Surasak Saokaew

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

BackgroundDespite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN.MethodsA comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model.ResultsA total of 4 studies with 55 SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls (general population) were found. SJS/TEN cases were found to be significantly associated with HLA-B*5801 allele in both groups of studies with matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population yielded similar findings.ConclusionWe found a strong and significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA-B*5801 allele screening may be considered in patients who will be treated with allopurinol.

Effectiveness of pharmacist-participated warfarin therapy management: a systematic review and meta-analysis.

Summary.  Objective: Although pharmacist‐participated warfarin therapy management (PWTM) has been accepted and implemented in various parts of the world, the evidence demonstrating the effects of PWTM compared with usual care on clinical outcomes is lacking. We performed a systematic review and meta‐analysis to compare the effects of PWTM with usual care on bleeding and thromboembolic outcomes. Methods: We searched MEDLINE, SCOPUS, EMBASE, IPA, CINAHL, Cochrane CENTRAL, Thai Index Medicus and Thai Medical Index, and reference lists of studies, without language restriction. Databases were searched from their inception to July 2009. The studies using warfarin as an anticoagulant with sufficient data for compilation of 2 × 2 tables were included. Both randomized controlled trials (RCTs) and non‐RCTs were considered. Two authors independently reviewed each study, assigned quality scores and extracted data for all outcomes using a standardized form. Pooled effect estimates (risk ratio; RR) were obtained using a random effects model. Result: Of 661 articles identified, 24 studies with 728,377 patients were included. In the random‐effects meta‐analysis of RCTs, the PWTM group had statistically significant effects on the prevention of total bleeding [RR, 0.51; 95% confidence interval (CI), 0.28–0.94]. However, the effects on major bleeding (RR, 0.64; 95% CI, 0.18–2.36), thromboembolic events (RR, 0.79; 95% CI, 0.33–1.93), all‐cause mortality (RR, 0.93; 95% CI, 0.41–2.13) and warfarin‐related mortality (RR, 0.65; 95% CI, 0.18–2.42) were not significant. Conclusion: Pharmacist’s participation in the management of warfarin therapy significantly reduces total bleeding, with a non‐significant trend towards decreases in other warfarin‐related complications.

Cost-effectiveness analysis of HLA-B*5801 testing in preventing allopurinol-induced SJS/TEN in Thai population.

Background Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), caused by allopurinol therapy, are strongly associated with the human leukocyte antigen (HLA), HLA-B*5801. Identification of HLA-B*5801 genotype before prescribing allopurinol offers the possibility of avoiding allopurinol-induced SJS/TEN. As there is a paucity of evidence about economic value of such testing, this study aims to determine the cost-effectiveness of HLA-B*5801 testing compared with usual care (no genetic testing) before allopurinol administration in Thailand. Methods and Finding A decision analytical and Markov model was used to estimate life time costs and outcomes represented as quality adjusted life years (QALYs) gained. The model was populated with relevant information of the association between gene and allopurinol-induced SJS/TEN, test characteristics, costs, and epidemiologic data for Thailand from a societal perspective. Input data were obtained from the literature and a retrospective database analysis. The results were expressed as incremental cost per QALY gained. A base-case analysis was performed for patients at age 30. A series of sensitivity analyses including scenario, one-way, and probabilistic sensitivity analyses were constructed to explore the robustness of the findings. Based on a hypothetical cohort of 1,000 patients, the incremental total cost was 923,919 THB (USD 29,804) and incremental QALY was 5.89 with an ICER of 156,937.04 THB (USD 5,062) per QALY gained. The cost of gout management, incidence of SJS/TEN, case fatality rate of SJS/TEN, and cost of genetic testing are considered very influential parameters on the cost-effectiveness value of HLA-B*5801 testing. Conclusions The genetic testing for HLA-B*5801 before allopurinol administration is considered a highly potential cost-effective intervention in Thailand. The findings are sensitive to a number of factors. In addition to cost-effectiveness findings, consideration of other factors including ethical, legal, and social implications is needed for an informed policy decision making.

