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Chromosome 22q11.2 deletion syndrome (22q11DS) is characterised by a complex behavioural phenotype including anxiety, attention-deficit/hyperactivity disorder and psychosis. In the current study, we aimed at improving our understanding of the heterogeneity of behavioural characteristics in a group of 129 young people (aged 4–22) with a confirmed 22q11.2 microdeletion and 116 age and gender matched typically developing controls. Half the participants with 22q11DS had behaviour characterised by emotion dysregulation. A cluster analyses, of the participants with 22q11DS, revealed four groups characterised by intact emotion regulation; predominantly internalizing problems; both internalizing and externalizing problems; and predominantly externalizing difficulties. Importantly, it was found that young people with 22q11DS whose emotion dysregulation was characterised by externalizing problems had the poorest levels of functioning. As our understanding of 22q11DS improves, it is becoming increasingly clear that we need a better understanding of how individual differences and psychosocial factors contribute to, and interact with one another, to result in the observable individual differences in the 22q11DS behavioural phenotype.

Involving people living with dementia in service design and planning has become more common in high-income countries. It remains rare in low- and middle-income countries where two-thirds of the world’s people with dementia live. In this commentary article, we explore the barriers to inclusion of people living with dementia in planning in low- and middle-income countries and make a case for the inclusion of people living with dementia in care and service planning. We suggest how this can be done at individual, community or national and state level using the following principles: 1) respecting the rights of people living with dementia to self-determination; 2) valuing people living with dementia’s unique understanding of dementia; 3) creating a culture of active inclusion which creates a space for people living with dementia to participate and 4) ensuring appropriate accommodations are in place to maximise participation.

Historically, the evaluation and assessment of the clinical response to treatment for canine back pain is subjective and relies on owner and clinician assessment of pain. This study evaluated the use of sequential infrared thermal images as a measure of the response of canine patients with back pain to a prescribed series of photobiomodulation therapy (PBMT) treatments. Qualifying participants had histories of pain and dysfunction associated with spinal osteoarthritis or intervertebral disk disease, or of non-specific uni- or bilateral back pain along the paravertebral epaxial muscles. Each patient was initially thermally imaged prior to PBMT treatment and then received multiple PBMT treatments delivered to the appropriate spinal area on days 1, 2, 3, and 4. Participants were reimaged on day 7. Thermal images provided an objective measure of superficial temperature changes over the area of PBMT treatment of each patient after the PBMT regimen. The temperature correlated with statistically significant changes in Colorado State University Canine Chronic Pain Scale scoring (CPS) and owner assessment using the Canine Brief Pain Inventory (CBPI), which includes a Pain Severity Score (PSS) and Pain Interference Score (PIS). The correlation of objective thermal imaging data with more subjective outcome measures suggests thermal imaging may be a valuable additional tool in monitoring therapy outcome.

This article provides descriptive insights of the experiences of family caregivers of persons living with dementia during the COVID-19 pandemic. Data were generated as part of a qualitative cross-national project to explore the costs and consequences of providing unpaid dementia care. Participants in Jamaica, who were recruited using community gatekeepers, information booths at health fairs, conferences, and other outreach events, were contacted by telephone to discuss their experiences of the pandemic. When face-to-face in-depth interview data collection was suspended due to the pandemic, ethical approval was received to contact all research participants who were informal unpaid family caregivers, both those whose care recipients had died and those who were active caregivers ( N = 19). Participants in this study were the 10 active family caregivers ( n F = 8; aged 45+; 60% from high socio-economic status). Their updates and reflections during these calls were documented in fieldnotes and analyzed for key themes. Data showed that the pandemic has illustrated the direct costs, both financial and otherwise, that informal dementia carers bear in Jamaica. It also intensified pre-existing challenges faced by family carers. We provide recommendations for sustainable support for family carers.

Evidence from middle-income countries indicates high and increasing prevalence of dementia and need for services. However, there has been little investment in care, treatment or support for people living with dementia and their carers. The Strengthening Responses to Dementia in Developing Countries (STRiDE) project aims to build both research capacity and evidence on dementia care and services in Brazil, Indonesia, India, Jamaica, Kenya, Mexico and South Africa. This article presents the Theory of Change (ToC) approach we used to co-design our research project and to develop a strategic direction for dementia care, treatment and support, with stakeholders. ToC makes explicit the process underlying how a programme will achieve its impact. We developed ToCs in each country and across the STRiDE project with researchers, practitioners, people living with dementia, carers and policymakers at different levels of government. This involved (1) an initial ToC workshop with all project partners (43 participants); (2) ToC workshops in each STRiDE country (22–49 participants in each); (3) comparison between country-specific and overall project ToCs; (4) review of ToCs in light of WHO dementia guidelines and action plan and (5) a final review. Our experiences suggest ToC is an effective way to generate a shared vision for dementia care, treatment and support among diverse stakeholders. However, the project contribution should be clearly delineated and use additional strategies to ensure appropriate participation from people living with dementia and their carers in the ToC process.

Background: Social and health inequities place marginalized populations at increased risk of contracting the novel coronavirus 2019 (COVID-19). While COVID-19 literature continues to accumulate, there remains a lack of comprehensive epidemiological data on COVID-19 in children. The study aims to identify demographic trends in disease severity amongst COVID-19 positive pediatric patients. Methods: We analyzed the medical records of 2217 laboratory-confirmed COVID-19 pediatric patients, ages 0-18, across Indiana. Working with Regenstrief Institute Center of Biomedical Informatics, data was extracted from the databases of Indiana Network for Patient Care, Indiana University Health, and Eskenazi Health from February 28th, 2020 to July 13th, 2020. Factors of interest were age, race, and ethnicity. The study assessed the clinical outcome of disease severity which was defined by one of the following clinical designations: outpatient management exclusively, emergency care without hospital admission, non-pediatric intensive care unit (PICU) hospitalization, PICU hospitalization, and death. Results: The laboratory confirmed COVID-19 pediatric cohort was composed of 12.2% (N= 270) Black or African American, 49.3% (N=1094) white, and 3.2% (N= 71) American Indian/Alaska Native, Asian/Pacific Islander, and Multiracial combined group. 34.4% of Black or African American patients required emergency (12.2%) or inpatient care (22.2%) while 24.4% white patients required emergency (7.0%) or inpatient care (17.3%). 17.6% of the cohort was 0-5 years old, 24.8% was 6-12 years old, and 57.6% was 13-18 years old. 30.9% of the 0-5 age group required emergency or inpatient care while the percentages of the 6-12 age group and 13-18 age group requiring emergency or inpatient care were 20.6% and 18.9%, respectively. Conclusion: While our data is preliminary and requires additional validation, our exploration of racial and age disproportionalities in pediatric coronavirus severity serves to expand on the current COVID-19 literature and understanding of this virus.

The STRiDE project sets out to support the development of effective dementia policy in middle-income countries (Brazil, India, Indonesia, Jamaica, Kenya, Mexico, and South Africa). As part of this it will generate new data about the prevalence of dementia for a subset of these countries. This study aims to identify the current estimates of dementia prevalence in these countries and where the gaps lie in the current literature. A systematic review was completed on 30th April 2019 across electronic databases, identifying dementia prevalence literature originating from any of the seven countries. Four hundred and twenty-nine records were identified following de-duplication; 28 studies met the inclusion criteria and were included in the systematic review. Pooled estimates of dementia prevalence ranged from 2% to 9% based on DSM-IV criteria; these figures were generally higher in studies using other diagnostic criteria (e.g. the 10/66 algorithm). Available prevalence data varied between countries. Only Brazil, Mexico and India had data derived from studies judged as having a low risk of bias. Irrespective of country, studies often were not explicit in detailing the representativeness of their sample, or whether there was non-response bias. Further transparent and externally valid dementia prevalence research is needed across the STRiDE countries.

To examine primary care provider (PCP) screening practice for obstructive sleep apnea (OSA) and predictive factors for screening habits. A secondary objective was to describe the polysomnography completion proportion and outcome. We hypothesized that both provider and child health factors would predict PCP suspicion of OSA.A computer decision support system that automated screening for snoring was implemented in 5 urban primary care clinics in Indianapolis, Indiana. We studied 1086 snoring children aged 1 to 11 years seen by 26 PCPs. We used logistic regression to examine the association between PCP suspicion of OSA and child demographics, child health characteristics, provider characteristics, and clinic site.PCPs suspected OSA in 20% of snoring children. Factors predicting PCP concern for OSA included clinic site (P .01; odds ratio [OR] = 0.13), Spanish language (P .01; OR = 0.53), provider training (P = .01; OR = 10.19), number of training years (P = .01; OR = 4.26) and child age (P .01), with the youngest children least likely to elicit PCP concern for OSA (OR = 0.20). No patient health factors (eg, obesity) were significantly predictive. Proportions of OSA suspicion were variable between clinic sites (range, 6-28%) and between specific providers (range, 0-63%). Of children referred for polysomnography (n = 100), 61% completed the study. Of these, 67% had OSA.Results suggest unexplained small area practice variation in PCP concern for OSA among snoring children. It is likely that many children at risk for OSA remain unidentified. An important next step is to evaluate interventions to support PCPs in evidence-based OSA identification.

