Browse publications by year: 2022

  1. Wan KS, Hairi NN, Mustapha F, Ismail M, Mohd Yusoff MF, Moy FM
    PeerJ, 2022;10:e13816.
    PMID: 36317122 DOI: 10.7717/peerj.13816
    BACKGROUND: Patients with diabetes have increased risks of cardiovascular diseases (CVD), and their LDL-cholesterol (LDL-C) has to be treated to target to prevent complications. We aim to determine the LDL-C trend and its predictors among patients with type 2 diabetes (T2D) in Malaysia.

    METHODS: This was a retrospective open cohort study from 2013 to 2017 among T2D patients in public primary health care clinics in Negeri Sembilan state, Malaysia. Linear mixed-effects modelling was conducted to determine the LDL-C trend and its predictors. The LDL-C target for patients without CVD was <2.6 mmol/L, whereas <1.8 mmol/L was targeted for those with CVD.

    RESULTS: Among 18,312 patients, there were more females (55.9%), adults ≥60 years (49.4%), Malays (64.7%), non-smokers (93.6%), and 45.3% had diabetes for <5 years. The overall LDL-C trend reduced by 6.8% from 2.96 to 2.76 mmol/L. In 2017, 16.8% (95% CI: 13.2-21.0) of patients without CVD and 45.8% (95% CI: 44.8-46.8) of patients with CVD achieved their respective LDL-C targets. The predictors for a higher LDL-C trend were younger adults, Malay and Indian ethnicities, females, dyslipidemia, and diabetes treatment with lifestyle modification and insulin. Longer diabetes duration, obesity, hypertension, retinopathy, statin therapy, achievement of HbA1c target and achievement of BP target were independent predictors for a lower LDL-C trend.

    CONCLUSIONS: The LDL-C trend has improved, but there are still gaps between actual results and clinical targets. Interventions should be planned and targeted at the high-risk populations to control their LDL-C.

    MeSH terms: Adult; Female; Humans; Cholesterol, LDL/therapeutic use; Retrospective Studies; Cohort Studies
  2. Marwali EM, Kekalih A, Yuliarto S, Wati DK, Rayhan M, Valerie IC, et al.
    BMJ Paediatr Open, 2022 Oct;6(1).
    PMID: 36645791 DOI: 10.1136/bmjpo-2022-001657
    BACKGROUND: The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.

    METHODS: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.

    RESULTS: A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).

    CONCLUSION: Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.

    MeSH terms: Adolescent; Child; Health Resources; Humans; Tuberculosis*; Pandemics
  3. Chan HT, Keung MHT, Nguyen I, Ip ELO, Chew SM, Siler D, et al.
    J Clin Virol Plus, 2022 Aug;2(3):100079.
    PMID: 35528049 DOI: 10.1016/j.jcvp.2022.100079
    OBJECTIVES: To examine the comparative stochasticity profile of six commercial SARS-CoV-2 nucleic acid amplification tests (NAATs) and how this may affect retesting paradigms.

    METHODS: Commercial quality control (QC) material was serially diluted in viral transport media to create a panel covering 10-10,000 copies/ml. The panel was tested across six commercial NAATs. A subset of high cycle threshold results was retested on a rapid PCR assay to simulate retesting protocols commonly used to discriminate false positives.

    RESULTS: Performance beyond the LOD differed among assays, with three types of stochasticity profiles observed. The ability of the rapid PCR assay to reproduce a true weak positive specimen was restricted to its own stochastic performance at the corresponding viral concentration.

    CONCLUSION: Stochastic performance of various NAATs overlap across low viral concentrations and affect retesting outcomes. Relying on retesting alone to discriminate false positives risk missing true positives even when a more sensitive assay is deployed for confirmatory testing.

  4. Kazeminia M, Salari N, Shohaimi S, Akbari H, Mohammadi M
    J Diabetes Metab Disord, 2022 Jun;21(1):1029-1036.
    PMID: 35673410 DOI: 10.1007/s40200-022-00974-9
    BACKGROUND: Type 2 diabetes is the most common diabetes in the world and constitutes a high percentage of diabetes cases. This study aims to determine the overall prevalence of gastrointestinal complaints in Iranian patients with type 2 diabetes.

