-2005 (n = 1,085,008) and (2) indices of offspring low academic achievement in a sub-cohort born 1992-1997 (n = 489,196). Associations were examined in the entire sample (i.e., related and unrelated individuals) with adjustment for measured covariates and, in order to account for unmeasured confounders shared within families, within differentially exposed cousins and siblings. We observed an association between labor induction and offspring ADHD diagnosis and low academic achievement in the population. However, these associations were fully attenuated after adjusting for measured covariates and unmeasured factors that cousins and siblings share. The results suggest that observed associations between labor induction and ADHD and low academic achievement may be due to genetic and/or shared environmental factors that influence both mothers' risk of labor induction and offspring neurodevelopment.NoneAccepte

Effects of the financial crisis and Troika austerity measures on health and health care access in Portugal.

Although Portugal has been deeply affected by the global financial crisis, the impact of the recession and subsequent austerity on health and to health care has attracted relatively little attention. We used several sources of data including the European Union Statistics for Income and Living Conditions (EU-SILC) which tracks unmet medical need during the recession and before and after the Troika's austerity package. Our results show that the odds of respondents reporting having an unmet medical need more than doubled between 2010 and 2012 (OR=2.41, 95% CI 2.01-2.89), with the greatest impact on those in employment, followed by the unemployed, retired, and other economically inactive groups. The reasons for not seeking care involved a combination of factors, with a 68% higher odds of citing financial barriers (OR=1.68, 95% CI 1.32-2.12), more than twice the odds of citing waiting times and inability to take time off work or family responsibilities (OR 2.18, 95% CI 1.20-3.98), and a large increase of reporting delaying care in the hope that the problem would resolve on its own (OR=13.98, 95% CI 6.51-30.02). Individual-level studies from Portugal also suggest that co-payments at primary and hospital level are having a negative effect on the most vulnerable living in disadvantaged areas, and that health care professionals have concerns about the impact of recession and subsequent austerity measures on the quality of care provided. The Portuguese government no longer needs external assistance, but these findings suggest that measures are now needed to mitigate the damage incurred by the crisis and austerity

Gestão de casos: adaptação de pacientes multimorbidos e cuidadores na Colômbia

Objective: Identify the points of consensus of decision makers, professionals, and users, regarding the fundamental aspects a Case Management Model should have in the Colombian context, to care for people with comorbidity and their family caregivers. Method: Descriptive study. Consensus decision-making among experts and convenience sampling. The Delphi method was applied in real time for two rounds. The analysis included arithmetic means to determine the most important and manageable proposals. Results: 25 experts participated in the first round and 23 in the second round. A greater consensus was obtained in: availability of economic resources to guarantee sufficient infrastructure and human resources; qualification of human resources; potentiate the figure of the nurse in case management; implementation of comprehensive health care pathways; information systems that facilitates the transition and connection of the users; plans for high engagement of social actors to promote self-management. Conclusion: The adaptation of the Case Management Model in the Colombian insurance system, allowed the identification of substantial factors to implement it in the macro, meso and micro levels of the health care system, recognized by the actors as highly fragmented.Objetivo: Identificar puntos de consenso de tomadores de decisiones, profesionales, y usuarios, frente a aspectos fundamentales que debe contener un Modelo de Gestión de Casos en el contexto colombiano, para atender personas en situación de pluripatología y sus cuidadores familiares. Método: Estudio descriptivo, Método consenso entre expertos, muestreo por conveniencia. Se realizó técnica Delphi de tiempo real en dos rondas. El análisis incluyó promedios aritméticos para determinar las propuestas más importantes y gobernables. Resultados: Participaron 25 expertos en la primera ronda y 23 en la segunda. Se obtuvo mayor consenso en: Mayor disponibilidad de recursos económicos para garantizar infraestructura y recursos humanos suficientes; cualificación de recurso humano; potenciar la figura de la enfermera gestora de casos; implementación de rutas de atención integrales; sistemas de información que faciliten el tránsito y conexión de los usuarios; planes de alta y vinculación de actores sociales para fomentar la autogestión. Conclusión: La adaptación del Modelo de GC en el sistema de aseguramiento colombiano, permitió identificar factores sustanciales para implementarlo en los niveles macro, meso y micro del sistema de salud, reconocido por los actores como altamente fragmentado.Objetivo: identificar os pontos em comum de tomadores de decisões, profissionais e usuários,perante aspectos fundamentais a considerar-se no Modelo de Gestão de Casos (MGC) no contexto colombiano, para atender as pessoas em situação de múltiplas patologias e os seus cuidadores familiares. Materiais e métodos: estudo descritivo. Método de consenso entre expertose amostragem por conveniência. Realizou0-se a técnica Delphi de tempo real em duas chances. A análise incluiu medias aritméticas para determinar as propostas mais importantes e governáveis. Resultados: participaram 25 expertos na primeira virada e 23 na segunda.Obteve-se maior consenso em: maior disponibilidade de recursos financeiros para garantir a infraestrutura e recursos humanos suficientes; qualificação do recurso humano; potenciar a figura da enfermeira gestora de casos; implementação de rotas de atendimento integrais; sistemas de informação que facilitem a transição e conexão entre os usuários; planos de alta vinculação de atores sociais para o fomento da autogestão. Conclusão: a adaptação do MGC no sistema de saúde colombiano, permitiu identificar fatores substanciais para implementá-lo nos níveis macro, intermediários e micro do sistema de saúde, reconhecido pelos atorescomo altamente fragmentado.