Introduction Pharmaceutical risk minimization programs involve interventions designed to support safe and appropriate use of medicines. Currently, information regarding the evaluation of these programs is not publicly reported in a standardized and transparent manner. To address this gap, we developed and piloted a quality reporting checklist entitled the Reporting recommendations Intended for pharmaceutical risk Minimization Evaluation Studies (RIMES). Methods Checklist development was guided by three sources: (1) a theoretical framework derived from program theory and process evaluation; (2) public health intervention design and evaluation principles; and (3) a review of existing quality reporting checklists. Two raters independently reviewed 10 recently published (2012–2016) risk minimization program evaluation studies using the proposed checklist. Inter-rater reliability of the checklist was assessed using Cohen’s Kappa and Gwet’s AC1. Results A 43-item checklist was generated. Results indicated substantial inter-rater reliability overall (κ = 0.65, AC1 = 0.65) and for three (key information, design and evaluation) of the four subscales (κ ≥ 0.64, AC1 ≥ 0.64). The fourth subscale (implementation) showed low reliability based on Cohen’s Kappa, but substantial reliability based on the AC1 (κ = 0.17, AC1 = 0.61). Conclusions The RIMES statement augments relevant elements from existing quality reporting guidelines with items that address aspects of intervention design, implementation and evaluation specific to pharmaceutical risk minimization programs. Our results show that the RIMES statement reliably measures key dimensions of reporting quality. This tailored checklist is an important first step in improving the reporting quality of risk minimization evaluation studies and may ultimately help to improve the quality of these interventions themselves.

Although there is increasing evidence of paternal influence on child outcomes such as language and cognition, researchers are not yet clear on the features of father-child play that are most valuable in terms of child development. Physical play such as rough and tumble play (RTP) is a favored type of father-child play in Western societies that has been linked to children's socioemotional competence. It is important, therefore, to determine the implications of this play for child development. In this review and meta-analysis, associations between father-child physical play and child behavior were examined. The review also focused on study methods. Sixteen studies are reviewed, N = 1,521 father-child dyads, 35% boys. Study characteristics such as definitions of physical play, play settings, play measures, and coding were examined. The meta-analysis found weak to moderate population effects for links between father-child physical play and child aggression, social competence, emotional skills, and self-regulation. Research investigating the effect of father-child physical play on children's development will be improved when definitions clearly identify the nature of play, settings facilitate boisterous play, and measures include frequency and quality of play interactions. This play shows promise as an enhancer of positive father-child relationships and a catalyst for child development.

PURPOSE In recent years, novel types of real-world evidence (RWE) have played a role in various decision-making processes relating to medicinal products, including regulatory approval, patient access, health technology assessment, safety monitoring, clinical use, and post-approval lifecycle management. We therefore reviewed the potential utility of RWE in the cycle of medicinal product benefit-risk (BR) assessment, communication/risk minimization and evaluation ("BRACE"). METHODS A convenience sample of illustrative studies was drawn from the published literature and examined. Specifically, we examined the purpose for using RWE, the type of RWE used, its novelty and how it might be integrated with other data and activities of the BRACE cycle, and how it contributed to regulatory decision-making. RESULTS Eight studies were selected with each illustrating a different activity in the BRACE cycle ranging from BR assessment in the preapproval setting, post-approval assessment of safety or effectiveness, communicating BR information to patients and healthcare professionals, and evaluating the effectiveness of risk minimization initiatives to support a positive BR balance. CONCLUSIONS RWE has an important role in informing regulatory decision-making regarding the BR management of medicines. With increasing digitalization, facilitating data collection and stakeholder engagement in health, this role is only expected to expand in the future. To reach the full potential of RWE, both regulators and sponsors will need to be familiar with a range of existing and emerging methods for generating and analyzing such evidence appropriately and achieve convergence regarding how different types of RWE can best be used to inform BR management and decision-making.

Purpose The purpose of this project was to improve the accuracy of newborn weight classification using a regional newborn growth reference (Olsen), an evidence-based method, to determine SGA, AGA and LGA in term infants compared to the current growth reference (Lubchenco). Design Quality improvement methods using Lewin's Change Theory guided the process. Setting/local problem At an academic medical center term infants were evaluated for weight-for-gestational age using the Lubchenco growth reference as well as other growth references based on provider preference. Patients All term newborns (N = 314) admitted to the newborn nursery during one month following a 3-months implementation of the practice change. Intervention/measurements Newborn nursery nursing staff and provider staff were provided education and training on using and interpreting the new growth reference. Results Use of the Olsen regional growth reference identified more infants as small and fewer infants as large for gestational age. Post hoc analysis with a more global growth reference (Fenton) also identified more infants as small and fewer infants as large for gestational age. There was no statistically significant difference between the Olsen or Fenton growth references. Conclusion Use of either of these two updated growth references more accurately classifies infant weight for gestational age compared to the Lubchenco growth reference, potentially decreasing newborn health risks such as hypoglycemia.

