Facilitators and barriers to attending postpartum screening in women with a recent pregnancy complicated by gestational diabetes mellitus: a qualitative study.

OBJECTIVE: Pregnant women with gestational diabetes mellitus (GDM) are 50% more likely to develop type II diabetes (T2D) within 6 months to 2 years after giving birth. Therefore, international guidelines recommend it is best practice for women diagnosed with GDM to attend screening for T2D 6-12 weeks postpartum and every 1-3 years thereafter for life. However, uptake of postpartum screening is suboptimal. This study will explore the facilitators of and barriers to attending postpartum screening for T2D that women experience. STUDY DESIGN: This was a prospective qualitative cohort study using thematic analysis. METHODS: A total of 27 in-depth, semistructured interviews were conducted over the telephone with women who had recent GDM. Interviews were recorded and transcribed, and data were analysed using thematic analysis. RESULTS: Facilitators of and barriers to attending postpartum screening were identified at three different levels: personal, intervention, and healthcare systems level. The most common facilitators identified were concern for their own health and having the importance of screening explained to them by a health professional. The most common barriers identified were confusion over the test and COVID-19. CONCLUSION: This study identified several facilitators of and barriers to attending postpartum screening. These findings will help to inform research and interventions for improving rates of attendance at postpartum screening to reduce the subsequent risk of developing T2D.

A direct test of the diathesis-stress model for depression.

The diathesis-stress theory for depression states that the effects of stress on the depression risk are dependent on the diathesis or vulnerability, implying multiplicative interactive effects on the liability scale. We used polygenic risk scores for major depressive disorder (MDD) calculated from the results of the most recent analysis from the Psychiatric Genomics Consortium as a direct measure of the vulnerability for depression in a sample of 5221 individuals from 3083 families. In the same we also had measures of stressful life events and social support and a depression symptom score, as well as DSM-IV MDD diagnoses for most individuals. In order to estimate the variance in depression explained by the genetic vulnerability, the stressors and their interactions, we fitted linear mixed models controlling for relatedness for the whole sample as well as stratified by sex. We show a significant interaction of the polygenic risk scores with personal life events (0.12% of variance explained, P-value=0.0076) contributing positively to the risk of depression. Additionally, our results suggest possible differences in the aetiology of depression between women and men. In conclusion, our findings point to an extra risk for individuals with combined vulnerability and high number of reported personal life events beyond what would be expected from the additive contributions of these factors to the liability for depression, supporting the multiplicative diathesis-stress model for this disease.

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

'A melting pot of cultures' -challenges in social adaptation and interactions amongst international medical students.

BACKGROUND: The internationalisation of higher level education and the profiles - nationalities, ethnicities and cultural identities - of students who migrate to undertake higher level education programmes in a different country are increasingly complex. This article explores the way in which cultural backgrounds impact the student's experiences of an international medical school, and how these experiences have the potential to inform the development and design of student support services for those students who are not coping well with the transition. METHODS: Thirty one first year students were interviewed by sixteen second year students who were trained and supervised by an experienced researcher. Three focus group discussions were also held. RESULTS: While many international students had lived in more than one country and region and spoke several languages, most reported difficulties in forming intercultural friendships, especially interactions outside of the academic setting. Some of the challenges faced were similar to what has been reported in the literature, such as difficulties with language and loss of established friendship networks. Other challenges to emerge in this study were the complex interrelatedness of the daily life challenges facing international students regarding the forming and importance of intercultural relations, which is impacted by gender, the presence of alcohol, languages spoken (in addition to English, which was the language used for medical education), and the dominance of the regional grouping the student belongs to. CONCLUSION: The challenges of adaptation and intercultural relations are increasing in complexity and it is important for higher level institutions who enrol international students to understand the nature of the pressures these students experience, outside as well as within the academic environment, and to support them in managing these transitions.

The creative turn in evidence for public health: community and arts-based methodologies.

