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Introduction: The COVID-19 pandemic presented an unprecedented challenge to the medical community, leading to numerous therapeutic interventions being explored. Convalescent plasma therapy (CPT), derived from recovered COVID-19 patients, was one such treatment used in the absence of proven therapies. However, its efficacy remained a topic of debate. Materials and Methods: This retrospective study aimed to assess the effectiveness of CPT in patients admitted to the intensive care unit (ICU) with moderate-to-severe COVID-19 infection. Data included comorbidities, treatment regimens, partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratios, oxygen therapy duration, and outcomes. Patients were divided into groups based on CPT receipt. Statistical analysis was performed to compare the two groups. Results: Out of 72 patients, 36 received CPT, and 36 did not. Patients who received CPT had longer ICU and hospital stays. The mortality rate was higher in the CPT group (50%) compared to the non-CPT group (22.2%). Patients with comorbidities experienced higher mortality rates. Notably, the CPT group exhibited improved PaO2/FiO2 ratios on day 2. Complications related to CPT were minimal. Conclusion: The use of CPT in COVID-19 treatment did not impact overall survival or hospital stay duration.

Reducing the stigma and discrimination faced by men who have sex with men (MSM) and transgender women (TGW) in healthcare settings is key to improving health outcomes. Using a one-group pre- and post-test design, we tested the efficacy of a theory-informed, multi-level pilot intervention (“Harmony”) among 98 healthcare workers (HCWs) to reduce sexual orientation and gender identity (SOGI)-related stigma and discrimination faced by MSM and TGW in two public hospitals. The intervention contained group-level (a half-day workshop) and individual-level (four videos) components. Using multi-level modelling, we compared knowledge, attitudes, and comfort level among HCWs across three timepoints: pre-intervention, post-intervention, and follow-up (2 months after the intervention). Client surveys were conducted among 400 MSM/TGW (two independent samples of 200 MSM/TGW) attending the intervention hospitals, before the intervention among HCWs and three months after the intervention. Generalised estimating equations assessed service users’ satisfaction with hospital services, discrimination experiences, and positive interactions with HCWs. Significant changes were observed in primary outcomes: 30% increase in positive attitude scores (incidence rate ratio (IRR) = 1.30, 95% CI 1.13–1.49) and 23% increase in the proportion of HCWs reporting being comfortable in providing care to MSM/TGW (IRR = 1.23, 95% CI 0.03–1.68). Similarly, there was a significant improvement in secondary outcomes (scores): support for non-discriminatory hospital policies (IRR = 1.08, 95% CI 1.004–1.15), the importance of asking SOGI questions in clinical history (IRR = 1.17, 95% CI 1.06–1.29), and perceived self-efficacy in providing clinical care (IRR = 1.13, 95% CI 1.01–1.27). Service users’ data provided corroborative evidence for intervention efficacy: e.g., 14% increase in the proportion of MSM reporting overall satisfaction with hospital services and 6% and 15% increase in the scores of positive interactions with HCWs in the combined sample of MSM/TGW and TGW, respectively. The Harmony intervention showed preliminary evidence for improving positive attitudes, comfort level, and understanding of the healthcare issues of MSM/TGW among HCWs, warranting large-scale implementation research.

Abstract Background Water insecurity disproportionally affects socially marginalized populations and may harm mental health. Lesbian, gay, bisexual, transgender and queer (LGBTQ) persons are at the nexus of social marginalization and mental health disparities; however, they are understudied in water insecurity research. Yet LGBTQ persons likely have distinct water needs. We explored associations between water insecurity and mental health outcomes among LGBTQ adults in Mumbai, India and Bangkok, Thailand. Methods This cross-sectional survey with a sample of LGBTQ adults in Mumbai and Bangkok assessed associations between water insecurity and mental health outcomes, including anxiety symptoms, depression symptoms, loneliness, alcohol misuse, COVID-19 stress and resilience. We conducted multivariable logistic and linear regression analyses to examine associations between water insecurity and mental health outcomes. Results Water insecurity prevalence was 28.9% in Mumbai and 18.6% in Bangkok samples. In adjusted analyses, in both sites, water insecurity was associated with higher likelihood of depression symptoms, anxiety symptoms, COVID-19 stress, alcohol misuse and loneliness. In Mumbai, water insecurity was also associated with reduced resilience. Conclusion Water insecurity was common among LGBTQ participants in Bangkok and Mumbai and associated with poorer well-being. Findings signal the importance of assessing water security as a stressor harmful to LGBTQ mental health.

