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Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p p HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

Optimal medical therapy (OMT) is recommended for patients with acute coronary syndrome (ACS) at discharge. This study aimed to assess temporal trends of OMT prescription as a five-drug regimen at discharge and its association with clinical outcomes in patients with ACS in Thailand.A retrospective cohort study was conducted in a tertiary-care medical center in Thailand. Data were collected from an electronic medical database. Patients were categorized into OMT or non-OMT groups based on their discharge medications. OMT was defined as a combination of aspirin and P2Y12 inhibitors, statins, beta-blockers, and angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. The primary outcome was 1-year all-cause mortality. The secondary outcome was major adverse cardiac events (MACE) which was defined as a composite of non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality. The prescription trends were also estimated. A multivariate Cox's proportional hazard model was used to assess the association of OMT prescriptions at discharge with all-cause mortality and MACE.A total of 3531 patients discharged with ACS [mean age, 69.5 (SD 12.4) years; 58.3% male] were identified. Only 42.6% were discharged with OMT. The rates of OMT prescriptions did not change over time. However, the prescription of OMT with high-intensity statin was significantly increased from 5.0% in 2013 to 38.3% in 2018 (p for trend0.001). Multivariable analyses indicated that OMT significantly reduced all-cause mortality (adjusted HR: 0.77; 95%CI: 0.63-0.95; p=0.012) and MACE (adjusted HR 0.84; 95%CI: 0.71-0.99; p = 0.044). Subgroup analysis indicated that patients receiving OMT with high-intensity statins exhibited survival benefits (adjusted HR: 0.72; 95%CI: 0.56-0.92; p=0.008).The five-drugs comprising OMT were associated with a reduction in all-cause mortality and MACE in patients with ACS. Nevertheless, OMT prescribing remains underused and could be enhanced in the real-world setting.

Objective To compare the effectiveness and rank order of physical therapy interventions, including conventional physical therapy (CPT), inspiratory muscle training (IMT), and early mobilization (EM) on mechanical ventilation (MV) duration and weaning duration. Data Sources PubMed, The Cochrane Library, Scopus, and CINAHL complete electronic databases were searched through August 2019. Study Selection Randomized controlled trials (RCTs) investigating the effect of IMT, EM, or CPT on MV duration and the weaning duration in patients with MV were included. Studies that were determined to meet the eligibility criteria by 2 independent authors were included. A total of 6498 relevant studies were identified in the search, and 18 RCTs (934 participants) were included in the final analysis. Data Extraction Data were extracted independently by 2 authors and assessed the study quality by the Cochrane risk-of-bias tool. The primary outcomes were MV duration and weaning duration. Data Synthesis Various interventions of physical therapy were identified in the eligible studies, including IMT, IMT+CPT, EM, EM+CPT, and CPT. The data analysis demonstrated that compared with CPT, IMT+CPT significantly reduced the weaning duration (mean difference; 95% confidence interval) (−2.60; −4.76 to −0.45) and EM significantly reduced the MV duration (−2.01; −3.81 to −0.22). IMT+CPT and EM had the highest effectiveness in reducing the weaning duration and MV duration, respectively. Conclusion IMT or EM should be recommended for improving the weaning outcomes in mechanically ventilated patients. However, an interpretation with caution is required due to the heterogeneity.

Background : : Acetaminophen is commonly used for the relief of pain and fever. Advocacy organizations recommend acetaminophen as the drug of choice in patients with kidney disease. Although some studies have suggested a risk of renal impairment after the use of acetaminophen, the effect of acetaminophen on the risk of renal impairment is unclear. The purpose of this research was to demonstrate any correlation linking acetaminophen treatment and renal impairment. Methods : : We performed a systematic review and meta-analysis of the association between acetaminophen and renal impairment in adults by searching Cochrane Library, PubMed, and Embase databases from initiation to June 16, 2019. Results : : Of 13,097 articles identified, 5 studies (2 cohort studies and 3 case-control studies) with a total of 13,114 participants were included. In the random-effects meta-analysis of the cohort study, acetaminophen use was shown to have statistically significant effects on the increased risk of renal impairment (adjusted odds ratio 1.23; 95% confidence interval, 1.07-1.40). The results of sensitivity and subgroup analyses also suggested that acetaminophen use increases the risk of renal impairment. The Egger’s test (P = 0.607) and Begg’s test (P = 0.732) revealed no apparent publication bias. Conclusion : : Acetaminophen is associated with a significantly increased risk of newly developing renal impairment in adults. Physicians who prescribe acetaminophen should be aware of potential adverse renal effects. A longitudinal study that further explores this association is warranted.

What is known and objective Hyponatremia is a common side effect of thiazide diuretics that can lead to increased mortality and hospitalization. A rapid and accurate screening tool is needed for rapid and appropriate management. In this study, we report on the development of a simple clinical screening tool for hyponatremia using thiazide diuretics. Methods This nested case-control study was performed by collecting data from 1 January 2015 to 30 June 2017. Univariable and multivariable logistic regressions were used to identify potential risk factors. The regression coefficients were converted into item scores by dividing each regression coefficient with the minimum coefficient in the model and rounding to the nearest integer. This value was then summed to the total score. The prediction power of the model was determined by the area under the receiver operating characteristic curve (AuROC). Results and discussion Six clinical risk factors, namely age ≥65 years, benzodiazepine use, history of a cerebrovascular accident, dose of hydrochlorothiazide ≥25 mg, female sex and statin use, were included in our ABCDF-S score. The model showed good power of prediction (AuROC 81.53%, 95% confidence interval [CI]: 78%-84%) and good calibration (Hosmer-Lemeshow X2 = 23.20; P = .39). The positive likelihood ratios of hyponatremia in patients with low risk (score ≤ 6) and high risk (score ≥ 8) were 0.26 (95% CI: 0.21-0.32) and 3.89 (95% CI: 3.11-4.86), respectively. What is new and conclusion The screening tool with six risk predictors provided a useful prediction index for thiazide-associated hyponatremia. However, further validation of the tool is warranted prior to its utilization in routine clinical practice.

Influenza is one of the most serious respiratory viral infections worldwide. Although several studies have reported that green tea catechins (GTCs) might prevent influenza virus infection, this remains controversial. We performed a systematic review and meta-analysis of eight studies with 5048 participants that examined the effect of GTC administration on influenza prevention. In a random-effects meta-analysis of five RCTs, 884 participants treated with GTCs showed statistically significant effects on the prevention of influenza infection compared to the control group (risk ratio (RR) 0.67, 95% CIs 0.51–0.89, p = 0.005) without evidence of heterogeneity (I2 = 0%, p = 0.629). Similarly, in three cohort studies with 2223 participants treated with GTCs, there were also statistically significant effects (RR 0.52, 95% CIs 0.35–0.77, p = 0.001) with very low evidence of heterogeneity (I2 = 3%, p = 0.358). Additionally, the overall effect in the subgroup analysis of gargling and orally ingested items (taking capsules and drinking) showed a pooled RR of 0.62 (95% CIs 0.49–0.77, p = 0.003) without heterogeneity (I2 = 0%, p = 0.554). There were no obvious publication biases (Egger’s test (p = 0.138) and Begg’s test (p = 0.103)). Our analysis suggests that green tea consumption is effective in the prophylaxis of influenza infections. To confirm the findings before implementation, longitudinal clinical trials with specific doses of green tea consumption are warranted.

