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Abstract Background S. pneumoniae (SPN) is the most common cause of pneumonia. The disease can be effectively prevented through immunisation. Since December 2020, the Malaysian Government has included the 10-valent pneumococcal conjugate vaccine (PCV10) for all infants born on or after 1 January 2020 as part of the National Immunisation Programme (NIP). However, the epidemiology of pneumonia remains poorly understood. To fill the knowledge gap, we established a multicentre surveillance study to understand the burden of pneumococcal pneumonia among young children in Peninsular Malaysia. Methods MY-Pneumo is a multicentre prospective case–control study conducted in three sentinel sites located in three different states of Peninsular Malaysia – Kuala Lumpur, Pahang, and Kelantan. A cohort of at least 500 incident cases and 500 controls is enrolled beginning in October 2021 and matched for age. Cases are hospitalised children

This study aimed to investigate the physiological, perceptual, and biomechanical differences between male and female soldiers across several military-relevant load and walking speed combinations. Eleven female and twelve male soldiers completed twelve 12 min walking trials at varying speeds (3.5 km·h−1, 5.5 km·h−1, 6.5 km·h−1) and with varying external loads (7.2 kg, 23.2 kg, 35.2 kg). Physiological (indirect calorimetry, heart rate), perceptual (perceived exertion), and biomechanical (spatiotemporal, kinematic, kinetic) outcomes were measured throughout each trial. Females had a lower aerobic capacity and lower body strength than males, which resulted in them working at a greater exercise intensity (%VO2peak and heart rate) but with a lower oxygen pulse. Females demonstrated higher breathing frequency and perceived exertion with specific loads. At selected loads and speeds, frontal and sagittal pelvis, hip, and knee motions and forces were greater for females. Females consistently displayed greater relative stride length and step width. In conclusion, this study demonstrates the importance of tailored interventions, periodisation, and nutritional strategies for female military personnel, given their higher relative work rate and increased injury risk during load carriage tasks. Understanding these differences is crucial for preparing female soldiers for the physical demands of military service.

Abstract Background Nexplanon implants are a common hormonal contraceptive modality. Though rare, these devices can embolize into the injured wall of the basilic vein, through the right heart, and finally wedge itself into a pulmonary artery. With adherence to the arterial wall over time, it becomes less amenable to endovascular retrieval. Patients may present with symptoms mimicking a pulmonary embolism, or without any symptoms at all. In asymptomatic cases, endovascular retrieval and/or surgery is required when patients wish to begin having children prior to biological inactivity. The current literature showed as little as nine case reports detailing lung tissue removal in the aim of reversing a patient’s implanted contraceptive device. Case presentation A 22-year-old asymptomatic active-duty Caucasian female presented for elective outpatient Nexplanon removal. The suspicion of possible implant migration arose when it was discovered to be non-palpable in her left arm. After plain film x-rays failed to localize the implant, a chest x-ray and follow-up Computed Tomography (CT) scan revealed that the Nexplanon had migrated to a distal branch of the left pulmonary artery. Due to the patient’s strong desires to begin having children, the decision was made for removal. Initial endovascular retrieval failed due to Nexplanon encapsulation within the arterial wall. Ultimately, the patient underwent a left video-assisted thoracoscopic surgery (VATS) for exploration and left lower lobe basilar S7–9 segmentectomy, which successfully removed the Nexplanon. Conclusions Implanted contraceptive devices can rarely result in migration to the pulmonary vasculature. These radiopaque devices are detectable on imaging studies if patients and clinicians are unable to palpate them. An endovascular approach should be considered first to spare lung tissue and avoid chest-wall incisions, but can be complicated by encapsulation and adherence to adjacent tissue. A VATS procedure with single-lung ventilation via a double-lumen endotracheal tube allows surgeons to safely operate on an immobilized lung while anesthesiologists facilitate single-lung ventilation. This patient’s case details the uncommon phenomenon of Nexplanon migration, and the exceedingly rare treatment resolution of lung resection to remove an embolized device.

ABSTRACT The Southampton pneumococcal carriage study of children under 5 years old continued during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present data from October 2018 to March 2023 describing prevalence of pneumococci and other pathobionts during the winter seasons before, during, and after the introduction of non-pharmaceutical interventions (NPIs) to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nasopharyngeal swabs were collected from children attending outpatient clinics at a secondary care hospital and community healthcare sites. Pre-NPIs, in 2019/2020, the carriage prevalence of pneumococci at the hospital site was 32% (n = 161 positive/499 participants). During NPIs, this fell to 19% (n = 12/64), although based on fewer participants compared to previous years due to COVID-19 restrictions on health-care attendance. In 2021/2022, after NPIs had eased, prevalence rebounded to 33% (n = 15/46) [compared to NPIs period, χ2 (1, N = 110) =2.78, P = 0.09]. Carriage prevalence at community healthcare sites fell significantly from 27% (n = 127/470) in 2019/2020 to 19% during the NPI period (n = 44/228) in 2020/2021 [χ2 (1, N = 698) =4.95, P = 0.026]. No rebound was observed in 2021/2022 [19% (n = 56/288)]. However, in a multivariate logistic regression model, neither site had a significantly lower carriage prevalence during the NPI period compared to the post NPI period. A reduction in serotype diversity was observed in 2020/2021. Carriage of Haemophilus influenzae was particularly affected by NPIs with a significant reduction observed. In conclusion, among children under 5 years of age, transient, modest, and statistically non-significant alterations in carriage of both Streptococcus pneumoniae and H. influenzae were associated with SARS-CoV-2 NPIs.IMPORTANCEStreptococcus pneumoniae (the pneumococcus) continues to be a major contributor to global morbidity and mortality. Using our long-running pediatric study, we examined changes in pneumococcal carriage prevalence in nearly 3,000 children under the age of 5 years between the winters of 2018/2019 and 2022/2023. This period coincided with the severe acute respiratory syndrome coronavirus 2 pandemic and, in particular, the implementation of national strategies to limit disease transmission in the UK. We observed a transient reduction of both Streptococcus pneumoniae and Haemophilus influenzae in these populations during this period of non-pharmaceutical interventions. This aligned with the reduction in invasive pneumococcal disease seen in the UK and is therefore a likely contributor to this phenomenon.

Abstract Background COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study’s objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children. Methods This cohort study identified children aged 5–17 years vaccinated with BNT162b2 matched with unvaccinated children. Participants and BNT162b2 vaccinations were identified in Optum and CVS Health insurance administrative claims databases linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. Results There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person-years; CVS Health, 44.1 per 10,000 person-years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36–40%]) and hospital/ED–diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56–65%]). VE estimates were lowest among children 5–11 years and during the Omicron-variant era. Conclusions Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED–diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era. Registration The study protocol was publicly posted on the BEST Initiative website ( https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf ).