IntroductionThe Government of Tamil Nadu, India, mandated wearing face masks in public places to combat the COVID-19 pandemic. We established face mask surveillance and estimated the prevalence of appropriate mask use (covering the nose, mouth, and chin) in the slums and non-slums of Chennai at different time points in 2021.MethodsWe conducted three serial cross-sectional surveys in the outdoors and indoors of Chennai in March, July, and October 2021. We observed the mask wearing among 3200 individuals in the outdoors and 1280 in the indoors. We divided the outdoor and indoor locations into slums and non-slums. In October 2021, we also surveyed 150 individuals from each of the 11 shopping malls in the city. We calculated the proportions and 95% confidence interval (95%CI) for the appropriate mask use in the outdoor, indoor, and malls by age, gender, region, and setting (slum and non-slum).ResultsWe observed 3200 individuals in the outdoor and 1280 individuals in the indoor setting, each from a slum and non-slum, during the three rounds of the study. In outdoor and indoors, males comprised three-fourths and middle-aged individuals were half the study population. Mask compliance changed significantly with time (p-value ConclusionThe mask compliance in Chennai outdoors during the COVID-19 pandemic was less than 50%, with variations across time points by gender, age groups, and geographical locations. We must develop more effective communication strategies for older age groups and crowded indoor settings.

IntroductionIndia has the second largest HIV epidemic in the world. Despite successes in epidemic control at the population level, a concentrated epidemic persists among gay and other men who have sex with men (MSM). However, India lags in implementation of biomedical prevention technologies, such as HIV pre-exposure prophylaxis (PrEP). In order to inform scale-up of new HIV prevention technologies, including those in the development pipeline, we assessed willingness to use oral PrEP, rectal microbicides, and HIV vaccines, and choices among product characteristics, among MSM in two major Indian cities.MethodsA cross-sectional survey was conducted with a discrete choice experiment (DCE), an established methodology for quantitively estimating end-user preferences in healthcare. Survey participants were randomly assigned to one of three questionnaire versions, each of which included a DCE for one prevention technology. Participants were recruited using chain-referral sampling by peer outreach workers, beginning with seeds in community-based organizations and public sex environments, in Chennai and Mumbai. DCE data were analyzed using random-parameters (mixed) logit (RPL) models.ResultsAmong participants (n = 600), median age was 25 years, with median monthly income of INR 9,000 (~US$125). Nearly one-third (32%) had completed a college degree and 82% were single/never married. A majority of participants (63%) reported condomless anal sex in the past month. The acceptability of all three products was universally high (≥90%). Across all three products, four attributes were significant predictors of acceptability-with efficacy consistently the most important attribute, and in decreasing order of preference, side-effects, dosing schedule, and venue. MSM varied in their preferences for product attributes in relation to their levels of education and income, and engagement in sex work and HIV risk behavior.ConclusionThis study provides empirical evidence to facilitate the integration of end users' preferences throughout design, testing, and dissemination phases of HIV prevention technologies. The findings also suggest action points and targets for interventions for diverse subgroups to support the effectiveness of combination HIV prevention among MSM in India.

Transgender women (TGW) in India, especially those who engage in sex work, are at high risk for HIV. Guided by the information-motivation-behavioral skills model and qualitative formative research findings, Sakhi (girlfriend), a 3-week smartphone-based pilot intervention consisting of short videos (one/week) and text messages (two/week), was implemented using a one-group pre- and post-test design to test its efficacy in promoting condom use and HIV testing among TGW (n = 50) who engage in sex work in Chennai. Changes in outcomes were assessed by conducting multivariable analyses using generalized estimating equations. Participants’ mean age was 26 years, and the mean monthly income was INR 21700 (USD 292). About one-third completed college, and 96% were HIV-negative. Significant changes in the desired direction were observed in the primary outcomes: condom use – decrease in the engagement of condomless anal sex with male partners (12% to 2%, p < 0.05) and HIV testing – increase in intentions to undergo HIV testing every 6 months (34% to 86%, p < 0.001); and in some of the secondary outcomes: decrease in alcohol use before sex, increase in intentions to use condoms consistently and increase in the well-being score. This study demonstrated the feasibility, acceptability, and preliminary efficacy of the Sakhi intervention and warrants a larger randomized trial among diverse subgroups in diverse settings.

Background: Smartphone use is increasing among transgender women (TGW), including those who engage in sex work. Current government-supported HIV prevention interventions focus on physical venue-based outreach among TGW, missing the opportunity to reach them through smartphone-based interventions. Objective: We examined the use of smartphones among TGW, especially in relation to social and sexual networking, and explored their perspectives on their willingness to use smartphone-based HIV prevention interventions. Materials and Methods: Through an exploratory descriptive-interpretive qualitative research design, we conducted 6 focus groups with a purposive sample of 30 TGW (70% in sex work) and 4 key informant in-depth interviews in Chennai and Hyderabad, India. Data were explored using framework analysis. Results: Through smartphones, TGW used social media (e.g., WhatsApp and Facebook) and dating applications for socialization, meeting sexual partners, and entertainment. Low-literacy TGW used voice or video messaging. TGW expressed interest in receiving short health-related videos and text messages on HIV, mental health, and gender transition. Conclusion: At-risk TGW could potentially be reached through smartphone-based online health promotion interventions, but those interventions need to be holistic – moving beyond HIV.

Background: Lung ultrasound (LUS) is increasingly used as an extension of physical examination, informing clinical diagnosis, and decision making. There is particular interest in the assessment of patients with pulmonary congestion and extravascular lung water, although gaps remain in the evidence base underpinning this practice as a result of the limited evaluation of its inter-rater reliability and comparison with more established radiologic tests. Methods: 30 patients undergoing haemodialysis were prospectively recruited to an observational cohort study (NCT01949402). Patients underwent standardised LUS assessment before, during and after haemodialysis; their total LUS B-line score was generated, alongside a binary label of whether appearances were consistent with an interstitial syndrome. LUS video clips were recorded and independently scored by two blinded expert clinician sonographers. Low-dose non-contrast thoracic CT, pre- and post dialysis, was used as a “gold standard” radiologic comparison. Results: LUS detected a progressive reduction in B-line scores in almost all patients undergoing haemodialysis, correlating with the volume of fluid removed once individuals with no or minimal B-lines upon pre-dialysis examination were discounted. When comparing CT scans pre- and post dialysis, radiologic evidence of the change in fluid status was only identified in a single patient. Conclusions: This is the first study to demonstrate that LUS detects changes in extravascular lung water caused by changing fluid status during haemodialysis using a blinded outcome assessment and that LUS appears to be more sensitive than CT for this purpose. Further research is needed to better understand the role of LUS in this and similar patient populations, with the aim of improving clinical care and outcomes.

Immune system function declines with age, a consequence of defects in hematopoietic stem cells (HSCs). Here the authors show that TAZ buffers age-related loss of PU.1 activity to maintain HSC functionality and identify the surface protein Clca3a1 as a marker of “young-like” HSCs, even in old mice.

BACKGROUND: Regular blood donation depletes iron stores. The assertion is that the vulnerable donor population requires a predictive standard operative procedure for early detection of iron store depletion, preventing them from developing iron-deficiency anemia. AIM: This study aims to study the potential effects of blood donation in the regular donor group using hematological and biochemical estimation of iron status parameters. STUDY SETTINGS AND DESIGN: This was a prospective cross-sectional study on regular blood donors, defined as those who have donated at least 3 times, the last donation being within the last 12 months and continues to donate at least once a year, at a tertiary care teaching hospital in Southern India. MATERIALS AND METHODS: The complete blood count (CBC) was performed on the Sysmex coulter, and the red cell indices were calculated. The ferritin and the soluble transferrin receptor (sTfR) assays were performed using Enzyme Immunoassays. STATISTICAL ANALYSIS USED: The comparison of CBC, serum ferritin, and sTfR assay with donation frequency and time since the last donation was carried out using an independent student's t-test for two groups. The statistical analysis was performed using SPSS for Windows version 20. RESULTS: A total of 323 regular blood donors (6 were females) were included in the study of which they were categorized into three, 211 donors with less than or equal to 10 donations, 84 those who had donated between 11 and 20 times and 28 who had donated more than 20 times. The red cell indices were reduced and different in the groups but not statistically significant except for mean corpuscular volume. About 15% of the study population had a transferrin level of 12.5 g/dL) for donation, or the red cell indices alone do not reflect the donor's actual iron status.

