Simplified Chronic Hepatitis B Antiviral Initiation Criteria in Thailand: An Economic Evaluation.

OBJECTIVES: Criteria for antiviral treatment initiation in Thailand were complex and difficult to implement. This study determined the cost-effectiveness of 2 simplified antiviral treatment initiation criteria among patients with chronic hepatitis B in Thailand. METHODS: A hybrid model of the decision tree and Markov model was developed. Two simplified antiviral treatment initiation criteria were the expanded criteria, treating patients with hepatitis B surface antigen positive and viral load (hepatitis B virus deoxyribonucleic acid) >2000 IU/mL or cirrhosis by tenofovir alafenamide (TAF), and the test-and-treat criteria, treating patients with hepatitis B surface antigen positive and viral load >10 IU/mL or cirrhosis by TAF. PubMed was searched from its inception to July 2023 to identify input parameters. Best supportive care was chosen for patients who were ineligible for TAF. Incremental cost-effectiveness ratio per quality-adjusted life-year (QALY) was calculated. RESULTS: The expanded criteria and the test-and-treat could reduce the occurrence of patients progressing to hepatocellular carcinoma. In particular, both criteria could reduce 4846 new cases of hepatocellular carcinoma per 100 000 patients. The incremental cost-effectiveness ratios for the expanded criteria and the test-and-treat criteria were 24 838 Thai baht (THB)/QALY and 163 060 THB/QALY, respectively. CONCLUSIONS: At the current willingness to pay of 160 000 THB/QALY, the expanded criteria were cost-effective, but the test-and-treat criteria were not cost-effective to be the simplified antiviral treatment initiation criteria for patients with chronic hepatitis B in Thailand.

Systematic review and network meta-analysis of efficacy and safety of interventions for preventing anti-tuberculosis drug induced liver injury.

Anti-tuberculosis drug induced liver injury (Anti-TB DILI) is the most common adverse events (AEs) necessitating therapy interruption but there is no preventing regimen. This study aimed to examine the efficacy and safety of herbs/alternative medicines for preventing anti-TB DILI. Relevant articles were identified through a systematic search in 5 international databases from inception till March 2022. All randomized controlled trials (RCT) assessing the effects of herbal or alternative medicines against anti-TB DILI were included. The network meta-analysis (NMA) was used to synthesize the evidence for preventing hepatotoxicity using a random-effects model. A total of 3423 patients from 14 RCTs were included. The NMA indicated that supplementation of Turmeric plus Tinospora cordifolia (RR 0.07; 95% CI 0.02 to 0.28), and N-acetyl cysteine (NAC) (RR 0.09; 95% CI 0.01 to 0.75) significantly reduced the incidence of anti-TB DILI compared with placebo. In addition, poly herbal product significantly reduced alkaline phosphatase (ALP) (MD - 21.80; 95% CI - 33.80 to - 9.80) and total bilirubin (Tbil) compared with placebo (MD - 0.51; 95% CI - 0.76 to - 0.26). There was no statistically significant difference in the occurrence of AEs in any intervention. In conclusion, Turmeric plus Tinospora cordifolia, NAC and poly-herbal product may provide benefit for preventing anti-TB DILI in TB patients. However, these findings are based on a small number of studies. Additional studies are warranted to confirm the findings.

Risk prediction algorithms in guiding antiviral therapy initiation among patients with chronic hepatitis B in Thailand: an economic evaluation and budget impact analysis.

OBJECTIVE: Several risk prediction algorithms have been developed to guide antiviral therapy initiation among patients with chronic hepatitis B (CHB). This study assessed the cost-effectiveness and budget impact of three risk prediction algorithms among patients with CHB in Thailand. METHODS: A decision tree with a Markov model was constructed. Three risk prediction algorithms were compared with current practices including HePAA, TREAT-B and REACH-B. PubMed was searched from its inception to December 2022 to identify inputs. Tenofovir alafenamide and best supportive care were selected for antiviral-eligible patients, and incremental cost-effectiveness ratios per quality-adjusted life year (QALY) were calculated. RESULTS: Our base case analysis showed that HePAA and REACH-B could provide better QALY (0.098 for HePAA and 0.921 for REACH-B) with decreased total healthcare costs (-10909 THB for HePAA and -8,637 THB for REACH-B). TREAT-B provided worse QALY (-0.144) with increased total healthcare costs (10,435 THB). The budget impacts for HePAA and REACH-B were 387 million THB and 3,653 million THB, respectively. CONCLUSION: HePAA and REACH-B algorithms are cost-effective in guiding antiviral therapy initiation. REACH-B is the most cost-effective option, but has a high budget impact. Policymakers should consider both cost-effectiveness and budget impact findings when deciding which algorithm should be implemented.

Efficacy and safety of herbal medicine on dementia and cognitive function: An umbrella review of systematic reviews and meta-analysis.

This study aims to summarize the effects of herbs on dementia and assess the strength of evidence. Six international and local databases were searched from inception to October 2021 for systematic reviews and meta-analyses of clinical trials investigated the effects of herbal medicine on dementia or cognitive function. Two researchers independently extracted data, assessed the methodological quality, and rated the credibility of evidence according to established criteria. Thirty-seven articles evaluating 13 herbal medicines were included. Of these, 65% were rated critically low using AMSTAR2. Of 90 unique outcomes, 41 (45.6%) were statistically significant based on random effects model (p ≤ .05). Only 3 herbs were supported by suggestive evidence whereas the others were supported by weak evidence. The suggestive evidence supported benefits of Chinese herbal medicine (CHM) plus pharmacotherapy (WMD:1.84; 95% CI: 1.34, 2.35) and Vinpocetine (WMD: -0.94; 95%CI: -1.50, -0.38) on improving cognitive function assessing by Montreal Cognitive Assessment and Syndrom-Kurz-Test, respectively. Moreover, suggestive evidence supported benefit of Huperzia serrata on improving Activities of Daily Living (WMD:-7.18; 95%CI: -9.12, -5.23). No SAE was reported. In conclusion, several herbs were used for improving dementia and cognitive function but recent evidence were limited by the small sample size and poor methodological quality. Therefore, further large and well-designed studies are needed to support the evidence.

Cost-Utility Analysis of Biologic Disease-Modifying Antirheumatic Drugs for Patients With Psoriatic Arthritis in Thailand.

OBJECTIVES: This study aimed to assess the cost-effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) for treating patients with psoriatic arthritis who failed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: A decision tree and Markov model were constructed to capture long-term costs and outcomes from a societal perspective. Patients with psoriatic arthritis who failed 2 previous csDMARDs were modeled over a 3-month cycle with a lifetime horizon. Clinical probabilities were derived from a published meta-analysis. Prices of bDMARDs were proposed by pharmaceutical companies. Other costs and utilities were based on data in Thailand. All costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratio and a series of sensitivity analyses were performed. RESULTS: All 11 bDMARDs (3 infliximab originator and biosimilars, 2 etanercept originator and biosimilar, golimumab, 2 secukinumab 150 mg and 300 mg, 3 adalimumab biosimilars) gained better quality-adjusted life-years (QALYs) with more costly than csDMARDs. Infliximab had the highest QALYs compared with other bDMARDs. Only secukinumab 150 mg showed the incremental cost-effectiveness ratio below the Thai threshold of 5152 US dollars per QALY. Cost of bDMARDs was the most influential factor. CONCLUSIONS: At the current price, secukinumab 150 mg shows the value for money in the Thai context. Price negotiation is of great importance for other bDMARDs.

Effects of pharmacist interventions on pain intensity: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Pharmacists can play an important role in pain management. OBJECTIVE(S): This review aims to summarize the effects of any type of pharmacist intervention, whether led by a pharmacist or in a supportive role, on pain intensity over time in individuals with pain of any etiology. METHODS: Three electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) were searched from inception to the end of May 2021 to identify randomized controlled trials (RCTs) that reported the effect of pharmacist interventions on pain intensity. Two reviewers independently extracted data and evaluated study quality. The analyses used a random-effects models and the Grading of Recommendations, Assessment, Development and Evaluation to rate the certainty of the evidence. The primary outcome was reduction in pain intensity and presented as standardized mean differences (SMD). RESULTS: Twelve RCTs including 1710 participants were included. Pooled estimate of 12 studies demonstrated a statistically significant reduction in pain intensity compared with control (SMD -0.22 [95% CI -0.31 to -0.12], I2 = 0%, low certainty). The intervention was more effective when a pharmacist delivered a combination of services comprising educational interventions, medication review, and pharmaceutical care services (SMD -0.24 [95% CI -0.35 to -0.13], I2 = 0%, moderate certainty). For educational interventions alone, no statistically significant difference was observed (SMD -0.15 [95% CI -0.45 to 0.15], I2 = 47.6%, low certainty). Pharmacist intervention was also effective in reducing pain intensity for patients with cancer-related pain (SMD -0.76 [95% CI -1.17 to -0.36], I2 = 0%, moderate certainty). CONCLUSION: There is some promising evidence to suggest that multicomponent pharmacist interventions including medication review or any other pharmaceutical care services, rather than merely educational interventions, are beneficial in reducing pain intensity, particularly in patients with chronic pain. High-quality RCTs are required to confirm the clinical significance of this findings before advocating for its widespread implication in clinical practice.

Efficacy and Safety of Eucalyptus for Relieving Cough: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To assess the efficacy and safety of Eucalyptus globulus Labill (Eucalyptus) on cough. Background: Cough is a common symptom of upper respiratory tract infections (URTIs) and bronchitis. Eucalyptus products are frequently used as over-the-counter cough medications but their efficacy and safety are uncertain. Methods: Randomized controlled trials (RCTs) investigating efficacy and safety of Eucalyptus for cough were systematically searched in electronic databases till February 2021. Two reviewers independently performed study selection, data extraction, and quality assessment. Clinical outcomes including improvement or resolution of overall cough symptoms, cough frequency (CF), and adverse events (AEs) of Eucalyptus were evaluated and analyzed using a random-effects model. Heterogeneity was evaluated using I2 and chi-squared test. Results: Six RCTs with 1,857 participants with cough were included in this study. Most of the included studies used Eucalyptus in combination formula (four of six studies). Based on Cochrane's risk of bias criteria, three of six studies (50%) were rated low risk of bias, whereas the remaining were judged as high risk of bias. This study found that Eucalyptus products are more effective than placebo in terms of improvement or resolution of overall cough symptoms with relative risk 1.45 (95% confidence interval (95% CI) 1.26-1.67). Whereas all Eucalyptus formulae reduced CF with weighted mean difference 0.44 (95% CI 0.28-0.60), when compared with placebo. There are no serious AEs associated with Eucalyptus during treatment periods. Mild-to-moderate gastrointestinal symptoms were common AEs reported in a comparable study between Eucalyptus and control groups. Conclusion: The findings indicate that Eucalyptus products are safe for use in cough related to respiratory diseases such as URTIs and bronchitis. However, their efficacy is minimal and of uncertain clinical importance. Further high-quality studies are still necessary to confirm this finding.

Economic Evaluation of Oral Nucleos(t)ide Analogues for Patients with Chronic Hepatitis B in Thailand.

BACKGROUND: Nucleos(t)ide analogues (NAs) are the main drug category used in the treatment of chronic hepatitis B (CHB). There is a need to update the economic evaluation of CHB treatment. OBJECTIVE: This study aimed to determine the cost effectiveness of NAs for CHB in Thailand. METHOD: We used a lifetime Markov model undertaken from a societal perspective. Tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), entecavir (ETV) with TDF or TAF as rescue medications, and lamivudine (LAM) with TDF or TAF rescue medications were compared with best supportive care (BSC). We performed a network meta-analysis to estimate the treatment effects of each NA on hepatitis B surface antigen (HBsAg) loss in an Asian population and performed an additional literature review to identify inputs. We calculated incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-years (QALYs) and performed sensitivity analyses. RESULTS: Compared with BSC, all NAs could improve patients' QALYs, with results ranging from 4.04 to 4.25 QALYs gained. TAF, TDF, LAM/TAF, and LAM/TDF yielded lower total lifetime costs than BSC, ranging from - $US1387 to - 814, whereas ETV/TAF and ETV/TDF yielded higher total lifetime costs than BSC, ranging from $US4965 to 4971. The ICER was $US1230/QALY for ETV/TDF and $US1228/QALY for ETV/TAF. Full incremental analysis showed that the ICER for LAM/TAF was $US1720/QALY compared with TAF. CONCLUSION: At current prices, TAF, TDF, LAM/TAF, and LAM/TDF are dominant options, and ETV/TAF or ETV/TDF are cost-effective options. LAM/TAF is the most cost-effective option, followed by TAF.

A meta-analysis of effects of CYP2C9 and CYP2C19 polymorphisms on phenytoin pharmacokinetic parameters.

Aim: Phenytoin is metabolized through CYP2C9 and CYP2C19. Polymorphisms of CYP2C9 and CYP2C19 may increase plasma concentration and side effects. Materials & methods: Systematic review and meta-analysis were performed to evaluate the effects of CYP2C9 and CYP2C19 polymorphism on pharmacokinetic parameters. PubMed, Science Direct, Cochrane library, and Thai databases were systematically searched. Results: Eight observational studies, comprising a total of 633 patients were included. Michaelis-Menten constant was significantly higher in the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups as compared with the control groups (CYP2C9EM/CYP2C19EM) at 2.16 and 1.55 mg/l (p < 0.00001, p < 0.0001). The maximum rate of action was significantly lower in the control groups as compared with the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups at 3.10 and 3.53 mg/kg/day (p = 0.00001, <0.0001). Conclusion: The dosage regimen for patients in the CYP2C9IM group to achieve phenytoin therapeutic levels was 2.1-3.4 mg/kg/day.

Aloe vera and health outcomes: An umbrella review of systematic reviews and meta-analyses.

This umbrella review aims to summarize the effects of Aloe vera on health outcomes and assess the strength of evidence. PubMed, Scopus, Embase, Cochrane database of systematic reviews, CINAHL, and AMED were searched from inception to October, 2019 for systematic reviews and meta-analyses of clinical trials that investigated the effects of Aloe vera on health outcomes. Two independent reviewers extracted data, assessed the methodological quality, and rated the credibility of evidence according to established criteria. Ten articles reporting 71 unique outcomes of Aloe vera were included. Of these, 47 (67%) were nominally statistically significant based on random-effects model (p ≤ .05). Only 3 outcomes were supported by highly suggestive evidence, whereas 42 outcomes were supported by weak evidence. The highly suggestive evidence supported benefits of Aloe vera in the prevention of second-degree infusion phlebitis (RR: 0.18, 95% CI: 0.10-0.32, p-value: 1.75 × 10-9 ) and chemotherapy-induced phlebitis based on overall incidence (OR: 0.13, 95% CI: 0.08-0.20, p-value: 9.68 × 10-20 ) and incidence of the second degree of severity (OR: 0.10, 95% CI: 0.07-0.14, p-value: 3.41 × 10-35 ). However, the majority of the evidence were limited by small sample size and poor methodological quality. Therefore, despite the overall favorable effect of Aloe vera, more robust studies are needed.

Efficacy and safety of pharmacological cachexia interventions: systematic review and network meta-analysis.

AIMS: Randomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia. METHODS: PubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI. RESULTS: 80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (≥400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (≥400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo. CONCLUSIONS: Our findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.

Systemic treatments for eczema: a network meta-analysis.

BACKGROUND: Eczema is a common and chronic, relapsing, inflammatory skin disorder. It seriously impacts quality of life and economic outcomes, especially for those with moderate to severe eczema. Various treatments allow sustained control of the disease; however, their relative benefit remains unclear due to the limited number of trials directly comparing treatments. OBJECTIVES: To assess the comparative efficacy and safety of different types of systemic immunosuppressive treatments for moderate to severe eczema using NMA and to generate rankings of available systemic immunosuppressive treatments for eczema according to their efficacy and safety. SEARCH METHODS: We searched the following databases up to August 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. SELECTION CRITERIA: All randomised controlled trials (RCTs) of systemic immunosuppressive agents for moderate to severe atopic eczema when compared against placebo or any other eligible eczema treatment. DATA COLLECTION AND ANALYSIS: We synthesised data using pair-wise analysis and NMA to compare treatments and rank them according to their effectiveness. Effectiveness was assessed primarily by determining the proportion of participants who achieved at least 75% improvement in the Eczema Area and Severity Index (EASI75) and improvement in the Patient-Oriented Eczema Measure (POEM). Safety was evaluated primarily by considering the proportion of participants with serious adverse events (SAEs) and infection. We deemed short-term follow-up as ≤ 16 weeks and long-term follow-up as > 16 weeks. We assessed the certainty of the body of evidence from the NMA for these primary outcomes using six domains of CiNEMA grading. MAIN RESULTS: We included a total of 74 studies, with 8177 randomised participants. Approximately 55% of participants were male, with average age of 32 years (range 2 to 84 years), although age and gender were unreported for 419 and 902 participants, respectively. Most of the included trials were placebo controlled (65%), 34% were head-to-head studies (15% assessed the effects of different doses of the same drug), and 1% were multi-armed studies with both an active comparator and a placebo. All trials included participants with moderate to severe eczema, but 62% of studies did not separate data by severity; 38% of studies assessed only severe eczema. The total duration of included trials ranged from 2 weeks to 60 months, whereas treatment duration varied from a single dose (CIM331, KPL-716) to 60 months (methotrexate (MTX)). Seventy studies were available for quantitative synthesis; this review assessed 29 immunosuppressive agents from three classes of interventions. These included (1) conventional treatments, with ciclosporin assessed most commonly; (2) small molecule treatments, including phosphodiesterase (PDE)-4 inhibitors, tyrosine kinase inhibitors, and Janus kinase (JAK) inhibitors; and (3) biological treatments, including anti-CD31 receptors, anti-interleukin (IL)-22, anti-IL-31, anti-IL-13, anti-IL-12/23p40, anti-OX40, anti-TSLP, anti-CRTH2, and anti-immunoglobulin E (IgE) monoclonal antibodies, but most commonly dupilumab. Most trials (73) assessed outcomes at a short-term duration ranging from 2 to 16 weeks, whereas 33 trials assessed long-term outcomes, with duration ranging from 5 to 60 months. All participants were from a hospital setting. Fifty-two studies declared a source of funding, and of these, pharmaceutical companies funded 88%. We rated 37 studies as high risk; 21, unclear risk, and 16, low risk of bias, with studies most commonly at high risk of attrition bias. Network meta-analysis suggests that dupilumab ranks first for effectiveness when compared with other biological treatments. Dupilumab is more effective than placebo in achieving EASI75 (risk ratio (RR) 3.04, 95% confidence interval (CI) 2.51 to 3.69) and improvement in POEM score (mean difference 7.30, 95% CI 6.61 to 8.00) at short-term follow-up (high-certainty evidence). Very low-certainty evidence means we are uncertain of the effects of dupilumab when compared with placebo, in terms of the proportion of participants who achieve EASI75 (RR 2.59, 95% CI 1.87 to 3.60) at longer-term follow-up. Low-certainty evidence indicates that tralokinumab may be more effective than placebo in achieving short-term EASI75 (RR 2.54, 95% CI 1.21 to 5.34), but there was no evidence for tralokinumab to allow us to assess short-term follow-up of POEM or long-term follow-up of EASI75. We are uncertain of the effect of ustekinumab compared with placebo in achieving EASI75 (long-term follow-up: RR 1.17, 95% CI 0.40 to 3.45; short-term follow-up: RR 0.91, 95% CI 0.28 to 2.97; both very low certainty). We found no evidence on ustekinumab for the POEM outcome. We are uncertain whether other immunosuppressive agents that targeted our key outcomes influence the achievement of short-term EASI75 compared with placebo due to low- or very low-certainty evidence. Dupilumab and ustekinumab were the only immunosuppressive agents evaluated for longer-term EASI75. Dupilumab was the only agent evaluated for improvement in POEM during short-term follow-up. Low- to moderate-certainty evidence indicates a lower proportion of participants with SAEs after treatment with QAW039 and dupilumab compared to placebo during short-term follow-up, but low- to very low-certainty evidence suggests no difference in SAEs during short-term follow-up of other immunosuppressive agents compared to placebo. Evidence for effects of immunosuppressive agents on risk of any infection during short-term follow-up and SAEs during long-term follow-up compared with placebo was of low or very low certainty but did not indicate a difference. We did not identify differences in other adverse events (AEs), but dupilumab is associated with specific AEs, including eye inflammation and eosinophilia. AUTHORS' CONCLUSIONS: Our findings indicate that dupilumab is the most effective biological treatment for eczema. Compared to placebo, dupilumab reduces eczema signs and symptoms in the short term for people with moderate to severe atopic eczema. Short-term safety outcomes from clinical trials did not reveal new safety concerns with dupilumab. Overall, evidence for the efficacy of most other immunosuppressive treatments for moderate to severe atopic eczema is of low or very low certainty. Given the lack of data comparing conventional with newer biological treatments for the primary outcomes, there remains high uncertainty for ranking the efficacy and safety of conventional treatments such as ciclosporin and biological treatments such as dupilumab. Most studies were placebo-controlled and assessed only short-term efficacy of immunosuppressive agents. Further adequately powered head-to-head RCTs should evaluate comparative long-term efficacy and safety of available treatments for moderate to severe eczema.

Efficacy and Safety of Mecobalamin on Peripheral Neuropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To assess the efficacy and safety of mecobalamin on peripheral neuropathy. Background: Mecobalamin is an active form of vitamin B12 that has been suggested to be beneficial in improving nerve conduction and neuropathic pain symptoms. Although it is already widely used in Asia for the treatment of peripheral neuropathies, its efficacy remains unclear. Methods: Relevant electronic databases were systematically searched for randomized controlled trials investigating the efficacy and safety of mecobalamin on peripheral neuropathy, from inception through December 2019. Study selection, data extraction, and quality assessment were performed independently by two reviewers. The clinical therapeutic efficacy, pain score, neuropathic symptom score, nerve conduction velocities (NCVs), and adverse events of mecobalamin were assessed and were pooled by using a random-effects model. Heterogeneity was assessed by I2 and chi-squared tests. Results: Fifteen studies with 1707 peripheral neuropathy patients caused by diabetic peripheral neuropathy and herpetic neuropathy were included. Based on Cochrane's risk of bias criteria, most of the included studies (11/15, 73%) were rated high risk of bias, whereas 20% and 7% were rated some concerns and low risk of bias, respectively. In terms of the proportion of patients achieving clinical therapeutic efficacy, mecobalamin alone (risk ratio [RR] = 1.17; 95% confidence interval [CI] 1.03-1.33) and mecobalamin in combination (RR = 1.32; 95% CI 1.21-1.45) are more effective than active control. For NCV outcomes, only mecobalamin combination treatment was effective. Neither mecobalamin alone nor mecobalamin in combination is effective on the pain score and neuropathic symptom outcomes. No serious adverse events associated with mecobalamin were reported during the treatment periods. Conclusion: Our findings indicate that mecobalamin in combination may be effective in improving clinical therapeutic efficacy and NCV outcomes for peripheral neuropathy patients, but the evidence is not clear for mecobalamin alone. More high-quality studies are required to confirm this finding.

The effects of cannabis, cannabinoids, and their administration routes on pain control efficacy and safety: A systematic review and network meta-analysis.

OBJECTIVES: To determine the effects of cannabis, cannabinoids, and their administration routes on pain and adverse euphoria events. DATA SOURCES: A systematic search was performed in PubMed, ScienceDirect, ClincalTrials.gov, Scopus, Cochrane Library, and Embase from inception until June 2017. STUDY SELECTION: Randomized controlled trials investigating the effects of cannabis or cannabinoids on pain reduction. DATA EXTRACTION: Two reviewers extracted and assessed the quality of studies by means of Cochrane risk of bias. Standardized mean difference (SMD) was calculated. Random-effects model was undertaken to pool the treatment effects. RESULTS: A total of 25 studies involving 2270 patients were included. We found that delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) (oromucosal route), THC (oromucosal route), and standardized dried cannabis (with THC; SCT; inhalation route) could reduce neuropathic pain score (SMD -0.41, 95% CI -0.7 to -0.1; -0.61, 95% CI -1.2 to -0.02; and -0.77, 95% CI -1.4 to -0.2; respectively). For nociceptive pain, only standardized cannabis extract (with THC; SCET) via oral route could reduce pain score (SMD -1.8, 95% C; -2.4 to -1.2). In cancer pain, THC/CBD via oromucosal route and THC via oral or oromucosal route could reduce pain score (SMD -0.7, 95% CI -1.2 to -0.2; and -2.1, 95% CI -2.8 to -1.4; respectively). No study was observed for THC/CBD via oral route or inhalation or THC via inhalation for cancer and nociceptive pain, SCET via oromucosal route or inhalation for neuropathic and cancer pain, THC via oromucosal route for nociceptive pain, and SCT via oromucosal or oral route for neuropathic, cancer, and nociceptive pain. Statistically significant increased risks of euphoria were observed in THC/CBD (oromucosal), THC (oromucosal), and SCT (inhalation). CONCLUSION: The use of cannabis and cannabinoids via certain administration routes could reduce different types of pain. Product developers could consider our findings as part of their product design so that the effective route of cannabis and cannabinoids for pain control can be achieved.

Effects of self-prepared hypertonic nasal saline irrigation in allergic rhinitis: A randomized controlled trial.

BACKGROUND: Nasal saline irrigation has been reported to be effective as an adjunctive therapy for allergic rhinitis (AR), but concerns about adverse events, supply problems, and high costs have limited its widespread clinical use. Aqueous 1.8% sodium chloride solution prepared by patients using drinking water (1.8% self-prepared hypertonic nasal saline irrigation; 1.8% SPHNSI) could solve some of these problems, but its clinical efficacy and safety need to be determined. OBJECTIVE: We aimed to compare the efficacy and safety of 1.8% SPHNSI and 0.9% commercial isotonic nasal saline irrigation (0.9% CINSI) in patients with AR. METHODS: A randomised, single-blinded, placebo-controlled trial was performed as a pilot study. Seventy-eight patients with AR were included. Each patient was randomised to nasal irrigation with 80 mL of either 1.8% SPHNSI or 0.9% CINSI twice-daily for 4 weeks. Randomised codes were generated using a computer and a block of 4 procedure. The primary outcome was improvement of quality of life scores in Thai patients with allergic rhinoconjunctivitis (Rcq-36). Secondary outcomes were clinical symptoms using total nasal symptom scores (TNSS) and adverse events. All outcomes were assessed by blinded assessors at baseline, week 2, and week 4. RESULTS: At week 4, nasal irrigation with 1.8% SPHNSI had significantly improved the Rcq-36 score (54% versus 50%; p < 0.032) and congestion symptom score (96% versus 84%; p < 0.018) compared to nasal irrigation with 0.9% CINSI. Adverse events were comparable for both groups at week 4. CONCLUSIONS: This pilot study indicates that regular use of 1.8% SPHNSI in AR patients for 4 weeks is safe and has superior efficacy to 0.9% CINSI for alleviating congestion and improving quality of life scores.

Weight Reduction and Pioglitazone are Cost-Effective for the Treatment of Non-Alcoholic Fatty Liver Disease in Thailand.

INTRODUCTION: This study evaluated lifetime liver-related clinical outcomes, costs of treatment, and the cost-effectiveness of treatment options for non-alcoholic fatty liver disease (NAFLD) in Thailand. METHODS: A cost-utility analysis using a lifetime Markov model was conducted among Thai patients with NAFLD, from a societal perspective. Pioglitazone, vitamin E, a weight reduction program, and usual care were investigated, with the outcomes of interest being the number of cirrhosis and hepatocellular carcinoma (HCC) cases, life expectancy, quality-adjusted life-years (QALYs), lifetime costs, and the incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed. RESULTS: When compared with usual care, a weight reduction program can prevent cirrhosis and HCC cases by 13.91% (95% credible interval [CrI] 0.97, 20.59) and 2.12% (95% CrI 0.43, 4.56), respectively; pioglitazone can prevent cirrhosis and HCC cases by 9.30% (95% CrI -2.52, 15.24) and 1.42% (95% CrI -0.18, 3.74), respectively; and vitamin E can prevent cirrhosis and HCC cases by 7.32% (95% CrI -4.64, 15.56) and 1.12% (95% CrI -0.81, 3.44), respectively. Estimated incremental life expectancy and incremental QALYs for all treatment options compared with usual care were approximately 0.06 years and 0.07 QALYs, respectively. The lifetime costs of both a weight reduction program and pioglitazone were less than usual care, while vitamin E was $3050 (95% CrI 2354, 3650). The weight reduction program dominated all other treatment options. The probability of being cost-effective in Thailand's willingness-to-pay threshold ($4546/QALY gained) was 76% for the weight reduction program, 22% for pioglitazone, 2% for usual care, and 0% for vitamin E. CONCLUSIONS: A weight reduction program can prevent cirrhosis and HCC occurrences, and dominates all other treatment options. Pioglitazone and vitamin E demonstrated a trend towards decreasing the number of cirrhosis and HCC cases.

Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis.

AIMS: To determine the most efficacious and acceptable treatments of agitation in dementia. METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks. RESULTS: Thirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses. CONCLUSIONS: Risperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.

Efficacy and Safety of Cissus quadrangularis L. in Clinical Use: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

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.

Effectiveness of pharmacy-based needle/syringe exchange programme for people who inject drugs: a systematic review and meta-analysis.

AIMS: To appraise the evidence critically for effectiveness of pharmacy-based needle/syringe exchange programmes (pharmacy-based NSPs) on risk behaviours (RBs), HIV/HCV prevalence and economic outcomes among people who inject drugs (PWID). DESIGN: Systematic review and meta-analysis. SETTING: Primary care setting. PARTICIPANTS: Of 1568 studies screened, 14 studies with 7035 PWID were included. MEASURES: PubMed, Embase, Web of Sciences, CENTRAL and Cochrane review databases were searched without language restriction from their inception to 27 January 2016. All published study designs with control groups that reported the effectiveness of pharmacy-based NSP on outcomes of interest were included. Outcomes of interest are risk behaviour (RB), HIV/hepatitis C virus (HCV) prevalence and economic outcomes. The estimates of pooled effects of these outcomes were calculated as pooled odds ratio (OR) with 95% confidence interval (CI) using a random-effects model. Heterogeneity was assessed by I2 and χ2 tests. FINDINGS: Most studies (nine of 14, 64.3%) were rated as having a serious risk of bias, while 28.6 and 7.1% were rated as having a moderate risk and low risk of bias, respectively. For sharing-syringe behaviour, pharmacy-based NSPs were significantly better than no NSPs for both main (OR = 0.50, 95% CI = 0.34-0.73; I2  = 59.6%) and sensitivity analyses, excluding studies with a serious risk of bias (OR = 0.52, 95% CI = 0.32-0.84; I2  = 41.4%). For safe syringe disposal and HIV/HCV prevalence, the evidence for pharmacy-based NSPs compared with other NSP or no NSP was unclear, as few of the studies reported this and most of them had a serious risk of bias. Compared with the total life-time cost of US$55 640 for treating a person with HIV infection, the HIV prevalence among PWID has to be at least 0.8% (for pharmacy-based NSPs) or 2.1% (for other NSPs) to result in cost-savings. CONCLUSIONS: Pharmacy-based needle/syringe exchange programmes appear to be effective for reducing risk behaviours among people who inject drugs, although their effect on HIV/HCV prevalence and economic outcomes is unclear.