Abstract Klebsiella pneumoniae is a Gram-negative Enterobacteriaceae that is classified by the World Health Organisation (WHO) as a Priority One ESKAPE pathogen. South and Southeast Asian countries are regions where both healthcare associated infections (HAI) and community acquired infections (CAI) due to extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant K. pneumoniae (CRKp) are of concern. As K. pneumoniae can also exist as a harmless commensal, the spread of resistance genotypes requires epidemiological vigilance. However there has been no significant study of carriage isolates from healthy individuals, particularly in Southeast Asia, and specially Malaysia. Here we describe the genomic analysis of respiratory isolates of K. pneumoniae obtained from Orang Ulu and Orang Asli communities in Malaysian Borneo and Peninsular Malaysia respectively. The majority of isolates were K. pneumoniae species complex (KpSC) 1 K. pneumoniae (n = 53, 89.8%). Four Klebsiella variicola subsp. variicola (KpSC3) and two Klebsiella quasipneumoniae subsp. similipneumoniae (KpSC4) were also found. It was discovered that 30.2% (n = 16) of the KpSC1 isolates were ST23, 11.3% (n = 6) were of ST65, 7.5% (n = 4) were ST13, and 13.2% (n = 7) were ST86. Only eight of the KpSC1 isolates encoded ESBL, but importantly not carbapenemase. Thirteen of the KpSC1 isolates carried yersiniabactin, colibactin and aerobactin, all of which harboured the rmpADC locus and are therefore characterised as hypervirulent. Co-carriage of multiple strains was minimal. In conclusion, most isolates were KpSC1, ST23, one of the most common sequence types and previously found in cases of K. pneumoniae infection. A proportion were hypervirulent (hvKp) however antibiotic resistance was low.

Abstract A synthetic lethal relationship exists between disruption of polymerase theta (Polθ), and loss of either 53BP1 or homologous recombination (HR) proteins, including BRCA1; however, the mechanistic basis of these observations are unclear. Here we reveal two distinct mechanisms of Polθ synthetic lethality, identifying dual influences of 1) whether Polθ is lost or inhibited, and 2) the underlying susceptible genotype. Firstly, we find that the sensitivity of BRCA1/2- and 53BP1-deficient cells to Polθ loss, and 53BP1-deficient cells to Polθ inhibition (ART558) requires RAD52, and appropriate reduction of RAD52 can ameliorate these phenotypes. We show that in the absence of Polθ, RAD52 accumulations suppress ssDNA gap-filling in G2/M and encourage MRE11 nuclease accumulation. In contrast, the survival of BRCA1-deficient cells treated with Polθ inhibitor are not restored by RAD52 suppression, and ssDNA gap-filling is prevented by the chemically inhibited polymerase itself. These data define an additional role for Polθ, reveal the mechanism underlying synthetic lethality between 53BP1, BRCA1/2 and Polθ loss, and indicate genotype-dependent Polθ inhibitor mechanisms.

Food is one of the basic necessities for human life. Nutritious food is essential for human health and helps oneself live up to our best potential as productive members of society. In spite of this, 3 billion people are estimated to have limited access to nutrient-rich food, and there are 768 million undernourished people in the globe today. There are still concerns with food systems and food security, despite the fast economic transformation of low-and middle-income nations in Maritime Southeast Asia and Oceania over the past 10 years. These issues include dwindling agricultural land, deforestation, ineffective food supply networks, environmental degradation, changing and unhealthy diets, non-communicable diseases, disappearing cultural legacy, and ineffective policies. These problems are exacerbated by climate change, natural hazards, and pandemic shocks. This review explores the perspectives of food systems that relates to all the elements and activities in transforming agri-food industry. In this paper, we discuss the challenges and solutions to transforming food systems in this region to achieve a sustainable and healthy diet for all, with the perspective of bringing the region closer toward the UN sustainable development goals. This paper is an outcome of the deliberations that took place during the Food Security in Small Islands and Developing States workshop in 2020. It also includes insights from subsequent expert group sessions that focused on the following topics: Agriculture and Food Systems; Nutrition, Health, and Culture; Innovations and Digitalization in Food Systems; as well as Policies Coordination and Future Shocks.

Abstract In 2016, the National Oceanic and Atmospheric Administration deployed the first iteration of an operational National Water Model (NWM) to forecast the water cycle in the continental United States. With many versions, an hourly, multi-decadal historic simulation is made available to the public. In all released to date, the files containing simulated streamflow contain a snapshot of model conditions across the entire domain for a single timestep which makes accessing time series a technical and resource-intensive challenge. In the most recent release, extracting a complete streamflow time series for a single location requires managing 367,920 files (~16.2 TB). In this work we describe a reproducible process for restructuring a sequential set of NWM steamflow files for efficient time series access and provide restructured datasets for versions 1.2 (1993–2018), 2.0 (1993–2020), and 2.1 (1979–2022). These datasets have been made accessible via an OPeNDAP enabled THREDDS data server for public use and a brief analysis highlights the latest version of the model should not be assumed best for all locations. Lastly we describe an R package that expedites data retrieval with examples for multiple use-cases.

Abstract Pneumococcal pneumonia remains a significant global public health issue. Malaysia has recently added the 10 valent pneumococcal conjugate vaccine to its national immunisation programme. Data on pneumococcal serotype epidemiology is vital for informing national vaccination policy. However, there remains a lack of representative population-based pneumococcal surveillance in Malaysia to help both the assessment of vaccine effectiveness in the country and to shape future vaccine policy. This review explores the history of pneumococcal vaccination, the burden of pneumococcal disease in Malaysia, and offers an insight into the prospects for reducing pneumococcal disease in Malaysia.

