ASHA-Led Community-Based Groups to Support Control of Hypertension in Rural India Are Feasible and Potentially Scalable.

Background: To improve the control of hypertension in low- and middle-income countries, we trialed a community-based group program co-designed with local policy makers to fit within the framework of India's health system. Trained accredited social health activists (ASHAs), delivered the program, in three economically and developmentally diverse settings in rural India. We evaluated the program's implementation and scalability. Methods: Our mixed methods process evaluation was guided by the United Kingdom Medical Research Council guidelines for complex interventions. Meeting attendance reports, as well as blood pressure and weight measures of attendees and adherence to meeting content and use of meeting tools were used to evaluate the implementation process. Thematic analysis of separate focus group discussions with participants and ASHAs as well as meeting reports and participant evaluation were used to investigate the mechanisms of impact. Results: Fifteen ASHAs led 32 community-based groups in three rural settings in the states of Kerala and Andhra Pradesh, Southern India. Overall, the fidelity of intervention delivery was high. Six meetings were delivered over a 3-month period to each of the intervention groups. The mean number of meetings attended by participants at each site varied significantly, with participants in Rishi Valley attending fewer meetings [mean (SD) = 2.83 (1.68)] than participants in West Godavari (Tukeys test, p = 0.009) and Trivandrum (Tukeys test, p < 0.001) and participants in West Godavari [mean (SD) = 3.48 (1.72)] attending significantly fewer meetings than participants in Trivandrum [mean (SD) = 4.29 (1.76), Tukeys test, p < 0.001]. Culturally appropriate intervention resources and the training of ASHAs, and supportive supervision of them during the program were critical enablers to program implementation. Although highly motivated during the implementation of the program ASHA reported historical issues with timely remuneration and lack of supportive supervision. Conclusions: Culturally appropriate community-based group programs run by trained and supported ASHAs are a successful and potentially scalable model for improving the control of hypertension in rural India. However, consideration of issues related to unreliable/insufficient remuneration for ASHAs, supportive supervision and their formal role in the wider health workforce in India will be important to address in future program scale up. Trial Registration: Clinical Trial Registry of India [CTRI/2016/02/006678, Registered prospectively].

Rapid assessment of prevalence of blindness and cataract surgery in Kabul province, Afghanistan.

OBJECTIVE: To estimate prevalence and causes of blindness and vision impairment and assess cataract surgical coverage and quality of cataract surgery in Kabul. METHODS AND ANALYSIS: A total of 3751 adults aged 50 years and above were recruited from 77 randomly selected clusters. Each participant underwent presenting and pinhole visual acuity assessment and lens examination. Those with pinhole visual acuity <6/12 in either eye had a dilated fundus examination to determine the cause of reduced vision. Those with apparent lens opacity were interviewed on barriers to cataract surgery. RESULTS: The age-adjusted and sex-adjusted prevalence of blindness was 2.4% (95% CI: 1.8% to 3.0%). Prevalence of severe, moderate and mild vision impairment was 2.2% (95% CI: 1.7% to 2.7%), 6.9% (95% CI: 6.0% to 7.9%) and 8.7% (95% CI: 7.5% to 9.8%), respectively. Cataract was the main cause of blindness (36.8%), severe (54.4%) and moderate (46.1%) vision impairment. Uncorrected refractive error was the leading cause of mild vision impairment (20.3%). Age-related macular degeneration was the second leading cause of blindness (23.0%). In people with a presenting visual acuity of <3/60, cataract surgical coverage was 89.7%, and effective cataract surgical coverage was 67.8%. The major barriers to uptake of the available cataract surgical services were the need for surgery was not felt (23.7%) and cost (22.0%). CONCLUSION: Kabul province has a high prevalence of blindness, largely due to cataract and age-related macular generation. The quality of cataract surgery is also lagging in terms of good visual outcomes. This calls for immediate efforts to improving the reach and quality of existing eye services and readiness to respond to the increasing burden of posterior eye disease.

Effectiveness of interventions to increase uptake and completion of treatment for diabetic retinopathy in low- and middle-income countries: a rapid review protocol.

BACKGROUND: Vision loss due to diabetic retinopathy can largely be prevented or delayed through treatment. Patients with vision-threatening diabetic retinopathy are typically offered laser or intravitreal injections which often require more than one treatment cycle. However, treatment is not always initiated, or it is not completed, resulting in poor visual outcomes. Interventions aimed at improving the uptake or completion of treatment for diabetic retinopathy can potentially help prevent or delay visual loss in people with diabetes. METHODS: We will search MEDLINE, Embase, Global Health and Cochrane Register of Studies for studies reporting interventions to improve the uptake of treatment for diabetic retinopathy (DR) and/or diabetic macular oedema (DMO), compared with usual care, in adults with diabetes. The review will include studies published in the last 20 years in the English language. We will include any study design that measured any of the following outcomes in relation to treatment uptake and completion for DR and/or DMO: (1) proportion of patients initiating treatment for DR and/or DMO among those to whom it is recommended, (2) proportion of patients completing treatment for DR and/or DMO among those to whom it is recommended, (3) proportion of patients completing treatment for DR and/or DMO among those initiating treatment and (4) number and proportion of DR and/or DMO rounds of treatment completed per patient, as dictated by the treatment protocol. For included studies, we will also report any measures of cost-effectiveness when available. Two reviewers will screen search results independently. Risk of bias assessment will be done by two reviewers, and data extraction will be done by one reviewer with verification of 10% of the papers by a second reviewer. The results will be synthesised narratively. DISCUSSION: This rapid review aims to identify and synthesise the peer-reviewed literature on the effectiveness of interventions to increase uptake and completion of treatment for DR and/or DMO in LMICs. The rapid review methodology was chosen in order to rapidly synthesise the available evidence to support programme implementers and policy-makers in designing evidence-based health programmes and public health policy and inform the allocation of resources. SYSTEMATIC REVIEW REGISTRATION: OSF osf.io/h5wgr.

Effectiveness of task-shifting for the detection of diabetic retinopathy in low- and middle-income countries: a rapid review protocol.

BACKGROUND: Diabetic retinopathy is the most common ocular complication of diabetes and a cause of vision loss in adults. Diabetic retinopathy screening leading to early identification of the disease followed by timely treatment, can prevent vision loss in people living with diabetes. A key barrier to the implementation of screening services in low- and middle-income countries is the low number of ophthalmologists per million population. Interventions that shift screening to non-ophthalmology cadres have been implemented in programmes in low- and middle-income countries and are routinely used in high-income countries. The aim of this rapid review is to summarise the published literature reporting the effectiveness of task-shifting interventions for the detection of diabetic retinopathy by non-ophthalmologists in low- and middle-income countries. METHODS: We will search MEDLINE, Embase, Global Health and Cochrane Register of Studies for studies reporting task-shifting interventions for diabetic retinopathy detection. The review will include studies published in the last 10 years in the English language. We will include any interventional or observational comparative study measuring outcomes in terms of participation or access to diabetic retinopathy detection services (uptake) and quality of diabetic retinopathy detection services (detection, severity, diagnostic accuracy). For included studies, cost-effectiveness of the task-shifting intervention will also be presented. Two reviewers will screen search results independently. The risk of bias assessment and data extraction will be carried out by one reviewer with verification of 10% of the papers by a second reviewer. The results will be synthesised narratively. DISCUSSION: Differences in health systems organization, structure and resources will determine the need and success of task-shifting interventions for DR screening. The review will examine how these interventions have been used and/or tested in LMICs. The results will be of interest to policy makers and programme managers tasked with designing and implementing services to prevent and manage diabetes and its complications in similar settings. SYSTEMATIC REVIEW REGISTRATION: OSF: https://osf.io/dfhg6/ .

Indicators for Assessing the Quality of Refractive Error Care.

SIGNIFICANCE: Quality refractive error care is essential for reducing vision impairment. Quality indicators and standardized approaches for assessing the quality of refractive error care need to be established. PURPOSE: This study aimed to develop a set of indicators for assessing the quality of refractive error care and test their applicability in a real-world setting using unannounced standardized patients (USPs). METHODS: Patient outcomes and three quality of refractive error care (Q.REC) indicators (1, optimally prescribed spectacles; 2, adequately prescribed spectacles; 3, vector dioptric distance) were developed using existing literature, refraction training standards, and consulting educators. Twenty-one USPs with various refractive errors were trained to visit optical stores across Vietnam to have a refraction, observe techniques, and order spectacles. Spectacles were assessed against each Q.REC indicator and tested for associations with vision and comfort. RESULTS: Overall, 44.1% (184/417) of spectacles provided good vision and comfort. Of the spectacles that met Q.REC indicators 1 and 2, 62.5 and 54.9%, respectively, provided both good vision and comfort. Optimally prescribed spectacles (indicator 1) were significantly more likely to provide good vision and comfort independently compared with spectacles that did not meet any indicator (good vision: 94.6 vs. 85.0%, P = .01; comfortable: 66.1 vs. 36.3%, P < .01). Adequately prescribed spectacles (indicator 2) were more likely to provide good comfort compared with spectacles not meeting any indicator (57.7 vs. 36.3%, P < .01); however, vision outcomes were not significantly different (85.9 vs. 85.0%, P = .90). Good vision was associated with a lower mean vector dioptric distance (P < .01) but not with comfort (P = .52). CONCLUSIONS: The optimally prescribed spectacles indicator is a promising approach for assessing the quality of refractive error care without additional assessments of vision and comfort. Using USPs is a practical approach and could be used as a standardized method for evaluating the quality of refractive error care.

Effectiveness of a scalable group-based education and monitoring program, delivered by health workers, to improve control of hypertension in rural India: A cluster randomised controlled trial.

BACKGROUND: New methods are required to manage hypertension in resource-poor settings. We hypothesised that a community health worker (CHW)-led group-based education and monitoring intervention would improve control of blood pressure (BP). METHODS AND FINDINGS: We conducted a baseline community-based survey followed by a cluster randomised controlled trial of people with hypertension in 3 rural regions of South India, each at differing stages of epidemiological transition. Participants with hypertension, defined as BP ≥ 140/90 mm Hg or taking antihypertensive medication, were advised to visit a doctor. In each region, villages were randomly assigned to intervention or usual care (UC) in a 1:2 ratio. In intervention clusters, trained CHWs delivered a group-based intervention to people with hypertension. The program, conducted fortnightly for 3 months, included monitoring of BP, education about hypertension, and support for healthy lifestyle change. Outcomes were assessed approximately 2 months after completion of the intervention. The primary outcome was control of BP (BP < 140/90 mm Hg), analysed using mixed effects regression, clustered by village within region and adjusted for baseline control of hypertension (using intention-to-treat principles). Of 2,382 potentially eligible people, 637 from 5 intervention clusters and 1,097 from 10 UC clusters were recruited between November 2015 and April 2016, with follow-up occurring in 459 in the intervention group and 1,012 in UC. Mean age was 56.9 years (SD 13.7). Baseline BP was similar between groups. Control of BP improved from baseline to follow-up more in the intervention group (from 227 [49.5%] to 320 [69.7%] individuals) than in the UC group (from 528 [52.2%] to 624 [61.7%] individuals) (odds ratio [OR] 1.6, 95% CI 1.2-2.1; P = 0.001). In secondary outcome analyses, there was a greater decline in systolic BP in the intervention than UC group (-5.0 mm Hg, 95% CI -7.1 to -3.0; P < 0.001) and a greater decline in diastolic BP (-2.1 mm Hg, 95% CI -3.6 to -0.6; P < 0.006), but no detectable difference in the use of BP-lowering medications between groups (OR 1.2, 95% CI 0.8-1.9; P = 0.34). Similar results were found when using imputation analyses that included those lost to follow-up. Limitations include a relatively short follow-up period and use of outcome assessors who were not blinded to the group allocation. CONCLUSIONS: While the durability of the effect is uncertain, this trial provides evidence that a low-cost program using CHWs to deliver an education and monitoring intervention is effective in controlling BP and is potentially scalable in resource-poor settings globally. TRIAL REGISTRATION: The trial was registered with the Clinical Trials Registry-India (CTRI/2016/02/006678).

Health outcomes for Australian Aboriginal and Torres Strait Islander children born preterm, low birthweight or small for gestational age: A nationwide cohort study.

OBJECTIVE: To examine health outcomes in Australian Aboriginal and Torres Strait Islander children experiencing perinatal risk and identify protective factors in the antenatal period. METHODS: Baby/Child cohorts of the Longitudinal Study of Indigenous Children, born 2001-2008, across four annual surveys (aged 0-8 years, N = 1483). Children with 'mild' and 'moderate-to-high' perinatal risk were compared to children born normal weight at term for maternal-rated global health and disability, and body-mass-index measured by the interviewer. RESULTS: Almost one third of children had experienced mild (22%) or moderate-to-high perinatal risk (8%). Perinatal risk was associated with lower body-mass-index z-scores (regression coefficients adjusted for pregnancy and environment factors: mild = -0.21, 95% CI = -0.34, -0.07; moderate-to-high = -0.42, 95% CI = -0.63, -0.21). Moderate-to-high perinatal risk was associated with poorer global health, with associations becoming less evident in models adjusted for pregnancy and environment factors; but not evident for disability. A range of protective factors, including cultural-based resilience and smoking cessation, were associated with lower risk of adverse outcomes. CONCLUSIONS: Perinatal risks are associated with Australian Aboriginal and Torres Strait children experiencing adverse health particularly lower body weight. Cultural-based resilience and smoking cessation may be two modifiable pathways to ameliorating health problems associated with perinatal risk.

Rapid assessment of avoidable blindness in Papua New Guinea: a nationwide survey.

OBJECTIVE: To estimate the prevalence and main causes of blindness and vision impairment in people aged 50 years and older in Papua New Guinea (PNG). DESIGN: National cross-sectional population-based survey in National Capital District (NCD), Highlands, Coastal and Islands regions. METHODS: Adults aged 50 years and above were recruited from 100 randomly selected clusters. Each participant underwent monocular presenting and pinhole visual acuity (VA) assessment and lens examination. Those with pinhole VA<6/12 in either eye had a dilated fundus examination to determine the primary cause of reduced vision. Those with obvious lens opacity were interviewed on barriers to cataract surgery. RESULTS: A total of 4818 adults were examined. The age-adjusted and sex-adjusted prevalence of blindness (VA <3/60), severe vision impairment (SVI, VA <6/60 but ≥3/60), moderate vision impairment (MVI, VA <6/18 but ≥6/60) and early vision impairment (EVI, VA <6/12 but ≥6/18) was 5.6% (95% CI 4.9% to 6.3%), 2.9% (95% CI 2.5% to 3.4%), 10.9% (95% CI 9.9% to 11.9%) and 7.3% (95% CI 6.6% to 8.0%), respectively. The main cause of blindness, SVI and MVI was cataract, while uncorrected refractive error was the main cause of EVI. A significantly higher prevalence of blindness, SVI and MVI occurred in the Highlands compared with NCD. Across all regions, women had lower cataract surgical coverage and spectacle coverage than men. CONCLUSIONS: PNG has one of the highest reported prevalence of blindness globally. Cataract and uncorrected refractive error are the main causes, suggesting a need for increased accessible services with improved resources and advocacy for enhancing eye health literacy.

Rapid assessment of avoidable blindness and diabetic retinopathy in people aged 50 years and older in the National Capital District of Papua New Guinea.

BACKGROUND/AIMS: To conduct an assessment of avoidable blindness, diabetes mellitus and diabetic retinopathy (DR) in adults aged 50 years and older in the National Capital District (NCD) region of Papua New Guinea (PNG). METHODS: A cross-sectional population-based survey was performed for which 25 clusters of 50 people aged ≥50 years were randomly selected from the NCD region. The standardised rapid assessment of avoidable blindness (RAAB) with diabetic retinopathy (+DR) methodology was used. Blindness was defined as presenting visual acuity <3/60 in the better eye. Participants were classified as having diabetes if they were known to have diabetes or if their random blood glucose level was ≥200 mg/dL. Dilated fundus examination and Scottish DR grading were performed. RESULTS: In total, 1192 out of 1250 eligible participants (95.4%) were examined. Of these, 7.8% had known or newly diagnosed diabetes. Seventy-one per cent of participants with known diabetes had a blood glucose level ≥200 mg/dL, and 82.9% had never had an ophthalmological examination for DR. Prevalence of DR and/or maculopathy was 46.4%. The age-adjusted and sex-adjusted prevalence of diabetes was estimated at 8.1% (95% CI 5.7% to 10.4%) in the population aged 50 years or older in the NCD region of PNG. CONCLUSIONS: Prevalence of diabetes in adults aged 50 years and older was lower than reported elsewhere in the region, and lower than other RAAB+DR surveys. Despite this, the prevalence of DR is high compared with other RAAB+DR surveys and demonstrates the need for increased awareness and accessibility to eye services for people with diabetes.

A peer-support lifestyle intervention for preventing type 2 diabetes in India: A cluster-randomized controlled trial of the Kerala Diabetes Prevention Program.

BACKGROUND: The major efficacy trials on diabetes prevention have used resource-intensive approaches to identify high-risk individuals and deliver lifestyle interventions. Such strategies are not feasible for wider implementation in low- and middle-income countries (LMICs). We aimed to evaluate the effectiveness of a peer-support lifestyle intervention in preventing type 2 diabetes among high-risk individuals identified on the basis of a simple diabetes risk score. METHODS AND FINDINGS: The Kerala Diabetes Prevention Program was a cluster-randomized controlled trial conducted in 60 polling areas (clusters) of Neyyattinkara taluk (subdistrict) in Trivandrum district, Kerala state, India. Participants (age 30-60 years) were those with an Indian Diabetes Risk Score (IDRS) ≥60 and were free of diabetes on an oral glucose tolerance test (OGTT). A total of 1,007 participants (47.2% female) were enrolled (507 in the control group and 500 in the intervention group). Participants from intervention clusters participated in a 12-month community-based peer-support program comprising 15 group sessions (12 of which were led by trained lay peer leaders) and a range of community activities to support lifestyle change. Participants from control clusters received an education booklet with lifestyle change advice. The primary outcome was the incidence of diabetes at 24 months, diagnosed by an annual OGTT. Secondary outcomes were behavioral, clinical, and biochemical characteristics and health-related quality of life (HRQoL). A total of 964 (95.7%) participants were followed up at 24 months. Baseline characteristics of clusters and participants were similar between the study groups. After a median follow-up of 24 months, diabetes developed in 17.1% (79/463) of control participants and 14.9% (68/456) of intervention participants (relative risk [RR] 0.88, 95% CI 0.66-1.16, p = 0.36). At 24 months, compared with the control group, intervention participants had a greater reduction in IDRS score (mean difference: -1.50 points, p = 0.022) and alcohol use (RR 0.77, p = 0.018) and a greater increase in fruit and vegetable intake (≥5 servings/day) (RR 1.83, p = 0.008) and physical functioning score of the HRQoL scale (mean difference: 3.9 score, p = 0.016). The cost of delivering the peer-support intervention was US$22.5 per participant. There were no adverse events related to the intervention. We did not adjust for multiple comparisons, which may have increased the overall type I error rate. CONCLUSIONS: A low-cost community-based peer-support lifestyle intervention resulted in a nonsignificant reduction in diabetes incidence in this high-risk population at 24 months. However, there were significant improvements in some cardiovascular risk factors and physical functioning score of the HRQoL scale. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12611000262909.

Cultural adaptation of a peer-led lifestyle intervention program for diabetes prevention in India: the Kerala diabetes prevention program (K-DPP).

BACKGROUND: Type 2 diabetes mellitus (T2DM) is now one of the leading causes of disease-related deaths globally. India has the world's second largest number of individuals living with diabetes. Lifestyle change has been proven to be an effective means by which to reduce risk of T2DM and a number of "real world" diabetes prevention trials have been undertaken in high income countries. However, systematic efforts to adapt such interventions for T2DM prevention in low- and middle-income countries have been very limited to date. This research-to-action gap is now widely recognised as a major challenge to the prevention and control of diabetes. Reducing the gap is associated with reductions in morbidity and mortality and reduced health care costs. The aim of this article is to describe the adaptation, development and refinement of diabetes prevention programs from the USA, Finland and Australia to the State of Kerala, India. METHODS: The Kerala Diabetes Prevention Program (K-DPP) was adapted to Kerala, India from evidence-based lifestyle interventions implemented in high income countries, namely, Finland, United States and Australia. The adaptation process was undertaken in five phases: 1) needs assessment; 2) formulation of program objectives; 3) program adaptation and development; 4) piloting of the program and its delivery; and 5) program refinement and active implementation. RESULTS: The resulting program, K-DPP, includes four key components: 1) a group-based peer support program for participants; 2) a peer-leader training and support program for lay people to lead the groups; 3) resource materials; and 4) strategies to stimulate broader community engagement. The systematic approach to adaptation was underpinned by evidence-based behavior change techniques. CONCLUSION: K-DPP is the first well evaluated community-based, peer-led diabetes prevention program in India. Future refinement and utilization of this approach will promote translation of K-DPP to other contexts and population groups within India as well as other low- and middle-income countries. This same approach could also be applied more broadly to enable the translation of effective non-communicable disease prevention programs developed in high-income settings to create context-specific evidence in rapidly developing low- and middle-income countries. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry: ACTRN12611000262909 . Registered 10 March 2011.

What Influences Parents' Fear about Children's Independent Mobility? Evidence from a State-Wide Survey of Australian Parents.

