Invariant natural killer T cells minimally influence gut microbiota composition in mice.

Invariant Natural Killer T (iNKT) cells are unconventional T cells that respond to glycolipid antigens found in microbes in a CD1d-dependent manner. iNKT cells exert innate-like functions and produce copious amounts of cytokines, chemokines and cytotoxic molecules within only minutes of activation. As such, iNKT cells can fuel or dampen inflammation in a context-dependent manner. In addition, iNKT cells provide potent immunity against bacteria, viruses, parasites and fungi. Although microbiota-iNKT cell interactions are not well-characterized, mounting evidence suggests that microbiota colonization early in life impacts iNKT cell homeostasis and functions in disease. In this study, we showed that CD1d-/- and Vα14 Tg mice, which lack and have increased numbers of iNKT cells, respectively, had no significant alterations in gut microbiota composition compared to their littermate controls. Furthermore, specific iNKT cell activation by glycolipid antigens only resulted in a transient and minimal shift in microbiota composition when compared to the natural drift found in our colony. Our findings demonstrate that iNKT cells have little to no influence in regulating commensal bacteria at steady state.Abbreviations: iNKT: invariant Natural Killer T cell; αGC: α-galactosylceramide.

Inequalities in life expectancy in Australia according to education level: a whole-of-population record linkage study.

BACKGROUND: Life expectancy in Australia is amongst the highest globally, but national estimates mask within-country inequalities. To monitor socioeconomic inequalities in health, many high-income countries routinely report life expectancy by education level. However in Australia, education-related gaps in life expectancy are not routinely reported because, until recently, the data required to produce these estimates have not been available. Using newly linked, whole-of-population data, we estimated education-related inequalities in adult life expectancy in Australia. METHODS: Using data from 2016 Australian Census linked to 2016-17 Death Registrations, we estimated age-sex-education-specific mortality rates and used standard life table methodology to calculate life expectancy. For men and women separately, we estimated absolute (in years) and relative (ratios) differences in life expectancy at ages 25, 45, 65 and 85 years according to education level (measured in five categories, from university qualification [highest] to no formal qualifications [lowest]). RESULTS: Data came from 14,565,910 Australian residents aged 25 years and older. At each age, those with lower levels of education had lower life expectancies. For men, the gap (highest vs. lowest level of education) was 9.1 (95 %CI: 8.8, 9.4) years at age 25, 7.3 (7.1, 7.5) years at age 45, 4.9 (4.7, 5.1) years at age 65 and 1.9 (1.8, 2.1) years at age 85. For women, the gap was 5.5 (5.1, 5.9) years at age 25, 4.7 (4.4, 5.0) years at age 45, 3.3 (3.1, 3.5) years at 65 and 1.6 (1.4, 1.8) years at age 85. Relative differences (comparing highest education level with each of the other levels) were larger for men than women and increased with age, but overall, revealed a 10-25 % reduction in life expectancy for those with the lowest compared to the highest education level. CONCLUSIONS: Education-related inequalities in life expectancy from age 25 years in Australia are substantial, particularly for men. Those with the lowest education level have a life expectancy equivalent to the national average 15-20 years ago. These vast gaps indicate large potential for further gains in life expectancy at the national level and continuing opportunities to improve health equity.

Exit strategies: optimising feasible surveillance for detection, elimination, and ongoing prevention of COVID-19 community transmission.

BACKGROUND: Following implementation of strong containment measures, several countries and regions have low detectable community transmission of COVID-19. We developed an efficient, rapid, and scalable surveillance strategy to detect remaining COVID-19 community cases through exhaustive identification of every active transmission chain. We identified measures to enable early detection and effective management of any reintroduction of transmission once containment measures are lifted to ensure strong containment measures do not require reinstatement. METHODS: We compared efficiency and sensitivity to detect community transmission chains through testing of the following: hospital cases; fever, cough and/or ARI testing at community/primary care; and asymptomatic testing; using surveillance evaluation methods and mathematical modelling, varying testing capacities, reproductive number (R) and weekly cumulative incidence of COVID-19 and non-COVID-19 respiratory symptoms using data from Australia. We assessed system requirements to identify all transmission chains and follow up all cases and primary contacts within each chain, per million population. RESULTS: Assuming 20% of cases are asymptomatic and 30% of symptomatic COVID-19 cases present for testing, with R = 2.2, a median of 14 unrecognised community cases (8 infectious) occur when a transmission chain is identified through hospital surveillance versus 7 unrecognised cases (4 infectious) through community-based surveillance. The 7 unrecognised community upstream cases are estimated to generate a further 55-77 primary contacts requiring follow-up. The unrecognised community cases rise to 10 if 50% of cases are asymptomatic. Screening asymptomatic community members cannot exhaustively identify all cases under any of the scenarios assessed. The most important determinant of testing requirements for symptomatic screening is levels of non-COVID-19 respiratory illness. If 4% of the community have respiratory symptoms, and 1% of those with symptoms have COVID-19, exhaustive symptomatic screening requires approximately 11,600 tests/million population using 1/4 pooling, with 98% of cases detected (2% missed), given 99.9% sensitivity. Even with a drop in sensitivity to 70%, pooling was more effective at detecting cases than individual testing under all scenarios examined. CONCLUSIONS: Screening all acute respiratory disease in the community, in combination with exhaustive and meticulous case and contact identification and management, enables appropriate early detection and elimination of COVID-19 community transmission. An important component is identification, testing, and management of all contacts, including upstream contacts (i.e. potential sources of infection for identified cases, and their related transmission chains). Pooling allows increased case detection when testing capacity is limited, even given reduced test sensitivity. Critical to the effectiveness of all aspects of surveillance is appropriate community engagement, messaging to optimise testing uptake and compliance with other measures.

Setting the research agenda for living with and beyond cancer with comorbid illness: reflections on a research prioritisation exercise.

BACKGROUND: People living with and beyond cancer are more likely to have comorbid conditions and poorer mental and physical health, but there is a dearth of in-depth research exploring the psychosocial needs of people experiencing cancer and comorbid chronic conditions. A patient partnership approach to research prioritisation and planning can ensure outcomes meaningful to those affected and can inform policy and practice accordingly, but can be challenging. METHODS: We aimed to inform priorities for qualitative inquiry into the experiences and support needs of people living with and beyond cancer with comorbid illness using a partnership approach. A three-step process including a patient workshop to develop a consultation document, online consultation with patients, and academic expert consultation was carried out. The research prioritisation process was also appraised and reflected upon. RESULTS: Six people attended the workshop, ten responded online and eight academic experts commented on the consultation document. Five key priorities were identified for exploration in subsequent qualitative studies, including the diagnostic journey, the burden of symptoms, managing medications, addressing the needs of informal carers, and service provision. Limitations of patient involvement and reflections on procedural ethics, and the challenge of making measurable differences to patient outcomes were discussed. CONCLUSIONS: Findings from this research prioritisation exercise will inform planned qualitative work to explore patients' experiences of living with and beyond cancer with comorbid illness. Including patient partners in the research prioritisation process adds focus and relevance, and feeds into future work and recommendations to improve health and social care for this group of patients. Reflections on the consultation process contribute to a broadening of understanding the field of patient involvement.

Identifying long-term psychological distress from single measures: evidence from a nationally representative longitudinal survey of the Australian population.

BACKGROUND: Single time-point assessments of psychological distress are often used to indicate chronic mental health problems, but the validity of this approach is unclear. The aims of this study were to investigate how a single assessment of distress relates to longer-term assessment and quantify misclassification from using single measures to indicate chronic distress. METHODS: Data came from the Household, Income and Labour Dynamics in Australia Survey, a nationally representative study of Australian adults. Psychological distress, measured with the Kessler10 and categorised into low (scores:10- < 12), mild (12- < 16), moderate (16- < 22) and high (22-50), has been assessed in the Survey biennially since wave 7. Among respondents who were aged ≥25 years and participated in all waves in which distress was measured, we describe agreement in distress categories, and using a mixed linear model adjusting for age and sex we estimate change in scores, over a two-, four-, six- and eight-year follow-up period. We applied weights, benchmarked to the Australian population, to all analyses. RESULTS: Two-years following initial assessment, proportions within identical categories of distress were 66.0% for low, 54.5% for mild, 44.0% for moderate and 50.3% for high, while 94.1% of those with low distress initially had low/mild distress and 81.4% with high distress initially had moderate/high distress. These patterns did not change materially as follow-up time increased. Over the full eight-year period, 77.3% of individuals with high distress initially reported high distress on ≥1 follow-up occasion. Age-and sex- adjusted change in K10 scores over a two-year period was 1.1, 0.5, - 0.7 and - 4.9 for low, mild, moderate and high distress, respectively, and also did not change materially as follow-up time increased. CONCLUSION: In the absence of repeated measures, single assessments are useful proxies for chronic distress. Our estimates could be used in bias analyses to quantify the magnitude of the bias resulting from use of single assessments to indicate chronic distress.

Head Tilt in Immunodeficient Mice Due to Contamination of Drinking Water by Burkholderia gladioli.

Immunodeficient mice in multiple holding rooms presented with head tilt, circling, spinning when picked up by the tail, dehydration, and lethargy. Burkholderia gladioli, a plant pathogen, was identified as the causative agent. Environmental testing revealed the presence of B. gladioli within the automatic watering system, water bottles, and sipper tubes. Here we describe steps taken to reduce the presence of this organism within the automatic watering system and water bottles. Facilities housing immunodeficient mice should take measures to minimize the accumulation of biofilm within their water-supply systems.

Pertussis vaccination in a cohort of older Australian adults following a cocooning vaccination program.

BACKGROUND: While recommendations to vaccinate adults against pertussis exist, information on uptake for adult tetanus-diphtheria-pertussis vaccine (Tdap) among older adults is limited. METHODS: We used data from the 45 and Up Study, a prospective cohort of adults aged ≥45 years who completed a questionnaire between 2012 and 2014 asking about pertussis vaccination. We evaluated Tdap uptake following a program providing free vaccine for adults in contact with young children between 2009 and 2012. RESULTS: Among 91,432 adults (mean age = 66.3 years, SD = 9.6), 3.1% (n = 2823) reported receiving Tdap prior to the program. This increased seven-fold to 21.8% (n = 19898) after the program finished. Tdap coverage was almost twice as high in women compared to men and among adults more likely to be grandparents than those not. CONCLUSION: These findings suggest that funding for a targeted program can help to substantially increase vaccination coverage as well as decrease disparities in the uptake of Tdap in different sub-groups.

Association between body mass index and laboratory-confirmed influenza in middle aged and older adults: a prospective cohort study.

BACKGROUND: Studies conducted during the 2009 influenza A (H1N1) pandemic found that obesity increases the risk of severe influenza including hospitalization and death. In this study, we examined the relationship of BMI with having laboratory-confirmed seasonal influenza and influenza-related respiratory hospitalization. METHODS: We linked a cohort of 246,494 adults aged ≥45 years with data on BMI to subsequent laboratory-confirmed influenza notifications and cause-specific hospitalizations from 2006 to 2015. Cox-proportional hazard models were used to estimate the risk of incident laboratory-confirmed influenza and influenza-related respiratory hospitalizations according to BMI, adjusting for age, sex and other covariates. RESULTS: After 1,840,408 person-years of follow-up, 1891 participants had laboratory-confirmed influenza notifications (crude rate 10.3/10,000 person-years) of whom 623 were hospitalized for a respiratory illness. Compared to those with healthy BMI (22.5 to <25.0 kg/m2), influenza incidence was respectively 27% (adjusted HR [aHR]: 1.27, 95% CI: 1.10-1.46) and 69% (aHR: 1.69, 1.24-2.29) greater among obese (BMI: 30 to <40 kg/m2) and very obese adults (40 to <50 kg/m2). The equivalent aHRs for hospitalization were 1.57 (95% CI: 1.22-2.01) and 4.81 (95% CI: 3.23-7.17). For every 5-unit BMI increase above 22.5 kg/m2, there was a 15% (aHR: 1.15, 95% CI: 1.09-1.22) increase in risk of having a diagnosis of influenza and 42% increase in hospitalization (aHR: 1.42, 95% CI: 1.30-1.60). These trends did not differ between the pandemic year (2009) and other years. CONCLUSIONS: Our results suggest that obese adults have a similar risk of hospitalization for seasonal influenza as adults with cardiovascular disease and diabetes, and should therefore  be equally prioritized for funded interventions such as targeted immunization programs.

Humane Endpoints for Guinea Pigs Used for Mycobacterium tuberculosis Vaccine Research.

Guinea pigs are a commonly used model for tuberculosis vaccine research. Loss of body weight is the most frequently described humane endpoint for animals used in these studies. During a chronic study, we noted labored breathing in some tuberculosis-infected guinea pigs. To develop consistent humane endpoints for these guinea pigs, we performed an observational study using multiple clinical signs. A combination of body weight loss, labored breathing, and activity level during handling estimated the time to euthanasia within approximately 7 d. Histologic severity scores of lesions in the cranial or caudal lung lobe (or both) supported clinical endpoints. This study presents humane endpoints for the refinement of studies using guinea pigs in tuberculosis research.

Lidocaine Hydrochloride Compared with MS222 for the Euthanasia of Zebrafish (Danio rerio).

Despite several shortcomings, MS222 is the most commonly used chemical agent for euthanasia of zebrafish. Although lidocaine hydrochloride has some advantages over MS222, its effectiveness as a euthanasia agent for zebrafish is unknown. Larvae at 9 to 16 d postfertilization were exposed to 250 mg/L MS222 or 400, 500, 600, 700, 800, 900, or 1000 mg/L lidocaine and observed for cessation of heartbeat. Adult zebrafish were exposed to 250 mg/L MS222 or 400, 500, or 600 mg/L lidocaine; times to loss of righting reflex, cessation of opercular movement, and complete recovery; body length; aversive behavior; and gross and microscopic evidence of acute toxicity were evaluated. The heartbeat was not lost from any larvae in any group, regardless of drug or dosage. For adults, time to loss of righting reflex was greatest in the 500-mg/L lidocaine group. Opercular movement ceased earlier in all lidocaine groups compared with the MS222 group. Fish in the 500-mg/L lidocaine group were smaller than those in other groups. Fewer fish in the lidocaine groups displayed aversive behavior (erratic swimming and piping) compared with the MS222 group. No fish in the lidocaine hydrochloride groups (n = 30) recovered from euthanasia, whereas one fish in the MS222 group did (n = 10). Neither the MS222 nor lidocaine groups showed any gross or histologic changes suggestive of acute toxicity. Our results suggest that lidocaine hydrochloride may be an effective alternative chemical euthanasia agent for adult zebrafish but should not be used in larval fish.

Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia.

Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband-parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽ 1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P = 1.5 × 10(-)(4)). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽ 0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P = 0.018) and de novo mutations (P = 0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N = 614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.

The Cancer, Lifestyle and Evaluation of Risk Study (CLEAR): Rationale and design of an unmatched "case-spouse control" study of over 10,000 participants in New South Wales, Australia.

