Exploring views on satisfaction with life in young children with chronic illness: an innovative approach to the collection of self-report data from children under 11

The objective of this study was to explore young children’s views on the impact of chronic illness on their life in order to inform future development of a patient-based self-report health outcome measure. We describe an approach to facilitating self-report views from young children with chronic illness. A board game was designed in order to obtain qualitative data from 39 children with a range of chronic illness conditions and 38 healthy controls ranging in age from 3 to 11 years. The format was effective in engaging young children in a self-report process of determining satisfaction with life and identified nine domains. The board game enabled children aged 5–11 years with chronic illness to describe the effects of living with illness on home, family, friends, school and life in general. It generated direct, non-interpreted material from children who, because of their age, may have been considered unable or limited their ability to discuss and describe how they feel. Obtaining this information for children aged 4 and under continues to be a challenge

School-Based Surveillance of Respiratory Pathogens on “High-Touch” Surfaces

In order to assess the presence of respiratory pathogens on “high-touch” surfaces and inform sanitation practices at schools, pre-selected surfaces in elementary schools in Seattle, WA, USA were sampled weekly and tested by RT-PCR for 25 viral respiratory pathogens (including SARS-CoV-2 retrospectively) and S. pneumoniae during 2019–2020 winter respiratory illness season. Viral pathogens (rhinovirus, adenovirus, influenza) known to cause respiratory illness were detected on commonly touched surfaces, especially wooden surfaces, and matched the patterns of circulating virus in the community

A unified ML framework for solubility prediction across organic solvents

We report a single machine learning (ML)-based model to predict the solubility of drug/drug-like compounds across 49 organic solvents, extensible to more. By adopting a cross-solvent data structure, we enable the exploitation of valuable relational information between systems. The effect is major, with even a single experimental measurement of a solute in a different solvent being enough to significantly improve predictions on it, and successive ones improving them further. Working with a sparse dataset of only 714 experimental data points spanning 75 solutes and 49 solvents (81% sparsity), a ML-based model with a prediction RMSE of 0.75 log S (g/100 g) for unseen solutes was produced. This compares favourably with conductor-like screening model for real solvents (COSMO-RS), an industry-standard model based on thermodynamic laws, which yielded a prediction RMSE of 0.97 for the same dataset. The error for our method reduced to a mean RMSE of 0.65 when one instance of the solute (in a different solvent) was included in the training data; this iteratively reduced further to 0.60, 0.57 and 0.56 when two, three and four instances were available, respectively. This standard of performance not only meets or exceeds those of alternative ML-based solubility models insofar as they can be compared but reaches the perceived ceiling for solubility prediction models of this type. In parallel, we assess the performance of the model with and without the addition of COSMO-RS output as an additional descriptor. We find that a significant benefit is gained from its addition, indicating that mechanistic methods can bring insight that simple molecular descriptors cannot and should be incorporated into a data-driven prediction of molecular properties where possible

Modelling Future Coronary Heart Disease Mortality to 2030 in the British Isles.

OBJECTIVE: Despite rapid declines over the last two decades, coronary heart disease (CHD) mortality rates in the British Isles are still amongst the highest in Europe. This study uses a modelling approach to compare the potential impact of future risk factor scenarios relating to smoking and physical activity levels, dietary salt and saturated fat intakes on future CHD mortality in three countries: Northern Ireland (NI), Republic of Ireland (RoI) and Scotland. METHODS: CHD mortality models previously developed and validated in each country were extended to predict potential reductions in CHD mortality from 2010 (baseline year) to 2030. Risk factor trends data from recent surveys at baseline were used to model alternative future risk factor scenarios: Absolute decreases in (i) smoking prevalence and (ii) physical inactivity rates of up to 15% by 2030; relative decreases in (iii) dietary salt intake of up to 30% by 2030 and (iv) dietary saturated fat of up to 6% by 2030. Probabilistic sensitivity analyses were then conducted. RESULTS: Projected populations in 2030 were 1.3, 3.4 and 3.9 million in NI, RoI and Scotland respectively (adults aged 25-84). In 2030: assuming recent declining mortality trends continue: 15% absolute reductions in smoking could decrease CHD deaths by 5.8-7.2%. 15% absolute reductions in physical inactivity levels could decrease CHD deaths by 3.1-3.6%. Relative reductions in salt intake of 30% could decrease CHD deaths by 5.2-5.6% and a 6% reduction in saturated fat intake might decrease CHD deaths by some 7.8-9.0%. These projections remained stable under a wide range of sensitivity analyses. CONCLUSIONS: Feasible reductions in four cardiovascular risk factors (already achieved elsewhere) could substantially reduce future coronary deaths. More aggressive polices are therefore needed in the British Isles to control tobacco, promote healthy food and increase physical activity

A rehabilitation intervention to promote physical recovery following intensive care: a detailed description of construct development, rationale and content together with proposed taxonomy to capture processes in a randomised controlled trial.

