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Changes to the Welsh curriculum are becoming apparent. The Williams Report culminated in recommendations for schools and initial teacher education (ITE) on the inclusion and teaching of Black Asian and Minority Ethnic histories in Wales. The subsequent Welsh Government ITE action plan was designed to ensure the pro‐active recruitment of trainee teachers from Black and racially minoritised backgrounds in Wales. As a result of this legislation, a team of ITE lecturers in a school of education in a Welsh university formed a research triad and larger research collective, the idea being that we needed to decolonise our own pedagogy and curriculum delivery and re‐imagine ITE within an anti‐racist paradigm. It was key to reflect on our ITE provision, ensuring that our curriculum delivery reflected the ambition of the new Curriculum for Wales,* which encourages practitioners to think differently on what they teach, how they teach and what they want young people to learn. Using a patchwork methodology—which included 'deep thinking and deep listening'—we examined our current ITE delivery and work that has been done thus far and looked at the gains and areas for development. It became clear that staff within our 'ITE research collective' were becoming more knowledgeable and confident in working within a racial dynamic, and consequently felt more able to impart knowledge when engaging with other ITE colleagues and students. This paper charts our ongoing journey and makes recommendations gained from our experiences. [ABSTRACT FROM AUTHOR]

Background: Whereas symptomatic endometriosis may affect work performance, the impact of endometriosis in the general community is not known. Aims: The associations between endometriosis and each of sick leave and work ability, were investigated in a large sample of non‐healthcare seeking women. Materials and Methods: This community‐based, cross‐sectional study recruited 6986 women, aged 18–39 years, from three eastern states of Australia between 11 November 2016 and 21 July 2017. Women were identified as having endometriosis if they had undergone a pelvic ultrasound and reported a diagnosis of endometriosis. Working women completed the Work Ability Index. Results: Participants were predominantly of European ancestry (73.1%) and 46.8% were overweight or had obesity. The prevalence of endometriosis was 5.4% (95%CI 4.9–6.0%) with the highest prevalence of 7.7% (95%CI 6.5 to 9.1%) for women aged 35–39 years. Among the 4618 working women, those with endometriosis had significantly more sick days from work (33.6% reported ≥10 days vs 13.5%, overall χ2P < 0.001). Endometriosis was associated with a greater likelihood of poor to moderate work ability, after adjusting for age, body mass index, ethnicity, relationship status, student status, insecure housing, being a carer for another person, parity, ever use of assisted reproductive technologies, and depressed mood (odds ratio 1.90, 95%CI 1.40–2.58, P < 0.001). Conclusions: This study provides new evidence that the negative impact of endometriosis on work attendance and work ability is not limited to women with prevalent symptoms and severe disease, but appears to encompass women across a broader spectrum of this condition in the community. [ABSTRACT FROM AUTHOR]

Objective: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain‐predicted age difference (brain‐PAD). Design: Prospective cohort study using data from NEURO and Sex Hormones in Older Women; substudies of the ASPirin in Reducing Events in the Elderly clinical trial. Patients: Community‐dwelling older women (aged 70+ years). Measurements: Oestrone, testosterone, dehydroepiandrosterone (DHEA), and sex‐hormone binding globulin (SHBG) were quantified from plasma samples collected at baseline. T1‐weighted magnetic resonance imaging was performed at baseline, 1 and 3 years. Brain age was derived from whole brain volume using a validated algorithm. Results: The sample comprised of 207 women not taking medications known to influence sex hormone concentrations. A statistically higher baseline brain‐PAD (older brain age relative to chronological age) was seen for women in the highest DHEA tertile compared with the lowest in the unadjusted analysis (p =.04). This was not significant when adjusted for chronological age, and potential confounding health and behavioural factors. Oestrone, testosterone and SHBG were not associated with brain‐PAD cross‐sectionally, nor were any of the examined sex hormones or SHBG associated with brain‐PAD longitudinally. Conclusion: No strong evidence of an association between circulating sex hormones and brain‐PAD. Given there is prior evidence to suggests sex hormones may be important for brain ageing, further studies of circulating sex hormones and brain health in postmenopausal women are warranted. [ABSTRACT FROM AUTHOR]

Objective: To explore the associations between endogenous testosterone blood concentrations and muscle mass, strength and performance in community dwelling women. Design, Patients and Measurements: Online databases, including Ovid MEDLINE, EMBASE and Web of Science, were searched for observational studies, with at least 100 female participants, reporting associations between endogenous testosterone blood concentrations and muscle mass, strength and performance. The findings were synthesized in a narrative review. Heterogeneity in study design and analysis precluded a meta‐analysis. Results: Of the 36 articles retrieved for full‐text review, 10 met the inclusion criteria. Eight studies were cross‐sectional, 1 longitudinal and 1 provided both cross‐sectional and longitudinal data. Testosterone was measured by liquid chromatography‐tandem mass spectrometry in two studies and by immunoassay in 8. An association between total testosterone and muscle mass, strength or performance in women was not found. The studies of calculated free or bioavailable testosterone and lean muscle mass reported a positive association, but no association was reported for muscle strength or performance. Each included study was limited by a high risk of bias in at least one assessed domain. Conclusions: This review does not support an association between testosterone and muscle mass, strength or performance in women. This, together with the reported associations between free or bioavailable testosterone and muscle mass should be interpreted cautiously due to the predominant use of immunoassay and the inaccuracy of calculated variables. Additionally, biological significance of nonprotein bound testosterone has not been established. Further studies examining the relationship between precisely measured testosterone and muscle mass and function in women are required. [ABSTRACT FROM AUTHOR]

There are a disproportionate number of teachers of colour (ToC) in Wales in comparison to pupils of colour. Teachers are less ethnically diverse than the pupils they are teaching with only 1.3% of teachers categorising themselves as being from a non‐White background. This paper sets out findings from research investigating recruitment into Initial Teacher Education (ITE) and the career progression of ToC in Wales. Through a qualitative case study approach, employing participant voice, it gives participants a platform to articulate their experiences. Sixty‐eight semi‐structured interviews took place and participants were a mixture of 14+ learners and serving teachers/leaders, all from diverse backgrounds. As a multi‐ethnic research team ourselves, we were aware of issues that participants faced within the Welsh school system, either as pupils or teachers, and were committed to carrying out the research, employing an empathetic lens. This was especially relevant as participants were relaying incidents of racism and racial trauma suffered, as well as sharing their achievements. This provided us with rich data, detailing lived experience and gave an insight into the unique experiences of teachers of colour, within a predominantly White school system in Wales and as a result, suggests what needs to change. [ABSTRACT FROM AUTHOR]

Yet despite readily available, safe menopausal hormone therapy (MHT) and non-hormonal interventions, over 85% of Australian women with bothersome symptoms are not receiving effective, approved therapy.[5] Although over 50% of post-menopausal women have vulvovaginal atrophy symptoms (vaginal dryness, itching, burning, dyspareunia, and urinary symptoms), fewer than 7% are prescribed effective, safe vaginal oestrogen therapy.[5] Menopause causes accelerated net bone loss. Keywords: Menopause; Hormones; Osteoporosis EN Menopause Hormones Osteoporosis 500 502 3 06/20/23 20230615 NES 230615 Lack of clinician knowledge, poor access to services, negative attitudes, and lagging research have led to substandard menopause-related health care The menopause is the permanent loss of ovarian reproductive function. New treatment options in menopausal therapy Meanwhile, treatment options and recommended prescribing have changed. Specialist menopause clinics or accredited menopause practitioners may improve access to treatment, particularly for women with complex care needs. [Extracted from the article]