Amid incremental progress in establishing an enabling legal and policy environment for lesbian, gay, bisexual, transgender and queer-identified people, and people with intersex variations (LGBTQI+) in India, evidence gaps on LGBTQI+ health are of increasing concern. To that end, we conducted a scoping review to map and synthesize the current evidence base, identify research gaps, and provide recommendations for future research. We conducted a scoping review using the Joanna Briggs Institute methodology. We systematically searched 14 databases to identify peer-reviewed journal articles published in English language between January 1, 2010 and November 20, 2021, that reported empirical qualitative, quantitative or mixed methods data on LGBTQI+ people’s health in India. Out of 3,003 results in total, we identified 177 eligible articles; 62% used quantitative, 31% qualitative, and 7% mixed methods. The majority (55%) focused on gay and other men who have sex with men (MSM), 16% transgender women, and 14% both of these populations; 4% focused on lesbian and bisexual women, and 2% on transmasculine people. Overall, studies reported high prevalence of HIV and sexually transmitted infections; multilevel risk factors for HIV; high levels of mental health burden linked to stigma, discrimination, and violence victimization; and non-availability of gender-affirmative medical care in government hospitals. Few longitudinal studies and intervention studies were identified. Findings suggest that LGBTQI+ health research in India needs to move beyond the predominant focus on HIV, and gay men/MSM and transgender women, to include mental health and non-communicable diseases, and individuals across the LGBTQI+ spectrum. Future research should build on largely descriptive studies to include explanatory and intervention studies, beyond urban to rural sites, and examine healthcare and service needs among LGBTQI+ people across the life course. Increased Indian government funding for LGBTQI+ health research, including dedicated support and training for early career researchers, is crucial to building a comprehensive and sustainable evidence base to inform targeted health policies and programs moving forward.

Introduction Electronic clinical decision support (eCDS) tools are used to assist clinical decision making. Using computer-generated algorithms with evidence-based rule sets, they alert clinicians to events that require attention. eCDS tools generating alerts using nudge principles present clinicians with evidence-based clinical treatment options to guide clinician behaviour without restricting freedom of choice. Although eCDS tools have shown beneficial outcomes, challenges exist with regard to their acceptability most likely related to implementation. Furthermore, the pace of progress in this field has allowed little time to effectively evaluate the experience of the intended user. This scoping review aims to examine the development and implementation strategies, and the impact on the end user of eCDS tools that generate alerts using nudge principles, specifically in the critical care and peri-anaesthetic setting.Methods and analysis This review will follow the Arksey and O’Malley framework. A search will be conducted of literature published in the last 15 years in MEDLINE, EMBASE, CINAHL, CENTRAL, Web of Science and SAGE databases. Citation screening and data extraction will be performed by two independent reviewers. Extracted data will include context, e-nudge tool type and design features, development, implementation strategies and associated impact on end users.Ethics and dissemination This scoping review will synthesise published literature therefore ethical approval is not required. Review findings will be published in topic relevant peer-reviewed journals and associated conferences.

Introduction Acute respiratory failure is a common clinical condition accounting for nearly 116 000 admissions in the UK hospitals. Acute type 2 respiratory failure is also called acute hypercapnic respiratory failure (AHRF) and characterised by an elevated arterial CO2 level of >6 kPa due to pump failure. Acute exacerbation of chronic obstructive pulmonary disease is the most common cause of AHRF. High-flow nasal therapy (HFNT) is a new oxygen delivery system that uses an oxygen-air blender to deliver flow rates of up to 60 L/min. The gas is delivered humidified and heated to the patient via wide-bore nasal cannula.Methods and analysis We hypothesised that HFNC as the initial oxygen administration method will reduce the number of patients with AHRF requiring non-invasive ventilation in patients at 6 hours post intervention when compared with low-flow nasal oxygen (LFO). A randomised single-centre unblinded controlled trial is designed to test our hypothesis. The trial will compare two oxygen administration methods, HFNT versus LFO. Patients will be randomised to one of the two arms if they fulfil the eligibility criteria. The sample size is 82 adult patients (41 HFNT and 41 LFO) presenting to the emergency department.Ethics and dissemination Ethical approval was obtained from the Office for Research Ethics Committees Northern Ireland (REC reference: 20/NI/0049). Dissemination will be achieved in several ways: (1) the findings will be presented at national and international meetings with open-access abstracts online and (2) in accordance with the open-access policies proposed by the leading research funding bodies we aim to publish the findings in high-quality peer-reviewed open-access journals.Trial registration number The trial was prospectively registered at the clinicaltrials.gov registry (NCT04640948) on 20 November 2020.