PURPOSE: To identify factors associated with generalized and stranger-specific parental fear (PF) about children's independent mobility (CIM), a critical aspect of physical activity. DESIGN: Cross-sectional survey; random sampling frame, minimum quotas of fathers, rural residents. SETTING: State of Victoria, Australia. SUBJECTS: Parents of children aged 9 to 15 years (n = 1779), 71% response rate. MEASURES: Validated measures of PF and fear of strangers (FoS); parent, child, social, and environmental factors. ANALYSIS: Unadjusted and adjusted linear regression stratified by child age (9-10; 11-13; 14-15). RESULTS: Adjusted models explained a substantial proportion of variance across all age groups (PF: 33.6%-36.7%; FoS: 39.1%-44.0%). Perceived disapproval from others was consistently associated with both outcomes (PF: ß =.11 to 23, p ≤ .05; FoS: ß =.17-.21, p ≤ .001) as was parents' perception of children's competence to travel safely (PF: ß = -.24 to -.11, p ≤ .05; FoS: ß = -.16 to -.13, p ≤ .01). Factors associated with FoS included having a female child (ß = -.21 to -.13, p ≤ .001), language other than English (ß = .09 to.11, p ≤ .01), and low levels of parent education (ß = -.14 to -08, p ≤ .05). CONCLUSION: The current study suggests that social norms, child competence, and perceptions about the benefits of CIM underpin PF. This evidence informs the development of interventions to reduce PF and promote CIM and children's physical activity.

Cluster randomised feasibility trial to improve the Control of Hypertension In Rural India (CHIRI): a study protocol.

INTRODUCTION: Hypertension is emerging in rural populations of India. Barriers to diagnosis and treatment of hypertension may differ regionally according to economic development. Our main objectives are to estimate the prevalence, awareness, treatment and control of hypertension in 3 diverse regions of rural India; identify barriers to diagnosis and treatment in each setting and evaluate the feasibility of a community-based intervention to improve control of hypertension. METHODS AND ANALYSIS: This study includes 4 main activities: (1) assessment of risk factors, quality of life, socioeconomic position and barriers to changes in lifestyle behaviours in ∼14 500 participants; (2) focus group discussions with individuals with hypertension and indepth interviews with healthcare providers, to identify barriers to control of hypertension; (3) use of a medicines-availability survey to determine the availability, affordability and accessibility of medicines and (4) trial of an intervention provided by Accredited Social Health Activists (ASHAs), comprising group-based education and support for individuals with hypertension to self-manage blood pressure. Wards/villages/hamlets of a larger Mandal are identified as the primary sampling unit (PSU). PSUs are then randomly selected for inclusion in the cross-sectional survey, with further randomisation to intervention or control. Changes in knowledge of hypertension and risk factors, and clinical and anthropometric measures, are assessed. Evaluation of the intervention by participants provides insight into perceptions of education and support of self-management delivered by the ASHAs. ETHICS AND DISSEMINATION: Approval for the overall study was obtained from the Health Ministry's Screening Committee, Ministry of Health and Family Welfare (India), institutional review boards at each site and Monash University. In addition to publication in peer-reviewed articles, results will be shared with federal, state and local government health officers, local healthcare providers and communities. TRIAL REGISTRATION NUMBER: CTRI/2016/02/006678; Pre-results.

Factors associated with trajectories of psychological distress for Australian fathers across the early parenting period.

PURPOSE: Little is known about the course of fathers' psychological distress and associated risk factors beyond the postnatal period. Therefore, the current study aimed to: (a) assess the course of distress over 7 years postnatally; (b) identify classes of fathers defined by their symptom trajectories; and (c) identify early postnatal factors associated with persistent symptoms. METHOD: Data from 2,470 fathers in the Longitudinal Study of Australian Children were analysed using latent growth modelling. Fathers' psychological distress was assessed using the Kessler-6 (Kessler et al. in Arch Psychiatry 60:184-189, 2003) when their children were aged 0-1, 2-3, 4-5 and 6-7 years. RESULTS: Overall, distress was highest in the first postnatal year and then decreased over time. Two distinct trajectories were identified. The majority of fathers (92%) were identified as having minimal distress in the first postnatal year which decreased over time, whilst 8% had moderate distress which increased over time. Low parental self-efficacy, poor relationship and job quality were associated with 'persistent and increasing distress'. CONCLUSIONS: Early postnatal factors associated with fathers' persistent distress were identified, providing opportunities for early identification and targeted early intervention.

Stressful life events and the onset of chronic diseases among Australian adults: findings from a longitudinal survey.

OBJECTIVES: This article examines the link between stressful life events and illness by considering both onset and reoccurrence of chronic illnesses. Using longitudinal data, we estimate the extent to which life events increase the likelihood of depression or anxiety, type 2 diabetes, cancer, coronary heart disease, circulatory disease, asthma and emphysema among Australian adults aged ≥21 years. METHODS: Longitudinal data were obtained from the nationally representative Household, Income and Labour Dynamics in Australia panel survey collected at waves 3 (2003), 7 (2007) and 9 (2009). Participants (N = 9222) answered life events questions relating to the preceding 12 months and chronic illnesses lasting (or expected to last for) 6 months. Weighted pooled and random effects logistic regressions were performed, controlling for confounders and previous illness, and also performed on subsamples delineated by reported illnesses in wave 3. RESULTS: Work-related stress [odds ratio (OR) = 1.54, P < 0.001] was positively associated with the onset of depression or anxiety. Personal stress increased the likelihood of the onset of depression or anxiety (OR = 1.70, P < 0.001), type 2 diabetes (OR = 1.47, P < 0.05) and circulatory diseases (OR = 1.72, P < 0.05), while family-related stress increased the likelihood of the onset of heart (OR = 1.32, P < 0.01) and circulatory diseases (OR = 1.32, P < 0.05). CONCLUSIONS: Independent of personal characteristics and key health measures (body mass index, hypertension and disability), these findings suggest that work-related, personal and family-related stressful life events contribute to the development and/or course of chronic diseases.

Postpartum maternal separation anxiety, overprotective parenting, and children's social-emotional well-being: longitudinal evidence from an Australian cohort.

Postpartum maternal separation anxiety refers to a mothers' experience of worry and concern about leaving her child for short-term separations. The long-term effects of high maternal separation anxiety on maternal parenting behaviors and child outcomes have been not been established empirically. The aim of this study was to ascertain the prospective relationships between maternal separation anxiety during the child's first year of life, and overprotective parenting and children's social and emotional functioning at age 2-3 years. Structural equation modeling with a large representative cohort of Australian mother-child dyads (N = 3,103) indicated that high maternal separation anxiety was associated with more overprotective parenting behaviors and poorer child socioemotional functioning at age 2-3 years. Findings suggest women with high postpartum maternal separation anxiety may sustain this vigilance across the first years following birth, promoting overprotective behaviors, and resulting in increased behavior problems in their children. Support for women around negotiating separation from their children early in parenthood may prevent the establishment of a repertoire of parenting behaviors that includes unnecessarily high vigilance, monitoring, and anxiety about separation.

Psychosocial risk factors associated with fathers' mental health in the postnatal period: results from a population-based study.

PURPOSE: Fathers' psychological distress in the postnatal period can have adverse effects on their children's wellbeing and development, yet little is known about the factors associated with fathers' distress. This paper examines a broad range of socio-demographic, individual, infant and contextual factors to identify those associated with fathers' psychological distress in the first year postpartum. METHODS: Secondary analysis of data from 3,219 fathers participating in the infant cohort of the Longitudinal Study of Australian Children at wave 1 when children were 0-12 months of age. RESULTS: Approximately 10 % of fathers reported elevated symptoms of psychological distress. Logistic regression analyses revealed that the risk factors were poor job quality, poor relationship quality, maternal psychological distress, having a partner in a more prestigious occupation and low parental self-efficacy. CONCLUSION: These findings provide new information to guide the assessment of fathers' risk for psychological distress in postnatal period. There are also important social policy implications related to workplace entitlements and the provision of services for fathers.

Father mental health during the early parenting period: results of an Australian population based longitudinal study.

PURPOSE: The primary objective of this study was to report on the occurrence of mental health difficulties for a large national sample of Australian fathers of children aged 0-5 years (n = 3,471). Secondary objectives were to compare fathers' mental health against normative data for the general male adult population, and to examine the course of mental health problems for fathers across the early childhood period. METHODS: Secondary analysis of data from the infant cohort of the Longitudinal Study of Australian Children at three waves when children were 0-12 months, 2-3 and 4-5 years. Comparative data on the prevalence of psychological distress in the Australian adult male population sourced from the National Survey of Mental Health and Wellbeing. RESULTS: Approximately nine per cent of fathers reported symptomatic or clinical psychological distress at each wave, as measured by the Kessler-6. Approximately 30 % reporting distress at wave 1 continued to report distress at a similar or worse level across waves 2 and 3. Fathers not living with their children also had high rates of distress (14 % at wave 1 and 10 % at wave 2). Finally, fathers in the present study had 1.38 increased odds (95 % CI 1.12-1.69) for psychological distress compared with the Australian adult male population. CONCLUSIONS: Fathers are at risk of experiencing postnatal mental health difficulties, which may persist across the early childhood period for some fathers. The results suggest routine assessment of fathers' wellbeing should be undertaken in the postnatal period with mental health interventions and support provided across the early childhood period.

Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes.