Objectives: The Centers for Medicare and Medicaid Services Severe Sepsis and Septic Shock Management Bundle (SEP‐1) assesses antibiotic administration, lactate measurement, and blood culture collection within 3 h of severe sepsis onset. The impact of the SEP‐1 3‐hour bundle among patients with severe sepsis is not extensively described. This investigation aimed to describe the impact of 3‐hour bundle compliance on 28‐day in‐hospital mortality in patients with severe sepsis. Study Design: This was a retrospective, propensity adjusted, nested case‐control study assessing the impact of compliance with a 3‐hour sepsis bundle among patients with severe sepsis. Setting: This study was conducted at a large, academic, tertiary care medical center in Detroit, Michigan from July 1, 2017 to December 31, 2019. Patients: Cases were defined as those suffering 28‐day in‐hospital mortality. Controls were defined as those surviving at or discharged by 28 days. Patients were separated based on 3‐hour bundle compliance or noncompliance. Nested and overall cohorts were assessed. Severe sepsis time zero was manually validated. Patients with shock, requiring vasopressors within 8 h of time zero, or those not meeting SEP‐1 inclusion criteria were excluded. Intervention: The primary outcome was the propensity adjusted odds of 28‐day in‐hospital mortality among 3‐hour bundle compliant versus noncompliant patients. Secondary outcomes included mortality for individual bundle element compliance, progression to septic shock, and predictors of mortality according to logistic regression. Results: A total of 325 compliant and 325 noncompliant patients were included. The median Sequential Organ Failure Assessment (SOFA) score was three in each group. There was no difference in propensity adjusted odds of mortality among those compliant versus noncompliant with the 3‐hour bundle (odds‐ratio [OR] 1.039; 95% CI: 0.721–1.497; p = 0.838) or with individual bundle elements. SOFA score and female sex were predictors of mortality. Conclusions: Three‐hour bundle compliance did not impact 28‐day in‐hospital mortality in patients with severe sepsis. Further research is needed to understand the impact of 3‐hour bundle compliance on mortality in severe sepsis. [ABSTRACT FROM AUTHOR]

Over half of antimicrobials ordered at hospital discharge are not optimized, many of which having longer than necessary durations or inappropriate for the indication. Unnecessary antimicrobial exposures increase the risks of adverse events, antibiotic resistance, and Clostridioides difficile infections. However, discharge prescribing often escapes the purview of inpatient antimicrobial stewardship programs and few interventions have been implemented to optimize antibiotic use during transitions of care (TOC). Herein, the aim was to highlight critical steps and challenges in the implementation of a TOC antimicrobial stewardship program designed to improve prescribing at hospital discharge. In a five‐hospital health system, a pharmacist‐led intervention was implemented during TOC, with the objective of improving oral antibiotic selection and duration. Among a multidisciplinary team of physicians, case managers, and nurses, the pharmacists engaged in three strategies: (a) early identification of patients to be discharged on oral antibiotics; (b) collaborative planning and communication regarding guideline‐recommended antibiotic selection and duration; and (c) facilitation of discharge antibiotic prescription with appropriate stop date. Barriers to completing the intervention on each patient in this experience included: timely identification of eligible patients prior to discharge, stewardship periods of reduced staffing during evenings and weekends, and onboarding of new staff and trainees to the process. Other major challenges that stewardship and pharmacy departments will face include adoption of best‐practice guidelines for discharge, obtaining support from local physician champions, extending the intervention to various service lines and departments with limited resources, and engaging stakeholders to support the program and intervention. This experience demonstrated that pharmacist‐led antimicrobial stewardship at discharge can be successful in both academic and community settings. [ABSTRACT FROM AUTHOR]

Although FHA may be transient, it has been demonstrated to have lasting impacts, including low bone mineral density25 and an increased association with angiographic coronary artery disease.26 Bone mineral density and vitamin D levels should be measured in all women who have had 6 months of amenorrhoea, or less if nutritional depletion is likely to have preceded the amenorrhoea. Given the potential adverse physical health outcomes associated with secondary amenorrhoea due to any cause, combined with the psychological consequences of delayed diagnosis as well as misdiagnosis, it is important that women with secondary amenorrhoea are fully assessed when they first present. As bone loss may commence after 6-12 months of amenorrhoea, hormone therapy in the form of oestrogen replacement with cyclic or continuous progestogen therapy should be commenced, to prevent bone loss if menstruation has not resumed within 6 months of appropriate intervention. Keywords: Bone diseases, endocrine; Hormone replacement therapy; Hormones; Pituitary hormones; Menstrual disorders; Gynecology EN Bone diseases, endocrine Hormone replacement therapy Hormones Pituitary hormones Menstrual disorders Gynecology 73 76 4 02/09/22 20220201 NES 220201 Functional hypothalamic amenorrhoea is common but often misdiagnosed, risking inappropriate management and compromised patient education and counselling Secondary amenorrhoea before the age of 45 years, not due to pregnancy or lactation, lasting over 3 months in a previously eumenorrhoeic woman, or 6 months if menses have been irregular,1 is a cause for concern. [Extracted from the article]

Workplace policies regarding women's reproductive and menopausal health are garnering global attention. The peri‐ and post‐menopause stages may be turbulent times for many women, with some experiencing debilitating symptoms and some none at all. While the symptoms of menopause should be recognised by employers due to their various impacts, the implementation of policies that pertain to all women can alienate older female workers by creating prejudice surrounding work capability. This piece identifies other avenues for the inclusion of menopausal symptoms through pre‐existing policy and highlights the issues facing menopausal women in this current age. [ABSTRACT FROM AUTHOR]

Purpose To create a curriculum innovation for early preclinical medical students to explore personal perspectives by listening to and learning from the lived experience of community‐living older adults. Method: Tell Me Your Story (TMYS) paired first‐year medical students (MS1s) with community‐dwelling older adult partners (OAPs) residing in the independent living portion of a continuing care retirement community (CCRC) for a half‐day educational experience. MS1s conducted 1‐hour semi‐structured interviews with their OAP and then formed small groups with geriatric faculty members to explore experiences and views that were either reinforced or challenged. The authors evaluated the effectiveness of this exercise using post‐activity surveys. A mixed‐methods analysis of 7 years of data (2013–2019) was conducted. Results: TMYS had 1251 MS1 participants from 2013 to 2019. Students completed 1052 surveys for a response rate of 84%. During the semi‐structured interview with OAP, the frequency of issues discussed included relationships (94%), professionalism/art of medicine (91%), healthcare accessibility (83%), death/dying/grieving/loss (72%), nutrition (69%), ethics (64%), and cultural competence (61%). Exactly 97% (n = 1023) responded that the overall organization was "good, very good or excellent." The most prominent themes identified by student responses highlighted person‐centered care, patient perspective, life experience/personal stories, and doctor–patient relationship. Fifty‐three faculty members completed the post‐program survey. Exactly 100% (53/53) rated the quality of this exercise as an educational experience high. Conclusion: TMYS was highly valued by students and provided an important experiential learning activity in preclinical medical education. Themes related to person‐centered care emerged from the intervention. [ABSTRACT FROM AUTHOR]

Objective: To document associations between anti‐Müllerian hormone (AMH) and circulating androgens in nonhealthcare‐seeking premenopausal women. Design: Community‐based, cross‐sectional study. Setting: Eastern states of Australia. Participants: Women aged 18–39 years not using systemic hormones, not pregnant or breastfeeding within 3 months, and not postmenopausal. Measurements: AMH, measured by the Beckman Access 2, 2 site immunometric assay from fresh samples, and testosterone, androstenedione, dehydroepiandrosterone (DHEA) and 11‐oxygenated C19 steroids, measured by liquid chromatography–tandem mass spectrometry. Results: Data were available for 794 women, median age of 33 years (range: 18–39). 76.1% were of European ancestry and 48.2% were parous. Serum AMH was positively associated with testosterone (rho =.29, p <.001) androstenedione (rho =.39, p <.001) and DHEA (rho =.10, p =.005) but not 11‐ketoandrostenedione or 11‐ketotestosterone. When adjusted for age, body mass index and smoking, using quantile regression, independent positive associations remained between AMH and testosterone (β coefficient: 20.90, 95% confidence interval [CI]: 13.79–28.03; p <.001) and androstenedione (β coefficient: 5.90, 95% CI: 3.76–8.03; p <.001). The serum concentration of testosterone was greater at the top AMH quintile than other quintiles (0.56 nmol/L [range: 0.21–1.90] vs. 0.36 nmol/L [range: 0.13–0.87]; p =.001) in women with self‐reported polycystic ovary syndrome. Conclusions: The positive associations between serum testosterone and androstenedione and AMH in premenopausal women is consistent with androgens directly or indirectly influencing AMH production during follicular development. As the highest AMH concentrations are most likely to be seen in women with multifollicular ovaries, it would be expected that women with multifollicular ovaries would have higher serum testosterone. Therefore, whether hyperandrogenemia and multifollicular ovaries should be considered independent characteristics of polycystic ovary syndrome warrants review. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of two anti‐Mullerian (AMH) assays over a range of concentrations, in samples collected from young women. Design: A cross‐sectional method‐comparison study of 168 non‐healthcare‐seeking women. Participants: Included women were aged 18–39 years, not recently pregnant, breast feeding or using systemic hormones. Measurements: Serum AMH levels were analysed with the Beckman Coulter Access 2 assay from fresh samples and the Ansh picoAMH assay using samples stored at −80°C, in a parallel setting. Comparisons between the two assays were examined using Bland‐Altman plots. Results: Participants had a mean ± SD age of 32.6 ± 5.4 years and body mass index of 28.1 ± 7.9 kg/m2, and 60.1% were parous. Although the assay results were highly correlated (Spearman correlation.982, P <.001), the relationship between the assays was nonlinear. Serum AMH values below 4 pmol/L were lower with the picoAMH assay compared with the Access AMH assay (mean difference in this range was −0.49 pmol/L), but for samples with a mean value above 10 pmol/L, the picoAMH assay consistently measured higher than the Access AMH assay (mean difference in this range was +8.2 pmol/L). As AMH concentrations increased the absolute discrepancy between the assays also increased. Conclusions: This study demonstrates that despite the high correlation between two commercially available AMH assays, the assays performed in a discordant manner at high and low concentrations. Hence, the results of these assays are not interchangeable, highlighting the need to establish specific reference limits for individual assays to guide clinical decision‐making and the challenge of establishing future universal cut‐offs for the application of AMH levels in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To assess economic and social drivers of dispensing antibiotics without prescription by community pharmacies in Nepal. Method: A survey was conducted among 111 pharmacy owners and managers in five districts. Information on demographic and economic characteristics of the pharmacies (e.g. revenue and profits from antibiotics) and their inclination to sell antibiotics without a physician's prescription under various scenarios (e.g. diarrhoea in a child) was collected. Univariate analysis was conducted to assess the demographic and economic characteristics. Bivariate analysis was conducted to examine the relationship between dispensing antibiotics without prescription and economic and social factors. Results: Azithromycin and amoxicillin were the most commonly dispensed antibiotics. The proportions of pharmacies reporting that they would 'most likely' or 'likely' dispense antibiotics without prescription to adult patients ranged from 36.9% (sore throat) to 67.6% (cough). The proportions for paediatric patients ranged from 62.2% (sore throat) to 80.2% (cough or diarrhoea). There was no consistent relationship between the likelihood of dispensing antibiotics and revenues, profits or the number of patients. Instead, dispensing behaviour was influenced by the pressure from the patient; the respondents were more likely to dispense antibiotics when the patient specifically asked for 'an antibiotic' rather than for 'a medicine', and 68.5% respondents ranked 'customer satisfaction' as the most important factor motivating their work. Conclusions: In Nepal, inappropriate sale of antibiotics by community pharmacists is high, particularly for paediatric patients. Additional research is needed to establish key drivers of this behaviour and to help design effective approaches to reducing AMR. [ABSTRACT FROM AUTHOR]

Objective: Sex steroid levels in women vary with increasing age from the age of 70 years (70+). Whether this reflects change within individuals with age or a survival advantage is not known. This study aimed to determine the stability of circulating sex steroids and SHBG over time in individual women aged 70+. Design: A prospective cohort study. Participants: 400 women, aged 70+ not using any sex steroid, anti‐androgen/oestrogen or glucocorticoid therapy. Main outcome measurements: Sex steroid concentrations, measured by liquid chromatography‐tandem mass spectrometry and sex hormone‐binding globulin (SHBG) by immunoassay, in paired blood samples drawn 3 years apart and analysed together. Results: 400 women, median (IQR) age 78.0 (8.6) years, were included in the analysis. Mean testosterone concentrations were statistically significantly higher in follow‐up samples compared with baseline. The change was modest (mean change 31 pmol/L, 95% confidence interval (CI) 2.4–59.8; p =.034), and an increase was not observed in all women. There was a statistically significant decline in mean body mass index (mean change −0.4 kg/m2, 95% CI 0.6 to −0.3; p <.001) and a significant increase in the mean serum SHBG concentration (mean change 4.0 nmol/L, 95% CI 2.7–5.4; p <.001). The change observed in testosterone was not explained by the observed change in SHBG. There was no significant change in the mean oestrone or dehydroepiandrosterone concentration. Conclusions: Testosterone concentrations in women aged 70+ were more likely to increase than decrease. Whether increasing testosterone concentrations in older women confer a survival advantage needs investigation. [ABSTRACT FROM AUTHOR]

Recommended Revisions to the National SEP-1 Sepsis Quality Measure: A commentary by the Society of Infectious Diseases Pharmacists on the Infectious Diseases Society of America Position Paper Keywords: sepsis; infectious diseases; septic shock EN sepsis infectious diseases septic shock 368 371 4 04/14/20 20200401 NES 200401 Following recent revisions to the U.S. Centers for Medicare & Medicaid Services Sepsis and Septic Shock Early Management Bundle (SEP-1) reporting requirement, the Infectious Diseases Society of America (IDSA) led a group of invested stakeholder organizations to develop a position paper of recommended revisions to further improve SEP-1. In addition to these specific comments on the recommendations from IDSA, SIDP also recommends general improvements in broad-spectrum antibiotic administration in patients with septic shock. [Extracted from the article]

Background: Although serum ferritin is considered a reliable indicator of iron stores, there are few data documenting the prevalence of low ferritin in representative samples of young women. Aims: To estimate the prevalence of low ferritin and to identify factors associated with low ferritin in young Australian women. Methods: Women, aged 18–39 years, living in the eastern states of Australia were recruited by email to a cross‐sectional, online questionnaire‐based study between November 2016 and July 2017. Participants not pregnant, breast feeding, taking hormonal contraception, using assisted reproduction or postmenopausal were invited to provide a blood sample. Results: Of the 3689 invited participants, 761 (23.1%) provided a sample and 736 women, mean (SD) age 31.7 (±5.6) years, were included in the analyses. The overall prevalence of serum ferritin <30 μg/L was 34.8% (95% confidence interval (CI) 31.4–38.3%), with 41.4% (35.1–48.0%) in NSW, 31.5% (26.4–37.1%) in Victoria and 32.6% (26.8–39.0%) in Queensland. Serum ferritin <30 μg/L was positively associated with the reporting of >2 days of heavy menstrual bleeding (adjusted odds ratio (AOR) 1.73, 95% CI 1.15–2.59), living in New South Wales (AOR 1.57, 95% CI 1.07–2.30), not working outside home (AOR 1.58, 95% CI 1.01–2.49), and inversely associated with never experiencing heavy menses (AOR 0.46, 95% CI 0.23–0.93) and obesity (AOR 0.32, 95% CI 0.21–0.50). Conclusions: This study demonstrates that serum ferritin below 30 μg/L is common amongst young Australian women. Healthcare professionals should note the association between low ferritin and heavy bleeding. [ABSTRACT FROM AUTHOR]

Optimal antimicrobial therapy for Enterococcus faecium bloodstream infection (EFBSI) in the solid organ transplant (SOT) population is not well defined. The purpose of this study was to describe the pharmacotherapy and outcomes of EFBSI in SOT patients. This was a single‐center retrospective cohort of SOT patients with EFBSI from 2013 to 2019. Susceptibility testing was performed with Vitek® 2 or Etest. Estimates of optimal DAP pharmacokinetic/pharmacodynamic exposures (dose <10 mg/kg, fAUC/MIC >27.4) were made from previously established literature and equations. Fifty‐one unique cases were included in the analysis. The median age was 61 years and liver (64%), intestinal (19%), and kidney (12%) were the most common organs transplanted. Most patients had indwelling central lines (75%) at the time of bacteremia; intra‐abdominal abscesses/fluid collections were present in 44% of patients and 8% had endocarditis. Nineteen (37%) patients had polymicrobial infections. The most common definitive antimicrobial regimens were as follows: DAP plus beta‐lactam (46%), DAP monotherapy (18%), and LZD (25%). Of the 33 patients that received DAP, 21% of E faecium isolates developed DAP resistance. 30‐day mortality was 25% overall but higher in patients who received an initial DAP dose <10 mg/kg (43% vs 13%). Vancomycin‐resistance, severity of illness, neutropenia, and source control were also associated with mortality. Inadequate DAP dosing for EFBSI may be associated with mortality in the SOT population. Larger, controlled analyses are necessary to determine the impact of optimized pharmacodynamics in this population. [ABSTRACT FROM AUTHOR]

Background: GATA‐binding protein 4 (GATA4) and Friend of GATA 2 protein (FOG2, also known as ZFPM2) form a heterodimer complex that has been shown to influence transcription of genes in a number of developmental systems. Recent evidence has also shown these genes play a role in gonadal sexual differentiation in humans. Previously we identified four variants in GATA4 and an unexpectedly large number of variants in ZFPM2 in a cohort of individuals with 46,XY Differences/Disorders of Sex Development (DSD) (Eggers et al, Genome Biology, 2016; 17: 243). Method: Here, we review variant curation and test the functional activity of GATA4 and ZFPM2 variants. We assess variant transcriptional activity on gonadal specific promoters (Sox9 and AMH) and variant protein–protein interactions. Results: Our findings support that the majority of GATA4 and ZFPM2 variants we identified are benign in their contribution to 46,XY DSD. Indeed, only one variant, in the conserved N‐terminal zinc finger of GATA4, was considered pathogenic, with functional analysis confirming differences in its ability to regulate Sox9 and AMH and in protein interaction with ZFPM2. Conclusions: Our study helps define the genetic factors contributing to 46,XY DSD and suggests that the majority of variants we identified in GATA4 and ZFPM2/FOG2 are not causative. [ABSTRACT FROM AUTHOR]

Background: In Australia many hormonal contraceptives are not Pharmaceutical Benefits Scheme (PBS) supported, hence the use of different formulations have not been quantified. Objectives: To document the use of hormonal contraceptives and factors associated with their use. Materials and methods: Cross‐sectional, online questionnaire‐based study of 6986 Australian women, aged 18–39 years, recruited by email invitation from two large, representative databases. Main outcome measures were the prevalence of use of hormonal contraceptives and associated socio‐demographic characteristics. Results: Of the 6600 potential hormone contraceptive users, 43.2% were current users. Most (63.6%) reported using a combined oral contraceptive (COC) of which 30.9% were non‐PBS‐supported anti‐androgenic progestin‐containing COCs. Use of long‐acting reversible contraceptives (LARC) or an injectable contraceptive was reported by 26.8%. Education beyond secondary school, being Australian born, rural residency, normal body mass index, age <25 years and nulliparity were significantly associated with hormonal contraceptive use. Women who reported polycystic ovary syndrome or acne were more likely to be taking a third or fourth generation COC (P < 0.0001) and endometriosis was significantly associated with intrauterine system (IUS) use. Third or fourth generation COC use was reported by 12.1% of obese, current smokers. Conclusion: An estimated one‐third of Australian women aged 18–39 are taking a non‐PBS‐supported anti‐androgenic progestin COC, highlighting inequity in access to COC options. That hormonal contraceptive use is higher in rural areas is a novel finding and the proportion of LARC or injectable use suggests that uptake in Australia is higher than previously reported. [ABSTRACT FROM AUTHOR]

Study Objective: Ceftarolinefosamil is a cephalosporin with broad clinical utility; however, limited data suggest that prolonged ceftaroline exposure may be associated with neutropenia. The objective was to determine drug and patient factors associated with neutropenia in patients receiving ceftaroline or ceftriaxone for deep‐seated infections. Design: Retrospective, ratio‐matched cohort study. Setting: Four acute‐care hospitals within an urban health care system. Patients: A total of 176 hospitalized adults who received definitive ceftaroline (44 patients) or ceftriaxone (132 patients) therapy for at least 7 days between January 2013 and April 2017 for any of the following indications: bone and joint infections (BJI), infective endocarditis (IE), or bloodstream infections (BSI). Measurements and Main Results: The primary outcome was development of neutropenia while receiving cephalosporin therapy, defined as an absolute neutrophil count (ANC) <1500 cells/mm3. Neutropenia severity and patient characteristics were described and compared between the ceftaroline and ceftriaxone groups. The median (interquartile range [IQR]) antibiotic prescription duration was 41 (29–44) days for the ceftaroline group and 40 (28–44) days for the ceftriaxone group (p=0.9). Cephalosporin indications were 112 (64%) BJI, 27 (15%) BSI, 16 (9%) IE, and 21 (12%) multiple infections; ceftaroline was more commonly used in BJI (p=0.03), and ceftriaxone was more commonly used in IE (p=0.01). Neutropenia developed in 16 (9%) patients: 8 (18%) in the ceftaroline group and 8 (6%) in the ceftriaxone group (p=0.03). Median (IQR) onset to neutropenia was 22 (15–28) days, and median (IQR) change in ANC was 2.86 (1.50–4.08) cells/mm3; most cases of neutropenia were mild (12 patients [75%]). The median (IQR) time to mild or moderate‐severe neutropenia was not significantly different (p=0.68): 22 (14–28) and 22 (21–36) days, respectively. Treatment was discontinued in 4 (25%) patients due to neutropenia. Ceftaroline use was independently associated with neutropenia (adjusted odds ratio 3.2, 95% confidence interval 1.2–10.5) after adjusting for lower body mass index strata (18.5–25 kg/m2). Conclusion: Prolonged ceftaroline use was an independent risk factor for developing mild neutropenia. Clinicians should be cognizant of ANC monitoring in scenarios where prolonged ceftaroline courses are prescribed. [ABSTRACT FROM AUTHOR]

Summary: Background: We investigated whether metformin prevents tamoxifen‐induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer. Methods: This was a single‐centre, randomized, double‐blind, placebo‐controlled, parallel group trial. Postmenopausal women with hormone receptor‐positive breast cancer taking tamoxifen were randomly allocated to metformin 850 mg or identical placebo, twice daily, for 52 weeks. Outcome measures included double endometrial thickness (ET) measured by transvaginal ultrasound, fasting insulin, glucose and IR estimated by the homeostasis model of assessment (HOMA‐IR). Results: A total of 112 women were screened and 102 randomized. Results are presented as median (range). The 101 women who took at least one dose of medication were aged 56 (43‐72) years, with 5(0.5‐28) years postmenopause, and had taken tamoxifen for 28.9 (0‐367.4) weeks. The baseline ET was 2.9 mm (1.4‐21.9) for the placebo group (n = 52) and 2.5 mm (1.3‐14.8) for the metformin group (n = 50). At 52 weeks, the median ET was statistically significantly lower for the metformin (n = 36) than for the placebo group (n = 45) (2.3 mm (1.4‐7.8) vs 3.0 (1.2‐11.3); P = 0.05). 13.3% allocated to placebo had an ET greater than 4 mm vs 5.7% for metformin (P = 0.26). There was no endometrial atypia or cancer. Compared with placebo, metformin resulted in significantly greater baseline‐adjusted reductions in weight (P < 0.001), waist circumference (0.03) and HOMA‐IR (P < 0.001). Conclusions: Metformin appears to inhibit tamoxifen‐induced endometrial changes and has favourable metabolic effects. Further research into the adjuvant use of metformin after breast cancer and to prevent EH and cancer is warranted. [ABSTRACT FROM AUTHOR]

Objective To characterize and identify risk factors for 30-day surgical site infections (SSIs) in patients with head and neck cancer who underwent microvascular reconstruction. Study Design Cross-sectional study with nested case-control design. Setting Nine American tertiary care centers. Subjects and Methods Hospitalized patients were included if they underwent head and neck cancer microvascular reconstruction from January 2003 to March 2016. Cases were defined as patients who developed 30-day SSI; controls were patients without SSI at 30 days. Postoperative antibiotic prophylaxis (POABP) regimens were categorized by Gram-negative (GN) spectrum: no GN coverage, enteric GN coverage, and enteric with antipseudomonal GN coverage. All POABP regimens retained activity against anaerobes and Gram-positive bacteria. Thirty-day prevalence of and risk factors for SSI were evaluated. Results A total of 1307 patients were included. Thirty-day SSI occurred in 189 (15%) patients; median time to SSI was 11.5 days (interquartile range, 7-17). Organisms were isolated in 59% of SSI; methicillin-resistant Staphylococcus aureus (6%) and Pseudomonas aeruginosa (9%) were uncommon. A total of 1003 (77%) patients had POABP data: no GN (17%), enteric GN (52%), and antipseudomonal GN (31%). Variables independently associated with 30-day SSI were as follows: female sex (adjusted odds ratio [aOR], 1.6; 95% CI, 1.1-2.2), no GN POABP (aOR, 2.2; 95% CI, 1.5-3.3), and surgical duration ≥11.8 hours (aOR, 1.9; 95% CI, 1.3-2.7). Longer POABP durations (≥6 days) or antipseudomonal POABP had no association with SSI. Conclusions POABP without GN coverage was significantly associated with SSI and should be avoided. Antipseudomonal POABP or longer prophylaxis durations (≥6 days) were not protective against SSI. Antimicrobial stewardship interventions should be made to limit unnecessary antibiotic exposures, prevent the emergence of resistant organisms, and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Antimicrobial management of viral pneumonia has proven to be a challenge in hospitalized immunocompromised patients. A host of factors contribute to the dilemma, such as diagnostic uncertainty, lack of organism identification, and clinical status of the patient. Respiratory virus panel (RVP) use was compared between 131 immunocompromised patients who received send‐out (n = 56) vs in‐house (n = 75) testing. Antimicrobial optimization interventions consisted of antiviral addition/discontinuation, antibiotic discontinuation/de‐escalation, or modification of immunosuppressive regimen. After implementation of an in‐house test with audit and feedback, turnaround time of the RVP was reduced from 46.7 to 5.5 hours (P < .001) and time to intervention was reduced from 52.1 to 13.9 hours (P < .001), yet the frequency of antimicrobial optimization interventions was unchanged (30.7% vs 35.7%). Differences were not observed in duration of empiric antibiotic therapy or length of stay. The overall discontinuation rate for patients tested with a RVP was low (4.6%), and those with positive RVP (n = 43) had antibiotics stopped in 14% of cases. Bacterial pneumonia coinfection was confirmed in 2 patients. Further systematic efforts should be taken to reduce antibiotic use in viral pneumonia and identify the major barriers in the immunocompromised population. [ABSTRACT FROM AUTHOR]