OBJECTIVES: To reduce average length of stay (ALOS) in infants with neonatal abstinence syndrome (NAS) transferred to the inpatient floor from the mother-infant unit. Secondarily, we aimed to reduce morphine exposure in these infants. METHODS: Using quality improvement methodology, we redesigned our approach to NAS on the inpatient floor. Key interventions included transitioning from a modified Finnegan Neonatal Abstinence Scoring System to the “Eat, Sleep, Console” method for withdrawal assessment, reeducation on nonpharmacologic interventions, and adding as-needed morphine as initial pharmacotherapy. Data for infants ≥35 weeks’ gestation with confirmed in utero opioid exposure and worsening symptoms of NAS requiring transfer to the inpatient floor were obtained, including ALOS, number of morphine doses, and total morphine amount administered. Infants with conditions requiring nothing by mouth for >12 hours or morphine initiation in the ICU were excluded. RESULTS: ALOS for infants (baseline n = 40; intervention n = 36) with NAS transferred to the inpatient floor decreased from 10.3 to 4.9 days. Average morphine administered decreased from 38 to 0.3 doses per infant. No infant in the intervention period required scheduled morphine. The percent of all infants transferred to the floor for NAS requiring any morphine decreased from 92% at baseline to 19% postimplementation. There were no observed adverse events or NAS-related readmissions in the intervention period. CONCLUSIONS: Transitioning to the Eat, Sleep, Console assessment with re-enforcement of nonpharmacologic care and use of as-needed morphine as initial pharmacotherapy resulted in a notably decreased ALOS and near elimination of postnatal opioid treatment of infants with NAS managed on our inpatient floor.

Antagonists of retinol-binding protein 4 (RBP4) impede ocular uptake of serum all-trans retinol (1) and have been shown to reduce cytotoxic bisretinoid formation in the retinal pigment epithelium (RPE), which is associated with the pathogenesis of both dry age-related macular degeneration (AMD) and Stargardt disease. Thus, these agents show promise as a potential pharmacotherapy by which to stem further neurodegeneration and concomitant vision loss associated with geographic atrophy of the macula. We previously disclosed the discovery of a novel series of nonretinoid RBP4 antagonists, represented by bicyclic [3.3.0]-octahydrocyclopenta[c]pyrrolo analogue 4. We describe herein the utilization of a pyrimidine-4-carboxylic acid fragment as a suitable isostere for the anthranilic acid appendage of 4, which led to the discovery of standout antagonist 33. Analogue 33 possesses exquisite in vitro RBP4 binding affinity and favorable drug-like characteristics and was found to reduce circulating plasma RBP4 levels in vivo in a robust manner (>90%).

Objective Nonalcoholic steatohepatitis (NASH) is a form of chronic liver disease (CLD): patients have an increased risk of developing cirrhosis, liver failure, and complications (e.g. hepatocellular carcinoma). NASH has a high clinical burden, and likely impairs patients’ health-related quality of life (HRQoL), but there are currently no licensed therapies. The objective of this robust pragmatic literature review was to identify and describe recent studies on the HRQoL burden of NASH from the patient perspective. Methods English-language primary research studies were identified that measured HRQoL in adults with NASH (population-based studies or clinical trials of pharmacological therapy). Searches were conducted in the following bibliographical databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), and Health Technology Assessment Database (HTA). Abstracts from selected congresses (2015/2016) were hand searched. Articles were assessed for relevance by two independent reviewers, and HRQoL data were extracted. Results A total of 567 de-duplicated abstracts were identified, and 20 full-text articles were reviewed. Eight studies were included: five quantitative, two interventional, and one qualitative. The quantitative and interventional studies measured HRQoL using the Short-Form 36 (SF-36) and the Chronic Liver Disease Questionnaire (CLDQ), and the qualitative study involved focus groups and individual interviews. Overall, the studies showed that NASH affects HRQoL, especially physical functioning, with many patients reporting being fatigued. In quantitative studies, overall, patients with NASH had a reduced HRQoL versus normative populations and nonalcoholic fatty liver disease (NAFLD) patients, but not versus chronic liver diseases. A longitudinal study showed that when weight loss was achieved, HRQoL improvement over 6 months was greater in patients with NASH versus NAFLD. Qualitative research suggested that, in addition to fatigue, other symptoms are also burdensome, having a broad negative impact on patients’ lives. The impact of pharmacological treatment on HRQoL was explored in only two included studies. Conclusions HRQoL is impaired in patients with NASH. Patients experience a range of symptoms, especially fatigue, and the impact on their lives is broad. Further research is needed to understand the HRQoL burden of NASH (e.g. assessing NASH-specific impacts not captured by SF-36 and CLDQ) and the impact of future NASH therapies on HRQoL.

We sought to create a new research and clinical instrument -the Influence and Motivation for Patient ACTivation in Diabetes care (IMPACT-D™) - to measure the degree to which patients with type 2 diabetes (T2DM) value health and believe they can influence it.Candidate items were generated via a literature review, expert opinion, and qualitative interviews and focus groups with T2DM patients in Chicago, IL and Chapel Hill, NC. Psychometric testing guided by item response theory was conducted among an online panel of 500 English-speaking adults with T2DM. Differential item functioning analyses evaluated item performance across key participant characteristics. To determine construct validity, IMPACT-D™ scores were compared to other general measures of personality and patient activation. A second study among 300 patients recruited from two internal medicine clinics further assessed associations between the IMPACT-D™ and health outcomes. Cognitive interviews confirmed patient understanding of IMPACT-D™ items and instructions.Exploratory factor analyses revealed a single-factor solution that included 6 items. The IMPACT-D™ demonstrated adequate reliability (α = 0.72) and moderate construct validity with patient activation (r = 0.51, p 0.001) and personality-conscientiousness subscales (r = 0.29, p 0.001). Higher scores on the IMPACT-D™ were associated with better physical health (r = 0.17, p = 0.003) and lower severity of depressive (r = -0.35, p 0.001) and anxiety (r = -0.28, p 0.001) symptoms. There were no significant differences by blood pressure (r = -0.0021, p = 0.9) or haemoglobin A1c (r = -0.069p = 0.2).The IMPACT-D holds potential for use in both clinical care and research applications. Future studies should evaluate how to best operationalize its use for both settings.

Policies to enhance bicycling are correlated with health outcomes. Research has yet to provide an adequate, empirically derived explanation for this finding.To examine a comprehensive model of a pathway potentially linking bicycle policies to overweight/obesity.Data representing multiple years between 2006 and 2012 from CDC, U.S. Census Bureau, U.S. Department of Transportation, and the Alliance for Biking and Walking were subjected to bivariate and multivariate analyses in 2013. A path model was created to explain the relationship between bicycle policies and overweight/obesity in the 48 largest U.S. cities.Zero-order correlations were significant between the number of bicycle policies and the percentage of workers bicycling to work and rates of overweight/obesity. These relationships did not remain statistically significant in the multivariate analysis. However, more bicycle policies were associated with a greater number of bicycle infrastructure components (p0.005). In turn, bicycling infrastructure components were positively related to the percentage of workers bicycling to work (p0.001), which was inversely associated with overweight/obesity rates (p0.05).The results of this study suggest that large cities with more policies aimed at promoting bicycling have fewer overweight/obese residents, partially because the policies are related to supportive bicycling infrastructures that promote bicycling to work.

Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4(-/-) mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%.

This paper examines how older adults living in rural Malawi explain and understand their sex lives. We present sex in this setting as a field in which broader understandings of ageing, aged identities, and conceptions of person- or adulthood in older age are played out and constructed. Qualitative data were collected from men (N=20) and women (N=23) aged 50 to around 90 using in-depth multiple dependent interviews (N=135) between 2008 and 2010. The giving and receipt of sexual pleasure was considered natural and God-given. Primarily understood as a matter of ‘power’, sex was on the one hand, beneficial to older bodies, but on the other, not accessible to such bodies. Declining sexual frequency was associated with declining desire for sex, or frustration stemming from continued desire for sex. These discourses emerged from the way the ageing body was constructed as a weakened body, incompatible with understandings of adulthood based on physical productivity. Older men and women used sex to discursively respond to these challenges to their adulthood in two ways. Firstly, sex was used to confirm strength, physical productivity, and therefore, identity as an ‘adult’. Secondly, adulthood itself was redefined as being based on moral, rather than physical productivity, and refraining from sex was used to demonstrate wisdom, self-control and therefore their ‘adult’ identity. Our results provide in-depth understanding of the ways constructions of ageing and sex can influence complex experiences of marital and non-marital sex in older age. We contribute to debates on sexuality in the gerontological literature by moving discussion beyond the presentation of continued sexuality as somehow exceptional or an indicator of successful ageing. Finally, in a setting of considerable HIV prevalence at older ages, our results challenge a preoccupation with fertility and chronological age in the collection of sexual health data in Africa.

Long-term care is provided for individuals – particularly older people – who have lost self-care capacity because of chronic illness or disability, to improve personal functioning and quality of life. Most long-term care today is provided by unpaid family caregivers, but state-provided and other services are growing in importance. There is increasing emphasis on providing care in community settings in preference to formal residential care settings. Financing of long-term care relies heavily on collective prepayment and out-of-pocket arrangements, with funding shifting increasingly onto service users and families. Self-directed support systems are being introduced in some countries. The future affordability of long-term care is a major challenge across the world.

Background: Although psychosocial care has been regarded as central to palliative and supportive care, there have been few empirically tested approaches to individual intervention. Aim: The subjective experience of advanced cancer patients receiving a new manualized brief individual psychotherapy, referred to as Managing Cancer and Living Meaningfully (CALM), was examined prior to the initiation of a randomized controlled trial testing the effectiveness of this intervention. Design: Semi-structured interviews were conducted with patients who had a diagnosis of advanced cancer, and who underwent the intervention. Setting/Participants: Patients were recruited from a large urban regional cancer center in Toronto, Canada. The 10 interviewees included seven women and three men. All had completed between three to six CALM sessions prior to the interview. Results: The CALM intervention was associated with profound and unique patient-identified benefits and no patient-identified risks or concerns. Five interrelated benefits of the intervention were identified: (1) a safe place to process the experience of advanced cancer; (2) permission to talk about death and dying; (3) assistance in managing the illness and navigating the healthcare system; (4) resolution of relational strain; and (5) an opportunity to ‘be seen as a whole person’ within the healthcare system. These benefits were regarded by participants as unique in their cancer journey. Conclusions: Findings from a qualitative study suggest that the CALM intervention provides substantial benefits for patients with advanced cancer prior to the end of life. Findings informed the development of a randomized controlled trial to evaluate the effectiveness of this intervention.

