Patient-reported outcomes with selpercatinib treatment in patients with RET-driven cancers in the phase I/II LIBRETTO-001 trial.

BACKGROUND: This post-hoc retrospective study describes long-term patient-reported outcomes (PROs) for REarranged during Transfection (RET)-altered non-small-cell lung cancer (NSCLC), medullary thyroid cancer (MTC), non-MTC thyroid cancer (TC), and tumor agnostic (TA) patients (Data cut-off: January 2023) from the LIBRETTO-001 trial. PATIENTS AND METHODS: Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). Patients with MTC also completed a modified version of the Systemic Therapy-Induced Diarrhea Assessment Tool (mSTIDAT). The proportion of patients with improved, stable, or worsened status after baseline was reported. PROs were summarized at 3 years (cycle 37) post-baseline for the NSCLC and MTC cohorts, and at 2 years (cycle 25) post-baseline for the TC and TA cohorts. Time-to-event outcomes (time to first improvement or worsening and duration of improvement) were reported. RESULTS: The baseline assessment was completed by 200 (63.3%), 209 (70.8%), 50 (76.9%), and 38 (73.1%) patients in the NSCLC, MTC, TC, and TA cohorts, respectively. The total compliance rate was 80%, 82%, 70%, and 85%, respectively. Approximately 75% (NSCLC), 81% (MTC), 75% (TC), and 40% (TA) of patients across all cohorts reported improved or stable QLQ-C30 scores at year 3 (NSCLC and MTC) or year 2 (TC and TA) with continuous selpercatinib use. Across cohorts, the median time to first improvement ranged from 2.0 to 19.4 months, the median duration of improvement ranged from 1.9 to 28.2 months, and the median time to first worsening ranged from 5.6 to 44.2 months. The total compliance rate for the mSTIDAT was 83.7% and the proportion of patients with MTC who reported diarrhea on the mSTIDAT was reduced from 80.8% at baseline to 35.6% at year 3. CONCLUSIONS: A majority of patients with RET-driven cancers improved or remained stable on most QLQ-C30 domains, demonstrating favorable health-related quality of life as measured by the QLQ-C30 during long-term treatment with selpercatinib.

Academic clinician frontline-worker wellbeing and resilience during the COVID-19 pandemic experience: Were there gender differences?

Prior research suggests COVID-19 has amplified stress on Academic Clinician Frontline-Workers (ACFW). The aim of this paper is: (1) to better understand the experiences of ACFW during the COVID-19 pandemic including their mental-emotional wellbeing, academic productivity, clinical experiences, and (2) to examine any gender differences. A cross-sectional survey was administered to University of Minnesota/M Health Fairview systems' faculty February-June 2021. Of the 291 respondents, 156 were clinicians, with 91 (58 %) identifying as Frontline-Workers (ACFW). Faculty wellbeing was assessed using validated measures in addition to measures of productivity and sociodemographics. For example, ACFW reported a higher Work-Family Conflict (WFC) scores compared to non-ACFW (26.5 vs. 24.1, p = 0.057) but did not report higher Family-Work Conflict (FWC) scores (17.7 vs. 16.3, p = 0.302). Gender sub-analyses, revealed that women ACFW compared to men ACFW reported higher WFC scores (27.7 vs. 24.1, p = 0.021) and FWC (19.3 vs. 14.3, p = 0.004). Academically, ACFW reported submitting fewer grants and anticipated delays in promotion and tenure due to the COVID-19 (p = 0.035). Results suggest COVID-19 has exacerbated ACFW stress and gender inequities. Reports of anticipated delay in promotion for ACFW may pose a challenge for the long-term academic success of ACFW, especially women ACFW. In addition, women may experience higher FWC and WFC as compared to men. Schools of academic medicine should consider re-evaluating promotion/tenure processes and creating resources to support women ACFW as well as ACFW caregivers.