Background: increasing numbers of patients are surviving critical illness, but survival may be associated with aconstellation of physical and psychological sequelae that can cause on going disability and reduced health-relatedquality of life. Limited evidence currently exists to guide the optimum structure, timing, and content of rehabilitationprogrammes. There is a need to both develop and evaluate interventions to support and expedite recovery during the post-ICU discharge period. This paper describes the construct development for a complex rehabilitationintervention intended to promote physical recovery following critical illness. The intervention is currently beingevaluated in a randomised trial (ISRCTN09412438; funder Chief Scientists Office, Scotland).Methods: the intervention was developed using the Medical Research Council (MRC) framework for developingcomplex healthcare interventions. We ensured representation from a wide variety of stakeholders includingcontent experts from multiple specialties, methodologists, and patient representation. The intervention constructwas initially based on literature review, local observational and audit work, qualitative studies with ICU survivors,and brainstorming activities. Iterative refinement was aided by the publication of a National Institute for Healthand Care Excellence guideline (No. 83), publicly available patient stories (Healthtalkonline), a stakeholder event incollaboration with the James Lind Alliance, and local piloting. Modelling and further work involved a feasibility trial and development of a novel generic rehabilitation assistant (GRA) role. Several rounds of external peer review during successive funding applications also contributed to development.Results: the final construct for the complex intervention involved a dedicated GRA trained to pre-definedcompetencies across multiple rehabilitation domains (physiotherapy, dietetics, occupational therapy, and speech/language therapy), with specific training in post-critical illness issues. The intervention was from ICU discharge to 3 months post-discharge, including inpatient and post-hospital discharge elements. Clear strategies to provide information to patients/families were included. A detailed taxonomy was developed to define and describe the processes undertaken, and capture them during the trial. The detailed process measure description, together with a range of patient, health service, and economic outcomes were successfully mapped on to the modifiedCONSORT recommendations for reporting non-pharmacologic trial interventions.Conclusions: the MRC complex intervention framework was an effective guide to developing a novel post-ICUrehabilitation intervention. Combining a clearly defined new healthcare role with a detailed taxonomy of process and activity enabled the intervention to be clearly described for the purpose of trial delivery and reporting. These data will be useful when interpreting the results of the randomised trial, will increase internal and external trial validity, and help others implement the intervention if the intervention proves clinically and cost effective

Increased Hospital-Based Physical Rehabilitation and Information Provision After Intensive Care Unit Discharge: The RECOVER Randomized Clinical Trial

Importance: critical illness results in disability and reduced health-related quality of life (HRQOL), but the optimum timing and components of rehabilitation are uncertain.Objective: to evaluate the effect of increasing physical and nutritional rehabilitation plus information delivered during the post–intensive care unit (ICU) acute hospital stay by dedicated rehabilitation assistants on subsequent mobility, HRQOL, and prevalent disabilities.Design, Setting, and Participants: a parallel group, randomized clinical trial with blinded outcome assessment at 2 hospitals in Edinburgh, Scotland, of 240 patients discharged from the ICU between December 1, 2010, and January 31, 2013, who required at least 48 hours of mechanical ventilation. Analysis for the primary outcome and other 3-month outcomes was performed between June and August 2013; for the 6- and 12-month outcomes and the health economic evaluation, between March and April 2014.Interventions: during the post-ICU hospital stay, both groups received physiotherapy and dietetic, occupational, and speech/language therapy, but patients in the intervention group received rehabilitation that typically increased the frequency of mobility and exercise therapies 2- to 3-fold, increased dietetic assessment and treatment, used individualized goal setting, and provided greater illness-specific information. Intervention group therapy was coordinated and delivered by a dedicated rehabilitation practitioner.Main Outcomes and Measures: the Rivermead Mobility Index (RMI) (range 0-15) at 3 months; higher scores indicate greater mobility. Secondary outcomes included HRQOL, psychological outcomes, self-reported symptoms, patient experience, and cost-effectiveness during a 12-month follow-up (completed in February 2014).Results: median RMI at randomization was 3 (interquartile range [IQR], 1-6) and at 3 months was 13 (IQR, 10-14) for the intervention and usual care groups (mean difference, −0.2 [95% CI, −1.3 to 0.9; P = .71]). The HRQOL scores were unchanged by the intervention (mean difference in the Physical Component Summary score, −0.1 [95% CI, −3.3 to 3.1; P = .96]; and in the Mental Component Summary score, 0.2 [95% CI, −3.4 to 3.8; P = .91]). No differences were found for self-reported symptoms of fatigue, pain, appetite, joint stiffness, or breathlessness. Levels of anxiety, depression, and posttraumatic stress were similar, as were hand grip strength and the timed Up & Go test. No differences were found at the 6- or 12-month follow-up for any outcome measures. However, patients in the intervention group reported greater satisfaction with physiotherapy, nutritional support, coordination of care, and information provision.Conclusions and Relevance: post-ICU hospital-based rehabilitation, including increased physical and nutritional therapy plus information provision, did not improve physical recovery or HRQOL, but improved patient satisfaction with many aspects of recovery

