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Abstract Objectives The primary objective is to evaluate the efficacy of camostat to prevent respiratory deterioration in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Secondary objectives include assessment of the ability of camostat to reduce the requirement for Coronavirus disease 2019 (COVID-19) related hospital admission and to reduce the requirement for supplementary oxygen and ventilation as treatment for SARS-CoV-2 infection, to evaluate overall mortality related to COVID-19 and to evaluate the efficacy of camostat by effect on clinical improvement. Research objectives include to assess change in COVID-19 symptom severity, to evaluate the ability of camostat to reduce viral load throughout duration of illness as well as translational research on host and viral genomics, serum antibody production, COVID-19 diagnostics, and validation of laboratory testing methods and biomarkers. Trial design SPIKE-1 is a randomised, multicentre, prospective, open label, community-based clinical trial. Eligible patients will be randomised 1:1 to the camostat treatment arm and control arm (best supportive care). The trial is designed to include a pilot phase recruiting up to 50 patients in each arm. An initial review at the end of the pilot phase will allow assessment of available data and inform the requirement for any protocol adaptations to include refinement of eligibility criteria to enrich the patient population and sample size calculations. Up to 289 additional patients will be randomised in the continuation phase of the trial. A formal interim analysis will be performed once 50% of the maximum sample size has been recruited Participants The trial will recruit adults (≥ 18 years) who score moderate to very high risk according to COVID-age risk calculation, with typical symptoms of COVID-19 infection as per Public Health England guidance or equivalent organisations in the UK, Health Protection Scotland, Public Health Wales, Public Health Agency (Northern Ireland) and with evidence of current COVID-19 infection from a validated assay. The trial is being conducted in the UK and patients are recruited through primary care and hospital settings. Intervention and comparator Eligible patients with be randomised to receive either camostat tablets, 200 mg four times daily (qds) for 14 days (treatment arm) or best supportive care (control arm). Main outcomes Primary outcome measure: the rate of hospital admissions requiring supplemental oxygen. Secondary outcome measures include: the rate of COVID-19 related hospital admission in patients with SARS-CoV-2 infection; the number of supplementary oxygen-free days and ventilator-free days measured at 28 days from randomisation; the rate of mortality related to COVID-19 one year from randomisation; the time to worst point on the nine-point category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019)) or deterioration of two points or more, within 28 days from randomisation. Research outcomes include the assessment of change in COVID-19 symptom severity on days 1-14 as measured by (1) time to apyrexia (maintained for 48 hrs) by daily self-assessment of temperature, time to improvement (by two points) in peripheral oxygenation saturation defined by daily self-assessment of fingertip peripheral oxygenation saturation levels, (3) assessment of COVID-19 symptoms using the Flu-iiQ questionnaire (determined by app recording and/or daily video call (or phone) consultation and (4) assessment of functional score (where possible) at screening, day 7 and 14. The ability of camostat to reduce viral load throughout duration of illness will be assessed by (1) change in respiratory (oropharyngeal/nasopharyngeal swab RT-PCR) log10 viral load from baseline to Days 7 and 14, (2) change in respiratory (saliva RT-PCR) log10 viral load from baseline to Days 1-14 and (3) change in upper respiratory viral shedding at Day 1 -14 measured as time to clearance of nasal SARS-CoV-2, defined as 2 consecutive negative swabs by qPCR. Additional translational research outcomes include assessment of host and viral genomics, serum antibody production and COVID-19 diagnostics at baseline and on Days 7 and 14. Randomisation Eligible patients will be randomised using an interactive web response system (IWRS) in a 1:1 ratio to one of two arms: (1) treatment arm or (2) control arm. Blinding (masking) The trial is open-label. Numbers to be randomised (sample size) The trial is designed to include a pilot and a continuation phase. Up to 100 patients (randomised 1:1 treatment and control arm) will be recruited in the pilot phase and a maximum of 289 patients (randomised 1:1 treatment and control) will be recruited as part of the continuation phase. The total number of patients recruited will not exceed 389. Trial Status Protocol version number v3 25 September 2020. Trial opened to recruitment on 04 August 2020. The authors anticipate recruitment to be completed by October 2021. Trial registration EudraCT 2020-002110-41; 18 June 2020 ClinicalTrials.gov NCT04455815 ; 02 July 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). Unpublished PK data provided under confidentiality agreement to the trial Sponsor has been removed from the background section of the protocol to allow for publication of the trial protocol. In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The data presented here are related and supplementary data to the research article “Implantation and long-term assessment of the stability and biocompatibility of a novel 98 channel suprachoroidal visual prosthesis in sheep” [1]. In Eggenberger et al., nine sheep of the Suffolk (N=2) and Dorper (N=7) breeds were implanted in the left eye with an electrically inactive, suprachoroidal retinal stimulator (Bionic Eye) for durations of up to 100 days. The surgical safety, implant stability and device biocompatibility were assessed. Intraocular pressure measurements, indirect and infrared ophthalmoscopy and optical coherence tomography were performed at fixed time points to evaluate the clinical effects of the surgery and device implantation. Post-mortem eye tissue collection and histology was performed to measure the effects of the intervention at the cellular level. The data, including a comprehensive collection of fundus, infrared, optical coherence tomography and histology images can be used as a reference for comparison with other research, for example, active retinal stimulators. Furthermore, these data can be used to evaluate the suitability of the sheep model, in particular Dorper sheep, for future research.