Background: Acute type two respiratory failure (AT2RF) is characterized by high carbon dioxide levels (PaCO2 >6kPa). Non-invasive ventilation (NIV), the current standard of care, has a high failure rate. High flow nasal therapy (HFNT) has potential additional benefits such as CO2 clearance, the ability to communicate and comfort. The primary aim of this systematic review is to determine whether HFNT in AT2RF improves 1) PaCO2, 2) clinical and patient-centred outcomes and 3) to assess potential harms. Methods: We searched EMBASE, MEDLINE and CENTRAL (January 1999-January 2021). Randomised controlled trials (RCTs) and cohort studies comparing HFNT with low flow nasal oxygen (LFO) or NIV were included. Two authors independently assessed studies for eligibility, data extraction and risk of bias. We used Cochrane risk of bias tool for RCTs and Ottawa-Newcastle scale for cohort studies. Results: From 727 publications reviewed, four RCTs and one cohort study (n=425) were included. In three trials of HFNT vs NIV, comparing PaCO2 (kPa) at last follow-up time point, there was a significant reduction at four hours (1 RCT; HFNT median 6.7, IQR 5.6 – 7.7 vs NIV median 7.6, IQR 6.3 – 9.3) and no significant difference at 24-hours or five days. Comparing HFNT with LFO, there was no significant difference at 30-minutes. There was no difference in intubation or mortality. Conclusions: This review identified a small number of studies with low to very low certainty of evidence. A reduction of PaCO2 at an early time point of four hours post-intervention was demonstrated in one small RCT. Significant limitations of the included studies were lack of adequately powered outcomes and clinically relevant time-points and small sample size. Accordingly, systematic review cannot recommend the use of HFNT as the initial management strategy for AT2RF and trials adequately powered to detect clinical and patient-relevant outcomes are urgently warranted.

BackgroundThe use of the internet and web-based platforms to obtain public health information and manage health-related issues has become widespread in this digital age. The practice is so pervasive that the first reaction to obtaining health information is to “Google it.” As SARS-CoV-2 broke out in Wuhan, China, in December 2019 and quickly spread worldwide, people flocked to the internet to learn about the novel coronavirus and the disease, COVID-19. Lagging responses by governments and public health agencies to prioritize the dissemination of information about the coronavirus outbreak through the internet and the World Wide Web and to build trust gave room for others to quickly populate social media, online blogs, news outlets, and websites with misinformation and conspiracy theories about the COVID-19 pandemic, resulting in people’s deviant behaviors toward public health safety measures. ObjectiveThe goals of this study were to determine what people learned about the COVID-19 pandemic through web searches, examine any association between what people learned about COVID-19 and behavior toward public health guidelines, and analyze the impact of misinformation and conspiracy theories about the COVID-19 pandemic on people’s behavior toward public health measures. MethodsThis infodemiology study used Google Trends’ worldwide search index, covering the first 6 months after the SARS-CoV-2 outbreak (January 1 to June 30, 2020) when the public scrambled for information about the pandemic. Data analysis employed statistical trends, correlation and regression, principal component analysis (PCA), and predictive models. ResultsThe PCA identified two latent variables comprising past coronavirus epidemics (pastCoVepidemics: keywords that address previous epidemics) and the ongoing COVID-19 pandemic (presCoVpandemic: keywords that explain the ongoing pandemic). Both principal components were used significantly to learn about SARS-CoV-2 and COVID-19 and explained 88.78% of the variability. Three principal components fuelled misinformation about COVID-19: misinformation (keywords “biological weapon,” “virus hoax,” “common cold,” “COVID-19 hoax,” and “China virus”), conspiracy theory 1 (ConspTheory1; keyword “5G” or “@5G”), and conspiracy theory 2 (ConspTheory2; keyword “ingest bleach”). These principal components explained 84.85% of the variability. The principal components represent two measurements of public health safety guidelines—public health measures 1 (PubHealthMes1; keywords “social distancing,” “wash hands,” “isolation,” and “quarantine”) and public health measures 2 (PubHealthMes2; keyword “wear mask”)—which explained 84.7% of the variability. Based on the PCA results and the log-linear and predictive models, ConspTheory1 (keyword “@5G”) was identified as a predictor of people’s behavior toward public health measures (PubHealthMes2). Although correlations of misinformation (keywords “COVID-19,” “hoax,” “virus hoax,” “common cold,” and more) and ConspTheory2 (keyword “ingest bleach”) with PubHealthMes1 (keywords “social distancing,” “hand wash,” “isolation,” and more) were r=0.83 and r=–0.11, respectively, neither was statistically significant (P=.27 and P=.13, respectively). ConclusionsSeveral studies focused on the impacts of social media and related platforms on the spreading of misinformation and conspiracy theories. This study provides the first empirical evidence to the mainly anecdotal discourse on the use of web searches to learn about SARS-CoV-2 and COVID-19.

Rationale Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up.Approach The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation.Reflection Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution.Discussion EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.

