Displaying publications 81 - 100 of 205 in total

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  1. van Doremalen N, Lambe T, Sebastian S, Bushmaker T, Fischer R, Feldmann F, et al.
    PLoS Negl Trop Dis, 2019 06;13(6):e0007462.
    PMID: 31170144 DOI: 10.1371/journal.pntd.0007462
    Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiVB, a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiVB also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiVB also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiVB vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiVB is a suitable candidate for further NiV vaccine pre-clinical development.
    Matched MeSH terms: Survival Analysis
  2. Shepard DS, Undurraga EA, Halasa YA
    PLoS Negl Trop Dis, 2013;7(2):e2055.
    PMID: 23437406 DOI: 10.1371/journal.pntd.0002055
    BACKGROUND: Dengue poses a substantial economic and disease burden in Southeast Asia (SEA). Quantifying this burden is critical to set policy priorities and disease-control strategies.

    METHODS AND FINDINGS: We estimated the economic and disease burden of dengue in 12 countries in SEA: Bhutan, Brunei, Cambodia, East-Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Viet Nam. We obtained reported cases from multiple sources--surveillance data, World Health Organization (WHO), and published studies--and adjusted for underreporting using expansion factors from previous literature. We obtained unit costs per episode through a systematic literature review, and completed missing data using linear regressions. We excluded costs such as prevention and vector control, and long-term sequelae of dengue. Over the decade of 2001-2010, we obtained an annual average of 2.9 million (m) dengue episodes and 5,906 deaths. The annual economic burden (with 95% certainty levels) was US$950m (US$610m-US$1,384m) or about US$1.65 (US$1.06-US$2.41) per capita. The annual number of disability-adjusted life years (DALYs), based on the original 1994 definition, was 214,000 (120,000-299,000), which is equivalent to 372 (210-520) DALYs per million inhabitants.

    CONCLUSION: Dengue poses a substantial economic and disease burden in SEA with a DALY burden per million inhabitants in the region. This burden is higher than that of 17 other conditions, including Japanese encephalitis, upper respiratory infections, and hepatitis B.

    Matched MeSH terms: Survival Analysis
  3. Leong PK, Sim SM, Fung SY, Sumana K, Sitprija V, Tan NH
    PLoS Negl Trop Dis, 2012;6(6):e1672.
    PMID: 22679522 DOI: 10.1371/journal.pntd.0001672
    BACKGROUND: Snake envenomation is a serious public health threat in the rural areas of Asian and African countries. To date, the only proven treatment for snake envenomation is antivenom therapy. Cross-neutralization of heterologous venoms by antivenom raised against venoms of closely related species has been reported. The present study examined the cross neutralizing potential of a newly developed polyvalent antivenom, termed Neuro Polyvalent Snake Antivenom (NPAV). NPAV was produced by immunization against 4 Thai elapid venoms.

    PRINCIPAL FINDINGS: In vitro neutralization study using mice showed that NPAV was able to neutralize effectively the lethality of venoms of most common Asiatic cobras (Naja spp.), Ophiophagus hannah and kraits (Bungarus spp.) from Southeast Asia, but only moderately to weakly effective against venoms of Naja from India subcontinent and Africa. Studies with several venoms showed that the in vivo neutralization potency of the NPAV was comparable to the in vitro neutralization potency. NPAV could also fully protect against N. sputatrix venom-induced cardio-respiratory depressant and neuromuscular blocking effects in anesthetized rats, demonstrating that the NPAV could neutralize most of the major lethal toxins in the Naja venom.

    CONCLUSIONS/SIGNIFICANCE: The newly developed polyvalent antivenom NPAV may find potential application in the treatment of elapid bites in Southeast Asia, especially Malaysia, a neighboring nation of Thailand. Nevertheless, the applicability of NPAV in the treatment of cobra and krait envenomations in Southeast Asian victims needs to be confirmed by clinical trials. The cross-neutralization results may contribute to the design of broad-spectrum polyvalent antivenom.

    Matched MeSH terms: Survival Analysis
  4. Jaya F, Win MN, Abdullah MR, Abdullah MR, Abdullah JM
    Neuroepidemiology, 2002 Jan-Feb;21(1):28-35.
    PMID: 11744823
    All patients with a first-ever stroke admitted to the HUSM (Hospital Universiti Sains Malaysia) from 1997 to 1998 were included in this study. All risk factors were determined and analysed prospectively. There were 158 cases of stroke admitted during the study period. The majority of the patients were Malays (86.1%), with a male preponderance. The mean age (SD) of the patients with stroke was 59.3 (12.28) years. Hypertension was present in both cerebral infarct and intracerebral haemorrhage patients at almost the same rate (65.2 and 69.2%, respectively). The overall mortality was 37%, and most patients died in the 1st month after stroke (34%). We hope this study will highlight the problems associated with the presentation and management of stroke in Southeast Asia.
    Matched MeSH terms: Survival Analysis
  5. Ghani RA, Zainudin S, Ctkong N, Rahman AF, Wafa SR, Mohamad M, et al.
    Nephrology (Carlton), 2006 Oct;11(5):386-93.
    PMID: 17014550
    Sepsis is characterized by an uncontrolled release of pro-inflammatory and anti-inflammatory mediators leading to immunoparalysis, cellular and humoral dysfunction, multiorgan dysfunction and death. This study evaluated the efficacy of high-volume haemofiltration (HVHF) compared with continuous venovenous haemofiltration (CVVH) in removing these inflammatory mediators. Clinical responses were assessed with the sequential organ failure assessment (SOFA) score.
    Matched MeSH terms: Survival Analysis
  6. Pan JW, Zabidi MMA, Ng PS, Meng MY, Hasan SN, Sandey B, et al.
    Nat Commun, 2020 Dec 22;11(1):6433.
    PMID: 33353943 DOI: 10.1038/s41467-020-20173-5
    Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.
    Matched MeSH terms: Survival Analysis
  7. Cheah HY, Šarenac O, Arroyo JJ, Vasić M, Lozić M, Glumac S, et al.
    Nanotoxicology, 2017 03;11(2):210-222.
    PMID: 28098511 DOI: 10.1080/17435390.2017.1285071
    Conjugation of Doxorubicin (DOX) to N-(2-hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA-DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA-DOX. Rats implanted with radio-telemetry device were administered intravenously with DOX (5 mg/kg), HPMA-DOX (5 mg DOX equivalent/kg) and HPMA copolymer and subjected to continuous cardiovascular monitoring and echocardiography for 140 days. We found that DOX-treated rats had ruffled fur, reduced body weight (BW) and a low survival rate. Although BP and HR were normal, spectral analysis indicated that their BP and HR variabilities were reduced. All rats exhibited typical signs of cardiotoxicity at histopathology. In contrast, HPMA-DOX rats gained weight over time and survived. Although BP, HR and related variabilities were unaffected, the left ventricular end diastolic volume (EDV) of these rats, as well as of the HPMA copolymer-treated rats, was found increased at the end of observation period. Additionally, HPMA copolymer caused microscopic injury of the heart tissue. All of these suggest the necessity of caution when employing HPMA as carrier for prolonged drug delivery. The current study also indicates the potential of radiotelemetric-spectral-echocardiography approach for improved preclinical cardiovascular risk assessment of polymer-drug conjugate and other nano-sized-drug constructs.
    Matched MeSH terms: Survival Analysis
  8. Prando C, Samarina A, Bustamante J, Boisson-Dupuis S, Cobat A, Picard C, et al.
    Medicine (Baltimore), 2013 Mar;92(2):109-122.
    PMID: 23429356 DOI: 10.1097/MD.0b013e31828a01f9
    Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation. Four of these 9 variants are recurrent, affecting 25 of the 30 reported kindreds, due to founder effects in specific countries. All patients are homozygous and display complete IL-12p40 deficiency. As a result, the patients lack detectable IL-12p70 and IL-12p40 and have low levels of interferon gamma (IFN-γ). The clinical features are characterized by childhood onset of bacille Calmette-Guérin (attenuated Mycobacterium bovis strain) (BCG) and Salmonella infections, with recurrences of salmonellosis (36.4%) more common than recurrences of mycobacterial disease (25%). BCG vaccination led to BCG disease in 40 of the 41 patients vaccinated (97.5%). Multiple mycobacterial infections were rare, observed in only 3 patients, whereas the association of salmonellosis and mycobacteriosis was observed in 9 patients. A few other infections were diagnosed, including chronic mucocutaneous candidiasis (n = 3), nocardiosis (n = 2), and klebsiellosis (n = 1). IL-12p40 deficiency has a high but incomplete clinical penetrance, with 33.3% of genetically affected relatives of index cases showing no symptoms. However, the prognosis is poor, with mortality rates of up to 28.6%. Overall, the clinical phenotype of IL-12p40 deficiency closely resembles that of interleukin 12 receptor β1 (IL-12Rβ1) deficiency. In conclusion, IL-12p40 deficiency is more common than initially thought and should be considered worldwide in patients with MSMD and other intramacrophagic infectious diseases, salmonellosis in particular.
    Matched MeSH terms: Survival Analysis
  9. Ho AFW, Hao Y, Pek PP, Shahidah N, Yap S, Ng YY, et al.
    Medicine (Baltimore), 2019 Mar;98(10):e14611.
    PMID: 30855446 DOI: 10.1097/MD.0000000000014611
    Studies are divided on the effect of day-night temporal differences on clinical outcomes in out-of-hospital cardiac arrest (OHCA). This study aimed to elucidate any differences in OHCA survival between day and night occurrence, and the factors associated with differences in survival.This was a prospective, observational study of OHCA cases across multinational Pan-Asian sites. Cases were divided according to time call received by dispatch centers into day (0700H-1900H) and night (1900H-0659H). Primary outcome was 30-day survival. Secondary outcomes were prehospital and hospital modifiable resuscitative characteristics.About 22,501 out of 55,881 cases occurred at night. Night cases were less likely to be witnessed (40.2% vs. 43.1%, P 
    Matched MeSH terms: Survival Analysis
  10. Ahmad P, Nawaz R, Qurban M, Shaikh GM, Mohamed RN, Nagarajappa AK, et al.
    Medicine (Baltimore), 2021 Sep 10;100(36):e27127.
    PMID: 34516504 DOI: 10.1097/MD.0000000000027127
    In Malaysia, oral cancer is very common and the reported 5-year survival of such patients is nearly 50% after treatment with surgery and radiotherapy, much lower than most of the developed countries. This study aimed to investigate the socio-demographic and clinicopathological parameters that influence the mortality rate of the patients suffering from oral squamous cell carcinoma (OSCC) in the Kelantanse population.In this retrospective study, data regarding socio-demographic, clinicopathological factors, and treatment outcome associated with OSCC were gathered from the archives of the medical records office of Hospital Universiti Sains Malaysia. For statistical analysis, simple and multiple logistic regression were performed. The significance level was set to P 
    Matched MeSH terms: Survival Analysis
  11. Kong YC, Bhoo-Pathy N, O'Rorke M, Subramaniam S, Bhoo-Pathy NT, See MH, et al.
    Medicine (Baltimore), 2020 Feb;99(6):e19093.
    PMID: 32028433 DOI: 10.1097/MD.0000000000019093
    Percutaneous biopsy in breast cancer has been associated with an increased risk of malignant cell seeding. However, the importance of these observations remains obscure due to lack of corroborating evidence from clinical studies. We determined whether method of biopsy is associated with breast cancer survival. This hospital registry-based cohort study included 3416 non-metastatic breast cancer patients diagnosed from 1993 to 2011 in a tertiary setting. Factors associated with biopsy methods were assessed. Multivariable Cox regression analysis was used to determine the independent prognostic impact of method of biopsy. Overall, 990 patients were diagnosed by core needle biopsy (CNB), 1364 by fine needle aspiration cytology (FNAC), and 1062 by excision biopsy. Excision biopsy was significantly associated with more favorable tumor characteristics. Radiotherapy modified the prognostic impact of biopsy method (Pinteraction 
    Matched MeSH terms: Survival Analysis
  12. Wan NurHazirah Wan Ahmad Kamil, Zuraiza Mohamad Zaini, Anand Ramanathan, Thomas Abraham, Rosnah Mohd Zain
    MyJurnal
    Introduction: Oral squamous cell carcinoma (OSCC) is a major health problem worldwide. The overall survival rate remains at 50% despite numerous studies and various treatment modalities in OSCC. The presence of lymph node metastasis in OSCC is well established as an independent prognostic factor. This present study aims to investigate the association of four tumour antigens; FJX-1, GNα12, IFITM3 and MAGED4B with the sociodemographic and clinicopathological parameters of OSCC. The potential use of these markers as a prognostic indicator of patient sur-vival and lymph node metastasis in OSCC was explored. Methods: 35 cases of OSCC with available formalin-fixed paraffin-embedded (FFPE) specimens involving the tongue, buccal mucosa, gingiva, alveolus and floor of mouth were evaluated by immunohistochemistry for FJX-1, GNA12, IFITM3 and MAGED4B expression. Assessment of the expression of these tumour antigens was based on the cellular sub-site, intensity and percentage of staining in the OSCC samples. Results: The expression of all four tumour markers were expressed in all samples (n=35) but none statistically associated with any clinicopathological or socio-demographic parameters. Survival analysis using Kaplan-Meier test showed high expression of GNA12, IFITM3 and MAGED4B individually with poor prognosis in OSCC patients. A combination of markers, GNA12 and MAGED4B demonstrated a significant association with pa-tient survival in OSCC (p=0.014). Multivariate analysis after adjustment for selected socio-demographic factors (age, gender, risk habits and sub-sites of the oral cavity) revealed that high expression of both MAGED4B and GNA12 remained as an independent prognostic factor for poor prognosis in OSCC (HRR =5.231, 95% CI 1.601,17.084; p=0.006). Conclusion: We concluded that high combined expression of both marker (Gα12 and mAGED4B) might be used as an independent prognostic indicator in OSCC.
    Matched MeSH terms: Survival Analysis
  13. Qudsiah Suliman, Salmiah Md. Said, Nor Afiah Mohd. Zulkefli, Lim Poh Ying, Tan Kit-Aun
    MyJurnal
    Introduction: Despite advancement of treatment modalities, Tuberculosis (TB) treatment interruption rate has glob- ally accelerating, calling for greater framework shifting towards psychosocial intervention. Similarly, Selangor state had reported the perturbing TB treatment interruption rate, which was figured persistently above 10% in the interval year of 2014 to 2018, thus signifies an empirical assessment on Information-Motivation-Behavioural skills (IMB) determinants of TB intensive phase treatment. This study aims to determine the time to intensive phase TB treatment interruption and its prognostic factors among newly diagnosed pulmonary Tuberculosis (PTB) smear positive patients in urban district Selangor. Methods: A multi-centric prospective cohort study will recruit 695 newly diagnosed PTB smear positive patients at treatment centres in urban districts, Selangor. This study will utilize validated self-admin- istered questionnaire and standardised data collection form (PROFORMA). At baseline, we will elicit information on IMB models constructs, additionally on socio-demographics, health service factors and clinical characteristics. Meanwhile, four points follow up will be executed to retrieve information on treatment status and time varying effects of body weight, treatment side effects, symptoms improvement and internalised stigma. Finally, survival analysis will be computed to identify the time to intensive phase treatment interruption and its prognostic factors. Conclusion: This study will enlighten IMB model determinants of intensive phase treatment interruption, hence to endeavour psychosocial elements in designing time relevant public health strategies in TB case management.
    Matched MeSH terms: Survival Analysis
  14. Norma S, Azmi MT, Rotina AB
    MyJurnal
    Introduction: Diabetes Mellitus is a chronic disease and major cause of chronic renal disease. Chronic renal disease can be prevented if known risk factors were been early detected. Albuminuria is the earliest clinical evidence of chronic renal disease. Objectives of this study is to identify the incidence of albuminuria and relationship between albuminuria with socio demographic and clinical factors such as blood sugar control, blood pressure control, excessive body mass index and hypercholesterolemia.
    Methodology: Data been collected from patient’s record that been regularly follow up at Primary Healthcare Clinics in Negeri Sembilan. Duration of study follow up was from the date of they been diagnosed of Diabetes Mellitus Type 2 until detection of albuminuria or 1st July 2007,end date of data collection then survival analysis been done.
    Result: Majority of study population was female 60.9% and Malay 69.7%. Mean age was 59.9 ± 10.7 and duration having Diabetes Mellitus was 7.0 ± 6.3 years. Only 22% achieved optimum glucose (HbA1c < 6.5%), controlled blood preassure 130/80 mmHg 42.3%, level of cholesterol <4.5 mmol/L only 22.7 %, 11.4% of patients having ideal body weight < 23 kg/m2. The incidence of Diabetes Mellitus Type 2 was 24.4 cases per 1000 population. The median of follow up duration was 22 years; with minimum follow up was 7 months and maximum 42 years. Survival analysis showed that the median of free albuminuria among cases was 22 years (CI 95%:16.5 – 27.4). The log rank test showed no significant relationship between high blood pressure, excessive body mass index and hypercholesterolemia with albuminuria. This study noted that the occurrence of albuminuria seems to be higher among those were hypertensive (26.6%), and excessive body mass index (24.7%).
    Conclusion: Percentage of Diabetes Mellitus Type 2 patient that achieved optimum clinical target still very low. Early detection of albuminuria is very important as preventive measure of diabetes nephropathy. Good blood pressure control and ideal body weight also prevent of occurring diabetes nephropathy complication.
    Keywords: Diabetes Mellitus Type 2, albuminuria, survival analysis.
    Matched MeSH terms: Survival Analysis
  15. Faridah K, Azmi MT
    MyJurnal
    Background : Foot ulcers and its complications are an important cause of morbidity and mortality in diabetes. The aim of this retrospective study is to determine the ulcer-free survival in diabetic foot and its relevant predictors in a cohort of diabetic patients in the primary health care setting.
    Methods : Data of newly diagnosed diabetics (n=1121) who received treatment in five health centers in the district of Kuala Langat, Selangor between 1st January 1999 until the 30th June 2008 were studied. Information was gathered by reviewing patient’s medical records. All patients were followed until 31st December 2008. The duration of ulcer-free survival was measured from the date of being diagnosed as diabetic until the development of the ulcer.
    Results : The total incidence of diabetic foot ulcer was 9.9% (n=111), with an average annual incidence of 1%. The total incidence of amputation was 1.2%. Mean age of being diagnosed having diabetic was 52+10.7 year old and mean age of being diagnosed having diabetic foot ulcer was 54.68+10.16 year old. The mean for overall ulcer-free survival was 99 months (95%CI:96-102). Male gender (LR=6.56; p=0.01), smokers (LR=3.94; p=0.04), low body mass index (LR=4.45; p=0.03), impaired renal function (LR=5.17; p=0.02) and long duration between follow-up (LR=25.10; p
    Matched MeSH terms: Survival Analysis
  16. Wu YL, Kim JH, Park K, Zaatar A, Klingelschmitt G, Ng C
    Lung Cancer, 2012 Aug;77(2):339-45.
    PMID: 22494567 DOI: 10.1016/j.lungcan.2012.03.012
    Maintenance therapy, commenced immediately after the completion of first-line chemotherapy, is a promising strategy for improving treatment outcomes in patients with non-small-cell lung cancer (NSCLC). The global phase III SequentiAl Tarceva in UnResectable NSCLC (SATURN) study evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib as maintenance treatment in NSCLC patients without progression after first-line chemotherapy. We report a retrospective subanalysis of Asian patients enrolled in SATURN. Patients with advanced NSCLC with no evidence of progression after four cycles of chemotherapy were randomized to receive erlotinib 150 mg/day or placebo, until progressive disease or limiting toxicity. The co-primary endpoints of SATURN were progression-free survival (PFS) in all patients and in those with positive EGFR immunohistochemistry (IHC) status. Secondary endpoints included overall survival (OS), disease control rate, safety, quality of life (QoL) and biomarker analyses. In total, 126 patients from East and South-East Asian centers were randomized (14% of the intent-to-treat population): 88 from Korea, 28 from China and 10 from Malaysia; one patient was excluded from this analysis due to Indian ethnicity. PFS was significantly prolonged in the erlotinib treatment arm, both overall (hazard ratio [HR]: 0.57; p=0.0067) and in patients with EGFR IHC-positive disease (HR=0.50; p=0.0057). There was a trend towards an increase in OS, which reached statistical significance in the EGFR IHC-positive subgroup (p=0.0233). The overall response rate was significantly higher with erlotinib compared with placebo (24% versus 5%; p=0.0025). Erlotinib was generally well tolerated and had no negative impact on QoL in this subpopulation. The most common treatment-related adverse events were rash, diarrhea and pruritus. Erlotinib was effective and well tolerated in Asian patients, producing benefits consistent with those observed in the overall SATURN population. Maintenance treatment with erlotinib appears to be a useful option for the management of Asian patients with advanced NSCLC without progression after first-line chemotherapy.
    Matched MeSH terms: Survival Analysis
  17. Elias MH, Baba AA, Azlan H, Rosline H, Sim GA, Padmini M, et al.
    Leuk. Res., 2014 Apr;38(4):454-9.
    PMID: 24456693 DOI: 10.1016/j.leukres.2013.12.025
    Discovery of imatinib mesylate (IM) as the targeted BCR-ABL protein tyrosine kinase inhibitor (TKI) has resulted in its use as the frontline therapy for chronic myeloid leukemia (CML) across the world. Although high response rates are observed in CML patients who receive IM treatment, a significant number of patients develop resistance to IM. Resistance to IM in patients has been associated with a heterogeneous array of mechanisms of which point mutations within the ABL tyrosine kinase domain (TKD) are the frequently documented. The types and frequencies of mutations reported in different population studies have shown wide variability. We screened 125 Malaysian CML patients on IM therapy who showed either TKI refractory or resistance to IM to investigate the frequency and pattern of BCR-ABL kinase domain mutations among Malaysian CML patients undergoing IM therapy and to determine the clinical significance. Mutational screening using denaturing high performance liquid chromatography (dHPLC) followed by DNA sequencing was performed on 125 IM resistant Malaysian CML patients. Mutations were detected in 28 patients (22.4%). Fifteen different types of mutations (T315I, E255K, G250E, M351T, F359C, G251E, Y253H, V289F, E355G, N368S, L387M, H369R, A397P, E355A, D276G), including 2 novel mutations were identified, with T315I as the predominant type of mutation. The data generated from clinical and molecular parameters studied were correlated with the survival of CML patients. Patients with Y253H, M351T and E355G TKD mutations showed poorer prognosis compared to those without mutation. Interestingly, when the prognostic impact of the observed mutations was compared inter-individually, E355G and Y253H mutations were associated with more adverse prognosis and shorter survival (P=0.025 and 0.005 respectively) than T315I mutation. Results suggest that apart from those mutations occurring in the three crucial regions (catalytic domain, P-loop and activation-loop), other rare mutations also may have high impact in the development of resistance and adverse prognosis. Presence of mutations in different regions of BCR-ABL TKD leads to different levels of resistance and early detection of emerging mutant clones may help in decision making for alternative treatment. Serial monitoring of BCR-ABL1 transcripts in CML patients allows appropriate selection of CML patients for BCR-ABL1 KD mutation analysis associated with acquired TKI resistance. Identification of these KD mutations is essential in order to direct alternative treatments in such CML patients.
    Matched MeSH terms: Survival Analysis
  18. Goh AY, Lum LC, Abdel-Latif ME
    Lancet, 2001 Feb 10;357(9254):445-6.
    PMID: 11273070
    The 24 h availability of intensive care consultants (intensivists) has been shown to improve outcomes in adult intensive care units (ICU) in the UK. We tested whether such availability would improve standardised mortality ratios when compared to out-of-hours cover by general paediatricians in the paediatric ICU setting of a medium-income developing country. The standardised mortality ratio (SMR) improved significantly from 1.57 (95%CI 1.25-1.95) with non-specialist care to 0.88 (95%CI 0.63-1.19) with intensivist care (rate ratio 0.56, 95% CI 0.47-0.67). Mortality odds ratio decreased by 0.234, 0.246 and 0.266 in the low, moderate and high-risk patients. 24 h availability of intensivists was associated with improved outcomes and use of resources in paediatric intensive care in a developing country.
    Matched MeSH terms: Survival Analysis
  19. Langhorne P, O'Donnell MJ, Chin SL, Zhang H, Xavier D, Avezum A, et al.
    Lancet, 2018 05 19;391(10134):2019-2027.
    PMID: 29864018 DOI: 10.1016/S0140-6736(18)30802-X
    BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels.

    METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month.

    FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics.

    INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes.

    FUNDING: Chest, Heart and Stroke Scotland.

    Matched MeSH terms: Survival Analysis
  20. Dehghan M, Mente A, Zhang X, Swaminathan S, Li W, Mohan V, et al.
    Lancet, 2017 Nov 04;390(10107):2050-2062.
    PMID: 28864332 DOI: 10.1016/S0140-6736(17)32252-3
    BACKGROUND: The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear.

    METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering.

    FINDINGS: During follow-up, we documented 5796 deaths and 4784 major cardiovascular disease events. Higher carbohydrate intake was associated with an increased risk of total mortality (highest [quintile 5] vs lowest quintile [quintile 1] category, HR 1·28 [95% CI 1·12-1·46], ptrend=0·0001) but not with the risk of cardiovascular disease or cardiovascular disease mortality. Intake of total fat and each type of fat was associated with lower risk of total mortality (quintile 5 vs quintile 1, total fat: HR 0·77 [95% CI 0·67-0·87], ptrend<0·0001; saturated fat, HR 0·86 [0·76-0·99], ptrend=0·0088; monounsaturated fat: HR 0·81 [0·71-0·92], ptrend<0·0001; and polyunsaturated fat: HR 0·80 [0·71-0·89], ptrend<0·0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs quintile 1, HR 0·79 [95% CI 0·64-0·98], ptrend=0·0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality.

    INTERPRETATION: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings.

    FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

    Matched MeSH terms: Survival Analysis
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