The weather determines the number of cases of tick paralysis in dogs and cats in eastern Australia, caused by Ixodes holocyclus, the eastern paralysis tick.

We studied over 222,000 cases of emergency veterinary consultations in four regions along the eastern coast of Australia. We found that cases of tick paralysis (TP) caused by the eastern paralysis tick, Ixodes holocyclus, accounted for 7.5% of these cases: >16,000 cases. The season of TP and the number (prevalence) of TP cases varied among regions and over the years. Our study of the association between weather and (i) the start of the season of TP, and (ii) the number of TP cases revealed much about the intricate relationship between the weather and I. holocyclus. We studied the effect of the hypothetical availability of isoxazoline-containing tick-preventative medicines and found that an increase in the availability of these medicines had significantly contributed to the decrease in TP cases. We found that the weather in winter accounted for the time of the year the season of TP starts whereas the weather in summer accounted for the number of TP cases in the TP season. Last, through a study of the effects of shifts in the climate under four hypothetical scenarios (warmer/cooler and drier/wetter than average), we propose that the start of the season of TP depends on how soon the weather in winter becomes suitable for the activity (e.g. host-seeking) and the development of I. holocyclus nymphs, and that the number of TP cases during the TP season depends on how many engorged female ticks and their eggs survive during summer.

Participation in the Global Corporate Challenge®, a Four-Month Workplace Pedometer Program, Reduces Psychological Distress.

BACKGROUND: Psychological distress (stress) has been linked to an increased risk of chronic diseases and is exacerbated by a range of workplace factors. Physical activity has been shown to alleviate psychological distress. Previous pedometer-based intervention evaluations have tended to focus on physical health outcomes. This study aimed to investigate the immediate and long-term changes in psychological distress in employees based in Melbourne, Australia after their participation in a four-month pedometer-based program in sedentary workplaces. METHODS: At baseline, 716 adults (aged 40 ± 10 years, 40% male) employed in primarily sedentary occupations, voluntarily enrolled in the Global Corporate Challenge© (GCC©), recruited from 10 Australian workplaces to participate in the GCC® Evaluation Study, completed the Kessler 10 Psychological Distress Scale (K10). Of these, 422 completed the K10 at baseline, 4 months and 12 months. RESULTS: Psychological distress reduced after participation in a four-month workplace pedometer-based program, which was sustained eight months after the program ended. Participants achieving the program goal of 10,000 steps per day or with higher baseline psychological distress had the greatest immediate and sustained reductions in psychological distress. Demographic predictors of immediate reduced psychological distress (n = 489) was having an associate professional occupation, younger age, and being 'widowed, separated or divorced'. CONCLUSIONS: Participation in a workplace pedometer-based program is associated with a sustained reduction in psychological distress. Low-impact physical health programs conducted in groups or teams that integrate a social component may be an avenue to improve both physical and psychological health in the workplace.

Social Isolation and Social Support Influence Health Service Utilisation and Survival after a Cardiovascular Disease Event: A Systematic Review.

Both cardiovascular disease (CVD) and social health carry high health and economic burdens. We undertook a systematic review to investigate the association between social isolation, low social support, and loneliness with health service utilisation and survival after a CVD event among people living in Australia and New Zealand. Four electronic databases were systematically searched for the period before June 2020. Two reviewers undertook the title/abstract screen. One reviewer undertook a full-text screen and data extraction. A second author checked data extraction. Of 756 records, 25 papers met our inclusion criteria. Included studies recruited 10-12,821 participants, aged 18-98 years, and the majority were males. Greater social support was consistently associated with better outcomes on four of the five themes (discharge destination, outpatient rehabilitation attendance, rehospitalisation and survival outcomes; no papers assessed the length of inpatient stay). Positive social health was consistently associated with better discharge designation to higher independent living. As partner status and living status did not align with social isolation and social support findings in this review, we recommend they not be used as social health proxies. Our systematic review demonstrates that social health is considered in cardiac care decisions and plays a role in how healthcare is being delivered (i.e., outpatient, rehabilitation, or nursing home). This likely contributes to our finding that lower social support is associated with high-intensity healthcare services, lower outpatient rehabilitation attendance, greater rehospitalisation and poorer survival. Given our evidence, the first step to improve cardiac outcomes is acknowledging that social health is part of the decision-making process. Incorporating a formal assessment of social support into healthcare management plans will likely improve cardiac outcomes and survival. Further research is required to assess if support person/s need to engage in the risk reduction behaviours themselves for outpatient rehabilitation to be effective. Further synthesis of the impact of social isolation and loneliness on health service utilisation and survival after a CVD event is required.

Joint Food and Water Insecurity Had a Multiplicative Effect on Women's Depression in Urban Informal Settlements in Makassar, Indonesia during the COVID-19 Pandemic.

BACKGROUND: Women living in urban informal settlements may be particularly vulnerable to the detrimental effects of the COVID-19 pandemic because of increased economic and psychosocial stressors in resource-limited environments. OBJECTIVES: The objective of this study was to assess the associations between food and water insecurity during the pandemic and depression among women living in the urban informal settlements in Makassar, Indonesia. METHODS: We implemented surveys at 3 time points among women enrolled in the Revitalizing Informal Settlements and their Environments trial. Depression was measured using the Center for Epidemiologic Studies Depression Scale-10 (CESD-10) between November and December 2019 and again between February and March 2021. Food insecurity was measured using questions from the Innovation for Poverty Action's Research for Effective COVID-19 Reponses survey and water insecurity was measured using the Household Water Insecurity Experiences Short Form. Both were measured between August and September 2020. We built 3 multivariate quantile linear regression models to assess the effects of water insecurity, food insecurity, and joint food and water insecurity during the COVID-19 pandemic on CESD-10 score. RESULTS: In models with the full sample (n = 323), food insecurity (ß: 1.48; 95% CI: 0.79, 2.17), water insecurity (ß: 0.13; 95% CI: -0.01, 0.26), and joint food and water insecurity (ß: 2.40; 95% CI: 1.43, 3.38) were positively associated with CESD-10 score. In subgroup analyses of respondents for whom we had prepandemic CESD-10 scores (n = 221), joint food and water insecurity (ß: 1.96; 95% CI: 0.78, 3.15) maintained the strongest relationship with CESD-10 score. A limitation of this study is that inconsistency in respondents from households across the survey waves reduced the sample size used for this study. CONCLUSIONS: Our results find a larger association between depression and joint resource insecurity than with water or food insecurity alone, underlining the importance of addressing food and water insecurity together, particularly as they relate to women's mental health and well-being.

The technology in cryotechnology.

The process of freezing biological material at extremely low temperatures is known as cryopreservation. To ensure the preservation of cells and tissues over an extended period of time, low temperatures are applied since biological processes, including the biochemical ones, come to a halt under cryogenic conditions and thus it is possible to maintain their structural and functional integrity. The field of cryopreservation gained more prominence in the 20th century and emerged as an unavoidable technology for different applications such as cell therapy, tissue engineering, or assisted fertilization. In this work we provide an overview of various technologies in the field of cryotechnology with regard to the freezing, storage and thawing of living cells. The first part covers the freezing process, starting with cryoprotective agents regarding their protection mechanisms and compositions, passing by cryo-imaging, micro-fluidic systems, and the currently available freezing and biobanking equipment. The second part focusses on the thawing process as well as the hypothermic preservation for the short-term storage of biological materials and constructs. Doi.org/10.54680/fr23610110112.

Implementing "from here to there": A case study of conceptual and practical challenges in implementation science.

There is a significant challenge in global health and development research that pivots on the difficulties of delivering (cost-)effective treatments or interventions that are scalable andtransferable across settings. That is, how does one deliver "true effects", proven treatments, into new settings? This is often addressed in pragmatic trials or implementation research in which one makes adjustments to the delivery of the treatment to ensure that it works here and there. In this critical analytical review, we argue that the approach mis-characterises the cause-effect relationship and fails to recognise the local, highly contextual nature of what it means to say an intervention "works". We use an ongoing randomised controlled trial (RCT)-an informal settlement redevelopment intervention in Indonesia and Fiji to reduce human exposure to pathogenic faecal contamination-as a vehicle for exploring the ideas and implications of identifying interventions that work in global health and development. We describe the highly contextualised features of the research and the challenges these would pose in attempts to generalise the results. In other words, we detail that which is frequently elided from most RCTs. As our critical lens, we us the work of American philosopher, Nancy Cartwright, who argued that research produces dappled regions of causal insights-lacunae against a backdrop of causal ignorance. Rather than learn about a relationship between a treatment and an outcome, we learn that in the right sort of context, a treatment reliably produces a particular outcome. Moving a treatment from here to there becomes, therefore, something of an engineering exercise to ensure the right factors (or "shields") are in place so the cause-effect is manifest. As a consequence, one cannot assume that comparative effectiveness or cost-effectiveness would be maintained.

Are social isolation, lack of social support or loneliness risk factors for cardiovascular disease in Australia and New Zealand? A systematic review and meta-analysis.

BACKGROUND: An international systematic review concluded that individuals with poor social health (social isolation, lack of social support or loneliness) are 30% more likely to develop coronary heart disease (CHD) and stroke. Notably, the two included Australian papers reported no association between social health and CHD or stroke. OBJECTIVE: We undertook a systematic review and meta-analysis to investigate the association between social isolation, lack of social support and loneliness and cardiovascular disease (CVD) incidence among people living in Australia and New Zealand. METHODS: Four electronic databases were systematically searched for longitudinal studies published until June 2020. Two reviewers undertook title/abstract screen and one reviewer undertook full-text screen and data extraction. Quality was assessed using the Newcastle - Ottawa Quality Assessment Scale. RESULTS: Of the 725 unique records retrieved, five papers met our inclusion criteria. These papers reported data from three Australian longitudinal datasets, with a total of 2137 CHD and 590 stroke events recorded over follow-up periods ranging from 3 to 16 years. Reports of two CHD and two stroke outcomes were suitable for meta-analysis. The included papers reported no association between social health and incidence of CVD in all fully adjusted models and most unadjusted models. CONCLUSIONS: Our systematic review is inconclusive as it identified only a few studies, which relied heavily on self-reported CVD. Further studies using medical diagnosis of CVD, and assessing the potential influence of residential remoteness, are needed to better understand the relationship between social health and CVD incidence in Australia and New Zealand.

Reforming the workers' compensation process for occupational lung disease among miners in South Africa: an efficiency study of claims assessment.

PURPOSE: The large burden of silicosis and tuberculosis (TB) in the South African mining industry, coupled with an under-resourcing of the compensation agencies responsible for certifying occupational lung disease, have resulted in serious backlogs. This work aimed to measure the efficiency gains from triaging occupational lung disease claims using claim type, years of mining exposure and computer aided detection (CAD) to save on scarce medical adjudicators. METHODS: During 2020, the compensation authority started to triage claims for TB and those of miners with < 10 years of service to two-person panels instead of the four-person panel plus radiologist used previously. Efficiency gain was calculated in medical person-units saved and reduction in delays. Different service thresholds predictive of silicosis were simulated, as well as the impact of pre-classification of chest X-rays with CAD using different combinations of sensitivity and specificity. RESULTS: The new triage system saved 20.3% in person-time units and reduced delays by 10-20 days. Without CAD the greatest efficiency gain (28%) was projected from dispensing with a mining service threshold and routing all non-TB claims to the small panels at the outset. Simulation of four different CAD sensitivity/specificity combinations yielded efficiency gains of 18.2-36.1%, with 31.1% judged the most realistic. Use of sensitivity of close to 100% would not be feasible because of the very low resulting specificity. CONCLUSION: Pre-adjudication triage of claims at the compensation agency is capable of saving a substantial proportion of adjudicator time and reducing certification delays. Additional efficiency gains are achievable by referring all claims to small panels to begin with and improvement of CAD performance for this ex-miner population.