To assess the efficacy and safety of low-dose prasugrel compared to clopidogrel based on the occurrence of major adverse cardiac events (MACEs) and major bleeding in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were systematically searched up to May 2020 to identify relevant randomized controlled trials (RCTs) and observational studies. A meta-analysis was conducted using a random effects model to estimate relative risks (RRs) with 95% confidence intervals (CIs). The primary efficacy and safety endpoints were MACE and major bleeding, respectively. Three RCTs (n = 2884) and five observational studies (n = 30,117) were included. A meta-analysis of RCTs revealed no significant differences in terms of MACE (RR 0.92, 95% CI 0.74 to 1.16) or major bleeding (RR 0.97, 95% CI 0.57 to 1.65) between low-dose prasugrel and clopidogrel. A meta-analysis of observational studies revealed no significant difference in terms of MACE (RR 1.13, 95% CI 0.82 to 1.55) between the two groups, but low-dose prasugrel was associated with a significantly increased risk of major bleeding (RR 1.33, 95% CI 1.02 to 1.72). We found that low-dose prasugrel was not associated with changes in MACE or major bleeding compared with clopidogrel in RCTs. However, analysis of data from observational studies revealed that low-dose prasugrel was associated with an increased risk of major bleeding compared with clopidogrel.

INTRODUCTION: Rotavirus gastroenteritis is the leading cause of severe diarrhoea among young children < 5 years old. Previous cost-effectiveness analyses on rotavirus (RV) vaccination in Thailand have generated conflicting results. The aim of this current study is to evaluate the economic impact of introducing RV vaccination in Thailand, using updated Thai epidemiological and cost data. METHODS: Both cost-utility analysis (CUA) and budget impact analysis (BIA) of human rotavirus vaccine (HRV) under a universal mass vaccination (UMV) programme were conducted. A published static, deterministic, cross-sectional population model was adapted to assess costs and health outcomes associated with RV vaccination among Thai children

Objective To examine the comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis (OM) in adult cancer patients. Methods We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489. Results A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance. Conclusions This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.

Background/Aims: COVID-19 has major effects on the clinical, humanistic, and economic outcomes among patients, particularly having severe symptoms or death. Smoking has been reported as one of the factors that increases severity and mortality rate among COVID-19 patients. However, the effect of smoking on such medical outcomes is still controversial. This study aims to conduct a systematic review and a meta-analysis (SR/MA) of the association between smoking and negative outcomes among COVID-19 patients. Method: Electronic databases, including PubMed, EMBASE, Cochrane Library, Science Direct, Google Scholar, were systematically searched, from the start of the database until 20 May 2020, for relevant published articles on smoking and COVID-19. All relevant studies were screened using a set of inclusion and exclusion criteria. The Newcastle–Ottawa Scale was used to assess the methodological quality of eligible articles. Random meta-analyses were conducted to estimate the odds ratio [OR] with 95% confidence interval [95%CI]. Publication bias was assessed using the funnel plot, Begg's test and Egger's test. All steps of SR/MA in this study were in line with PRISMA statement. The study protocol was registered with PROSPERO (CRD42020186638). Findings: A total of 510 studies were retrieved and reviewed and a final thirteen studies were included for meta-analysis. Both current smoking and former smoking can significantly increase the risk of disease severity (OR 1·51; 95% CI 1·06-2·15, p= 0·023, and OR 3·73; 95%CI 2·56-5·42, p

Over half of metabolic syndrome (MetS) patients have nonalcoholic fatty liver disease (NAFLD). To prevent its complications, standard routine screening is required, but the human-resource and budgetary implications need to be taken into consideration. This study compared the performances of 4 noninvasive scoring systems in predicting NAFLD in MetS patients. They were the fatty liver index, hepatic steatosis index, lipid accumulation product index, and nonalcoholic fatty liver disease in metabolic syndrome patients scoring system (NAFLD-MS). Scores were determined for 499 MetS patients, including 249 patients in a type 2 diabetes mellitus (T2DM) subgroup. Ultrasonography was used to diagnose NAFLD. The accuracies and performance of the scoring systems were analyzed using published cutoff values, and comparisons were made of their areas under receiver operating characteristic curves, sensitivities, specificities, positive and negative predictive values, and likelihood ratios. NAFLD was detected in 68% of the MetS patients and 77% of the MetS patients with T2DM. According to the areas under receiver operating characteristic curves, fatty liver index and hepatic steatosis index provided better performances in predicting NAFLD. NAFLD-MS provided the highest specificity of 99% among the MetS patients as a whole, and it provided even better accuracy with similar performance when applied to the subgroup of MetS patients with T2DM. The maximum cost avoidance from unnecessary ultrasonography was also reported by using NAFLD-MS. In terms of simplicity and ease of calculation, the lipid accumulation product index and NAFLD-MS are preferred. All 4 scoring systems proved to be acceptable for predicting NAFLD among MetS and T2DM patients in settings where the availability of ultrasonography is limited. NAFLD-MS provided the highest specificity and cost avoidance, and it is simple to use. All 4 systems can help clinicians decide further investigations.

Background: Air pollution is a global problem and also linked to respiratory diseases. Wildfire smog is a major cause of air pollution in the upper northern area of Thailand. Thus, in the current s...

Sajesh K Veettil,1 Peerawat Jinatongthai,2,3 Surakit Nathisuwan,4 Nattawat Teerawattanapong,2,3 Siew Mooi Ching,5,6 Kean Ghee Lim,7 Surasak Saokaew,3,8–10 Pochamana Phisalprapa,11 Christopher M Reid,12,13 Nathorn Chaiyakunapruk3,9,14,15 1Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia; 2Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 3School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia; 4Clinical Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 5Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 6Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Malaysia; 7Clinical School, Department of Surgery, International Medical University, Seremban, Malaysia; 8Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand; 9Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 10Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand; 11Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 12School of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 13School of Public Health, Curtin University, Perth WA, Australia; 14School of Pharmacy, University of Wisconsin, Madison, WI, USA; 15Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes (PICO), Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Subang Jaya, Malaysia Background: Various interventions have been tested as primary prevention of colorectal cancers (CRC), but comprehensive evidence comparing them is absent. We examined the effects of various chemopreventive agents (CPAs) on CRC incidence and mortality.Methods: We did a network meta-analysis based on a systematic review of randomized controlled trials (RCTs) that compared at least one CPA (aspirin, antioxidants, folic acid, vitamin B6, vitamin B12, calcium, vitamin D, alone or in combination) to placebo or other CPA in persons without history of CRC. Several databases were searched from inception up to March 2017. Primary outcomes were early and long-term CRC incidence and mortality.Results: Twenty-one RCTs comprising 281,063 participants, 9 RCTS comprising 160,101 participants, and 7 RCTs comprising 24,001 participants were included in the network meta-analysis for early risk of CRC incidence, long-term risk of CRC incidence and mortality, respectively. For early CRC incidence, no CPAs were found to be effective. For long-term CRC incidence and mortality, aspirin was the only intervention that showed protective effects with potential dose-dependent effects (risk ratio [RR], 0.74 [95% CI, 0.57–0.97] for high-dose [≥325 mg/day] and RR, 0.81 [95% CI, 0.67–0.98] for very-low-dose [≤100 mg/day]). Similar trend was found for mortality (RR, 0.43 [95% CI, 0.23–0.81] for low-dose [>100–325 mg/day] and RR, 0.65 [95% CI, 0.45–0.94] for very-low-dose). However, in net clinical benefit analysis, when combining risk estimates on mortality from CRC, cardiovascular disease, and pooled risk estimates of major gastrointestinal bleeding, low-dose aspirin provided the highest net survival gain (%) of 1.736 [95% CI, 1.010–2.434].Conclusion: Aspirin at the dose range of 75–325 mg/day is a safe and effective primary prevention for long-term CRC among people at average risk. None of the other CPAs were found to be effective. There may potentially be differential effects among various doses of aspirin that needs further investigation. Keywords: colorectal cancer, primary chemoprevention, chemopreventive agents, aspirin, network meta-analysis, net clinical benefit analysis

Azadirachta indica A. Juss var. siamensis Valeton or commonly known as Siamese neem is one of the most well-known plant in traditional Ayurvedic medicine. The aim of the present study was to investigate the relaxant effects of A. indica on isolated rat ileum contractions and its potential underlying mechanisms involved. The isometric contractions of ileum segments were investigated in organ baths for spontaneous activity and response to aqueous extract of Siamese neem flower (SNF). The spasmolytic action of the extract was also assessed on contraction induced by acetylcholine and high potassium. Our findings indicate that cumulative concentrations of SNF aqueous extract induced relaxant effect on spontaneous rat ileum contractions. The extract has also suppressed the cumulative concentration response curve for acetylcholine and pottasium ions-induced contraction. The presence and absence of propranol (antagonist of β-adrenergic receptor) and l-Name (antagonist of nitric oxide synthase) in SNF aqeous extract co-treatment demonstrated no significant different in term of contraction activity when compared to SNF extract treatment alone. The treatment of SNF extract caused a significant inhibition in tissue contraction stimulated by accumulation of calcium ions. Our results showed the relaxant effect of SNF aqueous extract on the isolated rat ileum. In short, the SNF aqueous extract exhibited an inhibitory effect on the spontaneous ileum contactions particularly on the contraction stimulated by acetylcholine and high potassium. The observed effect might acted through the modulation of calcium channels. This findings provide a pharmacological basis for the traditional use of SNF for the treatment of gastrointestinal spasms. Keywords: Siamese neem, Ileum, l-name, Propanolol, CaCl2

Objective To compare relative efficacy of different antibiotic therapies either with or without the addition of corticosteroids among adult patients with acute bacterial meningitis on all-cause mortality, neurological complications and any hearing loss. Methods We searched nine databases from inception to 8 February 2018 for randomized controlled trials evaluating pharmacological interventions and clinical outcomes in adult bacterial meningitis. An updated search from 9 February to 9 March 2020 was performed, and no new studies met the inclusion criteria. Study quality was assessed using the revised Cochrane Risk of Bias Tool. The Grading of Recommendations Assessment, Development and Evaluation system was used for quality of evidences evaluation. Meta-analyses were conducted to estimate the risk ratio with 95% confidence interval for both direct and indirect comparisons on the primary outcomes of all-cause mortality, neurologic sequelae and any hearing loss. The study was registered in PROSPERO (CRD42018108062). Results Nine RCTs were included in systematic review, involving 1,002 participants with a mean age ranging between 25.3 to 50.56 years. Six RCTs were finally included in the network-meta analysis. No significant difference between treatment was noted in meta-analysis. Network meta-analysis suggests that corticosteroids in combination with antibiotic therapy was more effective in reducing the risk of any hearing loss compared to mono antibiotic therapy (RR 0.64; 95%CI, 0.45 to 0.91, 4 RCTs, moderate certainty of evidence). Numerical lower risk of mortality and neurological complications was also shown for adjunctive corticosteroids in combination with antibiotic therapy versus mono antibiotic therapy (RR 0.65; 95%CI, 0.42 to 1.02, 6 RCTs, moderate certainty of evidence; RR 0.75; 95%CI, 0.47 to 1.18, 6 RCTs, moderate certainty of evidence). No differences were noted in the adverse events between different therapies. The overall certainty of evidence was moderate to very low for all primary outcomes examined. Conclusions Results of this study suggest that corticosteroids therapy in combination with antibiotic is more effective than mono antibiotic therapy in reducing the risk of any hearing loss in adult patients with acute bacterial meningitis. More well-design RCTs to investigate relative effective treatments in acute bacterial meningitis particularly in adult population should be mandated to aid clinicians in treatment recommendations.

Ethnopharmacological relevance Pueraria candollei var. mirifica (Airy Shaw & Suvat.) Niyomdham (commonly termed P. mirifica, PM) growing in upland Thailand has a long history as a postmenopausal rejuvenant therapy for indigenants. Its amelioration of menopause symptoms in clinical trials was assessed. Materials and methods International and Thai databases were searched from inception to February 2017. Clinical trials investigating effects of PM menopausal or postmenopausal women were included. Outcomes were self-reported menopausal symptoms, serum reproductive hormones, urino-genital tract function, and bone surrogates. Methodological quality was assessed by Cochrane risk-of-bias v2.0, and a 22-parameter quality score based on the CONSORT checklist for herbal medicines. Results Eight studies (9 articles) used data from 309 menopausal patients. Five-studies demonstrated that PM was associated with climacteric scores reduced by ~50% compared to baseline. Other PM studies using limited numbers of placebo participants suggested improved vaginal and other urogenital tract symptoms. Bone alkaline phosphatase halved (suggesting lowered bone turnover). Variable serum reproductive hormone levels suggested menopausal status differed between studies. PM active ingredients and sources were not defined. Adverse event rates (mastodynia, vaginal spotting, dizziness) were similar in all groups (PM, conjugated equine estrogen, and placebos) but serum C-reactive protein doubled. These studies had design and reporting deficiencies, high risks of biases, and low quality scores. Conclusions The efficacy of PM on menopausal symptoms remains inconclusive because of methodological short-comings especially placebo effects inherent in self-assessment/recall questionnaires and no PM standardization. PM efficacy and safety need a fundamental re-appraisal by: (i) cohort (retro- and prospective) studies on current users to define its traditional use for rejuvenation; (ii) tightly coupling long-term efficacy to safety of well-defined PM and multiple end-points; (iii) using study design related to current understanding of menopause progression and estrogen pharmacology (iv) robust pharmacovigilance.

Zingiber cassumunar Roxb. known locally as "Plai" in Thai, has been used for treating bruise, sprain and musculoskeletal pain. Several pre-clinical studies demonstrated the anti-inflammatory effect of Plai. However, current evidence of clinical effects of Plai is still unclear. This study aimed to determine the clinical efficacy and safety of Plai among all identified indications. Of the 808 articles identified by a systematic review, six studies were included. Four studies were randomized controlled trials, while two studies were quasi-experimental studies involving 178 patients in intervention group and 177 patients in control group. Duration of treatment ranged from 7days to 2 months. Our findings showed that 14% Plai cream had a strong trend of benefits in pain reduction for muscle pain and ankle sprain. However, evidence supporting the effects of Plai on acne vulgaris treatment and anti-histamine effect are still unclear.

Purpose To develop and evaluate a simple screening tool to assess hearing loss in newborns. A derived score was compared with the standard clinical practice tool. Methods This cohort study was designed to screen the hearing of newborns using transiently evoked otoacoustic emission and auditory brain stem response, and to determine the risk factors associated with hearing loss of newborns in 3 tertiary hospitals in Northern Thailand. Data were prospectively collected from November 1, 2010 to May 31, 2012. To develop the risk score, clinical-risk indicators were measured by Poisson risk regression. The regression coefficients were transformed into item scores dividing each regression-coefficient with the smallest coefficient in the model, rounding the number to its nearest integer, and adding up to a total score. Results Five clinical risk factors (Craniofacial anomaly, Ototoxicity, Birth weight, family history [Relative] of congenital sensorineural hearing loss, and Apgar score) were included in our COBRA score. The screening tool detected, by area under the receiver operating characteristic curve, more than 80% of existing hearing loss. The positive-likelihood ratio of hearing loss in patients with scores of 4, 6, and 8 were 25.21 (95% confidence interval [CI], 14.69-43.26), 58.52 (95% CI, 36.26-94.44), and 51.56 (95% CI, 33.74-78.82), respectively. This result was similar to the standard tool (The Joint Committee on Infant Hearing) of 26.72 (95% CI, 20.59-34.66). Conclusion A simple screening tool of five predictors provides good prediction indices for newborn hearing loss, which may motivate parents to bring children for further appropriate testing and investigations.

Background Accessibility of primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) in primary care settings is limited. Referring patients to PCI-capable hospitals might increase cardiac events. Hence, fibrinolytic injection before referring patients to PCI-capable settings decreases cardiac events, however, the effect of fibrinolytic injection before the referral has not been systematically evaluated. This study aimed to systematically review the effect of fibrinolytic injection before referring patients with STEMI to PCI-capable settings. Methods A systematic search with Embase, Cochrane CENTRAL, Google scholar, and PubMed was conducted. Studies conducted in patients with STEMI presented to non PCI-capable settings and compared fibrinolytic injection with no injection before referring patients to PCI-capable settings were included. The primary outcome was the composite outcomes of major adverse cardiac events (MACEs) at 30 days. Meta-analyses were performed using random-effect model. Results Of 912 articles, three RCTs and three non-RCTs were included. Based on RCTs, fibrinolytic injection before the referral has failed to decrease MACEs compared to non-fibrinolytic injection [relative risk (RR) 1.18; 95% confidence interval (CI), 0.89–1.57, p = 0.237]. Fibrinolytic injection has also failed to decrease mortality, re-infarction, and ischemic stroke. On the other hand, fibrinolytic injection was associated with a higher risk of major bleeding. Conclusions In non PCI-capable settings, fibrinolytic injection before referring patients with STEMI to PCI-capable settings has no clinical benefit but could increase risk of major bleeding. Clinicians might more carefully consider whether fibrinolytic injection should be used in patients with STEMI before the referral.

Cissus quadrangularis L. (Cissus) is a medicinal plant commonly used for centuries for various conditions, but lacks critical appraisal of its clinical effects. This study aimed to determine the efficacy and safety of Cissus in all conditions. Publications from 12 electronic databases were searched from inception through November 2016. A total of nine studies with 1108 patients were included. Each outcome was pooled using a random effects model. Effects of Cissus on hemorrhoid symptoms were not different from any comparators but had significant effects on bone pain. Effects of Cissus combination products on body weight reduction, low-density lipoprotein, triglyceride, total cholesterol, and fasting blood sugar were superior to placebo, with weighted mean difference of -5.19 kg (-8.82, -1.55), -14.43 mg/dl (-20.06, -8.80), -37.50 mg/dl (-48.71, -26.29), -50.50 mg/dl (-70.97, -30.04), and -10.39 mg/dl (-14.60, -6.18), respectively. No serious adverse effects were reported. Quality of evidence based on Grades of Recommendations Assessment Development and Evaluation (GRADE) indicated low (bone fractures) to high quality (hemorrhoids, body weight reduction).In conclusion, Cissus had benefit for bone fractures, but not for hemorrhoids. For obesity/overweight, only combination products are pooled and show benefit. However, high-quality studies remain needed. Copyright © 2017 John Wiley & Sons, Ltd.

Background Respiratory complications are some of the most common complications following thoracic surgery and can lead to higher perioperative morbidity and mortality. The purpose of this study was to develop a simple clinical score for prediction of respiratory complications after thoracic surgery, and determine the internal validity. Methods In this retrospective cohort study, all consecutive patients were aged 18 years and over and undergoing non-cardiac thoracic surgery at a tertiary-care university hospital. Respiratory complications included bronchospasm, atelectasis, pneumonia, respiratory failure, and adult respiratory distress syndrome within 30 days of surgery or before discharge. Results A total of 1488 patients were included over a 7-year period, and 15.8% (235 of 1488 patients) developed respiratory complications. The significant predictors of respiratory complications were chronic obstructive pulmonary disease, American Society of Anesthesiologist physical status ≥ 3, right-sided surgery, duration of surgery longer than 180 min, preoperative arterial oxygen saturation on room air Conclusions This study developed and internally validated a simple clinical risk score for prediction of respiratory complications following thoracic surgery. This score can be used to stratify high-risk patients, address modifiable risk factors for respiratory complications, and provide preventive strategies for improving postoperative outcomes.

A new Streptomyces species discovered from Sarawak mangrove soil is described, with the proposed name – Streptomyces monashensis sp. nov. (strain MUSC 1JT). Taxonomy status of MUSC 1JT was determined via polyphasic approach. Phylogenetic and chemotaxonomic properties of strain MUSC 1JT were in accordance with those known for genus Streptomyces. Based on phylogenetic analyses, the strains closely related to MUSC 1JT were Streptomyces corchorusii DSM 40340T (98.7%), Streptomyces olivaceoviridis NBRC 13066T (98.7%), Streptomyces canarius NBRC 13431T (98.6%) and Streptomyces coacervatus AS-0823T (98.4%). Outcomes of DNA–DNA relatedness between strain MUSC 1JT and its closely related type strains covered from 19.7 ± 2.8% to 49.1 ± 4.3%. Strain MUSC 1JT has genome size of 10,254,857 bp with DNA G + C content of 71 mol%. MUSC 1JT extract exhibited strong antioxidative activity up to 83.80 ± 4.80% in the SOD assay, with significant cytotoxic effect against colon cancer cell lines HCT-116 and SW480. Streptomyces monashensis MUSC 1JT (=DSM 103626T = MCCC 1K03219T) could potentially be a producer of novel bioactive metabolites; hence discovery of this new species may be highly significant to the biopharmaceutical industry as it could lead to development of new and useful chemo-preventive drugs.

Background A previous cost-effectiveness analysis (CEA) showed that Pneumococcal Conjugate Vaccine (PCV) 10 and PCV13 were not cost-effective for universal immunization among children in Thailand. Given recent changes in the evidence of efficacy, herd effects and price, a CEA of PCVs should be revisited. This study aimed to determine the cost-effectiveness of PCV10 and PCV13 compared to no PCV vaccination in Thai children. Material and methods A Markov model was developed under a societal perspective with a lifetime horizon. Inputs were derived from a comprehensive literature review. Costs were calculated using the Thai National Electronic Database and converted to the year 2017 value. All costs and outcomes were discounted at a rate of 3%. The findings were reported as incremental cost-effectiveness ratios (ICERs) in Thai Baht (THB) per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed. A cost-effectiveness acceptability curve was generated with the cost-effectiveness threshold of 160,000 THB/QALY. Results Base-case analysis of 2 + 1 dose schedule and five-year protection, with no consideration of herd effect showed that ICER for PCV10 was 170,437 THB/QALY, while ICER for PCV13 was 73,674 THB/QALY. With consideration of herd effect, both PCV10 and PCV13 had lower costs and higher QALYs compared to no PCV vaccination. Based on our probabilistic sensitivity analysis at willingness-to-pay of 160,000 THB/QALY, PCV13 had 93% of being cost-effective, while 4.7% and 2.3%, for PCV10 and no PCV vaccination, respectively. Conclusion At current prices, PCV13 is cost-effective, while PCV10 is not cost-effective in Thailand. When considering herd-effect, both PCV10 and PCV13 are cost-effective.

Air pollution exposure has been identified as being associated with childhood obesity. Nevertheless, strong evidence of such an association is still lacking. To analyze whether air pollution exposure affects childhood obesity, we conducted a systematic review and meta-analysis utilizing the PRISMA guidelines. Of 7343 studies identified, eight studies that investigated the effects of air pollutant characteristics, including PM2.5, PM10, PMcoarse, PMabsorbance, NOx, and NO2, on childhood obesity were included. The polled effects showed that air pollution is correlated with a substantially increased risk of childhood obesity. PM2.5 was found to be associated with a significantly increased risk (6%) of childhood obesity (OR 1.06, 95% CI 1.02–1.10, p = 0.003). In addition, PM10, PM2.5absorbance, and NO2 appeared to significantly increase the risk of obesity in children (OR 1.07, 95% CI 1.04–1.10, p < 0.00; OR 1.23, 95% CI 1.06–1.43, p = 0.07; and OR 1.10, 95% CI 1.04–1.16, p < 0.001, respectively). PMcoarse and NOx also showed trends towards being associated with an increased risk of childhood obesity (OR 1.07, 95% CI 0.95–1.20, p = 0.291, and OR 1.00, 95% CI 0.99–1.02, p = 0.571, respectively). Strong evidence was found to support the theory that air pollution exposure is one of the factors that increases the risk of childhood obesity.

Background: Controversy remains concerning the association of the all-cause mortality risk of hospitalized cardiovascular disease (CVD) patients with non-alcoholic fatty liver disease (NAFLD). This study investigated the risks of all-cause mortality among hospitalized CVD patients with NAFLD. Methods: We used related keywords to search for studies in 3 electronic databases: PubMed, EMBASE, and Cochrane Library. All eligible studies published up to April 2020 were reviewed. The findings of those studies reporting the mortality outcomes of hospitalized CVD patients with and without NAFLD were examined, and the various study results were pooled and analyzed using a random-effects model. A quality assessment using the Newcastle–Ottawa scale was performed on the studies selected for inclusion in a meta-analysis. Results: A total of 2135 studies were found, of which 3 were included in this meta-analysis. All studies were considered good quality. The mean age of the patients in the analysis was 73 years, and about half of them were men. The comorbidities reported were hypertension, diabetes mellitus, and dyslipidemia. The results showed that hospitalized CVD patients with NAFLD were at a significantly higher risk of all-cause mortality than non-NAFLD patients (adjusted hazard ratio of 2.08 [95% confidence interval, 1.56–2.59], P

Kaempferia parviflora (Krachaidum) is a medicinal plant in the family Zingiberaceae. Its rhizome has been used as folk medicine for many centuries. A number of pharmacological studies of Krachaidum had claimed benefits for various ailments. Therefore, this study aimed to systematically search and summarize the clinical evidences of Krachaidum in all identified indications. Of 683 records identified, 7 studies were included. From current clinical trials, Krachaidum showed positive benefits but remained inconclusive since small studies were included. Even though results found that Krachaidum significantly increased hand grip strength and enhanced sexual erotic stimuli, these were based on only 2 studies and 1 study, respectively. With regard to harmful effects, we found no adverse events reported even when Krachaidum 1.35 g/day was used. Therefore, future studies of Krachaidum are needed with regards to both safety and efficacy outcomes.

Although pneumococcal conjugate vaccines (PCVs) have been available for prevention of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae (S. pneumoniae) for over a decade, their adoption into national immunization programmes in low- and middle-income countries (LMICs) is still limited. Economic evaluations (EEs) play a crucial role in support of evidence-informed decisions. This systematic review aims to provide a critical summary of EEs of PCVs and identify key drivers of EE findings in LMICs. We searched Scopus, ISI Web of Science, PubMed, Embase and Cochrane Central from their inception to 30 September 2015 and limited the search to LMICs. The search was undertaken using the search strings ‘pneumococc* AND conjugat* AND (vaccin* OR immun*)’ AND ‘economic OR cost-effectiveness OR cost-benefit OR cost-utility OR cost-effectiveness OR cost-benefit OR cost-utility’ in the abstract, title or keyword fields. To be included, each study had to be a full EE of a PCV and conducted for an LMIC. Studies were extracted and reviewed by two authors. The review involved standard extraction of the study overview or the characteristics of the study, key drivers or parameters of the EE, assumptions behind the analyses and major areas of uncertainty. Out of 134 records identified, 22 articles were included. Seven studies used a Markov model for analysis, while 15 studies used a decision-tree analytic model. Eighteen studies performed a cost-utility analysis (CUA), with disability-adjusted life-years, quality-adjusted life-years or life-years gained as a measure of health outcome, while four studies focused only on cost-effectiveness analysis (CEA). Both CEA and CUA findings were provided by eight studies. Herd effects and serotype replacement were considered in 10 and 13 studies, respectively. The current evidence shows that both the 10-valent and 13-valent PCVs are probably cost effective in comparison with the 7-valent PCV or no vaccination. The most influential parameters were vaccine efficacy and coverage (in 16 of 22 studies), vaccine price (in 13 of 22 studies), disease incidence (in 11 of 22 studies), mortality from IPD and pneumonia (in 8 of 22 studies) and herd effects (in 4 of 22 studies). The findings were found to be supportive of the products owned by the manufacturers. Our review demonstrated that an infant PCV programme was a cost-effective intervention in most LMICs (in 20 of 22 studies included). The results were sensitive to vaccine efficacy, price, burden of disease and sponsorship. Decision makers should consider EE findings and affordability before adoption of PCVs.

Even though Insulin glargine (IGlar) has been available and used in other countries for more than a decade, it has not been adopted into Thai national formulary. This study aimed to evaluate the long-term cost effectiveness of IGlar versus neutral protamine Hagedorn (NPH) insulin in type 2 diabetes from the perspective of Thai Health Care System. A validated computer simulation model (the IMS CORE Diabetes Model) was used to estimate the long-term projection of costs and clinical outcomes. The model was populated with published characteristics of Thai patients with type 2 diabetes. Baseline risk factors were obtained from Thai cohort studies, while relative risk reduction was derived from a meta-analysis study conducted by the Canadian Agency for Drugs and Technology in Health. Only direct costs were taken into account. Costs of diabetes management and complications were obtained from hospital databases in Thailand. Both costs and outcomes were discounted at 3 % per annum and presented in US dollars in terms of 2014 dollar value. Incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analyses were also performed. IGlar is associated with a slight gain in quality-adjusted life years (0.488 QALYs), an additional life expectancy (0.677 life years), and an incremental cost of THB119,543 (US$3522.19) compared with NPH insulin. The ICERs were THB244,915/QALY (US$7216.12/QALY) and THB176,525/life-year gained (LYG) (US$5201.09/LYG). The ICER was sensitive to discount rates and IGlar cost. At the acceptable willingness to pay of THB160,000/QALY (US$4714.20/QALY), the probability that IGlar was cost effective was less than 20 %. Compared to treatment with NPH insulin, treatment with IGlar in type 2 diabetes patients who had uncontrolled blood glucose with oral anti-diabetic drugs did not represent good value for money at the acceptable threshold in Thailand.

Streptococcus suis (S. suis) is a gram-positive bacterial pathogen in pigs which can cause serious infections in human including meningitis, and septicaemia resulting in serious complications. There were discrepancies between different data and little is known concerning associated risk factors of S. suis. A systematic review and meta-analysis was conducted to investigate on S. suis infection risk factors in human. We searched eight relevant databases using the MeSH terms “Streptococcus suis” OR “Streptococcus suis AND infection” limited in human with no time nor language restriction. Out of 4,999 articles identified, 32 and 3 studies were included for systematic review and meta-analysis respectively with a total of 1,454 Streptococcus suis cases reported. S. suis patients were generally adult males and the elderly. The mean age ranged between 37 to 63 years. Meningitis was the most common clinical manifestation, and deafness was the most common sequelae found among survivors followed by vestibular dysfunction. Infective endocarditis was also noted as among the most common clinical presentations associated with high mortality rate in a few studies. Meta-analyses categorized by type of control groups (community control, and non-S. suis sepsis) were done among 850 participants in 3 studies. The combined odd ratios for studies using community control groups and non-S. Suis sepsis as controls respectively were 4.63 (95% CI 2.94–7.29) and 78.00 (95% CI 10.38–585.87) for raw pork consumption, 4.01 (95% CI 2.61–6.15) and 3.03 (95% CI 1.61–5.68) for exposure to pigs or pork, 11.47, (95% CI 5.68–23.14) and 3.07 (95% CI 1.81–5.18) for pig-related occupation and 3.56 (95% CI 2.18–5.80) and 5.84 (95% CI 2.76–12.36) for male sex. The results were found to be significantly associated with S. suis infection and there was non-significant heterogeneity. History of skin injury and underlying diseases were noted only a small percentage in most studies. Setting up an effective screening protocol and public health interventions would be effective to enhance understanding about the disease.

Patient Self-testing (PST) could be an option for present anticoagulation therapy monitoring, but current evidence on its cost-effectiveness is limited. This study aims to estimate the cost-effectiveness of PST to other different care approaches for anticoagulation therapy in Thailand, a low-to-middle income country (LMIC). A Markov model was used to compare lifetime costs and quality-adjusted life years (QALYs) accrued to patients receiving warfarin through PST or either anticoagulation clinic (AC) or usual care (UC). The model was populated with relevant information from literature, network meta-analysis, and database analyses. Incremental cost-effectiveness ratios (ICERs) were presented as the year 2015 values. A base-case analysis was performed for patients at age 45-year-old. Sensitivity analyses including one-way and probabilistic sensitivity analyses (PSA) were constructed to determine the robustness of the findings. From societal perspective, PST increased QALY by 0.87 and costs by 112,461 THB compared with UC. Compared with AC, PST increased QALY by 0.161 and costs by 21,019 THB. The ICER with PST was 128,697 (3625 USD) and 130,493 THB (3676 USD) per QALY gained compared with UC and AC, respectively. The probability of PST being cost-effective is 74.1% and 51.9%, compared to UC and AC, respectively, in Thai context. Results were sensitive to the efficacy of PST, age and frequency of hospital visit or self-testing. This analysis suggested that PST is highly cost-effective compared with usual care and less cost-effective against anticoagulation clinic. Patient self-testing strategy appears to be economically valuable to include into healthcare system within the LMIC context.

Background Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established. Methods Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA). Results In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80–160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70–0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44–0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300–325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68–1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59–0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33–0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal. Conclusion Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use. Electronic supplementary material The online version of this article (10.1186/s12885-017-3757-8) contains supplementary material, which is available to authorized users.

Human life expectancy is rapidly increasing with an associated increasing burden of chronic diseases, such as neurodegenerative diseases and cancer. However, there is limited progress in finding effective treatment for these conditions. For this reason, members of the genus Streptomyces have been explored extensively over the past decades as these filamentous bacteria are highly efficient in producing bioactive compounds with human health benefits. Being ubiquitous in nature, streptomycetes can be found in both terrestrial and marine environments. Previously, two Streptomyces strains (MUSC 137T and MUM 256) isolated from mangrove sediments in Peninsular Malaysia demonstrated potent antioxidant and cytotoxic activities against several human cancer cell lines on bioactivity screening. These results illustrate the importance of streptomycetes from underexplored regions aside from the terrestrial ecosystem. Here we provide the insights and significance of Streptomyces species in the search of anticancer and/or chemopreventive agents and highlight the impact of next generation sequencing on drug discovery from the Streptomyces arsenal.

Objectives To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection. Methods We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events. Results A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections. Conclusions Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Sajesh K Veettil,1 Nattawat Teerawattanapong,2 Siew Mooi Ching,3,4 Kean Ghee Lim,5 Surasak Saokaew,6–9 Pochamana Phisalprapa,10 Nathorn Chaiyakunapruk7,8,11,12 1School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia; 2Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 3Department of Family Medicine, Faculty of Medicine and Health Sciences, 4Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, 5Clinical School, Department ofSurgery, International Medical University, Seremban, Negeri Sembilan, 6Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, 7School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 8Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 9Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Thailand; 10Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 11School of Pharmacy, University of Wisconsin, Madison, USA; 12Health and Well-being Cluster, Global Asia Platform in the 21st Century (GA21) Platform, Monash University Malaysia, Selangor, Malaysia Background: Protective effects of several chemopreventive agents (CPAs) against colorectal adenomas have been well documented in randomized controlled trials (RCTs); however, there is uncertainty regarding which agents are the most effective.Methods: We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA) of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome). Using NMA, we ranked CPAs based on efficacy.Results: We identified 20 eligible RCTs enrolling 12,625 participants with a history of colorectal cancer or adenomas who were randomly assigned to receive either a placebo or one of 12 interventions. NMA using all trials demonstrated that celecoxib 800mg/day (relative risk [RR] 0.61, 95% confidence interval [CI] 0.45–0.83), celecoxib 400mg/day (RR 0.70, 95% CI 0.55–0.87), low-dose aspirin (RR 0.75, 95% CI 0.59–0.96) and calcium (RR 0.81, 95% CI 0.69–0.96) were significantly associated with a reduction in the recurrence of any adenomas. NMA results were consistent with those from pairwise meta-analysis. The evidence indicated a high (celecoxib), moderate (low-dose aspirin) and low (calcium) Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality. NMA ranking showed that celecoxib 800mg/day and celecoxib 400mg/day were the best CPAs, followed by low-dose aspirin and calcium. Considering advanced adenoma recurrence, only celecoxib 800mg/day and celecoxib 400mg/day were demonstrated to have a protective effect (RR 0.37, 95% CI0.27–0.52 vs RR 0.48, 95% CI 0.38–0.60, respectively).Conclusion: The available evidence from NMA suggests that celecoxib is more effective in reducing the risk of recurrence of colorectal adenomas, followed by low-dose aspirin and calcium. Since cyclooxygenase-2 (COX-2) inhibitors (eg, celecoxib) are associated with important cardiovascular events and gastrointestinal harms, more attention is warranted toward CPAs with a favorable benefit-to-risk ratio, such as low-dose aspirin and calcium. Keywords: colorectal adenomas, chemoprevention, systematic review, meta-analysis, network meta-analysis, randomized controlled trials

Reactive oxygen species and other radicals potentially cause oxidative damage to proteins, lipids, and DNA which may ultimately lead to various complications including mutations, carcinogenesis, neurodegeneration, cardiovascular disease, aging, and inflammatory disease. Recent reports demonstrate that Streptomyces bacteria produce metabolites with potent antioxidant activity that may be developed into therapeutic drugs to combat oxidative stress. This study shows that Streptomyces sp. MUM212 which was isolated from mangrove soil in Kuala Selangor, Malaysia, could be a potential source of antioxidants. Strain MUM212 was characterized and determined as belonging to the genus Streptomyces using 16S rRNA gene phylogenetic analysis. The MUM212 extract demonstrated significant antioxidant activity through DPPH, ABTS and superoxide radical scavenging assays and also metal-chelating activity of 22.03 ± 3.01%, 61.52 ± 3.13%, 37.47 ± 1.79%, and 41.98 ± 0.73% at 4 mg/mL, respectively. Moreover, MUM212 extract was demonstrated to inhibit lipid peroxidation up to 16.72 ± 2.64% at 4 mg/mL and restore survival of Vero cells from H2O2-induced oxidative damages. The antioxidant activities from the MUM212 extract correlated well with its total phenolic contents; and this in turn was in keeping with the gas chromatography–mass spectrometry analysis which revealed the presence of phenolic compounds that could be responsible for the antioxidant properties of the extract. Other chemical constituents detected included hydrocarbons, alcohols and cyclic dipeptides which may have contributed to the overall antioxidant capacity of MUM212 extract. As a whole, strain MUM212 seems to have potential as a promising source of novel molecules for future development of antioxidative therapeutic agents against oxidative stress-related diseases.

Streptomyces colonosanans MUSC 93JT, a novel strain isolated from mangrove forest soil located at Sarawak, Malaysia. The bacterium was noted to be Gram-positive and to form light yellow aerial and vivid yellow substrate mycelium on ISP 2 agar. The polyphasic approach was used to determine the taxonomy of strain MUSC 93JT and the strain showed a range of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. Phylogenetic and 16S rRNA gene sequence analysis indicated that closely related strains include Streptomyces malachitofuscus NBRC 13059T (99.2 % sequence similarity), Streptomyces missionensis NBRC 13063T (99.1 %) and Streptomyces phaeoluteichromatogenes NRRL 5799T (99.1 %). The DNA–DNA relatedness values between MUSC 93JT and closely related type strains ranged from 14.4 ± 0.1 % to 46.2 ± 0.4 %. The comparison of BOX-PCR fingerprints indicated MUSC 93JT exhibits a unique DNA profile. The genome of MUSC 93JT consists of 7,015,076 bp. The DNA G + C content was determined to be 69.90 mol%. The extract of strain MUSC 93JT was demonstrated to exhibit potent antioxidant activity via ABTS, metal chelating, and SOD assays. This extract also exhibited anticancer activity against human colon cancer cell lines without significant cytotoxic effect against human normal colon cells. Furthermore, the chemical analysis of the extract further emphasizes the strain is producing chemo-preventive related metabolites. Based on this polyphasic study of MUSC 93JT, it is concluded that this strain represents a novel species, for which the name Streptomyces colonosanans sp. nov. is proposed. The type strain is MUSC 93JT (=DSM 102042T =MCCC 1K02298T).

Background. This study evaluated the relative efficacy of strategies for the prevention of multidrug-resistant gram-negative bacteria (MDR-GNB) in adult intensive care units (ICUs). Methods. A systematic review and network meta-analysis was performed; searches of the Cochrane Library, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) included all randomized controlled trials and observational studies conducted in adult patients hospitalized in ICUs and evaluating standard care (STD), antimicrobial stewardship program (ASP), environmental cleaning (ENV), decolonization methods (DCL), or source control (SCT), simultaneously. The primary outcomes were MDR-GNB acquisition, colonization, and infection; secondary outcome was ICU mortality. Results. Of 3805 publications retrieved, 42 met inclusion criteria (5 randomized controlled trials and 37 observational studies), involving 62 068 patients (median age, 58.8 years; median APACHE [Acute Physiology and Chronic Health Evaluation] II score, 18.9). The majority of studies reported extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and MDR Acinetobacter baumannii. Compared with STD, a 4-component strategy composed of STD, ASP, ENV, and SCT was the most effective intervention (rate ratio [RR], 0.05 [95% confidence interval {CI}, .01-.38]). When ENV was added to STD+ASP or SCT was added to STD+ENV, there was a significant reduction in the acquisition of MDR A. baumannii (RR, 0.28 [95% CI, .18-.43] and 0.48 [95% CI, .35-.66], respectively). Strategies with ASP as a core component showed a statistically significant reduction the acquisition of ESBLproducing Enterobacteriaceae (RR, 0.28 [95% CI, .11-.69] for STD+ASP+ENV and 0.23 [95% CI, .07-.80] for STD+ASP+DCL). Conclusions. A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition. As some strategies were differential for certain bacteria, our study highlighted the need for further evaluation of the most effective prevention strategies.

Background Microbiome-directed therapies are increasingly used preoperatively and postoperatively to improve postoperative outcomes. Recently, the effectiveness of probiotics, prebiotics, and synbiotics in reducing postoperative complications (POCs) has been questioned. This systematic review aimed to examine and rank the effectiveness of these therapies on POCs in adult surgical patients. Methods We searched for articles from PubMed, Embase, Cochrane, Web of Science, Scopus, and CINAHL plus. From 2002 to 2015, 31 articles meeting the inclusion criteria were identified in the literature. Risk of bias and heterogeneity were assessed. Network meta-analyses (NMA) were performed using random-effects modeling to obtain estimates for study outcomes. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated. We then ranked the comparative effects of all regimens with the surface under the cumulative ranking (SUCRA) probabilities. Results A total of 2,952 patients were included. We found that synbiotic therapy was the best regimen in reducing surgical site infection (SSI) (RR = 0.28; 95% CI, 0.12-0.64) in adult surgical patients. Synbiotic therapy was also the best intervention to reduce pneumonia (RR = 0.28; 95% CI, 0.09-0.90), sepsis (RR = 0.09; 95% CI, 0.01-0.94), hospital stay (mean = 9.66 days, 95% CI, 7.60-11.72), and duration of antibiotic administration (mean = 5.61 days, 95% CI, 3.19-8.02). No regimen significantly reduced mortality. Conclusions This network meta-analysis suggests that synbiotic therapy is the first rank to reduce SSI, pneumonia, sepsis, hospital stay, and antibiotic use. Surgeons should consider the use of synbiotics as an adjunctive therapy to prevent POCs among adult surgical patients. Increasing use of synbiotics may help to reduce the use of antibiotics and multidrug resistance.