We develop a frequency domain template subtraction approach to attenuate the maternal ECG in the abdominal ECG measured from pregnant women. The proposed approach was tested on five public fetal ECG datasets simultaneously measured with ECG from the fetal scalp. The method’s performance was compared with the template subtraction approach in the time domain using the accuracy and association metrics. The accuracy was calculated by counting the number of fetal complexes in the processed data that coincided with the fetal complexes in the scalp fetal ECG. The association is quantified as the coherence between the processed data and the gold standard. The maximum coherence values calculated for each approach were compared using the paired t-test. Our results showed no difference in the accuracy between the frequency and time domain approach (p = 0.733). However, the association was higher between the frequency domain data and the gold standard compared to the template subtraction data and the gold standard (p = 0.049), indicating that the frequency domain approach yielded a signal that resembled that of the scalp ECG compared to the time domain approach.

BackgroundProgress in neonatal care has resulted in a 51% decrease in global neonatal mortality rates from 1990 to 2017. Enhanced survival will put pressure on health care systems to provide appropriate post-discharge, follow-up care but the scale of need for such care is poorly defined.MethodsWe conducted a retrospective cohort study of newborns discharged from 23 public hospital neonatal units (NBUs) in Kenya between January 2018 and June 2023 to identify initial follow-up needs. We first determined pragmatic follow-up categories based on survivors’ clinical conditions and morbidities. We then used individual phenotypes of individual babies to assign them to needing one or more forms of specialized clinical follow-up. We use descriptive statistics to estimate proportions of those with specific needs and patterns of need.FindingsAmong 136,249/159,792 (85.3%) neonates discharged, around one-third (33%) were low birth weight (

BackgroundReports on hypothermia from high-burden countries like Kenya amongst sick newborns often include few centers or relatively small sample sizes.ObjectivesThis study endeavored to describe: (i) the burden of hypothermia on admission across 21 newborn units in Kenya, (ii) any trend in prevalence of hypothermia over time, (iii) factors associated with hypothermia at admission, and (iv) hypothermia's association with inpatient neonatal mortality.MethodsA retrospective cohort study was conducted from January 2020 to March 2023, focusing on small and sick newborns admitted in 21 NBUs. The primary and secondary outcome measures were the prevalence of hypothermia at admission and mortality during the index admission, respectively. An ordinal logistic regression model was used to estimate the relationship between selected factors and the outcomes cold stress (36.0°C–36.4°C) and hypothermia (

The integration of gender concerns in crop breeding programs aims to improve the suitability and appeal of new varieties to both women and men, in response to concerns about unequal adoption of improved seed. However, few conventional breeding programs have sought to center social inclusion concerns. This community case study documents efforts to integrate gender into the maize-focused Seed Production Technology for Africa (SPTA) project using innovation history analysis drawing on project documents and the authors’ experiences. These efforts included deliberate exploration of potential gendered impacts of project technologies and innovations in the project’s approach to variety evaluation, culminating in the use of decentralized on-farm trials using the tricot approach. Through this case study, we illustrate the power of active and respectful collaborations between breeders and social scientists, spurred by donor mandates to address gender and social inclusion. Gender integration in this case was further facilitated by open-minded project leaders and allocation of funding for gender research. SPTA proved to be fertile ground for experimentation and interdisciplinary collaboration around gender and maize breeding, and has provided proof of concept for larger breeding projects seeking to integrate gender considerations.

