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Background Pelvic Floor Muscle Training (PFMT) has been shown to be effective for pelvic organ prolapse in women, but its implementation in routine practice is challenging due to lack of adequate specialist staff. It is important to know if PFMT can be delivered by different staff skill mixes, what barriers and facilitators operate in different contexts, what strategies enable successful implementation and what are the underlying mechanisms of their action. PROPEL intervention was designed to maximise the delivery of effective PFMT in the UK NHS using different staff skill mixes. We conducted a realist evaluation (RE) of this implementation to understand what works, for whom, in what circumstances and why. Methods Informed by the Realist and RE-AIM frameworks, the study used a longitudinal, qualitative, multiple case study design. The study took place in five, purposively selected, diverse NHS sites across the UK and proceeded in three phases to identify, test and refine a theory of change. Data collection took place at 4 time points over an 18 month implementation period using focus groups and semi-structured interviews with a range of stakeholders including service leads/managers, senior practitioners, newly trained staff and women receiving care in the new service models. Data were analysed using thematic framework approach adapted to identify Context, Mechanism and Outcome (CMO) configurations of the RE. Results A heightened awareness of the service need among staff and management was a mechanism for change, particularly in areas where there was a shortage of skilled staff. In contrast, the most established specialist physiotherapist-delivered PFMT service activated feelings of role protection and compromised quality, which restricted the reach of PFMT through alternative models. Staff with some level of prior knowledge in women’s health and adequate organisational support were more comfortable and confident in new role. Implementation was seamless when PFMT delivery was incorporated in newly trained staff’s role and core work. Conclusion Roll-out of PFMT delivery through different staff skill mixes is possible when it is undertaken by clinicians with an interest in women’s health, and carefully implemented ensuring adequate levels of training and ongoing support from specialists, multi-disciplinary teams and management.

To examine the attitudes to and knowledge and beliefs about homosexuality of nurses and allied professionals in two early parenting services in Australia.Early parenting services employ nurses and allied professionals. Access and inclusion policies are important in community health and early childhood service settings. However, little is known about the perceptions of professionals who work within early parenting services in relation to lesbian, gay, bisexual and transgender families.This is the final in a series of studies and was undertaken in two early parenting services in two states in Australia using a cross-sectional design with quantitative and qualitative approaches.Validated questionnaires were completed by 51 nurses and allied professionals and tested with chi-squared test of independence (or Fisher's exact test), Mann-Whitney U-test, Kruskal-Wallis one-way analysis of variance or Spearman's rank correlation. Thematic analysis examined qualitative data collected in a box for free comments.Of the constructs measured by the questionnaires, no significant relationships were found in knowledge, attitude and gay affirmative practice scores by sociodemographic variables or professional group. However, attitude scores towards lesbians and gay men were significantly negatively affected by conservative political affiliation (p = 0·038), held religious beliefs (p = 0·011) and frequency of praying (p = 0·018). Six overall themes were found as follows: respect, parenting role, implications for the child, management, disclosure, resources and training.The study provided an in-depth analysis of the attitudes, knowledge and beliefs of professionals in two early parenting services, showing that work is needed to promote acceptance of diversity and the inclusion of lesbian, gay, bisexual and transgender families in planning, developing, evaluating and accessing early parenting services.Access and inclusion plans for lesbian, gay, bisexual and transgender families are crucial in early parenting services in Australia and should be included in professional development programmes.

Objective: The objective of this paper is to report on the development and implementation of a community-based perinatal and infant mental health day program for mothers with psychiatric illness. The program was initiated through interagency collaboration between adult mental health, infant mental health and community child health services in Queensland, Australia in response to calls for an integrated approach that could be delivered state-wide if successful. Preliminary results of the program’s evaluation are provided. Method: A pre-post survey design was used to assess the influence the program had on maternal mental and emotional well-being and the maternal-infant relationship. Twenty-one women receiving treatment for perinatal mental illness gave consent to attend the 6-week day program integrating three currently separate and discrete services: adult mental health, infant mental health and community child health. Results: Clinically and statistically significant improvements were observed for maternal mental health, and parent-infant relationships following the program. Conclusions: These findings support interagency collaboration between adult mental health, infant mental health and community child health services to deliver services to women with mental illness with newborns and their families. The utility of using a collaborative approach in a community setting endorses more comprehensive and longer-term evaluation of effectiveness and cost benefit.

A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene) thiosemicarbazides was discovered as potent inhibitors of IKKβ. In this Letter we document our efforts at further optimization of this series, culminating in 2 with submicromolar potency in a HWB assay and efficacy in a CIA mouse model.

(R)-N-{1-[3-(4-Ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]-pyrimidin-2-yl]-ethyl}-N-pyridin-3-yl-methyl-2-(4-trifluoromethoxyphenyl)-acetamide (AMG 487) is a potent and selective orally bioavailable chemokine (C-X-C motif) receptor 3 (CXCR3) antagonist that displays dose- and time-dependent pharmacokinetics in human subjects after multiple oral dosing. Although AMG 487 exhibited linear pharmacokinetics on both days 1 and 7 at the 25-mg dose, dose- and time-dependent kinetics were evident at the two higher doses. Nonlinear kinetics were more pronounced after multiple dosing. Area under the plasma concentration-time curve from 0 to 24 h [AUC((0-24 h))] increased 96-fold with a 10-fold increase in dose on day 7 compared with a 28-fold increase in AUC((0-24 h)) on day 1. These changes were correlated with time- and dose-dependent decreases in the metabolite to parent plasma concentrations, suggesting that these changes result from a decrease in the oral clearance (CL) of AMG 487 (e.g., intestinal/hepatic first-pass metabolism and systemic CL). The biotransformation of AMG 487 is dependent on CYP3A and results in the formation of two primary metabolites, a pyridyl N-oxide AMG 487 (M1) and an O-deethylated AMG 487 (M2). One of these metabolites, M2, undergoes further metabolism by CYP3A. M2 has also been demonstrated to inhibit CYP3A in a competitive (K(i)=0.75 microM) manner as well as via mechanism-based inhibition (unbound K(I)=1.4 microM, k(inact)=0.041 min(-1)). Data from this study implicate M2-mediated CYP3A mechanism-based inhibition as the proximal cause for the time-dependent pharmacokinetics of AMG 487. However, the sequential metabolism of M2, nonlinear AMG 487 pharmacokinetics, and the inability to accurately determine the role of intestinal AMG 487 metabolism complicates the correlation between M2 plasma concentrations and the time-dependent AMG 487 pharmacokinetic changes.

The response of increasingly large numbers of American young men to compulsory military service is immigration to Canada. Viewing interaction between these men (and their wives) and their families, their society, and their new country of choice, provides insights into their commitments versus their alienation.