To examine the long-term effects of having one overweight or obese parent on child weight status and determine whether these effects vary according to parent sex. Prospective study: Longitudinal Study of Australian Children (LSAC). Two-parent families (N=3285) from the LSAC were included if height and weight data were available for both parents and their child at the 2004 and 2008 time points. Child weight status category (healthy, overweight, obese) in 2008 when the child was aged 8–9 years. Regression modelling was used to investigate how self-reported parent weight status in 2004 influenced measured child weight status 4 years later. Parent body mass index (BMI) was significantly correlated with child BMI, but there was no evidence of sex-specific associations between parent and child BMI correlations. The results from the regression analysis showed that having an overweight or obese father, but a healthy weight mother, significantly increased the odds of child obesity (odds ratio: 4.18, 95% confidence interval (CI): 1.01–17.33 and odds ratio: 14.88, 95% CI: 2.61–84.77, respectively), but the reverse scenario (overweight or obese mother with a healthy weight father) was not a significant predictor of child overweight or obesity (odds ratio: 2.52, 95% CI: 0.38–16.71 and odds ratio: 2.56, 95% CI: 0.31–21.26, respectively). Children with overweight or obese fathers are at a higher risk of becoming obese. This suggests that interventions are urgently required to test the efficacy of treating overweight fathers as a key strategy for childhood obesity prevention and/or treatment.

Rationale Evidence-based medicine (EBM) is commonly advocated as a ‘gold standard’ of clinical practice. A prominent definition of EBM is: the integration of best research evidence with clinical expertise and patient values. Over time, various versions of a conceptual model or framework for implementing EBM (i.e. how to practice EBM) have been developed. Aims and objectives This paper (i) traces the evolution of the different versions of the conceptual model; (ii) tries to make explicit the underlying goals, assumptions and logic of the various versions by exploring the definitions and meaning of the components identified in each model, and the methods suggested for integrating these into clinical practice; and (iii) offers an analytic critique of the various model iterations. Methods A literature review was undertaken to identify, summarize, and compare the content of articles and books discussing EBM as a conceptual model to guide physicians in clinical practice. Results Our findings suggest that the EBM model of clinical practice, as it has evolved over time, is largely belief-based, because it is lacking in empirical evidence and theoretical support. The model is not well developed and articulated in terms of defining model components, justifying their inclusion and suggesting ways to integrate these in clinical practice. Conclusion These findings are significant because without a model that clearly defines what constitutes an EBM approach to clinical practice we cannot (i) consistently teach clinicians how to do it and (ii) evaluate whether it is being done.

5-HT(1A) receptor knockout (1AKO) mice have a robust anxiety phenotype. Tissue-specific "rescue" strategies and electrophysiology have implicated a critical role for postsynaptic 5-HT(1A) receptors, particularly in the CA1 region of the hippocampus.In this study, we evaluated differences in membrane properties and synaptic activity in CA1 hippocampal pyramidal cells between 1AKOs and wild-type (WT) controls to better understand the cellular correlates of anxiety in this mouse model.Whole-cell patch-clamp recordings were conducted in CA1 pyramidal cells in hippocampal brain slices from 1AKOs and WTs that had previously been screened for anxiety with the elevated-plus maze. Spontaneous miniature inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs) and stimulus-evoked eIPSCs and eEPSCs were recorded in addition to the effect of the benzodiazepine agonist diazepam or the inverse agonist FG 7142 on γ-aminobutyric acid (GABA)ergic eIPSCs.Evoked EPSC amplitude was greater in 1AKOs than WTs. When subjects were pooled across genotypes, anxiety measures correlated with eEPSC amplitude, indicating enhanced postsynaptic glutamate synaptic activity under conditions of synaptic activation in anxious subjects. While GABA synaptic activity and sensitivity to diazepam were not affected by genotype or correlated with anxiety, sensitivity to the anxiogenic FG 7142 was smaller in anxious subjects.These data indicate enhanced postsynaptic glutamate receptor sensitivity and decreased GABAergic inhibition by a benzodiazepine inverse agonist in CA1 hippocampal neurons of anxious mice are produced by deletion of the 5-HT(1A) receptor. These data provide new information about interactions between 5-HT, GABA, and glutamate systems during the expression of chronic anxiety.

