Cotrimoxazole prophylaxis in HIV-infected individuals after completing anti-tuberculosis treatment in Thyolo, Malawi.

SETTING: Thyolo, rural southern Malawi. OBJECTIVES: To determine 1) the proportion who continue with cotrimoxazole prophylaxis for the prevention of opportunistic infections, and 2) the reasons for continuing or stopping prophylaxis, in human immunodeficiency virus (HIV) infected individuals with tuberculosis (TB) who complete anti-tuberculosis treatment. DESIGN: A cross-sectional study. METHODS: A questionnaire study of all HIV-infected TB patients who had been registered over a 3-month period to receive anti-tuberculosis treatment and cotrimoxazole prophylaxis and who had completed antituberculosis treatment 3-6 months earlier. RESULTS: Of 82 HIV-infected individuals who were alive at the time of interview, 76 (93%) were continuing with cotrimoxazole and wished to do so indefinitely. The most common reason for continuing the drug was to prevent illness associated with HIV, while the most common reason for stopping was long distances to the health facility. Ninety-six percent of patients received cotrimoxazole free of charge from a health centre. Of those who wished to continue indefinitely, the majority (63%) could not afford to pay for the drug. CONCLUSIONS: In a rural setting, the great majority of HIV-infected individuals continued with cotrimoxazole after completing anti-tuberculosis treatment. Making the drug available and providing it free of charge is essential if it is to remain accessible for longer term prevention

Passive Versus Active Tuberculosis Case Finding and Isoniazid Preventive Therapy Among Household Contacts in a Rural District of Malawi.

SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with active case finding among household contacts of smear-positive pulmonary tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of child contacts aged under 6 years who are placed on isoniazid (INH) preventive therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding was conducted among household contacts, and the uptake of INH preventive therapy in children was assessed. RESULTS: There were 189 index TB cases and 985 household contacts. Human immunodeficiency virus (HIV) prevalence among index cases was 69%. Prevalence of TB by passive case finding among 524 household contacts was 0.19% (191/100000), which was significantly lower than with active finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113 children received the drug. Transport costs associated with chest X-ray (CXR) screening were the major reason for low INH uptake. CONCLUSIONS: Where the majority of TB patients are HIV-positive, active case finding among household contacts yields nine times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH prophylaxis

A fast and versatile method for spectral emissivity measurement at high temperatures

International audienceIn this paper, the development of a new device for high temperature emissivity measurement is described. This device aims at measuring both spectral and total emissivity for a thermal range of 600–1000 °C. The main targeted properties of this device are versatility and simplicity. To achieve this, a rigorous selection of components such as heating systems, heat sources, sample holders, and measuring devices was made. Sample dimensions and the corresponding sample holder were optimized through a ray tracing model computation. Selection of sensors to compute the total emissivity was also discussed. A near-infrared (NIR) spectrometer and two mid-infrared (MIR) cameras equipped with optical filters covering the bandwidth of 3–5 and 7.5–13 μm were chosen for spectral measurements. The major impediment was the separation of the sample signal and various spurious signals emitted by the environment. A specific measurement methodology was then made for each bandwidth to resolve this issue. Platinum was chosen as the reference material for the device validation. Spectral emissivity measurements were then compared to values from a commercial spectrometer. A good agreement was found between NIR and MIR band I measurements, and a higher error rate was seen in MIR band II which is explained by a less favorable signal to noise ratio. Integrated emissivity is then calculated and compared to values found in the literature. A good agreement between these values is found, and similar trends with temperature are observed. The device is then validated for spectral and total emissivity measurements. Device versatility and simplicity allow for an easy adaptation to a large area of applications

Antihypertensive Treatment Fails to Control Blood Pressure During Exercise

An exaggerated blood pressure (BP) response to maximal exercise is an independent risk factor for cardiovascular events and mortality. It is unclear whether treating BP to guideline recommended levels could normalize the rise in BP during exercise, which is mediated by the metaboreflex. We aimed to assess the BP response to incremental exercise testing and metaboreflex activation in treated–controlled hypertension (n=16), treated–uncontrolled hypertension (n=16), and untreated hypertension (n=11) and 16 control participants with normal BP (n=16). All groups were matched for age and body mass index. BP was measured during an incremental V o 2 peak test on a cycle ergometer and during metaboreflex isolation using postexercise ischemia. Data were analyzed using 2-way ANOVA with Tukey test for multiple comparisons. Aerobic fitness was similar among groups ( P =0.97). The rise in absolute systolic BP from baseline at peak exercise was similar in controlled, uncontrolled, and untreated hypertension but greater compared with normotensive controls (Δ71±3, 81±7, 79±8.5 versus 47±5 mm Hg; P =0.0001). Metaboreflex sensitivity was also similar in controlled, uncontrolled, and untreated hypertension but augmented compared with normotensive controls (Δsystolic BP: 21±2, 28±2, 25±3 versus 12±2 mm Hg; P &lt;0.0001). An amplified pressor response to exercise occurred in patients taking antihypertensive medication, despite having controlled BP at rest and was potentially caused (in part) by enhanced metaboreflex sensitivity. Poor BP control during exercise, partially mediated by the metaboreflex, may contribute to the heightened risk of an adverse cardiovascular event even in treated–controlled patients. </jats:p

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing

<p>Abstract</p> <p>Background</p> <p>Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness.</p> <p>The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness.</p> <p>Methods/design</p> <p>This is a mixed methods pragmatic multicentre feasibility pilot study with four components:-</p> <p>(a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial.</p> <p>(b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience.</p> <p>(c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial.</p> <p>(d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions.</p> <p>Discussion</p> <p>The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim.</p> <p>Trial registration number</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN71327395">ISRCTN71327395</a> assigned 7^thJune 2010.</p

A chemical model for the atmosphere of hot Jupiters

Our purpose is to release a chemical network, and the associated rate coefficients, developed for the temperature and pressure range relevant to hot Jupiters atmospheres. Using this network, we study the vertical atmospheric composition of the two hot Jupiters (HD209458b, HD189733b) with a model that includes photolyses and vertical mixing and we produce synthetic spectra. The chemical scheme is derived from applied combustion models that have been methodically validated over a range of temperatures and pressures typical of the atmospheric layers influencing the observations of hot Jupiters. We compare the predictions obtained from this scheme with equilibrium calculations, with different schemes available in the literature that contain N-bearing species and with previously published photochemical models. Compared to other chemical schemes that were not subjected to the same systematic validation, we find significant differences whenever non-equilibrium processes take place. The deviations from the equilibrium, and thus the sensitivity to the network, are more important for HD189733b, as we assume a cooler atmosphere than for HD209458b. We found that the abundances of NH3 and HCN can vary by two orders of magnitude depending on the network, demonstrating the importance of comprehensive experimental validation. A spectral feature of NH3 at 10.5$\mu$m is sensitive to these abundance variations and thus to the chemical scheme. Due to the influence of the kinetics, we recommend the use of a validated scheme to model the chemistry of exoplanet atmospheres. Our network is robust for temperatures within 300-2500K and pressures from 10mbar up to a few hundreds of bars, for species made of C,H,O,N. It is validated for species up to 2 carbon atoms and for the main nitrogen species.Comment: 20 pages, 10 figures. Accepted for publication in Astronomy & Astrophysic

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding: UK Research and Innovation and National Institute for Health Research.UK Research and Innovation and National Institute for Health Research

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

BACKGROUND: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. METHODS: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. FINDINGS: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). INTERPRETATION: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. FUNDING: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

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

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders