Displaying publications 21 - 39 of 39 in total

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  1. Lee KKC, Chia Wu DB, Topachevskyi O, Delgleize E, DeAntonio R
    Value Health Reg Issues, 2013 May;2(1):64-74.
    PMID: 29702855 DOI: 10.1016/j.vhri.2013.01.012
    BACKGROUND: Pneumococcal universal vaccination in Hong Kong was introduced in 2009.

    OBJECTIVES: We assessed the health and economic impact of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PCV-10) compared with the current 13-valent pneumococcal conjugate vaccine (PCV-13) recommended for Hong Kong in 2011, providing new elements to be considered by public health authorities in the future decision-making process for pneumococcal vaccines in this country.

    METHODS: An analytical model was used to estimate the annual economic and health outcomes of invasive pneumococcal disease (IPD), community-acquired pneumonia, and acute otitis media (AOM), including nontypeable H. influenzae-related AOM, for a birth cohort in Hong Kong from the payer perspective with a 10-year horizon. Clinical impact including morbidity-mortality, quality-adjusted life-years (QALYs), incremental costs, and cost-effectiveness comparing PCV-10 and PCV-13 were estimated. Probabilistic sensitivity analyses by using alternate scenarios were performed.

    RESULTS: Model projections indicate that PCV-13 and PCV-10 have approximately equivalent impact on the prevention of deaths caused by IPD and pneumonia. PCV-13 is projected to prevent 6 additional cases of IPD, whereas PCV-10 is projected to prevent 13,229 additional AOM cases and 101 additional QALYs. For the base case, PCV-10 vaccination is estimated to save 44.6 million Hong Kong dollars (34.1 million Hong Kong dollars discounted). Sensitivity analysis indicated that PCV-10 would generate more QALYs and save costs as compared with PCV-13.

    CONCLUSIONS: Universal infant vaccination with new available pneumococcal vaccines is expected to generate a significant additional impact on reducing the burden of pneumococcal diseases in Hong Kong. PCV-10 vaccination would be potentially a cost-saving strategy compared with PCV-13 vaccination, generating better cost offsets and higher QALY gains.

  2. Wong WP, Coles J, Chambers R, Wu DB, Hassed C
    J Alzheimers Dis Rep, 2017 Dec 02;1(1):181-193.
    PMID: 30480237 DOI: 10.3233/ADR-170031
    Background: The current lack of an effective cure for dementia would exacerbate its prevalence and incidence globally. Growing evidence has linked mindfulness to cognitive and psychological improvements that could be relevant for mild cognitive impairment (MCI).

    Objective: To investigate whether mindfulness practice can improve health outcomes of MCI.

    Methods: The study is the first longitudinal mixed-methods observational study with a one-year follow-up period, that customized an eight-week group-based mindfulness training program for older adults with MCI (n = 14). Measures included cognitive function, psychological health, trait mindfulness, adherence to mindfulness practice, and everyday activities functioning as assessed at pre-intervention, post-intervention, and one-year follow-up. Repeated measures ANOVAs, Pearson's correlation analyses, and Mann-Whitney U tests were performed.

    Results: The MCI participants showed significant improvements in cognitive function (p 

  3. You R, Liu J, Wu DB, Qian X, Lyu B, Zhang Y, et al.
    Cancer Manag Res, 2019;11:10239-10248.
    PMID: 31824194 DOI: 10.2147/CMAR.S219722
    Objective: The purpose of this study was to evaluate the cost-effectiveness of the combined use of afatinib and epidermal growth factor receptor (EGFR) testing versus gemcitabine-cisplatin as the first-line treatment for patients with non-small cell lung cancer (NSCLC) in China.

    Methods: A decision-analytic model, based on clinical phase III trials, was developed to simulate patient transitions. Direct costs were estimated from the perspective of the Chinese healthcare system. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated over a 5-year lifetime horizon. Model robustness was conducted in sensitivity analyses.

    Results: For the base case, EGFR mutation testing followed by afatinib treatment for advanced NSCLC increased 0.15 QALYs compared with standard chemotherapy at an additional cost of $5069.12. The ICER for afatinib maintenance was $33,416.39 per QALY gained. The utility of PFS and the cost of afatinib had the most important impact on the ICER. Scenario analyses suggested that when a patient assistance program (PAP) was available, ICER decreased to $22,972.52/QALY lower than the willingness-to-pay (WTP) threshold of China ($26,508/QALY).

    Conclusion: Our results suggest that gene-guided maintenance therapy with afatinib with the PAP might be a cost-effective treatment option compared with gemcitabine - cisplatin in China.

  4. Abdul Rafar NR, Hong YH, Wu DB, Othman MF, Neoh CF
    Value Health Reg Issues, 2019 May;18:151-158.
    PMID: 31082795 DOI: 10.1016/j.vhri.2019.02.003
    OBJECTIVES: To systematically review and assess the quality of the economic evidence of adjuvant trastuzumab usage in early breast cancer in Asian countries.

    METHODS: Literature search was performed using 6 electronic databases (PubMed, Scopus, Ovid MEDLINE, EconLit, National Health Service Economic Evaluation Database, and ISI Web of Knowledge). The final search was performed in October 2018. All potential economic studies were then checked for eligibility. The reporting and methodological qualities of each study were independently assessed by 2 authors of this review, using the Consolidated Health Economic Evaluation Reporting Standards, Drummond, and Philips checklists. To compare the different currencies used in these studies, all costs were converted into US dollars (2016).

    RESULTS: A total of 6 studies were included; most of them were performed from the healthcare provider perspective. The incremental cost-effectiveness ratio for evaluation performed for a lifetime horizon were reported at $8573 and $20 816 per quality-adjusted life-year in 2 studies. The model outcome was generally sensitive to the changes in trastuzumab drug acquisition cost and discount rate, as well as its clinical effectiveness. For the quality assessment, all studies fulfilled more than 50% of the requirements in the Consolidated Health Economic Evaluation Reporting Standards, Drummond, and Philips checklists.

    CONCLUSIONS: Adjuvant trastuzumab therapy is considered a cost-effective option for early breast cancer in Asian countries including China, Iran, Japan, Singapore, and Taiwan. All studies were generally well conducted. Economic evaluations from the societal perspective, with inclusion of indirect and informal care costs, are warranted to facilitate informed decision making among policy makers.

  5. You R, Zhang Y, Wu DB, Liu J, Qian X, Luo N, et al.
    Front Pharmacol, 2020;11:456.
    PMID: 32425768 DOI: 10.3389/fphar.2020.00456
    Objective: This study aims to estimate the cost-effectiveness of yearly intravenous zoledronic acid treatment versus weekly oral alendronate for postmenopausal osteoporotic women in China.

    Methods: We used a Markov microsimulation model to compare the cost-effectiveness of zoledronic acid with alendronate in Chinese postmenopausal osteoporotic women with no fracture history at various ages of therapy initiation from health care payer perspective.

    Results: The incremental cost-effectiveness ratios (ICERs) for the zoledronic acid versus alendronate were $23,581/QALY at age 65 years, $17,367/QALY at age 70 years, $14,714/QALY at age 75 years, and $12,169/QALY at age 80 years, respectively. In deterministic sensitivity analyses, the study demonstrated that the two most impactful parameters were the annual cost of zoledronic acid and the relative risk of hip fracture with zoledronic acid. In probabilistic sensitivity analyses, the probabilities of zoledronic acid being cost-effective compared with alendronate were 70-100% at a willingness-to-pay of $29,340 per QALY.

    Conclusions: Among postmenopausal osteoporotic women in China, zoledronic acid therapy is cost-effective at all ages examined from health care payer perspective, compared with weekly oral alendronate. In addition, alendronate treatment is shown to be dominant for patients at ages 65 and 70 with full persistence. This study will help clinicians and policymakers make better decisions about the relative economic value of osteoporosis treatments in China.

  6. Cheng KJG, Rivera AS, Lam HY, Ulitin AR, Nealon J, Dizon R, et al.
    PLoS One, 2020;15(6):e0234715.
    PMID: 32555618 DOI: 10.1371/journal.pone.0234715
    Influenza-associated mortality has not been quantified in the Philippines. Here, we constructed multiple negative binomial regression models to estimate the overall and age-specific excess mortality rates (EMRs) associated with influenza in the Philippines from 2006 to 2015. The regression analyses used all-cause mortality as the dependent variable and meteorological controls, time, influenza A and B positivity rates (lagged for up to two time periods), and annual and semiannual cyclical seasonality controls as independent variables. The regression models closely matched observed all-cause mortality. Influenza was estimated to account for a mean of 5,347 excess deaths per year (1.1% of annual all-cause deaths) in the Philippines, most of which (67.1%) occurred in adults aged ≥60 years. Influenza A accounted for 85.7% of all estimated excess influenza deaths. The annual estimated influenza-attributable EMR was 5.09 (95% CI: 2.20-5.09) per 100,000 individuals. The EMR was highest for individuals aged ≥60 years (44.63 [95% CI: 4.51-44.69] per 100,000), second highest for children aged less than 5 years (2.14 [95% CI: 0.44-2.19] per 100,000), and lowest for individuals aged 10 to 19 years (0.48 [95% CI: 0.10-0.50] per 100,000). Estimated numbers of excess influenza-associated deaths were considerably higher than the numbers of influenza deaths registered nationally. Our results suggest that influenza causes considerable mortality in the Philippines-to an extent far greater than observed from national statistics-especially among older adults and young children.
  7. Rosli MR, Neoh CF, Wu DB, Hassan NW, Mahmud M, Rahimi A, et al.
    Pharm Pract (Granada), 2021 09 09;19(3):2397.
    PMID: 34621450 DOI: 10.18549/PharmPract.2021.3.2397
    Background: Successful diabetes treatment requires commitment and understanding of disease management by the patients.

    Objective: This trial aimed to evaluate the programme effectiveness of home medication review by community pharmacists (HMR-CP) in optimising diabetes care and reducing medication wastage.

    Methods: A randomised controlled trial was conducted on 166 patients with Type 2 Diabetes Mellitus (T2DM) who were randomly assigned to the intervention or control groups. The intervention group received HMR-CP at 0-month, 3-month, and 6-month. The primary outcome was haemoglobin A1c (HbA1c) while clinical outcomes, anthropometric data, and humanistic outcomes were the secondary outcomes. For the intervention group, drug-related problems (DRP) were classified according to the Pharmaceutical Care Network Europe Foundation (PCNE). Medication adherence was determined based on the Pill Counting Adherence Ratio (PCAR). The cost of medication wastage was calculated based on the total missed dose by the T2DM patients multiplied by the cost of medication. General linear model and generalised estimating equations were used to compare data across the different time-points within and between the groups, respectively.

    Results: No significant difference was observed in the demographic and anthropometric data at baseline between the two groups except for fasting blood glucose (FBG). There was a significant reduction in the HbA1c (-0.91%) and FBG (-1.62mmol/L) over the study period (p<0.05). A similar observation was noted in diastolic blood pressure (DBP) and total cholesterol (TC) but not in high-density lipoprotein (HDL), and anthropometric parameters. Both utility value and Michigan Diabetes Knowledge Test (MDKT) scores increased significantly over time. As for the intervention group, significant changes in PCAR (p<0.001) and the number of DRP (p<0.001) were noted.

    Conclusions: HMR-CP significantly improved the glycaemic control, QoL, medication adherence, and knowledge of T2DM patients as well as reduced the number of DRP and cost of medication wastage. However, the impact of HMR-CP on certain clinical and anthropometric parameters remains inconclusive and further investigation is warranted.

  8. Rehman IU, Wu DB, Pauline Lai SM, Palanisamy UD, Lim SK, Khan TM
    PMID: 29167792 DOI: 10.3389/fmed.2017.00189
    Introduction: Several tools have been developed to assess the severity of pruritus. In Malaysia, no tool has been validated to assess pruritus in patients with chronic kidney disease (CKD). Therefore, the aim of our study was to validate the Malay 5D itching scale (M5D-IS) among patients with CKD in Malaysia.

    Method: The English version of the 5D-IS was translated into Malay according to International Guidelines. Face and content validity was determined by an expert panel and pilot tested in patients with end-stage renal disease (ESRD). The M5D-IS was then validated in a tertiary hospital in Malaysia from May to June 2016. We recruited patients with (i.e., patients with ESRD) and without pruritus (i.e., patients with stage 1-3 CKD) (to determine if the M5D-IS could discriminate between the two groups), and administered the M5D-IS at baseline and 2 weeks later. Exploratory factor analysis was used to examine the construct validity. Internal consistency was assessed using Cronbach's alpha and intraclass correlation coefficient was calculated to assess the reliability of the instrument.

    Results: A total of 70 participants were recruited (response rate = 100%). The majority were males (51.4%) and Malay (67.1%). Exploratory factor analysis revealed that the 5D-IS had 2-factor loadings: "daily routine activity" and "pattern of itching," which explained 77.7% of the variance. The overall score of the M5D-IS, as well as for each domain, was significantly worse in participants with pruritus (9.83 ± 0.35), compared to those without pruritus (5.51 ± 0.93, p 

  9. Kotirum S, Muangchana C, Techathawat S, Dilokthornsakul P, Wu DB, Chaiyakunapruk N
    Front Public Health, 2017;5:289.
    PMID: 29209602 DOI: 10.3389/fpubh.2017.00289
    Current study aimed to estimate clinical and economic outcomes of providing the Haemophilus influenzae type b (Hib) vaccination as a national vaccine immunization program in Thailand. A decision tree combined with Markov model was developed to simulate relevant costs and health outcomes covering lifetime horizon in societal and health care payer perspectives. This analysis considered children aged under 5 years old whom preventive vaccine of Hib infection are indicated. Two combined Hib vaccination schedules were considered: three-dose series (3 + 0) and three-dose series plus a booster does (3 + 1) compared with no vaccination. Budget impact analysis was also performed under Thai government perspective. The outcomes were reported as Hib-infected cases averted and incremental cost-effectiveness ratios (ICERs) in 2014 Thai baht (THB) ($) per quality-adjusted life year (QALY) gained. In base-case scenario, the model estimates that 3,960 infected cases, 59 disability cases, and 97 deaths can be prevented by national Hib vaccination program. The ICER for 3 + 0 schedule was THB 1,099 ($34) per QALY gained under societal perspective. The model was sensitive to pneumonia incidence among aged under 5 years old and direct non-medical care cost per episode of Hib pneumonia. Hib vaccination is very cost-effective in the Thai context. The budget impact analysis showed that Thai government needed to invest an additional budget of 110 ($3.4) million to implement Hib vaccination program. Policy makers should consider our findings for adopting this vaccine into national immunization program.
  10. Kasahara-Kiritani M, Saga Y, Wakamatsu A, Wu DB, Tsai IC
    Asian J Psychiatr, 2023 Aug;86:103671.
    PMID: 37311333 DOI: 10.1016/j.ajp.2023.103671
    BACKGROUND: Real-world evidence on the benefits of long-acting injectable (LAI) antipsychotics (AP) in patients with schizophrenia is limited, especially in the employed population in Japan. This study evaluates the effectiveness of LAI AP in preventing re-hospitalization in patients with schizophrenia, including the employed population.

    METHODS: This retrospective, observational, population-based study used the Japan Medical Data Center (JMDC) health insurance claims database to identify patients having schizophrenia before or on the day of the first LAI AP prescription (index date), and receiving LAI AP between April 1, 2012 and December 31, 2019. The number of all-cause, psychiatric-, and schizophrenia-related hospitalizations at baseline (365 days before index date) and during the 1-year follow-up period were evaluated.

    RESULTS: Of the 1692 patients who received LAI AP during the study period, 146 were included (employed: 55 [37.7 %]; dependent: 91 [62.3 %]). The mean age was 37 years; 50.7 % (n = 74) were females. During baseline period, 61 (41.8 %) patients were not hospitalized. During the follow-up period, 67 (45.9 %) patients underwent hospitalization ≤ 7 days; all-cause: 100 (68.7 %); psychiatry-related: 104 (76.2 %); schizophrenia-related: 114 (78.1 %). A higher proportion of patients were hospitalization-free during the follow-up in the employed vs. dependent population: all cause: 69.1 % vs. 61.5 %; psychiatric-related 76.4 % vs. 67.0 %, schizophrenia-related: 87.3 % vs. 71.4 %.

    CONCLUSION: This study demonstrated the effectiveness of LAI AP in preventing hospitalization in Japan. During the follow-up period, patients with schizophrenia receiving LAI AP, including the employed population, had a significant decrease in hospitalization length and re-hospitalization rate compared to baseline.

  11. Toh LS, Lai PS, Wu DB, Wong KT, Low BY, Tan AT, et al.
    Patient Prefer Adherence, 2014;8:1365-81.
    PMID: 25328386 DOI: 10.2147/PPA.S65718
    Purpose: To develop and validate the English version of the Satisfaction Questionnaire for Osteoporosis Prevention (SQOP) in Malaysia.
    Methods: The SQOP was modified from the Osteoporosis Patient Satisfaction Questionnaire and developed based on literature review and patient interviews. Face and content validity were established via an expert panel. The SQOP consists of two sections: clinical services and types of counseling. There were 23 items in total, each with a five-point Likert-type response. Satisfaction score was calculated by converting the total score to a percentage. A higher score indicates higher satisfaction. English speaking, non-osteoporotic, postmenopausal women aged 50 years were included in the study. Participants were randomized to either the control or intervention group. Intervention participants were provided counseling, whereas control participants received none. Participants answered the SQOP at baseline and 2 weeks later.
    Results: A total of 140 participants were recruited (control group: n=70; intervention group: n=70). No significant differences were found in any demographic aspects. Exploratory factor analysis extracted seven domains. Cronbach’s α for the domains ranged from 0.531–0.812. All 23 items were highly correlated using Spearman’s correlation coefficient 0.469–0.996 (P<0.05), with no significant change in the control group’s overall test–retest scores, indicating that the
    SQOP achieved stable reliability. The intervention group had a higher score than the control group (87.91±5.99 versus 61.87±8.76; P<0.05), indicating that they were more satisfied than control participants. Flesch reading ease was 62.9.
    Conclusion: The SQOP was found to be a valid and reliable instrument for assessing patients’ satisfaction towards an osteoporosis screening and prevention service in Malaysia.
    Keywords: patient satisfaction, randomized controlled trial, postmenopausal women, screening
    Study site: primary care clinic, tertiary hospital, Malaysia
  12. Wu DB, Lee EH, Chung WS, Chow DP, Lee VW, Wong MC, et al.
    Psychiatry Res, 2013 Dec 30;210(3):745-50.
    PMID: 24012164 DOI: 10.1016/j.psychres.2013.07.012
    Schizophrenia is one of the most expensive psychiatric illnesses. This study compared retrospectively health-care resources consumed 12 months before and 24 months after risperidone long-acting injection (RLAI) treatment in Hong Kong. A mirror-image analysis was conducted using data (N=191) from three public hospitals in Hong Kong from 2003 to 2007. The main outcome measure was hospitalisation cost. Other secondary outcomes such as hospitalisation episodes, outpatient visits and adverse events were also compared. A predictive model was established using linear regression based on generalised estimating equations. Analysis showed that RLAI was associated with a reduction in hospitalisation cost by HK$10,001,390 (24.7%) (HK$40,418,694 vs. HK$30,417,303; P-value <0.05). Days of hospitalisation were reduced by 1538 days (10.1%) (15,271 vs. 13,733; P-value <0.05). The predictive model estimated that the hospitalisation cost of patients using RLAI was only 11.1% (3.1-3.93%, 95% confidence interval (CI)) compared to those receiving conventional antipsychotics combined with oral risperidone. Cost of hospitalisation was significantly reduced after RLAI therapy. However, results should be considered as indicative or suggestive only, due to potential channelling bias where certain drug regimens are preferentially prescribed to patients with particular conditions. The findings from our study may be useful in health-care decision making considering treatment options for schizophrenia in resource-limited settings.
  13. Rehman IU, Wu DB, Ahmed R, Khan NA, Rahman AU, Munib S, et al.
    Medicine (Baltimore), 2018 08;97(31):e10764.
    PMID: 30075491 DOI: 10.1097/MD.0000000000010764
    BACKGROUND: Pruritus adds to the complications of chronic kidney disease (CKD) patient and a well-recognized complication among the CKD patients. Majority of the patients on hemodialysis experience a generalized pruritus and patients reported being moderately to extremely disturbed by at least one of the sleep-related condition. This study aim to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-associated pruritus.

    METHODS: A multicentered, open-label, parallel group, prospective randomized controlled trial among patients suffering from CKD-associated pruritus with sleep disturbance, after randomization into control, and intervention group to be held at North West General Hospital and Research Center Peshawar, Pakistan and Institute of Kidney Diseases Peshawar, Pakistan.

    RESULTS: The primary outcome is to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-associated pruritus. After baseline assessment by Urdu version of 5D itch scale and Urdu version of Pittsburgh Sleep Quality Index (PSQI) and Urdu EQ-5D 3L, the intervention group will be given zolpidem 10 mg oral tablets and control group with acupressure on both foots on KI-1 acupoints for total of 6 minutes. Assessment will be done at weeks 4 and 8 from baseline by using Urdu version of 5D itch scale and Urdu version of PSQI and Urdu EQ-5D 3L, whereas safety profiling of zolpidem 10 mg tablet at week 6 from baseline and acupressure acceptability at week 6 from baseline. Analysis of covariance will be used to examine the differences in treatment effects between the intervention and control groups.

    CONCLUSION: Improvement of sleep quality and quality of life among patients with CKD-associated pruritus requires great importance. This study aims to improve the quality of sleep and quality of life among patients with hemodialysis suffering from CKD-associated pruritus.

  14. Wu DB, Yee CH, Ng CF, Lee SWH, Chaiyakunapruk N, Chang YS, et al.
    Front Pharmacol, 2018;9:1078.
    PMID: 30386234 DOI: 10.3389/fphar.2018.01078
    Background: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) is a common condition affecting men. Studies have shown that the prevalence of LUTS/BPH increases with age, which will cause considerable economic burden to the healthcare system and society. The aim of the present study was to evaluate the long term cost effectiveness of dutasteride and tamsulosin therapy compared to tamsulosin alone in men with BPH in Hong Kong. Methods: A Markov decision model was constructed to estimate the economic impact from a healthcare payers' perspective, which only included direct costs. Analyses were conducted for a 4-year time frame. Results: When compared to tamsulosin alone, combination therapy was more expensive but also more effective in preventing complications and reduced the need for surgery. Over life-time projection suggest that combination therapy will be cost-effective if the willingness-to pay threshold of USD 20,000. Conclusion: Findings of this study found that combination therapy of tamsulosin and dutasteride was more cost-effective compared to tamsulosin alone across a wide range of scenario.
  15. Toh LS, Lai PSM, Wu DB, Bell BG, Dang CPL, Low BY, et al.
    Osteoporos Sarcopenia, 2019 Sep;5(3):87-93.
    PMID: 31728426 DOI: 10.1016/j.afos.2019.09.001
    Objectives: To compare and assess the performance of 6 osteoporosis risk assessment tools for screening osteoporosis in Malaysian postmenopausal women.

    Methods: Six osteoporosis risk assessments tools (the Simple Calculated Osteoporosis Risk Estimation [SCORE], the Osteoporosis Risk Assessment Instrument, the Age Bulk One or Never Estrogen, the body weight, the Malaysian Osteoporosis Screening Tool, and the Osteoporosis Self-Assessment Tool for Asians) were used to screen postmenopausal women who had not been previously diagnosed with osteoporosis/osteopenia. These women also underwent a dual-energy X-ray absorptiometry (DXA) scan to confirm the absence or presence of osteoporosis.

    Results: A total of 164/224 participants were recruited (response rate, 73.2%), of which only 150/164 (91.5%) completed their DXA scan. Sixteen participants (10.7%) were found to have osteoporosis, whilst 65/150 (43.3%) were found to have osteopenia. Using precision-recall curves, the recall of the tools ranged from 0.50 to 1.00, whilst precision ranged from 0.04 to 0.14. The area under the curve (AUC) ranged from 0.027 to 0.161. The SCORE had the best balance between recall (1.00), precision (0.04-0.12), and AUC (0.072-0.161).

    Conclusions: We found that the SCORE had the best balance between recall, precision, and AUC among the 6 screening tools that were compared among Malaysian postmenopausal women.

  16. Lin CW, Lo S, Perng DS, Wu DB, Lee PH, Chang YF, et al.
    Shock, 2014 Mar;41(3):241-9.
    PMID: 24365881 DOI: 10.1097/SHK.0000000000000111
    The accumulation of autophagosomes in the terminal step of the autophagic process has recently emerged as a potentially maladaptive process in the septic heart and lung. However, the role of autophagy in the septic liver has not been ascertained. This study was investigated by first examining the entire sequence of the autophagic process in the liver of septic mice. Second, a novel pharmacotherapeutic approach was utilized to treat sepsis with autophagy enhancer/inhibitor. Sepsis was induced by cecal ligation and puncture (CLP). C57BL/6 mice received autophagy enhancer carbamazepine (CBZ), autophagy inhibitor 3-methyladenine (inhibition of autophagosomal formation), or chloroquine (impairment of autophagosomal clearance). We found that the whole autophagic process was activated at 4 h after CLP; however, it did not proceed to completion during the 4- to 24-h time period, as indicated by accumulated autophagosomes and decreased autophagic flux. Carbamazepine, which induced complete activation of the autophagic process, improved CLP survival. This protective effect was also associated with decreased cell death, inflammatory responses, and hepatic injury. However, disruption of autophagosomal clearance with chloroquine abolished the above protective effects in CBZ-treated CLP mice. 3-Methyladenine, which resulted in inhibition of the autophagosomal formation, did not show any above beneficial effects in CLP mice. Impaired autophagosome-lysome fusion resulting in incomplete activation of autophagy may contribute to sepsis-induced liver injury. Treatment with CBZ may serve a protective role in the septic liver, possibly through the effect of complete activation of autophagic process.
  17. Rahman FA, Abdullah SS, Manan WZWA, Tan LT, Neoh CF, Ming LC, et al.
    Front Pharmacol, 2018;9:238.
    PMID: 29970999 DOI: 10.3389/fphar.2018.00238
    There are various studies that have addressed the use of Cyclosporine among patients with acute myocardial infarction (AMI). However, to date there is hardly any concise and systematically structured evidence that debate on the efficacy and safety of Cyclosporine in AMI patients. The aim of this review is to systematically summarize the overall evidence from published trials, and to conduct a meta-analysis in order to determine the efficacy and safety of Cyclosporine vs. placebo or control among patients with AMI. All randomized control trial (RCT) published in English language from January 2000 to August 2017 were included for the systematic review and meta-analysis. A total of six RCTs met the inclusion and were hence included in the systematic review and meta-analysis. Based on the performed meta-analysis, no significant difference was found between Cyclosporine and placebo in terms of left ventricular ejection fraction (LVEF) improvement (mean difference 1.88; 95% CI -0.99 to 4.74; P = 0.2), mortality rate (OR 1.01; 95% Cl 0.60 to 1.67, P = 0.98) and recurrent MI occurrence (OR 0.65; 95% Cl 0.29 to 1.45, P = 0.29), with no evidence of heterogeneity, when given to patients with AMI. Cyclosporine also did not significantly lessen the rate of rehospitalisation in AMI patients when compared to placebo (OR 0.91; 95% Cl 0.58 to 1.42, P = 0.68), with moderate heterogeneity (I2 = 46%). There was also no significant improvement in heart failure events between Cyclosporine and placebo in AMI patients (OR 0.63; 95% Cl 0.31 to 1.29, P = 0.21; I2 = 80%). No serious adverse events were reported in Cyclosporine group across all studies suggesting that Cyclosporine is well tolerated when given to patients with AMI. The use of Cyclosporine in this group of patients, however, did not result in better clinical outcomes vs. placebo at improving LVEF, mortality rate, recurrent MI, rehospitalisation and heart failure event.
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