Acceptability measures of water, sanitation and hygiene interventions in low- and middle-income countries, a systematic review

BACKGROUND: Inadequate access to water, sanitation, and hygiene (WASH) is an environmental risk factor for poor health outcomes globally, particularly for children in low- and middle-income countries (LMIC). Despite technological advancements, many interventions aimed at improving WASH access return less than optimal results on long term impact, efficacy and sustainability. Research focus in the 'WASH sector' has recently expanded from investigating 'which interventions work' to 'how they are best implemented'. The 'acceptability' of an intervention is a key component of implementation that can influence initial uptake and sustained use. Acceptability assessments are increasingly common for health interventions in clinical settings. A broad scale assessment of how acceptability has been measured in the WASH sector, however, has not yet been conducted. METHODS/PRINCIPAL FINDINGS: We conducted a systematic literature review of intervention studies published between 1990 and 2021 that evaluated the acceptability of WASH interventions in LMIC settings. Using an implementation science approach, focused outcomes included how acceptability was measured and defined, and the timing of acceptability assessment. We conducted quality assessment for all included studies using the Cochrane Risk of Bias tool for randomised studies, and the Newcastle-Ottawa Scale for non-randomised studies. Of the 1238 records; 36 studies were included for the analysis, 22 of which were non-randomized interventions and 16 randomized or cluster-randomized trials. We found that among the 36 studies, four explicitly defined their acceptability measure, and six used a behavioural framework to inform their acceptability study design. There were few acceptability evaluations in schools and healthcare facilities. While all studies reported measuring WASH acceptability, the measures were often not comparable or described. CONCLUSIONS: As focus in WASH research shifts towards implementation, a consistent approach to including, defining, and measuring acceptability is needed

Protocol for a pragmatic feasibility randomised controlled trial of peer coaching for adults with long-term conditions: PEER CONNECT.

INTRODUCTION: Patients with low levels of knowledge, skills and confidence to manage their health and well-being (activation) are more likely to have unmet health needs, delay seeking healthcare and need emergency care. National Health Service England estimates that this may be applicable to 25%-40% of patients with long-term health conditions. Volunteer peer coaching may support people to increase their level of activation. This form of intervention may be particularly effective for people with low levels of activation. METHODS AND ANALYSIS: This single site, two-arm randomised controlled trial has been designed to assess the feasibility of conducting a definitive trial of volunteer peer health and well-being coaching for people with long-term health conditions (multiple sclerosis, rheumatic diseases or chronic pain) and low activation. Feasibility outcomes include recruitment and retention rates, and intervention adherence. We will measure patient activation, mental health and well-being as potential outcomes for a definitive trial. These outcomes will be summarised descriptively for each time point by allocated group and help to inform sample size calculation for the definitive trial. Criteria for progression to a full trial will be used. ETHICS AND DISSEMINATION: Ethical approval has been granted by the London - Surrey Research Ethics Committee, reference 21/LO/0715. Results from this feasibility trial will be shared directly with participants, presented at local, regional and national conferences and published in an open-access journal. TRIAL REGISTRATION NUMBER: ISRCTN12623577

Exploratory Analysis of TP53\textit{TP53} Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

$\textbf{Background:}$ Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic $\textit{TP53}$ mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). $\textbf{Methods and Findings:}$ We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific $\textit{TP53}$ assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The $\textit{TP53}$ mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22%) compared to 0.7% (IQR 0.3%-2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson $r$ = 0.59, $p$ 32 cm$^3$, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28-54) compared with a median time to nadir of 84 d (IQR 42-116) for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in multivariable analysis (hazard ratio 0.22, 95% CI 0.07-0.67, $p$ = 0.008). Conversely, a decrease in TP53MAF of ≤60% was associated with poor response and identified cases with TTP < 6 mo with 71% sensitivity (95% CI 42%-92%) and 88% specificity (95% CI 64%-99%). Specificity was improved when patients with recent drainage of ascites were excluded. Ascites drainage led to a reduction of TP53MAF concentration. The limitations of this study include retrospective design, small sample size, and heterogeneity of treatment within the cohort. $\textbf{Conclusions:}$ In this retrospective study, we demonstrated that ctDNA is correlated with volume of disease at the start of treatment in women with HGSOC and that a decrease of ≤60% in TP53MAF after one cycle of chemotherapy was associated with shorter TTP. These results provide evidence that ctDNA has the potential to be a highly specific early molecular response marker in HGSOC and warrants further investigation in larger cohorts receiving uniform treatment.This work was supported by Cancer Research UK Grant numbers: A15601 (JDB), A11906 (NR), A20240 (NR), A18072 (JDB). JDB was supported by the National Institute for Health Research Cambridge Biomedical Research Centre. CAP was supported in part by the Academy of Medical Sciences, the Wellcome Trust, British Heart Foundation and Arthritis Research UK

Bias correction of high-resolution regional climate model precipitation output gives the best estimates of precipitation in Himalayan catchments

The need to provide accurate estimates of precipitation over catchments in the Hindu Kush, Karakoram, and Himalaya mountain ranges for hydrological and water resource systems assessments is widely recognised, as is identifying precipitation extremes for assessing hydro‐meteorological hazards. Here, we investigate the ability of bias‐corrected Weather Research and Forecasting model output at 5 km grid spacing to reproduce the spatiotemporal variability of precipitation for the Beas and Sutlej river basins in the Himalaya, measured by 44 stations spread over the period 1980 to 2012. For the Sutlej basin, we find that the raw (uncorrected) model output generally underestimated annual, monthly, and (particularly low‐intensity) daily precipitation amounts. For the Beas basin, the model performance was better, although biases still existed. It is speculated that the cause of the dry bias over the Sutlej basin is a failure of the model to represent an early‐morning maximum in precipitation during the monsoon period, which is related to excessive precipitation falling upwind. However, applying a non‐linear bias‐correction method to the model output resulted in much better results, which were superior to precipitation estimates from reanalysis and two gridded datasets. These findings highlight the difficulty in using current gridded datasets as input for hydrological modelling in Himalayan catchments, suggesting that bias‐corrected high‐resolution regional climate model output is in fact necessary. Moreover, precipitation extremes over the Beas and Sutlej basins were considerably under‐represented in the gridded datasets, suggesting that bias‐corrected regional climate model output is also necessary for hydro‐meteorological risk assessments in Himalayan catchments

Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria.

The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms