Deng-lei Fu

Diabetes and Risk of Parkinson's Disease: An Updated Meta-Analysis of Case-Control Studies

Background Whether diabetes increases the risk of Parkinsons disease (PD) is still inconclusive. The objective of this updated meta-analysis is to synthesize evidence from case-control studies that evaluated the association between diabetes and the risk of PD. Methods Seven databases were searched to identify case-control studies that evaluated the association between diabetes and PD. The methodological quality of included studies was assessed using Newcastle-Ottawa scale. All data were analyzed using Review Manager 5.1 software. Subgroup analyses were also adopted, according to stratification on gender, geographic location, source of the control group, smoking, anti-diabetes drug prescription and duration of DM. Results Fourteen studies fulfilled inclusion criteria for meta-analysis, yielding a total of 21395 PD patients and 84579 control subjects. Individuals with diabetes were found to have a negative association with future PD (OR 0.75; 95% CI 0.58–0.98) in spite of significant heterogeneity. In subgroup analyses, the negative correlation was still found in studies from North America, non-PD control groups from general population, never smoking individuals, and DM ascertainment based on questionnaire or self-report. Stratification of gender and DM duration showed no significant association. No association was also found in European and Asian individuals, hospital-based controls, ever smoking subjects, DM assessment by medical record or physician diagnosis, and insulin prescription for DM. Conclusion Evidence from case-control studies suggested that diabetic individuals may have a decreased incidence of PD despite significant heterogeneity. More researches are warranted to clarify an understanding of the association between diabetes and risk of PD.

Ginsenoside Rg1 provides neuroprotection against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion through downregulation of aquaporin 4 expression

Ginsenoside Rg1 is regarded as one of main bioactive compounds responsible for pharmaceutical actions of ginseng with little toxicity and has been shown to have possibly neuroprotective effects. However, the mechanism of its neuroprotection for acute ischemic stroke is still elusive. The purpose of present study is thus to assess the neuroprotective effects of the ginsenoside Rg1 against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion, and then to explore the mechanisms for these neuroprotective effects by targeting aquaporin 4. Focal cerebral ischemia was induced by middle cerebral artery occlusion. Neurological examinations were performed by using Longas 5-point scale. Evans blue dye was used to investigate the effects of ginsenoside Rg1 on blood brain barrier permeability. Immunohistochemical analysis and real-time fluorescence quantitative polymerase chain reaction were used to assess aquaporin 4 expression. As a result, general linear model with repeated measures analysis of variance for neurological scores at 5 repeated measures showed that ginsenoside Rg1-treated group could significantly reduce the changing trend of neurological deficit scores when compared with the middle cerebral artery occlusion model group (p<0.05). Compared with the middle cerebral artery occlusion model group, ginsenoside Rg1 group has significantly decreased Evans blue content and reduced aquaporin 4 expression at each time point (p<0.05). In conclusion, ginsenoside Rg1 as a ginsenoside neuroprotective agent could improve neurological injury, attenuate blood brain barrier disruption and downregulate aquaporin 4 expression induced by cerebral ischemia/reperfusion insults in rats.

Clinical efficacy and safety of buyang huanwu decoction for acute ischemic stroke: a systematic review and meta-analysis of 19 randomized controlled trials

Buyang Huanwu Decoction (BHD) is a well-known traditional Chinese herbal prescription for treating stroke-induced disability. The objective of this study was to evaluate the efficacy and safety of BHD for acute ischemic stroke. A systematic literature search was performed in 6 databases until February 2012. Randomized controlled clinical trials (RCTs) that evaluate efficacy and safety of BHD for acute ischemic stroke were included. Nineteen RCTs with 1580 individuals were identified. The studies were generally of low methodological quality. Only one of the trial included death or dependency as a primary outcome measure. Only 4 trials reported adverse events. Meta-analysis showed the clinical effective rate of neurological deficit improvement favoring BHD when compared with western conventional medicines (WCM), P < 0.001. There is significant difference in the neurologic deficit score between the BHD treatment group and the WCM control group, P < 0.001. In Conclusion, BHD appears to improve neurological deficit and seems generally safe in patients with acute ischemic stroke. However, the current evidence is insufficient to support a routine use of BHD for acute ischemic stroke due to the poor methodological quality and lack of adequate safety data of the included studies. Further rigorously designed trials are required.

Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials

BackgroundInsomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia.MethodsA systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions.ResultsTwelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information.ConclusionsDespite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed.

