RadPhysBio: A Radiobiological Database for the Prediction of Cell Survival upon Exposure to Ionizing Radiation

: Based on the need for radiobiological databases, in this work, we mined experimental ionizing radiation data of human cells treated with X-rays, γ-rays, carbon ions, protons and α-particles, by manually searching the relevant literature in PubMed from 1980 until 2024. In order to calculate normal and tumor cell survival α and β coefficients of the linear quadratic (LQ) established model, as well as the initial values of the double-strand breaks (DSBs) in DNA, we used WebPlotDigitizer and Python programming language. We also produced complex DNA damage results through the fast Monte Carlo code MCDS in order to complete any missing data. The calculated α/β values are in good agreement with those valued reported in the literature, where α shows a relatively good association with linear energy transfer (LET), but not β. In general, a positive correlation between DSBs and LET was observed as far as the experimental values are concerned. Furthermore, we developed a biophysical prediction model by using machine learning, which showed a good performance for α, while it underscored LET as the most important feature for its prediction. In this study, we designed and developed the novel radiobiological 'RadPhysBio' database for the prediction of irradiated cell survival (α and β coefficients of the LQ model). The incorporation of machine learning and repair models increases the applicability of our results and the spectrum of potential users

Dietary fish oil did not prevent sleep deprived rats from a reduction in adipose tissue adiponectin gene expression

Sleep deprivation in humans has been related to weight gain and consequently, increased risk for insulin resistance. In contrast, there is a significant loss of weight in sleep deprived rats suggesting a state of insulin resistance without obesity interference. Thus, we aimed to assess the effects of a rich fish oil dietetic intervention on glucose tolerance, serum insulin and adiponectin, and adipose tissue gene expression of adiponectin and TNF-α of paradoxically sleep deprived (PSD) rats. The study was performed in thirty day-old male Wistar randomly assigned into two groups: rats fed with control diet (soybean oil as source of fat) and rats fed with a fish oil rich diet. After 45 days of treatment, the animals were submitted to PSD or maintained as home cage control group for 96 h. Body weight and food intake were carefully monitored in all groups. At the end of PSD period, a glucose tolerance test was performed and the total blood and adipose tissues were collected. Serum insulin and adiponectin were analyzed. Adipose tissues were used for RT-PCR to estimate the gene expression of adiponectin and TNF-α. Results showed that although fish oil diet did not exert any effect upon these measurements, PSD induced a reduction in adiponectin gene expression of retroperitoneal adipose tissues, with no change in serum adiponectin concentration or in adiponectin and TNF-α gene expression of epididymal adipose tissue. Thus, the stress induced by sleep deprivation lead to a desbalance of adiponectin gene expression

Prevenção da negligência e violência contra a criança e adolescente : para ensinar e aprender

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Self-management intervention to reduce pulmonary exacerbations by supporting treatment adherence in adults with cystic fibrosis: a randomised controlled trial

Introduction Recurrent pulmonary exacerbations lead to progressive lung damage in cystic fibrosis (CF). Inhaled medications (mucoactive agents and antibiotics) help prevent exacerbations, but objectively measured adherence is low. We investigated whether a multi-component (complex) self-management intervention to support adherence would reduce exacerbation rates over 12 months. Methods Between October 2017 and May 2018, adults with CF (aged ≥16 years; 19 UK centres) were randomised to the intervention (data-logging nebulisers, a digital platform and behavioural change sessions with trained clinical interventionists) or usual care (data-logging nebulisers). Outcomes included pulmonary exacerbations (primary outcome), objectively measured adherence, body mass index (BMI), lung function (FEV1) and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Analyses were by intent to treat over 12 months. Results Among intervention (n=304) and usual care (n=303) participants (51% female, median age 31 years), 88% completed 12-month follow-up. Mean exacerbation rate was 1.63/year with intervention and 1.77/year with usual care (adjusted ratio 0.96; 95% CI 0.83 to 1.12; p=0.64). Adjusted mean differences (95% CI) were in favour of the intervention versus usual care for objectively measured adherence (9.5% (8.6% to 10.4%)) and BMI (0.3 (0.1 to 0.6) kg/m2), with no difference for %FEV1 (1.4 (−0.2 to 3.0)). Seven CFQ-R subscales showed no between-group difference, but treatment burden reduced for the intervention (3.9 (1.2 to 6.7) points). No intervention-related serious adverse events occurred. Conclusions While pulmonary exacerbations and FEV1 did not show statistically significant differences, the intervention achieved higher objectively measured adherence versus usual care. The adherence difference might be inadequate to influence exacerbations, though higher BMI and lower perceived CF treatment burden were observed

