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BackgroundThe inappropriate use of prescription medication has recently garnered worldwide attention, but most national policies do not effectively provide for early detection or timely intervention. ObjectiveThis study aimed to develop and assess the validity of a model that can detect the inappropriate use of prescription medication. This effort combines a multiview and topic matching method. The study also assessed the validity of this approach. MethodsA multiview extension of the latent Dirichlet allocation algorithm for topic modeling was chosen to generate diagnosis-medication topics, with data obtained from the Chinese Monitoring Network for Rational Use of Drugs (CMNRUD) database. Topic mapping allowed for calculating the degree to which diagnoses and medications were similarly distributed and, by setting a threshold, for identifying prescription misuse. The Beijing Regional Prescription Review Database (BRPRD) database was used as the gold standard to assess the model’s validity. We also conducted a sensitivity analysis using random samples of validated prescriptions and evaluated the model’s performance. ResultsA total of 44 million prescriptions were used to generate topics using the diagnoses and medications from the CMNRUD database. A random sample (15,000 prescriptions) from the BRPRD was used for validation, and it was found that the model had a sensitivity of 81.8%, specificity of 47.4%, positive-predictive value of 14.5%, and negative-predictive value of 96.0%. The model showed superior stability under different sampling proportions. ConclusionsA method that combines multiview topic modeling and topic matching can detect the inappropriate use of prescription medication. This model, which has mediocre specificity and moderate sensitivity, can be used as a primary screening tool and will likely complement and improve the process of manually reviewing prescriptions.

Abstract Background Point-of-care testing (POCT) is commonly used in epidemiological surveys due to its various advantages, such as portability and immediate test results. The CardioChek® PA analyser 3-in-1 lipid panel measures total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. This study tested the reliability and diagnostic accuracy of the CardioChek® PA analyser using a 3-in-1 lipid panel. Methods A cross-sectional study design with quota sampling was used. A total of 203 respondents aged 18 years and above from a research centre in the Ministry of Health, Malaysia, were recruited. Venous blood was sent to the laboratory and tested with Siemens Atellica CH, while a POCT analyser was used for capillary blood measurements. Intraclass coefficient correlation (ICC) analysis was employed to determine the agreement between capillary and venous blood parameters. The diagnostic performance of the evaluated tests was evaluated using STATA version 12. Results The agreement between capillary and laboratory venous blood was moderate (0.64–0.67) for TC and HDL, good (0.75) for LDL and excellent (0.91) for TG). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were as follows: TC, 57.1%, 94.3%, 92.3% and 64.8%; TG, 76.0%, 100%, 100%, and 96.6%; HDL, 96.2%, 83.2%, 47.2% and 99.3%; and LDL, 81.0%, 100%, 100% and 68.3%, respectively. Conclusions The CardioChek® PA analyser showed acceptable diagnostic accuracy for screening high-risk individuals more often in places where laboratories are inaccessible. It could also be used in clinical settings where patients would benefit from swift treatment decisions.

Abstract Objectives Public Health Social Measures (PHSM) such as movement restriction movement needed to be adjusted accordingly during the COVID-19 pandemic to ensure low disease transmission alongside adequate health system capacities based on the COVID-19 situational matrix proposed by the World Health Organization (WHO). This paper aims to develop a mechanism to determine the COVID-19 situational matrix to adjust movement restriction intensity for the control of COVID-19 in Malaysia. Methods Several epidemiological indicators were selected based on the WHO PHSM interim guidance report and validated individually and in several combinations to estimate the community transmission level (CT) and health system response capacity (RC) variables. Correlation analysis between CT and RC with COVID-19 cases was performed to determine the most appropriate CT and RC variables. Subsequently, the CT and RC variables were combined to form a composite COVID-19 situational matrix (SL). The SL matrix was validated using correlation analysis with COVID-19 case trends. Subsequently, an automated web-based system that generated daily CT, RC, and SL was developed. Results CT and RC variables were estimated using case incidence and hospitalization rate; Hospital bed capacity and COVID-19 ICU occupancy respectively. The estimated CT and RC were strongly correlated [ρ = 0.806 (95% CI 0.752, 0.848); and ρ = 0.814 (95% CI 0.778, 0.839), p

Abstract Erectile dysfunction (ED) is a pervasive problem among men, often shrouded in silence and stigma. This manuscript analysed the National Health and Morbidity Survey 2019 data to identify the prevalence of moderate to severe ED among men aged 18 and above in Malaysia and describe its associated factors. Self-administered questionnaire on ED utilised a locally validated International Index of Erectile Function. Variables on sociodemographics, risky lifestyles and comorbidities were obtained via an interviewer-administered questionnaire. The prevalence was determined using complex sampling analysis, and logistic regression was used to determine the associated factors of ED. A sample of 2403 men aged ≥ 18 participated, with a moderate to severe ED prevalence was 31.6% (95% CI 28.8, 34.6). The mean (± SD) of the total score of IIEF-5 for overall respondents was 18.16 (± 4.13). Multiple logistic regression analysis revealed a significant association between moderate to severe ED among men aged 60 years and above, single or divorcee, men without formal, primary, and secondary education, non-government employees, unemployed, and retiree, as well as physically inactive men. Focused public health interventions are necessary to improve education in sexual health, increase health promotion programs, and promote healthy ageing across the population.

AIM: To analyze the current status, hotspots and trends of studies on the treatments of diabetic retinopathy.METHODS: Relevant literatures on diabetic retinopathy in Chinese National Knowledge Infrastructure(CNKI)and Web of Science core collection database were retrieved from creation to June 15, 2023, and CiteSpace 6.2.R2 and VOSviewer were used to conduct visualized analysis with the country/issuing institution, research author and keywords.RESULTS: A total of 5 919 Chinese literatures and 11 475 English literatures were included. The top three countries with global publications are the United States, China and the United Kingdom, respectively. The top three institutions for issuing articles at abroad are Harvard Medical School, Harvard University and Johns Hopkins University, while the top three institutions for issuing articles in China are the Eye Hospital of China Academy of Chinese Medical Science, Hunan University of Chinese Medicine, and Zhongshan Ophthalmic Center of Sun Yat-sen University. The research results of high-frequency keywords in both Chinese and English show that the laser photocoagulation, vitrectomy, traditional Chinese medicine therapy, vascular endothelial growth factor and ranibizumab are research hotspots.CONCLUSIONS: In recent years, the research hotspots of diabetic retinopathy mainly focus on surgery, vascular protective agents, traditional Chinese medicine therapy, anti-vascular endothelial growth factor, etc., and the research trend mainly focuses on anti-vascular endothelial growth factor drugs.

Abstract Background Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. Methods Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. Results T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. Conclusion This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis. Graphical Abstract

Introduction In 2022, the Advisory Committee on Immunization Practices (ACIP) updated its recommendation regarding hepatitis B vaccination and advised vaccination for all adults aged 19–59 regardless of risk factors and those 60 years and older with risk factors. Adults 60 years and older without known risk factors may also be vaccinated. Our project aimed to spread awareness of the updated hepatitis B virus (HBV) vaccination guideline and improve HBV vaccination rates among veterans in a resident-based primary care clinic.Methods Preintervention data were collected from October to December 2021 and post intervention data were collected from March to May 2022; patients seen in the clinic during these months were included. Patients were considered immune against HBV if they had positive anti-hepatitis B surface antigen and susceptible to infection if the hepatitis B panel was negative. Interventions included educating each resident group regarding current guidelines via multifaceted modalities. In addition, a reminder for checking hepatitis B status was embedded in the veterans affairs (VA) electronic medical record.Results In the preintervention period from October to December 2021, a total of 1242 veterans were seen. 532 veterans had previous screening for hepatitis B immunity in the chart with 378 veterans negative for hepatitis B surface antibody. Of those 378 veterans, only 35 were vaccinated against hepatitis B during the time period studied. In the postintervention period, 1174 veterans were seen and 559 had prior hepatitis B immunity screening with 430 veterans negative for hepatitis B surface antibody. Of the 430 veterans with no immunity against HBV, 123 received hepatitis B vaccination during the time period studied, which is an increase of greater than 20% in the number of veterans vaccinated.Discussion Our data suggest that HBV vaccination rate was suboptimal among the veteran population. A low-cost intervention could be beneficial in integrating new vaccination guidelines in the VA standard of care. Increased awareness of the updated HBV vaccination guideline would likely help to achieve the goal of full vaccination among the veteran population.

Abstract Background Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with ventricular arrhythmia, heart failure (HF), and sudden death. Thromboembolism is also an important and serious complication of ARVC/D. However, the etiology of ARVC/D and thromboembolism and their association with genetic mutations are unclear. Methods Genomic DNA samples of peripheral blood were conducted for whole-exome sequencing (WES) and Sanger sequencing in the ARVC/D family. Then, we performed bioinformatics analysis for genes susceptible to cardiomyopathies and arrhythmias. Further, we analyzed how the potential pathogenic mutations were affecting the hydrophobicity and phosphorylation of amino acids and their joint pathogenicity by ProtScale, NetPhos and ORVAL algorisms. Results We discovered a Chinese Han family of ARVC/D with right ventricular HF (RVHF), cerebral thromboembolism, arrhythmias (atrial fibrillation, atrial standstill, multifocal ventricular premature, complete right bundle block and third-degree atrioventricular block) and sudden death. Based on the WES data, the variants of LMNA p.A242V, LAMA4 p.A225P and RYR2 p.T858M are highly conserved and predicated as “deleterious” by SIFT and MetaSVM algorithms. Their CADD predicting scores are 33, 27.4 and 25.8, respectively. These variants increase the hydrophobicity of their corresponding amino acid residues and their nearby sequences by 0.378, 0.266 and 0.289, respectively. The LAMA4 and RYR2 variants lead to changes in protein phosphorylation at or near their corresponding amino acid sites. There were high risks of joint pathogenicity for cardiomyopathy among these three variants. Cosegregation analysis indicated that LMNA p.A242V might be an important risk factor for ARVC/D, electrocardiogram abnormality and cerebral thromboembolism, while LAMA4 p.A225P may be a pathogenic etiology of ARVC/D and hereditary electrocardiogram abnormality. Conclusions The LMNA p.A242V may participate in the pathogenesis of familial ARVC/D with RVHF and cerebral thromboembolism, while LAMA4 p.A225P may be associated with ARVC/D and hereditary electrocardiogram abnormality.

BackgroundExcision repair cross-complementing group 1 (ERCC1) was considered a potential candidate gene for ischemic stroke, and its polymorphisms might be associated with the susceptibility to ischemic stroke.MethodsA total of 513 patients with ischemic stroke and 550 control subjects were recruited. The expression levels of ERCC1 messenger RNA (mRNA) in peripheral blood mononuclear cells and its protein in plasma were detected by quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Rs3212986 polymorphism of ERCC1 was detected by PCR-restriction fragment length polymorphism (RFLP-PCR) and was confirmed by sequencing. The association between the ERCC1 rs3212986 polymorphism or its expression and ischemic stroke was further analyzed.ResultsThe ERCC1 mRNA level in patients with ischemic stroke was lower than that in the control group (P < 0.05). However, the ERCC1 protein level in patients with ischemic stroke was higher than that in the control group (P < 0.05). The A allele of rs3212986 was associated with increased ischemic stroke risk (OR = 1.287, 95% CI = 1.076–1.540, P = 0.006). The association between rs3212986 polymorphism and ischemic stroke susceptibility was found in both recessive (OR = 2.638, 95% CI = 1.744–3.989, P < 0.001) and additive models (OR = 1.309, 95% CI = 1.028–1.667, P = 0.031), respectively. Similar results were obtained in the recessive model (OR = 2.015, 95% CI = 1.087–3.704, P = 0.026) after adjusting for demographic information and other variables. Additionally, the level of ERCC1 mRNA in the CC/CA genotype was higher than that in the AA genotype (P < 0.05).ConclusionIt was suggested that the ERCC1 rs3212986 polymorphism was associated with ischemic stroke susceptibility in a Chinese Han population and that an A allele of rs3212986 was related to increased ischemic stroke risk. The altered ERCC1 expression level caused by the rs3212986 polymorphism might participate in the pathophysiological process of ischemic stroke.

Background: Point-of-care testing (POCT) is commonly used in epidemiological surveys due to its various advantages, such as portability and immediate test results. The CardioChek® PA analyser 3-in-1 lipid panel measures total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. This study tested the reliability and diagnostic accuracy of the CardioChek® PA analyser using a 3-in-1 lipid panel. Methods: A cross-sectional study design with quota sampling was used. A total of 203 respondents aged 18 years and above from a research centre in the Ministry of Health, Malaysia, were recruited. Venous blood was sent to the laboratory and tested with Siemens Atellica CH, while a POCT analyser was used for capillary blood measurements. Intraclass coefficient correlation (ICC) analysis was employed to determine the agreement between capillary and venous blood parameters. The diagnostic performance of the evaluated tests was evaluated using STATA version 12. Results: The agreement between capillary and laboratory venous blood was moderate (0.64–0.67) for TC and HDL, good (0.75) for LDL and excellent (0.91) for TG). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were as follows: TC, 57.1%, 94.3%, 92.3% and 64.8%; TG, 76.0%, 100%, 100%, and 96.6%; HDL, 96.2%, 83.2%, 47.2% and 99.3%; and LDL, 81.0%, 100%, 100% and 68.3%, respectively. Conclusions: The CardioChek® PA analyser showed acceptable diagnostic accuracy for screening high-risk individuals more often in places where laboratories are inaccessible. It could also be used in clinical settings where patients would benefit from swift treatment decisions. [ABSTRACT FROM AUTHOR]

PurposeMutation in the USH2A gene is the most common cause of inherited retinal dystrophy (IRD), including non-syndromic retinitis pigmentosa (RP) and Usher syndrome II (USH2). Gene editing and therapy targeting USH2A, especially the hotspot region, would benefit a large proportion of IRD patients. In this study, we comprehensively analyzed the genetic spectrum of the USH2A gene, aiming to identify global hot spot mutations in USH2A-related IRDs and differences in hot spot regions across continents.Materials and methodsA retrospective USH2A-related IRD study was conducted, including our IRD cohort, and reported USH2A studies worldwide.ResultsA total of 3,972 mutated USH2A alleles of approximately 1,935 patients were collected from 33 cohort studies worldwide, containing 102 alleles of 51 patients in our IRD cohort. Mutations in exon 13 were the most common, reaching 18.4% globally and a higher frequency of 22% in America, 19.2% in Europe, and a lower 12% in East Asia. Pathogenic mutations that affected 10 of the 72 exons of USH2A, exon 2, exon 13, exon 41–43, exon 50, exon 54, exon 57, exon 61, and exon 63 in total were responsible for half of global USH2A mutant alleles. With base editors including adenine base editor (ABE), cytidine base editor (CBE), and glycosylase base editor (GBE), 76.3% of single nucleotide variations (SNVs) and 58% of all mutations in USH2A are correctable. Meantime, four novel pathogenic mutations were revealed in our IRD cohort, p. (Val1130Cysfs*72), p. (Ala2139fs*14), p. (Gly4139Arg), and p. (Val4166Cysfs*7).ConclusionIn this study, we revealed four novel mutations, expanding the spectrum of USH2A mutations, and importantly presented global hotspot exons and mutations of USH2A as well as the proportion of SNVs that can be restored by different base editors, providing a perspective for exploring high-efficiency and broader-reaching gene editing and gene therapies.

BackgroundExisting anthropometric studies for respirator designs are based on the head and facial dimensions of Americans and Chinese nationals, with no studies for multi-ethnic countries like Malaysia. This study aimed to create head and facial morphological database for Malaysia, specifically to identify morphological differences between genders, ethnicities, and birthplaces, as well as predictors of the dimensions.DesignA cross-sectional study.SettingMalaysia.ParticipantsA nation-wide cross-sectional study using a complex survey design with two stage-stratified random sampling was conducted among 3,324 participants, aged 18 years and above who were also participants of the National Health and Morbidity Survey 2020.Primary and secondary outcomesThe study collected data on sociodemographic, measurement of Body Mass Index (BMI) and 10 head and facial dimensions (3 dimensions were measured using direct measurement, and 7 others using Digimizer software for 2-dimension images). Linear regression was performed to determine the association between gender, ethnicity, birthplace, age and BMI and the dimensions.ResultsThere were significant differences in all the dimensions between sex, birthplace and ethnicity (p < 0.005). Further analysis using linear regression showed sex, ethnicity, birthplace, age and BMI were significant predictors of the dimensions. In comparison to studies from the United States and China, our study population had a wider interpupillary distance and nose breadth for both male and female participants, but smaller bigonial breadth and smaller minimal frontal breadth.ConclusionThese findings could assist in the design and sizing of respirators that will fit Malaysians and possibly other Southeast Asian population.

Depression is the most common mental health problem affecting adolescents globally, wherein its increasing prevalence together with the negative health impacts escalates the need for further research in this area. This work determined the prevalence and factors associated with depressive symptoms among young adolescents in Malaysia. A total of 1350 adolescent aged 13 to 14 years in school across nine secondary schools in Selangor state, Malaysia participated in a cross-sectional study. Independent variables were examined using the using the Global School-Based Student Health Survey included age, gender, ethnicity, alcohol intake, smoking and illicit drug use, loneliness, bullying, parental marital status, income and supervision; and the Health Literacy and Stigma questionnaire examined mental health literacy levels. Depressive symptoms were the dependent variable which was examined using the Center for Epidemiology Study Depression (CESD) instrument. Prevalence of depressive symptoms among all participants was 19 % (95% CI [16.9, 21.2]), with a higher prevalence of depressive symptoms being reported among females 26.3% (95% CI [23.0, 29.8]) compared to males 11.7% (95% CI [9.4, 14.4]). Determinants namely females (AOR = 3.83; 95% CI [2.66, 5.52]), smoking (AOR = 6.16; 95% CI [3.15, 12.05]), been bullied (AOR = 3.70; 95% CI [2.51, 5.47]), felt lonely (AOR = 10.46; 95% CI [7.09, 15.42]) and having no parental supervision (AOR = 1.79; 95% CI [1.26, 2.53]) significantly increased the odds of depressive symptoms among all adolescents in the multivariate model. In addition, feeling lonely, being bullied and smoking were identified as common significant determinants of depressive symptoms across both genders. Feeling lonely (65% to 71%) and being bullied (10% to 19%) were ranked as the most important determinants of depressive symptoms among young adolescents. Tackling these factors would be instrumental in helping decision makers formulate depression prevention strategies and activities for adolescents.