Background: Monovalent booster/additional doses of COVID-19 vaccines were first authorized in August 2021 in the United States. We evaluated the real-world effectiveness of receipt of a monovalent booster/additional dose of COVID-19 vaccine compared with receiving a primary vaccine series without a booster/additional dose. Methods: Cohorts of individuals receiving a COVID-19 booster/additional dose after receipt of a complete primary vaccine series were identified in 2 administrative insurance claims databases (Optum, CVS Health) supplemented with state immunization information system data between August 2021 and March 2022. Individuals with a complete primary series but without a booster/additional dose were one-to-one matched to boosted individuals on calendar date, geography, and clinical factors. COVID-19 diagnoses were identified in any medical setting, or specifically in hospitals/emergency departments (EDs). Propensity score-weighted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated with Cox proportional hazards models; vaccine effectiveness (VE) was estimated as 1 minus the HR by vaccine brand overall and within subgroups of variant-specific eras, immunocompromised status, and homologous/heterologous booster status. Results: Across both data sources, we identified 752,165 matched pairs for BNT162b2, 410,501 for mRNA-1273, and 11,398 for JNJ-7836735. For any medically diagnosed COVID-19, meta-analyzed VE estimates for BNT162b2, mRNA-1273, and JNJ-7836735, respectively, were: BNT162b2, 54% (95% CI, 53%-56%); mRNA-1273, 58% (95% CI, 56%-59%); JNJ-7836735, 34% (95% CI, 23%-44%). For hospital/ED-diagnosed COVID-19, VE estimates ranged from 70% to 76%. VE was generally lower during the Omicron era than the Delta era and for immunocompromised individuals. There was little difference observed by homologous or heterologous booster status. Conclusion: The original, monovalent booster/additional doses were reasonably effective in real-world use among the populations for which they were indicated during the study period. Additional studies may be informative in the future as new variants emerge and new vaccines become available.Registration: The study protocol was publicly posted on the BEST Initiative website (https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf).

Summary: Skeletal muscle protein levels are governed by the relative rates of muscle protein synthesis (MPS) and breakdown (MPB). The mechanisms controlling these rates are complex, and their integrated behaviors are challenging to study through experiments alone. The purpose of this study was to develop and analyze a kinetic model of leucine-mediated mTOR signaling and protein metabolism in the skeletal muscle of young adults. Our model amalgamates published cellular-level models of the IRS1-PI3K-Akt-mTORC1 signaling system and of skeletal-muscle leucine kinetics with physiological-level models of leucine digestion and transport and insulin dynamics. The model satisfactorily predicts experimental data from diverse leucine feeding protocols. Model analysis revealed that total levels of p70S6K are a primary determinant of MPS, insulin signaling substantially affects muscle net protein balance via its effects on MPB, and p70S6K-mediated feedback of mTORC1 signaling reduces MPS in a dose-dependent manner.

IntroductionWearable near-infrared spectroscopy (NIRS) measurements of muscle oxygen saturation (SmO2) demonstrated good test–retest reliability at rest. We hypothesized SmO2 measured with the Moxy monitor at the vastus lateralis (VL) would demonstrate good reliability across intensities. For relative reliability, SmO2 will be lower than volume of oxygen consumption (V̇O2) and heart rate (HR), higher than concentration of blood lactate accumulation ([BLa]) and rating of perceived exertion (RPE). We aimed to estimate the reliability of SmO2 and common physiological measures across exercise intensities, as well as to quantify within-participant agreement between sessions.MethodsTwenty-one trained cyclists completed two trials of an incremental multi-stage cycling test with 5 min constant workload steps starting at 1.0 watt per kg bodyweight (W·kg−1) and increasing by 0.5 W kg−1 per step, separated by 1 min passive recovery intervals until maximal task tolerance. SmO2, HR, V̇O2, [BLa], and RPE were recorded for each stage. Continuous measures were averaged over the final 60 s of each stage. Relative reliability at the lowest, median, and highest work stages was quantified as intraclass correlation coefficient (ICC). Absolute reliability and within-subject agreement were quantified as standard error of the measurement (SEM) and minimum detectable change (MDC).ResultsComparisons between trials showed no significant differences within each exercise intensity for all outcome variables. ICC for SmO2 was 0.81–0.90 across exercise intensity. ICC for HR, V̇O2, [BLa], and RPE were 0.87–0.92, 0.73–0.97, 0.44–0.74, 0.29–0.70, respectively. SEM (95% CI) for SmO2 was 5 (3–7), 6 (4–9), and 7 (5–10)%, and MDC was 12%, 16%, and 18%.DiscussionOur results demonstrate good-to-excellent test-retest reliability for SmO2 across intensity during an incremental multi-stage cycling test. V̇O2 and HR had excellent reliability, higher than SmO2. [BLa] and RPE had lower reliability than SmO2. Muscle oxygen saturation measured by wearable NIRS was found to have similar reliability to V̇O2 and HR, and higher than [BLa] and RPE across exercise intensity, suggesting that it is appropriate for everyday use as a non-invasive method of monitoring internal load alongside other metrics.

ABSTRACT: Objectives: To analyse the genome sequences of four archival Acinetobacter nosocomialis clinical isolates (designated AC13, AC15, AC21 and AC25) obtained from Terengganu, Malaysia in 2011 to determine their genetic relatedness and basis of antimicrobial resistance. Methods: Antimicrobial susceptibility profiles of the A. nosocomialis isolates were determined by disk diffusion. Genome sequencing was performed using the Illumina NextSeq platform. Results: The four A. nosocomialis isolates were cefotaxime resistant whereas three isolates (namely, AC13, AC15 and AC25) were tetracycline resistant. The carriage of the blaADC-255-encoded cephalosporinase gene is likely responsible for cefotaxime resistance in all four isolates. Phylogenetic analysis indicated that the three tetracycline-resistant isolates were closely related, with an average nucleotide identity of 99.9%, suggestive of nosocomial spread, whereas AC21 had an average nucleotide identity of 97.9% when compared to these three isolates. The tetracycline-resistant isolates harboured two plasmids: a 13476 bp Rep3-family plasmid of the GR17 group designated pAC13-1, which encodes the tetA(39) tetracycline-resistance gene, and pAC13-2, a 4872 bp cryptic PriCT-1-family plasmid of a new Acinetobacter plasmid group, GR60. The tetA(39) gene was in a 2 001 bp fragment flanked by XerC/XerD recombination sites characteristic of a mobile pdif module. Both plasmids also harboured mobilisation/transfer-related genes. Conclusions: Genome sequencing of A. nosocomialis isolates led to the discovery of two novel plasmids, one of which encodes the tetA(39) tetracycline-resistant gene in a mobile pdif module. The high degree of genetic relatedness among the three tetracycline-resistant A. nosocomialis isolates is indicative of nosocomial transmission.

Abstract Streptococcus pneumoniae continues to cause significant disease burden. Whilst pneumococcal conjugate vaccines (PCV) have substantially reduced this burden, serotype replacement partially negates this success due to increased disease associated with non-vaccine serotypes (NVTs). Continued surveillance is therefore essential to provide crucial epidemiological data. Annual cross-sectional surveillance of paediatric pneumococcal carriage was started in Southampton, UK following PCV7 roll-out in 2006. Nasopharyngeal swabs were collected from children

Cite this article: Bone Joint Res 2022;11(8):514–517.

