Patient perceptions and understanding of pressure ulcer risk in the community: Empirical Research Qualitative

Aims To explore patient perceptions and understanding of their pressure ulcer risk and how information is communicated between a nurse and patient in the home setting. Design A pragmatic qualitative research design including community-dwelling patients, who were deemed at risk of developing a pressure ulcer. Methods Observation of routine interactions between nurse and patient regarding their pressure ulcer risk and semi-structured interviews with 15 community patients following the nursing interaction. Results Four key overarching themes emerged from the data analysis that were related to patient perceptions and understanding of pressure ulcer risk. These included Pressure Ulcer Awareness, Importance of Repositioning, Healthy Eating and Risk Interpretation. Conclusion Patient perception and understanding of pressure ulcer risk is different from the scientific, professional view. Patient risk perception was based on heuristics and wider personal factors and social influences. Impact The study provides important new insights into clinical practice in relation to how pressure ulcer advice and information are provided and interpreted in the community setting. Reporting Method Adhered to the Standards for Reporting Qualitative Research (SRQR) Patient or Public Contribution A small selection of patients within the NHS Trust in which the research was conducted contributed to the design of the study, in particular some of the interview questions and timing

A combined imaging, deformation and registration methodology for predicting respirator fitting

N95/FFP3 respirators have been critical to protect healthcare workers and their patients from the transmission of COVID-19. However, these respirators are characterised by a limited range of size and geometry, which are often associated with fitting issues in particular sub-groups of gender and ethnicities. This study describes a novel methodology which combines magnetic resonance imaging (MRI) of a cohort of individuals (n = 8), with and without a respirator in-situ, and 3D registration algorithm which predicted the goodness of fit of the respirator. Sensitivity analysis was used to optimise a deformation value for the respirator-face interactions and corroborate with the soft tissue displacements estimated from the MRI images. An association between predicted respirator fitting and facial anthropometrics was then assessed for the cohort

Middle and Late Pleistocene environmental history of the Marsworth area, south-central England

To elucidate the Middle and Late Pleistocene environmental history of south-central England, we report the stratigraphy, sedimentology, palaeoecology and geochronology of some deposits near the foot of the Chiltern Hills scarp at Marsworth, Buckinghamshire. The Marsworth site is important because its sedimentary sequences contain a rich record of warm stages and cold stages, and it lies close to the Anglian glacial limit. Critical to its history are the origin and age of a brown pebbly silty clay (diamicton) previously interpreted as weathered till. The deposits described infill a river channel incised into chalk bedrock. They comprise clayey, silty and gravelly sediments, many containing locally derived chalk and some with molluscan, ostracod and vertebrate remains. Most of the deposits are readily attributed to periglacial and fluvial processes, and some are dated by optically stimulated luminescence to Marine Isotope Stage (MIS) 6. Although our sedimentological data do not discriminate between a glacial or periglacial interpretation of the diamicton, amino-acid dating of three molluscan taxa from beneath it indicates that it is younger than MIS 9 and older than MIS 5e. This makes a glacial interpretation unlikely, and we interpret the diamicton as a periglacial slope deposit. The Pleistocene history reconstructed for Marsworth identifies four key elements: (1) Anglian glaciation during MIS 12 closely approached Marsworth, introducing far-travelled pebbles such as Rhaxella chert and possibly some fine sand minerals into the area. (2) Interglacial environments inferred from fluvial sediments during MIS 7 varied from fully interglacial conditions during sub-stages 7e and 7c, cool temperate conditions during sub-stage 7b or 7a, temperate conditions similar to those today in central England towards the end of the interglacial, and cool temperate conditions during sub-stage 7a. (3) Periglacial activity during MIS 6 involved thermal contraction cracking, permafrost development, fracturing of chalk bedrock, fluvial activity, slopewash, mass movement and deposition of loess and coversand. (4) Fully interglacial conditions during sub-stage 5e led to renewed fluvial activity, soil formation and acidic weathering

Predicting forefoot-orthosis interactions in rheumatoid arthritis using computational modelling

Foot orthoses are prescribed to reduce forefoot plantar pressures and pain in people with rheumatoid arthritis. Computational modelling can assess how the orthoses affect internal tissue stresses, but previous studies have focused on a single healthy individual. This study aimed to ascertain whether simplified forefoot models would produce differing biomechanical predictions at the orthotic interface between people with rheumatoid arthritis of varying severity, and in comparison to a healthy control. The forefoot models were developed from magnetic resonance data of 13 participants with rheumatoid arthritis and one healthy individual. Measurements of bony morphology and soft tissue thickness were taken to assess deformity. These were compared to model predictions (99th% shear strain and plantar pressure, max. pressure gradient, volume of soft tissue over 10% shear strain), alongside clinical data including body mass index and Leeds Foot Impact Scale–Impairment/Footwear score (LFIS-IF). The predicted pressure and shear strain for the healthy participant fell at the lower end of the rheumatoid models’ range. Medial first metatarsal head curvature moderately correlated to all model predicted outcomes (0.529 < r < 0.574, 0.040 < p < 0.063). BMI strongly correlated to all model predictions except pressure gradients (0.600 < r < 0.652, p < 0.05). There were no apparent relationships between model predictions and instances of bursae, erosion and synovial hypertrophy or LFIS-IF score. The forefoot models produced differing biomechanical predictions between a healthy individual and participants with rheumatoid arthritis, and between individuals with rheumatoid arthritis. Models capable of predicting subject specific biomechanical orthotic interactions could be used in the future to inform more personalised devices to protect skin and soft tissue health. While the model results did not clearly correlate with all clinical measures, there was a wide range in model predictions and morphological measures across the participants. Thus, the need for assessment of foot orthoses across a population, rather than for one individual, is clear

The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Cardiovascular diseases and their associated risk factors remain the main cause of mortality in western societies. In order to assess the prevalence of cardiovascular risk factors (CVRFs) in the Caucasian population of Lausanne, Switzerland, we conducted a population-based study (Colaus Study). A secondary aim of the CoLaus study will be to determine new genetic determinants associated with CVRFs.</p> <p>Methods</p> <p>Single-center, cross-sectional study including a random sample of 6,188 extensively phenotyped Caucasian subjects (3,251 women and 2,937 men) aged 35 to 75 years living in Lausanne, and genotyped using the 500 K Affymetrix chip technology.</p> <p>Results</p> <p>Obesity (body mass index ≥ 30 kg/m²), smoking, hypertension (blood pressure ≥ 140/90 mmHg and/or treatment), dyslipidemia (high LDL-cholesterol and/or low HDL-cholesterol and/or high triglyceride levels) and diabetes (fasting plasma glucose ≥ 7 mmol/l and/or treatment) were present in 947 (15.7%), 1673 (27.0%), 2268 (36.7%), 2113 (34.2%) and 407 (6.6%) of the participants, respectively, and the prevalence was higher in men than in women. In both genders, the prevalence of obesity, hypertension and diabetes increased with age.</p> <p>Conclusion</p> <p>The prevalence of major CVRFs is high in the Lausanne population in particular in men. We anticipate that given its size, the depth of the phenotypic analysis and the availability of dense genome-wide genetic data, the CoLaus Study will be a unique resource to investigate not only the epidemiology of isolated, or aggregated CVRFs like the metabolic syndrome, but can also serve as a discovery set, as well as replication set, to identify novel genes associated with these conditions.</p

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Treatment effects may remain the same even when trial participants differed from the target population

Objective RCTs have been criticised for lacking external validity. We assessed whether a trial in people with type I diabetes mellitus (T1DM) mirrored the wider population, and applied sample-weighting methods to assess the impact of differences on our trial's findings. Study design and setting The REPOSE trial was nested within a large UK cohort capturing demographic, clinical and quality of life (QoL) data for people with T1DM undergoing structured diabetes-specific education. We firstly assessed whether our RCT participants were comparable to this cohort using propensity score modelling. Following this we re-weighted the trial population to better match the wider cohort and re-estimated the treatment effect. Results Trial participants differed from the cohort in regards to sex, weight, HbA1c and also QoL and satisfaction with current treatment. Nevertheless, the treatment effects derived from alternative model weightings were similar to that of the original RCT. Conclusions Our RCT participants differed in composition to the wider population but the original findings were unaffected by sampling adjustments. We encourage investigators take steps to address criticisms of generalisability, but doing so is problematic: external data, even if available, may contain limited information and analyses can be susceptible to model misspecification

Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy.

HIV-associated cryptococcal meningitis is by far the most common cause of adult meningitis in many areas of the world that have high HIV seroprevalence. In most areas in Sub-Saharan Africa, the incidence of cryptococcal meningitis is not decreasing despite availability of antiretroviral therapy, because of issues of adherence and retention in HIV care. In addition, cryptococcal meningitis in HIV-seronegative individuals is a substantial problem: the risk of cryptococcal infection is increased in transplant recipients and other individuals with defects in cell-mediated immunity, and cryptococcosis is also reported in the apparently immunocompetent. Despite therapy, mortality rates in these groups are high. Over the past 5 years, advances have been made in rapid point-of-care diagnosis and early detection of cryptococcal antigen in the blood. These advances have enabled development of screening and pre-emptive treatment strategies aimed at preventing the development of clinical infection in patients with late-stage HIV infection. Progress in optimizing antifungal combinations has been aided by evaluation of the clearance rate of infection by using serial quantitative cultures of cerebrospinal fluid (CSF). Measurement and management of raised CSF pressure, a common complication, is a vital component of care. In addition, we now better understand protective immune responses in HIV-associated cases, immunogenetic predisposition to infection, and the role of immune-mediated pathology in patients with non-HIV associated infection and in the context of HIV-associated immune reconstitution reactions