Abstract Background Innovation is needed to produce sustained improvements in bacterial sexually transmitted infections (STI) testing given suboptimal access and uptake among sexually active gay, bisexual or other men who have sex with men (GBM). Yet, the STI testing processes and technologies that best address local testing barriers among GBM in Toronto is unknown. We aimed to explore men’s perspectives regarding STI testing services for GBM to identify and prioritize new STI testing interventions in Toronto, Ontario, Canada. Methods We conducted four focus groups with twenty-seven GBM in 2017: two with cisgender men living with HIV, one with cisgender HIV-negative men, and one with transgender men. Twenty-seven men participated in the focus groups with 40% 18–30 years of age, 48% self-identifying as white, and the remainder self-identifying as Middle Eastern, Latino/Hispanic, Asian/Pacific Islander, South Asian, First Nations, African/Caribbean/Black, or mixed race. 59% of participants self-identified as living with HIV. Participants were asked about their STI testing experiences in Toronto, barriers and facilitators to testing, and ideal STI testing process. Focus groups were audio recorded, transcribed verbatim, and analyzed using thematic analysis. Results Core concepts included how clinical context, bacterial STI testing delivery, and interactions with healthcare providers can create barriers and recommendations for ways to improve. Regarding clinical context, participants desired more clinics with accessible locations/hours; streamlined testing that minimized use of waiting rooms and wait times; and improved clinic ambience. Bacterial STI testing delivery recommendations included standardization to ensure consistency in sexual history intake, tests offered, follow-up and public health reporting between clinics. Men also recommended reducing the multistep process testing by offering components such as lab requisitions and results online. Participants also recommended interactions with healthcare providers be professional and non-judgmental, offer compassionate and competent care with destigmatizing and lesbian, gay, bisexual and trans (LGBT) affirming communication. Conclusion Concrete and practical solutions for improving existing sexual health services and facilitating optimal STI testing include streamlining testing options and providing patient-centred, LGBT-affirming care to enable optimal STI testing.

Welcome to the McGill Journal of Medicine (MJM) LMCC review. This podcast series was created to aid medical students studying for the Canadian Medical Council (MCC)’s licensing exam. Each episode is created based on specific LMCC objectives and is divided into 2 parts. In part one we provide an overview of the topic with the help of experts in the field, followed by Part 2 where we review LMCC styled questions to help consolidate knowledge. In this episode, we welcome our expert advisor, Dr. Alice Cheng, Endocrinologist and Associate Professor at the University of Toronto to speak on LMCC Objective 37-1* Glucose Abnormalities. This episode was written by Meryem Talbo and Dr. Alice Cheng, edited by Esther Kang, Katherine Lan and Susan Wang. Please see our website www.mjmmed.com for more information, including a link to show notes.

Welcome to the McGill Journal of Medicine (MJM) LMCC review. This podcast series was created to aid medical students studying for the Canadian Medical Council’s licensing exam. Each episode is created based on specific LMCC objectives and is divided into 2 parts. In part one we provide an overview of the topic with the help of experts in the field, followed by Part 2 where we review LMCC styled questions to help consolidate knowledge. In this episode, we welcome our expert advisor, Dr. Alice Cheng, Endocrinologist and Associate Professor at the University of Toronto to speak on LMCC Objective 37-2* Diabetes Mellitus. This episode was written by Susan Wang & Dr. Alice Cheng, edited by Esther Kang, Meryem Talbo and Katherine Lan. Please see our website www.mjmmed.com for more information, including a link to show notes.

