Antidepressant use in late gestation and risk of postpartum haemorrhage: a retrospective cohort study

Objective: To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH). Design: Retrospective cohort study. Tertiary teaching hospital in Adelaide, Australia. Population: A total of 30 198 women delivering between 2002 and 2008. Methods: Relative risks adjusted for maternal sociodemographics and comorbidities (aRRs) were calculated for PPH, comparing women with late-gestation exposure to antidepressants (n = 558), women with a psychiatric illness but no antidepressant use (n = 1292), and women with neither antenatal exposures (n = 28 348). Additional sensitivity analyses were undertaken, examining associations with severe PPH and postpartum anaemia. Main Outcome Measures: The primary outcome was PPH, defined as a recorded blood loss of ≥500 mL for vaginal deliveries and ≥1000 mL for caesarean sections. Secondary outcomes included severe PPH (≥1000 mL blood loss, irrespective of method of delivery), and the presence of postpartum anaemia (identified from hospital medical records). Results: Compared with unexposed controls, women exposed to antidepressants had an increased risk of PPH (aRR 1.53; 95% confidence interval, 95% CI 1.25-1.86), whereas no increased risk was observed for women with a psychiatric illness but no antidepressant use (aRR 1.04; 95% CI 0.89-1.23). In sensitivity analyses, late gestation antidepressant exposure was associated with an increased risk of severe PPH (aRR 1.84; 95% CI 1.39-2.44), as well as postpartum anaemia (aRR 1.80; 95% CI 1.46-2.22). Conclusions: Exposure to antidepressants in late gestation was associated with a significantly increased risk of PPH. Although potential confounding by unmeasured factors cannot be ruled out, these findings suggest a direct effect of antidepressant exposure on PPH.LE Grzeskowiak, R McBain, GA Dekker, VL Clifto

Interpretación errónea del concepto de entropía

Background Cetylpyridinium chloride (CPC) and sodium fluoride augment oral hygiene by inactivating bacteria and inhibiting enamel demineralisation, respectively. However, there are few reports in the literature documenting the antibacterial efficacy of their combined use in mouthrinses. We have used six experimental systems to compare the antibacterial effects of mouthrinses containing 0.075 % CPC (test rinse, TR) or 0.075 % CPC with sodium fluoride (test fluoride rinse, TFR). Results Effects against planktonic bacteria were determined using viable counting (for Streptococcus mutans and salivary bacteria), a redox dye (for Actinomyces viscosus and salivary bacteria) and viable counting (for ex vivo oral rinses). Effects against saliva-derived biofilms were quantified using confocal microscopy and differential viable counting. Inhibition of biofilm formation was evaluated by pre-treating hydroxyapatite coupons with mouthrinses prior to inoculation. Otherwise-identical controls without CPC (control rinse and control fluoride rinse, CR and CFR, respectively), were included throughout. Compared to the controls, TFR and TR demonstrated significant antimicrobial effects in the redox assays, by viable counts (>3 log reductions) and in oral rinse samples (>1.25 log reductions, p 3 log difference, p < 0.05). Overall, there were no consistent differences in the activities of TR and TFR. Conclusions Sodium fluoride did not influence the antibacterial and anti-biofilm potency of CPC-containing formulations, supporting the combined use of CPC and sodium fluoride in mouthrinses to control oral bacteria and protect tooth enamel

A Drunken Bee: Sunthorn Phu And The Buddhist Landscapes Of Early Bangkok

Although Sunthorn Phu (1786-1855) is considered the ‘Shakespeare of Thailand,’ he is still relatively unknown outside of his home country and, although he spent almost twenty years as an ordained monk, is virtually never thought of as a poet who has anything to do with Buddhism. This study takes Phu’s nirat, a classical genre of Thai journeying poetry, as a new source for excavating Thai Buddhism of the early nineteenth-century. It argues that we must expand the bounds of what we consider Buddhist literature to include popular vernacular literature such as that of Sunthorn Phu. Making use of theoretical approaches to interpreting landscape such as that of Tim Ingold and Edward Casey amongst others, this study argues for understanding Phu’s poetry as a record of a particular way of seeing and engaging with the Buddhist landscape. Phu’s nirat are taken in turn to explore particular sites - cities and rivers, Buddha footprints, temples and ruins and the forest and the ocean, respectively – in order to understand how Buddhist values inhered in and were thought through via the landscape itself. Examined in this way, a poem like Phu’s Nirat to Golden Mountain Temple can be understood as a trenchant political critique which depicts early Bangkok as a Buddhist kingdom in dharmic decline. Similarly, Phu’s nirat to the forests of Suphanburi can be understood as both a poetic treatise against practices of transformation such as alchemy as well as an oblique critique of a feudal system where one’s karmic merit is largely determined at one’s birth. Studying the nirat of Sunthorn Phu gives us a window onto the Buddhism of one particular time and place. It is Buddhism as an ongoing process of living, feeling and contesting within the bounded world of the landscape of early Bangkok

Simulating ‘that jaw drop moment’: challenging heteronormative assumptions in a novel clinical consultation skills session with undergraduate medical students

IntroductionThis paper discusses the design and impact of a clinical consultation skills session for undergraduate medicalstudents in context of diverse sexual orientation, gender identity and expression, and sex characteristics. Existingteaching approaches omit opportunities for application and skills practice. This innovation seeks to address this gap.MethodsSenior medical undergraduate students participated in actor-facilitated standardized simulated patient role-play. Thescenarios utilized a structure akin to the end of year final observed objective structured clinical examination. Plando-study-act cycles involving facilitator observation, verbal and written feedback from students and actors,confidential student evaluations, and peer evaluation contributed to session modification and improvement.FindingsThe teaching session offered students the opportunity to practice exam-style simulated patient consultations,communication and empathy skills. Improvements made following the first iteration were reflected in positivestudent evaluations in the second iteration.Discussion and ConclusionSimulated consultations using standardised scenarios represent an accepted format for medical education. Wedemonstrated it is possible to include topics that frequently give rise to discrimination and stigma from medicalprofessionals whilst maintaining expected learning outcomes. Student evaluations identify the acceptability andvalue of the topics for medical education. We present a viable option for integration into medical education

Hippocampal gabaergic inhibitory interneurons

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record In the hippocampus GABAergic local circuit inhibitory interneurons represent only ~10–15% of the total neuronal population; however, their remarkable anatomical and physiological diversity allows them to regulate virtually all aspects of cellular and circuit function. Here we provide an overview of the current state of the field of interneuron research, focusing largely on the hippocampus. We discuss recent advances related to the various cell types, including their development and maturation, expression of subtype-specific voltage-and ligand-gated channels, and their roles in network oscillations. We also discuss recent technological advances and approaches that have permitted high-resolution, subtype-specific examination of their roles in numerous neural circuit disorders and the emerging therapeutic strategies to ameliorate such pathophysiological conditions. The ultimate goal of this review is not only to provide a touchstone for the current state of the field, but to help pave the way for future research by highlighting where gaps in our knowledge exist and how a complete appreciation of their roles will aid in future therapeutic strategies.National Institute of Child Health and Human Developmen

Effects of formulation on microbicide potency and mitigation of the development of bacterial insusceptibility

Risk assessments of the potential for microbicides to select for reduced bacterial susceptibility have been based largely on data generated through the exposure of bacteria to microbicides in aqueous solution. Since microbicides are normally formulated with multiple excipients, we have investigated the effect of formulation on antimicrobial activity and the induction of bacterial insusceptibility. We tested 8 species of bacteria (7 genera) before and after repeated exposure (14 passages), using a previously validated gradient plating system, for their susceptibilities to the microbicides benzalkonium chloride, benzisothiozolinone, chlorhexidine, didecyldimethyl ammonium chloride, DMDM-hydantoin, polyhexamethylene biguanide, thymol, and triclosan in aqueous solution (nonformulated) and in formulation with excipients often deployed in consumer products. Susceptibilities were also assessed following an additional 14 passages without microbicide to determine the stability of any susceptibility changes. MICs and minimum bactericidal concentrations (MBC) were on average 11-fold lower for formulated microbicides than for nonformulated microbicides. After exposure to the antimicrobial compounds, of 72 combinations of microbicide and bacterium there were 19 ≥4-fold (mean, 8-fold) increases in MIC for nonformulated and 8 ≥4-fold (mean, 2-fold) increases in MIC for formulated microbicides. Furthermore, there were 20 ≥4-fold increases in MBC (mean, 8-fold) for nonformulated and 10 ≥4-fold (mean, 2-fold) increases in MBC for formulated microbicides. Susceptibility decreases fully or partially reverted back to preexposure values for 49% of MICs and 72% of MBCs after further passage. In summary, formulated microbicides exhibited greater antibacterial potency than unformulated actives and susceptibility decreases after repeated exposure were lower in frequency and extent

