Topical Traditional Chinese Medicines for Cancer Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Safe and effective management of cancer-related pain is a worldwide challenge. In the search for treatment options, natural products used in Chinese herbal medicines (CHMs) have received attention in clinical studies for their effects on cancer-related pain. The objective of this systematic review is to evaluate the clinical evidence for topically applied CHMs as adjunctive treatments for cancer pain management. METHODS: Nine biomedical databases and 4 clinical trial registries were searched for randomized-controlled trials (RCTs) that reported measures of pain and/or quality of life. Risk of bias was assessed using the Cochrane tool. Meta-analysis employed mean difference (MD) with 95% confidence intervals (random effects). RESULTS: Twenty (20) RCTs (1636 participants) met the inclusion criteria. Meta-analyses were grouped based on the comparisons and outcome measures. For pain intensity, there was a greater reduction in the topical CHM group versus placebo (MD -0.72 [-1.04, -0.40]), no difference when compared to tramadol (MD -0.15 [-0.38, 0.08]), and a greater reduction when topical CHMs were combined with conventional analgesic medications (MD -0.67 [-0.93, -0.40]). Analgesic onset time was reduced in the CHM group compared to tramadol (MD -26.02 [-27.57, -24.47] minutes), and for CHMs combined with conventional medications (MD -19.17 [-21.83, -16.52] minutes). When CHMs were combined with analgesic medications, improvements were found for duration of analgesia (MD 1.65 [0.78, 2.51] hours), analgesic maintenance dose (MD -31.72 [-50.43, -13.01] milligrams/day), and quality of life. CONCLUSION: Addition of topical CHMs to conventional analgesic medications was associated with improved outcomes for pain intensity, some other pain-related outcomes, and measures of quality of life. Limitations included methodological issues in some studies and considerable heterogeneity in some pooled results.

Chinese Herbal Medicine for Mild Cognitive Impairment Using Montreal Cognitive Assessment: A Systematic Review.

Background: Mild cognitive impairment (MCI) prevalence is estimated at 6%-12% of the population. It is possible that early treatment at the MCI stage could reduce progression to more severe cognitive impairment. The Montreal Cognitive Assessment (MoCA) is a sensitive measure used to assess changes in cognitive function. Various Chinese herbal medicines (CHMs) have been tested for effects on MCI using MoCA. Objectives: To evaluate the clinical evidence for CHMs on MoCA scores in MCI. Design: Five biomedical databases in English and Chinese language were searched for randomized controlled trials that compared orally administered CHMs with a control group and assessed changes in cognition using MoCA. Analyses were based on the comparison, control intervention, and study duration. Mean differences and 95% confidence intervals were calculated to evaluate treatment effects. For each study, risk of bias was assessed according to the Cochrane tool. Results: Nineteen studies were included with 16 contributing to the data analyses. Three studies were placebo controlled. Nine compared a CHM with a pharmacotherapy, three combined a CHM with a pharmacotherapy, and one combined CHM with cognitive training. In the two placebo-controlled studies of 24-week duration, results favored the CHMs at end of treatment. Conclusions: The systematic review suggests that the oral application of certain CHMs improved scores on MoCA by 1.76-2.34 points compared with placebo in people with MCI after 24 weeks of treatment. However, these two studies used different CHM formulations. Two studies that tested the same CHM formulation, Bu Yang Huan Wu Tang, in combination with donepezil, reported improvement in the integrative groups, but the studies were not blind and the durations were only 8-12 weeks. Overall, methodological weaknesses limited the strength of the evidence. The herbal formulae included ingredients that have received considerable research attention for their effects on memory and cognition. PROSPERO international prospective register of systematic reviews protocol registration number: CRD42018099650.

Comparisons between traditional medicines and pharmacotherapies for Alzheimer disease: A systematic review and meta-analysis of cognitive outcomes.

OBJECTIVES: To evaluate the clinical evidence for traditional medicines (TMs) used in East Asia on measures of cognition in Alzheimer disease, determine the effect sizes at different time points for the TMs and pharmacotherapies, and assess the tolerability of the TMs. METHODS: We searched 12 databases in English, Chinese, and Japanese for eligible randomised controlled trials that compared orally administered TMs with pharmacotherapy and reported cognitive outcomes. Meta-analyses were conducted for Alzheimer's Disease Assessment Scale-cognitive subscale and/or Mini-Mental State Examination (MMSE). Mean differences and 95% confidence intervals were calculated to evaluate treatment effects. RESULTS: Thirty randomised controlled trials met inclusion criteria. Twenty-nine compared TMs with donepezil. Single studies provided comparisons with galantamine, rivastigmine, or memantine. There were no significant differences between the TM and donepezil groups at 12 or 24 weeks for Alzheimer's Disease Assessment Scale-cognitive subscale or MMSE. Improvements over baseline were significant for MMSE at 12 and 24 weeks within the TM and donepezil groups and remained significant at 1 year. Effect sizes were reduced in the 3 double-blind studies. At 24 weeks, donepezil 10 mg/d generally produced greater improvements in MMSE than 5 mg/d. Tolerability reporting was incomplete and inconsistent between studies. CONCLUSIONS: The results suggested that the clinical benefits of the TMs were not less than donepezil at comparable time points, with both groups showing improvements. However, lack of blinding in most studies and other design and measurement issues are likely to have resulted in overestimation of effect sizes in both groups. Further well-designed studies are needed.

Variation in Placebo Effect Sizes in Clinical Trials of Oral Interventions for Management of the Behavioral and Psychological Symptoms of Dementia (BPSD): A Systematic Review and Meta-Analysis.

Increasing placebo effect sizes over time have been reported in randomized controlled trials (RCTs) for outcomes related to psychiatric symptoms. The Neuropsychiatric Inventory (NPI) is a key outcome measure in clinical trials of the behavioral and psychological symptoms of dementia (BPSD). Accurate placebo effect size estimates for NPI are needed for sample size calculations in order to adequately power future studies. This study investigated variation in placebo effect sizes for NPI in RCTs testing oral interventions for BPSD. A search of PubMed was conducted in April 2016 for two-armed, double-blinded, placebo-controlled RCTs testing any oral intervention for management of BPSD using the NPI. Meta-analysis was conducted of baseline versus end of treatment placebo group data of included studies. Twenty-five RCTs published from 2000 to 2015 were included. Substantial variation in placebo effect sizes was detected. Participants in placebo groups showed greater improvements in recent studies compared with earlier studies. Subgroup analyses indicated robustness of this finding. From 2000 to 2008 there was no significant change in total NPI scores within placebo groups (12 studies; 1,056 participants), whereas from 2009 to 2015 there was significant improvement (mean difference: -2.68; 95% confidence interval: -4.38, -0.99; z = 3.10; p = 0.002, random effects; I2 = 76%; 13 studies; 1,170 participants). This increase in NPI effect sizes in placebo groups has important implications for power calculations for future clinical trials of BPSD. Effect size estimates for NPI need to be based on more recent studies.

Herbal medicine for management of the behavioural and psychological symptoms of dementia (BPSD): A systematic review and meta-analysis.

Management of the behavioural and psychological symptoms of dementia remains a challenge worldwide. Herbal medicines may play a role in the development of new interventions. To determine effects of herbal medicines for management of the behavioural and psychological symptoms of dementia, meta-analysis was conducted of 31 controlled trials (3613 participants). Frequently tested herbal medicines were the Ginkgo biloba leaf extract EGb 761 (seven studies) and the multi-ingredient formula Yokukansan (eight studies). Sixteen studies tested other herbal medicines. Improvements were detected in Neuropsychiatric Inventory scores in EGb 761 groups compared to placebo (MD -3.46 [-5.94, -0.98]; I2 = 93%; n = 1757) and Yokukansan groups compared to no treatment (SMD -0.53 [-0.86, -0.21]; I2 = 0%; n = 150). Cognitive scores were improved in EGb 761 groups while Yokukansan did not appear to affect cognitive function. Of the other herbal medicines, there were improvements in the behavioural and psychological symptoms of dementia and cognitive outcomes in two of four placebo-controlled studies. EGb 761 and Yokukansan appeared safe and well tolerated. Adverse effects and dropouts were not reported consistently for the other herbal medicines. Weaknesses of these included short durations, small sample sizes, lack of blinding and other risks of bias. Well-designed studies are needed to further investigate the reported effects of these interventions on the behavioural and psychological symptoms of dementia.

Chinese Herbal Medicine for Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Cognitive Outcomes.

Mild cognitive impairment (MCI) is a condition that may be prodromal to the development of dementia. There remain, as yet, no approved pharmaceutical interventions for MCI. Chinese herbal medicines (CHMs) have a long history of use for cognitive impairments and some plant ingredients have shown neuroprotective actions in experimental studies. This review assesses the current clinical evidence from controlled clinical trials for the effects of CHMs on cognitive outcomes as measured by Mini-mental state examination (MMSE) or Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Fifty one studies (4026 participants) were included. These compared CHM with placebo, supportive care, pharmaceutical treatment or combined CHM with a pharmaceutical in an integrative setting. For the eight randomised controlled trials (RCTs) of comparisons with placebo, MMSE was significantly higher in the CHM groups (MD 1.56 [0.78, 2.34] I2 = 85%, n = 503), similarly for eight RCTs of comparisons with supportive care (MD 1.77 [1.33, 2.21] I2 = 0%, n = 555). Benefits were also evident in comparisons with some pharmaceuticals and with integrative treatment. The small size of most studies and methodological weaknesses mean that these results should be interpreted with caution. Further studies employing rigorous methods are required to investigate the potential benefits of these CHMs for MCI. Copyright © 2016 John Wiley & Sons, Ltd.