Though none of the included trials reported severe adverse events possibly related to Huperzine A, we cannot draw firm conclusions about the safety ofHuperzine A since seven trials did not report information on safety. The duration of treatment in most trials was 8 weeks or 12 weeks, so the potential beneficial or harmful effect ofHuperzine A for treatment of AD might only result from symptomatic changes and short treatment duration, which is consistent with the findings of a previous review . The included trials used different doses ofHuperzine A, varying from 0.2mg to 0.8 mg daily. One trial  reported Huperzine A was generally well-tolerated at doses of up to 0.4 mg BID for 24 weeks, even in subjects unable to take other cholinesterase inhibitors. Since most participants with Alzheimer’s disease require lifelong treatment, the long-term safety of the treatment is still an important concern. We recommend that further studies should pay attention to the monitoring and reporting of adverse events and long-term safety by designing a longer duration of treatment and a long-term follow-up.
Abstract We performed a systematicreviewandmeta-analysisofrandomized placebo-controlled trials that studied non-neurogenic overactive bladder patients who were treated with 100 units of onabotulinumtoxinA or placebo. The primary purpose of our study was to evaluate the clinical effectiveness with regard to urinary urgency, urinary frequency, nocturia, and incontinence episodes. Our secondary purpose consisted of evaluating the adverse effects. Our initial search yielded 532 entries. Of these, seven studies met all the inclusion criteria (prospective, randomized, placebo-controlled studies, 3 points on the Jadad scale) and were selected for analysis. For all primary endpoints, the toxin was more effective than placebo (p < 0.0001; 95% conﬁdence interval [95CI]), namely: urgency (mean difference ¼ -2.07; 95CI ¼ [-2.55–1.58]), voiding frequency (mean difference ¼ - 1.64; 95CI ¼ [-2.10–1.18]), nocturia (mean difference ¼ -0.25; 95CI ¼ [-0.39–0.11]) and incontinence episodes (mean difference ¼ -2.06; 95CI¼ [-2.60–1.52]). The need for intermittent catheterization and the occurrence of urinary tract infection (UTI) were more frequent in patients treated with onabotulinumtoxinA than in patients treated with placebo (p < 0.0001). Compared with placebo, onabotulinumtoxinA had signiﬁcantly and clinically relevant reductions in overactive bladder symptoms and is associated with higher incidence of intermittent catheterization and UTI.
However, we should admit that there exis- ted certain inherent limitations in the trials inclu- ded in our meta-analysis that cannot be ignored when interpreting our data. The major limitation is that our findings are partially based on indirect evidence. Although ITC allows indirect estimates to be calculated, they can be subject to potential biases and uncertainties (59). Such an indirect tre- atment comparison has to be regarded as a com- plementary assessment to clinicaltrials, because it cannot substitute direct evidence. However, in the absence of any head-to-head comparison, the indirect treatment comparison approach should be regarded as the most valuable way of estimating treatment effects in a statistically accurate man- ner (60). A systematicreviewandmeta-analysis was conducted at an appropriate time with enou- gh high quality data available for extraction by a comprehensive and robust search strategy. Also, the statistical power of this systematicreview was limited by the small sample sizes of these studies, which ranged from 54 to 903 participants. It is well known that smaller studies are prone to pu- blication bias and generate less reliable estimates of the size effect for any association. In Supple- mentary Figures 2-7, these funnel plots show an asymmetrical distribution of studies with low sta- tistical power clearly. We applied a rigorous in- clusion/exclusion criterion, different subgroups to identify studies, fully outcomes of interest (PFS, OS, ORR), bias adjusted data, strict criteria with Jadad scales to evaluate the quality of the inclu- ded studies, and advanced network analysisof HR for PFS. Here, we provide up-to-date information of the network diagram of HR for PFS with regard to the current targeted therapies on mRCC which may worth reference on the clinical decision.
Methods: CENTRAL, MEDLINE, and EMBASE, were searched from inception to January 2019. Double-masked randomized placebo-controlled trials, assessing any anti-TNF vs. best medical intervention/standard of care in adults with chronic NIU were considered. The PRISMA and SAMPL guidelines were followed. The risk of bias was assessed using the Cochrane risk of bias tool. Overall quality of the evidence was assessed according to GRADE. PROSPERO registration: #CRD42016039068. The primary efficacy and safety outcomes were preservation of visual acuity (VA) and withdrawals due to adverse events, respectively. Meta-analysisof efficacy analysis was not performed due to significant clinical heterogeneity between studies’ population and interventions.