Background Mechanical ventilation for acute respiratory failure is one of the most common indications for admission to intensive care units (ICUs). Airway mucus clearance is impaired in these patients medication, impaired mucociliary motility, increased mucus production etc. and mucoactive agents have the potential to improve outcomes. However, studies to date have provided inconclusive results. Despite this uncertainty, mucoactives are used in adult ICUs, although the extent of use and perceptions about place in therapy are not known. Aims and Objectives We aim to describe the use of mucoactive agents in mechanically ventilated patients in UK adult critical care units. Specifically, our objectives are to describe clinicians perceptions about the use of mucoactive agents, understand the indications and anticipated benefits, and describe the prevalence and type of mucoactive agents in use. Methods We conducted three surveys. Firstly, a practitioner-level survey aimed at nurses, physiotherapists and doctors to elucidate individual practitioners perceptions about the use of mucoactive agents. Secondly, a critical care unit-level survey aimed at pharmacists to understand how these perceptions translate into practice. Thirdly, a point prevalence survey to describe the extent of prescribing and range of products in use. The practitioner-level survey was disseminated through the UK Intensive Care Society for completion by a multi-professional membership. The unit-level and point prevalence surveys were disseminated cthrough the UK Clinical Pharmacy Association for completion by pharmacists. Results The individual practitioners survey ranked ‘thick secretions’ as the main reason for commencing mucoactive agents determined using clinical assessment. The highest ranked perceived benefit for patient centred outcomes was the duration of ventilation. Of these respondents, 79% stated that further research was important and 87% expressed support for a clinical trial. The unit-level survey found that mucoactive agents were used in 83% of units. The most highly ranked indication was again ‘thick secretions’ and the most highly ranked expected patient centred clinical benefit being improved gas exchange and reduced ventilation time. Only five critical care units provided guidelines to direct the use of mucoactive agents (4%). In the point prevalence survey, 411/993 (41%) of mechanically ventilated patients received at least one mucoactive agent. The most commonly administered mucoactives were inhaled sodium chloride 0.9% (235/993, 24%), systemic carbocisteine (161/993, 16%) and inhaled hypertonic sodium cloride (127/993, 13%). Conclusions Mucoactive agents are used extensively in mechanically ventilated adult patients in UK ICUs to manage ‘thick secretions’, with a key aim to reduce the duration of ventilation. There is widespread support for clinical trials to determine the optimal use of mucoactive agent therapy in this patient population.

Abstract Background Postoperative pulmonary complications (PPC) and peri-operative myocardial infarction (MI) have a significant impact on the long-term mortality of surgical patients. Patients undergoing one-lung ventilation (OLV) for surgery are at a high risk of developing these complications. These complications could be associated with intensive care unit (ICU) admissions and longer hospital stay with associated resource and economic burden. Simvastatin, a HMG-CoA reductase enzyme inhibitor has been shown to have pleiotropic anti-inflammatory effects as well as being endothelial protective. The benefits of statins have been shown in various observational studies and in small proof-of-concept studies. There is an urgent need for a well-designed, large clinical trial powered to detect clinical outcomes. The Prevention HARP 2 trial will test the hypothesis ‘simvastatin 80 mg when compared to placebo will reduce cardiac and pulmonary complications in patients undergoing elective oesophagectomy, lobectomy or pneumonectomy’. Methods/design The Prevention HARP 2 trial is a UK multi-centre, randomised, double-blind, placebo-controlled trial. Adult patients undergoing elective oesophagectomy, lobectomy or pneumonectomy will be eligible. Patients who are already on statins will be excluded from this trial. Patients will be randomised to receive simvastatin 80 mg or matched placebo for 4 days pre surgery and for up to 7 days post surgery. The primary outcome is a composite outcome of PPC and MI within 7 days post surgery. Various secondary outcome measures including clinical outcomes, safety outcomes and health economic outcomes will be collected. The study aims to recruit 452 patients in total across 12 UK sites. Discussion The results of the Prevention HARP 2 trial should add to our understanding of the benefits of peri-operative statins and influence clinical decision-making. Analysis of blood and urine samples from the patients will provide insight into the mechanism of simvastatin action. Trial registration International Standard Randomised Controlled Trials registry, ID: ISRCTN48095567. Registered on 11 November 2016.

Cost–volume–profit (CVP) analysis is a widely used decision tool across many business disciplines. The current literature on stochastic applications of the CVP model is limited in that the model is studied under the restrictive forms of the Gaussian and Lognormal distributions. In this paper we introduce the Mellin Transform as a methodology to generalize stochastic modeling of the CVP problem. We demonstrate the versatility of using the Mellin transform to model the CVP problem, and present a generalization of the CVP model when the contribution margin and sales volume are both defined by continuous random distributions.