Aim: The aim of this study is to determine the antimicrobial efficacy of aqueous and ethanol extracts of Euclea divinorum Hiern against some root canal microorganisms compared to conventional root canal irrigants. Settings and Design: An in vitro laboratory study at the University of Nairobi. Materials and Methods: E. divinorum branches were collected, dried, and ground into coarse powder. The aqueous filtrates were lipolyzed while the ethanol filtrates were reduced under vacuum and oven-dried into powder. Growth inhibition of cell cultures from pure strains of Enterococcus faecalis (ATCC® 29212™), Streptococcus mutans (ATCC ®25175™), Staphylococcus aureus (ATCC® 25923™), Fusobacterium nucleatum (ATCC®25586™), Lactobacillus acidophilus (ATCC® 4356™), and Candida albicans (ATCC® 24433™) by the extracts were determined using tenfold liquid microdilution incubated for 24 and 48 h at 37°C. Cytotoxicity of the extracts was compared to those of 5.25% sodium hypochlorite, 2% chlorhexidine gluconate, and 17% ethylenediaminetetraacetic acid (EDTA). The one-way analysis of variance and Tukey's HSD test were used to test for differences between the mean growth inhibition of the extracts and the controls. Results: Fifty mg/ml ethanol extract had the highest growth inhibition at 99% ±3.04, 95% confidence interval (CI) (9.24, 100.755) against F. nucleatum followed by S. aureus at 97.22% ±3.77, 95% CI (95.04, 99.39) for 48 h incubation. S. mutans, L. acidophilus, and C. albicans showed resistance to the cytotoxic effects of the plant extracts. The mean growth inhibitions of 50 mg/ml ethanol extract against E. faecalis, and S. aureus were similar to those of 5.25% sodium hypochlorite and 17% EDTA for 24 h incubation while being higher against F. nucleatum at P < 0.01(Tukey's HSD). Conclusion: Fifty mg/ml E. divinorum extracts showed growth inhibition against E. faecalis, S. aureus, and F. nucleatum which was similar to the efficacy of 5.25% sodium hypochlorite. S. mutans, L. acidophilus, and C. albicans showed resistance to the cytotoxic effects of the extracts.

Objectives To characterise adoption and explore specific clinical and patient factors that might influence pulse oximetry and oxygen use in low-income and middle-income countries (LMICs) over time; to highlight useful considerations for entities working on programmes to improve access to pulse oximetry and oxygen.Design A multihospital retrospective cohort study.Settings All admissions (n=132 737) to paediatric wards of 18 purposely selected public hospitals in Kenya that joined a Clinical Information Network (CIN) between March 2014 and December 2020.Outcomes Pulse oximetry use and oxygen prescription on admission; we performed growth-curve modelling to investigate the association of patient factors with study outcomes over time while adjusting for hospital factors.Results Overall, pulse oximetry was used in 48.8% (64 722/132 737) of all admission cases. Use rose on average with each month of participation in the CIN (OR: 1.11, 95% CI 1.05 to 1.18) but patterns of adoption were highly variable across hospitals suggesting important factors at hospital level influence use of pulse oximetry. Of those with pulse oximetry measurement, 7% (4510/64 722) had hypoxaemia (SpO2

Background Most of the deaths among neonates in low-income and middle-income countries (LMICs) can be prevented through universal access to basic high-quality health services including essential facility-based inpatient care. However, poor routine data undermines data-informed efforts to monitor and promote improvements in the quality of newborn care across hospitals.Methods Continuously collected routine patients’ data from structured paper record forms for all admissions to newborn units (NBUs) from 16 purposively selected Kenyan public hospitals that are part of a clinical information network were analysed together with data from all paediatric admissions ages 0–13 years from 14 of these hospitals. Data are used to show the proportion of all admissions and deaths in the neonatal age group and examine morbidity and mortality patterns, stratified by birth weight, and their variation across hospitals.Findings During the 354 hospital months study period, 90 222 patients were admitted to the 14 hospitals contributing NBU and general paediatric ward data. 46% of all the admissions were neonates (aged 0–28 days), but they accounted for 66% of the deaths in the age group 0–13 years. 41 657 inborn neonates were admitted in the NBUs across the 16 hospitals during the study period. 4266/41 657 died giving a crude mortality rate of 10.2% (95% CI 9.97% to 10.55%), with 60% of these deaths occurring on the first-day of admission. Intrapartum-related complications was the single most common diagnosis among the neonates with birth weight of 2000 g or more who died. A threefold variation in mortality across hospitals was observed for birth weight categories 1000–1499 g and 1500–1999 g.Interpretation The high proportion of neonatal deaths in hospitals may reflect changing patterns of childhood mortality. Majority of newborns died of preventable causes (>95%). Despite availability of high-impact low-cost interventions, hospitals have high and very variable mortality proportions after stratification by birth weight.

