Displaying publications 261 - 280 of 280 in total

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  1. Chan SC, Beh HC, Jeevajothi Nathan J, Sahadeevan Y, Patrick Engkasan J, Chuah SY, et al.
    J Glob Health, 2023 Aug 11;13:03047.
    PMID: 37563918 DOI: 10.7189/jogh.13.03047
  2. Lee PY, Cheong AT, Ghazali SS, Salim H, Wong J, Hussein N, et al.
    NPJ Prim Care Respir Med, 2021 07 07;31(1):38.
    PMID: 34234145 DOI: 10.1038/s41533-021-00250-y
    Asthma self-management is a crucial component of asthma management. We sought to explore healthcare professionals' (HCPs') perceptions on barriers to asthma self-management implementation in primary care. We recruited 26 HCPs from six public primary care clinics in a semi-urban district of Malaysia in 2019. The analysis was done inductively. HCPs described barriers that resonated with the "COM-B" behaviour change framework. Capability-related issues stemmed from a need for specific self-management skills training. Opportunity-related barriers included the need to balance competing tasks and limited, poorly tailored resources. Motivation-related barriers included lack of awareness about self-management benefits, which was not prioritised in consultations with perceived lack of receptiveness from patients. These were compounded by contextual barriers of the healthcare organisation and multilingual society. The approach to implementation of asthma self-management needs to be comprehensive, addressing systemic, professional, and patient barriers and tailored to the local language, health literacy, and societal context.
  3. Cheong AT, Lee PY, Shariff-Ghazali S, Salim H, Hussein N, Ramli R, et al.
    NPJ Prim Care Respir Med, 2021 Nov 29;31(1):47.
    PMID: 34845205 DOI: 10.1038/s41533-021-00257-5
    Implementing asthma guideline recommendations is challenging in low- and middle-income countries. We aimed to explore healthcare provider (HCP) perspectives on the provision of recommended care. Twenty-six HCPs from six public primary care clinics in a semi-urban district of Malaysia were purposively sampled based on roles and experience. Focus group discussions were guided by a semi-structured interview guide and analysed thematically. HCPs had access to guidelines and training but highlighted multiple infrastructure-related challenges to implementing recommended care. Diagnosis and review of asthma control were hampered by limited access to spirometry and limited asthma control test (ACT) use, respectively. Treatment decisions were limited by poor availability of inhaled combination therapy (ICS/LABA) and free spacer devices. Imposed Ministry of Health programmes involving other non-communicable diseases were prioritised over asthma. Ministerial policies need practical resources and organisational support if quality improvement programmes are to facilitate better management of asthma in public primary care clinics.
  4. Durani LW, Hamezah HS, Ibrahim NF, Yanagisawa D, Nasaruddin ML, Mori M, et al.
    J Alzheimers Dis, 2018;64(1):249-267.
    PMID: 29889072 DOI: 10.3233/JAD-170880
    We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.
  5. Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Bellier JP, et al.
    Exp Gerontol, 2018 Oct 01;111:53-64.
    PMID: 29981398 DOI: 10.1016/j.exger.2018.07.002
    Decrease in multiple functions occurs in the brain with aging, all of which can contribute to age-related cognitive and locomotor impairments. Brain atrophy specifically in hippocampus, medial prefrontal cortex (mPFC), and striatum, can contribute to this age-associated decline in function. Our recent metabolomics analysis showed age-related changes in these brain regions. To further understand the aging processes, analysis using a proteomics approach was carried out. This study was conducted to identify proteome profiles in the hippocampus, mPFC, and striatum of 14-, 18-, 23-, and 27-month-old rats. Proteomics analysis using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins in the striatum. Of these proteins, 97 in the hippocampus, 25 in mPFC, and 5 in striatum were differentially expressed with age. The altered proteins were classified into three ontologies (cellular component, molecular function, and biological process) containing 44, 38, and 35 functional groups in the hippocampus, mPFC, and striatum, respectively. Most of these altered proteins participate in oxidative phosphorylation (e.g. cytochrome c oxidase and ATP synthase), glutathione metabolism (e.g. peroxiredoxins), or calcium signaling pathway (e.g. protein S100B and calmodulin). The most prominent changes were observed in the oldest animals. These results suggest that alterations in oxidative phosphorylation, glutathione metabolism, and calcium signaling pathway are involved in cognitive and locomotor impairments in aging.
  6. Wahab S, Yong LL, Chieng WK, Yamil M, Sawal NA, Abdullah NQ, et al.
    Front Psychiatry, 2021;12:680393.
    PMID: 34819880 DOI: 10.3389/fpsyt.2021.680393
    Background: Natural disasters may physically and psychologically affect individuals and their surrounding community. This study determines the prevalence of post-traumatic stress (PTS) symptoms and its association with maladaptive trauma-related cognition and resilience among adolescents post-earthquake. Materials and Methods: Data were collected, in this cross-sectional study, during an intervention program post-earthquake held in a state high school located at Lombok, Indonesia. The study sample engaged students 14-19 years of age using the purposive sampling method. The questionnaires used to measure PTS symptoms, maladaptive trauma-related cognition, and resilience were Children's Revised Impact of Event Scale-13 (CRIES-13), Child Post-Traumatic Cognitions Inventory (CPTCI), and Child and Youth Resilience Measure-Revised (CYRM-R), respectively. Results: The prevalence of PTS symptoms was 69.9%. Among the respondents, 61.37% were female and 56.48% had mothers with lower educational levels. Using multiple linear regression, the final predictors of PTS symptoms were excessive reactions (e.g., wailing loudly, miserable shrieking) of proxy during earthquake (β = 3.283, p = 0.005), maladaptive trauma-related cognition (β = 0.224, p = 0.002), and resilience (β = 0.192, p < 0.001) with female gender (β = 7.350, p < 0.001) as a control variable. Through simple linear regression, victims who witnessed injury or death during the earthquake (p = 0.003), had a proxy died during the earthquake (p = 0.01), and trapped victims or those who had difficulty escaping (p = 0.01) were identified to potentially predict the occurrence of PTS symptoms, warranting further study. Conclusion: The presence of excessive proxy reactions during the earthquake, maladaptive trauma-related cognition, and resilience in adolescents exposed to a natural disaster are worth targeting and prioritizing in future post-disaster interventions.
  7. Kim JD, Son I, Kwon WK, Sung TY, Sidik H, Kim K, et al.
    J Korean Med Sci, 2018 01 22;33(4):e28.
    PMID: 29318795 DOI: 10.3346/jkms.2018.33.e28
    BACKGROUND: Isoflurane, a common anesthetic for cardiac surgery, reduced myocardial contractility in many experimental studies, few studies have determined isoflurane's direct impact on the left ventricular (LV) contractile function during cardiac surgery. We determined whether isoflurane dose-dependently reduces the peak systolic velocity of the lateral mitral annulus in tissue Doppler imaging (S') in patients undergoing cardiac surgery.