Quantitative faecal immunochemical tests to guide colorectal cancer pathway referral in primary care. A systematic review, meta-analysis and cost-effectiveness analysis

Background Faecal immunochemical tests may be better than symptoms alone at identifying which patients who present to primary care with symptoms are at high risk of colorectal cancer and should have a colonoscopy. This could reduce waiting lists and patient anxiety/discomfort and enable earlier treatment of colorectal cancer. The threshold used will affect how well faecal immunochemical tests work, with a higher threshold resulting in fewer referrals but a greater chance of missing disease. Objective What is the most clinically effective and cost-effective way to use faecal immunochemical tests to reduce the number of people without significant bowel pathology who are referred to the suspected cancer pathway for colorectal cancer, taking into consideration potential colonoscopy capacity constraints for urgent and non-urgent referrals? Tests were HM-JACKarc, OC-Sensor, FOB Gold, NS-Prime, QuikRead go, IDK TurbiFIT, IDK Hb, IDK Hb/Hp complex and IDKHb+Hb/Hp ELISAs. Design Systematic review, meta-analysis and cost-effectiveness analyses were conducted. Review methods Searches across four databases and six registries were conducted (December 2022). Diagnostic accuracy studies conducted in patients presenting to or referred from primary care with symptoms suggestive of colorectal cancer using any reference standard were included. Risk of bias was assessed with quality assessment of diagnostic test accuracy studies version 2. For each test, sensitivity and specificity were pooled at all reported thresholds and summary estimates were provided at all possible thresholds within the observed range. Comparative accuracy between tests was considered. Other outcomes, for example test uptake, failure and patient acceptability, were also extracted. Cost-effectiveness analysis methods A mathematical model was developed to compare three different diagnostic strategies that used quantitative faecal immunochemical tests in primary care patients with symptoms of colorectal cancer to determine subsequent management pathways. The model assessed the health outcomes and costs associated with each strategy over a lifetime horizon from the perspective of the United Kingdom National Health Service and Personal Social Services, using evidence from published literature and other sources. Results Syntheses of sensitivity and specificity were conducted for HM-JACKarc (n = 16 studies), OC-Sensor (n = 11 studies) and FOB Gold (n = 3 studies). No synthesis was conducted for QuikRead go, NS-Prime IDK Hb or IDK Hb/Hp as there was only one study for each. No eligible studies were found for IDK Hb+Hb/Hp or for IDK TurbiFIT. Other outcomes (e.g. patient acceptability) were also synthesised. Model results suggest that faecal immunochemical tests generate a positive incremental net monetary benefit compared with current care, typically in the range of £200–350 per patient, regardless of the threshold used, for the majority of faecal immunochemical tests strategies assessed. These conclusions were robust to the sensitivity analyses undertaken. Conclusions For all faecal immunochemical test brands, there are strategies at which the incremental net monetary benefit is positive compared with current care. The exact brand and threshold(s) that generate the greatest incremental net monetary benefit could not be robustly determined due to the similarity of incremental net monetary benefit values, parameter uncertainty and the possibility of omissions from the model structure. Future work More data are needed on comparative diagnostic test accuracy and whether different thresholds should be used in some patients (e.g. anaemic, male/female, younger/older). Study registration This study is registered as PROSPERO CRD42022383580. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135637) and is published in full in Health Technology Assessment; Vol. 29, No. 46. See the NIHR Funding and Awards website for further award information

Transitioning from the “Three Delays” to a focus on continuity of care: a qualitative analysis of maternal deaths in rural Pakistan and Mozambique

publishedVersio

An intervention to support adherence to inhaled medication in adults with cystic fibrosis : the ACtiF research programme including RCT