INTRODUCTION: The New South Wales (NSW) Cancer, Lifestyle and Evaluation of Risk Study (CLEAR) is an open epidemiological bioresource, using an all cancer unmatched case-spouse control design. Participant characteristics and selected confirmed associations are compared to published estimates: current smoking and lung cancer; country of birth and melanoma; body mass index (BMI) and bowel cancer; and paternal history of prostate cancer and prostate cancer, to illustrate the validity of this design. MATERIAL AND METHODS: Cases are NSW residents, ≥18 years, with an incident cancer of any type. Controls are cancer-free spouses of cases. Participants complete a consent form, a questionnaire, and provide an optional blood sample. For analyses, odds ratios for males and females are calculated for cancers and exposures of interest, by sex-matching controls to cases. RESULTS: 10,816 participants (8569 cases, 2247 controls, 54% female) recruited to-date, median age: 61.6 y cases, 61.3 y controls. The top five cancer types are female breast (n=1691), prostate (n=1102), bowel (n=888), melanoma (n=608), and lung (n=265). Adjusted odds ratios (OR) were: 20.65 (95% CI: 13.25-32.19) for lung cancer in current versus never smokers; 1.16 (1.05-1.28) for bowel cancer per 5 kg/m(2) increment in BMI; 1.41 (1.01-1.96) for melanoma in Australian-born compared to those born in UK/Ireland; and 2.47 (1.82-3.37) for prostate cancer in men with versus without a paternal history of prostate cancer. DISCUSSION: This study design, where controls are the spouses of cases diagnosed with a variety of cancers and which are analysed unmatched, avoids potential biases due to overmatching, considered problematic in standard case-spouse control studies, and illustrates that risk estimates analysed are consistent with the published literature. CLEAR methodology provides a practical design to advance local knowledge on the causes of various leading and emerging cancers.

Risk factors for herpes zoster in a large cohort of unvaccinated older adults: a prospective cohort study.

We analysed data from a prospective cohort of 255,024 adults aged ⩾45 years recruited from 2006-2009 to identify characteristics associated with a zoster diagnosis. Diagnoses were identified by linkage to pharmaceutical treatment and hospitalization records specific for zoster and hazard ratios were estimated. Over 940,583 person-years, 7771 participants had a zoster diagnosis; 253 (3·3%) were hospitalized. After adjusting for age and other factors, characteristics associated with zoster diagnoses included: having a recent immunosuppressive condition [adjusted hazard ratio (aHR) 1·58, 95% confidence interval (CI) 1·32-1·88], female sex (aHR 1·36, 95% CI 1·30-1·43), recent cancer diagnosis (aHR 1·35, 95% CI 1·24-1·46), and severe physical limitation vs. none (aHR 1·33, 95% CI 1·23-1·43). The relative risk of hospitalization for zoster was higher for those with an immunosuppressive condition (aHR 3·78, 95% CI 2·18-6·55), those with cancer (aHR 1·78, 95% CI 1·24-2·56) or with severe physical limitations (aHR 2·50, 95% CI 1·56-4·01). The novel finding of an increased risk of zoster diagnoses and hospitalizations in those with physical limitations should prompt evaluation of the use of zoster vaccine in this population.

The need to disentangle key concepts from ecosystem-approach jargon.

The ecosystem approach--as endorsed by the Convention on Biological Diversity (CDB) in 2000-is a strategy for holistic, sustainable, and equitable natural resource management, to be implemented via the 12 Malawi Principles. These principles describe the need to manage nature in terms of dynamic ecosystems, while fully engaging with local peoples. It is an ambitious concept. Today, the term is common throughout the research and policy literature on environmental management. However, multiple meanings have been attached to the term, resulting in confusion. We reviewed references to the ecosystem approach from 1957 to 2012 and identified 3 primary uses: as an alternative to ecosystem management or ecosystem-based management; in reference to an integrated and equitable approach to resource management as per the CBD; and as a term signifying a focus on understanding and valuing ecosystem services. Although uses of this term and its variants may overlap in meaning, typically, they do not entirely reflect the ethos of the ecosystem approach as defined by the CBD. For example, there is presently an increasing emphasis on ecosystem services, but focusing on these alone does not promote decentralization of management or use of all forms of knowledge, both of which are integral to the CBD's concept. We highlight that the Malawi Principles are at risk of being forgotten. To better understand these principles, more effort to implement them is required. Such efforts should be evaluated, ideally with comparative approaches, before allowing the CBD's concept of holistic and socially engaged management to be abandoned or superseded. It is possible that attempts to implement all 12 principles together will face many challenges, but they may also offer a unique way to promote holistic and equitable governance of natural resources. Therefore, we believe that the CBD's concept of the ecosystem approach demands more attention.