    METHODS: During isoflurane-supplemented remifentanil-based anesthesia for patients undergoing cardiac surgery with preoperative LV ejection fraction greater than 50% (n = 20), we analyzed the changes of S' at each isoflurane dose increment (1.0, 1.5, and 2.0 minimum alveolar concentration [MAC]: T1, T2, and T3, respectively) with a fixed remifentanil dosage (1.0 μg/min/kg) by using transesophageal echocardiography.

    RESULTS: Mean S' values (95% confidence interval [CI]) at T1, T2, and T3 were 10.5 (8.8-12.2), 9.5 (8.3-10.8), and 8.4 (7.3-9.5) cm/s, respectively (P < 0.001 in multivariate analysis of variance test). Their mean differences at T1 vs. T2, T2 vs. T3, and T1 vs. T3 were -1.0 (-1.6, -0.3), -1.1 (-1.7, -0.6), and -2.1 (-3.1, -1.1) cm/s, respectively. Phenylephrine infusion rates were significantly increased (0.26, 0.22, and 0.47 μg/kg/min at T1, T2, and T3, respectively, P < 0.001).

    CONCLUSION: Isoflurane increments (1.0-2.0 MAC) dose-dependently reduced LV systolic long-axis performance during cardiac surgeries with a preserved preoperative systolic function.

  8. Azlan UK, Khairul Annuar NA, Mediani A, Aizat WM, Damanhuri HA, Tong X, et al.
    Front Pharmacol, 2022;13:1035220.
    PMID: 36686668 DOI: 10.3389/fphar.2022.1035220
    Neurodegenerative diseases (NDs) are sporadic maladies that affect patients' lives with progressive neurological disabilities and reduced quality of life. Neuroinflammation and oxidative reaction are among the pivotal factors for neurodegenerative conditions, contributing to the progression of NDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS) and Huntington's disease (HD). Management of NDs is still less than optimum due to its wide range of causative factors and influences, such as lifestyle, genetic variants, and environmental aspects. The neuroprotective and anti-neuroinflammatory activities of Moringa oleifera have been documented in numerous studies due to its richness of phytochemicals with antioxidant and anti-inflammatory properties. This review highlights up-to-date research findings on the anti-neuroinflammatory and neuroprotective effects of M. oleifera, including mechanisms against NDs. The information was gathered from databases, which include Scopus, Science Direct, Ovid-MEDLINE, Springer, and Elsevier. Neuroprotective effects of M. oleifera were mainly assessed by using the crude extracts in vitro and in vivo experiments. Isolated compounds from M. oleifera such as moringin, astragalin, and isoquercitrin, and identified compounds of M. oleifera such as phenolic acids and flavonoids (chlorogenic acid, gallic acid, ferulic acid, caffeic acid, kaempferol, quercetin, myricetin, (-)-epicatechin, and isoquercitrin) have been reported to have neuropharmacological activities. Therefore, these compounds may potentially contribute to the neuroprotective and anti-neuroinflammatory effects. More in-depth studies using in vivo animal models of neurological-related disorders and extensive preclinical investigations, such as pharmacokinetics, toxicity, and bioavailability studies are necessary before clinical trials can be carried out to develop M. oleifera constituents into neuroprotective agents.
  9. Abu Bakar ZH, Damanhuri HA, Makpol S, Wan Kamaruddin WMA, Abdul Sani NF, Amir Hamzah AIZ, et al.
    J Alzheimers Dis, 2019;70(s1):S43-S62.
    PMID: 30594926 DOI: 10.3233/JAD-180511
    BACKGROUND: Many studies on biochemical and psychological variables have aimed to elucidate the association between aging and cognitive function. Demographic differences and protein expression have been reported to play a role in determining the cognitive capability of a population.

    OBJECTIVE: This study aimed to determine the effect of age on the protein profile of Malay individuals and its association with cognitive competency.

    METHODS: A total of 160 individuals were recruited and grouped accordingly. Cognitive competency of each subject was assessed with several neuropsychological tests. Plasma samples were collected and analyzed with Q Exactive HF Orbitrap. Proteins were identified and quantitated with MaxQuant and further analyzed with Perseus to determine differentially expressed proteins. PANTHER, Reactome, and STRING were applied for bioinformatics output.

    RESULTS: Our data showed that the Malay individuals are vulnerable to the deterioration of cognitive function with aging, and most of the proteins were differentially expressed in concordance. Several physiological components and pathways were shown to be involved, giving a hint of a promising interpretation on the induction of aging toward the state of the Malays' cognitive function. Nevertheless, some proteins have shown a considerable interaction with the generated protein network, which provides a direction of focus for further investigation.

    CONCLUSION: This study demonstrated notable changes in the expression of several proteins as age increased. These changes provide a promising platform for understanding the biochemical factors affecting cognitive function in the Malay population. The exhibited network of protein-protein interaction suggests the possibility of implementing regulatory intervention in ameliorating Malay cognitive function.

  10. Abdul Sani NF, Ahmad Damanhuri MH, Amir Hamzah AIZ, Abu Bakar ZH, Tan JK, Nor Aripin KN, et al.
    Free Radic Res, 2018 Sep;52(9):1000-1009.
    PMID: 30079776 DOI: 10.1080/10715762.2018.1506877
    Ageing is associated with increased oxidative stress accompanied by cognitive decline. The aim of this study was to evaluate oxidative stress biomarkers and their possible relationship with cognitive performances during ageing among the Malay population. Approximately 160 healthy Malay adults aged between 28 and 79 years were recruited around Selangor and Klang Valley. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA), forward digit span (FDS), backward digit span (BDS), digit symbol, Rey Auditory Verbal Learning Test immediate recalled [RAVLT(I)] and delayed recalled [RAVLT(D)], and visual reproduction immediate recalled (VR-I) and delayed recalled (VR-II). DNA damage, plasma protein carbonyl and malondialdehyde (MDA) levels were also determined. Cognitive function test showed significant lower scores of MoCA, BDS, RAVLT(I), RAVLT(D), digit symbol, VR-I, and VR-II in the older age group (60 years old) compared with the 30-, 40-, and 50-year-old group. The extent of DNA damage was sequential with age: 60 > 50 > 40 > 30, whereas protein carbonyl was higher in 40-, 50-, and 60-year-old groups compared with the youngest group (30 years old). However, the MDA level was observed unchanged in all age groups. Approximately 21.88% of the participants had cognitive impairment. Multiple logistic regression analysis revealed that DNA damage and protein carbonyl levels are predictors for cognitive impairment in healthy Malays. In conclusion, cognitive decline occurred in healthy adult Malay population at an early age of 30 years old with corresponding higher DNA damage and protein oxidation.
  11. Tan JK, Zakaria SNA, Gunasekaran G, Abdul Sani NF, Nasaruddin ML, Jaafar F, et al.
    Oxid Med Cell Longev, 2023;2023:4416410.
    PMID: 36785791 DOI: 10.1155/2023/4416410
    Aging is a complex process characterized by progressive loss of functional abilities due to the accumulation of molecular damages. Metabolomics could offer novel insights into the predictors and mechanisms of aging. This cross-sectional study is aimed at identifying age-associated plasma metabolome in a Malay population. A total of 146 (90 females) healthy participants aged 28-69 were selected for the study. Untargeted metabolomics profiling was performed using liquid chromatography-tandem mass spectrometry. Association analysis was based on the general linear model. Gender-associated metabolites were adjusted for age, while age-associated metabolites were adjusted for gender or analyzed in a gender-stratified manner. Gender-associated metabolites such as 4-hydroxyphenyllactic acid, carnitine, cortisol, and testosterone sulfate showed higher levels in males than females. Deoxycholic acid and hippuric acid were among the metabolites with a positive association with age after being adjusted for gender, while 9(E),11(E)-conjugated linoleic acid, cortisol, and nicotinamide were negatively associated with age. In gender-stratified analysis, glutamine was one of the common metabolites that showed a direct association with age in both genders, while metabolites such as 11-deoxy prostaglandin F2β, guanosine monophosphate, and testosterone sulfate were inversely associated with age in males and females. This study reveals several age-associated metabolites in Malays that could reflect the changes in metabolisms during aging and may be used to discern the risk of geriatric syndromes and disorders later. Further studies are required to determine the interplay between these metabolites and environmental factors on the functional outcomes during aging.
  12. Loo JL, Mohamad Kamal NA, Goon JA, Ahmad Damanhuri H, Tan JAC, Abdul Murad NA, et al.
    Front Psychiatry, 2021;12:698911.
    PMID: 34916966 DOI: 10.3389/fpsyt.2021.698911
    Background: Oxidative stress markers are found to be linked with depression and suicide attempts in bipolar disorder (BD), although the role of DNA damage as a marker of suicidal ideation and attempt has yet to be determined. We aim to investigate the association between DNA damage and suicidal behaviour, i.e., suicidal ideation and suicide attempt, among suicidal ideators in BD patients while accounting for clinical and psychosocial risk factors. Methods: A cross-sectional study was conducted in the Universiti Kebangsaan Malaysia Medical Centre on 62 consecutive BD patients diagnosed using the M.I.N.I. Neuropsychiatric Interview and 26 healthy control participants. Socio-demographic and clinical assessments were performed using the Columbia Suicide Severity Rating Scale (C-SSRS) for lifetime suicidal ideation and attempt, Quick Inventory of Depressive Symptomatology (QIDS) for depression severity, Clinical Global Impression for Bipolar Disorder (CGI-BD) for illness severity [both mania (CGI-Mania) and major depressive episode (CGI-MDE)], Social Readjustment Rating Scale (SRRS) for change in life events, and Barratt Impulsiveness Scale (BIS) for behavioural impulsivity. The degree of DNA damage in peripheral blood samples was determined using a standard protocol of comet assay. Results: Multivariable logistic regression revealed higher scores of CGI-MDE as the sole significant factor for lifetime suicidal ideation (OR = 1.937, 95% CI = 1.799-2.076). Although initial bivariate analysis showed a significant association between DNA damage, malondialdehyde (MDA), catalase (CAT), and suicidal behaviour, the findings were not seen in multivariable logistic regression. Bivariate subgroup analysis showed that moderate and severe DNA damage (p = 0.032 and p = 0.047, respectively) was significantly associated with lifetime suicide attempts among lifetime suicidal ideators. The study is the first to look at the connexion between DNA damage and suicidal risk in bipolar patients. It is limited by the small sample size and lack of information on illicit substance use. Conclusions: More severe DNA damage was significantly associated with lifetime suicide attempts among lifetime suicidal ideators in BD. However, the severity of depression was found to be independently associated with lifetime suicidal ideation per se rather than DNA damage in BD. Larger prospective studies are required to ascertain the potential of DNA damage as a biomarker for the transition from suicidal ideation to a suicide attempt.
  13. Yap KH, Azmin S, Abdul Manan H, Yahya N, Ahmad N, Tajurudin FW, et al.
    Parkinsonism Relat Disord, 2024 Jul;124:107013.
    PMID: 38843619 DOI: 10.1016/j.parkreldis.2024.107013
    INTRODUCTION: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease characterized by increasingly worsening ataxia and non-ataxia features, negatively impacting patients' quality of life. This study was designed to test formally evaluate whether oral trehalose was effective in SCA3 patients.

    METHODS: In this double-blind, randomized controlled trial, SCA3 patients received either 100 g oral trehalose or 30 g maltose to improve ataxia severity over six months. We also measured other clinical (non-ataxia), patient-reported (quality of life, motivations), and safety endpoints. An unscheduled interim analysis was conducted using two-way ANOVAs to analyze the interaction between time (baseline, 3-months, 6-months) and intervention (Trehalose vs. Placebo).

    RESULTS: Fifteen participants (Trehalose = 7 vs. Placebo = 8) completed the study at the time of interim analysis. There was no interaction effect on the ataxia severity, and available data suggested an estimated sample size of 132 (66 per arm) SCA3 patients required to demonstrate changes in a 6-month trial. There were significant interaction effects for executive function (ƞ2 = 0.28-0.43). Safety data indicated that 100 g oral trehalose was well-tolerated.

    CONCLUSION: We performed an unplanned interim analysis due to a slow recruitment rate. The new estimated sample size was deemed unfeasible, leading to premature termination of the clinical trial. In this small, current sample of SCA3 patients, 100 g oral trehalose did not differentially impact on ataxia severity compared to placebo. Interestingly, our findings may suggest an improvement in executive function. Future efforts will require a large multi-country, multi-center study to investigate the potential effect of trehalose.

  14. Hanafi S, Hassan R, Bahar R, Abdullah WZ, Johan MF, Rashid ND, et al.
    Am J Blood Res, 2014;4(1):33-40.
    PMID: 25232503
    The aim of this study was to adapt MARMS with some modifications to detect beta mutation in our cohort of thalassemia patients. We focused only on transfusion-dependent thalassemia Malay patients, the predominant ethnic group (95%) in the Kelantanese population. Eight mutations were identified in 46 out of 48 (95.83%) beta thalassemia alleles. Most of the patients (54.2%) were compound heterozygous with co-inheritance Cd 26 (G>A). The frequencies of spectrum beta chain mutation among these patients are presented in Table 2. Among the transfusion dependent beta thalassemia Malay patients studied, 26 patients were found to be compound heterozygous and the main alleles were Cd 26 (G>A). Compound heterozygous mutation of Cd 26 (G>A) and IVS 1-5 (G>C) were 12 (46.2%), Cd 26 (G>A) and Cd 41/42 (TTCT) were 9 (34.6%), Cd 26 (G>A) and IVS 1-1 (G>C) were 2 (7.7%) respectively. Meanwhile the minority were made of a single compound heterozygous of Cd 26 (G>A) and Cd 71/72, Cd 26 (>A) and Cd 17 (A>T), Cd 26 (G>A) and -28 (G>A) respectively. Twenty out of forty six patients were shown to have homozygous of IVS 1-5 (G>C) were 2 (10.0%), Cd 26 (G>A) were 15 (75.0%), Cd 19 (A>G) were 1 (5.0%), and IVS 1-1 (G>T) were 2 (10.0%). The beta chain mutations among the Kelantanese Malays followed closely the distribution of beta chain mutations among the Thais and the Malays of the Southern Thailand. The G-C transition at position 5 of the IVS 1-5 mutation was predominant among the Malay patients. In conclusion, this method has successfully identified the mutation spectrum in our cohort of transfusion-dependent beta thalassemia patients, and this method is equally effective in screening for mutation among thalassemia patients.
  15. Jamshed SQ, Elkalmi R, Rajiah K, Al-Shami AK, Shamsudin SH, Siddiqui MJ, et al.
    J Infect Dev Ctries, 2014;8(6):780-5.
    PMID: 24916878 DOI: 10.3855/jidc.3833
    This study is aimed to investigate the understanding of antibiotic use and antibiotic resistance and its correlate factors among final-year medical and pharmacy students at International Islamic University Malaysia (IIUM).
  16. Agarwal D, Hanafi NS, Khoo EM, Parker RA, Ghorpade D, Salvi S, et al.
    J Glob Health, 2021;11:04065.
    PMID: 34737865 DOI: 10.7189/jogh.11.04065
    Background: Our previous scoping review revealed limitations and inconsistencies in population surveys of chronic respiratory disease. Informed by this review, we piloted a cross-sectional survey of adults in four South/South-East Asian low-and middle-income countries (LMICs) to assess survey feasibility and identify variables that predicted asthma or chronic obstructive pulmonary disease (COPD).

    Methods: We administered relevant translations of the BOLD-1 questionnaire with additional questions from ECRHS-II, performed spirometry and arranged specialist clinical review for a sub-group to confirm the diagnosis. Using random sampling, we piloted a community-based survey at five sites in four LMICs and noted any practical barriers to conducting the survey. Three clinicians independently used information from questionnaires, spirometry and specialist reviews, and reached consensus on a clinical diagnosis. We used lasso regression to identify variables that predicted the clinical diagnoses and attempted to develop an algorithm for detecting asthma and COPD.

    Results: Of 508 participants, 55.9% reported one or more chronic respiratory symptoms. The prevalence of asthma was 16.3%; COPD 4.5%; and 'other chronic respiratory disease' 3.0%. Based on consensus categorisation (n = 483 complete records), "Wheezing in last 12 months" and "Waking up with a feeling of tightness" were the strongest predictors for asthma. For COPD, age and spirometry results were the strongest predictors. Practical challenges included logistics (participant recruitment; researcher safety); misinterpretation of questions due to local dialects; and assuring quality spirometry in the field.

    Conclusion: Detecting asthma in population surveys relies on symptoms and history. In contrast, spirometry and age were the best predictors of COPD. Logistical, language and spirometry-related challenges need to be addressed.

  17. Hoshide S, Yamamoto K, Katsurada K, Yano Y, Nishiyama A, Wang JG, et al.
    Hypertens Res, 2023 Jan;46(1):3-8.
    PMID: 36229522 DOI: 10.1038/s41440-022-00994-1
  18. Shang X, Peng Z, Ye Y, Asan, Zhang X, Chen Y, et al.
    EBioMedicine, 2017 Sep;23:150-159.
    PMID: 28865746 DOI: 10.1016/j.ebiom.2017.08.015
    Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.
  19. Landoni G, Lomivorotov V, Pisano A, Nigro Neto C, Benedetto U, Biondi Zoccai G, et al.
    Contemp Clin Trials, 2017 08;59:38-43.
    PMID: 28533194 DOI: 10.1016/j.cct.2017.05.011
    OBJECTIVE: There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small randomized controlled trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable.

    DESIGN: Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio.

    SETTING: Tertiary and University hospitals.

    INTERVENTIONS: Patients (n=10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia.

    MEASUREMENTS AND MAIN RESULTS: The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-day death or non-fatal myocardial infarction (composite endpoint); cardiac mortality at 30day and at one year; incidence of hospital re-admission during the one year follow-up period and duration of intensive care unit, and hospital stay. The sample size is based on the hypothesis that volatile anesthetics will reduce 1-year unadjusted mortality from 3% to 2%, using a two-sided alpha error of 0.05, and a power of 0.9.

    CONCLUSIONS: The trial will determine whether the simple intervention of adding a volatile anesthetic, an intervention that can be implemented by all anesthesiologists, can improve one-year survival in patients undergoing coronary artery bypass graft surgery.

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