Background People with cystic fibrosis frequently have low levels of adherence to inhaled medications. Objectives The objectives were to develop and evaluate an intervention for adults with cystic fibrosis to improve adherence to their inhaled medication. Design We used agile software methods to develop an online platform. We used mixed methods to develop a behaviour change intervention for delivery by an interventionist. These were integrated to become the CFHealthHub intervention. We undertook a feasibility study consisting of a pilot randomised controlled trial and process evaluation in two cystic fibrosis centres. We evaluated the intervention using an open-label, parallel-group randomised controlled trial with usual care as the control. Participants were randomised in a 1 : 1 ratio to intervention or usual care. Usual care consisted of clinic visits every 3 months. We undertook a process evaluation alongside the randomised controlled trial, including a fidelity study, a qualitative interview study and a mediation analysis. We undertook a health economic analysis using both a within-trial and model-based analysis. Setting The randomised controlled trial took place in 19 UK cystic fibrosis centres. Participants Participants were people aged ≥ 16 years with cystic fibrosis, on the cystic fibrosis registry, not post lung transplant or on the active transplant list, who were able to consent and not using dry-powder inhalers. Intervention People with cystic fibrosis used a nebuliser with electronic monitoring capabilities. This transferred data automatically to a digital platform. People with cystic fibrosis and clinicians could monitor adherence using these data, including through a mobile application (app). CFHealthHub displayed graphs of adherence data as well as educational and problem-solving information. A trained interventionist helped people with cystic fibrosis to address their adherence. Main outcome measures Randomised controlled trial – adjusted incidence rate ratio of pulmonary exacerbations meeting the modified Fuchs criteria over a 12-month follow-up period (primary outcome); change in percentage adherence; and per cent predicted forced expiratory volume in 1 second (key secondary outcomes). Process evaluation – percentage fidelity to intervention delivery, and participant and interventionist perceptions of the intervention. Economic modelling – incremental cost per quality-adjusted life-year gained. Results Randomised controlled trial – 608 participants were randomised to the intervention (n = 305) or usual care (n = 303). To our knowledge, this was the largest randomised controlled trial in cystic fibrosis undertaken in the UK. The adjusted rate of exacerbations per year (primary outcome) was 1.63 in the intervention and 1.77 in the usual-care arm (incidence rate ratio 0.96, 95% confidence interval 0.83 to 1.12; p = 0.638) after adjustment for covariates. The adjusted difference in mean weekly normative adherence was 9.5% (95% confidence interval 8.6% to 10.4%) across 1 year, favouring the intervention. Adjusted mean difference in forced expiratory volume in 1 second (per cent) predicted at 12 months was 1.4% (95% confidence interval –0.2% to 3.0%). No adverse events were related to the intervention. Process evaluation – fidelity of intervention delivery was high, the intervention was acceptable to people with cystic fibrosis, participants engaged with the intervention [287/305 (94%) attended the first intervention visit], expected mechanisms of action were identified and contextual factors varied between randomised controlled trial sites. Qualitative interviews with 22 people with cystic fibrosis and 26 interventionists identified that people with cystic fibrosis welcomed the objective adherence data as proof of actions to self and others, and valued the relationship that they built with the interventionists. Economic modelling – the within-trial analysis suggests that the intervention generated 0.01 additional quality-adjusted life-years at an additional cost of £865.91 per patient, leading to an incremental cost-effectiveness ratio of £71,136 per quality-adjusted life-year gained. This should be interpreted with caution owing to the short time horizon. The health economic model suggests that the intervention is expected to generate 0.17 additional quality-adjusted life-years and cost savings of £1790 over a lifetime (70-year) horizon; hence, the intervention is expected to dominate usual care. Assuming a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, the probability that the intervention generates more net benefit than usual care is 0.89. The model results are dependent on assumptions regarding the duration over which costs and effects of the intervention apply, the impact of the intervention on forced expiratory volume in 1 second (per cent) predicted and the relationship between increased adherence and drug-prescribing levels. Limitations Number of exacerbations is a sensitive and valid measure of clinical change used in many trials. However, data collection of this outcome in this context was challenging and could have been subject to bias. It was not possible to measure baseline adherence accurately. It was not possible to quantify the impact of the intervention on the number of packs of medicines prescribed. Conclusions We developed a feasible and acceptable intervention that was delivered to fidelity in the randomised controlled trial. We observed no statistically significant difference in the primary outcome of exacerbation rates over 12 months. We observed an increase in normative adherence levels in a disease where adherence levels are low. The magnitude of the increase in adherence may not have been large enough to affect exacerbations. Future work Given the non-significant difference in the primary outcome, further research is required to explore why an increase in objective normative adherence did not reduce exacerbations and to develop interventions that reduce exacerbations. Trial registration Work package 3.1: Current Controlled Trials ISRCTN13076797. Work packages 3.2 and 3.3: Current Controlled Trials ISRCTN55504164