Background: We propose that arts based methodologies can be of value in the production and exchange of evidence in supporting public health related policy. This article reports on a collaborative piece of work resulting from two projects which took place in a former coal mining town in South Wales. Methods: We used a participatory framework whereby researchers, community members and artists co-produced 'evidence' through the creative arts to inform public policy. We collected a range of data using a number of different techniques, including interviews, focus groups and observation, but also included an extensive range of creative activities. Results: The data provided a diverse range of perspectives on how people of different ages live their lives. The People's Platform was a performance-based debate which was the culmination of the collaboration. The show involved a series of short performances with time for facilitated discussion in-between. It was felt that the show facilitated knowledge exchange on health and wellbeing issues that are usually difficult to express and understand through traditional forms of evidence. Conclusion: Whilst arts-based approaches are not free from risk, they offer an alternative form of knowledge as a necessary complement to the range of data available to policy makers.

A Cross-Sectional Study of Antibiotic Prescribing for Childhood Upper Respiratory Tract Infections in Irish General Practice

Introduction This study aimed to analyse antibiotic prescribing in cases of upper respiratory tract infection (URTI) in children under 6 years attending Irish daytime and out-of-hours General Practice (GP) services. There have been large scale changes in entitlements for free GP care for this group in recent years. Methods A cross-sectional study of children under 6 years with URTI presentations was performed, over a two-week period for three years from 2015 to 2017. Factors associated with antibiotic prescription and preferred antibiotic compliance were examined using multivariate logistic regression. Results 1,007 Under-6 patients presented with an URTI in our sample over the study period. Following introduction of free GP care, patients were 50% less likely to receive an antibiotic prescription. Overall antibiotic prescribing fell from 70% to 50% in daytime services and from 72% to 60% in the out-of-hours setting. Patients presenting to out-of-hours services were more likely to receive an antibiotic (OR: 1.42) and less likely to receive a deferred antibiotic (OR: 0.53). One quarter to one third of all prescriptions were for deferred antibiotics. Year-on-year trends showed a 13% decrease in prescriptions and 13% increase in preferred antibiotic use. Conclusion The introduction of free GP care led to significant reductions in antibiotic prescribing, which may be due to changes in health seeking behaviour by parents or other reasons. Antibiotic prescribing was more commonplace in the out-of-hours setting, and rates remains high by international standards. This study underlines the importance of ongoing work around GP antimicrobial stewardship, particularly in the out-of-hours setting.

Meta-analysis of genome-wide association studies of anxiety disorders.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.

Measuring choice for adults with an intellectual disability - a factor analysis of the adapted daily choice inventory scale.

BACKGROUND: For most people, choice making is an everyday occurrence, but for adults with an intellectual disability (ID), such opportunities are often limited, if not, absent. Defining choice, and related opportunity capacity and supports continue to feature prominently in academic, practice and policy discourse within the field of ID as reflected in the range of measures available. This paper examines the factor analytic properties of an adapted 14-item choice inventory scale. METHOD: Presence and type of choice were recorded in wave 1 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing using a choice inventory scale adapted for the Irish context for 753 participants with ID over age 40 years. Analysis included both an exploratory and confirmatory factor analysis. Descriptive statistics on choice by type of living arrangement, type of interview (proxy, self or supported) and level of ID are presented. RESULTS: Exploratory factor analysis indicates good model fit when using both a 3-item and 4-item response with the 4-item version suggesting a two-factor model. Further exploration of this two-factor model through confirmatory factor analysis highlighted an improved fit for the 4-item model. Further improvement in model fit is found when four item pairs are co-varied within the model. CONCLUSION: Two broad types of choice were found to exist for adults with ID - everyday decisions and key life decisions. In addition, the factor analysis support for the inclusion of a 'no choice' response may help reduce the potential for missing data.

The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects.

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

The use of technology enhanced learning in health research capacity development: lessons from a cross country research partnership.

