Search results
Found 37809 matches for
Congratulations to Simon Leedham BSc PhD QMUL, MB BS London, FRCP, Professor of Gastroenterology and Wellcome Trust Senior Research Fellow in Clinical Science in the Wellcome Trust Centre for Human Genetics, has been appointed to the Professorship of Molecular and Population Genetics in the Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine. He took up the post on 1 October 2020 and will be a Fellow of Queen's College, Oxford.
Factors influencing Thai university students' decisions to take COVID-19 vaccine booster doses: a cross-sectional survey.
BACKGROUND: We aimed to describe the acceptance of COVID-19 vaccine booster doses and factors influencing this among Thai university students. METHODS: A cross-sectional survey was conducted between July and September 2022. All university students in Thailand were eligible to participate. We explored the acceptance rate of COVID-19 vaccine booster doses and regular vaccines (if available) among university students. Associations between factors influencing the acceptance of vaccination were analyzed by multiple logistic regression analysis. RESULTS: A total of 322 participants were surveyed (78.9% female, age 18 to 49 years (mean = 22.6, standard deviation = 5.47)). Most participants (85.7%) were undergraduate students (Bachelor level), and a proportion (84.8%) had a background in health sciences studies. The proportions who accepted booster doses and regular vaccines were 52.8% and 69.3%, respectively. Vaccine accessibility was found to be significantly associated with the acceptance of booster doses (adjusted odds ratio (AOR) = 2.77, 95% confidence interval (CI) = 1.10-6.97), while the availability of scientific evidence (AOR = 3.44, 95% CI = 1.21-9.77) was significantly associated with the acceptance of regular vaccines. CONCLUSIONS: This study contributes to addressing the knowledge gap regarding acceptance of COVID-19 vaccine booster doses among university students in Thailand. Our findings revealed that vaccine accessibility and the availability of scientific evidence, as well as vaccination costs, influenced individuals' decisions around accepting vaccine booster doses. Further research should focus on the dynamics of vaccine acceptance to facilitate the development of targeted strategies and support vaccination policymaking in Thailand.
A National audit of the care of patients with acute kidney injury in England and Wales in 2019 and the association with patient outcomes.
BackgroundAcute kidney injury (AKI) is a common complication of hospitalisations. This national audit assessed the care received by patients with AKI in hospital Trusts in England and Wales.MethodsTwenty four hospital Trusts across England and Wales took part. Patients with AKI stage2/3 were identified using the UK Renal Registry AKI master patient index. Data was returned through a secure portal with linkage to hospital episode statistic mortality and hospitalisation data. Completion rates of AKI care standards and regional variations in care were established.Results989 AKI episodes were included in the analyses. In-hospital 30-day mortality was 31-33.1% (AKI 2/3). Standard AKI interventions were completed in >80% of episodes. Significant inter-hospital variation remained in attainment of AKI care standards after adjustment for age and sex. Recording of urinalysis (41.9%) and timely imaging (37.2%) were low. Information on discharge summaries relating to medication changes/re-commencement and follow-up blood tests associated with reduced mortality. No quality indicators relating to clinical management associated with mortality. Better communication on discharge summaries associated with reduced mortality.ConclusionsOutcomes for patients with AKI in hospital remain poor. Regional variation in care exists. Work is needed to assess whether improving and standardising care improves patient outcomes.
High-risk Escherichia coli clones that cause neonatal meningitis and association with recrudescent infection.
Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.
A review of new challenges and solutions to the timely and effective implementation of clinical research responses to high priority diseases of epidemic and pandemic potential: A scoping review protocol
Background: Conducting and implementing clinical research response during pandemic and epidemic diseases outbreaks are often fraught with challenges due to their unprecedented nature. In previous research, challenges to the implementation of clinical research responses during pandemic and epidemic outbreaks were identified and solutions suggested. While the emergence of the Covid-19 pandemic has, on one hand, highlighted new and unresolved challenges, several novel solutions such as the Randomised Evaluation of Covid-19 Therapy (RECOVERY) trial were also implemented and reported in the literature. This scoping review, therefore, aims to synthesise and update solutions to the barriers affecting the implementation of clinical research responses during new, emerging or re-emerging diseases of pandemic and epidemic potential, to further inform strategies that would enhance pandemic and epidemic preparedness and response. Methods: This scoping review will be conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis- Extension for Scoping Reviews (PRISMA-ScR). Search will be conducted in six scientific databases: Ovid MEDLINE, Ovid Global Health, OVID PsycINFO, Ovid Embase, Scopus Epistemonikos, and complemented by a grey literature search in Google Scholar. Terms related to clinical trial, high consequence infectious diseases and the PEARLES domains will be used in the search. Two reviewers will independently screen retrieved articles in Rayyan software. Descriptive data of studies will be extracted into a pre-developed Microsoft Excel template while qualitative data related to the PEARLES solutions or barriers will be coded in NVivo. Results will be synthesised thematically and presented in a narrative style. Conclusions: This scoping review will synthesise new and updated solutions to the PEARLES challenges encountered during the implementation of clinical research responses to high consequence epidemics and pandemics. Furthermore, it will examine how challenges and proposed solutions identified prior to the emergence of Covid-19 have been addressed and tested in real time.
Obesity Differs from Diabetes Mellitus in Antibody and T Cell Responses Post COVID-19 Recovery.
Obesity and type 2 diabetes (DM) are risk factors for severe COVID-19 outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with obesity and DM in Bangladesh. In this cross-sectional study, SARS-CoV-2-specific antibody and T cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, obesity was associated with decreased neutralising antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8+ T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T cell responses after adjustment for obesity and other confounders. Obesity is associated with lower neutralising antibody levels and higher T cell responses to SARS-CoV-2 post COVID-19 recovery, while antibody or T cell responses remain unaltered in DM.
Stable isotope ratio analysis: an emerging tool to trace the origin of falsified medicines
Falsified medicines pose a serious threat to global public health. Over the past few decades, the number of public health issues and seizures of falsified medicines has dramatically increased across the world. The development of new analytical techniques for the identification and traceability of these products hold great promise for innovation to help curtail the high number of deaths caused by the lack of adequate treatments and in combating the criminals responsible for manufacturing these products. This review presents the main approaches, based on stable isotope ratios of the bio-elements, mainly Isotope Ratio Mass Spectrometry and Site-specific Natural Isotopic Fractionation by Nuclear Magnetic Resonance, that can contribute to identifying the origin of these products, both in terms of geographical origin and raw materials employed as well as for the batch controls by the producers.
Spatio-temporal spread of artemisinin resistance in Southeast Asia
Current malaria elimination targets must withstand a colossal challenge–resistance to the current gold standard antimalarial drug, namely artemisinin derivatives. If artemisinin resistance significantly expands to Africa or India, cases and malaria-related deaths are set to increase substantially. Spatial information on the changing levels of artemisinin resistance in Southeast Asia is therefore critical for health organisations to prioritise malaria control measures, but available data on artemisinin resistance are sparse. We use a comprehensive database from the WorldWide Antimalarial Resistance Network on the prevalence of non-synonymous mutations in the Kelch 13 (K13) gene, which are known to be associated with artemisinin resistance, and a Bayesian geostatistical model to produce spatio-temporal predictions of artemisinin resistance. Our maps of estimated prevalence show an expansion of the K13 mutation across the Greater Mekong Subregion from 2000 to 2022. Moreover, the period between 2010 and 2015 demonstrated the most spatial change across the region. Our model and maps provide important insights into the spatial and temporal trends of artemisinin resistance in a way that is not possible using data alone, thereby enabling improved spatial decision support systems on an unprecedented fine-scale spatial resolution. By predicting for the first time spatio-temporal patterns and extents of artemisinin resistance at the subcontinent level, this study provides critical information for supporting malaria elimination goals in Southeast Asia.
Comparison of WHO versus national COVID-19 therapeutic guidelines across the world: not exactly a perfect match.
BACKGROUND: The COVID-19 pandemic affected all WHO member states. We compared and contrasted the COVID-19 treatment guidelines of each member state with the WHO COVID-19 therapeutic guidelines. METHODS: Ministries of Health or accessed National Infectious Disease websites and other relevant bodies and experts were contacted to obtain national guidelines (NGs) for COVID-19 treatment. NGs were included only if they delineated specific pharmacological treatments for COVID-19, which were stratified by disease severity. We conducted a retrospective review using the adapted Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG) survey checklist and a derived comparative metric based on the WHO guidelines was performed. RESULTS: COVID-19 therapeutics NGs could be obtained from 109 of the 194 WHO member states. There was considerable variation in guidelines and in disease severity stratifications. Therapeutic recommendations in many NGs differed substantially from the WHO guidelines. Overall in late 2022, 93% of NGs were recommending at least one treatment which had proved to be ineffective in large randomised trials, and was not recommended by WHO. Corticosteroids were not recommended in severe disease in nearly 10% of NGs despite overwhelming evidence of their benefit. NGs from countries with low-resource settings showed the greatest divergence when stratified by gross domestic product per year, Human Development Index and the Global Health Security Index. DISCUSSION: Our study is limited to NGs that were readily accessible, and it does not reflect the availability of recommended medicines in the field. Three years after the start of the SARS-CoV-2 pandemic, available COVID-19 NGs vary substantially in their therapeutic recommendations, often differ from the WHO guidelines, and commonly recommend ineffective, unaffordable or unavailable medicines.
From Llama to Nanobody: A Streamlined Workflow for the Generation of Functionalised VHHs
Nanobodies are recombinant antigen-specific single domain antibodies (VHHs) derived from the heavy chain–only subset of camelid immunoglobulins. Their small molecular size, facile expression, high affinity, and stability have combined to make them unique targeting reagents with numerous applications in the biomedical sciences. From our work in producing nanobodies to over sixty different proteins, we present a standardised workflow for nanobody discovery from llama immunisation, library building, panning, and small-scale expression for prioritisation of binding clones. In addition, we introduce our suites of mammalian and bacterial vectors, which can be used to functionalise selected nanobodies for various applications such as in imaging and purification.
Research ethics and artificial intelligence for global health: perspectives from the global forum on bioethics in research.
The ethical governance of Artificial Intelligence (AI) in health care and public health continues to be an urgent issue for attention in policy, research, and practice. In this paper we report on central themes related to challenges and strategies for promoting ethics in research involving AI in global health, arising from the Global Forum on Bioethics in Research (GFBR), held in Cape Town, South Africa in November 2022. The GFBR is an annual meeting organized by the World Health Organization and supported by the Wellcome Trust, the US National Institutes of Health, the UK Medical Research Council (MRC) and the South African MRC. The forum aims to bring together ethicists, researchers, policymakers, research ethics committee members and other actors to engage with challenges and opportunities specifically related to research ethics. In 2022 the focus of the GFBR was "Ethics of AI in Global Health Research". The forum consisted of 6 case study presentations, 16 governance presentations, and a series of small group and large group discussions. A total of 87 participants attended the forum from 31 countries around the world, representing disciplines of bioethics, AI, health policy, health professional practice, research funding, and bioinformatics. In this paper, we highlight central insights arising from GFBR 2022. We describe the significance of four thematic insights arising from the forum: (1) Appropriateness of building AI, (2) Transferability of AI systems, (3) Accountability for AI decision-making and outcomes, and (4) Individual consent. We then describe eight recommendations for governance leaders to enhance the ethical governance of AI in global health research, addressing issues such as AI impact assessments, environmental values, and fair partnerships. The 2022 Global Forum on Bioethics in Research illustrated several innovations in ethical governance of AI for global health research, as well as several areas in need of urgent attention internationally. This summary is intended to inform international and domestic efforts to strengthen research ethics and support the evolution of governance leadership to meet the demands of AI in global health research.
Reduced Acetazolamide Dosing in Countering Altitude Illness: A Comparison of 62.5 vs 125 mg (the RADICAL Trial).
IntroductionNorth American guidelines propose 125 mg acetazolamide twice daily as the recommended prophylactic dose to prevent acute mountain sickness (AMS). To our knowledge, a dose lower than 125 mg twice daily has not been studied.MethodsWe conducted a prospective, double-blind, randomized, noninferiority trial of trekkers to Everest Base Camp in Nepal. Participants received the reduced dose of 62.5 mg twice daily or the standard dose of 125 mg twice daily. Primary outcome was incidence of AMS, and secondary outcomes were severity of AMS and side effects in each group.ResultsSeventy-three participants had sufficient data to be included in the analysis. Overall incidence of AMS was 21 of 38 (55.3%) in reduced-dose and 21 of 35 (60.0%) in standard-dose recipients. The daily incidence rate of AMS was 6.7% (95% CI 2.5-10.9) for each individual in the reduced-dose group and 8.9% (95% CI 4.5-13.3) in the standard-dose group. Overall severity of participants' Lake Louise Score was 1.014 in the reduced-dose group and 0.966 in the standard-dose group (95% CI 0.885-1.144). Side effects were similar between the groups.ConclusionsThe reduced dose of acetazolamide at 62.5 mg twice daily was noninferior to the currently recommended dose of 125 mg twice daily for the prevention of AMS. Low incidence of AMS in the study population may have limited the ability to differentiate the treatment effects. Further research with more participants with greater rates of AMS would further elucidate this reduced dosage for preventing altitude illness.
Physiological responses during ascent to high altitude and the incidence of acute mountain sickness.