Rhizoma coptidis: A potential cardiovascular protective agent

Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality in both the developed and developing world. Rhizoma coptidis (RC), known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae, such as Coptis chinensis Franch, C. deltoidea C.Y. Cheng et Hsiao, and C. teeta Wall which has been used by Chinese medicinal physicians for more than 2000 years. In China, RC is a common component in traditional medicines used to treat CVD associated problems including obesity, diabetes mellitus, hyperlipidemia, hyperglycemia and disorders of lipid metabolism. In recent years, numerous scientific studies have sought to investigate the biological properties of RC to provide scientific evidence for its traditional medical uses. RC has been found to exert significant beneficial effects on major risk factors for CVDs including anti-atherosclerotic effect, lipid-lowering effect, anti-obesity effect and anti-hepatic steatosis effect. It also has myocardioprotective effect as it provides protection from myocardial ischemia-reperfusion injury. These properties have been attributed to the presence of bioactive compounds contained in RC such as berberine, coptisine, palmatine, epiberberine, jatrorrhizine, and magnoflorine; all of which have been demonstrated to have cardioprotective effects on the various parameters contributing to the occurrence of CVD through a variety of pathways. The evidence available in the published literature indicates that RC is a herb with tremendous potential to reduce the risks of CVDs, and this review aims to summarize the cardioprotective properties of RC with reference to the published literature which overall indicates that RC is a herb with remarkable potential to reduce the risks and damage caused by CVDs.

The effects of metformin on ovarian cancer: a systematic review.

Objective The potential therapeutic effects of metformin on several cancers were reported. However, the evidence of the effects of metformin on ovarian cancer is still limited and inconclusive. This systematic review and meta-analysis study aims to summarize the existing evidence of the therapeutic effects of metformin on ovarian cancer. Methods We performed systematic searches using electronic databases including PubMed and EMBASE until December 2012. Key words included “metformin” AND (“ovarian cancer” OR “ovary tumor”). All human studies assessing the effects of metformin on ovarian cancer were eligible for inclusion. All articles were reviewed independently by 2 authors with a standardized approach for the purpose of study, study design, patient characteristics, exposure, and outcomes. The data were pooled using a random-effects model. Results Of 190 studies retrieved, only 3 observational studies and 1 report of 2 randomized controlled trials were included. Among those studies, 2 reported the effects of metformin on survival outcomes of ovarian cancer, whereas the other 2 reported the effects of metformin on ovarian cancer prevention. The findings of studies reporting the effects on survival outcomes indicated that metformin may prolong overall, disease-specific, and progression-free survival in ovarian cancer patients. The results of studies reporting the effects of metformin on ovarian cancer prevention were meta-analyzed. It indicated that metformin tended to decrease occurrence of ovarian cancer among diabetic patients with the pooled odds ratio of 0.57 (95% confidence interval, 0.16–1.99). Conclusions Our findings showed the potential therapeutic effects of metformin on survival outcomes of ovarian cancer and ovarian cancer prevention. However, most of the evidence was observational studies. There is a call for further well-conducted controlled clinical trials to confirm the effects of metformin on ovarian cancer survival and ovarian cancer prevention.

Insights into Bacteriophage Application in Controlling Vibrio Species

Bacterial infections from various organisms including Vibrio sp. pose a serious hazard to humans in many forms from clinical infection to affecting the yield of agriculture and aquaculture via infection of livestock. Vibrio sp. is one of the main foodborne pathogens causing human infection and is also a common cause of losses in the aquaculture industry. Prophylactic and therapeutic usage of antibiotics has become the mainstay of managing this problem, however, this in turn led to the emergence of multidrug resistant strains of bacteria in the environment; which has raised awareness of the critical need for alternative non-antibiotic based methods of preventing and treating bacterial infections. Bacteriophages – viruses that infect and result in the death of bacteria – are currently of great interest as a highly viable alternative to antibiotics. This article provides an insight into bacteriophage application in controlling Vibrio species as well underlining the advantages and drawbacks of phage therapy.

The Pharmacoeconomics of Breakthrough Cancer Pain

ABSTRACT Breakthrough cancer pain (BTP) has a significant impact on patients’ activities of daily living, family, and the society; however, the economic ramifications of BTP are largely unknown. This review aims to summarize the available pharmacoeconomics studies of BTP in the context of the availability of several formulations of rapid-onset opioids administered by various routes, which are significantly more expensive than oral opioids. A systematic literature search of PubMed and Tufts registry through August 2012 was conducted using key words including “breakthrough cancer pain” and “cost effectiveness.” After exclusion of irrelevant articles, a total of six articles were included. Studies reviewed include two economic survey studies, two quality improvement projects, and two decision-analytic models. These studies demonstrate BTP causes significant financial burden to patients and society through increased hospitalization and health care utilization. Only one study comparing placebo with intranasal fentanyl spray, oral transmucosal fentanyl citrate, and oral transmucosal fentanyl buccal tablet has demonstrated the cost-effectiveness of these rapid-onset opioids for the treatment of BTP. Overall, there is a lack of pharmacoeconomic studies for BTP management with rapid-onset opioids. Further study is warranted assessing the net benefit of rapid-onset opioids to oral opioids to assist decision-making by patients, clinicians, and payers.

Safety of herbal products in Thailand: An analysis of reports in the thai health product vigilance center database from 2000 to 2008

AbstractBackground: The use of herbal products continues to expand rapidly across the world and concerns regarding the safety of these products have been raised. In Thailand, Thai Vigibase, developed by the Health Product Vigilance Center (HPVC) under the Thai Food and Drug Administration, is the national database that collates reports from health product surveillance systems and programmes. Thai Vigibase can be used to identify signals of adverse events in patients receiving herbal products. Objectives: The purpose of the study was to describe the characteristics of reported adverse events in patients receiving herbal products in Thailand. Methods: Thai Vigibase data from February 2000 to December 2008 involving adverse events reported in association with herbal products were used. This database includes case reports submitted through the spontaneous reporting system and intensive monitoring programmes. Under the spontaneous reporting system, adverse event reports are collected nationwide via a national network of 22 regional centres covering more than 800 public and private hospitals, and health service centres. An intensive monitoring programme was also conducted to monitor the five single herbal products listed in the Thai National List of Essential Medicines (NLEM), while another intensive monitoring programme was developed to monitor the four single herbal products that were under consideration for inclusion in the NLEM. The database contained patient demographics, adverse events associated with herbal products, and details on seriousness, causality and quality of reports. Descriptive statistics were used for data analyses. Results: A total of 593 reports with 1868 adverse events involving 24 different products were made during the study period. The age range of individuals was 1–86 years (mean 47 years). Most case reports were obtained from the intensive monitoring programme. Of the reports, 72% involved females. The herbal products for which adverse events were frequently reported were products containing turmeric (44%), followed by andrographis (10%), veld grape (10%), pennywort (7%), plai (6%), jewel vine (6%), bitter melon (5%) and snake plant (5%). Gastrointestinal problems were the most common adverse effect reported. Serious adverse events included Stevens-Johnson syndrome, anaphylactic shock and exfoliative dermatitis. Conclusions: Adverse event reports on herbals products were diverse, with most of them being reported through intensive monitoring programmes. Thai Vigibase is a potentially effective data source for signal detection of adverse events associated with herbal products.

Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives

Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs.

Cost-effectiveness of pharmacist-participated warfarin therapy management in Thailand

INTRODUCTION Although pharmacist-participated warfarin therapy management (PWTM) is well established, the economic evaluation of PWTM is still lacking particularly in Asia-Pacific region. The objective of this study was to estimate the cost-effectiveness of PWTM in Thailand using local data where available. METHODS A Markov model was used to compare lifetime costs and quality-adjusted life years (QALYs) accrued to patients receiving warfarin therapy through PWTM or usual care (UC). The model was populated with relevant information from both health care system and societal perspectives. Input data were obtained from literatures and database analyses. Incremental cost-effectiveness ratios (ICERs) were presented as year 2012 values. A base-case analysis was performed for patients at age 45 years old. Sensitivity analyses including one-way and probabilistic sensitivity analyses were constructed to determine the robustness of the findings. RESULTS From societal perspective, PWTM and UC results in 39.5 and 38.7 QALY, respectively. Thus, PWTM increase QALY by 0.79, and increase costs by 92,491 THB (3,083 USD) compared with UC (ICER 116,468 THB [3,882.3 USD] per QALY gained). While, from health care system perspective, PWTM also results in 0.79 QALY, and increase costs by 92,788 THB (3,093 USD) compared with UC (ICER 116,842 THB [3,894.7 USD] per QALY gained). Thus, PWTM was cost-effective compared with usual care, assuming willingness-to-pay (WTP) of 150,000 THB/QALY. Results were sensitive to the discount rate and cost of clinic set-up. CONCLUSION Our finding suggests that PWTM is a cost-effective intervention. Policy-makers may consider our finding as part of information in their decision-making for implementing this strategy into healthcare benefit package. Further updates when additional data available are needed.