Adaptation of the methotrexate in rheumatoid arthritis knowledge questionnaire (MiRAK) for use with parents of children with juvenile idiopathic arthritis (JIA)

Background: Although Methotrexate (MTX) is one of the most commonly prescribed disease-modifying drugs in JIA no questionnaire exists that assesses the knowledge of parents about this drug. A 60-item questionnaire was recently developed to measure rheumatoid arthritis (RA) patients’ knowledge about MTX; the Methotrexate in Rheumatoid Arthritis Knowledge Test (MiRAK; Ciciriello et al. (Arthritis Rheum 62:10–1009, 2010)). This study aimed to adapt the MiRAK for parents of children with JIA. Methods: Adaption of the MiRAK involved: 1) email consultations with clinicians working in the field of paediatric rheumatology (Panel 1) to ascertain the potential adaptations of the MiRAK from a clinical perspective, 2) synthesis of clinicians’ suggestions by a panel of experts, researchers and MiRAK developers (Panel 2) to reach consensus on which items needed to be modified and create a draft Methotrexate in Juvenile Idiopathic Arthritis Knowledge Test (MiJIAK), 3) a review of the draft by 5 parents of children with JIA (Panel 3) using the cognitive ‘think-aloud’ method, 4) a second consultation with Panel 2 to review parents’ suggestions and determine the final items. Results: A total of 9 items remained unchanged, e.g. “Methotrexate is effective at relieving joint stiffness”, 19 were deemed inappropriate in the paediatric setting and deleted, e.g. “It is safe to become pregnant 3 weeks after methotrexate has been stopped”, 32 underwent editorial changes largely to indicate that the questionnaire was about the children with JIA, e.g. “If you forget to give a dose of Methotrexate, you can still take it the next day” became “If your child misses a dose of Methotrexate, they can still take it the next day”, and 1 new item was added. A new 42-item questionnaire was produced and was found to be well understood by parents of children with JIA. Conclusions: The systematic modification of the MiRAK, a patient-centred MTX knowledge questionnaire, has generated a comprehensive new questionnaire for use in the JIA setting. The wide consultation process, including cognitive testing, has ensured the tool is both relevant and acceptable to clinicians and will therefore be a valuable addition in understanding the parents’ perspective of this treatment in JIA

Formulation of Biocides Increases Antimicrobial Potency and Mitigates the Enrichment of Non-Susceptible Bacteria in Multi-Species Biofilms

The current investigation aimed to generate data to inform the development of risk-assessments of biocide usage. Stabilised domestic drain biofilm microcosms were exposed daily over six months to increasing concentrations (0.01 to 1 %) of the biocide benzalkonium chloride in simple aqueous solution (BAC-s) or in a complex formulation (BAC-f) representative of a domestic cleaning agent. Biofilms were analysed by culture, differentiating by bacterial functional group and by BAC or antibiotic susceptibility. Bacterial isolates were identified by 16S rRNA sequencing and changes in biofilm composition were assessed by high throughput sequencing. Exposure to BAC-f resulted in significantly larger reductions in viable bacteria than BAC-s, whilst bacterial diversity greatly decreased during exposure to both BAC-s and BAC-f, as evidenced by sequencing and viable counts. Increases in the abundance of bacteria exhibiting reduced antibiotic or BAC susceptibility following exposure to BAC at 0.1 % were significantly greater for BAC-s than BAC-f. Bacteria with reduced BAC and antibiotic susceptibility were generally suppressed by higher BAC concentrations and formulation significantly enhanced this effect. Significant decreases in the antimicrobial susceptibility of bacteria isolated from the systems before and after long-term BAC exposure were not detected. In summary, dose-dependent suppression of bacterial viability by BAC was enhanced by formulation. Biocide exposure decreased bacterial diversity and transiently enriched organisms with lower antimicrobial susceptibility that were subsequently supressed by exposure to 1% BAC-f, the concentration most closely reflecting deployment in formulated products

Variable effects of exposure to formulated microbicides on antibiotic susceptibility in firmicutes and proteobacteria

