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System science approaches are increasingly used to explore complex public health problems. Quantitative methods, such as participatory dynamic simulation modelling, can mobilise knowledge to inform health policy decisions. However, the analytic and practical steps required to turn collaboratively developed, qualitative system maps into rigorous and policy-relevant quantified dynamic simulation models are not well described. This paper reports on the processes, interactions and decisions that occurred at the interface between modellers and end-user participants in an applied health sector case study focusing on diabetes in pregnancy. An analysis was conducted using qualitative data from a participatory dynamic simulation modelling case study in an Australian health policy setting. Recordings of participatory model development workshops and subsequent meetings were analysed and triangulated with field notes and other written records of discussions and decisions. Case study vignettes were collated to illustrate the deliberations and decisions made throughout the model development process. The key analytic objectives and decision-making processes included: defining the model scope; analysing and refining the model structure to maximise local relevance and utility; reviewing and incorporating evidence to inform model parameters and assumptions; focusing the model on priority policy questions; communicating results and applying the models to policy processes. These stages did not occur sequentially; the model development was cyclical and iterative with decisions being re-visited and refined throughout the process. Storytelling was an effective strategy to both communicate and resolve concerns about the model logic and structure, and to communicate the outputs of the model to a broader audience. The in-depth analysis reported here examined the application of participatory modelling methods to move beyond qualitative conceptual mapping to the development of a rigorously quantified and policy relevant, complex dynamic simulation model. The analytic objectives and decision-making themes identified provide guidance for interpreting, understanding and reporting future participatory modelling projects and methods.

Background Systems science methods such as dynamic simulation modelling are well suited to address questions about public health policy as they consider the complexity, context and dynamic nature of system-wide behaviours. Advances in technology have led to increased accessibility and interest in systems methods to address complex health policy issues. However, the involvement of policy decision makers in health-related simulation model development has been lacking. Where end-users have been included, there has been limited examination of their experience of the participatory modelling process and their views about the utility of the findings. This paper reports the experience of end-user decision makers, including senior public health policy makers and health service providers, who participated in three participatory simulation modelling for health policy case studies (alcohol related harm, childhood obesity prevention, diabetes in pregnancy), and their perceptions of the value and efficacy of this method in an applied health sector context. Methods Semi-structured interviews were conducted with end-user participants from three participatory simulation modelling case studies in Australian real-world policy settings. Interviewees were employees of government agencies with jurisdiction over policy and program decisions and were purposively selected to include perspectives at different stages of model development. Results The ‘co-production’ aspect of the participatory approach was highly valued. It was reported as an essential component of building understanding of the modelling process, and thus trust in the model and its outputs as a decision-support tool. The unique benefits of simulation modelling included its capacity to explore interactions of risk factors and combined interventions, and the impact of scaling up interventions. Participants also valued simulating new interventions prior to implementation in the real world, and the comprehensive mapping of evidence and its gaps to prioritise future research. The participatory aspect of simulation modelling was time and resource intensive and therefore most suited to high priority complex topics with contested options for intervening. Conclusion These findings highlight the value of a participatory approach to dynamic simulation modelling to support its utility in applied health policy settings.

A major limitation to understanding the etiopathogenesis of environmental enteric dysfunction (EED) is the lack of a comprehensive, reproducible histologic framework for characterizing the small bowel lesions. We hypothesized that the development of such a system will identify unique histology features for EED, and that some features might correlate with clinical severity. Duodenal endoscopic biopsies from two cohorts where EED is prevalent (Pakistan, Zambia) and North American children with and without gluten sensitive enteropathy (GSE) were processed for routine hematoxylin & eosin (H&E) staining, and scanned to produce whole slide images (WSIs) which we shared among study pathologists via a secure web browser-based platform. A semi-quantitative scoring index composed of 11 parameters encompassing tissue injury and response patterns commonly observed in routine clinical practice was constructed by three gastrointestinal pathologists, with input from EED experts. The pathologists then read the WSIs using the EED histology index, and inter-observer reliability was assessed. The histology index was further used to identify within- and between-child variations as well as features common across and unique to each cohort, and those that correlated with host phenotype. Eight of the 11 histologic scoring parameters showed useful degrees of variation. The overall concordance across all parameters was 96% weighted agreement, kappa 0.70, and Gwet's AC 0.93. Zambian and Pakistani tissues shared some histologic features with GSE, but most features were distinct, particularly abundance of intraepithelial lymphocytes in the Pakistani cohort, and marked villous destruction and loss of secretory cell lineages in the Zambian cohort. We propose the first EED histology index for interpreting duodenal biopsies. This index should be useful in future clinical and translational studies of this widespread, poorly understood, and highly consequential disorder, which might be caused by multiple contributing processes, in different regions of the world.

In pulmonary tuberculosis (PTB), morbidity during treatment and residual pulmonary disability can be under-estimated. Among adults with smear-positive PTB at an outpatient clinic in Papua, Indonesia, we assessed morbidity at baseline and during treatment, and 6-month residual disability, by measuring functional capacity (six-minute walk test [6MWT] and pulmonary function), quality of life (St George's Respiratory Questionnaire [SGRQ]) and Adverse Events ([AE]: new symptoms not present at outset). Results were compared with findings in locally-recruited volunteers. 200 PTB patients and 40 volunteers were enrolled. 6WMT was 497m (interquartile range 460-529) in controls versus 408m (IQR 346-450) in PTB patients at baseline (p<0.0001) and 470m (IQR 418-515) in PTB patients after 6 months (p=0.02 versus controls). SGRQ total score was 0 units (IQR 0-2.9) in controls, versus 36.9 (27.4-52.8) in PTB patients at baseline (p<0.0001) and 4.3 (1.7-8.8) by 6 months (p<0.0001). Mean percentage of predicted FEV1 was 92% (standard deviation 19.9) in controls, versus 63% (19.4) in PTB patients at baseline (p<0.0001) and 71% (17.5) by 6 months (p<0.0001). After 6 months, 27% of TB patients still had at least moderate-severe pulmonary function impairment, and 57% still had respiratory symptoms, despite most achieving 'successful' treatment outcomes, and reporting good quality of life. More-advanced disease at baseline (longer illness duration, worse baseline X-ray) and HIV positivity predicted residual disability. AE at any time during treatment were common: itch 59%, arthralgia 58%, headache 40%, nausea 33%, vomiting 16%. We found high 6-month residual pulmonary disability and high AE rates. Although PTB treatment is highly successful, the extent of morbidity during treatment and residual impairment could be overlooked if not specifically sought. Calculations of PTB-related burden of disease should acknowledge that TB-related morbidity does not stop at 6 months. Early case detection and treatment are key in minimising residual impairment.

Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference -3%, 95% CI -19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI -9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes. ClinicalTrials.gov. Registry number: NCT00677339.

The Australian Capital Territory ‘It's Your Move!’ (ACT‐IYM) was a three‐year (2012–2014) systems intervention to prevent obesity among adolescents. The ACT‐IYM project involved three intervention schools and three comparison schools and targeted secondary students aged 12–16 years. The intervention consisted of multiple initiatives at individual, community, and school policy level to support healthier nutrition and physical activity. Intervention school‐specific objectives related to increasing active transport, increasing time spent physically active at school, and supporting mental wellbeing. Data were collected in 2012 and 2014 from 656 students. Anthropometric data were objectively measured and behavioural data self‐reported. Proportions of overweight or obesity were similar over time within the intervention (24.5% baseline and 22.8% follow‐up) and comparison groups (31.8% baseline and 30.6% follow‐up). Within schools, two of three the intervention schools showed a significant decrease in the prevalence of overweight and obesity (p<0.05). There was some evidence of effectiveness of the systems approach to preventing obesity among adolescents. The incorporation of systems thinking has been touted as the next stage in obesity prevention and public health more broadly. These findings demonstrate that the use of systems methods can be effective on a small scale.

Other factors apart from hypoalbuminemia and low protein intake must develop kwashiorkor (7), such as extracellular matrix (ECM) degradation and lymphatic damage (6). [...]it was previously shown that edema in children with kwashiorkor resolved even when they were treated with a protein-deficient diet (8), and despite a small increase in serum albumin concentration among children whose oedema resolved or improved, serum albumin concentrations remained far below clinically recognized norms in children (6,9). [...]some of the immune function effects stated in the review are not borne out by the cited references. [...]kwashiorkor in children peaks at around 2 years of age, often after weaning. The neonatal gnotobiotic pigs were fed a diet deficient in macronutrients before 4 days of age. [...]these porcine models may have different intestinal development than children with kwashiorkor, and the cause of the edema may relate to immature intestinal development or other causes. [...]the reported similarities between the immune function of children with kwashiorkor and gnotobiotic pig models cannot be used to establish the face validity of the porcine model.

The study population is thus not representative of the population most at risk of hospitalisation and death from COVID-19 infection in the UK, including care home residents and people with dementia and Parkinson's disease.7 Data for the primary outcome were available for 25 054 (97%) participants. 105 (1%) of 12 529 people in the molnupiravir plus usual care group and 98 (1%) of 12 525 in the usual care group were hospitalised or died (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; posterior probability of superiority 0·33).6 The study provides strong evidence that molnupiravir does not reduce the already low frequency of hospitalisation and death among high-risk—but not necessarily the highest risk—highly vaccinated adults in the community infected mainly with the omicron variant of COVID-19. Both treatments can be prescribed by general practitioners (and dispensed through community pharmacies) to people at high risk of severe illness who test positive for COVID-19, including all people aged 70 years or older. A large proportion of people enrolled in PANORAMIC would not be eligible for subsidised treatment in Australia.8 The advice in Australia is that molnupiravir should be considered for use only if nirmatrelvir–ritonavir is contraindicated or unsuitable.9 However, the many potential drug interactions with nirmatrelvir–ritonavir mean that molnupiravir is the dominant antiviral being used to treat people aged 70 years or older (especially in care homes).

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons.

Disease transmission patterns are needed to inform public health interventions, but remain largely unknown for avian influenza H5N1 virus infections. A recent study on the 139 outbreaks detected in Indonesia between 2005 and 2009 found that the type of exposure to sources of H5N1 virus for both the index case and their household members impacted the risk of additional cases in the household. This study describes the disease transmission patterns in those outbreak households. We compared cases (n = 177) and contacts (n = 496) in the 113 sporadic and 26 cluster outbreaks detected between July 2005 and July 2009 to estimate attack rates and disease intervals. We used final size household models to fit transmission parameters to data on household size, cases and blood-related household contacts to assess the relative contribution of zoonotic and human-to-human transmission of the virus, as well as the reproduction number for human virus transmission. The overall household attack rate was 18.3% and secondary attack rate was 5.5%. Secondary attack rate remained stable as household size increased. The mean interval between onset of subsequent cases in outbreaks was 5.6 days. The transmission model found that human transmission was very rare, with a reproduction number between 0.1 and 0.25, and the upper confidence bounds below 0.4. Transmission model fit was best when the denominator population was restricted to blood-related household contacts of index cases. The study only found strong support for human transmission of the virus when a single large cluster was included in the transmission model. The reproduction number was well below the threshold for sustained transmission. This study provides baseline information on the transmission dynamics for the current zoonotic virus and can be used to detect and define signatures of a virus with increasing capacity for human-to-human transmission.