Background: Micro-organisms are the primary causative agents of endodontic infections. Phenotype based procedures for bacterial identification has certain drawbacks especially, when investigating the microbiota of root-filled teeth. Thus, more sensitive methods like Polymerase chain reaction (PCR) can provide results that are more accurate and reliable for the microbial prevalence in the root filled teeth. Aim: In this study, we have investigated twenty symptomatic root-filled teeth with chronic apical periodontitis for the prevalence of Enterococcus faecalis and Candida albicans in the root filled teeth associated with symptomatic cases with or without periradicular lesions. Materials and Methods: Microbiological samples were taken from the canals immediately after removal of previous gutta percha cones using aseptic techniques. After removal of root canal filling, samples were obtained with paper points placed in the canal. Paper points were transferred to a cryotube containing "Tris EDTA" buffer and immediately frozen at −20°C. Results: By PCR amplification of the samples using taxon specific primers, E. faecalis was found to be prevalent species, detected in 65% of the cases and C. albicans was detected in 35% of cases. Conclusion: The results of the study shows that geographical influence and dietary factors might have some role to play in the prevalence of the species like C. albicans and presence of E. faecalis confirming the assertion of previous culture-dependent and independent approaches for the microbiological survey of root filled teeth.

ObjectivesBroad international guidelines and studies in the context of individual clinical trials highlight the centrality of community stakeholder engagement in conducting ethically rigorous HIV prevention trials. We explored and identified challenges and facilitators for community stakeholder engagement in biomedical HIV prevention trials in diverse global settings. Our aim was to assess and deepen the empirical foundation for priorities included in the GPP guidelines and to highlight challenges in implementation that may merit further attention in subsequent GPP iterations.MethodsFrom 2008-2012 we conducted an embedded, multiple case study centered in Thailand, India, South Africa and Canada. We conducted in-depth interviews and focus groups with respondents from different trial-related subsystems: civil society organization representatives, community advocates, service providers, clinical trialists/researchers, former trial participants, and key HIV risk populations. Interviews/focus groups were recorded, and coded using thematic content analysis. After intra-case analyses, we conducted cross-case analysis to contrast and synthesize themes and sub-themes across cases. Lastly, we applied the case study findings to explore and assess UNAIDS/AVAC GPP guidelines and the GPP Blueprint for Stakeholder Engagement.ResultsAcross settings, we identified three cross-cutting themes as essential to community stakeholder engagement: trial literacy, including lexicon challenges and misconceptions that imperil sound communication; mistrust due to historical exploitation; and participatory processes: engaging early; considering the breadth of "community"; and, developing appropriate stakeholder roles. Site-specific challenges arose in resource-limited settings and settings where trials were halted.ConclusionsThis multiple case study revealed common themes underlying community stakeholder engagement across four country settings that largely mirror GPP goals and the GPP Blueprint, as well as highlighting challenges in the implementation of important guidelines. GPP guidance documents could be strengthened through greater focus on: identifying and addressing the community-specific roots of mistrust and its impact on trial literacy activities; achieving and evaluating representativeness in community stakeholder groups; and addressing the impact of power and funding streams on meaningful engagement and independent decision-making.

Recruitment of low- and middle-income country volunteers from most-at-risk populations in HIV vaccine trials is essential to vaccine development. In India, men who have sex with men (MSM) are at disproportionately high risk for HIV infection and an important population for trial recruitment. Investigations of willingness to participate (WTP) in HIV vaccine trials have focused predominantly on individual-level determinants. We explored multi-level factors associated with WTP among MSM in India.We conducted 12 focus groups (n = 68) with low socioeconomic MSM in Chennai and Mumbai, and 14 key informant interviews with MSM community leaders and service providers. Focus groups/interviews were recorded, transcribed and translated into English. Two bilingual investigators conducted thematic analysis using line-by-line coding and a constant comparative method, with member-checking by community representatives.Factors associated with WTP were evidenced across the social ecology of MSM-social-structural: poverty, HIV-, sexual- and gender non-conformity stigma, institutionalized discrimination and government sponsorship of trials; community-level: endorsement by MSM community leaders and organizations, and fear of within-group discrimination; interpersonal: anticipated family discord, partner rejection, having financially-dependent family members and disclosure of same-sex sexuality; and individual-level: HIV vaccine trial knowledge and misconceptions, safety concerns, altruism and preventive misconception.Pervasive familial, community and social-structural factors characteristic of the Indian sociocultural context may complicate individual-focused approaches to WTP and thereby constrain the effectiveness of interventions to support recruitment and retention in HIV vaccine trials. Interventions to reduce stigma and discrimination against MSM and people living with HIV, capacity-building of MSM community organizations and transparent communications tailored to the knowledge and educational level of local communities may support meaningful engagement of MSM in HIV vaccine trials. Vigilance in providing fair but not excessive compensation and healthcare benefits and in mitigating preventive misconception are warranted to support ethical conduct of trials among MSM in India.