BACKGROUND: With the recognition of the need for research capacity strengthening for advancing health and development, this research capacity article explores the use of technology enhanced learning in the delivery of a collaborative postgraduate blended Master's degree in Malawi. Two research questions are addressed: (i) Can technology enhanced learning be used to develop health research capacity?, and: (ii) How can learning content be designed that is transferrable across different contexts? METHODS: An explanatory sequential mixed methods design was adopted for the evaluation of technology enhanced learning in the Masters programme. A number of online surveys were administered, student participation in online activities monitored and an independent evaluation of the programme conducted. RESULTS: Remote collaboration and engagement are paramount in the design of a blended learning programme and support was needed for selecting the most appropriate technical tools. Internet access proved problematic despite developing the content around low bandwidth availability and training was required for students and teachers/trainers on the tools used. Varying degrees of engagement with the tools used was recorded, and the support of a learning technologist was needed to navigate through challenges faced. CONCLUSION: Capacity can be built in health research through blended learning programmes. In relation to transferability, the support required institutionally for technology enhanced learning needs to be conceptualised differently from support for face-to-face teaching. Additionally, differences in pedagogical approaches and styles between institutions, as well as existing social norms and values around communication, need to be embedded in the content development if the material is to be used beyond the pilot resource-intensive phase of a project.

International students' experience of a western medical school: a mixed methods study exploring the early years in the context of cultural and social adjustment compared to students from the host country.

BACKGROUND: Few studies have addressed the challenges associated with international students as they adapt to studying medicine in a new host country. Higher level institutions have increasing numbers of international students commencing programmes. This paper explores the experiences of a cohort of students in the early years of medical school in Ireland, where a considerable cohort are from an international background. METHODS: A mixed exploratory sequential study design was carried out with medical students in the preclinical component of a five year undergraduate programme. Data for the qualitative phase was collected through 29 semi-structured interviews using the peer interview method. Thematic analysis from this phase was incorporated to develop an online questionnaire combined with components of the Student Adaptation to College Questionnaire and Student Integration Questionnaire. First year students were anonymously surveyed online. The Mokken Scaling procedure was used to investigate the students' experiences, both positive and negative. RESULTS: Three main themes are identified; social adjustment, social alienation and cultural alienation. The response rate for the survey was 49% (467 Respondents). The Mokken Scaling method identified the following scales (i) Positive experience of student life; (ii) Social alienation, which comprised of negative items about feeling lonely, not fitting in, being homesick and (iii) Cultural alienation, which included the items of being uncomfortable around cultural norms of dress and contact between the sexes. With the threshold set to H = 0.4. Subscales of the positive experiences of student life scale are explored further. CONCLUSIONS: Overall student adjustment to a western third level college was good. Students from regions where cultural distance is greatest reported more difficulties in adjusting. Students from these regions also demonstrate very good adaptation. Some students from the host country and more similar cultural backgrounds were also struggling. Acculturation is more complex than being associated with cultural distance and worthy of further exploration.

Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned.

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).

Carer burden in apathy and impulse control disorders in Parkinson's disease.

BACKGROUND: The neuropsychiatric complications of Parkinson's disease (PD), which include behaviour disturbances such as apathy and the impulse control disorders (ICDs), may have a significant effect on patients with PD and their carers. The contribution of these behaviour disorders to carer burden is less understood. Therefore, the aim of this study was to explore the relationship that apathy and ICDs have with carer burden. METHODS: Non-demented (n = 71) PD-carer dyads (spouse or adult child) participated in the study. The PD participants were divided into three behavioural groups: ICD (n = 21), apathy (n = 22) and controls (n = 28). The three groups were compared for level of burden in their carers by using the Zarit Burden Interview. The PD participants were rated for levels of apathy, impulsivity and motor and psychiatric symptoms. Using a multivariate analysis, we sought the PD-related predictors of carer burden. RESULTS: Significantly, greater burden was seen in carers of PD participants with ICDs (p = 0.002) or apathy (p = 0.004), compared with carers of PD participants without such behavioural disturbances. Linear regression models revealed that attentional ability accounted for burden in carers of the group with apathy, whereas dopaminergic load and depression accounted for burden in carers of the group with impulsivity. CONCLUSION: PD-related behaviour disturbances, such as apathy and ICDs, as well as psychiatric complications, have significant negative implications for burden of care.

Comparison of laparoscopic adjustable gastric banding (LAGB) with other bariatric procedures; a systematic review of the randomised controlled trials.