Heart Association, the American Society for Nutrition, the National Institute of Diabetes and Digestive and Kidney Diseases, the Canadian Diabetes Association, the Canadian Nutrition Society, the Calorie Control Council, the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, the International Life Sciences Institute North America, the International Life Sciences Institute Brazil, the University of South Carolina, the University of Alabama at Birmingham, the Canadian Sugar Institute, Oldways Preservation Trust, the Nutrition Foundation of Italy, Abbott Laboratories, Pulse Canada, Dr. Pepper Snapple Group, Corn Refiners Association, and the Coca-Cola Company. He is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of both the Canadian Diabetes Association and the European Association for the Study of Diabetes, and he is on the American Society for Nutrition writing panel for a scientific statement on the metabolic and nutritional effects of fructose, sucrose and high-fructose corn syrup. He is a member of the Carbohydrate Quality Consortium and an unpaid scientific advisor for the Food, Nutrition and Safety Program of the International Life Science Institute North America. His wife is an employee of Unilever Canada. No competing interests were declared by EV, SBM, AIC, AM, VHJ, LSAA, and LL. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
The electronic databases that were used included PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Chinese Biomedical Literature Database (SinoMed). These databases were searched without language restriction from their inceptions until July 2014. Search terms con- sisted of three groups: disease (sudden sensorineural hearing loss and other related terms); in- tervention (acupuncture and other related terms) and study type (randomized controlled trial and other related terms). The different search terms for the above databases are shown in S1 Table. The three groups of terms were combined and the search results were downloaded into Endnote libraries for each database. The results for all searches were combined, and the dupli- cates were removed. We also checked the reference lists of eligible articles obtained from additional studies.
The objective of the present study was to determine the effectiveness of the regular practice of traditional resistance training (RT) on systolic (SBP) and diastolic blood pressure (DBP) in normotensive elderly persons. A systematicreviewofrandomizedclinicaltrialsandmeta-analyses was performed. Searches were performed without language restrictions in different databases. Randomizedclinicaltrials published from 1966 to 2010 that assessed the effects of traditional RT on resting blood pressure (BP) and/or for the treatment of high BP were included. Only studies that assessed the effects of traditional RT on elderly adults, regardless of the number of exercises, with the presence of a control group and comparisons between groups, were included. Twenty-nine studies were found, but only six met the inclusion criteria. The mean difference was used for meta-analysis, using a 95% confidence interval and a random effect model. Traditional RT induced a significant decrease in SBP (-6.63 mmHg; p=0.02) but not in DBP (-3.34 mmHg; p=0.11). These results suggest that traditional RT may be a non-pharmacological strategy for the control of BP in the elderly.
A total of 5491 citations were identified by using our search strategy (PubMed, SciELO, EMBASE, and Cochrane databases, provided 4984, 29, 276, and 202 articles respectively) we excluded 5,084 abstracts after initial screening, and assessed 407 full-text articles for eligibility. Of these, 391 studies did not meet inclu- sion criteria (animal trials, no outcome data available, abstracts, retrospective, duplicate population not randomized, comparison between two endoscopic procedures, comparison of a different technique of the same endoscopic treatment and not relevant). Thus, 16 prospective randomizedclinicaltrials were selected for the final analysis. The schematic diagram of the study selection is illustrated in FIGURE 1. The characteristics of the included studies are summarized in TABLE 1.
Several methodological weaknesses may limit the validity and generalizability of this meta-analysis. First, there are no studies involving patients from North America or Africa. The studies included were conducted in Italy, Croatia, Turkey, Korea, and China. It is well established that antibiotic resistance profiles of H. pylori vary among different geographical regions for which a pharmacoge- nomic difference could exist (38). Such resistance profiles are likely to significantly impact the efficacy of moxifloxacin- based triple therapy, and thus may limit the generalizability of these results to African or American populations. Second, heterogeneity among trials can be another limitation of the meta-analysis; there were many factors causing heterogeneity, such as different regimens of drugs and duration. Third, ethnic differences might be another cause of heterogeneity, which may lead to different responses to H. pylori eradication therapy. Therefore, more high-quality, multicenter, randomized, controlled trials from other countries and regions are necessary.
Pancreatic carcinoma is one of the deadliest cancers. It is the only cancer with relative five-year survival rates that are less than 10%. This is due, in part, to the fact that 80% of patients have advanced unresectable disease at the time of diagnosis . For patients that are not surgical candidates, chemotherapy is typically offered. However, the response rate to standard systemic chemotherapy is very low. Gemcitabine (GEM), the most commonly used first-line drug in pancreatic cancer, only has a 5–15% response rate. In addition, GEM in combination with other anti-cancer drugs does not significantly improve survival . The median survival time for patients with advanced pancreatic cancer is less than 6 months and the 1-year survival rate is less than 18% [3,4,5,6].
Objective: For nearly a century, penetrating keratoplasty has been the surgical technique of choice in the management of corneal changes. However, in recent years, several lamellar keratoplasty techniques have been developed, modified or improved, especially techniques for replacing the posterior portion, for the correction of bullous keratopathy. The aim of this study was to evaluate the effectiveness and safety of endothelial keratoplasty versus penetrating keratoplasty for pseudophakic and aphakic bullous keratopathy. Methods: A systematicreviewof the literature was carried out, and the main electronic databases were searched. The date of the most recent search was from the inception of the electronic databases to December 11, 2015. Two authors independently selected relevant clinicaltrials, assessed their methodological quality and extracted data. Results: The electronic search yielded a total of 893 published papers from the electronic databases. Forty-four full-text articles were retrieved for further consideration. Of these 44 full-text articles, 33 were excluded because they were all case series studies; therefore, ten studies (with one further publication) met the inclusion criteria: one randomizedclinical trial with two publications; three controlled studies; and six cohort studies. The clinicaland methodological diversity found in the included studies meant that it was not possible to combine studies in a meta- analysis. Conclusions: There is no robust evidence that endothelial keratoplasty is more effective and safe than penetrating keratoplasty for improving visual acuity and decreasing corneal rejection for pseudophakic and aphakic bullous keratopathy. There is a need for further randomized controlled trials.
This review identified a number ofrandomized controlled trials (RCTs), most of moderate-to-high quality, which eval- uated the use of probiotics in upper and lower respiratory tract infections in children. The presentation, the doses, the different strains, the different mechanisms, and the time of probiotic administration caused these studies to dis- play great heterogeneity and alterations in the sensitivity analysis, making it difficult to perform a concomitant meta- analysis. Analyzing the primary outcomes of this review regarding symptom reduction, time ofdisease duration, andof new episodes of the disease, the latter was shown to be the objective of most RCTs, demonstrating that in six studies there was a reduction of new episodes of respiratory infec- tions, three others found no difference in results, and two did not report this outcome. It was also found that a small number ofclinicaltrials showed adverse events with the use of probiotics, with mild cases that did not require hospital treatment.
Although we tried to conduct a thorough reviewof the existing literature, this present analysis has limitations inherent to any systematicreview. First, the incidences of arterial thromboembolic events showed significant heterogeneity among the included studies. This may reflect differences in sample sizes, disease types, interventions, concomitant treatment, study durations, and many other factors among these studies. Despite these differences, the risk ratios reported by all of these studies showed remarkable homogeneity. In addition, combination data by using a random- effects model may be able to achieve more conservative estimates. Second, the included trials were done at various clinical centers, and the ability to detect arterial thromboembolic events and the classification of events might vary among these institutions, which could result in a bias of reported incidence rates. Third, only published studies were included in the present meta-analysis. To avoid the publication bias, we searched in multiple databases. In addition, to find potential publication biases, we explored asymmetry in funnel plots and detect heterogeneity using Egger’s linear regression, and no publication bias was found. Finally, the findings of this meta-analysis are based on the study level, not on patient-level source data, and some confounding factors cannot be properly assessed and incorporated into the results.
Meta-analysisof this study suggests that use of CHM (listed in Table S1 in File S1) may improve the clinical pregnancy rate (from 36.2% to 53.2%), ongoing pregnancy rate and implantation rate of the embryos for IVF, regardless of the time of concurrent administration. The clinical pregnancy rate in the control group (36.2%) and the average number of transferred embryos (2–3) are similar to data reported elsewhere [SART: www.sart.org]. However, due to the high risk of bias observed with the trials, the significant differences found with the meta-analysis are unlikely to be accurate. Thus, the findings must be interpreted with great caution as the included trials are generally of poor quality and there are small numbers oftrials with a relatively small sample size.
