IntroductionMalawi has a substantial burden of chronic respiratory diseases (CRDs) which cause significant morbidity and loss of economic productivity, affecting patients, families and health ...systems. Pulmonary rehabilitation (PR) is a highly recommended non-pharmacological intervention in the clinical management of people with CRDs. However, Malawi lacks published evidence on the implementation of PR for people with CRDs. This trial will test the feasibility and acceptability of implementing a culturally appropriate hospital-based PR programme among adults with functionally limiting CRDs at Queen Elizabeth Central Hospital in Blantyre, Malawi.Methods and analysisThis is a single-centre mixed-methods pre–post single-arm feasibility trial. Ten patients aged ≥18 years, with a spirometry confirmed diagnosis of a CRD and breathlessness of ≥2 on the modified Medical Research Council dyspnoea scale, will be consecutively recruited. Their baseline lung function, exercise tolerance and health status will be assessed; including spirometry, Incremental Shuttle Walk Test and Chronic Obstructive Pulmonary Disease Assessment Test, respectively. Pretrial semistructured in-depth interviews will explore their experiences of living with CRD and potential enablers and barriers to their PR uptake. Along with international PR guidelines, these data will inform culturally appropriate delivery of PR. We initially propose a 6-week, twice-weekly, supervised centre-based PR programme, with an additional weekly home-based non-supervised session. Using combination of researcher observation, interaction with the participants, field notes and informal interviews with the participants, we will assess the feasibility of running the programme in the following areas: participants’ recruitment, retention, engagement and protocol adherence. Following programme completion (after 6 weeks), repeat assessments of lung function, exercise tolerance and health status will be conducted. Quantitative changes in clinical outcomes will be described in relation to published minimal clinically important differences. Post-trial semistructured interviews will capture participants’ perceived impact of the PR programme on their quality of life, enablers, and barriers to fully engaging with the programme, and allow iteration of its design.Ethics and disseminationEthical approval for this trial was obtained from University of Malawi College of Medicine Research and Ethics Committee (COMREC), Blantyre, Malawi (protocol number: P.07/19/2752) and University of Leicester Research Ethics Committee, Leicester, UK (ethics reference: 31574). The results of the trial will be disseminated through oral presentations at local and international scientific conferences or seminars and publication in a peer-reviewed journal. We will also engage the participants who complete the PR trial and the Science Communication Department at Malawi-Liverpool-Wellcome Trust Clinical Research Programme to organise community outreach activities within Blantyre to educate communities about CRDs and PR. We will also broadcast our trial results through national radio station programmes such as the weekly “Thanzi la Onse” (Health of All) programme by Times Radio Malawi. We will formally present our trial results to Blantyre District Health Office and Malawi Ministry of Health.Trial registration numberISRCTN13836793.
Studies on pH stress in marine animals typically focus on direct or species-specific aspects. We here test the hypothesis that a drop to pH = 7.6 indirectly affects the intra- and interspecific ...interactions of benthic invertebrates by means of chemical communication. We recorded fitness-relevant behaviours of small hermit crabs
Diogenes pugilator
, green shore crabs
Carcinus maenas
, and harbour ragworms
Hediste diversicolor
in response to short-term pH drop, and to putative stress metabolites released by conspecifics or gilt-head sea bream
Sparus aurata
during 30 min of acute pH drop. Not only did acute pH drop itself impair time to find a food cue in small hermit crabs and burrowing in harbour ragworms, but similar effects were observed under exposure to pH drop-induced stress metabolites. Stress metabolites from
S. aurata
, but not its regular control metabolites, also induced avoidance responses in all recipient species. Here, we confirm that a short-term abrupt pH drop, an abiotic stressor, has the capacity to trigger the release of metabolites which induce behavioural responses in conspecific and heterospecific individuals, which can be interpreted as a behavioural cost. Our findings that stress responses can be indirectly propagated through means of chemical communication warrant further research to confirm the effect size of the behavioural impairments caused by stress metabolites and to characterise their chemical nature.
IntroductionDespite growing evidence of the long-term impact of tuberculosis (TB) on quality of life, Global Burden of Disease (GBD) estimates of TB-related disability-adjusted life years (DALYs) do ...not include post-TB morbidity, and evaluations of TB interventions typically assume treated patients return to pre-TB health. Using primary data, we estimate years of life lost due to disability (YLDs), years of life lost due to premature mortality (YLL) and DALYs associated with post-TB cardiorespiratory morbidity in a low-income country.MethodsAdults aged ≥15 years who had successfully completed treatment for drug-sensitive pulmonary TB in Blantyre, Malawi (February 2016–April 2017) were followed-up for 3 years with 6-monthly and 12-monthly study visits. In this secondary analysis, St George’s Respiratory Questionnaire data were used to match patients to GBD cardiorespiratory health states and corresponding disability weights (DWs) at each visit. YLDs were calculated for the study period and estimated for remaining lifespan using Malawian life table life expectancies. YLL were estimated using study mortality data and aspirational life expectancies, and post-TB DALYs derived. Data were disaggregated by HIV status and gender.ResultsAt treatment completion, 222/403 (55.1%) participants met criteria for a cardiorespiratory DW, decreasing to 15.6% after 3 years, at which point two-thirds of the disability burden was experienced by women. Over 90% of projected lifetime-YLD were concentrated within the most severely affected 20% of survivors. Mean DWs in the 3 years post-treatment were 0.041 (HIV-) and 0.025 (HIV+), and beyond 3 years estimated as 0.025 (HIV-) and 0.010 (HIV+), compared with GBD DWs of 0.408 (HIV+) and 0.333 (HIV-) during active disease. Our results imply that the majority of TB-related morbidity occurs post-treatment.ConclusionTB-related DALYs are greatly underestimated by overlooking post-TB disability. The total disability burden of TB is likely undervalued by both GBD estimates and economic evaluations of interventions, particularly those aimed at early diagnosis and prevention.
BackgroundNHS England recommends non-invasive continuous positive airway pressure (CPAP) as a possible treatment for type 1 respiratory failure associated with COVID-19 pneumonitis, either to avoid ...intubation or as a ceiling of care. However, data assessing this strategy are sparse, especially for the use of CPAP as a ceiling of care, and particularly when delivered outside of a traditional critical care environment. We describe a cohort of patients from Liverpool, UK, who received CPAP on a dedicated respiratory surge unit at the start of the second wave of the COVID-19 pandemic in UK.MethodsRetrospective cohort analysis of consecutive patients receiving CPAP for the treatment of respiratory failure secondary to COVID-19 on the respiratory surge unit at the Royal Liverpool Hospital, Liverpool, UK from 21 September until 30 November 2020.Results88 patients were included in the analysis. 56/88 (64%) were deemed suitable for escalation to invasive mechanical ventilation (IMV) and received CPAP as a trial; 32/88 (36%) received CPAP as a ceiling of care. Median age was 63 years (IQR: 56–74) and 58/88 (66%) were men. Median SpO2/FiO2 immediately prior to CPAP initiation was 95 (92–152). Among patients for escalation to IMV, the median time on CPAP was 6 days (IQR 4–7) and survival at day 30 was 84% (47/56) with 14/56 (25%) escalated to IMV. Of those patients for whom CPAP was ceiling of care, the median duration of CPAP was 9 days (IQR 7–11) and 18/32 (56%) survived to day 30. Pulmonary barotrauma occurred in 9% of the cohort. There were no associations found on multivariant analysis that were associated with all-cause 30-day mortality.ConclusionsWith adequate planning and resource redistribution, CPAP may be delivered effectively outside of a traditional critical care setting for the treatment of respiratory failure due to COVID-19. Clinicians delivering CPAP to patients with COVID-19 pneumonitis should be alert to the dangers of pulmonary barotrauma. Among patients who are for escalation of care, the use of CPAP may avoid the need for IMV in some patients. Our data support the NHS England recommendation to consider CPAP as a ceiling of care.
In Sub-Saharan Africa cross-sectional studies report a high prevalence of abnormal lung function indicative of chronic respiratory disease. The natural history and health impact of this abnormal lung ...function in low-and middle-income countries is largely unknown.
A cohort of 1481 adults representative of rural Chikwawa in Malawi were recruited in 2014 and followed-up in 2019. Respiratory symptoms and health-related quality of life (HRQoL) were quantified. Lung function was measured by spirometry.
1232 (83%) adults participated; spirometry was available for 1082 (73%). Mean (SD) age 49.5 (17.0) years, 278(23%) had ever smoked, and 724 (59%) were women. Forced expiratory volume in one second (FEV1) declined by 53.4 ml/year (95% CI: 49.0, 57.8) and forced vital capacity (FVC) by 45.2 ml/year (95% CI: 39.2, 50.5) . Chronic airflow obstruction increased from 9.5% (7.6, 11.6%) in 2014 to 17.5% (15.3, 19.9%) in 2019. There was no change in diagnosed asthma or in spirometry consistent with asthma or restriction. Rate of FEV1 decline was not associated with diagnosed Chronic obstructive pulmonary disease (COPD), asthma, or spirometry consistent with asthma, COPD, or restriction. HRQoL was adversely associated with respiratory symptoms (dyspnoea, wheeze, cough), previous tuberculosis, declining FEV1 and spirometry consistent with asthma or restriction. These differences exceeded the minimally important difference.
In this cohort, the increasing prevalence of COPD is associated with the high rate of FEV1 decline and lung function deficits present before recruitment. Respiratory symptoms and sub-optimal lung function are independently associated with reduced HRQoL.
This was funded by a New Investigator Research Grant from the Medical Research Council (Ref: MR/L002515/1), a joint Global Health Trials Grant from the Medical Research Council, UK Department for International Development and Wellcome Trust (Ref: MR/K006533/1, a US National Institutes for Health R56 Grant (Ref: R56ES023566) and by the National Institute for Health Research (NIHR) (project reference 16/136/35) using UK aid from the UK Government to support global health research.
Autophagy-related genes have been closely associated with intestinal homeostasis. BECLIN1 is a component of Class III phosphatidylinositol 3-kinase complexes that orchestrate autophagy initiation and ...endocytic trafficking. Here we show intestinal epithelium-specific BECLIN1 deletion in adult mice leads to rapid fatal enteritis with compromised gut barrier integrity, highlighting its intrinsic critical role in gut maintenance. BECLIN1-deficient intestinal epithelial cells exhibit extensive apoptosis, impaired autophagy, and stressed endoplasmic reticulum and mitochondria. Remaining absorptive enterocytes and secretory cells display morphological abnormalities. Deletion of the autophagy regulator, ATG7, fails to elicit similar effects, suggesting additional novel autophagy-independent functions of BECLIN1 distinct from ATG7. Indeed, organoids derived from BECLIN1 KO mice show E-CADHERIN mislocalisation associated with abnormalities in the endocytic trafficking pathway. This provides a mechanism linking endocytic trafficking mediated by BECLIN1 and loss of intestinal barrier integrity. Our findings establish an indispensable role of BECLIN1 in maintaining mammalian intestinal homeostasis and uncover its involvement in endocytic trafficking in this process. Hence, this study has important implications for our understanding of intestinal pathophysiology.
Background
Smoking rather than injecting heroin has become more common over the last 20 years. Although there is an increasing body of evidence describing high levels of chronic obstructive pulmonary ...disease (COPD) in people who smoke heroin, there is limited evidence documenting the impact of the long-term condition on this population group.
Aim
This study aimed to describe the experiences of people who smoke heroin with COPD in Liverpool, UK.
Design & setting
Participants were purposefully sampled for this qualitative study. They included adults enrolled in an opioid replacement clinic run by Addaction in Liverpool, who had already engaged with spirometry testing for COPD as part of a previous study.
Method
Semi-structured interviews were performed with participants with spirometrically confirmed COPD in opioid replacement clinics. Data were analysed using a framework analysis approach.
Results
Sixteen potential participants were invited to take part in the study, of which 10 agreed and were interviewed. Three themes common to all interviews were identified: functional measures of lung health that impacted on their activities of daily living; inhaler and medication perceptions with erratic use that was not concordant with their prescription; and the impact of difficulties accessing care.
Conclusion
These findings, along with previous studies highlighting the prevalence of COPD in this population, warrant efforts to integrate community COPD and opioid replacement services to improve outcomes for this vulnerable population.