BACKGROUND: Bariatric surgery can provide efficient weight loss and improvement in obesity-related co-morbidities in adults. Laparoscopic adjustable gastric banding (LAGB) comprised 30.3% of all bariatric procedures between 2009 and 2010 in the UK. This review evaluates the level 1 evidence for change in co-morbidities, quality of life (QoL) and weight provided by LAGB compared with other bariatric procedures. METHOD: Systematic literature search of MEDLINE, EMBASE and CENTRAL (1988 to May 2011) was performed. Only randomised controlled trials (RCTs) were included. Studies with non-surgical comparators, open gastric banding procedures or adolescent participants were excluded. Primary outcome was change in co-morbidities. Secondary outcomes included QoL, weight loss, complications, operation time and length of stay. RESULTS: Five RCTs met the inclusion criteria. Vertical banded gastroplasty, sleeve gastrectomy and gastric bypass were compared to LAGB. Co-morbidities were reported in two studies and QoL in one. LAGB was comparable to other procedures for both of these outcomes. All five trials showed LABG to be effective in weight loss, however all comparative procedures resulted in greater weight loss. Operative time and length of hospital stay were significantly shorter with LAGB. Short-term complications were found to be consistently lower in the LAGB group. Evidence was divided with respect to long-term complications. CONCLUSION: Co-morbidities and QoL are poorly reported and showed no difference between LAGB and other bariatric procedures. Evidence suggests that LAGB is not the most effective surgical procedure to reduce weight. LAGB is associated with lower early complications and shorter operative time and length of stay, and therefore may be preferable to patients.

Behavioural disorders, disability and quality of life in Parkinson's disease.

BACKGROUND: although non-motor symptoms of Parkinson's disease (PD) are known to adversely affect disability and health-related quality of life, the impact that specific disorders of reward and motivation have remains unclear. Impulse control disorders are more likely in those with a younger disease onset although there is no strong evidence to date that apathy is related to age of onset or correlated with a longer duration of disease. OBJECTIVE: to examine the effects of apathy and impulse controls disorders on disability and health-related quality of life. METHODS: a total of 99 non-demented participants with PD (35 with impulse control disorders, 26 with apathy and 38 with neither behavioural complication) were assessed using the Unified Parkinson's Disease Rating Scale (Activities of Daily Living component) and the Schwab-England scale to evaluate disability, and the PDQ (eight items) to assess quality of life. RESULTS: quality of life was reduced in both behavioural groups compared with participants without either condition. Disability was greater in the group with apathy. Variation in disability score (56%, P < 0.001) was explained by greater levels of apathy, depression, motor impairment and longer disease duration. Variation in quality of life score (54%, P < 0.001) was explained by higher levels of impulsivity, depression, dopaminergic load, motor complications, working memory problems and younger age at onset. CONCLUSION: apathy and impulsivity negatively impact on disability and health-related quality of life, emphasising the importance of effective diagnosis and management of these PD-related behavioural disturbances.

Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer.

Moloney Murine Leukemia Virus (MoMuLV) causes T cell neoplasms in rodents but is not known to be a pathogen in primates. The core protein and enzyme genes of the MoMuLV genome together with an amphotropic envelope gene are utilized to engineer the cell lines that generate retroviral vectors for use in current human gene therapy applications. We developed a producer clone that generates a very high concentration of retroviral vector particles to optimize conditions for gene insertion into pluripotent hematopoietic stem cells. This producer cell line also generates a much lower concentration of replication-competent virus that arose through recombination. Stem cells from rhesus monkeys were purified by immunoselection with an anti-CD34 antibody, incubated in vitro for 80-86 h in the presence of retroviral vector particles with accompanying replication-competent virus and used to reconstitute recipients whose bone marrow had been ablated by total body irradiation. The retroviral vector genome was detected in circulating cells of five of eight transplant recipients of CD34+ cells and in the circulating cells of two recipients of infected, unfractionated bone marrow mononuclear cells. Three recipients of CD34+ cells had a productive infection with replication-competent virus. Six or seven mo after transplantation, each of these animals developed a rapidly progressive T cell neoplasm involving the thymus, lymph nodes, liver, spleen, and bone marrow. Lymphoma cells contained 10-50 copies of the replication-competent virus, but lacked the retroviral vector genome. We conclude that replication-competent viruses arising from producer cells making retroviral vectors can be pathogenic in primates, which underscores the importance of carefully screening retroviral producer clones used in human trials to exclude contamination with replication-competent virus.