BackgroundSwimmers commonly access performance metrics such as lap splits, distance, and pacing information between work bouts while they rest. Recently, a new category of tracking devices for swimming was introduced with the FORM Smart Swim Goggles (FORM Goggles). The goggles have a built-in see-through display and are capable of tracking and displaying distance, time splits, stroke, and pace metrics in real time using machine learning and augmented reality through a heads-up display. The purpose of this study was to assess the validity and reliability of the FORM Goggles compared with video analysis for stroke type, pool length count, pool length time, stroke rate, and stroke count in recreational swimmers and triathletes.MethodA total of 36 participants performed mixed swimming intervals in a 25-m pool across two identical 900-m swim sessions performed at comparable intensities with 1 week interval. The participants wore FORM Goggles during their swims, which detected the following five swim metrics: stroke type, pool length time, pool length count, stroke count, and stroke rate. Four video cameras were positioned on the pool edges to capture ground truth video footage, which was then manually labeled by three trained individuals. Mean (SD) differences between FORM Goggles and ground truth were calculated for the selected metrics for both sessions. The absolute mean difference and mean absolute percentage error were used to assess the differences of the FORM Goggles relative to ground truth. The test–retest reliability of the goggles was assessed using both relative and absolute reliability metrics.ResultsCompared with video analysis, the FORM Goggles identified the correct stroke type at a rate of 99.7% (N = 2,354 pool lengths, p

Ancient grasslands are lost through transformation to agriculture, mining, and urban expansion. Land-use change leads to ecosystem degradation and a subsequent loss of biodiversity. Globally, degraded grasslands have become a priority for restoration efforts to recover lost ecosystem services. Although the ecological and social benefits of woody species and grasses are well documented, limited research has considered the use of forbs for restoration purposes despite their benefits (e.g., C sequestration and medicinal uses). The aim of this study was to determine if Crinum bulbispermum (Burm.f.) Milne-Redh. & Schweick., a medicinal geophyte, could form part of restoration initiatives to restore mine soils in grasslands of the South African Highveld. A pot experiment was conducted to assess the performance of C. bulbispermum in a random design, with three soil treatments varying in level of degradation and metal contamination. The plants were monitored for 12 months, and the morphological characters were measured monthly to assess performance and survival. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the soil and plant tissue concentration of potentially toxic metals. The results indicated that mine tailings negatively affected the growth and development of C. bulbispermum. Although the survival rates indicated that it could survive on tailings, its below-par productivity indicated that the species is not ideal for restoration purposes unless the tailings are ameliorated with topsoil. Although there was root accumulation of metals (Co, Cd, Cu, Mo, and Zn), there was no translocation to the bulbs and leaves, which makes C. bulbispermum suitable for medicinal use even when grown on metal-enriched soil. This species may not be viable for phytoremediation but is a contender to be used in phytostabilization due to its ecological advantages and the fact that it does not accumulate or store metals. These findings underscore the importance of considering geophytes in grassland restoration strategies, expanding their ecological and societal benefits beyond conventional approaches.

Abstract Background Provision of virtual health care (VHC) home monitoring for patients who are experiencing mild to moderate COVID-19 illness is emerging as a central strategy for reducing pressure on acute health systems. Understanding the enablers and challenges in implementation and delivery of these programs is important for future implementation and re-design. The aim of this study was to explore the perspectives of staff involved with the implementation and delivery, and the experience of patients managed by, a VHC monitoring service in Melbourne, Australia during the COVID-19 pandemic. Methods A descriptive qualitative approach informed by naturalist inquiry was used. Staff interviews were analysed using the Consolidated Framework for Implementation Research (CFIR). Patient experience was captured using a survey and descriptive statistics were used to describe categorical responses while content analysis was used to analyse free text responses as they related to the CFIR. Finally, data from the interviews and patient experience were triangulated to see if patient experience validated data from staff interviews. Results All 15 staff were interviewed, and 271 patients were surveyed (42%). A total of four final overarching themes emerged: service implementation enablers, service delivery benefits for patients, fragmentation of care, and workforce strengths. 19 subthemes aligned with 18 CFIR constructs from staff and patient data. Conclusion Rapid implementation was enabled through shared resources, dividing implementation tasks between senior personnel, engaging furloughed healthcare staff in design and delivery, and having a flexible approach that allowed for ongoing improvements. Benefits for patients included early identification of COVID-19 deterioration, as well as provision of accurate and trustworthy information to isolate safely at home. The main challenges were the multiple agencies involved in patient monitoring, which may be addressed in the future by attributing responsibility for monitoring to a single agency.

Abstract Background Monitoring COVID-19 testing volumes and test positivity is an integral part of the response to the pandemic. We described the characteristics of individuals who were tested and tested positive for SARS-CoV-2 during the pre-vaccine phase of the pandemic in the United States (U.S.). Methods This descriptive study analyzed three U.S. electronic health record (EHR) databases (Explorys, Academic Health System, and OneFlorida) between February and November 2020, identifying patients who received an interpretable nucleic acid amplification test (NAAT) result. Test-level data were used to characterize the settings in which tests were administered. Patient-level data were used to calculate test positivity rates and characterize the demographics, comorbidities, and hospitalization rates of COVID-19-positive patients. Results Over 40% of tests were conducted in outpatient care settings, with a median time between test order and result of 0–1 day for most settings. Patients tested were mostly female (55.6–57.7%), 18–44 years of age (33.9–41.2%), and Caucasian (44.0–66.7%). The overall test positivity rate was 13.0% in Explorys, 8.0% in Academic Health System, and 8.9% in OneFlorida. The proportion of patients hospitalized within 14 days of a positive COVID-19 NAAT result was 24.2–33.1% across databases, with patients over 75 years demonstrating the highest hospitalization rates (46.7–69.7% of positive tests). Conclusions This analysis of COVID-19 testing volume and positivity patterns across three large EHR databases provides insight into the characteristics of COVID-19-tested, COVID-19-test-positive, and hospitalized COVID-19-test-positive patients during the early phase of the pandemic in the U.S.

