Effects of turmeric (Curcuma longa) supplementation on glucose metabolism in diabetes mellitus and metabolic syndrome: An umbrella review and updated meta-analysis.

AIMS: This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and its related bioactive compounds on glycemic and metabolic parameters in patients with type 2 diabetes (T2DM), prediabetes, and metabolic syndrome (MetS) together with a sub-group analysis of different CL preparation forms. METHODS: An umbrella review (UR) and updated systematic reviews and meta-analyses (SRMAs) were conducted to evaluate the effects of CL compared with a placebo/standard treatment in adult T2DM, prediabetes, and MetS. The MEDLINE, Embase, The Cochrane Central Register of Control Trials, and Scopus databases were searched from inception to September 2022. The primary efficacy outcomes were hemoglobin A1C (HbA1C) and fasting blood glucose (FBG). The corrected covered area (CCA) was used to assess overlap. Mean differences were pooled across individual RCTs using a random-effects model. Subgroup and sensitivity analyses were performed for various CL preparation forms. RESULTS: Fourteen SRMAs of 61 individual RCTs were included in the UR. The updated SRMA included 28 studies. The CCA was 11.54%, indicating high overlap across SRMAs. The updated SRMA revealed significant reduction in FBG and HbA1C with CL supplementation, obtaining a mean difference (95% confidence interval [CI]) of -8.129 (-12.175, -4.084) mg/dL and -0.134 (-0.304, -0.037) %, respectively. FBG and HbA1C levels decreased with all CL preparation forms as did other metabolic parameters levels. The results of the sensitivity and subgroup analyses were consistent with those of the main analysis. CONCLUSION: CL supplementation can significantly reduce FBG and HbA1C levels and other metabolic parameters in T2DM and mitigate related conditions, including prediabetes and MetS. TRIAL REGISTRATION: PROSPERO (CRD42016042131).

The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials.

BACKGROUND: Curcumin supplementation may promote weight loss and ameliorate obesity-related complications through its antioxidative and anti-inflammatory properties. OBJECTIVE: An umbrella review and updated meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effect of curcumin supplementation on anthropometric indices. METHODS: Systematic reviews and meta-analyses (SRMAs) of RCTs were identified from electronic databases (Medline, Scopus, Cochrane, and Google Scholar) up to 31 March, 2022, without language restriction. SRMAs were included if they assessed curcumin supplementation on any of the following: BMI, body weight (BW), or waist circumference (WC). Subgroup analyses were performed, stratifying by patient types, severity of obesity, and curcumin formula. The study protocol was a priori registered. RESULTS: From an umbrella review, 14 SRMAs with 39 individual RCTs were included with a high degree of overlap. In addition, searching was updated from the last search of included SRMAs in April 2021 up to 31 March, 2022, and we found 11 additional RCTs, bringing the total up to 50 RCTs included in the updated meta-analyses. Of these, 21 RCTs were deemed of high risk of bias. Curcumin supplementation significantly reduced BMI, BW, and WC with mean differences (MDs) of -0.24 kg/m2 (95% CI: -0.32, -0.16 kg/m2), -0.59 kg (95% CI: -0.81, -0.36 kg), and -1.32 cm (95% CI: -1.95, -0.69 cm), respectively. The bioavailability-enhanced form reduced BMI, BWs, and WC more, with MDs of -0.26 kg/m2 (95% CI: -0.38, -0.13 kg/m2), -0.80 kg (95% CI: -1.38, -0.23 kg) and -1.41 cm (95% CI: -2.24, -0.58 cm), respectively. Significant effects were also seen in subgroups of patients, especially in adults with obesity and diabetes. CONCLUSIONS: Curcumin supplementation significantly reduces anthropometric indices, and bioavailability-enhanced formulas are preferred. Augmenting curcumin supplement with lifestyle modification should be an option for weight reduction. This trial was registered at PROSPERO as CRD42022321112 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022321112).

Incremental net monetary benefit of biologic therapies in moderate to severe asthma: a systematic review and meta-analysis of economic evaluation studies.

OBJECTIVES: This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using biologic therapies as an add-on treatment to standard therapy in patients with moderate to severe asthma. METHODS: We performed a comprehensive search in several databases published until April 2022. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year on any biologic therapies as an add-on treatment for moderate to severe asthma in patients of all ages. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were pooled across studies using a random-effects model, stratified by country income level (high-income countries (HICs) and low- and middle-income countries (LMICs)) and perspectives (health care or payer perspective (HCPP) and societal perspective (SP)) and age group (>12 years and 6-11 years). Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 32 comparisons from 25 studies were included. Pooled INB indicated that the use of omalizumab as an add-on treatment to standard therapy in those aged >12 years was not cost-effective in HICs from the HCPP (n = 8, INB, -6,341 (95% CI, -$25,000 to $12,210), I2=86.18%) and SP (n = 5, -$14,000 (-$170,000 to $140,000), I2=75.64%). A similar finding was observed in those aged 6-11 years from the HCPP in LMICs (n = 2, -$45,000 (-$73,000 to $17,000), I2=00.00%). Subgroup analyses provided no explanations of the potential sources of heterogeneity. CONCLUSION: The use of biologic therapies in moderate to severe asthma is not cost-effective compared to standard treatment alone.

Treatment outcomes of advanced hepatocellular carcinoma in real-life practice: Chemotherapy versus multikinase inhibitors.

BACKGROUND: Multikinase inhibitors (MKIs) represent the main treatment options for advanced hepatocellular carcinoma (aHCC). However, accessibility in developing countries is limited. A chemotherapy, Fluorouracil and Oxaliplatin (FOLFOX), offers a less expensive treatment. Therefore, this study sought to compare the clinical effectiveness of FOLFOX with Sorafenib as a first-line treatment for aHCC in real-life practice. METHODS: A retrospective aHCC cohort from four Thai hospitals was investigated for patients who received FOLFOX or Sorafenib between 2013-2019. Multiple imputation by chained equations addressed missing covariate data in a treatment effect model using Weight-adjusted-censoring inverse-probability-weighted regression adjustment; overall survival (OS) and progression-free survival (PFS) were estimated. RESULTS: A total of 504 patients were included, (Sorafenib [n = 382] and FOLFOX [n = 122]). The treatment effect model estimated a median OS for Sorafenib and FOLFOX of 11.38 and 8.22 months, representing a significantly shorter OS (95% confidence interval) of -3.16 (-6.21, -0.11) months for FOLFOX, p = 0.042. A significant shorter median PFS of FOLFOX to Sorafenib of -2.13 (-3.03, -1.24) months, p < 0.001, was reported. CONCLUSION: Despite significantly shorter median OS and PFS than Sorafenib, FOLFOX still extended OS by 8.22 months. This evidence may offer clinical utility to physicians considering treatment options for aHCC in low resource settings.

Tropical Oil Consumption and Cardiovascular Disease: An Umbrella Review of Systematic Reviews and Meta Analyses.

The health effects of saturated fat, particularly tropical oil, on cardiovascular disease are unclear. We investigated the effect of tropical oil (palm and coconut oils), lard, and other common vegetable oils (soybean and rice bran oils) that are widely used in tropical and Asian countries on lipid profiles. We performed an umbrella review of meta-analyses and systematic reviews. Electronic databases (Medline, Scopus, Embase, and Cochrane) were searched up to December 2018 without language restriction. We identified nine meta-analyses that investigated the effect of dietary oils on lipid levels. Replacement of polyunsaturated fatty-acid-rich oils (PUFAs) and monounsaturated FA-rich oils (MUFAs) with palm oil significantly increased low-density lipoprotein cholesterol (LDL-c), by 3.43 (0.44-6.41) mg/dL and 9.18 (6.90-11.45) mg/dL, respectively, and high-density lipoprotein cholesterol (HDL-c), by 1.89 (1.23-2.55) mg/dL and 0.94 (-0.07-1.97) mg/dL, respectively. Replacement of PUFAs with coconut oil significantly increased HDL-c and total cholesterol -by 2.27 (0.93-3.6) mg/dL and 5.88 (0.21-11.55) mg/dL, respectively-but not LDL-c. Substituting lard for MUFAs and PUFAs increased LDL-c-by 8.39 (2.83-13.95) mg/dL and 9.85 (6.06-13.65) mg/dL, respectively-but not HDL-c. Soybean oil substituted for other PUFAs had no effect on lipid levels, while rice bran oil substitution decreased LDL-c. Our findings show the deleterious effect of saturated fats from animal sources on lipid profiles. Replacement of unsaturated plant-derived fats with plant-derived saturated fats slightly increases LDL-c but also increases HDL-c, which in turn may exert a neutral effect on cardiovascular health.

The effects of vitamin E supplementation on malondialdehyde as a biomarker of oxidative stress in haemodialysis patients: a systematic review and meta-analysis.

BACKGROUND: Haemodialysis (HD) patients tend to have higher levels of oxidative stress (OS), associated with increased morbidity and premature mortality, compared to the general population. Levels of malondialdehyde (MDA), a biomarker of OS, are reduced by the antioxidant properties of vitamin E (VE) but outcomes from randomised control trials of VE supplementation on MDA in HD patients have been inconsistent. METHODS: We undertook a systematic review and meta-analysis of adult HD patients from VE supplementation studies with measures of MDA. The following search criteria of MEDLINE and EMBASE were considered from inception to January 2020: 'dialysis' AND 'Vitamin E OR tocopherol' AND 'malondialdehyde OR MDA'. Two reviewers independently extracted study data and assessed risk of bias. Mean MDA levels and standard deviation were determined before and after VE supplementation. Standardised mean difference (SMD) and standard error were calculated as the within person difference and units of measure were not consistently recorded across all studies. The SMD were pooled using random effects meta-analysis. RESULTS: The SMD of MDA levels from 18 comparisons was significantly lower in HD patients following VE supplementation (- 1.55; confidence interval: - 2.17 to - 0.94, P < 0.00001). There were significant levels of heterogeneity between studies (I2 value = 91%; P < 0.00001) with evidence of potential publication bias toward smaller studies. CONCLUSIONS: Our findings support the use of VE to reduce the effects of OS in HD patients although high levels of heterogeneity and variation in the methodological approaches used by some studies highlight the need for further investigation.

Effect of tomato, lycopene and related products on blood pressure: A systematic review and network meta-analysis.

BACKGROUND: A number of randomized controlled trials (RCTs) have been conducted to evaluate the hypotensive effects of tomato, lycopene, and related products. However, the findings were conflicting, partly due to differences in the types of products investigated. Therefore, this study aimed to assess and compare the hypotensive effects of different tomato-related preparations through a network meta-analysis based on randomized controlled trials. STUDY DESIGN: A systematic review and network meta-analysis. METHODS: A network meta-analysis based on a systematic review of RCTs comparing the effect of various tomato, lycopene and related products versus placebo on blood pressure in adults was performed. PubMed, EMBASE, SCOPUS, and Clinicaltrial.gov databases were searched up to October 2020 without language restrictions. The primary outcomes were systolic and diastolic blood pressure. Mean differences (MDs) along with 95% confidence intervals (CIs) were estimated and pooled using a random-effects model. Heterogeneity was assessed using the global inconsistency test. RESULTS: A total of 11 studies including six forms of tomato, lycopene and related products met the inclusion criteria. Among these trials, eight (N = 617) and seven trials (N = 501) were included in the analysis of systolic (SBP) and diastolic blood pressure (DBP) outcomes, respectively. The standardized tomato extract (STE) significantly decreased SBP compared to placebo, with a pooled MD (95% CI) of -5.89 (-9.13 to -2.64) mmHg. The effect on DBP was not significant, with a pooled MD (95% CI) of -3.51 (-7.39 to 0.38) mmHg. Subgroup analysis in hypertensive patients showed that STE significantly reduced both SBP and DBP with pooled MDs (95% CIs) of -8.09 (-11.52 to -4.67) and -4.25 (-6.97 to -1.53) mmHg, respectively, compared to placebo. Other forms of tomato, including other dose ranges of standardized tomato extract, tomato-containing diet, lycopene-free preparation, and synthetic lycopene, did not show consistent and significant effects on either SBP or DBP in all analyses. CONCLUSION: Standardized tomato extract (STE) significantly decreased SBP compared to placebo in a mixed population of healthy volunteers and hypertensive patients. The BP-lowering effect was more pronounced among hypertensive patients. No significant BP effects were seen with other forms of tomato, lycopene and related products in the overall population or any subgroup of the population.

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 antiscabietic agents: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Many drugs have been used to treat scabies, but it is unclear which of them is the most efficacious. OBJECTIVE: To evaluate the comparative efficacy and safety of antiscabietic agents. METHODS: A systematic review of randomized controlled trials was conducted. Direct and network meta-analyses were applied to 13 antiscabietic agents on 3 outcomes (cure, persistent itching, and adverse events). Their probability of having highest efficacy and safety was estimated and ranked. RESULTS: A network meta-analysis of 52 trials including 9917 patients indicated that permethrin (the reference treatment) had a significantly higher cure rate than sulfur, malathion, lindane, crotamiton, and benzyl benzoate. Combination permethrin plus oral ivermectin had a nonsignificantly higher cure rate than permethrin. Combination permethrin plus oral ivermectin was ranked highest in terms of cure, topical ivermectin in terms of persistent itching, and synergized pyrethrins in terms of adverse events. On the basis of clustered ranking, permethrin, oral ivermectin, and synergized pyrethrins seemed to retain balance between cure and adverse events. LIMITATIONS: There are small numbers of trials and patients in some comparisons and a high risk of bias in some trials. CONCLUSION: There is no 1 treatment that ranked highest in all aspects. Physicians should consider the drug's efficacy and safety profiles, along with ease of administration.

Calcium and Vitamin D Supplementation for Prevention of Preeclampsia: A Systematic Review and Network Meta-Analysis.

Vitamin D supplementation effects with or without calcium in pregnancy for reducing risk of preeclampsia and gestational or pregnancy induced hypertension are controversial. Literature was systematically searched in Medline, Scopus and Cochrane databases from inception to July 2017. Only randomized controlled trials (RCTs) in English were selected if they had any pair of interventions (calcium, vitamin D, both, or placebo). Systematic review with two-step network-meta-analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs with 28,000 women were eligible. A direct meta-analysis suggested that calcium, vitamin D, and calcium plus vitamin D could lower risk of preeclampsia when compared to placebo with the pooled risk ratios (RRs) of 0.54 (0.41, 0.70), 0.47 (0.24, 0.89) and 0.50 (0.32, 0.78), respectively. Results of network meta-analysis were similar with the corresponding RRs of 0.49 (0.35, 0.69), 0.43 (0.17, 1.11), and 0.57 (0.30, 1.10), respectively. None of the controls were significant. Efficacy of supplementation, which was ranked by surface under cumulative ranking probabilities, were: vitamin D (47.4%), calcium (31.6%) and calcium plus vitamin D (19.6%), respectively. Calcium supplementation may be used for prevention for preeclampsia. Vitamin D might also worked well but further large scale RCTs are warranted to confirm our findings.

Efficacy of home-based non-pharmacological interventions for treating depression: a systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVES: To systematically review and compare the efficacy of all available home-based non-pharmacological treatments of depression. DESIGN: Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Scopus and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched since inceptions to 7 August 2016. ELIGIBILITY CRITERIA: Randomised controlled trials comparing the efficacy of home-based non-pharmacological interventions with usual care of patients with depression were included in the review. MAIN OUTCOMES: Depression symptom scores and disease remission rates at the end of treatment. RESULTS: Seventeen studies were included in the review. Home-based non-pharmacological interventions were categorised as (1) home-based psychological intervention, (2) home-based exercise intervention, (3) combined home-based psychological intervention with exercise intervention and (4) complementary medicine. Complementary medicine approaches were excluded from the meta-analysis due to heterogeneity. The standardised mean differences of post-treatment depression symptom scores between usual care groups and home-based psychological intervention, home-based exercise intervention and combined home-based psychological intervention with exercise intervention were âˆ'0.57 (95% CI âˆ'0.84 to âˆ'0.31), âˆ'1.03 (95% CI âˆ'2.89 to 0.82) and âˆ'0.78 (95% CI âˆ'1.09 to âˆ'0.47), respectively. These results suggest that only home-based psychological intervention and combined home-based psychological intervention with exercise intervention could significantly decrease depression scores. Compared with usual care groups, the disease remission rate was also significantly higher for home-based psychological intervention (pooled risk ratio=1.53; 95% CI 1.19 to 1.98) and combined home-based psychological intervention with exercise intervention (pooled risk ratio=3.47; 95% CI 2.11 to 5.70). Of all the studied interventions, combined home-based psychological intervention with exercise intervention had the highest probability of resulting in disease remission. CONCLUSION: Our study confirms the efficacy of home-based psychological intervention and combined home-based psychological intervention with exercise intervention in the treatment of depression. Combined home-based psychological intervention and exercise intervention was the best treatment and should be considered for inclusion in clinical guidelines for managing depression.

Associations between nocturnal urinary 6-sulfatoxymelatonin, obstructive sleep apnea severity and glycemic control in type 2 diabetes.

Reduced nocturnal secretion of melatonin, a pineal hormone under circadian control, and obstructive sleep apnea have been both identified as risk factors for the development of type 2 diabetes mellitus. Whether they interact to impact glycemic control in patients with existing type 2 diabetes is not known. Therefore, this study explores the relationships between obstructive sleep apnea, melatonin and glycemic control in type 2 diabetes. As diabetic retinopathy may affect melatonin secretion, we also explore the relationship between retinopathy, melatonin and glycemic control. Fifty-six non-shift workers with type 2 diabetes, who were not using beta-blockers, participated. Most recent hemoglobin A1c (HbA1c) levels and the results of ophthalmologic examinations were obtained from medical records. Obstructive sleep apnea was diagnosed using an ambulatory device. Sleep duration and fragmentation were recorded by 7-day wrist actigraphy. The urinary 6-sulfatoxymelatonin/creatinine ratio, an indicator of nocturnal melatonin secretion, was measured in an overnight urine sample. Mediation analyses were applied to explore whether low nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio could be a causal link between increasing obstructive sleep apnea severity [as measured by an Apnea Hypopnea Index (AHI)] and poorer glycemic control, and between the presence of retinopathy and glycemic control. AHI and HbA1c were log-scale (ln) transformed. Obstructive sleep apnea was found in 76.8%, and 25.5% had diabetic retinopathy. The median (interquartile range) of urinary 6-sulfatoxymelatonin/creatinine ratio was 12.3 (6.0, 20.1) ng/mg. Higher lnHbA1c significantly correlated with lower 6-sulfatoxymelatonin/creatinine ratio (p = 0.04) but was not directly associated with OSA severity. More severe obstructive sleep apnea (lnAHI, p = 0.01), longer diabetes duration (p = 0.02), retinopathy (p = 0.01) and insulin use (p = 0.03) correlated with lower urinary 6-sulfatoxymelatonin/creatinine ratio, while habitual sleep duration and fragmentation did not. A mediation analysis revealed that lnAHI negatively correlated with urinary 6-sulfatoxymelatonin/creatinine ratio (coefficient = -2.413, p = 0.03), and urinary 6-sulfatoxymelatonin/creatinine negatively associated with lnHbA1c (coefficient = -0.005, p = 0.02), after adjusting for covariates. Mediation analysis indicated that the effect of lnAHI on lnHbA1c was indirectly mediated by urinary 6-sulfatoxymelatonin/creatinine ratio (B = 0.013, 95% CI: 0.0006, 0.0505). In addition, having retinopathy was significantly associated with reduced nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio, and an increase in HbA1c by 1.013% of its original value (B = -0.013, 95% CI: -0.038, -0.005). In conclusion, the presence and severity of obstructive sleep apnea as well as the presence of diabetic retinopathy were associated with lower nocturnal melatonin secretion, with an indirect adverse effect on glycemic control. Intervention studies are needed to determine whether melatonin supplementation may be beneficial in type 2 diabetes patients with obstructive sleep apnea.

The efficacy of local infiltration analgesia in the early postoperative period after total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Local infiltration analgesia (LIA) has emerged as an alternative treatment for postoperative pain after total knee arthroplasty (TKA). Its efficacy remains inconclusive with inconsistent results from previous studies and meta-analyses. There is no agreement on which local anaesthetic agent and infiltration technique is most effective and well tolerated. OBJECTIVE: The objective was to compare LIA after primary TKA with placebo or no infiltration in terms of early postoperative pain relief, mobilisation, length of hospital stay (LOS) and complications when used as a primary treatment or as an adjunct to regional anaesthesia. The role of injection sites, postoperative injection or infusion and multimodal drug injection with ketorolac were also explored. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: A literature search was performed using PubMed and SCOPUS up to September 2015. ELIGIBILITY CRITERIA: RCTs comparing LIA with placebo or no infiltration after primary TKA in terms of pain score and opioid consumption at 24 and 48 h, mobilisation, LOS and complications were included. RESULTS: In total 38 RCTs were included. LIA groups had lower pain scores, opioid consumption and postoperative nausea and vomiting, higher range of motion at 24 h and shorter LOS than no injection or placebo. After subgroup analysis, intraoperative peri-articular but not intra-articular injection had lower pain score at 24 h than no injection or placebo with the pooled mean difference of pain score at rest of -0.89 [95% CI (-1.40 to -0.38); I = 92.0%]. Continuing with postoperative injection or infusion reduced 24-h pain score with the pooled mean difference at rest of -1.50 [95% CI (-1.92 to -1.08); I = 60.5%]. There was no additional benefit in terms of pain relief during activity, opioid consumption, range of movement or LOS when LIA was used as an adjunct to regional anaesthesia. Four out of 735 patients receiving LIA reported deep knee infection, three of whom had had postoperative catheter placement. CONCLUSION: LIA is effective for acute pain management after TKA. Intraoperative peri-articular but not intra-articular injection may be helpful in pain control up to 24 h. The use of postoperative intra-articular catheter placement is still inconclusive. The benefit of LIA as an adjunctive treatment to regional anaesthesia was not demonstrated.

A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury.

BACKGROUND: Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis. METHODS: A double-blind randomized placebo-controlled trial was performed. Tuberculosis patients were randomly allocated to receive placebo or silymarin. The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4. Antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione and malondialdehyde assays) were assessed. The risks of antiTB-DILI between the two groups were compared. A number need to treat was estimated. RESULTS: A total of 55 out of 70 expected numbers of patients were enrolled. There were 1/27 (3.7%) and 9/28 (32.1%) patients who developed antiTB-DILI in the silymarin and the placebo groups. Risk reduction was 0.28 (0.10, 0.47), i.e., receiving silymarin was 28% at lower risk for antiTB-DILI than placebo. This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients. Median (IQR) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 (15, 415) IU/L and 31.5 (20, 184) IU/L (p = 0.455). The decline of SOD level at week 4 in the silymarin group was less than the placebo group (p < 0.027). CONCLUSIONS: Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study [Clinicaltrials.Gov Identifier Nct01800487].

Maggot therapy for chronic ulcer: a retrospective cohort and a meta-analysis.

BACKGROUND/OBJECTIVE: Maggot wound therapy (MWT) has been used in various wounds including diabetic foot ulcers, venous leg ulcers, pressure ulcers, and acute surgical wounds. However, the efficacy of MWT therapy has been controversial. We therefore conducted a cohort study and a meta-analysis to assess MWT effects. METHODS: A retrospective cohort study was performed in diabetic foot ulcer (DFU) patients who were treated with MWT or conventional wound therapy (CWT) in Thailand. The Kaplan-Meier curve was applied to estimate the healing probability. A meta-analysis was performed to pool our study with four previous cohort studies identified from Medline and Scopus. RESULTS: The estimated incidence of wound healing was 5.7/100 (95% CI: 4.49, 7.32) patients-week, and the median time to healing was 14 weeks. The hazard ratio (HR) of wound healing was 7.87 times significantly higher in the MWT than the CWT (p < 0.001) after adjusting for duration and size of ulcers, ankle brachial index (ABI), and glycated hemoglobin (HbA1c). Meta-analysis was applied and suggested that the treatment effects were moderately heterogeneous {Chi-square = 6.18 [degrees of freedom (d.f.) = 4]; p = 0.186; I(2) = 35.2%}, with the pooled risk ratio (RR) of 1.77 [95% confidence intervals (CI) = 1.01, 3.11], i.e., the chance of wound healing was 20% significantly higher with MWT than CWT. The average costs of treatment in patients with DFU were lower in the MWT group than in the CWT group, with medians of US$292.82 and US$490, respectively. CONCLUSION: Our evidence suggests that MWT is significantly better for wound healing and more cost-effective than CWT. An updated meta-analysis or large scale randomized controlled trial (RCT) is required to confirm this effect.

Management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network meta-analysis.

CONTEXT: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is common, but trial evidence is conflicting and therapeutic options are controversial. OBJECTIVE: To conduct a systematic review and network meta-analysis comparing mean symptom scores and treatment response among α-blockers, antibiotics, anti-inflammatory drugs, other active drugs (phytotherapy, glycosaminoglycans, finasteride, and neuromodulators), and placebo. DATA SOURCES: We searched MEDLINE from 1949 and EMBASE from 1974 to November 16, 2010, using the PubMed and Ovid search engines. STUDY SELECTION: Randomized controlled trials comparing drug treatments in CP/CPPS patients. DATA EXTRACTION: Two reviewers independently extracted mean symptom scores, quality-of-life measures, and response to treatment between treatment groups. Standardized mean difference and random-effects methods were applied for pooling continuous and dichotomous outcomes, respectively. A longitudinal mixed regression model was used for network meta-analysis to indirectly compare treatment effects. DATA SYNTHESIS: Twenty-three of 262 studies identified were eligible. Compared with placebo, α-blockers were associated with significant improvement in symptoms with standardized mean differences in total symptom, pain, voiding, and quality-of-life scores of -1.7 (95% confidence interval [CI], -2.8 to -0.6), -1.1 (95% CI, -1.8 to -0.3), -1.4 (95% CI, -2.3 to -0.5), and -1.0 (95% CI, -1.8 to -0.2), respectively. Patients receiving α-blockers or anti-inflammatory medications had a higher chance of favorable response compared with placebo, with pooled RRs of 1.6 (95% CI, 1.1-2.3) and 1.8 (95% CI, 1.2-2.6), respectively. Contour-enhanced funnel plots suggested the presence of publication bias for smaller studies of α-blocker therapies. The network meta-analysis suggested benefits of antibiotics in decreasing total symptom scores (-9.8; 95% CI, -15.1 to -4.6), pain scores (-4.4; 95% CI, -7.0 to -1.9), voiding scores (-2.8; 95% CI, -4.1 to -1.6), and quality-of-life scores (-1.9; 95% CI, -3.6 to -0.2) compared with placebo. Combining α-blockers and antibiotics yielded the greatest benefits compared with placebo, with corresponding decreases of -13.8 (95% CI, -17.5 to -10.2) for total symptom scores, -5.7 (95% CI, -7.8 to -3.6) for pain scores, -3.7 (95% CI, -5.2 to -2.1) for voiding, and -2.8 (95% CI, -4.7 to -0.9) for quality-of-life scores. CONCLUSIONS: α-Blockers, antibiotics, and combinations of these therapies appear to achieve the greatest improvement in clinical symptom scores compared with placebo. Anti-inflammatory therapies have a lesser but measurable benefit on selected outcomes. However, beneficial effects of α-blockers may be overestimated because of publication bias.

Discrepant influence of vitamin D status on parathyroid hormone and bone mass after two years of calcium supplementation.

OBJECTIVE: To investigate the influence of vitamin D status on parathyroid hormone and bone mass after a 2-year supplementation of calcium alone. PATIENTS AND METHODS: Randomized, double-blind, placebo-controlled clinical trial, in healthy postmenopausal women without osteoporosis: three hundred and thirty-six subjects aged 60-97 years were studied and randomized to receive elemental calcium 500 mg/day (n = 175) or placebo (n = 161) for 2 years. MEASUREMENTS: Changes in parathyroid hormone (PTH) and bone mineral density (BMD) from baseline and vitamin D status. Values are presented as means +/- SD. RESULTS: After 2 years, subjects with calcium supplementation had significant decrease in plasma PTH level (4.4 +/- 1.7 vs 4.7 +/- 1.9 pmol/l, P < 0.01), improved lumbar BMD (1.031 +/- 0.12 vs 1.004 +/- 0.12 g/cm(2), P < 0.001) and total hip BMD (0.890 +/- 0.10 vs 0.883 +/- 0.10 g/cm(2), P < 0.001) without change in femoral neck BMD. In the placebo group, PTH level significantly increased (4.8 +/- 1.6 vs 4.5 +/- 1.5 pmol/l, P < 0.001), lumbar BMD slightly increased (1.027 +/- 0.14 vs 1.018 +/- 0.14 g/cm(2), P < 0.001), total hip and femoral neck BMD decreased (0.876 +/- 0.11 vs 0.887 +/- 0.11 g/cm(2), P < 0.001 and 0.783 +/- 0.10 vs 0.798 +/- 0.10 g/cm(2), P < 0.001, respectively). When subjects were classified according to baseline 25-hydroxyvitamin D [25(OH)D] levels into those with 25(OH)D in the lower tertile (lowVitD) and those in the middle and upper tertiles combined (normVitD). The degree of PTH suppression after calcium supplementation was significantly higher in the normVitD compared to the lowVitD groups (-5.6 +/- 26.7%vs 1.3 +/- 27.2%, P < 0.05). No effect of vitamin D status on the change in lumbar BMD after calcium supplementation was demonstrated. Despite the higher suppression of PTH, there was a slight decrease in femoral neck BMD after calcium supplementation in the normVitD group while femoral neck BMD was more or less maintained in the lowVitD group (-0.6 +/- 3.2%vs 0.5 +/- 2.9%, P < 0.05). CONCLUSION: Calcium supplementation appears to affect femoral bone mass less in Thai postmenopausal women with adequate vitamin D status, despite higher suppression of PTH.