Stress-related psychiatric disorders such as anxiety and depression involve dysfunction of the serotonin [5-hydroxytryptamine (5-HT)] system. Previous studies have found that the stress neurohormone corticotropin-releasing factor (CRF) inhibits 5-HT neurons in the dorsal raphe nucleus (DRN)in vivo. The goals of the present study were to characterize the CRF receptor subtypes (CRF-R1 and -R2) and cellular mechanisms underlying CRF–5-HT interactions. Visualized whole-cell patch-clamp recording techniques in brain slices were used to measure spontaneous or evoked GABA synaptic activity in DRN neurons of rats and CRF effects on these measures. CRF-R1 and -R2-selective agonists were bath applied alone or in combination with receptor-selective antagonists. CRF increased presynaptic GABA release selectively onto 5-HT neurons, an effect mediated by the CRF-R1 receptor. CRF increased postsynaptic GABA receptor sensitivity selectively in 5-HT neurons, an effect to which both receptor subtypes contributed. CRF also had direct effects on DRN neurons, eliciting an inward current in 5-HT neurons mediated by the CRF-R2 receptor and in non-5-HT neurons mediated by the CRF-R1 receptor. These results indicate that CRF has direct membrane effects on 5-HT DRN neurons as well as indirect effects on GABAergic synaptic transmission that are mediated by distinct receptor subtypes. The inhibition of 5-HT DRN neurons by CRFin vivomay therefore be primarily an indirect effect via stimulation of inhibitory GABA synaptic transmission. These results regarding the cellular mechanisms underlying the complex interaction between CRF, 5-HT, and GABA systems could contribute to the development of novel treatments for stress-related psychiatric disorders.

OBJECTIVE:The American Academy of Pediatrics recommends intramuscular (IM) vitamin K prophylaxis for all newborns to prevent vitamin K deficiency bleeding. Given the serious implications of late-onset vitamin K deficiency bleeding, our objective was to examine factors influencing parents’ decisions to refuse IM vitamin K prophylaxis.METHODS:Parents intending to refuse IM vitamin K prophylaxis at delivery were recruited from 5 community hospitals, 1 academic medical center, and 2 birthing centers in a single Southeastern state. Participants completed a written survey including demographics, birth and parenting decisions (eg, breastfeeding), and open-ended questions about their vitamin K information sources, concerns, and knowledge of risks.RESULTS:The incidence of refusal was highest at the birthing centers. Fifty-four parents intending to refuse IM vitamin K completed the survey. Most were white (78%), over age 30 (57%), and college graduates (65%). All reported intention to exclusively breastfeed. Most refused hepatitis B vaccine (90%) and erythromycin eye ointment (77%). The most common source of information was the Internet (70%). Concerns included synthetic or toxic ingredients (37%), excessive dose (28%), and side effects (24%). Eighty-three percent of parents reported awareness of risks associated with vitamin K refusal. However, only 6 parents (11%) decided to accept IM prophylaxis.CONCLUSIONS:This study provides an understanding of the concerns, mindset, and information sources used by parents refusing IM vitamin K. Educating parents about the importance of IM prophylaxis should begin in the prenatal period and must address concerns parents identify on the Internet.

This paper presents a conceptual framework which captures the macro-environmental and micro-level contexts and processes of a woman's pathway to terminating her pregnancy or seeking abortion-related care. The framework has global applicability, across legal contexts and safety spectra. It can be applied at all points in the reproductive lifespan and all marital statuses. The purpose of this framework is to identify and specify the most salient aspects of abortion decision-making across populations. Social scientists as well as policy and programme planners can use the framework to highlight aspects of the macro/micro environment that facilitate or hinder women's abilities to terminate unwanted pregnancies safely and in a timely manner.