Abstract Background A community health programme in Narok County in Kenya aimed to improve skilled birth assistance during childbirth through two demand side interventions. First, traditional birth attendants (TBAs) were co-opted into using their influence to promote use of skilled birth attendants (SBAs) at health facilities during delivery, and to accompany pregnant women to health facilities in return for a Ksh500 (Approximately USD5 as of August 2016) cash incentive for each pregnant mother they accompanied. Secondly, a free Motherpack consisting of a range of baby care items was given to each mother after delivering at a health facility. This paper estimates the impact of these two interventions on trends of facility deliveries over a 36-month period here. Methods Dependency or inferred causality was estimated between reorientation of TBAs and provision of Motherpacks with changes in facility delivery numbers. The outcome variable consists of monthly facility delivery data from 28 health facilities starting from January 2013 to December 2015 obtained from the District Health Information Systems 2 (DHIS2). Data were collected on the 13th, 14th or 15th of each month, resulting in a total of 35 collections, over 35 months. The intervention data consisted of the starting month for each of the two interventions at each of the 28 facilities. A negative binomial generalized linear model framework is applied to model the relationship as all variables were measured as count data and were overdispersed. All analyses were conducted using R software. Findings During the 35 months considered, a total of 9095 health facility deliveries took place, a total of 408 TBAs were reached, and 2181 Motherpacks were distributed. The reorientation of TBAs was significant (p = 0.009), as was the provision of Motherpacks (p = .0001). The number of months that passed since the start of the intervention was also found to be significant (p = 0.033). The introduction of Motherpacks had the greatest effect on the outcome (0.2), followed by TBA intervention (0.15). Months since study start had a much lower effect (0.05). Conclusion Collaborating with TBAs and offering basic commodities important to mothers and babies (Motherpacks) immediately after delivery at health facilities, can improve the uptake of health facility delivery services in poor rural communities that maintain a strong bias for TBA assisted home delivery.

Tay-Sachs and Sandhoff diseases are lethal inborn errors of acid β-N-acetylhexosaminidase activity, characterized by lysosomal storage of GM2 ganglioside and related glycoconjugates in the nervous system. The molecular events that lead to irreversible neuronal injury accompanied by gliosis are unknown; but gene transfer, when undertaken before neurological signs are manifest, effectively rescues the acute neurodegenerative illness in Hexb-/- (Sandhoff) mice that lack β-hexosaminidases A and B. To define determinants of therapeutic efficacy and establish a dynamic experimental platform to systematically investigate cellular pathogenesis of GM2 gangliosidosis, we generated two inducible experimental models. Reversible transgenic expression of β-hexosaminidase directed by two promoters, mouse Hexb and human Synapsin 1 promoters, permitted progression of GM2 gangliosidosis in Sandhoff mice to be modified at pre-defined ages. A single auto-regulatory tetracycline-sensitive expression cassette controlled expression of transgenic Hexb in the brain of Hexb-/- mice and provided long-term rescue from the acute neuronopathic disorder, as well as the accompanying pathological storage of glycoconjugates and gliosis in most parts of the brain. Ultimately, late-onset brainstem and ventral spinal cord pathology occurred and was associated with increased tone in the limbs. Silencing transgenic Hexb expression in five-week-old mice induced stereotypic signs and progression of Sandhoff disease, including tremor, bradykinesia, and hind-limb paralysis. As in germline Hexb-/- mice, these neurodegenerative manifestations advanced rapidly, indicating that the pathogenesis and progression of GM2 gangliosidosis is not influenced by developmental events in the maturing nervous system.