Microbicides are broad-spectrum antimicrobial agents that generally interact with multiple pharmacological targets. While they are widely deployed in disinfectant, antiseptic, and preservative formulations, data relating to their potential to select for microbicide or antibiotic resistance have been generated mainly by testing the compounds in much simpler aqueous solutions. In the current investigation, antibiotic susceptibility was determined for bacteria that had previously exhibited decreased microbicide susceptibility following repeated exposure to microbicides either in formulation with sequestrants and surfactants or in simple aqueous solution. Statistically significant increases in antibiotic susceptibility occurred for 12% of bacteria after exposure to microbicides in formulation and 20% of bacteria after exposure to microbicides in aqueous solutions, while 22% became significantly less susceptible to the antibiotics, regardless of formulation. Of the combinations of a bacterium and an antibiotic for which British Society for Antimicrobial Chemotherapy breakpoints are available, none became resistant. Linear modeling taking into account phylogeny, microbicide, antibiotic, and formulation identified small but significant effects of formulation that varied depending on the bacterium and microbicide. Adaptation to formulated benzalkonium chloride in particular was more likely to increase antibiotic susceptibility than adaptation to the simple aqueous solution. In conclusion, bacterial adaptation through repeated microbicide exposure was associated with both increases and decreases in antibiotic susceptibility. Formulation of the microbicide to which the bacteria had previously adapted had an identifiable effect on antibiotic susceptibility, but it effect was typically small relative to the differences observed among microbicides. Susceptibility changes resulting in resistance were not observed. IMPORTANCE The safety of certain microbicide applications has been questioned due to the possibility that microbicide exposure could select for microbicide and antibiotic resistance. Evidence that this may happen is based mainly on in vitro experiments where bacteria have been exposed to microbicides in aqueous solution. Microbicides are, however, normally deployed in products formulated with surfactants, sequestrants, and other compounds. While this may influence the frequency and extent of susceptibility changes, few studies reported in the literature have assessed this. In the current investigation, therefore, we have investigated changes in antibiotic susceptibility in bacteria which exhibited decreased microbicide susceptibility following repeated exposure to microbicides in simple aqueous solutions and in formulation. We report that the microbicide formulation had an identifiable effect on antibiotic susceptibility, but it was typically small relative to the differences observed among microbicides. We did not observe susceptibility changes resulting in resistance

The nature and prevalence of psychological problems in New Zealand primary healthcare: a report on Mental Health and General Practice Investigation ( MaGPIe)

Aims This paper describes the methods used in a study of the prevalence and types of common mental disorders among patients attending New Zealand general practices, and reports some key findings from the first phase of the study. The study also aimed to determine the degree of associated disability and other factors influencing recognition, management, course and outcome of these disorders, and subsequent papers will address these issues. Methods General practitioners (GPs) were selected randomly. In the first phase of the study, all adult attenders at each practice on selected days were administered a short questionnaire, the General Health Questionnaire (GHQ-12), which screens for psychological symptoms. The GP recorded the reasons for each consultation, and was interviewed at the end of each day about selected patients to determine their opinion about the type of psychological problems experienced. Selected patients were then visited in their own homes and an extensive interview conducted, which included the Composite International Diagnostic Interview (CIDI) to determine mental health status, the World Health Organization’s Disability Assessment Schedule (WHODAS) to determine disability, and a detailed exploration of use of health services. In the second phase of the study, patients were contacted by telephone at three, six, nine and 12 months, and both patients and GPs were re-interviewed at 12 months. Results The study achieved a very high response rate among the GPs (90%). Nearly all eligible patients (93%) completed the GHQ screening, and their response rate was 70% for the first-phase interview. GPs thought that 54% of female and 46% of male patients had experienced some level of psychological problems in the past year. GHQ screening also found that more than half of those attending their general practitioner experienced some psychological symptoms at initial screening, and the CIDI interview found that more than one in three had a diagnosable mental disorder during the past 12 months. The most common mental disorders were depressive, anxiety and substance use disorders. These disorders were more common among younger than older general practice attenders, and comorbidity was high. Conclusions Mental health problems are very common among general practice attenders. Contrary to the prevailing view that general practitioners seldom identify psychological problems in their patients, they identified about half their patients as having some type of psychological problems in the past year, although they considered that these were moderate or severe in about only one in ten patients. Further work from this large New Zealand study will focus on the nature of the relationship between disorder and disability, and on the recognition, management and outcome of psychological problems