How informed is consent in vulnerable populations? Experience using a continuous consent process during the MDP301 vaginal microbicide trial in Mwanza, Tanzania

BACKGROUND: HIV prevention trials conducted among disadvantaged vulnerable at-risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania. METHODS: A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs) conducted immediately after their 4, 24 and 52 week follow-up visits. RESULTS: 99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews). In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy. CONCLUSIONS: Providing information to trial participants in a focussed, locally-appropriate manner, using methods developed in consultation with the community, and within a continuous informed-consent framework resulted in high levels of comprehension and message retention in this setting. This approach may represent a model for researchers conducting HIV prevention trials among other vulnerable populations in resource-poor settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64716212

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

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

Print-and-Peel Fabrication for Microfluidics: What’s in it for Biomedical Applications?

This article reviews the development and the advances of print-and-peel (PAP) microfabrication. PAP techniques provide means for facile and expedient prototyping of microfluidic devices. Therefore, PAP has the potential for broadening the microfluidics technology by bringing it to researchers who lack regular or any accesses to specialized fabrication facilities and equipment. Microfluidics have, indeed, proven to be an indispensable toolkit for biological and biomedical research and development. Through accessibility to such methodologies for relatively fast and easy prototyping, PAP has the potential to considerably accelerate the impacts of microfluidics on the biological sciences and engineering. In summary, PAP encompasses: (1) direct printing of the masters for casting polymer device components; and (2) adding three-dimensional elements onto the masters for single-molding-step formation of channels and cavities within the bulk of the polymer slabs. Comparative discussions of the different PAP techniques, along with the current challenges and approaches for addressing them, outline the perspectives for PAP and how it can be readily adopted by a broad range of scientists and engineers

Architecture of the Chugach accretionary complex as revealed by detrital zircon ages and lithologic variations: Evidence for Mesozoic subduction erosion in south-central Alaska

Subduction erosion is an important process at convergent margins but evidence in the geologic record is scarce because the involved materials are typically lost into the mantle. Detrital zircon dating of accretionary complex sediment allows us to document episodic growth that can be linked to possible triggers. Detrital zircons (n = 2508) from the Mesozoic Chugach accretionary complex, southern Alaska, have U-Pb ages that record progressive subduction accretion punctuated by two periods of tectonic erosion. Lithology and maximum depositional ages permit division of the Chugach accretionary complex into four main units. The oldest, the blueschist-greenschist unit, represents partially subducted sediment associated with a Jurassic oceanic arc, with subduction erosion from 180 to 170 Ma. The end of this erosion period is dated by the oldest maximum depositional age of the Potter Creek assemblage, a \u3c156-169 Ma unit consisting of chert, argillite, and volcanic rocks. A trondhjemite pluton that intrudes the forearc was caused by ridge subduction at 125 Ma and resulted in a second period of subduction erosion lasting until 104 Ma. The end of Aptian-Albian erosion was marked by deposition of massive sandstone and conglomerate of the 101-91 Ma McHugh Creek assemblage. This infl ux of clastic sediment is interpreted to have occurred in response to the collision of Wrangellia with North America. This event and the erosional event preceding it steepened the forearc region, allowing mass wasting of forearc crust into the trench, filling it by 89 Ma, the oldest maximum depositional age of the Valdez Group fl ysch. Clasts in conglomerate include granodiorite from the basement of the Talkeetna arc dated from 199 ± 3 Ma to 179 ± 3 Ma, and sandstone clasts with maximum depositional ages of 100 Ma. From 89 Ma to at least 72 Ma, the Valdez Group fl ysch was deposited via turbidite fans onto the oceanic crust beyond the trench and accreted as imbricate thrust slices that retained coherent bedding. The source for detrital zircons in the Potter Creek assemblage is likely a Middle-Late Jurassic oceanic arc, possibly the Talkeetna arc. The abundance of zircons from ash fall tuffs is consistent with easterly winds and suggests the Chugach accretionary complex was south of latitude 25oN in the Late Jurassic. The dominant source for the Albian McHugh Creek assemblage and the Upper Cretaceous Valdez Group fl ysch was likely the arc associated with the Coast Mountains batholith. Jurassic (ca. 165 Ma) zircons in the McHugh Creek assemblage could have been derived from exhumed plutons, or may be secondcycle zircons derived from the Potter Creek assemblage. The first appearance of Proterozoic and Archean zircons in the Valdez Group records the breakdown of topographic barriers formed by the accreted arc terranes as rivers encroached into continental North America by the middle Late Cretaceous. © 2013 Geological Society of America

The epidemiology of HIV and HSV-2 infections among women participating in microbicide and vaccine feasibility studies in Northern Tanzania.

OBJECTIVES: To prepare for future HIV prevention trials, we conducted prospective cohort studies among women working in food and recreational facilities in northern Tanzania. We examined the prevalence and incidence of HIV and HSV-2, and associated risk factors. METHODS: Women aged 18-44 years working in food and recreational facilities were screened to determine their eligibility for the studies. Between 2008-2010, HIV-negative women were enrolled and followed for 12 months. At enrolment and 3-monthly, we collected socio-demographic and behavioural data, and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections. Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models. RESULTS: We screened 2,229 and enrolled 1,378 women. The median age was 27 years (interquartile range, IQR 22, 33), and median duration working at current facility was 2 years. The prevalences of HIV at screening and HSV-2 at enrolment were 16% and 67%, respectively. Attendance at the 12-month visit was 86%. HIV and HSV-2 incidence rates were 3.7 (95% confidence interval, CI: 2.8,5.1) and 28.6 (95% CI: 23.5,35.0)/100 person-years, respectively. Women who were separated, divorced, or widowed were at increased risk of HIV (adjusted incidence rate ratio, aRR = 6.63; 95% CI: 1.97,22.2) and HSV-2 (aRR = 2.00; 95% CI: 1.15,3.47) compared with married women. Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0-1 partner (aRR = 4.75; 95% CI: 2.10,10.8), while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education (aRR = 0.42; 95% CI: 0.22,0.82). CONCLUSIONS: HIV and HSV-2 rates remain substantially higher in this cohort than in the general population, indicating urgent need for effective interventions. These studies demonstrate the feasibility of conducting trials to test new interventions in this highly-mobile population

Music Participation for Older People: Five Choirs in Victoria, Australia

In Australia and across the globe music participation by older people active in the community has the potential to enhance quality of life. A recent review of the literature found clear evidence of numerous benefits from participation in active music making that encompass the social, physical and psychological. This article reports on five phenomenological case studies of community singing groups comprised of older people active in the community in Melbourne, Victoria. These studies are part of a research project, Well-being and Ageing: Community, Diversity and the Arts in Victoria that began in 2008. Interview data were analysed using interpretative phenomenological analysis and are reported under three overarching themes: Social connection, A sense of well-being, and Musical engagement. For older people in these studies singing in community choirs offered opportunities for social cohesion, positive ageing, and music learning that provided a sense of personal and group fulfilment, community engagement and resilience. (PsycINFO Database Record (c) 2019 APA, all rights reserved