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  1. Rajaram N, Jaganathan M, Muniandy K, Rajoo Y, Zainal H, Rahim N, et al.
    BMC Health Serv Res, 2023 Mar 01;23(1):206.
    PMID: 36859265 DOI: 10.1186/s12913-023-09046-x
    BACKGROUND: Improving help-seeking behaviour is a key component of down-staging breast cancer and improving survival, but the specific challenges faced by low-income women in an Asian setting remain poorly characterized. Here, we determined the extent of help-seeking delay among Malaysian breast cancer patients who presented at late stages and explored sub-groups of women who may face specific barriers.

    METHODS: Time to help-seeking was assessed in 303 women diagnosed with advanced breast cancer between January 2015 and March 2020 at a suburban tertiary hospital in Malaysia. Two-step cluster analysis was conducted to identify subgroups of women who share similar characteristics and barriers. Barriers to help-seeking were identified from nurse interviews and were analyzed using behavioural frameworks.

    RESULTS: The average time to help-seeking was 65 days (IQR = 250 days), and up to 44.5% of women delayed by at least 3 months. Three equal-sized clusters emerged with good separation by time to help-seeking (p 

  2. Albitar O, Harun SN, Zainal H, Ibrahim B, Sheikh Ghadzi SM
    Biomed Res Int, 2020;2020:9872936.
    PMID: 31998804 DOI: 10.1155/2020/9872936
    Background and Objective: Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models.

    Methods: A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded.

    Results: Twelve studies were included in this review. Clozapine pharmacokinetics was described as one-compartment with first-order absorption and elimination in most of the studies. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models.

    Conclusions: Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors such as genetic polymorphisms, metabolic factors, and significant drug-drug interactions in a well-designed population pharmacokinetic model in the future, taking into account the incorporation of larger sample size and more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.

  3. Siddiqui S, Zainal H, Harun SN, Sheikh Ghadzi SM
    Clin Nutr ESPEN, 2019 02;29:213-223.
    PMID: 30661689 DOI: 10.1016/j.clnesp.2018.10.002
    BACKGROUND: The contribution of dietary factors in the development and progression of pre-diabetes has been increasingly recognized. However, due to high variability in dietary habits measurement of dietary intake remains one of the most challenging tasks in this population. Food frequency questionnaire (FFQ) which investigates usual dietary intake can be used to identify frequent consumption of foods such as dietary fat, fiber, grains that are linked to the risk of pre-diabetes.

    METHOD: This systematic review was conducted to identify and describe FFQs that measure dietary intake of pre-diabetic patients and to examine their relative validity and reliability. The systematic search was done through electronic databases such as PubMed, CINAHL, PsycINFO, ProQuest and Scopus. Methodological quality of included studies and results of study outcome was also summarized in this review.

    RESULT: The search identified 445 papers, of which 18 studies reported 15 FFQs, met inclusion criteria. Most of the FFQs (n = 12) were semi-quantitative while three were frequency measures with portion size estimation of selected food items. Test-retest reliability of FFQ was reported in 7 (38.3%) studies with the correlation coefficient of 0.33-0.92. Relative validity of FFQ was reported in 16 (88.8%) studies with the range of correlation coefficient of 0.08-0.83. Dietary patterns rich in carbohydrate, fat, animal protein and n-3 fatty acids were associated with increased risk of pre-diabetes.

    CONCLUSION: No well-established disease-specific FFQ identified in the literature. Development of a valid, practical and reliable tool is needed for better understanding of the impact of diet in pre-diabetic population.

  4. Siddiqui S, Zainal H, Harun SN, Ghadzi SMS
    Clin Nutr ESPEN, 2020 10;39:165-172.
    PMID: 32859312 DOI: 10.1016/j.clnesp.2020.06.022
    BACKGROUND: Diabetes mellitus is a leading cause of preventable deaths and becomes a major public health concern in Malaysia. Multiple studies have reported the association between diet quality and glycemic parameters among known diabetic subjects. Its influence in individuals with borderline diabetes (i.e. pre-diabetes) or unknown diabetes is still unclear.

    OBJECTIVE: The objective of this study was to assess the association between diet quality evaluated by healthy eating index (HEI) with the glucose outcome in individuals with distinct diabetes progression stages, as well as to identify causal factors in relation to their diabetes status.

    METHOD: A cross-sectional study was conducted at clinical care setting in Universiti Sains Malaysia (USM) between October 2018-March 2019. Normoglycemic controls (n = 47), at-risk of pre-diabetes (n = 58), pre-diabetes (n = 24) as well as individuals with undiagnosed diabetes (n = 18) were queried about their habitual diet by using Food Frequency Questionnaire (FFQ). Correlation analyses were performed to examine the relationship between HEI score and 1) Fasting plasma glucose (FPG) 2) postprandial blood glucose (2-HPP) and glycosylated hemoglobin (HbA1c). Multinomial regression was performed to identify predictors associated with diabetes status of study participants.

    RESULT: Overall, diet quality of study participants was unsatisfactory with the mean score of 58.05 ± 9.07 that need improvement. Total HEI score was negatively correlated with the 2-HPP levels in pre-diabetic patients (r = - 0.45, p = 0.05). No significant association was revealed between glycemic parameters and total HEI score among other groups. Age, body mass index (BMI), triglycerides and female gender were positively correlated with the risk of pre-diabetes, at-risk of pre-diabetes and undiagnosed diabetes (p 

  5. Tan JA, Khoo ET, Al-Chalabi MMM, Mohd Zainal H, Wan Sulaiman WA
    Cureus, 2023 Jul;15(7):e42572.
    PMID: 37637587 DOI: 10.7759/cureus.42572
    Conjunctival melanoma is a rare and potentially deadly tumor. Therefore, adequate oncological resection is essential, commonly leading to total orbital exenteration, which causes patients' extensive functional and cosmetic impairment. As a result, it is essential to reconstruct the orbital region post-exenteration to obliterate the cavity, provide adequate and pliable cutaneous covering, and restore a stable vascularized tissue that can withstand adjuvant radiotherapy. In recent years, the techniques used for orbital reconstruction have included the transorbital temporoparietal fascial flap, the anterolateral thigh flap, and local flaps, such as the paramedian forehead flap. A free radial forearm flap is currently not commonly used for orbital reconstruction due to potential donor site morbidity and cosmetic issues. In our case, we report a free radial forearm fasciocutaneous flap that has been utilized with promising surgical outcomes to reconstruct the orbital region following orbital exenteration.
  6. Elhefnawy M, Noor Harun S, Leykhim T, Tangiisuran B, Zainal H, Looi I, et al.
    Cureus, 2023 Dec;15(12):e50794.
    PMID: 38239519 DOI: 10.7759/cureus.50794
    Objectives Compared with the first stroke, neurological impairment caused by stroke recurrence is more serious, more difficult to treat, and has a higher mortality rate, especially among ischemic stroke (IS) patients with diabetes mellitus (DM). Although there are established correlations between factors and IS recurrence, there were some issues regarding the naive hazard of IS recurrence with no risk factor influence, and how does the baseline hazard differ among patients with DM and non-DM? To answer all these questions, two time-to-event (TTE) models of recurrent IS after the index IS were developed among IS patients with DM and non-DM. Method A total of 7697 patients with an index IS attack were extracted from the Malaysian Registry of Neurology and stratified according to DM status. Several parametric survival models were evaluated using nonlinear mixed-effect modeling software (NONMEM 7.5). The final model was determined according to the lowest objective function value, graphical evaluation, numerical diagnostics, and clinical plausibility. Additionally, the final model was validated internally and temporally using Kaplan-Meier visual predictive checks (KM-VPCs). Results One hundred ninety-five (5.82%) of 3493 DM patients and 138 (3.28%) of 4204 non-DM patients developed a recurrent IS with a maximum follow-up of 7.37 years. Gompertz's model best fitted the data. With no influence on risk factors, the index IS attack was predicted to contribute to the hazard of recurrent IS by 0.356 and 0.253 within the first six months after the index IS among patients with and without DM, respectively. Even after six months of index IS, the recurrent IS baseline hazard was not equal to zero among both groups (0.0023, 0.0018). Moreover, after incorporating the time and risk factors, the recurrent hazards increased exponentially during the first three years after the index IS followed by an exponential reduction afterward. The recurrent IS predictors among DM patients were ischemic heart disease (IHD) and hyperlipidemia (HPLD). IHD and HPLD increased the hazard of recurrent IS by 2.40 and 1.88 times, respectively, compared to those without IHD and HPLD before index IS (HR, 2.40 (1.79-3.20)), and (HR, 1.88 (1.44-2.45)) respectively. Conclusion The baseline hazard was the highest during the first six months after the index IS. Moreover, receiving medications for secondary prevention failed to demonstrate a significant association with reducing IS recurrence among IS patients with DM, suggesting a need for more intensive patient screening and new strategies for secondary prevention among IS patients with DM.
  7. Siddiqui S, Zainal H, Harun SN, Sheikh Ghadzi SM, Ghafoor S
    Diabetes Metab Syndr, 2020 07 08;14(5):1243-1252.
    PMID: 32688241 DOI: 10.1016/j.dsx.2020.06.069
    BACKGROUND: Prediabetes is a risk state for the future development of type 2 diabetes. Previously, it was evident that the risk factors for diabetes differ by gender. However, conclusive evidence regarding the gender difference in modifiable risk factors associated with the presence of pre-diabetes is still lacking.

    AIMS: To systematically identify and summarize the available literature on whether the modifiable risk factors associated with prediabetes displays similar relationship in both the genders.

    METHODS: A systematic search was performed on electronic databases i.e. PubMed, EBSCOhost, and Scopus using "sex", "gender", "modifiable risk factors" and "prediabetes" as keywords. Reference list from identified studies was used to augment the search strategy. Methodological quality and results from individual studies were summarized in tables.

    RESULTS: Gender differences in the risk factor association were observed among reviewed studies. Overall, reported association between risk factors and prediabetes apparently stronger among men. In particular, abdominal obesity, dyslipidemia, smoking and alcohol drinking habits were risk factors that showed prominent association among men. Hypertension and poor diet quality may appear to be stronger among women. General obesity showed stringent hold, while physical activity not significantly associated with the risk of prediabetes in both the genders.

    CONCLUSIONS: Evidence suggests the existence of gender differences in risk factors associated with prediabetes, demands future researchers to analyze data separately based on gender. The consideration and the implementation of gender differences in health policies and in diabetes prevention programs may improve the quality of care and reduce number of diabetes prevalence among prediabetic subjects.

  8. Elhefnawy ME, Sheikh Ghadzi SM, Albitar O, Tangiisuran B, Zainal H, Looi I, et al.
    Front Neurol, 2023;14:1118711.
    PMID: 37188311 DOI: 10.3389/fneur.2023.1118711
    BACKGROUND: There are established correlations between risk factors and ischemic stroke (IS) recurrence; however, does the hazard of recurrent IS change over time? What is the predicted baseline hazard of recurrent IS if there is no influence of variable predictors? This study aimed to quantify the hazard of recurrent IS when the variable predictors were set to zero and quantify the secondary prevention influence on the hazard of recurrent ischemic stroke.

    METHODS: In the population cohort involved in this study, data were extracted from 7,697 patients with a history of first IS attack registered with the National Neurology Registry of Malaysia from 2009 to 2016. A time-to-recurrent IS model was developed using NONMEM version 7.5. Three baseline hazard models were fitted into the data. The best model was selected using maximum likelihood estimation, clinical plausibility, and visual predictive checks.

    RESULTS: Within the maximum 7.37 years of follow-up, 333 (4.32%) patients had at least one incident of recurrent IS. The data were well described by the Gompertz hazard model. Within the first 6 months after the index IS, the hazard of recurrent IS was predicted to be 0.238, and 6 months after the index attack, it reduced to 0.001. The presence of typical risk factors such as hyperlipidemia [HR, 2.22 (95%CI: 1.81-2.72)], hypertension [HR, 2.03 (95%CI: 1.52-2.71)], and ischemic heart disease [HR, 2.10 (95%CI: 1.64-2.69)] accelerated the hazard of recurrent IS, but receiving antiplatelets (APLTs) upon stroke decreased this hazard [HR, 0.59 (95%CI: 0.79-0.44)].

    CONCLUSION: The hazard of recurrent IS magnitude differs during different time intervals based on the concomitant risk factors and secondary prevention.

  9. Akhtar A, Khan AH, Zainal H, Ahmad Hassali MA, Ali I, Ming LC
    Front Public Health, 2020;8:601961.
    PMID: 33324603 DOI: 10.3389/fpubh.2020.601961
    Background: Unnecessary antimicrobial use is an emerging problem throughout the world. To design future interventions to ensure rational antimicrobial use and decrease the risk of antimicrobial resistance, physician's knowledge and prescribing practices of antimicrobials should be assessed. Therefore, the main objective of this study is to investigate the physician's knowledge along with their prescribing patterns of antimicrobials in their health care system. Methods: The present qualitative study was conducted in a tertiary care public hospital located at Penang island, situated in Northwest of Malaysia. A total of 12 semi-structured, face to face interviews were conducted with purposive sampling technique. Physicians recruited had different specialties. All interviews were audio recorded, then transcribed into English language and analyze by thematic content analysis. Results: Four major themes were identified: (1) prescribing patterns of physicians regarding antimicrobials; (2) physician's knowledge about antimicrobials; (3) antimicrobial resistance; (4) satisfaction with management of infections. Physicians believed in regular educational activities and updates about the latest antimicrobial guidelines may change the prescribing behavior of physicians to optimize the use of antimicrobials. This may lead to decrease in burden of antimicrobial resistance in their health care system. Physicians emphasized that stricter rules and regular monitoring of antimicrobial use should be implemented to overcome the main challenges of antimicrobial resistance. Conclusion: Different factors were identified to assist optimized use of antimicrobials and decrease the risk of antimicrobial resistance. The present study helps to design targeted future interventions to ensure rational antimicrobial use and decrease the impact of antimicrobial resistance in Malaysia.
  10. Akhtar A, Ahmad Hassali MA, Zainal H, Ali I, Khan AH
    Front Public Health, 2021;9:657199.
    PMID: 34733812 DOI: 10.3389/fpubh.2021.657199
    Background: Urinary tract infections (UTIs) are the second most prevalent infection among the elderly population. Hence, the current study aimed to evaluate the prevalence of UTIs among older adults, medication regimen complexity, and the factors associated with the treatment outcomes of elderly patients infected with UTIs. Methods: A retrospective cross-sectional study was conducted at the Department of Urology, Hospital Pulau Pinang, Malaysia. The patients ≥65 years of age were included in the present study with a confirmed diagnosis of UTIs from 2014 to 2018 (5 years). Results: A total of 460 patients met the inclusion criteria and were included in the present study. Cystitis (37.6%) was the most prevalent UTI among the study population followed by asymptomatic bacteriuria (ASB) (31.9%), pyelonephritis (13.9%), urosepsis (10.2%), and prostatitis (6.4%). Unasyn (ampicillin and sulbactam) was used to treat the UTIs followed by Bactrim (trimethoprim/sulfamethoxazole), and ciprofloxacin. The factors associated with the treatment outcomes of UTIs were gender (odd ratio [OR] = 1.628; p = 0.018), polypharmacy (OR = 0.647; p = 0.033), and presence of other comorbidities (OR = 2.004; p = 0.002) among the study population. Conclusion: Cystitis is the most common UTI observed in older adults. Gender, the burden of polypharmacy, and the presence of comorbidities are the factors that directly affect the treatment outcomes of UTIs among the study population.
  11. Zainal H, Zainab AN
    Health Info Libr J, 2011 Sep;28(3):216-25.
    PMID: 21831221 DOI: 10.1111/j.1471-1842.2011.00943.x
    BACKGROUND: The aim of this study was to examine Malaysian contributions in the field of biomedical and health sciences.
    METHODS: In this study, 3697 publications affiliated to Malaysian addresses from the sci database between 1990 and 2005 were sampled. This study also explored publication productivity trends, authorship and collaboration pattern, core journals used, and citations obtained.
    RESULTS: Main contributions were journal articles (73.3%). Most authors (63.7%) contributed only one article and 16.1% produced over 30-68 publications. Multi-authored works were the norm. The productive authors were named either first or second in publications. There were active collaborations with authors from Asia-Pacific countries (35%) and Europe (30%). The majority of publications were contributed by institutions of higher learning (87%). Core journals used follow quite close to Bradford's zonal ratios of 44:152:581. The active research areas were identified. About 71.3% of publications received citations especially those published from 1995 to 1999.
    CONCLUSION: This study helped librarians identify active researchers, active research areas and journals relevant to biomedical and health sciences researchers and useful when producing reports to university management and planning medical collection policies and deciding on journal subscriptions and cancellations.
  12. Dharmaraj B, Diong NC, Shamugam N, Sathiamurthy N, Mohd Zainal H, Chai SC, et al.
    Indian J Thorac Cardiovasc Surg, 2021 Jan;37(1):82-88.
    PMID: 33442211 DOI: 10.1007/s12055-020-00972-7
    Chest wall resection is defined as partial or full-thickness removal of the chest wall. Significant morbidity has been recorded, with documented respiratory failure as high as 27%. Medical records of all patients who had undergone chest wall resection and reconstruction were reviewed. Patients' demographics, length of surgery, reconstruction method, size of tumor and chest wall defect, histopathological result, complications, duration of post-operative antibiotics, and hospital stay were assessed. From 1 April 2017 to 30 April 2019, a total of 20 patients underwent chest wall reconstructive surgery. The median age was 57 years, with 12 females and 8 males. Fourteen patients (70%) had malignant disease and 6 patients (30%) had benign disease. Nine patients underwent rigid reconstruction (titanium mesh for sternum and titanium plates for ribs), 6 patients had non-rigid reconstruction (with polypropylene or composite mesh), and 5 patients had primary closure. Nine patients (45%) required closure with myocutaneous flap. Complications were noted in 70% of patients. Patients who underwent primary closure had minor complications. In total, 66.7% of patients who had closure with either fasciocutaneous or myocutaneous flaps had threatened flap necrosis. Two patients developed pneumonia and 3 patients (15%) had respiratory failure requiring tracheostomy and prolonged ventilation. There was 1 mortality (5%) in this series. In conclusion, chest wall resections involving large defects require prudent clinical judgment and multidisciplinary assessments in determining the choice of chest wall reconstruction to improve outcomes.
  13. Arcari L, Hinojar R, Engel J, Freiwald T, Platschek S, Zainal H, et al.
    Int J Cardiol, 2020 05 01;306:102-108.
    PMID: 32169347 DOI: 10.1016/j.ijcard.2020.03.002
    AIMS: Profound left ventricular (LV) hypertrophy with diastolic dysfunction and heart failure is the cardinal manifestation of heart remodelling in chronic kidney disease (CKD). Previous studies related increased T1 mapping values in CKD with diffuse fibrosis. Native T1 is a non-specific readout that may also relate to increased intramyocardial fluid. We examined concomitant T1 and T2 mapping signatures and undertook comparisons with other hypertrophic conditions.

    METHODS: In this prospective multicentre study, consecutive CKD patients (n = 154) undergoing routine clinical cardiac magnetic resonance (CMR) imaging were compared with patients with hypertensive (HTN, n = 163) and hypertrophic cardiomyopathy (HCM, n = 158), and normotensive controls (n = 133).

    RESULTS: Native T1 was significantly higher in all patient groups, whereas native T2 in CKD only (p 

  14. Haslbauer JD, Lindner S, Valbuena-Lopez S, Zainal H, Zhou H, D'Angelo T, et al.
    Int J Cardiol, 2019 Jan 15;275:179-186.
    PMID: 30360992 DOI: 10.1016/j.ijcard.2018.10.023
    BACKGROUND: Cancer-related treatment is associated with development of heart failure and poor outcome in cancer-survivors. T1 and T2 mapping by cardiovascular magnetic resonance (CMR) may detect myocardial injury due to cancer-related treatment.

    METHODS: Patients receiving cancer-related treatment regimes underwent screening of cardiac involvement with CMR, either within 3 months (early Tx) or >12 months (late Tx) post-treatment. T1 and T2 mapping, cardiac function, strain, ischaemia-testing, scar-imaging and serological cardiac biomarkers were obtained.

    RESULTS: Compared to age/gender matched controls (n = 57), patients (n = 115, age (yrs): median(IQR) 48(28-60), females, n = 60(52%) had reduced left ventricular ejection fraction (LV-EF) and strain, and higher native T1 and T2. The early Tx group (n = 52) had significantly higher native T1, T2 and troponin levels compared to the late Tx group, indicating myocardial inflammation and oedema (p 

  15. Chen M, Arcari L, Engel J, Freiwald T, Platschek S, Zhou H, et al.
    Int J Cardiol Heart Vasc, 2019 Sep;24:100389.
    PMID: 31304234 DOI: 10.1016/j.ijcha.2019.100389
    Background: Patients with chronic kidney disease (CKD) have considerable cardiovascular morbidity and mortality. Aortic stiffness is an independent predictor of cardiovascular risk and related to left ventricular remodeling and heart failure. Myocardial fibrosis is the pathophysiological hallmark of the failing heart.

    Methods and results: An observational study of consecutive CKD patients (n = 276) undergoing comprehensive clinical cardiovascular magnetic resonance imaging. The relationship between aortic stiffness, myocardial fibrosis, left ventricular remodeling and the severity of chronic kidney disease was examined. Compared to age-gender matched controls with no known kidney disease (n = 242), CKD patients had considerably higher myocardial native T1 and central aortic PWV (p ≪ 0.001), as well as abnormal diastolic relaxation by E/e' (mean) by echocardiography (p ≪ 0.01). A third of all patients had LGE, with similar proportions for the presence and the (ischaemic and non-ischaemic) pattern between the groups. PWV was strongly associated with and age, NT-proBNP and native T1 in both groups, but not with LGE presence or type; the associations were amplified in severe CKD stages. In multivariate analyses, PWV was independently associated with native T1 in both groups (p ≪ 0.01) with near two-fold increase in adjusted R2 in the presence of CKD (native T1 (10 ms) R2, B(95%CI) CKD vs. non-CKD 0.28, 0.2(0.15-0.25) vs. 0.18, 0.1(0.06-0.15), p ≪ 0.01).

    Conclusions: Aortic stiffness and interstitial myocardial fibrosis are interrelated; this association is accelerated in the presence of CKD, but independent of LGE. Our findings reiterate the significant contribution of CKD-related factors to the pathophysiology of cardiovascular remodeling.

  16. Elhefnawy ME, Sheikh Ghadzi SM, Tangiisuran B, Zainal H, Looi I, Ibrahim KA, et al.
    Int J Gen Med, 2021;14:1205-1212.
    PMID: 33854362 DOI: 10.2147/IJGM.S303641
    BACKGROUND AND PURPOSE: Factors associated with ischemic stroke (IS) recurrence and the contribution of pharmacological treatment as secondary preventions among nondiabetics especially in the non-elderly population are unclear and not widely investigated. This was a population-based study that aimed to identify recurrent IS predictors and to determine the possible impact of secondary preventive medications on the IS recurrence in non-elderly adults with or without diabetes.

    METHODS: Data of 3386 patients <60 years old who had a history of index IS were extracted from the Malaysian National Neurology Registry (NNEUR) from 2009 to 2016. Recurrent IS was defined as any IS event recorded after the index IS in the NNEUR database. Multivariate logistic regression analysis was performed by using SPSS version 22.

    RESULTS: Ischemic heart disease (IHD) was the significant predictor of IS recurrence in non-elderly adults both with or without diabetes (adjusted odds ratio (AOR) of 3.210; 95%CI: 1.909-5.398 and 2.989; 95%CI: 1.515-5.894) respectively). Receiving antiplatelet as secondary stroke prevention (AOR: 0.194; 95%CI: 0.046-0.817) and continuation of antidiabetic medication after the index IS event (AOR: 0.510; 95%CI: 0.298-0.872) reduced the odds of IS recurrence only in non-elderly diabetic adults. Among non-elderly adults without diabetes, hyperlipidemia and every increased in 1 mmHg of systolic blood pressure significantly increased the odds of IS recurrence following the indexing event (AOR: 1.796; 95%CI: 1.058-3.051 and 1.009; 95%CI: 1.002-1.016 respectively).

    CONCLUSION: IHD was found as the main predictor of IS recurrence regardless of diabetes status in non-elderly adults after the index IS event. Receiving antidiabetic and antiplatelet medications upon discharge after index IS were significant predictors of recurrent IS in non-elderly diabetic adults. A proper randomized clinical trial may be required to determine the impact of secondary preventive medication on IS recurrence, especially in non-elderly adults.

  17. de Leuw P, Arendt CT, Haberl AE, Froadinadl D, Kann G, Wolf T, et al.
    JACC Cardiovasc Imaging, 2021 Aug;14(8):1548-1557.
    PMID: 33865770 DOI: 10.1016/j.jcmg.2021.01.042
    OBJECTIVES: The goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART).

    BACKGROUND: PLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood.

    METHODS: This prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization).

    RESULTS: A total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/m2 [49 to 77 g/m2] vs. 57 g/m2 [49 to 64 g/m2]), and N-terminal pro-B-type natriuretic peptide (109 pg/l [25 to 337 pg/l] vs. 48 pg/l [23 to 82 pg/l]) (all p 

  18. Vitamin E in Neuroprotection Study (VENUS) Investigators, Hor CP, Fung WY, Ang HA, Lim SC, Kam LY, et al.
    JAMA Neurol, 2018 04 01;75(4):444-452.
    PMID: 29379943 DOI: 10.1001/jamaneurol.2017.4609
    Importance: Management of painful diabetic peripheral neuropathy remains challenging. Most therapies provide symptomatic relief with varying degrees of efficacy. Tocotrienols have modulatory effects on the neuropathy pathway and may reduce neuropathic symptoms with their antioxidative and anti-inflammatory activities.

    Objective: To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy.

    Design, Setting, and Participants: The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited.

    Interventions: Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 μg thrice daily, in both groups.

    Main Outcomes and Measures: The primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result.

    Results: Of 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, -1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses.

    Conclusions and Relevance: Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration.

    Trial Registration: National Medical Research Registry Identifier: NMRR-10-948-7327 and clinicaltrials.gov Identifier: NCT01973400.

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