Antimicrobial-impregnated bone cement ( AIBC) is a staple of contemporary orthopedic surgery and has been used to either treat or prevent prosthetic joint infection. Applied intraoperatively during primary arthroplasty or prosthetic joint exchange, this drug-delivery vehicle has become a popular means of maximizing drug concentrations within a joint space while minimizing systemic exposure. Antimicrobial characteristics conducive to cement loading include availability of a crystalline powder formulation, molecular characteristics, minimal impact on cement integrity, and other variables promoting drug elution. Antimicrobials most commonly incorporated into cements are vancomycin and aminoglycosides, usually in combination due to synergistic antibacterial activity and enhanced cement elution. Other classes include the β-lactams, lipopeptides, oxazolidinones, and antifungals. With the exception of several commercially available AIBCs, most products are compounded extemporaneously without a formal safety or efficacy assessment. Few randomized controlled trials have been conducted to assess the benefit or optimal use of these cement preparations, and variable methodology renders cross-study comparison challenging. Given the lack of standardization and multidisciplinary oversight often seen with practical AIBC use, additional data are needed. This review presents information intended to guide AIBC preparation, selection, dosing, and safe use. In addition, opportunities for best practice development, antimicrobial stewardship, and future research are discussed. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to determine the incidence of and risk factors for surgical site infections in microvascular reconstruction for patients with head and neck cancer. Methods One hundred seventeen patients with head and neck cancer undergoing microvascular reconstruction received postoperative surgical infection prophylaxis and were followed for 30 days. Surgical infection prophylaxis was categorized by empiric spectrum of activity. Risk factors for surgical site infection development and cumulative incidence of surgical site infections were characterized. Results Thirty-seven patients developed surgical site infection (cumulative surgical site infection incidence of 31.6%). Risk factors identified in logistic regression include alcohol use (odds ratio [OR] = 2.704; 95% confidence interval [CI] = 1.029-7.106), increased surgical duration (OR = 1.403; 95% CI = 1.185-1.661), American Society of Anesthesiologists (ASA) class IV (OR = 3.075; 95% CI = 1.000-9.459), and lack of postoperative gram-negative coverage (OR = 15.139; 95% CI = 3.083-74.347). Conclusion Alcohol use, longer surgical duration, and lack of gram-negative postoperative prophylactic coverage are modifiable risk factors for surgical site infection development. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1454, 2016 [ABSTRACT FROM AUTHOR]

A clinical practice audit was undertaken to share an Australian experience of the use of micronised progesterone ( mP) 100 mg daily as part of menopausal hormone therapy ( MHT). Ninety-nine women attending a single practitioner were offered the option of mP as a component of MHT, under the Australian Authorised Prescriber Scheme, over 2.5 years. Each of their files was independently audited. The mean age at commencement was 55.0 ( SD 6.6) years. Of the 93 postmenopausal women, 7 were lost to follow-up, 18 discontinued and treatment was ongoing for 68. The mean duration of treatment for those ongoing was 1.7 ( SD 0.5) years, and for those who discontinued, 0.6 ( SD 0.6) years. The most common side effect was unscheduled bleeding, which was also the most common reason for discontinuation (5/18 women). None of the 15 women who had a transvaginal ultrasound examination had an endometrial thickness >5 mm. Of the 41 women who had at least one blood progesterone measurement performed, the median value was 11.3 (range 0.7-138) nmol/L. This audit indicates that mP is well tolerated when prescribed as MHT. Although there was no evidence of endometrial hyperplasia, further research is needed to establish the safety of mP for continuous combined MHT use. [ABSTRACT FROM AUTHOR]

The article discusses as study that evaluated the use of complementary and alternative medicines (CAMs) for the treatment of menopause vasomotor symptoms (VMS). Topics covered include measurement of symptom severity and frequency using the Menopause-specific Quality of Life questionnaire for 2,020 Australian women aged 40-65. Results showed the use of phytoestrogens at 6.2%, primrose oil at 3.91% and CAM at 13.22% for VMS and use of fish or krill oil and glucosamine for other symptoms.

Objective The aim of this study was to examine the effects of testosterone on verbal learning and memory in postmenopausal women. Design Randomized, placebo-controlled trial in which participants were randomized (1:1) to transdermal testosterone gel 300 mcg/day, or identical placebo, for 26 weeks. Patients Ninety-two postmenopausal women aged 55-65 years, on no systemic sex hormone therapy. Measurements The primary outcome was the score for the International Shopping List Task ( ISLT) of CogState. Secondary outcomes included other CogState domains, the Psychological General Well-Being Index ( PGWB) and safety variables. Results Eighty-nine women, median age 60 years, were included in the primary analysis. Testosterone treatment resulted in statistically significantly better performance for the ISLT (improved verbal learning and memory) compared with placebo, adjusted for age and baseline score (mean difference 1·57; 95% CI 0·13, 3·01) P = 0·03). There were no significant differences for other CogState domains or the PGWB scores. At 26 weeks, the median total testosterone was 1·7 n m (interquartile range ( IQR) 1·1, 2·4) in the testosterone group and 0·4 n m ( IQR 0·3, 0·5) in the placebo group. Conclusions The small but statistically significant effect of testosterone treatment on verbal learning and memory in postmenopausal women provides the basis for further clinical trials. [ABSTRACT FROM AUTHOR]

Objective The increased prevalence of osteoarthritis (OA) in postmenopausal women suggests that changes in either circulating sex steroid concentrations or the tissue response to sex steroids may have a role in the pathogenesis of OA. The aim of this study was to examine whether circulating sex steroid concentrations are associated with the incidence of total knee and total hip replacement for OA. Methods Study subjects (n = 2,621; all women) were recruited in 1990-1994 from the Melbourne Collaborative Cohort Study (MCCS). Circulating sex steroid concentrations were measured in blood samples obtained from the women at the time of recruitment. The incidence of total knee and total hip replacement for OA during 2001-2011 was determined by linking the MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry. Results During the followup period, 115 women had undergone total knee replacement and 99 had undergone total hip replacement for OA. Greater log-transformed concentrations of estradiol were associated with a lower incidence of knee replacement (hazard ratio [HR] 0.70, 95% confidence interval [95% CI] 0.50-0.96), and greater log-transformed concentrations of androstenedione were associated with a lower incidence of hip replacement (HR 0.70, 95% CI 0.52-0.93). In contrast, greater log-transformed concentrations of sex hormone binding globulin (SHBG) were associated with a higher incidence of hip replacement (HR 1.70, 95% CI 1.05-2.77). Conclusion A lower estradiol concentration is a risk factor for knee OA, while a lower androstenedione concentration and higher SHBG concentration are risk factors for hip OA in women. These findings suggest that circulating sex steroids have a role in the pathogenesis of OA, and that modifying these steroid concentrations may provide a potential strategy for the prevention and treatment of knee and hip OA. [ABSTRACT FROM AUTHOR]