    METHODS: The articles were extracted based on entry and exit criteria by searching the Cochrane (Embase), ScienceDirect databases. Scopus PubMed; And Web of Science (WoS), based on PRISMA 2009. To evaluate the studies, a 22-item STROBE checklist was selected and related items were used.

    RESULTS: The probability of publication bias in reporting the results was examined by the Egger test (P = 0.891). The prevalence rate of gastrointestinal complaints in patients with type 2 diabetes in Iran in 10 studies was 52.3% (95% CI: 33.4-70.7%). The results of metargression showed a significant difference between the sample size and the prevalence of gastrointestinal complaints in patients with type 2 diabetes (P 

  5. Chan JS, Nurul-Ain M, Mohamad NF, Wan Hitam WH, Thavaratnam LK
    Neuroophthalmology, 2022;46(4):258-263.
    PMID: 35859635 DOI: 10.1080/01658107.2021.2014892
    Optic neuritis associated with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis poses a novel challenge and is recognised as being part of overlapping antibody-associated demyelinating syndromes. We report a case of a 10-year-old girl who first presented with anti-NMDAR encephalitis and later developed four episodes of left optic neuritis. Blurring of vision, pain on eye movement, and headache were the striking features in all episodes of optic neuritis. For each recurrent episode of optic neuritis she was treated with intravenous methylprednisolone, following which visual acuity, colour vision, and visual field improved to normal. Neuroimaging was unremarkable. Myelin oligodendrocyte glycoprotein and aquaporin-4 antibody tests were negative. She developed a relapse of anti-NMDAR encephalitis after recurrent episodes of optic neuritis despite being on azathioprine. Intravenous immunoglobulin and cycles of cyclophosphamide were started, and she has been free from optic neuritis and encephalitis for more than one year since. Optic neuritis and anti-NMDAR encephalitis are reversible with intensive immunotherapy. Early and accurate diagnosis can lead to better management of this condition.
  6. Jamaludin NA, Jamaluddin JAF, Rahim MA, Mohammed Akib NA, Ratmuangkhwang S, Mohd Arshaad W, et al.
    PeerJ, 2022;10:e13706.
    PMID: 35860045 DOI: 10.7717/peerj.13706
    The spotted sardinella, Amblygaster sirm (Walbaum, 1792), is a commercial sardine commonly caught in Malaysia. Lack of management of these marine species in Malaysian waters could lead to overfishing and potentially declining fish stock populations. Therefore, sustainable management of this species is of paramount importance to ensure its longevity. As such, molecular information is vital in determining the A. sirm population structure and management strategy. In the present study, mitochondrial DNA Cytochrome b was sequenced from 10 A. sirm populations: the Andaman Sea (AS) (two), South China Sea (SCS) (six), Sulu Sea (SS) (one), and Celebes Sea (CS) (one). Accordingly, the intra-population haplotype diversity (Hd) was high (0.91-1.00), and nucleotide diversity (π) was low (0.002-0.009), which suggests a population bottleneck followed by rapid population growth. Based on the phylogenetic trees, minimum spanning network (MSN), population pairwise comparison, and F ST,and supported by analysis of molecular variance (AMOVA) and spatial analysis of molecular variance (SAMOVA) tests, distinct genetic structures were observed (7.2% to 7.6% genetic divergence) between populations in the SCS and its neighboring waters, versus those in the AS. Furthermore, the results defined A. sirm stock boundaries and evolutionary between the west and east coast (which shares the same waters as western Borneo) of Peninsular Malaysia. In addition, genetic homogeneity was revealed throughout the SCS, SS, and CS based on the non-significant F STpairwise comparisons. Based on the molecular evidence, separate management strategies may be required for A. sirm of the AS and the SCS, including its neighboring waters.
    MeSH terms: Animals; China; Conservation of Natural Resources*; Fisheries*; Fishes/genetics; Mitochondria/genetics; Phylogeny
  7. Aziz Alimul Hidayat A, Chen WL, Nor RM, Uliyah M, Badriyah FL, Ubudiyah M
    PeerJ, 2022;10:e13764.
    PMID: 35910779 DOI: 10.7717/peerj.13764
    OBJECTIVE: This study aims to determine the factors associated with patient care manager role and the implementation of the clinical pathway among nurses in private hospitals.

