Sustaining effective COVID-19 control in Malaysia through large-scale vaccination

Introduction: As of 3rd June 2021, Malaysia is experiencing a resurgence of COVID-19 cases. In response, the federal government has implemented various non-pharmaceutical interventions (NPIs) under a series of Movement Control Orders and, more recently, a vaccination campaign to regain epidemic control. In this study, we assessed the potential for the vaccination campaign to control the epidemic in Malaysia and four high-burden regions of interest, under various public health response scenarios. Methods: A modified susceptible-exposed-infectious-recovered compartmental model was developed that included two sequential incubation and infectious periods, with stratification by clinical state. The model was further stratified by age and incorporated population mobility to capture NPIs and micro-distancing (behaviour changes not captured through population mobility). Emerging variants of concern (VoC) were included as an additional strain competing with the existing wild-type strain. Several scenarios that included different vaccination strategies (i.e. vaccines that reduce disease severity and/or prevent infection, vaccination coverage) and mobility restrictions were implemented. Results: The national model and the regional models all fit well to notification data but underestimated ICU occupancy and deaths in recent weeks, which may be attributable to increased severity of VoC or saturation of case detection. However, the true case detection proportion showed wide credible intervals, highlighting incomplete understanding of the true epidemic size. The scenario projections suggested that under current vaccination rates complete relaxation of all NPIs would trigger a major epidemic. The results emphasise the importance of micro-distancing, maintaining mobility restrictions during vaccination roll-out and accelerating the pace of vaccination for future control. Malaysia is particularly susceptible to a major COVID-19 resurgence resulting from its limited population immunity due to the country's historical success in maintaining control throughout much of 2020

Factors associated with asymptomatic COVID-19 patients in Petaling District, Selangor, Malaysia

The rapid spread of the Coronavirus disease 2019 (COVID-19) worldwide has led the World Health Organization to declare COVID-19 outbreak as a pandemic on March 11, 2020. As the local studies on factors leading to the absence or presence of clinical illness among the COVID-19 cases are sparse, the study aims to determine the factors associated with asymptomatic COVID-19 patients in Petaling District, Selangor, Malaysia. Data on COVID-19 patients were extracted from the database of confirmed cases in Petaling District Health Office, Selangor, Malaysia from 3rd February 2020 to 30th April 2020. An asymptomatic laboratory-confirmed case is a person infected with COVID-19 who does not develop any symptoms. The study included socio-demographic variables, the detailed information on clinical manifestations and co-morbidity of the patients. Descriptive and multiple logistic regression analyses were conducted to determine the factors associated with asymptomatic patients. The overall COVID-19 patients in Petaling District were 434. Approximately 70% (n= 292) of the patients were symptomatic while 32.7% (n= 142) were asymptomatic. Multivple logistic regression analyses revealed that factors significantly associated with asymptomatic patients were age below 40 years old (aOR: 1.79, 95% CI 1.11, 2.86), non-Malaysians (aOR: 3.22, 95% CI 1.44, 7.19) and local cases (aOR: 2.51, 95% CI 1.42, 4.42). Gender, ethnicity, co-morbidity and township were not significantly associated with asymptomatic patients. Approximately one-third of COVID-19 patients were asymptomatic and the risk factors identified were younger age, non-Malaysians and local cases. Rigorous epidemiological investigation is helpful in identifying COVID-19 cases among these group of people who are asymptomatic

COVID-19 collaborative modelling for policy response in the Philippines, Malaysia and Vietnam

Mathematical models that capture COVID-19 dynamics have supported public health responses and policy development since the beginning of the pandemic, yet there is limited discourse to describe features of an optimal modelling platform to support policy decisions or how modellers and policy makers have engaged with each other. Here, we outline how we used a modelling software platform to support public health decision making for the COVID-19 response in the Western Pacific Region (WPR) countries of the Philippines, Malaysia and Viet Nam. This perspective describes an approach to support evidence-based public health decisions and policy, which may help inform other responses to similar outbreak events. The platform we describe formed the basis for one of the inaugural World Health Organization (WHO) Western Pacific (WPRO) Innovation Challenge awards, and was backed by collaboration between epidemiological modellers, those providing public health advice, and policy makers

Cellular Mechanism Underlying Hydrogen Sulfide Mediated Epithelial K+ Secretion in Rat Epididymis

As a novel gasotransmitter, hydrogen sulfide (H2S) elicits various physiological actions including smooth muscle relaxation and promotion of transepithelial ion transport. However, the pro-secretory function of H2S in the male reproductive system remains largely unclear. The aim of this study is to elucidate the possible roles of H2S in modulating rat epididymal intraluminal ionic microenvironment essential for sperm storage. The results revealed that endogenous H2S-generating enzymes cystathionine β-synthetase (CBS) and cystathionine γ-lyase (CSE) were both expressed in rat epididymis. CBS located predominantly in epithelial cells whilst CSE expressed primarily in smooth muscle cells. The relative expression level of CBS and CSE escalated from caput to cauda regions of epididymis, which was paralleled to the progressively increasing production of endogenous H2S. The effect of H2S on epididymal epithelial ion transportation was investigated using short-circuit current (ISC), measurement of intracellular ion concentration and in vivo rat epididymal microperfusion. Our data showed that H2S induced transepithelial K+ secretion via adenosine triphosphate-sensitive K+ (KATP) channel and large conductance Ca2+-activated K+ (BKCa) channel. Transient receptor potential vanilloid 4 (TRPV4) channel-mediated Ca2+ influx was implicated in the activation of BKCa channel. In vivo studies further demonstrated that H2S promoted K+ secretion in rat epididymal epithelium. Inhibition of endogenous H2S synthesis caused a significant decrease in K+ concentration of cauda epididymal intraluminal fluid. Moreover, our data demonstrated that high extracellular K+ concentration actively depressed the motility of cauda epididymal sperm in a pH-independent manner. Collectively, the present study demonstrated that H2S was vital to the formation of high K+ concentration in epididymal intraluminal fluid by promoting the transepithelial K+ secretion, which might contribute to the maintenance of the cauda epididymal sperm in quiescent dormant state before ejaculation

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Non-invasive diagnostic tests for Helicobacter pylori infection

BACKGROUND: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES: To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS: We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA: We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as13C or14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS: We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS: In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions

A Clustering Algorithm for Heterogeneous Wireless Sensor Networks Based on Solar Energy Supply

Limited battery power directly affects the performance and survival time of sensor networks. In this study, solar energy was used to provide additional energy for sensor nodes, and a clustering algorithm for heterogeneous wireless sensor networks (WSNs) based on a solar energy supply is proposed. A cluster head is selected on the basis of the self-replenishment state and the remaining energy of the nodes. A cluster-head selection mechanism and network layer multi-hop routing are adopted to balance the energy consumption of the network. A set of experiments showed that the proposed algorithm can effectively prolong the network lifetime, improve the stability and efficiency of the network, and balance the energy consumption compared with other algorithms under the same environmental energy supply