Scalp Acupuncture for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Scalp acupuncture (SA) is a commonly used therapeutic approach for stroke throughout China and elsewhere in the world. The objective of this study was to assess clinical efficacy and safety of SA for acute ischemic stroke. A systematical literature search of 6 databases was conducted to identify randomized controlled trials (RCTs) of SA for acute ischemic stroke compared with western conventional medicines (WCMs). All statistical analyses were performed by the Rev Man Version 5.0. Eight studies with 538 participants were included in the studies. The studies were deemed to have an unclear risk of bias based on the Cochrane Back Review Group. Compared with the WCM, 6 RCTs showed significant effects of SA for improving neurological deficit scores (P < 0.01); 4 RCTs showed significant effects of SA for favoring the clinical effective rate (P < 0.01) However, the adverse events have not been documented. In conclusion, SA appears to be able to improve neurological deficit score and the clinical effective rate when compared with WCM, though the beneficial effect from SA is possibly overvalued because of generally low methodology of the included trials. No evidence is available for adverse effects. Rigorous well-designed clinical trials are needed.

Epidemiology of complementary and alternative medicine use in patients with Parkinson's disease.

Parkinsons disease (PD) is a common and debilitating neurodegenerative disorder without a known neuroprotective cure. Currently, an increasing number of patients with PD resort to complementary and alternative medicine (CAM). This study aimed to determine the epidemiology of CAM use for PD worldwide. Methodological issues included the definition of CAM, running a search strategy using five databases, and citation tracking. Six studies estimated the prevalence of CAM use for PD to be between 25.7% and 76%. The response rates in these surveys varied from 81% to 100%. Frequently utilized forms of therapy were acupuncture, massage, herbs, and vitamins/health supplements, and these therapies were mainly used to improve the associated motor symptoms of PD. However, only 11% to 20% of these patients were referred to use CAM by a healthcare professional. Of the sociodemographic and disease-specific factors, CAM use was correlated with female sex, age, age at onset of PD, longer duration of PD, degree of education, higher income, rural location, comorbidity for indications, levodopa load, and severe motor symptoms. These results suggested that CAM use is widespread among patients with PD worldwide, but the largely unexamined use of CAM requires more attention. Moreover, there is a lack of communication between physicians and patients, increasing the risks associated with CAM use and the potential for adverse events.

Rhubarb root and rhizome-based Chinese herbal prescriptions for acute ischemic stroke: A systematic review and meta-analysis

BACKGROUND Traditional Chinese Medicine has been using in stroke victims for thousands of years, and the rhubarb root and rhizome (RRR)-based Chinese herbal prescription is one of the principle treatments for stroke. The objective of this study is to systematically assess the clinical efficacy and safety of RRR-based prescriptions for acute ischemic stroke. METHODS A systematic literature search in six databases was performed to identify randomized controlled trials (RCTs), which compared RRR-based prescriptions with western conventional medicine (WCM) for acute ischemic stroke. The methodological quality of RCTs was assessed independently based on the 12 criteria recommended by the Cochrane Back Review Group. RESULTS A total of 968 participants were included in 12 eligible studies. All trials were deemed to have high a risk of bias. RRR-based prescriptions have a significant effect on the improvement of the clinical efficacy rate (n=10), Barthel Index scores (n=5), National Institutes of Health Stroke Scale scores (n=2), Glasgow Coma Scale scores (n=1), and neurological deficit scores (n=5) when compared with WCM controls (p<0.05 or p<0.01). Six trials reported that there were no adverse events, while no mention of adverse effect monitoring was reported in the other 6 studies. CONCLUSIONS Despite the apparently positive findings, it is premature to recommend the routine use of RRR-based prescriptions for acute ischemic stroke because methodological flaws undermine the strength of our findings. However, this work identifies an area, which is worthy of improvement and development for further research. Larger sample-sizes and rigorously designed RCTs are required in the future.

Xiaoxuming decoction for acute ischemic stroke: A systematic review and meta-analysis

ETHNOPHARMACOLOGICAL RELEVANCE Xiaoxuming decoction (XXMD) is a well-known traditional Chinese herbal prescription in treatment of patients with stroke. The objective of this study is to assess the efficacy and safety of XXMD for acute ischemic stroke. MATERIALS AND METHODS A systematic literature search was conducted in 6 databases until June 2012 to identify randomized controlled trials (RCTs) of XXMD for acute ischemic stroke compared with western conventional medicine (WCM). The primary outcome measures were National Institutes of Health Stroke Scale (NIHSS) scores and modified Rankin Scale (mRS) scores. The secondary outcome measures were the clinical effective rate and adverse events at the end of treatment course. The methodological quality of RCTs was assessed independently using 12-item criteria according to the Cochrane Back Review Group. All data were analyzed using Review Manager 5.0 software. RESULTS Eight RCTs with 601 individuals published from 1992 to 2012 were identified. The studies were deemed to have a high risk of bias. Compared with WCM, 1 RCT showed significant effects of XXMD for improving mRS after stroke (p<0.05); 3 RCTs for improving NIHSS scores [n=186, weighted mean difference (WMD): -1.86, 95% CI: -3.25 to -0.48, z=2.63, p<0.01]; 7 RCTs for improving the clinical effective rate [n=531, risk ratio (RR)=1.17, 95% CI, 1.09 to 1.26, z=4.38, p<0.01]. Five trials contained safety assessments and stated that no adverse event was found, whereas the other 3 trials did not provide the information about adverse events. CONCLUSIONS This systematic review showed positive but weak evidence of XXMD for acute ischemic stroke because of the poor methodological quality and the small quantity of the included trials. The difficulties of fitting Chinese herbal medicine (CHM) into the double blinded RCTs have raised as follows: (A) traditional Chinese medicine (TCM) as whole systems of healthcare offers unique methodological and theoretical challenges for RCTs; (B) suspicions against the placebo and unwillingness to stop taking other CHMs make recruitment more difficulty, time-consumption, and cost; (C) the shortcomings of the TCM diagnostic process includes the lack of standardization in terminology, disagreement of pattern differentiation (Bianzheng), and neglect of formula corresponding to syndrome (TCM Zheng); (D) It is difficult to design credible herbal placebos with similar appearance, smells and tastes to the experimental CHM and at the same time is absent of any pharmacological activity; (E) the achieving efficacy of CHM complex interventions is often nonspecific and the outcome measures is subjective using Chinese quantitative instrument.

Clinical efficacy and safety of Chinese herbal medicine for Wilson's disease: A systematic review of 9 randomized controlled trials

Wilsons disease is an autosomal recessive disorder of copper metabolism. Despite being treatable, there is no universally accepted treatment regimen. Currently, various Chinese herbal medicines (CHMs) are widely used in the treatment of Wilsons disease in China, but there is a lack of reliable scientific evidence for the effectiveness of such therapies. The objective of this systematic review is to assess the clinical efficacy and safety of CHM as an alternative or/and adjuvant therapy for Wilsons disease. A systematic literature search in different medical databases was performed to identify randomized controlled trials comparing CHM as monotherapy or CHM as adjuvant therapy with western conventional medical therapy in the treatment of Wilsons disease. A total of 687 participants were included in nine eligible studies. The main findings are that CHM as monotherapy or adjuvant therapy for Wilsons disease may be able to improve the clinical symptoms, to promote the urinary copper excretion, to ameliorate liver function and/or liver cirrhosis, and has fewer adverse effects in comparison with western conventional medication. Furthermore, CHM generally appeared to be safe and well tolerated in patients with Wilsons disease. However, the evidence presented in this review are insufficient to warrant a clinical recommendation due to the generally low methodological quality of the included studies. In conclusion, CHM seems to be beneficial and safe for Wilsons disease, but high-quality evidences are still needed to further evaluate this therapy. Therefore, additional well-designed, randomized, placebo-controlled clinical trials are needed.

Chinese Herbal Medicine Paratherapy for Parkinson's Disease: A Meta-Analysis of 19 Randomized Controlled Trials

Parkinsons disease (PD) is a common and debilitating neurodegenerative disorder that needs long-term levodopa administration and can result in progressive deterioration of body functions, daily activities and participation. The objective of this meta-analysis evaluates the clinical efficacy and safety of Chinese herbal medicine (CHM) as an adjunct therapy for PD patients. Methodological issues include a systematic literature search between 1950 and April 2011 to identify randomized trials involving CHM adjuvant therapy versus western conventional treatment. The outcome measures assessed were the reduction in scores of Unified Parkinsons Disease Rating Scale (UPDRS) and adverse effects. 19 trials involving 1371 participants were included in the meta-analysis. As compared to western conventional treatment, CHM adjuvant therapy resulted in greater improvement in UPDRS I, II, III, IV scores, and UPDRS I–IV total scores (P < 0.001). Adverse effects were reported in 9 studies. The side effects in CHM adjuvant therapy group were generally less than or lighter than the conventional treatment group. In conclusion, CHM adjuvant therapy may potentially alleviate symptoms of PD and generally appeared to be safe and well tolerated by PD patients. However, well-designed, randomized, placebo-controlled clinical trials are still needed due to the generally low methodological quality of the included studies.