    METHODS: This study was conducted from January-July 2021 using the cross-sectional approach. The sample consisted of 168 nurses working in a private hospital in Surabaya City, East Java, Indonesia. Meanwhile, the data were collected using the Patient Care Manager Role Scale (PCMRS) and analyzed by multiple logistic regression to find the correlation between the variables.

    RESULTS: A higher percentage of nurses namely 64.3% had compliance in COVID-19 clinical pathways with an average PCMRS score of 27.81 ± 2.43. Nurses with a high-level patient care manager role level had a significant compliance risk with odds ratio [OR] 440.137, 95% confidence interval [CI] [51.850-3736.184], and p-value = 0.000 compared to those with a low role.

    CONCLUSION: The role of patient care manager and compliance with COVID-19 clinical pathways correlated significantly. Based on the results, several actions are needed for the early identification of patient service managers' roles to ensure compliance with COVID-19 clinical pathways and reduce the number of cases in Indonesia.

    MeSH terms: Cross-Sectional Studies; Patient Care; Humans; Hospitals, Private; Critical Pathways*
  8. Abu Bakar SA, Syed Mohamed Shahruddin SNS, Ismail N, Wan Md Adnan WAH
    PeerJ, 2022;10:e13694.
    PMID: 35935256 DOI: 10.7717/peerj.13694
    The estimation of biological age (BA) is an important asymptomatic measure that can be used to understand the physical changes and the aging process of a living being. Factors that contribute towards profiling the human biological age can be diverse. Therefore, this study focuses on developing a BA model for patients with Chronic Kidney Disease (CKD). The procedure commences with the selection of significant biomarkers using a correlation test. Appropriate weighting is then assigned to each selected biomarker using the indexing method to produce a BA index. The BA index is matched to the age variation within the sample to acquire additional terms for the chronological age leading ultimately to the estimated BA. From a sample of 190 patients (133 trained data and 57 testing data) obtained from the University of Malaya Medical Centre (UMMC), Malaysia, the intensity of the BA is found to be between three to nine years from the chronological age. Visual observations further validate the high similarities between the training and testing data sets.
    MeSH terms: Aging; Humans; Models, Biological; Physical Examination*; Biomarkers
  9. Yew CT, Gurumoorthy N, Nordin F, Tye GJ, Wan Kamarul Zaman WS, Tan JJ, et al.
    PeerJ, 2022;10:e13704.
    PMID: 35979475 DOI: 10.7717/peerj.13704
    HIV-1 derived lentiviral vector is an efficient transporter for delivering desired genetic materials into the targeted cells among many viral vectors. Genetic material transduced by lentiviral vector is integrated into the cell genome to introduce new functions, repair defective cell metabolism, and stimulate certain cell functions. Various measures have been administered in different generations of lentiviral vector systems to reduce the vector's replicating capabilities. Despite numerous demonstrations of an excellent safety profile of integrative lentiviral vectors, the precautionary approach has prompted the development of integrase-deficient versions of these vectors. The generation of integrase-deficient lentiviral vectors by abrogating integrase activity in lentiviral vector systems reduces the rate of transgenes integration into host genomes. With this feature, the integrase-deficient lentiviral vector is advantageous for therapeutic implementation and widens its clinical applications. This short review delineates the biology of HIV-1-erived lentiviral vector, generation of integrase-deficient lentiviral vector, recent studies involving integrase-deficient lentiviral vectors, limitations, and prospects for neoteric clinical use.
    MeSH terms: Genetic Vectors/genetics; Genome; Transgenes
  10. Rameez MR, Muhamad Ariffin MH
    Cureus, 2022 Dec;14(12):e32459.
    PMID: 36644053 DOI: 10.7759/cureus.32459
    Neglected spinal tuberculosis with severe kyphosis is uncommon. Spinal tuberculosis can present with back pain, neurological deficits, cold abscesses, or severe deformities. Diagnosis is made using laboratory, imaging, and tissue studies. Management can be done medically or surgically. As neurological deficits or severe deformities worsen, most surgeons prefer a surgical option. There have been different opinions regarding the surgical approach for spinal tuberculosis. This is a case of neglected spinal tuberculosis with severe kyphotic deformity treated with single-stage posterior instrumentation and fusion without any complications within in a three-year follow-up period.
  11. Subbiah D, Asiff NH, Hamzah N, Samsudin A
    Cureus, 2022 Dec;14(12):e32498.
    PMID: 36644099 DOI: 10.7759/cureus.32498
    Encephalocraniocutaneous lipomatosis (ECCL) or Haberland syndrome is a neurocutaneous disorder of the skin, eye, and central nervous system. A three-month-old girl was referred to our center for further management of a large left eye corneal dermoid. At birth, a small lesion was noted. Magnetic resonance imaging (MRI) around the first week of life showed an extraocular dermoid cyst measuring 1 mm x 7 mm, dysplasia of the left greater wing of sphenoid, closed-lip schizencephaly of the left parietal lobe, and polymicrogyria. During examination under anesthesia at our center, we found that the corneal dermoid had grown in size to 17 mm x 16 mm, with posterior embryotoxon, a hazy cornea, and intraocular pressure of 26 mmHg. With the anterior segment dysgenesis and secondary glaucoma, we started Gutt Timo-Comod BD. Serial MRI imaging at four months of age revealed further enlargement of the dermoid, a new left retrobulbar mass, and multiple intracranial lipomas. A diagnosis of ECCL was made at this point based on the MRI and clinical findings. A multidisciplinary meeting was held among ophthalmology, neurosurgery, radiology, and otorhinolaryngology (ORL) teams, which concluded that surgical intervention such as tumor debulking might cause more harm than benefit. Hence, she was planned to undergo close monitoring with serial MRIs and only for surgical intervention, in the presence of airway compression or any neurological deficits. The ophthalmologist should be aware of the specific radiological and clinical findings in ECCL as management of the condition would be best through a multidisciplinary approach.
  12. Islam MS, Phoungthong K, Ismail Z, Othman IK, Shahid S, Ishak DSM, et al.
    PMID: 36644961 DOI: 10.1080/10934529.2022.2148811
    The spreading of sewage sludge from wastewater treatment plants and various industries arouses the growing interest due to the contamination by trace elements. Sludges were collected from one sewage treatment plant and two industries in Dhaka City, Bangladesh to assess physicochemical parameters and total and fraction content of trace elements like Cr, Ni, Cu, As, Cd, Pb, Fe, Mn and Zn in sludges. We evaluated the bioavailability of theses metals by determining their speciation by sequential extraction, each metal being distributed among five fractions: exchangeable fraction, bound to carbonate fraction, Fe-Mn oxide bound fraction, organic matter bound fraction and residual fractions. We found that all the analyzed sludges had satisfactory properties from an agronomic quality point of view. The average concentration (mg/kg) of trace metals in sludge samples were in the following decreasing order Fe (12807) > Cr (200) > Mn (158) > Zn (132) > Cu (68.2) > Ni (42.5) > Pb (36.4) > As (35.1) > Cd (3.7). The results of the sequential extraction showed that Cr, Ni, Cu, Fe and Mn were largely associated with the residual fraction where As, Cd and Pb was dominantly associated with the exchangeable and carbonate bound fractions and Zn showed a considerable proportion in carbonate bound fraction. These results showed that regulations must take into account the bioavailability with regard to the characteristics of the agricultural soils on which sludge will be spread.
    MeSH terms: Bangladesh; Cadmium; Lead; Sewage/chemistry; Trace Elements*
  13. Boonhok R, Sangkanu S, Phumjan S, Jongboonjua R, Sangnopparat N, Kwankaew P, et al.
    PeerJ, 2022;10:e13657.
    PMID: 35811814 DOI: 10.7717/peerj.13657
    BACKGROUND: Curcumin is an active compound derived from turmeric, Curcuma longa, and is known for its benefits to human health. The amoebicidal activity of curcumin against Acanthamoeba triangularis was recently discovered. However, a physiological change of intracellular pathways related to A. triangularis encystation mechanism, including autophagy in the surviving amoeba after curcumin treatment, has never been reported. This study aims to investigate the effect of curcumin on the survival of A. triangularis under nutrient starvation and nutrient-rich condition, as well as to evaluate the A. triangularis encystation and a physiological change of Acanthamoeba autophagy at the mRNA level.

    METHODS: In this study, A. triangularis amoebas were treated with a sublethal dose of curcumin under nutrient starvation and nutrient-rich condition and the surviving amoebas was investigated. Cysts formation and vacuolization were examined by microscopy and transcriptional expression of autophagy-related genes and other encystation-related genes were evaluated by real-time PCR.

    RESULTS: A. triangularis cysts were formed under nutrient starvation. However, in the presence of the autophagy inhibitor, 3-methyladenine (3-MA), the percentage of cysts was significantly reduced. Interestingly, in the presence of curcumin, most of the parasites remained in the trophozoite stage in both the starvation and nutrient-rich condition. In vacuolization analysis, the percentage of amoebas with enlarged vacuole was increased upon starvation. However, the percentage was significantly declined in the presence of curcumin and 3-MA. Molecular analysis of A. triangularis autophagy-related (ATG) genes showed that the mRNA expression of the ATG genes, ATG3, ATG8b, ATG12, ATG16, under the starvation with curcumin was at a basal level along the treatment. The results were similar to those of the curcumin-treated amoebas under a nutrient-rich condition, except AcATG16 which increased later. On the other hand, mRNA expression of encystation-related genes, cellulose synthase and serine proteinase, remained unchanged during the first 18 h, but significantly increased at 24 h post treatment.

    CONCLUSION: Curcumin inhibits cyst formation in surviving trophozoites, which may result from its effect on mRNA expression of key Acanthamoeba ATG-related genes. However, further investigation into the mechanism of curcumin in A. triangularis trophozoites arrest and its association with autophagy or other encystation-related pathways is needed to support the future use of curcumin.

    MeSH terms: Amoeba*; Animals; Humans; Trophozoites/physiology
  14. El Tantawi M, Sabbagh HJ, Alkhateeb NA, Quritum M, Abourdan J, Qureshi N, et al.
    PeerJ, 2022;10:e13555.
    PMID: 35860046 DOI: 10.7717/peerj.13555
    BACKGROUND: Oral manifestations and lesions could adversely impact the quality of people's lives. COVID-19 infection may interact with smoking and the impact on oral manifestations is yet to be discovered.

    OBJECTIVES: The aim of this study was to assess the self-reported presence of oral lesions by COVID-19-infected young adults and the differences in the association between oral lesions and COVID-19 infection in smokers and non-smokers.

    METHODS: This cross-sectional multi-country study recruited 18-to-23-year-old adults. A validated questionnaire was used to collect data on COVID-19-infection status, smoking and the presence of oral lesions (dry mouth, change in taste, and others) using an online platform. Multi-level logistic regression was used to assess the associations between the oral lesions and COVID-19 infection; the modifying effect of smoking on the associations.

    RESULTS: Data was available from 5,342 respondents from 43 countries. Of these, 8.1% reported COVID-19-infection, 42.7% had oral manifestations and 12.3% were smokers. A significantly greater percentage of participants with COVID-19-infection reported dry mouth and change in taste than non-infected participants. Dry mouth (AOR=, 9=xxx) and changed taste (AOR=, 9=xxx) were associated with COVID-19- infection. The association between COVID-19-infection and dry mouth was stronger among smokers than non-smokers (AOR = 1.26 and 1.03, p = 0.09) while the association with change in taste was stronger among non-smokers (AOR = 1.22 and 1.13, p = 0.86).

    CONCLUSION: Dry mouth and changed taste may be used as an indicator for COVID-19 infection in low COVID-19-testing environments. Smoking may modify the association between some oral lesions and COVID-19-infection.

    MeSH terms: Adolescent; Adult; Cross-Sectional Studies; Humans; Smoking/adverse effects; Xerostomia*; Young Adult
  15. Al-Mhanna SB, Wan Ghazali WS, Mohamed M, Rabaan AA, Santali EY, H Alestad J, et al.
    PeerJ, 2022;10:e13664.
    PMID: 35935260 DOI: 10.7717/peerj.13664
    BACKGROUND: Cancer is a huge group of diseases that can affect various body parts of humans but also has a psychological, societal, and economic impact. Physical activity can improve the quality of life (QOL) and immunity, while moderate intensity exercise can reduce the probability of this lethal disease. The current study aimed to determine the effect of physical activity on immune markers and QOL in cancer patients as well as to evaluate cancer-related fatigue (CRF) and its association with physical activity.

    METHODOLOGY: Before starting the study, the study protocol was registered in PROSPERO (registration number CRD42021273292). An electronic literature search was performed by combining MeSH terminology and keywords used with the Boolean operators "OR" and "AND" to find relevant published studies on PubMed, Scopus, Cochrane, and ScienceDirect databases. The Joanna Briggs Institute (JBI) critical evaluation checklist was used to assess the quality of selected studies, while the GRADE approach was used to see the quality of evidence.

    RESULTS: A total of 13,931 studies were retrieved after the search on databases. After the scrutiny of studies by reading the title of articles and the inclusion/exclusion criteria, a total of 54 studies were selected for further screening by reading the full texts. In the final, a total of nine studies were selected for the current systematic review and proceeded for data extraction. The patients who were doing different exercises showed improvements in immunity, QOL, and reduction in CRF. A significant reduction in tumour necrosis factor-α (TNF-α), C reactive protein (CRP), interleukin-8 (IL-8), IL-6, and an increase in natural killer (NK) cells levels was also observed.

    CONCLUSIONS: The exercise program is safe and beneficial to improve the quality of life and immunity markers before, during, and after cancer treatment. Physical exercise may also help patients to overcome the adverse effects of the treatment and to reduce the chance of developing new tumours in the future.

    MeSH terms: Exercise Therapy; Humans; Quality of Life*; Biomarkers; Exercise
  16. Hudson J, Cruickshank M, Quinton R, Aucott L, Aceves-Martins M, Gillies K, et al.
    Lancet Healthy Longev, 2022 Jun;3(6):e381-e393.
    PMID: 35711614 DOI: 10.1016/S2666-7568(22)00096-4
    BACKGROUND: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD.

    METHODS: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005.

    FINDINGS: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk.

    INTERPRETATION: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone.

    FUNDING: National Institute for Health Research Health Technology Assessment Programme.

    MeSH terms: Aged; Heart Failure*; Humans; Hypogonadism*; Male; Myocardial Infarction*; Testosterone
  17. Munirah MP, Norhayati MN, Noraini M
    Int J Environ Res Public Health, 2022 Sep 16;19(18).
    PMID: 36141931 DOI: 10.3390/ijerph191811658
    Insomnia is a common complaint affecting human performance in daily life activities. This study aimed to analyze the effects of Crocus sativus on insomnia. Methods: PRISMA guidelines were used according to the PICOS model. A systematic search of PubMed/Medline and the Cochrane Library was undertaken for literature until December 2021. A random effects model was used with I2 statistic to assess heterogeneity and a GRADE assessment was used to assess the quality of the outcomes. Eight articles were included, involving 431 participants. Crocus sativus reduced insomnia severity (SMD: 0.53; 95%CI: -0.05 to 1.11; I2 statistic = 59%; p = 0.08) and increased sleep quality (SMD 0.89, 95% CI 0.10 to 1.68; I2 statistic = 90%; p = 0.03; 6 studies, 308 participants, very low-quality evidence) and duration (SMD: 0.57; 95%CI: 0.21 to 0.93; I2 statistic = 40%; p = 0.002; 5 studies; 220 participants, moderate-quality evidence) compared with the placebos. Although there is limited evidence of a very low- to moderate-quality, Crocus sativus may benefit people with insomnia. This non-pharmacological intervention may reduce the chance of adults with insomnia taking sedative-hypnotic medication, thus reducing dependency and withdrawal symptoms.
    MeSH terms: Adult; Humans; Hypnotics and Sedatives; Crocus*
  18. Cheah KSL, Abdullah Z, Xiao M
    Int J Environ Res Public Health, 2022 Sep 16;19(18).
    PMID: 36141967 DOI: 10.3390/ijerph191811697
    Universities across China have set up crisis management teams (CMTS) to deal with the crisis brought on by the COVID-19 pandemic. This study focuses on how the paternalistic leadership practices of a Chinese university CMT influence crisis strategic decisions by managing conflict. These relationships were verified using hierarchical regression analysis on 312 samples from the surveyed university during the pandemic and found the following: benevolent leadership and moral leadership have positive effects on decision quality. However, unlike most studies on paternalistic leadership, in crisis situations, the negative effects of authoritarian leadership disappear under the mediating effect of affective conflict. This means that affective conflict within CMT fully mediates the relationship between authoritarian leadership and decision quality, and partially mediates the relationship between moral leadership and decision quality, while cognitive conflict partially mediates the relationship between benevolent leadership and crisis decision quality. It indicates that a CMT must stimulate and maintain a certain level of cognitive conflict while suppressing affective conflict to achieve high-quality crisis decision-making. This state can be achieved by practicing lower levels of authoritarian leadership and maintaining high levels of moral and benevolent leadership practices.
    MeSH terms: China/epidemiology; Humans; Leadership*; Universities; Pandemics
  19. Abdul Rahim AA, Jeffree MS, Ag Daud DM, Pang N, Sazali MF
    Int J Environ Res Public Health, 2022 Sep 16;19(18).
    PMID: 36141974 DOI: 10.3390/ijerph191811704
    Musculoskeletal disorder (MSD) is a major health problem, which can lead to an enormous burden to the institution as well as chronic disability to the individual. Teachers are at risk of developing MSD due to the exposure to various ergonomic risk factors. Teachers of special education, for example, are expected to perform extra duty such as lifting and moving students, feeding food, changing diapers, and helping them in ambulation. Although there is an adequate amount of scientific research on MSD's prevalence and its risk factors among regular teachers, only few studies have focused on special education teachers. This review aimed to address these gaps by describing the evidence from various papers on the prevalence of MSD among regular and special education teachers and the related risk factors. The papers have been gathered using electronic databases, including PubMed, Science Direct, Google Scholar, and Springer. The prevalence of MSD among regular teachers ranges from 48.7% to 73.7%, while the prevalence ranges from 38.7% to 94% in special education teachers. Risk factors, such as individual (age, duration of teaching, working hours, and work burden), physical (teaching activities, affected body areas), and psychological factors (stress, anxiety, fear), were identified. From the review, it is recommended to implement ergonomically designed workplaces, comprehensive ergonomic training, psychological approaches, and functional training among teachers at risk.
    MeSH terms: Education, Special; Humans; Human Engineering; Risk Factors; Prevalence
  20. Firus Khan AY, Ramli AS, Abdul Razak S, Mohd Kasim NA, Chua YA, Ul-Saufie AZ, et al.
    Int J Environ Res Public Health, 2022 Sep 19;19(18).
    PMID: 36142062 DOI: 10.3390/ijerph191811789
    Cardiovascular disease (CVD) has been a burden to many developing countries for decades, including Malaysia. Although various steps have been taken to prevent and manage CVD, it remains the leading cause of morbidity and mortality. The rising prevalence of CVD risk factors such as hypertension, hypercholesterolaemia, diabetes, overweight and obesity is the main driving force behind the CVD epidemic. Therefore, a nationwide health study coined as the Malaysian Health and Wellbeing Assessment (MyHEBAT) was designed. It aimed to investigate the prevalence of CVD and the associated risk factors in the community across Malaysia. The MyHEBAT study recruited participants (18-75 years old) through community health screening programmes from 11 states in Malaysia. The MyHEBAT study was further divided into two sub-studies, namely, the Cardiovascular Risk Epidemiological Study (MyHEBAT-CRES) and the MyHEBAT Familial Hypercholesterolaemia Study (MyHEBAT-FH). These studies assessed the prevalence of CVD risk factors and the prevalence of FH in the community, respectively. The data garnered from the MyHEBAT study will provide information for healthcare providers to devise better prevention and clinical practice guidelines for managing CVD in Malaysia.
    MeSH terms: Adolescent; Adult; Aged; Humans; Hypercholesterolemia*; Hyperlipidemias*; Middle Aged; Registries; Risk Factors; Prevalence; Risk Assessment; Young Adult
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