How weight change is modelled in population studies can affect research findings: empirical results from a large-scale cohort study.

OBJECTIVES: To investigate how results of the association between education and weight change vary when weight change is defined and modelled in different ways. DESIGN: Longitudinal cohort study. PARTICIPANTS: 60 404 men and women participating in the Social, Environmental and Economic Factors (SEEF) subcomponent of the 45 and Up Study-a population-based cohort study of people aged 45 years or older, residing in New South Wales, Australia. OUTCOME MEASURES: The main exposure was self-reported education, categorised into four groups. The outcome was annual weight change, based on change in self-reported weight between the 45 and Up Study baseline questionnaire and SEEF questionnaire (completed an average of 3.3 years later). Weight change was modelled in four different ways: absolute change (kg) modelled as (1) a continuous variable and (2) a categorical variable (loss, maintenance and gain), and relative (%) change modelled as (3) a continuous variable and (4) a categorical variable. Different cut-points for defining weight-change categories were also tested. RESULTS: When weight change was measured categorically, people with higher levels of education (compared with no school certificate) were less likely to lose or to gain weight. When weight change was measured as the average of a continuous measure, a null relationship between education and annual weight change was observed. No material differences in the education and weight-change relationship were found when comparing weight change defined as an absolute (kg) versus a relative (%) measure. Results of the logistic regression were sensitive to different cut-points for defining weight-change categories. CONCLUSIONS: Using average weight change can obscure important directional relationship information and, where possible, categorical outcome measurements should be included in analyses.

Body mass index and incident hospitalisation for cardiovascular disease in 158 546 participants from the 45 and Up Study.

OBJECTIVE: To investigate the relationship between fine gradations in body mass index (BMI) and risk of hospitalisation for different types of cardiovascular disease (CVD). DESIGN, SUBJECTS AND METHODS: The 45 and Up Study is a large-scale Australian cohort study initiated in 2006. Self-reported data from 158 546 individuals with no history of CVD were linked prospectively to hospitalisation and mortality data. Hazard ratios (HRs) of incident hospitalisation for specific CVD diagnoses in relation to baseline BMI categories were estimated using Cox regression, adjusting for age, sex, region of residence, income, education, smoking, alcohol intake and health insurance status. RESULTS: There were 9594 incident CVD admissions over 583 100 person-years among people with BMI≥20 kg m(-2), including 3096 for ischaemic heart disease (IHD), 1373 for stroke, 411 for peripheral vascular disease (PVD) and 320 for heart failure. The adjusted HR of hospitalisation for all CVD diagnoses combined increased significantly with increasing BMI (P(trend) <0.0001)). The HR of IHD hospitalisation increased by 23% (95% confidence interval (95% CI): 18-27%) per 5 kg m(-2) increase in BMI (compared to BMI 20.0-22.49 kg m(-2), HR (95% CI) for BMI categories were: 22.5-24.99=1.25 (1.08-1.44); 25-27.49=1.43 (1.24-1.65); 27.5-29.99=1.64 (1.42-1.90); 30-32.49=1.63 (1.39-1.91) and 32.5-50=2.10 (1.79-2.45)). The risk of hospitalisation for heart failure showed a significant, but nonlinear, increase with increasing BMI. No significant increase was seen with above-normal BMI for stroke or PVD. For other specific classifications of CVD, HRs of hospitalisation increased significantly with increasing BMI for: hypertension; angina; acute myocardial infarction; chronic IHD; pulmonary embolism; non-rheumatic aortic valve disorders; atrioventricular and left bundle-branch block; atrial fibrillation and flutter; aortic aneurysm; and phlebitis and thrombophlebitis. CONCLUSION: The risk of hospitalisation for a wide range of CVD subtypes increases with relatively fine increments in BMI. Obesity prevention strategies are likely to benefit from focusing on bringing down the mean BMI at the population level, in addition to targeting those with a high BMI.

Mental health services for children exposed to armed conflict: Médecins Sans Frontières' experience in the Democratic Republic of Congo, Iraq and the occupied Palestinian territory.