A systematic review of oncoplastic volume replacement breast surgery: oncological safety and cosmetic outcome.

INTRODUCTION: Oncoplastic breast conserving surgery allows higher volume excision to achieve oncological safety with minimal aesthetic compromise. The primary outcome of this study was to assess the oncological safety in the setting of volume replacement oncoplastic breast conserving surgery. The secondary objective was to assess cosmetic outcome. METHODS: A systematic literature review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to explore the oncological safety of oncoplastic breast conserving surgery, with particular focus on volume replacement. Resection margin rates, re-excision rates, conversion to mastectomy rates, local and distant disease recurrence, volume replacement techniques, cosmetic outcomes and patient-reported outcome measures were assessed. FINDINGS: The search criteria identified 155 articles, of which 40 met the inclusion criteria. These studies included 2,497 patients with a mean age of 47.8 years (range 38.4-59.6 years), a body mass index of 24.3kg/m2 (22.1-28.0kg/m2), with a mean follow-up of 37.1 months (6-125 months). A variety of volume replacement techniques were used, most commonly latissimus dorsi and chest wall perforator flaps. Whole mean pathological tumour size was 29.7mm (17-65mm) and mean specimen weight was 123.6g (46.5-220g). Mean re-excision rate was 7.2% and completion mastectomy rate was 2.3%. Locoregional and distant recurrence rate was 2.5% (0-8.1%) and 3.1% (0-14.6%), respectively. There were a variety of patient-reported outcome measures employed, with overall good to excellent outcomes. CONCLUSIONS: This review demonstrates that volume replacement oncoplastic breast conserving surgery is a safe option in terms of re-excision, completion mastectomy rates, and local and distant recurrence. Available patient-related outcome measures and cosmetic assessment tend towards better outcomes compared with wide local excision and mastectomy. However, data are significantly limited, with a paucity of high-level evidence, and it is therefore necessary to be cautious regarding the strength and interpretation of data in this review. Further prospective studies are required on this subject.

Chronic heat stress in tropical urban informal settlements.

The health and economic impacts of extreme heat on humans are especially pronounced in populations without the means to adapt. We deployed a sensor network across 12 informal settlements in Makassar, Indonesia to measure the thermal environment that people experience inside and outside their homes. We calculated two metrics to assess the magnitude and frequency of heat stress conditions, wet bulb temperature and wet bulb globe temperature, and compared our in situ data to that collected by weather stations. We found that informal settlement residents experience chronic heat stress conditions, which are underestimated by weather stations. Wet bulb temperatures approached the uppermost limits of human survivability, and wet bulb globe temperatures regularly exceeded recommended physical activity thresholds, both in houses and outdoors. Under a warming climate, a growing number of people living informally will face potentially severe impacts from heat stress that have likely been previously overlooked or underestimated.

Indo-Pacific Walker circulation drove Pleistocene African aridification.

Today, the eastern African hydroclimate is tightly linked to fluctuations in the zonal atmospheric Walker circulation1,2. A growing body of evidence indicates that this circulation shaped hydroclimatic conditions in the Indian Ocean region also on much longer, glacial-interglacial timescales3-5, following the development of Pacific Walker circulation around 2.2-2.0 million years ago (Ma)6,7. However, continuous long-term records to determine the timing and mechanisms of Pacific-influenced climate transitions in the Indian Ocean have been unavailable. Here we present a seven-million-year-long record of wind-driven circulation of the tropical Indian Ocean, as recorded in Mozambique Channel Throughflow (MCT) flow-speed variations. We show that the MCT flow speed was relatively weak and steady until 2.1 ± 0.1 Ma, when it began to increase, coincident with the intensification of the Pacific Walker circulation6,7. Strong increases during glacial periods, which reached maxima after the Mid-Pleistocene Transition (0.9-0.64 Ma; ref. 8), were punctuated by weak flow speeds during interglacial periods. We provide a mechanism explaining that increasing MCT flow speeds reflect synchronous development of the Indo-Pacific Walker cells that promote aridification in Africa. Our results suggest that after about 2.1 Ma, the increasing aridification is punctuated by pronounced humid interglacial periods. This record will facilitate testing of hypotheses of climate-environmental drivers for hominin evolution and dispersal.

Community-engaged healthcare model for currently under-served individuals involved in the healthcare system.

In the US, many people are excluded from healthcare structures and systems, due to multiple macro and micro factors. Poverty, health ecosystems, mental health, and community amenities are some of the issues confronting those who are not able to access appropriate support. This population is often referred to as 'high needs, high cost' (HNHC), a term that has been applied to refer to people who repeatedly utilize services without significant benefit (we have replaced this term with 'currently under-served'; C-US). For many traditional health solutions may not address the fundamental issues confronting their health. Community-Engaged Healthcare (CEH) is an approach that equips members of the community to levy power to advocate for their own health or social solutions, designing their own interventions to address needs with support from health providers. A realist review was conducted to identify the existing literature around CEH. This yielded ten papers that were reviewed by at least two authors and rated in terms of quality. A model describing the processes underpinning CEH was then iteratively generated, resulting in additional terms that were used in a second review of the literature. A further 16 peer-reviewed articles were identified and were independently reviewed and quality rated. These articles were used to refine further iterations of the model and included in the review where appropriate. The resulting model schematically posits a set of relational factors identified to be important in the establishment of CEH. Notably, the transfer of autonomy and power over health decision-making processes is emphasized, which will require revolutionary thinking about how healthcare is delivered for patients.

A planetary health model for reducing exposure to faecal contamination in urban informal settlements: Baseline findings from Makassar, Indonesia.

BACKGROUND: The intense interactions between people, animals and environmental systems in urban informal settlements compromise human and environmental health. Inadequate water and sanitation services, compounded by exposure to flooding and climate change risks, expose inhabitants to environmental contamination causing poor health and wellbeing and degrading ecosystems. However, the exact nature and full scope of risks and exposure pathways between human health and the environment in informal settlements are uncertain. Existing models are limited to microbiological linkages related to faecal-oral exposures at the individual level, and do not account for a broader range of human-environmental variables and interactions that affect population health and wellbeing. METHODS: We undertook a 12-month health and environmental assessment in 12 flood-prone informal settlements in Makassar, Indonesia. We obtained caregiver-reported health data, anthropometric measurements, stool and blood samples from children < 5 years, and health and wellbeing data for children 5-14 years and adult respondents. We collected environmental data including temperature, mosquito and rat species abundance, and water and sediment samples. Demographic, built environment and household asset data were also collected. We combined our data with existing literature to generate a novel planetary health model of health and environment in informal settlements. RESULTS: Across the 12 settlements, 593 households and 2764 participants were enrolled. Two-thirds (64·1%) of all houses (26·3-82·7% per settlement) had formal land tenure documentation. Cough, fever and diarrhoea in the week prior to the survey were reported among an average of 34.3%, 26.9% and 9.7% of children aged < 5 years, respectively; although proportions varied over time, prevalence among these youngest children was consistently higher than among children 5-14 years or adult respondents. Among children < 5 years, 44·3% experienced stunting, 41·1% underweight, 12.4% wasting, and 26.5% were anaemic. There was self- or carer-reported poor mental health among 16.6% of children aged 5-14 years and 13.9% of adult respondents. Rates of potential risky exposures from swimming in waterways, eating uncooked produce, and eating soil or dirt were high, as were exposures to flooding and livestock. Just over one third of households (35.3%) had access to municipal water, and contamination of well water with E. coli and nitrogen species was common. Most (79·5%) houses had an in-house toilet, but no houses were connected to a piped sewer network or safe, properly constructed septic tank. Median monthly settlement outdoor temperatures ranged from 26·2 °C to 29.3 °C, and were on average, 1·1 °C warmer inside houses than outside. Mosquito density varied over time, with Culex quinquefasciatus accounting for 94·7% of species. Framed by a planetary health lens, our model includes four thematic domains: (1) the physical/built environment; (2) the ecological environment; (3) human health; and (4) socio-economic wellbeing, and is structured at individual, household, settlement, and city/beyond spatial scales. CONCLUSIONS: Our planetary health model includes key risk factors and faecal-oral exposure pathways but extends beyond conventional microbiological faecal-oral enteropathogen exposure pathways to comprehensively account for a wider range of variables affecting health in urban informal settlements. It includes broader ecological interconnections and planetary health-related variables at the household, settlement and city levels. It proposes a composite framework of markers to assess water and sanitation challenges and flood risks in urban informal settlements for optimal design and monitoring of interventions.

Introduction of an assessment toolkit associated with increased rate of DLB diagnosis.

BACKGROUND: Dementia with Lewy bodies (DLB) and dementia in Parkinson's disease (PDD) are recognised to be under-recognised in clinical practice in the UK, with only one third to a half of expected cases diagnosed. We aimed to assess whether clinical diagnostic rates could be increased by the introduction of a structured assessment toolkit for clinicians. METHODS: We established baseline diagnostic rates for DLB and PDD in four memory clinics and three movement disorder/Parkinson's disease (PD) clinics in two separate geographical regions in the UK. An assessment toolkit specifically developed to assist with the recognition and diagnosis of DLB and PDD was then introduced to the same clinical teams and diagnostic rates for DLB and PDD were reassessed. For assessing DLB diagnosis, a total of 3820 case notes were reviewed before the introduction of the toolkit, and 2061 case notes reviewed after its introduction. For PDD diagnosis, a total of 1797 case notes were reviewed before the introduction of the toolkit and 3405 case notes after it. Mean values and proportions were analysed using Student's t test for independent samples and χ2 test, respectively. RESULTS: DLB was diagnosed in 4.6% of dementia cases prior to the introduction of the toolkit, and 6.2% of dementia cases afterwards, an absolute rise of 1.6%, equal to a 35% increase in the number of DLB cases diagnosed when using the toolkit (χ2 = 4.2, P = 0.041). The number of PD patients diagnosed with PDD was not found overall to be significantly different when using the toolkit: 9.6% of PD cases before and 8.2% of cases after its introduction (χ2 = 1.8, P = 0.18), though the ages of PD patients assessed after the toolkit's introduction were lower (73.9 years vs 80.0 years, t = 19.2, p < 0.001). CONCLUSION: Introduction of the assessment toolkit was associated with a significant increase in the rate of DLB diagnosis, suggesting that a structured means of assessing symptoms and clinical features associated with DLB can assist clinicians in recognising cases. The assessment toolkit did not alter the overall rate of PDD diagnosis, suggesting that alternate means may be required to improve the rate of diagnosis of dementia in Parkinson's disease.

Study design, rationale and methods of the Revitalising Informal Settlements and their Environments (RISE) study: a cluster randomised controlled trial to evaluate environmental and human health impacts of a water-sensitive intervention in informal settlements in Indonesia and Fiji.