Introduction Ekbom Syndrome is a rare condition presenting as a uni-thematic delusional belief of parasitosis. Affected individuals are often socially isolated presenile females. The syndrome is characterised by kinaesthetic hallucinations of insect infestation with persistent pruritis. First described by Karl Ekbom in 1938, presentations are rare, often presenting initially to primary care and dermatological services. We report a case of an older adult female referred to Community Mental Health Team following multiple presentations to the primary care physician with subsequent diagnosis of Ekbom Syndrome. Objectives To illustrate a rare case report of Ekbom Syndrome, managed successfully in the community in Ireland. Methods A retrospective case study. Data was reviewed from available psychiatric and medical records including laboratory testing. Results A 69 year old Catholic Nun was referred to the CMHT for psychiatric assessment. The patient presented to the CMHT appointment as distressed. She reported a 15 year history with significant deterioration 4 months prior, of progressive symptoms of a ‘crawling and biting sensation’ all over her body, alongside intermittent anxiety related to the infestation. The patient acknowledged that she had visited her primary care physician on multiple occasions seeking resolution. On one occasion the patient brought a sample of the alleged parasites inside a small container, ‘matchbox sign’. A professional pest control agency had recently been employed to decontaminate her bedroom in the parish house of which she is resident in. She described a rigid routined, daily washing of clothes. Medical history was significant for pituitary gland adenoma 30years prior, with pituitary excision twice secondary to visual disturbance and reoccurrence. She was on lifelong thyroid replacement with acceptable postoperative functioning. The patient was commenced on Aripiprazole oral medication and received psychoeducation via Specialist Mental Health Nursing Outreach. Pimozide was deemed unsuitable due to presence of numerous cardiac risk factors. Physical and delusional psychopathology resolved in a trajectory fashion with aripiprazole titration. It was hypothesised that the patient had premorbid anakastic personality traits, exacerbated by the COVID19 pandemic prior to presentation. Conclusions Patients with delusional parasitosis can have complex medical and social histories and may present to psychiatry as a last resort. These clinical presentations can occur after periods of dermatological input and following extensive efforts to decontaminate their physical surroundings. Psychotic symptoms of Ekbom Syndrome may be effectively controlled with psychotropic therapy and patients benefit from psychoeducation about their rare disorder. Disclosure of Interest None Declared

Near-infrared spectroscopy (NIRS) quantifies muscle oxygenation (SmO2) during exercise. Muscle oxygenation response to self-paced, severe-intensity cycling remains unclear. Observing SmO2 can provide cycling professionals with the ability to assess muscular response, helping optimize decision-making. We aimed to describe the effect of self-paced severe intensity bouts on SmO2, measured noninvasively by a wearable NIRS sensor on the vastus lateralis (VL) muscle, and examine its reliability. We hypothesized a greater desaturation response with each bout, whereas, between trials, good reliability would be observed. Fourteen recreationally trained, and trained cyclists completed a ramp test to determine the power output (PO) at the respiratory compensation point (RCP). Athletes completed two subsequent visits of 50-minute sessions that included four severe-intensity bouts done at 5% above RCP PO. Muscle oxygenation in the VL was monitored using a wearable NIRS device. Measures included mean PO, heart-rate (HR), cadence, and SmO2 at bout onset, during work (work SmO2), and ΔSmO2. The bouts were compared using a one-way repeated measures ANOVA. For significant differences, a Fisher's least square difference post-hoc analysis was used. A two-way repeated measures ANOVA was used using trial and bout as main factors. Intraclass correlations (ICC) were used to quantify relative reliability for mean work, and standard error of the measurement (SEM) was used to quantify absolute agreement of mean work SmO2. Both PO and cadence showed no effect of bout or trial. Heart-rate at bout 2 (168 ± 8 bpm) and 4 (170 ± 7 bpm) were higher than bout 1 (160 ± 6 bpm). Onset SmO2 (%) response significantly increased in the final two bouts of the session. Mean work SmO2 increased across bouts, with the highest value displayed in bout 4 (36 ± 22%). ΔSmO2 showed a smaller desaturation response during bout 4 (27 ± 10%) compared to bout 3 (31 ± 10%). Mean work SmO2 ICC showed good reliability (ICC = 0.87), and SEM was 12% (CI 9-15%). We concluded that a non-invasive, affordable, wearable NIRS sensor demonstrated the heterogeneous muscle oxygenation response during severe intensity cycling bouts with good reliability in trained cyclists.

BackgroundTo fully leverage the potential of the early care and education (ECE) setting for childhood obesity prevention, initiatives must not intervene solely at the organizational level, but rather they should also address the health needs of the ECE workers. Workers suffer disproportionately high rates of obesity, and have reported low confidence in modeling and promoting healthy eating and activity behaviors. However, information regarding the effectiveness of improving ECE workers' health behaviors or whether such improvements elicit meaningful change in the ECE environment and/or the children in their care is limited.MethodThe proposed study will integrate a staff wellness intervention into a nationally recognized, ECE obesity prevention initiative (Go NAPSACC). Go NAPSACC+ Staff Wellness program will be assessed using a clustered randomized controlled trial including 84 ECE centers, 168 workers, and 672 2-5-year-old children. Centers will be randomly assigned to 1) standard "Go NAPSACC" or 2) Go NAPSACC+ Staff Wellness. Outcome measures will assess impact on dietary intake and PA behaviors of 2-5-year-old children at 6 months (primary aim) and 12 months. Secondarily, we will compare the impact of the intervention on centers' implementation of healthy weight practices and the effect on ECE workers' diet quality and PA at 6- and 12 months.DiscussionThis trial expects to increase our understanding of how ECE worker's personal health behaviors impact the health behaviors of the children in their care and the ECE environment.Trial registrationClinicalTrials.gov: NCT05656807, registered on 19 December 2022. Protocol version 1.0, 22 March 2023.

Youth footballers need to be developed to meet the technical, tactical, and physical demands of professional level competition, ensuring that the transition between competition levels is successful. To quantify the physical demands, peak match intensities have been measured across football competition tiers, with team formations and tactical approaches shown to influence these physical demands. To date, no research has directly compared the physical demands of elite youth and professional footballers from a single club utilising common formations and tactical approaches. The current study quantified the total match and peak match running demands of youth and professional footballers from a single Australian A-League club. GPS data were collected across a single season from both a professional (n = 19; total observations = 199; mean ± SD; 26.7 ± 4.0 years) and elite youth (n = 21; total observations = 59; 17.9 ± 1.3 years) team. Total match demands and peak match running demands (1–10 min) were quantified for measures of total distance, high-speed distance [>19.8 km·h-1] and average acceleration. Linear mixed models and effect sizes identified differences between competition levels. No differences existed between competition levels for any total match physical performance metric. Peak total and high-speed distances demands were similar between competitions for all moving average durations. Interestingly, peak average acceleration demands were lower (SMD = 0.63–0.69) in the youth players across all moving average durations. The data suggest that the development of acceleration and repeat effort capacities is crucial in youth players for them to transition into professional competition.

Cluster of differentiation 38 (CD38) is an ecto-enzyme expressed primarily on immune cells that metabolizes nicotinamide adenine dinucleotide (NAD+) to adenosine diphosphate ribose or cyclic ADP-ribose and nicotinamide. Other substrates of CD38 include nicotinamide adenine dinucleotide phosphate and nicotinamide mononucleotide, a critical NAD+ precursor in the salvage pathway. NAD+ is an important coenzyme involved in several metabolic pathways and is a required cofactor for the function of sirtuins (SIRTs) and poly (adenosine diphosphate-ribose) polymerases. Declines in NAD+ levels are associated with metabolic and inflammatory diseases, aging, and neurodegenerative disorders. To inhibit CD38 enzyme activity and boost NAD+ levels, we developed TNB-738, an anti-CD38 biparatopic antibody that pairs two non-competing heavy chain-only antibodies in a bispecific format. By simultaneously binding two distinct epitopes on CD38, TNB-738 potently inhibited its enzymatic activity, which in turn boosted intracellular NAD+ levels and SIRT activities. Due to its silenced IgG4 Fc, TNB-738 did not deplete CD38-expressing cells, in contrast to the clinically available anti-CD38 antibodies, daratumumab, and isatuximab. TNB-738 offers numerous advantages compared to other NAD-boosting therapeutics, including small molecules, and supplements, due to its long half-life, specificity, safety profile, and activity. Overall, TNB-738 represents a novel treatment with broad therapeutic potential for metabolic and inflammatory diseases associated with NAD+ deficiencies.Abbreviations: 7-AAD: 7-aminoactinomycin D; ADCC: antibody dependent cell-mediated cytotoxicity; ADCP: antibody dependent cell-mediated phagocytosis; ADPR: adenosine diphosphate ribose; APC: allophycocyanin; cADPR: cyclic ADP-ribose; cDNA: complementary DNA; BSA: bovine serum albumin; CD38: cluster of differentiation 38; CDC: complement dependent cytotoxicity; CFA: Freund’s complete adjuvant; CHO: Chinese hamster ovary; CCP4: collaborative computational project, number 4; COOT: crystallographic object-oriented toolkit; DAPI: 4′,6-diamidino-2-phenylindole; DNA: deoxyribonucleic acid; DSC: differential scanning calorimetry; 3D: three dimensional; εNAD+: nicotinamide 1,N6-ethenoadenine dinucleotide; ECD: extracellular domain; EGF: epidermal growth factor; FACS: fluorescence activated cell sorting; FcγR: Fc gamma receptors; FITC: fluorescein isothiocyanate; HEK: human embryonic kidney; HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; IgG: immunoglobulin; IFA: incomplete Freund’s adjuvant; IFNγ: Interferon gamma; KB: kinetic buffer; kDa: kilodalton; KEGG: kyoto encyclopedia of genes and genomes; LDH: lactate dehydrogenase; M: molar; mM: millimolar; MFI: mean fluorescent intensity; NA: nicotinic acid; NAD: nicotinamide adenine dinucleotide; NADP: nicotinamide adenine dinucleotide phosphate; NAM: nicotinamide; NGS: next-generation sequencing; NHS/EDC: N-Hydroxysuccinimide/ ethyl (dimethylamino propyl) carbodiimide; Ni-NTA: nickel-nitrilotriacetic acid; nL: nanoliter; NK: natural killer; NMN: nicotinamide mononucleotide; OD: optical density; PARP: poly (adenosine diphosphate-ribose) polymerase; PBS: phosphate-buffered saline; PBMC: peripheral blood mononuclear cell; PDB: protein data bank; PE: phycoerythrin; PISA: protein interfaces, surfaces, and assemblies: PK: pharmacokinetics; mol: picomolar; RNA: ribonucleic acid; RLU: relative luminescence units; rpm: rotations per minute; RU: resonance unit; SEC: size exclusion chromatography; SEM: standard error of the mean; SIRT: sirtuins; SPR: surface plasmon resonance; µg: microgram; µM: micromolar; µL: microliter

Peak match running intensities have recently been introduced to quantify the peak running demands of football competition, across incremental time intervals, to inform training practices. However, their between-match variation is yet to be comprehensively reported, limiting the ability to determine meaningful changes in peak match running intensities. The current study aimed to quantify the between-match variability in peak match running intensities across discrete moving average durations (1–10 min). GPS data were collected from 44 elite football players across 68 matches (mean ± SD; 13 ± 10 observations per player). For inclusion players must have completed 70mins of a match across a minimum of two matches. Performance metrics included total and high-speed (> 19.8 km·h-1) running distances and average acceleration (m·s -2), expressed relative to time. For each metric, the coefficient of variation and smallest worthwhile difference were calculated. The peak match running intensity data was similar to previously reported data from various football competitions. The between-match CV of relative total distance ranged between 6.8–7.3%, with the CV for average acceleration and relative high-speed running being 5.4–5.8% and 20.6–29.8%, respectively. The greater variability observed for relative high-speed running is likely reflective of the varying constraints and contextual factors that differ between matches. The reported between-match variability helps to provide context when interpreting match performance and prescribing training drills using peak match running intensity data.

Summary: Seasonal rhythms are endogenous timing mechanisms that allow animals living at temperate latitudes to synchronize their physiology to the seasons. Human viral respiratory disease is prevalent in the winter at temperate latitudes, but the role of endogenous mechanisms in these recurring annual patterns is unclear. The Common Cold Project is a repository of data describing the experimental viral challenge of 1,337 participants across the seasons of the year. We report a secondary analysis of these data to investigate if susceptibility to the common cold is associated with day length. The majority of the participants (78%) showed signs of infection but only 32% developed clinical signs of disease, and the probability of infection was significantly higher in longer day lengths (summer), but the disease was more likely in short (winter) day lengths. The persistence of winter disease patterns in experimental conditions supports the role of endogenous seasonality in human susceptibility to viral infection.

The imbalance between the supply and demand of ecosystem services (ESs) is one of the main reasons for ecological degradation, which significantly impacts human well-being and ecological safety. Spatial heterogeneity of ES supply–demand, ES tradeoffs, and the socioecological environment calls for zoning management, while few studies have combined the above three aspects in dividing management zones and proposed strategies. Using the City Belt along the Yellow River in Ningxia in northwestern China as a case study, this study quantified the supply and demand for five key ESs (crop production, carbon sequestration, nutrient retention, sand fixation, and recreational opportunity), analyzed ES tradeoffs/synergies and bundles through correlation analysis and the self-organizing map (SOM) method, and investigated their socioecological driving mechanisms through a random forest model and the SOM method. Management zones were proposed and differentiated suggestions were provided through overlaying ES bundles and driver clusters. The results suggested that crop production, carbon sequestration, and nutrient retention mostly correlated to the same intrinsic ecological process, resulting in consistent synergies among these three ESs at both supply and demand sides. On the contrary, the variance in interactions between the two ESs of sand fixation and recreational opportunity and the other three ESs is due to the low similarity of their intrinsic ecological processes and external driving mechanisms. Fourteen socioecological factors could effectively explain the spatial heterogeneity of ES supply, demand, and match degree. Fourteen management zones with similar ecological problems and socioecological environments were delineated, and differentiated suggestions were provided for each zone. Adopting both ES characteristics and the socioecological environment into zoning management could effectively detect ecological problems and help to promote management suggestions in different socioecological contexts. This framework could offer new insights for integrating ESs into actual decision-making and ecosystem management.

Loop diuretics and antibiotics are commonly co-prescribed across many clinical care settings. Loop diuretics may alter antibiotic pharmacokinetics (PK) via several potential drug interactions. A systematic review of the literature was performed to investigate the impact of loop diuretics on antibiotic PK. The primary outcome metric was the ratio of means (ROM) of antibiotic PK parameters such as area under the curve (AUC) and volume of distribution (Vd) on and off loop diuretics. Twelve crossover studies were amenable for metanalysis. Coadministration of diuretics was associated with a mean 17% increase in plasma antibiotic AUC (ROM 1.17, 95% CI 1.09–1.25, I2 = 0%) and a mean decrease in antibiotic Vd by 11% (ROM 0.89, 95% CI 0.81–0.97, I2 = 0%). However, the half-life was not significantly different (ROM 1.06, 95% CI 0.99–1.13, I2 = 26%). The remaining 13 observational and population PK studies were heterogeneous in design and population, as well as prone to bias. No large trends were collectively observed in these studies. There is currently not enough evidence to support antibiotic dosing changes based on the presence or absence of loop diuretics alone. Further studies designed and powered to detect the effect of loop diuretics on antibiotic PK are warranted in applicable patient populations.

The carriage of bacterial pathogens in the human upper respiratory tract (URT) is associated with a risk of invasive respiratory tract infections, but the related epidemiological information on this at the population level is scarce in Malaysia. This study aimed to investigate the URT carriage of Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa among 100 university students by nasal and oropharyngeal swabbing. The presence of S. aureus, K. pneumoniae and P. aeruginosa was assessed via swab culture on selective media and PCR on the resulting isolates. For S. pneumoniae, H. influenzae and N. meningitidis, their presence was assessed via multiplex PCR on the total DNA extracts from chocolate agar cultures. The carriage prevalence of H. influenzae, S. aureus, S. pneumoniae, K. pneumoniae, N. meningitidis and P. aeruginosa among the subjects was 36%, 27%, 15%, 11%, 5% and 1%, respectively, by these approaches. Their carriage was significantly higher in males compared to females overall. The S. aureus, K. pneumoniae and P. aeruginosa isolates were also screened by the Kirby-Bauer assay, in which 51.6% of S. aureus were penicillin-resistant. The outcomes from carriage studies are expected to contribute to informing infectious disease control policies and guidelines.

Abstract Background Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect. Methods We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT) (n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time—Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR). Results There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G − 0.23 s (0.27) versus group GT − 0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: − 20.83 mmHg s (24.54 vs. − 21.20 mmHg s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine − 2.0 ng/ml (− 117.1, 14.8) versus − 0.5 ng/ml (− 19.6, 9.4); p = 0.60. Conclusion The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation. Trial registration: The local research ethics committee approved the study (National Research Ethics Service-NRES Committee, East of England): REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.

Abstract Background Pneumococcal pneumonia is the leading cause of under-five mortality globally. The surveillance of pneumococcal serotypes is therefore vital for informing pneumococcal vaccination policy and programmes. Pneumococcal conjugate vaccines (PCVs) have been available as an option in the private healthcare setting and beginning December 2020, PCV10 was incorporated as part of routine national immunisation programme (NIP) in Malaysia. We searched existing literature on pneumococcal serotype distribution across Malaysia to provide an overall view of this distribution before the implementation of PCV10. Methods Online databases (PubMed, Ovid MEDLINE and Scopus), reference lists of articles identified, and grey literature (Malaysian Ministry of Health website, WHO website) were systematically searched for relevant literature on pneumococcal serotype distribution across Malaysia up to 10th November 2020. No lower date limit was set to maximise the number of target reports returned. Results of serotypes were split by age categories, including ≤5 years, > 5 years and unreported for those that did not specify. Results The search returned 18 relevant results, with a total of 2040 isolates. The most common serotypes across all disease types were 19F (n = 313, 15.3% [95%CI: 13.8–17.0]), 23F (n = 166, 8.1% [95%CI: 7.0–9.4]), 14 (n = 166, 8.1% [95%CI: 7.0–9.4]), 6B (n = 163, 8.0% [95%CI: 6.9–9.2]) and 19A (n = 138, 6.8% [95%CI: 5.8–7.9]). Conclusion Four of the most common serotypes across all isolate sources in Malaysia are covered by PCV10, while PCV13 provides greater serotype coverage in comparison to PCV10. There is still a need for surveillance studies, particularly those investigating serotypes in children under 5 years of age, to monitor vaccine effectiveness and pneumococcal population dynamic following implementation of PCV10 into routine immunisation.

Background Post–percutaneous coronary intervention (PCI) fractional flow reserve ≥0.90 is an accepted marker of procedural success, and a cutoff of ≥0.95 has recently been proposed for post‐PCI instantaneous wave‐free ratio. However, stability of nonhyperemic pressure ratios (NHPRs) post‐PCI is not well characterized, and transient reactive submaximal hyperemia post‐PCI may affect their precision. We performed this study to assess stability and reproducibility of NHPRs post‐PCI. Methods and Results Fifty‐seven patients (age, 63.77±10.67 years; men, 71%) underwent hemodynamic assessment immediately post‐PCI and then after a recovery period of 10, 20, and 30 minutes and repeated at 3 months. Manual offline analysis was performed to derive resting and hyperemic pressure indexes (Pd/Pa resting pressure gradient, mathematically derived instantaneous wave‐free ratio, resting full cycle ratio, and fractional flow reserve) and microcirculatory resistances (basal microvascular resistance and index of microvascular resistance). Transient submaximal hyperemia occurring post‐PCI was demonstrated by longer thermodilution time at 30 minutes compared with immediately post‐PCI; mean difference of thermodilution time was 0.17 seconds (95% CI, 0.07–0.26 seconds; P=0.04). Basal microcirculatory resistance was also higher at 30 minutes than immediately post‐PCI; mean difference of basal microvascular resistance was 10.89 mm Hg.s (95% CI, 2.25–19.52 mm Hg.s; P=0.04). Despite this, group analysis confirmed no significant differences in the values of resting whole cycle pressure ratios (Pd/Pa and resting full cycle ratio) as well as diastolic pressure ratios (diastolic pressure ratio and mathematically derived instantaneous wave‐free ratio). Whole cardiac cycle NHPRs demonstrated the best overall stability post‐PCI, and 1 in 5 repeated diastolic NHPRs crossed the clinical decision threshold. Conclusions Whole cycle NHPRs demonstrate better reproducibility and clinical precision post‐PCI than diastolic NHPRs, possibly because of less perturbation from predominantly diastolic reactive hyperemia and left ventricular stunning. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03502083; Unique identifier: NCT03502083 and URL: https://clinicaltrials.gov/ct2/show/NCT03076476; Unique identifier: NCT03076476.

Abstract Introduction Pneumonia is a leading cause of death in Malaysia. Whilst many studies have reported the aetiology of pneumonia in Western countries, the epidemiology of pneumonia in Malaysia remains poorly understood. As carriage is a prerequisite for disease, we sought to improve our understanding of the carriage and antimicrobial resistance (AMR) of respiratory tract pathogens in Malaysia. The rural communities of Sarawak are an understudied part of the Malaysian population and were the focus of this study, allowing us to gain a better understanding of bacterial epidemiology in this population. Methods A population-based survey of bacterial carriage was undertaken in participants of all ages from rural communities in Sarawak, Malaysia. Nasopharyngeal, nasal, mouth and oropharyngeal swabs were taken. Bacteria were isolated from each swab and identified by culture-based methods and antimicrobial susceptibility testing conducted by disk diffusion or E test. Results 140 participants were recruited from five rural communities. Klebsiella pneumoniae was most commonly isolated from participants (30.0%), followed by Staphylococcus aureus (20.7%), Streptococcus pneumoniae (10.7%), Haemophilus influenzae (9.3%), Moraxella catarrhalis (6.4%), Pseudomonas aeruginosa (6.4%) and Neisseria meningitidis (5.0%). Of the 21 S. pneumoniae isolated, 33.3 and 14.3% were serotypes included in the 13 valent PCV (PCV13) and 10 valent PCV (PCV10) respectively. 33.8% of all species were resistant to at least one antibiotic, however all bacterial species except S. pneumoniae were susceptible to at least one type of antibiotic. Conclusion To our knowledge, this is the first bacterial carriage study undertaken in East Malaysia. We provide valuable and timely data regarding the epidemiology and AMR of respiratory pathogens commonly associated with pneumonia. Further surveillance in Malaysia is necessary to monitor changes in the carriage prevalence of upper respiratory tract pathogens and the emergence of AMR, particularly as PCV is added to the National Immunisation Programme (NIP).

COVID-19 infections have contributed to substantial increases in hospitalizations. This study describes demographics, baseline clinical characteristics and treatments, and clinical outcomes among U.S. patients admitted to hospitals with COVID-19 during the prevaccine phase of the pandemic. A total of 20,446 hospitalized patients with a positive COVID-19 nucleic acid amplification test were identified from three large electronic health record databases during 5 February–30 November 2020 (Academic Health System: n = 4504; Explorys; n = 7492; OneFlorida: n = 8450). Over 90% of patients were ≥30 years of age, with an even distribution between sexes. At least one comorbidity was recorded in 84.6–96.1% of patients; cardiovascular and respiratory conditions (28.8–50.3%) and diabetes (25.6–44.4%) were most common. Anticoagulants were the most frequently reported medications on or up to 28 days after admission (44.5–81.7%). Remdesivir was administered to 14.1–24.6% of patients and increased over time. Patients exhibited higher COVID-19 severity 14 days following admission than the 14 days prior to and on admission. The length of in-patient hospital stay ranged from a median of 4 to 6 days, and over 85% of patients were discharged alive. These results promote understanding of the clinical characteristics and hospital-resource utilization associated with hospitalized COVID-19 over time.

Abstract Background Psychotic experiences (PEs) are not uncommon in young people and are associated with both psychopathology and compromised global functioning. Although psychotic experiences are transient (short-lived, self-resolving and non-recurring) for most people who report them, few studies have examined the association between early transient PEs and later functioning in population samples. Additionally, studies using self-report measures of interpersonal and educational/ vocational difficulties are lacking. The aim of this study was to examine the relationship between transient psychotic experiences and self-reported interpersonal and educational/vocational difficulties in adolescence and young adulthood. Methods Participants were 103 young people from a longitudinal population-based study cohort of mental health in Ireland. They attended for baseline clinical interviews in childhood (age 11–13) and were followed up in young adulthood (age 19–25). Participants who reported psychotic experiences at baseline but not at follow-up were classified as having transient psychotic experiences. Data from both time-points were used to examine the association between transient psychotic experiences and self-reported interpersonal and educational/ vocational difficulties in young adulthood using poisson regression modelling. Results Young people with a history of transient psychotic experiences reported significantly higher interpersonal (adj IRR: 1.83, 95%ileCI: 1.10–3.02, p = .02) and educational/vocational (adj IRR: 2.28, 95%ileCI: 1.43–3.64, p = .001) difficulties during adolescence. However, no significant differences in interpersonal (adj IRR: 0.49, 95%ileCI: 0.10–2.30, p = .37) or educational/vocational (adj IRR: 0.88, 95%ileCI: 0.37–2.08, p = .77) difficulties were found in young adulthood. Self-reported interpersonal and educational/vocational difficulties in young people both with and without a history of transient psychotic experiences decreased between adolescence and young adulthood. Conclusions Young people with transient psychotic experiences have increased interpersonal and educational/vocational difficulties in adolescence but these may not persist into the young adult years. This finding indicates that early psychotic experiences may not confer high risk for long-term interpersonal or educational/vocational deficits among young people who experience these phenomena transiently.

Abstract Much microbiome research has focused on populations that are predominantly of European descent, and from narrow demographics that do not capture the socio-economic and lifestyle differences which impact human health. Here we examined the airway microbiomes of the Orang Asli, the indigenous peoples of Malaysia. A total of 130 participants were recruited from two sites in the north-eastern state of Terengganu in Peninsular Malaysia. Using 16S rRNA sequencing, the nasal microbiome was significantly more diverse in those aged 5–17 years compared to 50+ years (p = 0.023) and clustered by age (PERMANOVA analysis of the Bray–Curtis distance, p = 0.001). Hierarchical clustering of Bray–Curtis dissimilarity scores revealed six microbiome clusters. The largest cluster (n = 28; 35.4%) had a marked abundance of Corynebacterium. In the oral microbiomes Streptococcus, Neisseria and Haemophilus were dominant. Using conventional microbiology, high levels of Staphylococcus aureus carriage were observed, particularly in the 18–65 age group (n = 17/36; 47.2% 95% CI: 30.9–63.5). The highest carriage of pneumococci was in the