Given that maternal morbidity and mortality from unsafe abortion persist, especially in Africa, there is a pressing need to understand the abortion decision-making process. However, little is known about men's influence on and involvement in women's abortion decision making and care seeking.A qualitative study was conducted at the largest public provider of abortion-related care in Zambia. Thematic framework analysis was used to categorize and synthesize data from in-depth interviews conducted in 2013 with 71 women who received a safe abortion and 41 who received care following an incomplete (unsafe) abortion.Men influenced whether women sought a safe or unsafe abortion; their actions, lack of action and anticipated actions-negative and positive-reflected broader gender inequities. Abandonment by men, and the desire to avoid disclosing pregnancy to men because of fear of their reactions or interference, were important influences on some women's decision to seek abortion, on the secrecy and urgency with which abortion was pursued and on the level of risk assumed. However, other women discussed men's positive influences on their abortion care seeking. In this setting of low awareness of the legality and availability of abortion, some men used their greater social and economic resources to facilitate safe abortion by providing information and paying for care.Increasing knowledge about the legality and availability of safe abortion is vital not only among sexually active women, but also among those they confide in, including men.Contexto: Dado que, especialmente en África, persiste la morbilidad y mortalidad materna derivada del aborto inseguro, hay una necesidad apremiante de comprender el proceso de toma de decisiones asociado con el aborto. Sin embargo, es poco lo que se sabe sobre la influencia e involucramiento de los hombres en la toma de decisiones de las mujeres y en la búsqueda de atención médica relativa al aborto. Métodos: Se condujo un estudio cualitativo en la institución pública proveedora de servicios relacionados con el aborto más grande de Zambia. Se usó análisis de marco temático para categorizar y sintetizar datos de entrevistas en profundidad realizadas en 2013 con 71 mujeres que recibieron servicios de aborto seguro y 41 que recibieron atención posterior a un aborto incompleto (inseguro). Resultados: Los hombres ejercieron influencia sobre las mujeres en cuanto a la búsqueda de un aborto seguro o inseguro; sus acciones, la falta de acción y las acciones anticipadas —negativas y positivas— revelaron amplias inequidades de género. El abandono por parte de los hombres y el deseo de evitar la revelación del embarazo a los hombres debido al temor de sus reacciones o interferencias, influyeron de manera importante tanto en las decisiones de algunas mujeres a la hora de buscar un aborto, como en el secreto y urgencia con que se procuró el aborto y el nivel de riesgo asumido. Sin embargo, otras mujeres hablaron acerca de la influencia positiva de los hombres en su búsqueda de atención relativa al aborto. En este entorno de baja conciencia sobre la legalidad y disponibilidad del aborto, algunos hombres utilizaron sus amplios recursos sociales y económicos para facilitar el aborto seguro al proporcionar información y pagar por los servicios. Conclusiones: Aumentar el conocimiento sobre la legalidad y disponibilidad del aborto seguro es vital, no solo entre las mujeres sexualmente activas, sino también entre las personas en las que ellas confían, incluidos los hombres.Contexte: Étant donné la persistance de la morbidité et de la mortalité maternelles entourant l'avortement non médicalisé, en Afrique surtout, le besoin de comprendre le processus décisionnel de l'avortement est impérieux. On en sait cependant peu sur l'influence des hommes et leur implication dans la décision des femmes d'avorter et leur recherche de soins. Méthodes: Une étude qualitative a été effectuée dans les locaux du plus grand prestataire public de soins liés à l'avortement en Zambie. L'étude a procédé par analyse de cadre thématique pour catégoriser et synthétiser les données d'entretiens en profondeur menés en 2013 avec 71 femmes qui avaient obtenu un avortement médicalisé et 41 ayant reçu des soins suite à un avortement incomplet (non médicalisé). Résultats: La décision d'obtenir un avortement, médicalisé ou non, est influencée par les hommes. Leurs actes, leur inaction et leurs actes anticipés—négatifs comme positifs—sont le reflet de plus vastes inégalités de genre. L'abandon par les hommes, de même que le désir d'éviter de révéler une grossesse aux hommes de peur de leur réaction ou ingérence, influencent fortement la décision prise par certaines femmes de se faire avorter, le secret et l'urgence de l'obtention de l'avortement et le niveau de risque assumé. D'autres femmes décrivent cependant l'influence positive des hommes sur leur recherche de soins suite à un avortement. Dans ce contexte de faible sensibilisation à la légalité et à la disponibilité de l'avortement, certains hommes utilisent leurs plus grandes ressources sociales et économiques pour faciliter l'avortement médicalisé, par l'apport d'information et l'acquittement du coût des soins.La connaissance accrue de la légalité et de la disponibilité de l'avortement médicalisé est vitale, non seulement parmi les femmes sexuellement actives, mais aussi parmi les personnes à qui elles se confient, y compris les hommes.

Research on HIV infection and sexual behaviour in sub-Saharan Africa typically focuses on individuals aged 15–49 years, under the assumption that both become less relevant for older individuals. We test this assumption using data from rural Malawi to compare sexual behaviour and HIV infection among individuals aged 15–49 with individuals aged 50–64 and 65 years and over. Although general declines with age were observed, levels of sexual activity and HIV remained considerable: 26.7 percent and 73.8 percent of women and men aged 65 and older reported having sex in the last year, respectively; men’s average number of sexual partners remained above one; and HIV prevalence is significantly higher for men aged 50–64 (8.9 percent) than men aged 15–49 (4.1 percent). We conclude that older populations are relevant to studies of sexual behaviour and HIV risk. Their importance is likely to increase as access to antiretrovirals in Africa increases. We recommend inclusion of adults aged over 49 years in African HIV/AIDS research and prevention efforts.

In the search for new antibacterial agents, the enzyme FabI has been identified as an attractive target. Employing a structure guided approach, the previously reported ene-amide series of FabI inhibitors were expanded to include 2,3,4,5-tetrahydro-1H-pyrido[2,3-b and e][1,4]diazepines. These novel series incorporate additional H-bonding functions and can be more water soluble than their naphthyridinone progenitors; diazepine 16c is shown to be efficacious in a mouse infection model.