BACKGROUND: Armed conflict has broad-ranging impacts on the mental health and wellbeing of children and adolescents. Mental health needs greatly exceed service provision in conflict settings, particularly for these age groups. The provision and targeting of appropriate services requires better understanding of the characteristics and requirements of children and adolescents exposed to armed conflict. METHODS: Routine patient and programme monitoring data were analysed for patients <20 years of age attending mental health services provided by Médecins Sans Frontières (MSF) in three countries affected by armed conflict: the Democratic Republic of Congo (DRC), Iraq and the occupied Palestinian territory (oPt). The demographic characteristics, presenting mental health complaint, attributed precipitating event, services provided and short-term outcomes for mental health services users in each country are described. RESULTS: Between 2009 and 2012, 3025 individuals <20 years of age presented for care in DRC and Iraq, and in 2012 in oPt, constituting 14%, 17.5% and 51%, respectively, of all presentations to MSF mental health services in those three countries. The most common precipitating event was sexual violence in DRC (36.5%), domestic violence in Iraq (17.8%) and incarceration or detention in oPt (33%). Armed conflict-related precipitants were reported by 25.9%, 55.0% and 76.4% of youths in DRC, Iraq and oPt, respectively. The most common presenting complaints in children and adolescents were anxiety-related, followed by mood-related, behaviour-related and somatisation problems; these varied according to country and precipitating event. Although a high proportion (45.7%) left programmes early, 97% of those who completed care self-reported improvement in their presenting complaint. CONCLUSIONS: Brief trauma-focused therapy, the current MSF mental health therapeutic intervention, appears to be effective in reducing symptoms arising from the experience of trauma. Although inferences on outcomes are limited by high default rates, this provides a feasible tool for addressing the mental health needs of children exposed to armed conflict. Priorities for future research include understanding why children and adolescents constitute a small proportion of patients in some programmes, why many leave care early and how to address these issues, but this research must occur within the context of efforts to provide access to mental health services for children.

Prospective cohort study of body mass index and the risk of hospitalisation: findings from 246361 participants in the 45 and Up Study.

OBJECTIVE: To quantify the risk of hospital admission in relation to fine increments in body mass index (BMI). DESIGN, SETTING, AND PARTICIPANTS: Population-based prospective cohort study of 246,361 individuals aged greater than or equal to 45 years, from New South Wales, Australia, recruited from 2006-2009. Self-reported data on BMI and potential confounding/mediating factors were linked to hospital admission and death data. MAIN OUTCOMES: Cox-models were used to estimate the relative risk (RR) of incident all-cause and diagnosis-specific hospital admission (excluding same day) in relation to BMI. RESULTS: There were 61,583 incident hospitalisations over 479,769 person-years (py) of observation. In men, hospitalisation rates were lowest for BMI 20-<25 kg m(-2) (age-standardised rate: 120/1000 py) and in women for BMI 18.5-<25 kg m(-2) (102/1000 py); above these levels, rates increased steadily with increasing BMI; rates were 203 and 183/1000 py, for men and women with BMI 35-50 kg m(-2), respectively. This pattern was observed regardless of baseline health status, smoking status and physical activity levels. After adjustment, the RRs (95% confidence interval) per 1 kg m(-2) increase in BMI from ≥ 20 kg m(-2) were 1.04(1.03-1.04) for men and 1.04(1.04-1.05) for women aged 45-64; corresponding RRs for ages 65-79 were 1.03(1.02-1.03) and 1.03(1.03-1.04); and for ages ≥ 80 years, 1.01(1.00-1.01) and 1.01(1.01-1.02). Hospitalisation risks were elevated for a large range of diagnoses, including a number of circulatory, digestive, musculoskeletal and respiratory diseases, while being protective for just two-fracture and hernia. CONCLUSIONS: Above normal BMI, the RR of hospitalisation increases with even small increases in BMI, less so in the elderly. Even a small downward shift in BMI, among those who are overweight not just those who are obese, could result in a substantial reduction in the risk of hospitalisation.