Acute mountain sickness (AMS) occurs when there is failure of acclimatisation to high altitude. The aim of this study was to describe the relationship between physiological variables and the incidence of AMS during ascent to 5300 m. A total of 332 lowland-dwelling volunteers followed an identical ascent profile on staggered treks. Self-reported symptoms of AMS were recorded daily using the Lake Louise score (mild 3-4; moderate-severe ≥5), alongside measurements of physiological variables (heart rate, respiratory rate (RR), peripheral oxygen saturation (SpO2 ) and blood pressure) before and after a standardised Xtreme Everest Step-Test (XEST). The overall occurrence of AMS among participants was 73.5% (23.2% mild, 50.3% moderate-severe). There was no difference in gender, age, previous AMS, weight or body mass index between participants who developed AMS and those who did not. Participants who had not previously ascended >5000 m were more likely to get moderate-to-severe AMS. Participants who suffered moderate-to-severe AMS had a lower resting SpO2 at 3500 m (88.5 vs. 89.6%, p = 0.02), while participants who suffered mild or moderate-to-severe AMS had a lower end-exercise SpO2 at 3500 m (82.2 vs. 83.8%, p = 0.027; 81.5 vs. 83.8%, p 2 (OR 0.870, p 5000 m (OR 2.740, p-value 0.003) predicted the development of moderate-to-severe AMS. The Xtreme Everest Step-Test offers a simple, reproducible field test to help predict AMS, albeit with relatively limited predictive precision.
Intentional pesticide poisoning and pesticide suicides in Nepal.
IntroductionIntentional pesticide poisoning is a major clinical and public health problem in agricultural communities in low and middle income countries like Nepal. Bans of highly hazardous pesticides (HHP) reduce the number of suicides. We aimed to identify these pesticides by reviewing data from major hospitals across the country and from forensic toxicology laboratories.MethodsWe retrospectively reviewed medical records of 10 hospitals for pesticide poisoned patients and two forensic laboratories of Nepal from April 2017 to February 2020. The poison was identified from the history, referral note, and clinical toxidrome in the hospitals and from gas chromatography analysis in the laboratories. Data on demographics, poison, and patient outcome were recorded on a data collection sheet. Simple descriptive analysis was performed.ResultsAmong hospital cases (n = 4148), the commonest form of poisoning was self-poisoning (95.8%) while occupation poisoning was rare (0.03%). Case fatality was 5.3% (n = 62). Aluminum phosphide (n = 38/62, 61.3%) was the most commonly identified lethal pesticide for deaths. Forensic toxicology laboratories reported 2535 deaths positive for pesticides, with the compounds most commonly identified being organophosphorus (OP) insecticides (n = 1463/2535; 57.7%), phosphine gas (n = 653/2535; 25.7%; both aluminum [11.8%] and zinc [0.4%] phosphide) and organochlorine insecticides (n = 241/2535; 9.5%). The OP insecticide most commonly identified was dichlorvos (n = 273/450, 60.6%).ConclusionThe data held in the routine hospital medical records were incomplete but suggested that case fatality in hospitals was relatively low. The pesticides identified as causing most deaths were dichlorvos and aluminum phosphide. Since this study was completed, dichlorvos has been banned and the most toxic formulation of aluminum phosphide removed from sale. Improving the medical record system and working with forensic toxicology laboratories will allow problematic HHPs to be identified and the effects of the bans in reducing deaths monitored.
Case Report: Gastric Mucormycosis- a rare but important differential diagnosis of upper gastrointestinal bleeding in an area of Helicobacter pylori endemicity.
A 57 years female from the hills of Nepal presented with upper gastrointestinal bleeding with gastric ulcer evident on endoscopy. Though initially treated with Helicobacter pylori ( H. pylori) eradication therapy alone, biopsy later on revealed both mucormycosis and H. pylori infection. She was then treated with antifungals liposomal amphotericin B followed by posaconazole which led to complete recovery. Mucormycosis is a rare but life-threatening fungal disease of immunocompromised host though our patient was immunocompetent. If recognized and treated at early stage, as in our patient, prognosis is good. A high index of suspicion is required for considering this disease in H. pylori endemic regions such as Nepal, and is crucial for early recognition and treatment.
Varied Reproductive Histories of Ethnically Tibetan Women.
BackgroundThe U.N. health and well-being goals for 2030 focus on maternal and child health outcomes, among others. Challenges to meeting those goals vary widely throughout Nepal owing to the range of sociocultural factors, infrastructural limitations, physical geography and altitudes. This article explores sociocultural and biological influences on fertility and child survival among ethnically Tibetan women in Nepal.MethodsThis is a cross sectional study of 430 women, age 46-86 years old, citizens of Nepal and native residents above 3500m in Mustang District, who provided interview and physiological data. Univariate Poisson regression analyses selected significant variables to include in multivariate Poisson regressions investigating the number of pregnancies, livebirths, child survival and death outcomes.ResultsEarlier age at first pregnancy, later age at last pregnancy, and miscarriages associated with more pregnancies. Miscarriages and stillbirths associated with fewer livebirths. Higher maternal BMI and FEV6 associated with fewer children dying before age 15. Marital characteristics (status, type, continuity), contraceptive use, relative wealth, and education influenced these covariates.ConclusionsLow maternal pulmonary function and nutritional status predict poorer child survival in Upper Mustang. Addressing poor lung function and nutrition may improve reproductive outcomes among ethnically Tibetan women living at high altitude.