Study Objectives To describe the implementation of vancomycin dosing and monitoring practices recommended by the consensus guidelines in a diverse sample of hospitals, and to identify needs for quality improvement and research. Design Cross-sectional study using an online survey instrument. Setting Making a Difference in Infectious Diseases Pharmacotherapy ( MAD- ID) Research Network. Participants A total of 163 respondents from MAD- ID who work in antimicrobial stewardship and represent unique hospitals. Measurements and Main Results The survey population represented a wide range of patient populations (96% adult, 49% pediatric, and 23% long-term care) and settings (52% not-for-profit nonuniversity, 31% university based, and 11% for profit). Automatic consultation of pharmacy services for all vancomycin dosing was reported in 51% of the institutions. Among the dosing and monitoring practices endorsed by the consensus guidelines, participant institutions commonly followed these recommendations: use of trough concentrations without peak concentrations, maintenance of trough concentration higher than 10 mg/L, and target trough concentrations of 15-20 mg/L for complicated infections. In contrast, there was less consistent application of appropriate timing of trough concentrations, use of loading doses, and use of actual body weight. The remaining challenges and controversies surrounding vancomycin dosing are discussed. Conclusion Despite the availability of consensus guideline recommendations, practices for dosing and monitoring of vancomycin are not universally applied. The findings of this survey highlight many opportunities for future research and quality improvement strategies. [ABSTRACT FROM AUTHOR]

Aim: To investigate vitamin D status among older women and to explore relationships between vitamin D and fracture risk and vertebral fractures. Methods: A total of 267 general practitioners recruited 2466 women aged >70 years with no known osteoporosis or fragility fracture. Serum 25-hydroxy vitamin D (25(OH)D), bone mineral density by dual-energy X-ray absorptiometry (DXA) and vertebral fracture on thoracolumbar X-ray were determined. Results: A total of 2368 women, median age 76 years, provided data and of these 13% were on vitamin D supplements. 25(OH)D levels were available for 907 (44.1%) of those not taking vitamin D. 88.3% of these had a level below 75 nmol/L. Serum 25(OH)D was negatively associated with age (P = 0.003) and body mass index (P < 0.001), and positively associated with lower latitude, femoral neck DXA T-score (P = 0.044) and being Caucasian (P < 0.001). Conclusions: The vitamin D status of community-dwelling older Australian women is inadequate, yet the use of supplements is low. [ABSTRACT FROM AUTHOR]

Background There is no evidence of benefit in terms of survival or quality of life for intensive surveillance of women with early breast cancer ( BC) and current guidelines reflect this. We have examined whether Victorian women, nearly 4 years from a diagnosis of localized BC, were being managed according to these guidelines. Methods Participants are women in the BUPA Health Foundation Health and Wellbeing after Breast Cancer prospective cohort study. All participants completed an enrolment questionnaire within 12 months of diagnosis and then completed follow-up questionnaires every 12 months thereafter. In the third follow-up questionnaire, completed nearly 4 years from the time of diagnosis, women were asked about imaging tests they had in the previous 12 months. Results The analysis was completed on 673 women who were stage 1 at the time of diagnosis and had not reported evidence of recurrence or a new BC since diagnosis. Of the 673, 603 (89.5%) reported having had a mammogram in the previous 12 months and 319 (52.9% of those having a mammogram) reported a breast ultrasound. Seventy-one per cent of women reported no other imaging investigations in the previous 12 months. Conclusions Our study shows that, nearly 4 years from diagnosis, Australian practitioners are generally adhering to guidelines about imaging surveillance of BC survivors. Practitioners could use the guidelines for the education of BC survivors about appropriate health surveillance. [ABSTRACT FROM AUTHOR]

The authors comment on the role of pharmacists in the management of infectious diseases in line with a paper by Doctor Allen Antworth and colleagues about the successful implementation of a care bundle for candidemia as an expansion of an existing interdisciplinary antimicrobial stewardship program. The authors explain the importance of care bundle approaches. The authors highlight how the study addressed the challenge in improving the science of antimicrobial stewardship.

Study Objective To evaluate a clinical pathway using daptomycin in patients with bacteremia caused by methicillin-resistant Staphylococcus aureus ( MRSA) isolates exhibiting vancomycin minimum inhibitory concentrations (MICs) greater than 1 mg/L. Design Two-phase quasi-experimental study. Setting Level I trauma center in Detroit, Michigan. Patients The study population consisted of a total of 170 patients with MRSA bacteremia susceptible to vancomycin: 70 patients who had initial blood MRSA isolates exhibiting a vancomycin MIC > 1 mg/L and were treated with vancomycin were included in phase I (retrospective baseline period [2005-2007]) and 100 patients who were switched to daptomycin after initial vancomycin therapy according to the institutional MRSA bacteremia treatment pathway were included in phase II (the period after implementation of the treatment pathway [2008-2010]). Intervention The MRSA bacteremia treatment pathway was as follows: vancomycin therapy was initiated, optimizing target trough concentrations to 15-20 mg/L; for isolates demonstrating vancomycin MICs greater than 1 mg/L, therapy was switched to daptomycin, initiated at dosages of 6 mg/kg/day or higher. Measurements and Main Results Infection characteristics, patient outcomes, and costs were evaluated. Patient characteristics were similar between the phase I and phase II groups. Phase II patients were more likely to achieve clinical success than were phase I patients (75.0% vs 41.4%, p<0.001). Phase II patients demonstrated a shorter total hospital length of stay and shorter durations of inpatient therapy, fever, and bacteremia. Treatment during phase I was independently associated with failure. Nine patients during phase I experienced nephrotoxicity, and two patients during phase II experienced increases in creatine kinase level. Costs were similar between phases I and II ($18,385 vs $19,755, p>0.05), although the hospital readmission rate was higher in phase I (33% vs 21%, p=0.08). Conclusion Among the patients with bacteremia who had MRSA isolates that exhibited elevated vancomycin MICs, the switch to daptomycin improved clinical success without increasing treatment cost. [ABSTRACT FROM AUTHOR]

Objective Sex hormone-binding globulin (SHBG) is a robust predictor of insulin resistance. Whether this is independent of circulating sex steroid levels remains uncertain. The aim of this study was to investigate the determinants of SHBG in postmenopausal women and whether the relationship between SHBG and insulin resistance is independent of oestrogen and androgen levels. Design A cross-sectional study of naturally and surgically menopausal women. Participants Seven hundred and sixty three postmenopausal women not using any systemic hormone therapy, mean age 54·4 ± 5·8 years, recruited in the US, Canada, Australia, UK and Sweden between July 2004 and February 2005. Measurements Relationships between log-transformed (ln) SHBG and ln homoeostasis model assessment for insulin resistance (HOMA-IR) were explored, taking into account age, body mass index (BMI), blood pressure (BP) and circulating oestradiol, oestrone, testosterone and dihydrotestosterone. Results Taking into account age, race, years since menopause, menopause type, BMI, BP, prior postmenopausal hormone use and the sex steroids measured, 34·4% of the variation in SHBG could be explained by the model that included negative contributions by HOMA-IR, BMI and diastolic BP, and a positive contribution by total testosterone ( P < 0·001). None of the sex steroids made independent contributions to HOMA-IR, which was best explained by the model that included BMI, SHBG, systolic BP and surgical menopause, with each variable being positively related to HOMA-IR ( r2 = 0·3152, P = 0·03). Conclusions The relationship between SHBG and HOMA-IR, as an estimate of insulin resistance, is not explained by endogenous oestrogen and androgen levels and is, at least in part, independent of BMI in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objective: To explore the beliefs held by breast cancer (BC) survivors about the factors that contribute to the development of their BC. Methods: The BUPA Health Foundation Health and Well-being after Breast Cancer Study is a prospective cohort study of 1684 women recruited within 12 months of their first diagnosis with invasive BC. Participants completed an enrollment questionnaire (EQ), first follow-up questionnaire (FQ1) and a second follow-up questionnaire (FQ2), 12 months and 24 months post-EQ, respectively. In the FQ2, women were asked whether they believed anything contributed to the development of their BC and whether they had made lifestyle changes since the FQ1. Well-being was assessed at the FQ2 using the Psychological General Well-being Index (PGWB). Results: In total, 1496/1684 women completed the FQ2 and 43.5% reported belief in a factor that may have contributed to their developing BC. These women were more likely to be younger ( p<0.0001) and educated beyond high school ( p<0.0001). Stress (58.1%) was the most common reason given, followed by previous use of hormone therapy (17.0%) and a family history of any cancer (9.8%). Women who believed stress contributed to their BC had lower PGWB scores than other study participants (70.9 ± 16.1, n = 361 versus 77.3 ± 14.9, n = 1071, mean difference = 6.4, 95% CI: 4.6-8.2 p<0.0001) and were more likely to have made lifestyle changes since their BC diagnosis. Conclusions: Many women with BC believe that stress has contributed to their condition. Women who held this belief were more likely to adopt strategies to reduce stress than those who did not. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Study Objective To compare clinical outcomes and costs in patients treated with the new vancomycin guidelines recommending goal serum trough concentrations of 15-20 mg/L versus patients treated with vancomycin doses targeting trough concentrations 5-20 mg/L prior to the new guidelines. Design Retrospective quasi-experimental study. Setting Urban level I trauma center. Patients A total of 200 patients treated with vancomycin for at least 72 hours for confirmed, complicated methicillin-resistant Staphylococcus aureus ( MRSA) bacteremia during one of two study phases relative to the implementation of the vancomycin dosing guidelines targeting serum trough concentrations of 15-20 mg/L: 2005-2007 (preperiod phase) and 2008-2010 (postperiod phase). One hundred patients in each phase were matched in a 1:1 ratio according to diagnosis, any concomitant nephrotoxic agents (e.g., aminoglycosides, colistin, acyclovir), and age ± 5 years. Measurements and Main Results Patients in the preperiod had significantly lower success rates with vancomycin than those in the postperiod (45% vs 60%, p=0.034). Median length of stay ( LOS) was not significantly higher in patients in the preperiod versus postperiod (15 days vs 13.5 days; p=0.28), and patients in the preperiod received a longer median duration of vancomycin versus those in the postperiod (13 days vs 8.5 days; p<0.001). No statistically significant difference was noted in total hospital costs for patients treated with vancomycin during the preperiod versus the postperiod ($32,754 vs $27,709, p=0.147). However, total drug and monitoring costs of vancomycin were significantly higher for patients in the postperiod. Initial vancomycin trough levels were significantly lower in patients in the preperiod versus postperiod (12.3 mg/L vs 15.8 mg/L, p=0.02). Patients in the preperiod had lower rates of nephrotoxicity than those in the postperiod, although this difference was not statistically significant (15% vs 18%; p=0.85). Median (interquartile range) LOS was significantly longer in patients who developed nephrotoxicity compared with patients who did not develop nephrotoxicity (17 days [11.5-36.5 days] vs 14 days [9-24 days], p=0.017). Costs associated with measurement of serum creatinine concentrations and vancomycin trough levels as well as labor were significantly higher in patients who developed nephrotoxicity. Conclusion Higher vancomycin trough concentrations improved outcomes in patients with complicated MRSA bacteremia. In addition, more aggressive dosing was shown to significantly decrease overall duration of vancomycin therapy, which may affect total hospital LOS and cost. Patients who experienced nephrotoxicity had a significantly longer hospital LOS. Additional studies evaluating optimal therapy for MRSA bacteremia in a larger cohort of matched patients are warranted. [ABSTRACT FROM AUTHOR]