To date, there is only one systematicreviewandmeta- analysis published in English examining compensatory sweating after the treatment of PH (8). The review only included studies in which sympathectomy was used to treat PH, and the papers included not only randomized controlled trials (RCTs) but also clinicaltrials because of the limited number of RCTs. ETS is used to treat not only PH but also facial blushing, facial hyperhidrosis, and axillary hyperhidrosis, among other conditions. Recently, several RCT studies on treating facial blushing and axillary hyperhidrosis have been published (9,10).
Background. Coronary heart disease (CHD) is the leading cause of death among adults in developed countries. It is caused by diseaseof the coronary arteries, the blood vessels that supply the heart with oxygen and nutrients. With age, inflammatory deposits (atherosclerotic plaques) coat the walls of these arteries and restrict the heart’s blood supply, causing angina (chest pains that are usually relieved by rest), shortness of breath, and, if these plaques rupture or break, heart attacks (myocardial infarctions), which can reduce the heart’s function or even be fatal. The key risk factors for CHD are smoking, physical inactivity, and poor diet. Blood cholesterol levels are altered by consuming dietary fats. There are three main types of dietary fats—‘‘saturated’’ fatty acids (SFA) and unsaturated fatty acids; the latter can be ‘‘mono’’ unsaturated (MUFA) or ‘‘poly’’ unsaturated (PUFA). Eating SFA-rich foods (for example, meat, butter, and cheese) increases the amount of LDL-C in the blood but also increases HDL-C (the ‘‘good’’ cholesterol) and decreases triglycerides. Eating foods that are rich in unsaturated fatty acids (for example, vegetable oils and fatty fish) decreases the amount of LDL-C and triglycerides in the blood and also raises HDL-C.
Laboratory. Santa Catarina State University – Florianópolis (SC), Brazil. ABSTRACT | Several exercise modalities improve the symptoms of Parkinson’s Disease (PD). Among the variety of physical exercises, Nordic walking has been used. The aim of this study was to summarize scientiic literature on efects of Nordic walking on patients with PD by a systematicreviewofrandomizedclinicaltrials. The following electronic databases were selected: MEDLINE by Pubmed, Cochrane, PEDro, SCOPUS and Web of Science and articles identiied by manual search, without restriction of date and language. The reviewers evaluated the articles and selected studies according to the eligibility criteria. The following data were extracted from the selected studies: publication identiication, participants’ characteristics (sex, age, disease stage, duration ofdisease), experimental intervention characteristics, control group characteristics, duration, follow-up time, outcome measures and main results. Nordic walking programs with moderate and high intensities, with a minimum of 12 sessions of 60 minutes in a period from 6 to 24 weeks promoted positive efects on the severity, gait, balance, quality of life, functional capacity and motor function in patients with PD.
The only study involving triple therapy in patients with acute uncomplicated brucellosis is that of Ranjbar , which investigated combined doxycycline, rifampicin and amikacin. Amikacin was administered parenterally for one week, and the other two antibiotics for 8–12 weeks. This regimen, which is longer than the standard treatment, is potentially disadvantageous in terms of therapeutic adherence and cost. Furthermore, a comparison was made with combined doxycycline-rifampicin, and no clear differences were observed concerning therapeutic efficacy. The conclusions were based on the disappearance of fever after two weeks of treatment, a time extremely long for evaluating the clinical response which, as already stated, occurred in all studies within the first few days of the start of treatment [56,66]. Other studies of triple therapy were performed in patients presenting osteoarticular brucellosis [15,35], and therefore the conclusions of these studies cannot be extrapolated to patients with uncomplicated brucellosis. As a result, this triple therapy cannot be recommended as the treatment of choice for human brucellosis until data supporting its usefulness is obtained in randomizedclinicaltrials.
exacerbations. Methods: This was a systematicreviewandmeta-analysisofrandomizedclinicaltrials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major indings of this systematicreviewandmeta-analysis were that LAMAs signiicantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, andof serious adverse events. Keywords: Pulmonary disease, chronic obstructive; Muscarinic antagonists; Adrenergic beta-agonists; Bronchodilator agents; Aerosol/therapeutic use; Disease management.