BACKGROUND AND PURPOSE: Imatinib is a clinically important inhibitor of tyrosine kinases that are dysregulated in chronic myelogenous leukaemia and gastrointestinal stromal tumours. Inter-individual variation in imatinib pharmacokinetics is extensive, and influences drug safety and efficacy. Hepatic cytochrome P450 (CYP) 3A4 has been implicated in imatinib N-demethylation, but the clearance of imatinib decreases during prolonged therapy. CYP3A phenotype correlates with imatinib clearance at the commencement of therapy, but not at steady state. The present study evaluated the possibility that multiple CYPs may contribute to imatinib oxidation in liver. EXPERIMENTAL APPROACH: Imatinib biotransformation in human liver microsomes (n= 20) and by cDNA-expressed CYPs was determined by LC-MS. Relationships between imatinib N-demethylation and other drug metabolizing CYPs were assessed. KEY RESULTS: N-desmethylimatinib formation was correlated with microsomal oxidation of the CYP3A4 substrates testosterone (ρ= 0.60; P < 0.01) and midazolam (ρ= 0.46; P < 0.05), and the CYP2C8 substrate paclitaxel (ρ= 0.58; P < 0.01). cDNA-derived CYPs 2C8, 3A4, 3A5 and 3A7 supported imatinib N-demethylation, but 10 other CYPs were inactive; in kinetic studies, CYP2C8 was a high-affinity enzyme with a catalytic efficiency ∼15-fold greater than those of CYPs 3A4 and 3A5. The CYP3A inhibitors ketoconazole and troleandomycin, and the CYP2C8 inhibitors quercetin and paclitaxel decreased imatinib oxidation. From molecular modelling, the imatinib structure could be superimposed on a pharmacophore for CYP2C8 substrates. CONCLUSIONS AND IMPLICATIONS: CYP2C8 and CYPs 3A contribute to imatinib N-demethylation in human liver. The involvement of CYP2C8 may account in part for the wide inter-patient variation in imatinib pharmacokinetics observed in clinical practice.

Impaired irinotecan biotransformation in hepatic microsomal fractions from patients with chronic liver disease.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The anticancer agent irinotecan is a prodrug that is hydrolyzed by hepatic carboxylesterase to its active and toxic metabolite SN-38 and oxidized by CYP3A4 to its inactive metabolite APC. Irinotecan therapy is complicated by co-administered drugs that inhibit CYP3A4 and decrease APC formation and that indirectly increase SN-38 formation. Dose adjustment in cancer patients with liver disease has been recommended. WHAT THIS STUDY ADDS: In microsomal fractions from patients with severe hepatic dysfunction both APC and SN-38 formation were decreased due to down-regulation of CYP3A4 and carboxylesterase enzymes. Thus relative SN-38 : APC formation was preserved. In some fractions the SN-38:APC ratio was increased, thus providing a possible explanation for clinical reports of increased SN-38 exposure in some patients with liver dysfunction. Close monitoring of SN-38 formation in patients with severe liver disease is warranted. AIMS: Dose modification with the anticancer agent irinotecan is recommended in patients with severe liver dysfunction. This study evaluated the impact of liver disease on the relative formation of phase I products of irinotecan biotransformation in human microsomes in vitro. METHODS: Microsomes from subjects with normal liver function and liver dysfunction (n=20) were assessed for irinotecan biotransformation and the expression of cytochrome P450 (CYP) 3A4 and carboxylesterase (CES) enzymes. RESULTS: Liver disease down-regulated CYP3A4 expression (median 33% of control, range 0-126%, P<0.05) and impaired CYP3A4-dependent oxidation of irinotecan to the inactive 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC) (median 0.2, range 0-1.21 pmol mg protein(-1) min(-1) compared with median 0.66, range 0-2.35 in control, P<0.01). CES-mediated hydrolysis of irinotecan to 7-ethyl-10-hydroxycamptothecin (SN-38) was also impaired in liver disease (median 8.38, range 0-20.7 pmol mg protein(-1) min(-1) compared with median 13.3, range 0-28.9 in control, P<0.05). In seven of 20 liver disease microsomes neither metabolite was detected but in three the SN-38:APC ratio was high (41-68) compared with the remaining 10 samples (ratio 11-36). CONCLUSIONS: Down-regulation of CYP3A4 in liver disease decreased APC formation from irinotecan. SN-38 production was decreased and CES1 and 2 were down-regulated in most samples. However, in a subset of disease samples SN-38 production was relatively high because CYP3A4 activity was markedly impaired. This may account for clinical reports of increased SN-38 exposure in some patients with liver disease. Dose adjustments in cancer patients with liver disease who receive irinotecan are important and circulating SN-38 concentrations should be monitored closely.