Important features about a screening programme for newborn infants are that it should accurately, without too many false positives, detect a disease that is serious, where effective management is ...readily available and early presymptomatic detection and intervention should reduce morbidity and mortality. The screening test must be applicable to the general neonatal population and the whole programme should have an acceptable cost, relative to the potential benefit. A definitive follow up test that distinguishes true positives from false positives should be readily available. Following diagnosis, treatment should be instituted in a timely manner. It is essential that the programme is subjected to appropriate monitoring and quality assurance to ensure that the intended outcome is delivered. Most diseases detected by newborn screening are rare, and severe combined immunodeficiency (SCID) is no exception. Affecting approximately 14 infants a year in England, SCID is caused by mutations in one of a number of genes responsible for development of T-lymphocytes. Affected infants appear well at birth but present by a few months of age with recurrent or persistent infection and failure to thrive.
Noncommunicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults.
We set out to explore the ...prevalence and determinants of noncommunicable respiratory disease among adults living in Chikhwawa District, Malawi.
We performed a cross-sectional study among adults in communities participating in a randomized controlled trial of a cleaner-burning biomass-fueled cookstove intervention (CAPS Cooking and Pneumonia Study) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, and personal exposure to air pollution (particulate matter <2.5 μm in aerodynamic diameter PM
and carbon monoxide CO). Weighted prevalence estimates were calculated; multivariable and intention-to-treat analyses were done.
One thousand four hundred eighty-one participants (mean SD age, 43.8 17.8 yr; 57% female) were recruited. The prevalence of chronic respiratory symptoms, spirometric obstruction, and restriction were 13.6% (95% confidence interval CI, 11.9-15.4), 8.7% (95% CI, 7.0-10.7), and 34.8% (95% CI, 31.7-38.0), respectively. Median 48-hour personal PM
and CO exposures were 71.0 μg/m
(interquartile range IQR, 44.6-119.2) and 1.23 ppm (IQR, 0.79-1.93), respectively. Chronic respiratory symptoms were associated with current/ex-smoking (odds ratio OR, 1.59; 95% CI, 1.05-2.39), previous tuberculosis (OR, 2.50; 95% CI, 1.04-15.58), and CO exposure (OR, 1.46; 95% CI, 1.04-2.05). Exposure to PM
was not associated with any demographic, clinical, or spirometric characteristics. There was no effect of the CAPS intervention on any of the secondary trial outcomes.
The burden of chronic respiratory symptoms, abnormal spirometry, and air pollution exposures in adults in rural Malawi is of considerable potential public health importance. We found little evidence that air pollution exposures were associated with chronic respiratory symptoms or spirometric abnormalities and no evidence that the CAPS intervention had effects on the secondary trial outcomes. More effective prevention and control strategies for noncommunicable respiratory disease in sub-Saharan Africa are needed. Clinical trial registered with www.isrctn.com (ISRCTN 59448623).
Non-communicable lung disease and exposure to air pollution are major problems in sub-Saharan Africa. A high burden of chronic respiratory symptoms, spirometric abnormalities and air pollution ...exposures has been found in Malawian adults; whether the same would be true in children is unknown.
This cross-sectional study of children aged 6-8 years, in rural Malawi, included households from communities participating in the Cooking and Pneumonia Study (CAPS), a trial of cleaner-burning biomass-fuelled cookstoves. We assessed; chronic respiratory symptoms, anthropometry, spirometric abnormalities (using Global Lung Initiative equations) and personal carbon monoxide (CO) exposure. Prevalence estimates were calculated, and multivariable analyses were done.
We recruited 804 children (mean age 7.1 years, 51.9% female), including 476 (260 intervention; 216 control) from CAPS households. Chronic respiratory symptoms (mainly cough (8.0%) and wheeze (7.1%)) were reported by 16.6% of children. Average height-for-age and weight-for-age z-scores were -1.04 and -1.10, respectively. Spirometric abnormalities (7.1% low forced vital capacity (FVC); 6.3% obstruction) were seen in 13.0% of children. Maximum CO exposure and carboxyhaemoglobin levels (COHb) exceeded WHO guidelines in 50.1% and 68.5% of children, respectively. Children from CAPS intervention households had lower COHb (median 3.50% vs 4.85%, p=0.006) and higher FVC z-scores (-0.22 vs -0.44, p=0.05) than controls.
The substantial burden of chronic respiratory symptoms, abnormal spirometry and air pollution exposures in children in rural Malawi is concerning; effective prevention and control strategies are needed. Our finding of potential benefit in CAPS intervention households calls for further research into clean-air interventions to maximise healthy lung development in children.
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