Centella asiatica (L.) Urb. has been used as an herbal brain tonic for mental disorders and enhancing memory, but no review of the overall evidence of C. asiatica and cognitive function has been conducted. This study aims to determine the effects of C. asiatica on cognitive function and its related properties. The current systematic review includes five randomized controlled trials (RCTs) conducted to determine the effect of C. asiatica alone and six RCTs conducted to determine the effect of C. asiatica-containing products. Meta-analysis indicated that there are no significant differences in all cognitive function domains of C. asiatica when compared to placebo. However, it could improve mood by increasing alert scores [SMD: 0.71 (95% CI; 0.01 to 1.41); I2 = 30.5%] and decreasing anger scores at 1 hour after treatment [SMD: −0.81 (95%CI; −1.51 to −0.09); I2 = 36.6%]. None of the studies reported adverse effects of C. asiatica. In conclusion, there is not strong evidence to support the use of C. asiatica for cognitive function improvement in each cognitive domain. C. asiatica could improve alertness and relieve anger. However, some limitations should be aware including dose regimen, plant preparation, standardization, and product variation. Future well-designed clinical trials using suitable doses of standardized C. asiatica are still needed.

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.

With a high prevalence of chronic kidney disease (CKD) in type 2 diabetes (T2DM) in Thailand, the appropriate treatment for the patients has become a major concern. This study aimed to evaluate long-term cost-effective of dipeptidyl peptidase-4 (DPP-4) inhibitor monothearpy vs sulfonylurea (SFU) monotherapy in people with T2DM and CKD.A validated IMS CORE Diabetes Model was used to estimate the long-term costs and outcomes. The efficacy parameters were identified and synthesized using a systematic review and meta-analysis. Baseline characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. Costs were expressed in 2014 US Dollars. Outcomes were presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty.From a societal perspective, treatment with DPP-4 inhibitors yielded more quality-adjusted life years (QALYs) (0.024) at a higher cost (66,000 Thai baht (THB) or1,829.27 USD) per person than SFU, resulting in the ICER of2.7 million THB/QALY (74,833.70 USD/QALY). The cost-effectiveness results were mainly driven by differences in HbA1c reduction, hypoglycemic events, and drug acquisition cost of DPP-4 inhibitors. At the ceiling ratio of 160,000 THB/QALY (4,434.59 USD/QALY), the probability that DPP-4 inhibitors are cost-effective compared to SFU was less than 10%.Compared to SFU, DPP-4 inhibitor monotherapy is not a cost-effective treatment for people with T2DM and CKD in Thailand.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide and is associated with substantial socioeconomic burden. Despite considerable research, including numerous randomised controlled trials (RCTs) and systematic reviews assessed the effect of various chemopreventive interventions for CRC, there remains uncertainty regarding the comparative effectiveness of these agents. No network meta-analytic study has been published to evaluate the efficacies of these agents for CRC. Therefore, the aim of this study is to summarise the direct and indirect evidence for these interventions to prevent CRC in average-high risk individuals, and to rank these agents for practical consideration. Methods: We will acquire eligible studies through a systematic search of MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials, CINAHL plus, IPA and clinicaltrials.gov website. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcomes are the incidence of CRC, the incidence/recurrence of any adenoma or change in polyp burden (number or size). Quantitative synthesis or meta-analysis will be considered. We will also construct a network meta-analysis (NMA) to improve precision of the comparisons among chemo-preventive interventions by combining direct and indirect evidence. The probability of each treatment being the best and/or safest, the number-needed-to-treat [NNT; 95% credible interval (CrIs)], and the number-needed-to-harm (NNH; 95% CrIs) will be calculated to provide measures of treatment efficacy. The GRADE approach will be used to rate the quality of evidence of estimates derived from NMA. Results: This protocol has been registered (registration number: CRD42015025849) with the PROSPERO (International Prospective Register of Systematic Reviews). The procedures of this systematic review and NMA will be conducted in accordance with the PRISMA-compliant guideline. The results of this systematic review and NMA will be submitted to a peer-reviewed journal for publication. Conclusions: To the best of our knowledge, this study will be the first NMA to identify the comparative effectiveness of interventions for the prevention of CRC. The results of our study will update evidence for chemoprevention of CRC, identify key areas for future research, and provide a framework for conducting large systematic reviews involving indirect comparisons.

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.

Non-alcoholic fatty liver disease (NAFLD) can progress from simple steatosis to hepatocellular carcinoma. None of tools have been developed specifically for high-risk patients. This study aimed to develop a simple risk scoring to predict NAFLD in patients with metabolic syndrome (MetS). A total of 509 patients with MetS were recruited. All were diagnosed by clinicians with ultrasonography-confirmed whether they were patients with NAFLD. Patients were randomly divided into derivation (n=400) and validation (n=109) cohort. To develop the risk score, clinical risk indicators measured at the time of recruitment were built by logistic regression. Regression coefficients were transformed into item scores and added up to a total score. A risk scoring scheme was developed from clinical predictors: BMI ≥25, AST/ALT ≥1, ALT ≥40, type 2 diabetes mellitus and central obesity. The scoring scheme was applied in validation cohort to test the performance. The scheme explained, by area under the receiver operating characteristic curve (AuROC), 76.8% of being NAFLD with good calibration (Hosmer-Lemeshow χ =4.35; P=.629). The positive likelihood ratio of NAFLD in patients with low risk (scores below 3) and high risk (scores 5 and over) were 2.32 (95% CI: 1.90-2.82) and 7.77 (95% CI: 2.47-24.47) respectively. When applied in validation cohort, the score showed good performance with AuROC 76.7%, and illustrated 84%, and 100% certainty in low- and high-risk groups respectively. A simple and non-invasive scoring scheme of five predictors provides good prediction indices for NAFLD in MetS patients. This scheme may help clinicians in order to take further appropriate action.

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.

To examine clinical outcomes of theophylline use in patients with chronic obstructive pulmonary disease (COPD) receiving inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA). Electronic data from five hospitals located in Northern Thailand between January 2011 and December 2015 were retrospectively collected. Propensity score (PS) matching (2:1 ratio) technique was used to minimize confounding factors. The primary outcome was overall exacerbations. Secondary outcomes were exacerbation not leading to hospital admission, hospitalization for exacerbation, hospitalization for pneumonia, and all-cause hospitalizations. Cox’s proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI). After PS matching, of 711 patients with COPD (mean age: 70.1 years; 74.4% male; 60.8% severe airflow obstruction), 474 theophylline users and 237 non-theophylline users were included. Mean follow-up time was 2.26 years. Theophylline significantly increased the risk of overall exacerbation (aHR: 1.48, 95% CI: 1.11–1.96; p = 0.008) and exacerbation not leading to hospital admission (aHR: 1.47, 95% CI: 1.06–2.03; p = 0.020). Theophylline use did not significantly increase the risk of hospitalization for exacerbation (aHR: 1.11, 95% CI: 0.79–1.58; p = 0.548), hospitalization for pneumonia (aHR: 1.28, 95% CI: 0.89–1.84; p = 0.185), and all-cause hospitalizations (aHR: 1.03, 95% CI: 0.80–1.33; p = 0.795). Theophylline use as add-on therapy to ICS and LABA might be associated with an increased risk for overall exacerbation in patients with COPD. A large-scale prospective study of theophylline use investigating both safety and efficacy is warranted.

Background:Protective effects of calcium supplementation against colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Our objective was to update and systematically evaluate the evidence for calcium supplementation taking into conside

Background:The prevalence of nonalcoholic fatty liver disease (NAFLD) has significantly increased over the last decades. Despite existence of several interventions, there remains unclear which interventions work the best.Methods:A systematic review and network meta-analysis of randomized tri