Risk of complications and mortality following recurrent and non-recurrent Clostridioides difficile infection: a retrospective observational database study in England

Background Clostridioides difficile infection (CDI) increases the risk of complications and mortality. We assessed the magnitude of these outcomes in a large cohort of English patients with initial and recurrent CDI. Aim To compare the risk of complications and all-cause mortality, within 12 months, among hospitalized patients ≥18 years old with hospital-associated- (HA-) CDI and recurrent CDI. Methods Patients with HA-CDI during 2002–2013 were identified using inpatient hospital data linked to primary care and death data. Each HA-CDI case was frequency matched to two hospitalized patients without CDI on age group, sex, calendar year of admission, admission method and number of hospital care episodes. A second CDI episode starting on days 13–56 was defined as recurrence. Risks of mortality and complications at 12 months were analysed using Cox proportional hazard models. Findings We included 6862 patients with HA-CDI and 13,724 without CDI. Median age was 81.0 years (IQR 71.0–87.0). Patients with HA-CDI had more comorbidities than those without CDI, and significantly higher risks of mortality (adjusted hazard ratio (95% confidence interval) 1.77 (1.67–1.87)) and complications (1.66 (1.46–1.88)) within 12 months from hospital admission. Of those with HA-CDI, 1140 (16.6%) experienced CDI recurrence. Patients with recurrent versus non-recurrent CDI also had significantly increased risk of mortality (1.32 (1.20–1.45)) and complications (1.37 (1.01–1.84)) in the 12 months from the initial CDI. Conclusions HA-CDI (versus no CDI) and recurrent CDI are both associated with significantly higher risks of complications or death within 12 months of the initial CDI episode

MyChEMBL: A Virtual Platform for Distributing Cheminformatics Tools and Open Data

MyChEMBL is an open virtual platform which provides a free, secure, standardised and easy to use chemoinformatics environment for bioactivity data mining, machine learning, application development, learning and teaching. The main technical features of myChEMBL along with its applications and future plans are discussed here.FWN – Publicaties zonder aanstelling Universiteit Leide

Bright spots as climate-smart marine spatial planning tools for conservation and blue growth

Marine spatial planning that addresses ocean climate-driven change (‘climate-smart MSP’) is a global aspiration to support economic growth, food security and ecosystem sustainability. Ocean climate change (‘CC’) modelling may become a key decision-support tool for MSP, but traditional modelling analysis and communication challenges prevent their broad uptake. We employed MSP-specific ocean climate modelling analyses to inform a real-life MSP process; addressing how nature conservation and fisheries could be adapted to CC. We found that the currently planned distribution of these activities may become unsustainable during the policy's implementation due to CC, leading to a shortfall in its sustainability and blue growth targets. Significant, climate-driven ecosystem-level shifts in ocean components underpinning designated sites and fishing activity were estimated, reflecting different magnitudes of shifts in benthic versus pelagic, and inshore versus offshore habitats. Supporting adaptation, we then identified: CC refugia (areas where the ecosystem remains within the boundaries of its present state); CC hotspots (where climate drives the ecosystem towards a new state, inconsistent with each sectors’ present use distribution); and for the first time, identified bright spots (areas where oceanographic processes drive range expansion opportunities that may support sustainable growth in the medium term). We thus create the means to: identify where sector-relevant ecosystem change is attributable to CC; incorporate resilient delivery of conservation and sustainable ecosystem management aims into MSP; and to harness opportunities for blue growth where they exist. Capturing CC bright spots alongside refugia within protected areas may present important opportunities to meet sustainability targets while helping support the fishing sector in a changing climate. By capitalizing on the natural distribution of climate resilience within ocean ecosystems, such climate-adaptive spatial management strategies could be seen as nature-based solutions to limit the impact of CC on ocean ecosystems and dependent blue economy sectors, paving the way for climate-smart MSP

Under-reporting of foetal alcohol spectrum disorders: an analysis of hospital episode statistics

<p>Abstract</p> <p>Background</p> <p>Internationally, 0.97 per 1,000 live births are affected by foetal alcohol syndrome (FAS). However, prevalence intelligence has been limited in the UK, hindering the development of appropriate services. This analysis compares hospital admissions over time, between regions and with alcohol-related admissions for adult females to assess whether established patterns (such as the North experiencing elevated harms) can be identified.</p> <p>Methods</p> <p>A retrospective analysis of hospital admissions data (April 2002 to March 2008) for foetal alcohol spectrum disorder (FASD)-related conditions: foetal alcohol syndrome (dysmorphic) (n = 457); foetus and newborn affected by maternal use of alcohol (n = 157); maternal care for (suspected) damage to foetus from alcohol (n = 285); and 322,161 women admitted due to alcohol-related conditions.</p> <p>Results</p> <p>Whilst the rate of admission for alcohol-related conditions in women aged 15-44 years increased significantly by 41% between 2002/03 and 2007/08 (p < 0.0001), no such increases were seen in the numbers of FASD-related conditions (all p < 0.05). Established regional rates of admission for alcohol-related conditions in women aged 15-44 years old were not associated with admission for FASD-related conditions.</p> <p>Conclusions</p> <p>It would be expected that the North West and North East regions, known to have higher levels of alcohol harm would have higher levels of FASD-related conditions. However, this was not reflected in the incidence of such conditions, suggesting under-reporting. With incomplete datasets, intelligence systems are severely limited, hampering efforts to develop targeted interventions. Improvements to intelligence systems, practitioner awareness and screening are essential in tackling this.</p

Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: Study design, and baseline urinary, bowel and sexual function and quality of life

Objectives: To present the baseline patient-reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external-beam conformal radiotherapy for localized prostate cancer and to compare results with other populations. Materials and Methods: A total of 1643 randomized men, aged 50-69 years and diagnosed with clinically localized disease identified by prostate-specific antigen (PSA) testing, in nine UK cities in the period 1999-2009 were included. Validated PROMs for disease-specific (urinary, bowel and sexual function) and condition-specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire-Urinary Incontinence [ICIQ-UI], 2001 onwards; the International Continence Society short-form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12-item short-form health survey [SF-12]; EuroQol quality-of-life survey, the EQ-5D-3L) were assessed at prostate biopsy clinics before randomization. Descriptive statistics are presented by treatment allocation and by men's age at biopsy and PSA testing time points for selected measures. Results: A total of 1438 participants completed biopsy questionnaires (88%) and 77-88% of these were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65-70 years), whilst urinary bother and physical health were somewhat worse than in younger men (49-54 years, all P < 0.001). Bowel health, urinary function and depression were unaltered by age, whilst mental health and anxiety were better in older men (P < 0.001). Only minor differences existed in mental or physical health, anxiety and depression between PSA testing and biopsy assessments. Conclusion: The ProtecT trial baseline PROMs response rates were high. Symptom frequencies and generic quality of life were similar to those observed in populations screened for prostate cancer and control subjects without cancer

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study

BACKGROUND: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. METHODS: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. FINDINGS: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. INTERPRETATION: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. FUNDING: None

On the Role of the Difference in Surface Tensions Involved in the Allosteric Regulation of NHE-1 Induced by Low to Mild Osmotic Pressure, Membrane Tension and Lipid Asymmetry

The sodium-proton exchanger 1 (NHE-1) is a membrane transporter that exchanges Na+ for H+ ion across the membrane of eukaryotic cells. It is cooperatively activated by intracellular protons, and this allosteric regulation is modulated by the biophysical properties of the plasma membrane and related lipid environment. Consequently, NHE-1 is a mechanosensitive transporter that responds to osmotic pressure, and changes in membrane composition. The purpose of this study was to develop the relationship between membrane surface tension, and the allosteric balance of a mechanosensitive transporter such as NHE-1. In eukaryotes, the asymmetric composition of membrane leaflets results in a difference in surface tensions that is involved in the creation of a reservoir of intracellular vesicles and membrane buds contributing to buffer mechanical constraints. Therefore, we took this phenomenon into account in this study and developed a set of relations between the mean surface tension, membrane asymmetry, fluid phase endocytosis and the allosteric equilibrium constant of the transporter. We then used the experimental data published on the effects of osmotic pressure and membrane modification on the NHE-1 allosteric constant to fit these equations. We show here that NHE-1 mechanosensitivity is more based on its high sensitivity towards the asymmetry between the bilayer leaflets compared to mean global membrane tension. This compliance to membrane asymmetry is physiologically relevant as with their slower transport rates than ion channels, transporters cannot respond as high pressure-high conductance fast-gating emergency valves

Evaluating the evidence for models of life course socioeconomic factors and cardiovascular outcomes: a systematic review

BACKGROUND: A relatively consistent body of research supports an inverse graded relationship between socioeconomic status (SES) and cardiovascular disease (CVD). More recently, researchers have proposed various life course SES hypotheses, which posit that the combination, accumulation, and/or interactions of different environments and experiences throughout life can affect adult risk of CVD. Different life course designs have been utilized to examine the impact of SES throughout the life course. This systematic review describes the four most common life course hypotheses, categorizes the studies that have examined the associations between life course SES and CVD according to their life course design, discusses the strengths and weaknesses of the different designs, and summarizes the studies' findings. METHODS: This research reviewed 49 observational studies in the biomedical literature that included socioeconomic measures at a time other than adulthood as independent variables, and assessed subclinical CHD, incident CVD morbidity and/or mortality, and/or the prevalence of traditional CVD risk factors as their outcomes. Studies were categorized into four groups based upon life course design and analytic approach. The study authors' conclusions and statistical tests were considered in summarizing study results. RESULTS: Study results suggest that low SES throughout the life course modestly impacts CVD risk factors and CVD risk. Specifically, studies reviewed provided moderate support for the role of low early-life SES and elevated levels of CVD risk factors and CVD morbidity and mortality, little support for a unique influence of social mobility on CVD, and consistent support for the detrimental impact of the accumulation of negative SES experiences/conditions across the life course on CVD risk. CONCLUSIONS: While the basic life course SES study designs have various methodologic and conceptual limitations, they provide an important approach from which to examine the influence of social factors on CVD development. Some limitations may be addressed through the analysis of study cohorts followed from childhood, the evaluation of CVD risk factors in early and middle adulthood, and the use of multiple SES measures and multiple life course analysis approaches in each life course study