INTRODUCTION: Increasing urban populations have led to the growth of informal settlements, with contaminated environments linked to poor human health through a range of interlinked pathways. Here, we describe the design and methods for the Revitalising Informal Settlements and their Environments (RISE) study, a transdisciplinary randomised trial evaluating impacts of an intervention to upgrade urban informal settlements in two Asia-Pacific countries. METHODS AND ANALYSIS: RISE is a cluster randomised controlled trial among 12 settlements in Makassar, Indonesia, and 12 in Suva, Fiji. Six settlements in each country have been randomised to receive the intervention at the outset; the remainder will serve as controls and be offered intervention delivery after trial completion. The intervention involves a water-sensitive approach, delivering site-specific, modular, decentralised infrastructure primarily aimed at improving health by decreasing exposure to environmental faecal contamination. Consenting households within each informal settlement site have been enrolled, with longitudinal assessment to involve health and well-being surveys, and human and environmental sampling. Primary outcomes will be evaluated in children under 5 years of age and include prevalence and diversity of gastrointestinal pathogens, abundance and diversity of antimicrobial resistance (AMR) genes in gastrointestinal microorganisms and markers of gastrointestinal inflammation. Diverse secondary outcomes include changes in microbial contamination; abundance and diversity of pathogens and AMR genes in environmental samples; impacts on ecological biodiversity and microclimates; mosquito vector abundance; anthropometric assessments, nutrition markers and systemic inflammation in children; caregiver-reported and self-reported health symptoms and healthcare utilisation; and measures of individual and community psychological, emotional and economic well-being. The study aims to provide proof-of-concept evidence to inform policies on upgrading of informal settlements to improve environments and human health and well-being. ETHICS: Study protocols have been approved by ethics boards at Monash University, Fiji National University and Hasanuddin University. TRIAL REGISTRATION NUMBER: ACTRN12618000633280; Pre-results.

Computer-aided detection for tuberculosis and silicosis in chest radiographs of gold miners of South Africa.

BACKGROUND: For over one hundred years, the gold mining sector has been a considerable source of tuberculosis (TB) and silicosis disease burden across Southern Africa. Reading chest radiographs (CXRs) is an expert and time-intensive process necessary for the screening and diagnosis of lung disease and the provision of evidence for compensation claims. Our study explores the use of computer-aided detection (CAD) of TB and silicosis in CXRs of a population with a high incidence of both diseases.METHODS: A set of 330 CXRs with human expert-determined classifications of silicosis, TB, silcotuberculosis and normal were provided to four health technology companies. The ability of each of their respective CAD systems to predict disease was assessed using receiver operating characteristic curve analysis of the under the curve metric.RESULTS: Three of the four systems differentiated accurately between TB and normal images, while two differentiated accurately between silicosis and normal images. Inclusion of silicotuberculosis images reduced each system's ability to detect either disease. In differentiating between any abnormal from normal CXR, the most accurate system achieved both a sensitivity and specificity of 98.2%.CONCLUSION: The current ability of CAD to differentiate between TB and silicosis is limited, but its use as a mass screening tool for both diseases shows considerable promise.

Household Water Storage Management, Hygiene Practices, and Associated Drinking Water Quality in Rural India.

Household drinking water storage is commonly practiced in rural India. Fecal contamination may be introduced at the water source, during collection, storage, or access. Within a trial of a community-level water supply intervention, we conducted five quarterly household-level surveys to collect information about water, sanitation, and hygiene practices in rural India. In a random subsample of households, we tested stored drinking water samples for Escherichia coli, concurrently observing storage and access practices. We conducted 9961 surveys and collected 3296 stored water samples. Stored water samples were frequently contaminated with E. coli (69%), and E. coli levels were the highest during the wet season. Most households contributing two or more drinking water samples had detectable E. coli in some (47%) or all (44%) samples. Predictors of stored water contamination with E. coli included consumption of river water and open defecation; consumption of reverse osmosis-treated water and safe water access practices appeared to be protective. Until households can be reached with on-premises continuous safe water supplies, suboptimal household water storage practices are likely to continue. Improvements to source water quality alone are unlikely to prevent exposure to contaminated drinking water unless attention is also given to improving household water storage, access, and sanitation practices.