Spontaneous dorsal cord herniations are very rare, with only 3 reported cases published in the literature. We report a case of a 15-year-old girl, presenting with progressive symptoms of myelopathy, diagnosed with dorsal cord herniation. She was managed surgically. The herniated arachnoid forming the cyst wall was opened to find a dorsally herniated mass of the dorsal spinal cord. The dura was opened above and below the herniation and then around it to free the herniating nodule of the spinal cord. The nodule was not reducible and was partially amputated for biopsy, and to facilitate dural closure. The patient's post-operative course was uneventful with no fresh deficits. Lower limb weakness improved to 5/5 power with normal gait at 3 months follow-up. We speculate, after a literature review, that the dorsal cord herniation is a 'dorsal trans-dural appendage of the spinal cord' possibly resulting from (a) abnormal migration of neural crest cells during formation of dorsal meninges; or (b) abnormal differentiation of neural crest cells; or (c) abnormal signaling by the neural crest cells., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

The Sri Sathya Sai Central Trust (SSSCT) was founded in 1972 as a public charitable trust with the objectives of providing free education, healthcare, and public utility benefits without any discrimination. The neurosurgery department at the Sri Sathya Sai Institute of Higher Medical Sciences (SSSIHMS), Bangalore, one of SSSCT's many hospitals, has been offering comprehensive services with state-of-the-art facilities for a diverse range of disorders since 2001. Operating on a unique "no-cost-to-patient" model and guided by an ethos of altruism introduced by its founder Sri Sathya Sai Baba, the department has successfully provided high-quality neurosurgical care to a large number of patients. This article reviews the genesis of the department, its milestones over more than two decades, and the contributions of leaders who have played an important role in shaping the department., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Schwannoma arising from a pure motor cranial nerve in sporadic cases is a rare finding. We report adult female patient presented with a seizure without oculomotor palsy. On evaluation, she was diagnosed with cystic oculomotor schwannoma and underwent surgery. She developed oculomotor palsy postoperatively. Here, we describe a rare sporadic cystic oculomotor schwannoma., Competing Interests: Conflict of Interest None declared., (Association for Helping Neurosurgical Sick People. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Fusiform aneurysms of the distal anterior cerebral artery (DACA) are infrequent. Clip reconstruction and sequential progressive clipping have been described in the management of giant thrombosed DACA aneurysms.1,2 Customized revascularization with bypass, side-to-side anastomosis, and trapping of the aneurysmal segment have also been performed for treating DACA aneurysms.3-12 We present a 2-dimensional operative video of superficial temporal artery (STA) to distal anterior cerebral artery bypass, followed by trapping of the aneurysm-bearing segment. A 57-yr-old lady presented with a large ruptured subcallosal fusiform DACA aneurysm (WFNS grade 1, Fisher grade 1). Angiography revealed a 1.3 × 0.9 cm fusiform aneurysm in the DACA.  Informed consent was secured from the patient and her family for the surgery and permission was obtained for the publication of the patient's image/surgical video. The frontal and parietal branches of the STA were dissected. The parietal branch was explanted and used as a free interposition graft between the frontal branch (end-to-end anastomosis) and calloso-marginal artery (end-to-side anastomosis). After confirming blood flow through the bypass using Doppler, the aneurysm was trapped and excised.  The patient had an uneventful recovery. Her postoperative computed tomography (CT) head revealed no evidence of neurological insult. The patency of the bypass conduit and the complete removal of the aneurysm were confirmed using a digital subtraction angiogram. Histopathological examination revealed an eccentric atheromatous plaque with a lipid core. There was no evidence of intraplaque hemorrhage. This extended STA graft utilizing the frontal and parietal branches of the STA, and its implantation into the distal ACA, offers a novel bypass strategy for tackling fusiform aneurysms of the DACA. Anastomosis to the calloso-marginal artery ensured perfusion of the ACA territory through the pericallosal artery during temporary occlusion., (© Congress of Neurological Surgeons 2021.)