Study Objective. To evaluate the clinical response and safety of high-dose daptomycin for treatment of complicated gram-positive infections. Design. Multicenter, retrospective, observational, case series analysis. Setting. Five academic medical centers in four major United States cities. Patients. Two hundred fifty adults, not undergoing dialysis, who received high-dose daptomycin (≥ 8 mg/kg/day) for at least 72 hours for complicated gram-positive infections between January 1, 2005, and March 1, 2010. Measurements and Main Results. Clinical and microbiologic outcomes were assessed at the end of high-dose daptomycin therapy. Safety evaluations were recorded for all patients, and when available, baseline, end-of-therapy, and highest observed serum creatine phosphokinase (CPK) levels were recorded. Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) were the primary organisms isolated. The median dose of daptomycin was 8.9 mg/kg/day (interquartile range [IQR] 8.0-10.0 mg/kg/day). The median duration of daptomycin during hospitalization for MRSA and VRE infection was 10 days (IQR 5-16 days) and 13 days (IQR 6-18 days), respectively. Among the 250 patients, high-dose daptomycin was primarily used as salvage therapy after vancomycin treatment (184 patients [73.6%]). Primary infections included complicated bacteremia (119 patients [47.6%1), endocarditis (59 [23.6%]), skin or wound (70 [28.0%]), and bone or joint (67 [26.8%]). Overall, clinical response and microbiologic success were assessed in 83.6% (209/250 patients) and 80.3% (175/218 patients), respectively. Isolates from 13 patients (5.2%) developed nonsusceptibility to daptomycin, with most of these patients having extended vancomycin exposure. Three patients (1.2%) developed an adverse event attributable to high-dose daptomycin therapy, with the event considered either mild or moderate in severity The median end-of-therapy CPK level was 39 U/L (IQR 26-67 U/L). No significant correlation was found between daptomycin dose and highest observed CPK level. Conclusion. Daptomycin dosages of 8 mg/kg/day or greater may be safe and effective in patients with complicated gram-positive infections. Further clinical studies are warranted. [ABSTRACT FROM AUTHOR]

Study Objective. To assess and validate the effectiveness of a newly constructed vancomycin dosing nomogram in achieving target trough serum concentrations of 15-20 mg/L. Design. Prospective multicenter study. Setting. Five tertiary care teaching hospitals. Patients. A total of 200 adults who required vancomycin dosages targeted to attain recommended trough vancomycin serum concentrations of 15-20 mg/L. Intervention. The new nomogram, which based dosing on weight and renal function, was used to calculate patients' initial vancomycin dosages. Serum trough concentrations were measured before the fourth or fifth dose, and dosages were adjusted as needed. Measurements and Main Results. Median patient age was 56 years (interquartile range [IQR] 49-65 yrs), median weight was 71.2 kg (IQR 63-85 kg), and median creatinine clearance was 66.5 ml/minute (IQR 52-82 ml/min). The median initial vancomycin trough concentration achieved was 17.5 mg/L (IQR 15.0-20.0 mg/L), with 116 patients (58%) achieving the initial target trough of 15-20 mg/L. The median percent error was 13.6%, and the mean ± SD error for predicted versus actual serum trough concentrations was -0.50 ± 0.021 mg/L. One hundred fifty-four patients (77%) eventually achieved the trough target concentration within a median of 2 days. One hundred forty patients (70%) achieved initial troughs of 14-21 mg/L and 160 (80%) achieved troughs of 13-22 mg/L. Nine patients (4.5%) experienced nephrotoxicity while receiving vancomycin, which occurred after a median of 8 days of therapy. The median initial vancomycin trough concentration for these patients was 18.5 mg/L (IQR 15.3-19.3 mg/L), with eight of the nine patients having trough concentrations of 15 mg/L or greater. Conclusion. Fifty-eight percent of patients achieved the target trough of 15-20 mg/L (median 17.5 mg/L). The performance of the nomogram improved to 80% when the trough range was adjusted to 13-22 mg/L. Caution should be applied when using this nomogram. The nomogram should not replace clinical judgment, and dosage adjustments should be based on pharmacokinetic-pharmacodynamic targets and clinical response. [ABSTRACT FROM AUTHOR]

Phylogenetic analysis of a collection of rabies viruses that currently circulate in Canadian big brown bats ( Eptesicus fuscus) identified five distinct lineages which have emerged from a common ancestor that existed over 400 years ago. Four of these lineages are regionally restricted in their range while the fifth lineage, comprising two-thirds of all specimens, has emerged in recent times and exhibits a recent demographic expansion with rapid spread across the Canadian range of its host. Four of these viral lineages are shown to circulate in the US. To explore the role of the big brown bat host in dissemination of these viral variants, the population structure of this species was explored using both mitochondrial DNA and nuclear microsatellite markers. These data suggest the existence of three subpopulations distributed in British Columbia, mid-western Canada (Alberta and Saskatchewan) and eastern Canada (Quebec and Ontario), respectively. We suggest that these three bat subpopulations may differ by their level of female phylopatry, which in turn affects the spread of rabies viruses. We discuss how this bat population structure has affected the historical spread of rabies virus variants across the country and the potential impact of these events on public health concerns regarding rabies. [ABSTRACT FROM AUTHOR]

The available clinical evidence supports efficacy of testosterone therapy for the treatment of postmenopausal women with hypoactive sexual desire disorder (HSDD) who have undergone a comprehensive clinical evaluation. Although few preparations designed to deliver an appropriate dose of testosterone for women are available, use of testosterone by women for the management of HSDD is widespread. Issues that continue to simulate debate in this therapeutic area include whether HSDD is a condition that merits pharmacotherapy, how effective is such treatment and whether testosterone therapy is safe. Hence the question, should women receive androgen replacement therapy, and if so, how? [ABSTRACT FROM AUTHOR]

To improve timely ante-mortem human rabies diagnosis, methods to detect viral RNA by TaqMan-based quantitative reverse transcriptase polymerase chain reactions (qRT-PCRs) have been developed. Three sets of two primers and one internal dual-labeled probe for each primer set that target distinct conserved regions of the rabies virus N gene were designed and evaluated. Using a collection of 203 isolates representative of the world-wide diversity of rabies virus, all three primers/probe sets were shown to detect a wide range of rabies virus strains with very few detection failures; the RABVD1 set in particular was the most broadly reactive. These qRT-PCR assays were shown to be quantitative over a wide range of viral titer and were 100-1,000 times more sensitive than nested RT-PCR; however, both the standard and real-time PCR methods yielded concordant results when used to test a collection of archived human suspect samples. The qRT-PCR assay was employed to monitor virus load in the saliva of a rabies virus-infected patient undergoing the Milwaukee treatment protocol. However in this case it would appear that reduction of the viral load in the patient's saliva over time did not appear to correlate well with clearance of viral components from the brain. J. Med. Virol. 81:1484-1497, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

As an alternative to adaptation, tests may also be developed simultaneously in multiple languages. Although the items on such tests could vary substantially, scores from these tests may be used to make the same types of decisions about different groups of examinees. The ability to make such decisions is contingent upon setting performance standards for each exam that allow for comparable interpretations of test results. This article describes a standard setting process used for a multilingual high school literacy assessment constructed under these conditions. This methodology was designed to address the specific challenges presented by this testing program including maintaining equivalent expectations for performance across different student populations. The validity evidence collected to support the methodology and results is discussed along with recommendations for future practice. [ABSTRACT FROM AUTHOR]

Objectives: Urinary incontinence in women is common and has a significant impact on the physical, psychological and socio-economic aspects of life. The aims of this study were to review the published reports on the prevalence and incidence of urinary incontinence in Australian women and to examine the methodological issues associated with these studies. Methods: Electronic searches of Medline, EMBASE and the Current Index to Nursing and Allied Health Literature databases were undertaken using ‘Medical Subject Heading’ terms and ‘free text’ words. We retrieved papers that investigated the prevalence and/or incidence of urinary incontinence in Australian women and were published in English after 1980. Methodological data from each study were tabulated. Results: Seven studies were identified which examined the prevalence of urinary incontinence and two studies that reported its incidence. The prevalence of urinary incontinence varied between 12.8% and 46.0%. Study heterogeneity was a consequence of response rates, the inclusion of women in institutional care, the method of data collection, the questions used to identify different types of urinary incontinence and the way these questions were reported, the period over which the urinary incontinence had occurred and the severity of the incontinence. Two studies which examined incidence provided evidence that urinary incontinence can be a transient phenomenon. Conclusions: Research into the incidence and prevalence of urinary incontinence in Australian women exhibits significant heterogeneity in the findings due to methodological limitations. There is a need for future studies to employ validated instruments and give careful attention to the selection of participants and the reporting of age-specific data. [ABSTRACT FROM AUTHOR]

Although knee malalignment is a risk factor for the progression of unicompartmental knee osteoarthritis (OA), it is unclear how this relationship is mediated. Cartilage defects are known to predate cartilage loss and the onset of knee OA, and it may be that knee malalignment increases the risk of unicompartmental knee cartilage defects. Knee radiographs and MRI were performed on a total of 202 subjects, 36.6% of whom had radiographic knee OA, to determine the relationship between static knee alignment and knee cartilage defects. Analyses were performed for the entire cohort, as well as for healthy and OA subgroups. For every 1° increase in a valgus direction, there was an associated reduced risk of the presence of cartilage defects in the medial compartment of subjects with knee OA ( p = 0.02), healthy subjects ( p = 0.002), and the combined ( p < 0.001) group. Moreover, for every 1° increase in a valgus direction, there was an associated increased risk of the presence of lateral cartilage defects in the OA group ( p = 0.006), although the relationship between change toward genu valgum and lateral compartment cartilage defects did not persist for the healthy group ( p = 0.16). This cross-sectional study has demonstrated that knee alignment is associated with the risk for compartment specific knee cartilage defects in both healthy and arthritic people. Given that the natural history of cartilage volume reduction appears to be predated by the presence of cartilage defects, whether knee alignment affects the longitudinal progression from cartilage defects to cartilage loss requires further examination. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:225-230, 2008 [ABSTRACT FROM AUTHOR]

Study Objective. To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated skin and skin structure infections. Design. Prospective, open-label study. Setting. Level 1 trauma center in Detroit, Michigan. Patients. Fifty-three adult patients with complicated skin and skin structure infections at risk for methicillin-resistant Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a matched cohort of 212 patients treated with vancomycin. Intervention. Patients in the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at least 3 days but not more than 14 days. Historical controls received at least 3 days of vancomycin dosed to achieve trough concentrations of 5-20 µg/ml. Measurements and Main Results. Outcomes evaluated included blinded assessments of clinical resolution, duration of therapy, and costs. The most common diagnoses were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%). Microbiology differed significantly between groups, with S. aureus found in 27 patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions of patients with clinical improvement or resolution of their infections on days 3 and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin groups, respectively (p<0.01 for both comparisons), and 100% at the end of therapy in both groups. Among patients with complete resolution of their infections (41 patients [77%] with daptomycin vs 89 patients [42%] with vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days, respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001). Conclusions. Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin. This study suggests that daptomycin is a cost-effective alternative to vancomycin for complicated skin and skin structure infections. [ABSTRACT FROM AUTHOR]

The relationship between an initial mechanical event causing brain tissue deformation and delayed neurodegeneration in vivo is complex because of the multiplicity of factors involved. We have used a simplified brain surrogate based on rat hippocampal slices grown on deformable silicone membranes to study stretch-induced traumatic brain injury. Traumatic injury was induced by stretching the culture substrate, and the biological response characterized after 4 days. Morphological abnormalities consistent with traumatic injury in humans were widely observed in injured cultures. Synaptic function was significantly reduced after a severe injury. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 attenuated neuronal damage, prevented loss of microtubule-associated protein 2 immunoreactivity and attenuated reduction of synaptic function. In contrast, the NMDA receptor antagonists 3-[( R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and GYKI53655, were neuroprotective in a moderate but not a severe injury paradigm. Nifedipine, an L-type voltage-dependent calcium channel antagonist was protective only after a moderate injury, whereas ω-conotoxin attenuated damage following severe injury. These results indicate that the mechanism of damage following stretch injury is complex and varies depending on the severity of the insult. In conclusion, the pharmacological, morphological and electrophysiological responses of organotypic hippocampal slice cultures to stretch injury were similar to those observed in vivo. Our model provides an alternative to animal testing for understanding the mechanisms of post-traumatic delayed cell death and could be used as a high-content screen to discover neuroprotective compounds before advancing to in vivo models. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to evaluate whether subclinical thyroid disease is associated with impaired health-related quality of life and a more adverse cardiovascular disease risk profile. Design A community-based cross-sectional study. Setting and participants A total of 1423 non-healthcare-seeking women, aged 18–75 years were randomly recruited from the community via the electoral roll from April 2002 to August 2003. Main outcome measures These were the scores for the Short-Form 36 (SF-36), the Psychological General Well-being Index (PGWI), thyroid hormone levels, serum lipids and high sensitivity C-reactive protein (hsCRP). Subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (SCHyper) were defined as serum TSH > 4·0 mIU/l and < 0·5 mIU/l, respectively, with a normal free thyroxine (free T4) level. Results Evaluable data were available for all participants. 10·7% of all women had an abnormal TSH value. The prevalence of a low TSH level by age group ranged from 1·2% to 6·4%, whereas the prevalence of an elevated TSH level ranged from 2·8% to 9·2% and increased with age ( P = 0·002). There were no significant differences between women with SCH or SCHyper and age-matched controls for the total PGWI score or the Mental and Physical Component Scores of the SF-36. Women with SCH were no different from controls for serum lipids or hsCRP. Using linear regression, SCH vs. euthyroidism did not make an independent contribution to variation in either total cholesterol or triglycerides, with or without adjustment for age ± age2 ± BMI. Conclusions Our data indicate that subclinical thyroid disease in women in the community is not associated with lower well-being or impaired health-related quality of life and SCH is not associated with increased serum markers of CVD risk. [ABSTRACT FROM AUTHOR]

This article describes a seven-phase model of personal conflict over worldview, frame of irony, and styles in organizational settings that is tested in the context of church organizations. Finally, adversarial and collaborative approaches for resolving conflict are examined. [ABSTRACT FROM AUTHOR]