Cost-Effectiveness of Pre-Referral Antimalarial, Antibacterial, and Combined Rectal Formulations for Severe Febrile Illness

BACKGROUND: Malaria and bacterial infections account for most infectious disease deaths in developing countries. Prompt treatment saves lives, but rapid deterioration often prevents the use of oral therapies; delays in reaching health facilities providing parenteral interventions are common. Rapidly and reliably absorbed antimalarial/antibacterial rectal formulations used in the community could prevent deaths and disabilities. Rectal antimalarial treatments are currently available; rectal antibacterial treatments are yet to be developed. Assessment of the likely cost-effectiveness of these interventions will inform research priorities and implementation. METHODS AND FINDINGS: The burden of malaria and bacterial infections worldwide and in Sub-Saharan and Southern Africa (SSA) and South and South-East Asia (SEA) was summarised using published data. The additional healthcare costs (USD) per death and per Disability Adjusted Life Year (DALY) avoided following pre-referral treatment of severe febrile illness with rectal antimalarials, antibacterials or combined antimalarial/antibacterials in populations at malaria risk in SSA/SEA were assessed. 46 million severe malaria and bacterial infections and 5 million deaths occur worldwide each year, mostly in SSA/SEA. At annual delivery costs of 0.02 dollars/capita and 100% coverage, rectal antimalarials (2 dollars per dose) would avert 240,000 deaths in SSA and 7,000 deaths in SEA at 5 and 177 dollars per DALY avoided, respectively; rectal antibacterials (2 dollars per dose) would avert 130,000 deaths in SSA and 27,000 deaths in SEA at 19 and 97 dollars per DALY avoided, respectively. Combined rectal formulations (2.50 dollars per dose) would avert 370,000 deaths in SSA and 33,000 deaths in SEA at 8 and 79 dollars per DALY avoided, respectively, and are a cost-effective alternative to rectal antimalarials or antibacterials alone. CONCLUSIONS: Antimalarial, antibacterial and combined rectal formulations are likely to be cost-effective interventions for severe febrile illness in the community. Attention should focus on developing effective rectal antibacterials and ensuring that these lifesaving treatments are used in a cost-effective manner

Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation.

The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.This work was funded by ERC starting grant Relieve IMDs (L.V., N.H.), the Cambridge Hospitals National Institute for Health Research Biomedical Research Center (L.V., N.H., F.S.), the Evelyn trust (N.H.) and the EU Fp7 grant TissuGEN (M.CDB.). FS has been supported by an Addenbrooke’s Charitable Trust Clinical Research Training Fellowship and a joint MRC-Sparks Clinical Research Training Fellowship.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nbt.327

People and Things on the Move: Domestic Material Culture, Poverty and Mobility in Victorian London

© 2016, The Author(s). The development of what Mayne and Lawrence (Urban History 26: 325–48, 1999) termed “ethnographic” approaches to studying nineteenth-century households and urban communities has gathered momentum in recent years. As such research agendas have taken hold and been applied to new contexts, so critiques, methodological developments, and new intellectual and theoretical currents, have provided opportunities to enhance and develop approaches. This article contributes to this on-going process. Drawing upon household archaeological research on Limehouse, a poor neighborhood in Victorian London, and inspired by the theoretical insights provided by the “new mobilities paradigm,” it aims to place “mobility” as a central and enabling intellectual framework for understanding the relationships between people, place, and poverty. Poor communities in nineteenth-century cities were undeniably mobile and transient. Historians and archaeologists have often regarded this mobility as an obstacle to studying everyday life in such contexts. However, examining temporal routines and geographical movements across a variety of time frames and geographical scales, this article argues that mobility is actually key to understanding urban life and an important mechanism for interpreting the fragmented material and documentary traces left by poor households in the nineteenth-century metropolis.We are grateful to the UK’s Arts and Humanities Research Council who funded the research upon which this paper is based (Grant Reference AH/E002285/1): ‘Living in Victorian London: Towards a Material History of Everyday Domestic Life in the Nineteenth-Century Metropolis

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders