Rotigotine Transdermal Patch in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Background and Methods

The efficacy and safety of rotigotine transdermal patch in Parkinson’s disease (PD) were studied in some clinical trials. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy, tolerability, and safety of rotigotine transdermal patch versus placebo in PD.

Results

Six randomized controlled trials (1789 patients) were included in this meta-analysis. As compared with placebo, the use of rotigotine resulted in greater improvements in Unified Parkinson’s Disease Rating Scale activities of daily living score (weighted mean difference [WMD] –1.69, 95% confidence interval [CI] –2.18 to –1.19), motor score (WMD –3.86, 95% CI –4.86 to –2.86), and the activities of daily living and motor subtotal score (WMD –4.52, 95% CI –5.86 to –3.17). Rotigotine was associated with a significantly higher rate of withdrawals due to adverse events (relative risk [RR] 1.82, 95% CI 1.29–2.59), and higher rates of application site reactions (RR 2.92, 95% CI 2.29–3.72), vomiting (RR 5.18, 95% CI 2.25–11.93), and dyskinesia (RR 2.52, 95% CI 1.47–4.32) compared with placebo. No differences were found in the relative risks of headache, constipation, back pain, diarrhea, or serious adverse events.

Conclusions

Our meta-analysis showed that the use of rotigotine can reduce the symptoms of PD. However, rotigotine was also associated with a higher incidence of adverse events, especially application site reactions, compared with placebo.     

Effects of Thyroid Dysfunction and the Thyroid-Stimulating Hormone Levels on the Risk of Atrial Fibrillation: A Systematic Review and Dose-Response Meta-Analysis from Cohort Studies

ObjectiveTo explore the relationship between thyroid dysfunction, thyroid-stimulating hormone (TSH) levels, and risks of atrial fibrillation (AF) in studies and conduct a dose-response meta-analysis on the correlation between the TSH levels and risk of AF.MethodsThirteen studies from 5 databases with 649 293 subjects (mean age, 65.1 years) were included. The dose-response meta-analysis was conducted by comparing the risk ratios (RRs) and 95% confidence intervals (CIs) for incident AF associated with different levels of TSH (vs TSH level of 0 mU/L) across studies. Data were collected until October 25, 2021.ResultsSubclinical hyperthyroidism, subclinical hypothyroidism, and clinical hyperthyroidism were associated with an increased risk of AF (RR, 1.70; 95% CI, 1.11-2.62; RR, 1.23; 95% CI, 1.05-1.44; and RR, 2.35; 95% CI, 1.07-5.16, respectively), whereas clinical hypothyroidism was not associated with the significantly increased risk of AF (RR, 1.20; 95% CI, 0.72-1.99). A nonlinear relationship was observed in 2 models (crude model, P_nonlinear < .001; adjusted model, P_nonlinear = .0391) between the TSH levels and risks of AF.ConclusionsOur study indicated that subclinical hyperthyroidism, subclinical hypothyroidism, clinical hyperthyroidism were associated with the risk of AF, and the results for the TSH levels and risk of AF were mixed, which showed a U-shaped relationship.     

Percutaneous coronary intervention versus medical therapy for chronic total coronary occlusions: a systematic review and meta-analysis of randomised trials

Background

The results of chronic total occlusion percutaneous coronary intervention (CTO-PCI) trials are inconclusive. Therefore, we studied whether CTO-PCI leads to improvement of clinical endpoints and patient symptoms when combining all available randomised data.

Methods and results

This meta-analysis was registered in PROSPERO prior to starting. We performed a literature search and identified all randomised trials comparing CTO-PCI to optimal medical therapy alone (OMT). A total of five trials were included, comprising 1790 CTO patients, of whom 964 were randomised to PCI and 826 to OMT. The all-cause mortality was comparable between groups at 1‑year [risk ratio (RR) 1.70, 95% confidence interval (CI) 0.50–5.80, p = 0.40] and at 4‑year follow-up (RR 1.14, 95% CI 0.38–3.40, p = 0.81). There was no difference in the incidence of major adverse cardiac events (MACE) between groups at 1 year (RR 0.69, 95% CI 0.36–1.33, p = 0.27) and at 4 years (RR 0.85, 95% CI 0.60–1.22, p = 0.38). Left ventricular function and volumes at follow-up were comparable between groups. However, the PCI group had fewer target lesion revascularisations (RR 0.28, 95% CI 0.15–0.52, p < 0.001) and was more frequently free of angina at 1‑year follow-up (RR 0.65, 95% CI 0.50–0.84, p = 0.001), although the scores on the subscales of the Seattle Angina Questionnaire were comparable.

Conclusion

In conclusion, in this meta-analysis of 1790 CTO patients, CTO-PCI did not lead to an improvement in survival or in MACE as reported at long-term follow-up of up to 4 years, or to improvement of left ventricular function. However, CTO-PCI resulted in less angina and fewer target lesion revascularisations compared to OMT.

     

Age-Related Macular Degeneration Is Associated with Less Physical Activity among US Adults: Cross-Sectional Study

BackgroundWe have a limited understanding of the effects of age-related macular degeneration (AMD) on physical activity (PA), and we have no prevalence estimates of the daily movement patterns among Americans with AMD. Therefore, we examined the association between AMD and PA and provided estimates of the daily movement patterns of Americans with AMD.MethodsData from the 2005-2006 National Health and Nutrition Examination Survey were used, including 1,656 adults (40-85 yrs). Retinal imaging was performed to classify individuals as no AMD, early AMD, or late AMD. Participants wore an ActiGraph 7164 accelerometer for 7 days to measure PA behavior.Results93.2% of participants with late AMD were in the least desirable group (not sufficiently active and having a negative light intensity-sedentary behavior balance). After adjustments (including age), participants with late AMD, as compared to those with no AMD, engaged in 50% less moderate-to-vigorous physical activity (MVPA) (RR = 0.50; 95% CI: 0.28-0.90). When visual acuity was entered into the model along with the other covariates, the association between late AMD and MVPA was no longer significant (RR = 0.54; 95% CI: 0.29-1.01), suggesting that visual acuity may partially mediate this relationship.ConclusionsIndividuals with late AMD engage in very little moderate-to-vigorous physical activity. Visually acuity, in part, explains the relationship between late AMD and PA.     

Ultrasound-guided versus anatomic landmark-guided vascular access in cardiac electrophysiology procedures: A systematic review and meta-analysis

IntroductionElectrophysiology (EP) procedures are nowadays the gold-standard method for tachyarrhythmia treatment with impressive success rates, but also with a considerable risk of complications, mainly vascular. A systematic review and meta-analysis was performed to evaluate the safety of ultrasound (US)-guided femoral vein access in EP procedures compared to the traditional anatomic landmark-guided method.MethodsWe searched Pubmed (MEDLINE), Embase, Web of Science, and Cochrane electronic databases for relevant entries, dated from January 1st, 2000 to June 30th, 2021. Only observational studies and randomized controlled trials were included in this analysis. Data extraction included study details, patient characteristics, procedure details, and all types of vascular complications. Complications were classified as major if any intervention, prolongation of hospitalization, or readmission was required.Results9 studies (1 randomized controlled trial and 8 observational), with 7858 participants (3743 in the US-guided group, 4115 in the control group), were included in the meta-analysis. Overall vascular complication rates were significantly decreased in the US-guided group compared to the control group (1.2 versus 3.2%, RR = 0.38, 95% CI, 0.27–0.53), in all EP procedures. Sub-group analysis of AF ablation procedures yielded similar results (RR 0.41, 95% CI, 0.29–0.58, p < 0.00001). The event reduction effect was significant for both major and minor vascular complications.ConclusionUS-guided vascular access in EP procedures is associated with significantly reduced vascular complications, compared to the standard anatomic landmark-guided approach, regardless of procedure complexity.     

Comparison of New Glucose-Lowering Drugs on the Risk of Pancreatitis in Type 2 Diabetes: A Network Meta-Analysis

ObjectiveTo explore whether new glucose-lowering drugs increase the risk of pancreatitis in individuals with type 2 diabetes. This present network meta-analysis aimed to investigate the risk of pancreatitis associated with the use of glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus.MethodsPubMed, Web of Science, Embase, and the Cochrane Library were searched. The literature was published from the date of their inception to July 21, 2021, including placebo-controlled or head-to-head trials of 2 new glucose-lowering drugs. The relative ratio (RR) and 95% confidence interval (CI) were used to assess the risk of GLP-1 agonists and DPP-4 inhibitors for pancreatitis or pancreatic cancer among patients with type 2 diabetes.ResultsSeventeen studies were identified, covered 102 257 participants. The pooled results showed a neutral relationship between GLP-1 agonists and pancreatitis (overall RR, 0.96; 95% CI, 0.31-3.00) or pancreatic cancer (overall RR, 1.10; 95% CI, 0.31-4.10) compared with placebo. Meanwhile, DPP-4 inhibitors were not associated with the increased risk of pancreatitis (overall RR, 1.60; 95% CI, 0.25-11.00) or pancreatic cancer (overall RR, 0.79; 95% CI, 0.26-2.40). Among them, lixisenatide and saxagliptin may be the safest drugs compared with other drugs according to the ranking of probability. Sensitivity and subgroup analysis confirmed the stability of the core results.ConclusionThe most obvious finding of this study is that GLP-1 agonists and DPP-4 inhibitors are safe with respect to the risk of pancreatitis and pancreatic cancer compared with placebo. This conclusion may provide useful evidence for correlated clinical researches.     

Significantly Increased Risk of Cancer in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis

ObjectiveTo conduct a review and meta-analysis of the effect of diabetes mellitus on the incidence of and mortality attributable to cancer at any anatomic site.MethodsWe performed a search of MEDLINE and the Cochrane Library for pertinent articles published from the origin of these databases to July 5, 2010, and included them in a qualitative review and meta-analysis of the risk of all-cancer incidence and mortality in patients with diabetes.ResultsAmong patients with diabetes (n = 257,222) in 12 cohort studies, the cancer incidence was about 7%. The cancer mortality was approximately 3% among patients with diabetes (n = 152,091) in 19 cohort studies. The pooled adjusted risk ratio (RR) of all-cancer incidence was significantly elevated—RR, 1.10 (95% confidence interval [CI], 1.04 to 1.17) overall; RR, 1.14 (CI, 1.06 to 23) for men; and RR, 1.18 (CI, 1.08 to 1.28) for women. Diabetes was also associated with an increased RR of mortality across all cancer types—RR, 1.16 (CI, 1.03 to 1.30) overall; RR, 1.10 (CI, 0.98 to 1.23) for men; and RR, 1.24 (CI, 1.11 to 1.40) for women.ConclusionCancer prevention and early detection by appropriate screening methods in patients with diabetes should be important components of clinical management and investigation, inasmuch as the exponentially increasing prevalence of diabetes will translate into substantial clinical and public health consequences on a global scale. (Endocr Pract. 2011;17:616-628)     

Effects of stem cells on non-ischemic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials

Background aimsTo assess the impacts of stem cell therapy on clinical outcomes in patients with non-ischemic cardiomyopathy (NICM). The effect of stem cell therapy on prognosis is unclear and controversial.MethodsThe authors performed a systematic review and meta-analysis of the effects of autologous stem cell transplantation in patients with NICM on a composite outcome of all-cause mortality and heart transplantation, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association (NYHA) classification, 6-minute walk test (6-MWT) distance and serum brain natriuretic peptide (BNP) level, considering studies published before March 19, 2020.ResultsTwelve trials with 623 subjects met inclusion criteria. Compared with the control group, stem cell therapy improved LVEF (weighted mean difference [WMD], 4.08%, 95% confidence interval [CI], 1.93–6.23, P = 0.0002) and 6-MWT distance (WMD, 101.49 m, 95% CI, 45.62–157.35, P = 0.0004) and reduced BNP level (–294.94 pg/mL, 95% CI, –383.97 to –205.90, P < 0.00001) and NYHA classification (–0.70, 95% CI, –0.98 to –0.43, P < 0.00001). However, LVEDD showed no significant difference between the two groups (WMD, –0.09 cm, 95% CI, –0.23 to 0.06, P = 0.25). In 10 studies (535 subjects) employing the intracoronary route for cell delivery, mortality and heart transplantation were decreased (risk ratio [RR], 0.73, 95% CI, 0.52–1.00, P = 0.05). Furthermore, in four studies (248 subjects) with peripheral CD34+ cells, either all-cause mortality (RR, 0.44, 95% CI, 0.23–0.86, P = 0.02) or mortality and heart transplantation (RR, 0.45, 95% CI, 0.27–0.77, P = 0.003) improved in the treatment group compared with the control. The trial sequential analysis suggested the information size of LVEF, 6-WMT and BNP has been adequate for evidencing the benefits of stem cells on NICM. However, to determine the potential survival benefit, more clinical data are required to make the statistical significance in meta-analysis more conclusive.ConclusionsThis meta-analysis demonstrates that stem cell therapy may improve survival, exercise capacity and cardiac ejection fraction in NICM, which suggests that stem cells are a promising option for NICM treatment.     

Gastric dilatation and intestinal obstruction mimicking acute coronary syndrome with dynamic electrocardiographic changes

Background

Hyperuricemia may be associated with an increased risk of coronary heart disease (CHD) mortality; however, the results from prospective studies are conflicting. The objective of this study was to assess the association between hyperuricemia and risk of CHD mortality by performing a meta-analysis.

Methods

Pubmed and Embase were searched for relevant prospective cohort studies published until July 2015. Studies were included only if they reported data on CHD mortality related to hyperuricemia in a general population. The pooled adjusted relative risk (RR) was calculated using a random-effects model.

Results

A total of 14 studies involving 341 389 adults were identified. Hyperuricemia was associated with an increased risk of CHD mortality (RR: 1.14; 95 % CI: 1.06–1.23) and all-cause mortality (RR: 1.20; 95 % CI: 1.13–1.28). For each increase of 1 mg/dl of serum uric acid (SUA), the overall risks of CHD and all-cause mortality increased by 20 and 9 %, respectively. According to the gender subgroup analyses, hyperuricemia increased the risk of CHD mortality in women (RR: 1.47; 95 % CI: 1.21–1.73) compared to men (RR: 1.10; 95 % CI: 1.00–1.19). The risk of all-cause mortality was greater in women.

Conclusions

Hyperuricemia may modestly increase the risk of CHD and all-cause mortality. Future research is needed to determine whether urate–lowering therapy has beneficial effects for reducing CHD mortality.

     

Obesity and Risk of Hip Fracture in Adults: A Meta-Analysis of Prospective Cohort Studies

Background

Many observational studies assessed the association between obesity and risk of hip fracture in adults, but reported controversial results. Our goal was to evaluate the association between obesity and risk of hip fracture in adults by conducting a meta-analysis of prospective cohort studies.

Methods

Three databases, PubMed, Embase and Web of Science, were searched through May 2012 to identify eligible cohort studies. Either a fixed- or a random-effects model was used to calculate the pooled relative risk (RR) with its 95% confidence interval (95%CI).

Results

Fifteen prospective cohort studies involving a total 3,126,313 participants were finally included into this meta-analysis. Overall, adults with obesity compared with the normal weight group had a significantly decreased risk of hip fracture (RR: 0.66, 95% CI 0.57 to 0.77, P<0.001). Meta-analyses by the adjusted status of RRs also suggested adults with obesity compared with the reference group had a significantly decreased risk of hip fracture (adjusted RR: 0.48, 95% CI 0.39 to 0.58, P<0.001; unadjusted RR: 0.66, 95% CI 0.56 to 0.78, P<0.001). Subgroup analyses by gender suggested individuals with obesity had a significantly decreased risk for developing hip fracture compared with the reference group in both men (RR 0.54, 95% CI 0.48 to 0.60, P<0.001) and women (RR 0.70, 95% CI 0.58 to 0.84, P<0.001). No evidence of publication bias was observed in this meta-analysis.

Conclusions

This meta-analysis of prospective cohort studies suggests that obesity significantly decreases the risk of hip fracture in adults, and obesity is probably a protective factor of hip fracture in adults.     

Compliance with Once-Daily versus Twice or Thrice-Daily Administration of Antibiotic Regimens: A Meta-Analysis of Randomized Controlled Trials

Objective

To investigate whether compliance of patients to antibiotic treatment is better when antibiotics are administered once than multiple times daily.

Methods

We performed a systematic search in PubMed and Scopus databases. Only randomized controlled trials were considered eligible for inclusion. Compliance to antibiotic treatment was the outcome of the meta-analysis.

Results

Twenty-six studies including 8246 patients with upper respiratory tract infections in the vast majority met the inclusion criteria. In total, higher compliance was found among patients treated with once-daily treatment than those receiving treatment twice, thrice or four times daily [5011 patients, RR=1.22 (95% CI, 1.11, 1.34]. Adults receiving an antibiotic once-daily were more compliant than those receiving the same antibiotic multiple times daily [380 patients, RR=1.09 (95% CI, 1.02, 1.16)]. Likewise, children that received an antibiotic twice-daily were more compliant than those receiving the same antibiotic thrice-daily [2118 patients, RR=1.10 (95% CI, 1.02, 1.19)]. Higher compliance was also found among patients receiving an antibiotic once compared to those receiving an antibiotic of different class thrice or four times daily [395 patients, RR=1.20 (95% CI, 1.12, 1.28)]. The finding of better compliance with lower frequency daily was consistent regardless of the study design, and treatment duration.

Conclusion

This meta-analysis showed that compliance to antibiotic treatment might be associated with higher when an antibiotic is administered once than multiple times daily for the treatment of specific infections and for specific classes of antibiotics.     

Efficacy and safety of transcatheter arterial chemoembolization combined with ginsenosides in hepatocellular carcinoma treatment

BackgroundTranscatheter arterial chemoembolization (TACE) is a standard therapy to treat hepatocellular carcinoma (HCC), but often limited for its complications. Ginsenosides, including total ginsenosides (GS), Rg3, Rh2 and CK, have been clinically used as adjuvants of TACE in HCC therapy. However, partial clinical observations concerning the efficacy and safety of the combinational treatment were contradictory.PurposeTo investigate the efficacy and safety of TACE and ginsenosides combination for HCC therapy.MethodsRandomized controlled trials (RCTs) regarding TACE and ginsenosides for HCC up to May 2021 were screened from six databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information and Web of Science). The outcomes of tumor response, adverse reactions (ADRs), quality of life (QOL), survival rates (OS) and liver function were extracted and evaluated by meta-analysis, respectively.ResultsA total of 18 RCTs with 1308 HCC patients were enrolled, and most of the eligible studies had unclear bias risk. Compared with TACE, combining ginsenosides improved objective response rate [ORR, risk ratio (RR) 1.39, 95% confidence intervals (CI) 1.20∼1.61], disease control rate (DCR, RR 1.21, 95% CI 1.12∼1.30), QOL (RR 1.54, 95% CI 1.25∼1.90), one- (RR 1.37, 95% CI 1.16∼1.62) and two- (RR 1.43, 95% CI 1.06∼1.95) year OS, and A level of Child-pugh, as well as reduced the risks of nausea and vomiting, pyrexia, ache, hyperbilirubinemia, anorexia, fatigue, leukopenia, thrombocytopenia and myelosuppression. Subgroup analyses showed that both short- and long- treatment durations of ginsenosides enhanced the A level of Child-pugh, and reduced nausea and vomiting, ache and hyperbilirubinemia. Besides, combining Rg3 benefited DCR, ORR and QOL, and alleviated nausea and vomiting, hyperbilirubinemia, leukopenia, myelosuppression, thrombocytopenia and α-fetoprotein, while combining GS alleviated nausea and vomiting, ache and hyperbilirubinemia, combining Rh2 alleviated thrombocytopenia, and combining CK alleviated nausea and vomiting, pyrexia, ache and leukopenia, respectively.ConclusionThe results suggested that combining ginsenosides could continuously benefit the efficacy and safety of TACE in HCC treatment, and Rg3 is the prior selection during the combination.     

The impact of COVID–19 lockdown on dengue transmission in Sri Lanka; A natural experiment for understanding the influence of human mobility

BackgroundDengue is one of the major public health problems in Sri Lanka. Its outbreak pattern depends on a multitude of drivers, including human mobility. Here we evaluate the impact of COVID–19 related mobility restriction (lockdown) on the risk of dengue in Sri Lanka.MethodologyTwo-stage hierarchical models were fitted using an interrupted time-series design based on the notified dengue cases, January 2015 to July 2020. In the first stage model, the district level impact was estimated using quasi-Poisson regression models while accounting for temporal trends. Estimates were pooled at zonal and national levels in the second stage model using meta-analysis. The influence of the extended period of school closure on dengue in children in the western province was compared to adults.FindingsStatistically significant and homogeneous reduction of dengue risk was observed at all levels during the lockdown. Overall an 88% reduction in risk (RR 0.12; 95% CI from 0.08 to 0.17) was observed at the national level. The highest impact was observed among children aged less than 19 years showing a 92% reduction (RR 0.8; 95% CI from 0.03 to 0.25). We observed higher impact in the dry zone having 91% reduction (RR 0.09; 95% CI from 0.05 to 0.15) compared to wet zone showing 83% reduction (RR 0.17; 95% CI from 0.09 to 0.30). There was no indication that the overall health-seeking behaviour for dengue had a substantial influence on these estimates.SignificanceThis study offers a broad understanding of the change in risk of dengue during the COVID–19 pandemic and associated mobility restrictions in Sri Lanka. The analysis using the mobility restrictions as a natural experiment suggests mobility patterns to be a very important driver of dengue transmission.     

Perioperative Antibiotics to Prevent Acute Endophthalmitis after Ophthalmic Surgery: A Systematic Review and Meta-Analysis

BackgroundPost-operative endophthalmitis is a rare and dreaded complication in ophthalmic operations because it often induces irreparable vision loss. Although many ophthalmological studies aimed at reducing the rate of endophthalmitis have been performed around the world, controversy continues to surround some issues, including the choice of antimicrobials and their route of administration, duration and timing. The aim of this study is to investigate some of these unresolved issues.MethodsA systematic review and meta-analysis of randomized controlled trials and observational studies was performed. The PubMed, EMBASE, Cochrane Library and Clinical Trials databases were searched to identify studies published until Feb. 2016. The relative risk (RR) for each clinical outcome data is presented with 95% confidence intervals (CIs). Pooled estimates of effects were calculated using random-effect models.ResultsThirty-four studies from twenty-four reports involving 1264797 eyes were included in this analysis. Endophthalmitis occurred, on average, in one out of 6177 eyes when intracameral vancomycin/moxifloxacin were used and in one out of 1517 eyes when intracameral vancomycin/moxifloxacin were not used. The relative risk (95% CI) of endophthalmitis was reduced to 0.20 (0.10, 0.42) when intracameral antibiotics were used (p<0.0001). The subconjunctival injection of antibiotics was not superior to other administration routes included in this study (RR = 1.67, 95% CI (0.55, 5.05), p = 0.36). A statistically significant difference was found in the rate of endophthalmitis between the use and lack of use of topical antibiotics (RR = 0.65, 95% CI (0.43, 0.99), p = 0.04). However, no statistically significant difference was found in microbial isolation rates between these groups (RR = 0.77, 95% CI (0.34, 1.75), p = 0.53). When long-term and short-term use of topical antibiotics before surgery were compared, a statistically significant difference was found in microbial isolation rates (RR = 0.57, 95% CI (0.44, 0.74), p<0.0001).ConclusionsThis meta-analysis concluded intracameral antibiotics are effective at preventing endophthalmitis in ocular surgery. A randomized controlled trial confirms the efficacy of cefuroxime but recent large cohort studies support the efficacy of vancomycin/moxifloxacin intracamerally. Intracameral antibitoics are superior to subconjunctival injections but that irrigation antibitoic data are not of enough quality to make a comparison. Different results were found in two clinical outcomes between the use or lack of use of topical antibiotic therapy, we did not find sufficient evidence to conclude that its use prevents endophthalmitis.     

Common Immunosuppressive Monotherapy for Graves’ Ophthalmopathy: A Meta-Analysis

BackgroundSeveral immunosuppressive therapeutic regimens are widely used to treat Graves’ ophthalmopathy (GO), including oral glucocorticoids (OGC), intravenous glucocorticoids (IVGC), retrobulbar injections of glucocorticoids (ROGC) and orbital radiotherapy (OR). The priority among these is unknown. This meta-analysis investigated the efficacy and tolerability of the above regimens.MethodsThe PubMed, EMBASE, and Cochrane Library databases and the Chinese Biomedicine Database were searched up to November 18, 2014. Randomized controlled trials (RCTs) comparing monotherapies (OGC, IVGC, ROGC and OR) in patients with moderate-to-severe active GO were selected. The main efficacy measures were the response rate, the standard mean difference (SMD) in the reduction in the clinical activity score (CAS) and the mean difference (MD) in proptosis from baseline to the end of treatment. The main tolerability measure was the risk ratio (RR) for adverse events. The pooled estimates and 95% confidence intervals (95% CIs) were calculated using the RevMan software, version 5.1.ResultsSeven published RCTs involving 328 participants were included in the present meta-analysis, including IVGC versus OGC (3 trials), ROGC versus OGC (3 trials) and OR versus OGC (1 trial). IVGC was more effective than OGC in response rate (RR = 1.48, 95% CI = 1.18–1.87) and had an obvious CAS reduction (SMD = 0.69, 95% CI = 0.13–1.25). IVGC caused fewer adverse events than OGC. ROGC and OGC had no statistically significant difference in response rate (RR = 1.16, 95% CI = 0.94–1.42). OR also did not differ significantly compared with OGC (RR = 0.93, 95% CI = 0.54–1.60). ROGC and OR had fewer adverse events, such as weight gain, compared with OGC.ConclusionsFor patients with GO in the moderate-to-severe active phase, current evidence gave priority to IVGC, which had a statistically significant advantage over OGC and caused fewer adverse events. ROGC and OR did not provide greater efficacy than OGC, although better tolerability and fewer adverse events were shown.     

Complications after breast reconstruction with alloplastic material in breast cancer patients submitted or not to post mastectomy radiotherapy

Background and purposeBreast reconstruction following mastectomy is a relevant element of breast cancer treatment. The purpose of this study was to evaluate the influence of radiotherapy (RT) on local complications in patients with breast cancer that had undergone breast reconstruction with alloplastic material.Materials and methodsRetrospective study of breast cancer patients submitted to mastectomy and breast reconstruction from 2009 to 2013. Clinical and treatment variables were correlated with early and late complications.Results251 patients were included; mean age was 49.7 (25 to 78) years. Reconstruction was immediate in 94% of the patients, with 88% performed with a temporary tissue expander. Postoperative radiotherapy (RT) was delivered to 167 patients (66.5%). Early complications were present in 26.3% of the patients. Irradiated patients presented 5.4% incidence of late complications versus 2.4% for non-irradiated patients (p = 0.327). Diabetes (OR = 3.41 95% CI: 1.23–9.45, p = 0.018) and high body mass index (BMI) (OR = 2.65; 95% CI: 1.60–4.37, p < 0.0001) were the main risk factors. The overall incidence of late complications was 4.4%, with predominance of severe capsular contracture (8/11). Arterial hypertension (OR = 4.78; 95% CI: 1.97–11.63, p = 0.001), BMI (OR = 0.170; 95% CI: 0.048–0.607, p = 0.006) and implant placement (OR = 3.55; 95% CI: 1.26–9.99, p = 0.016) were related to late complications.ConclusionsThe overall rate of complications was low in this population. Radiotherapy delivery translated into a higher but not statistically significant risk of late complications when compared with the non-irradiated patients. Already well-known clinical risk factors for complications after breast reconstruction were identified.     

A Meta-Analysis of the Relative Risk of Mortality for Type 1 Diabetes Patients Compared to the General Population: Exploring Temporal Changes in Relative Mortality

Aims

Type 1 diabetes has been associated with an elevated relative risk (RR) of mortality compared to the general population. To review published studies on the RR of mortality of Type 1 diabetes patients compared to the general population, we conducted a meta-analysis and examined the temporal changes in the RR of mortality over time.

Methods

Systematic review of studies reporting RR of mortality for Type 1 diabetes compared to the general population. We conducted meta-analyses using a DerSimonian and Laird random effects model to obtain the average effect and the distribution of RR estimates. Sub-group meta-analyses and multivariate meta-regression analysis was performed to examine heterogeneity. Summary RR with 95% CIs was calculated using a random-effects model.

Results

26 studies with a total of 88 subpopulations were included in the meta-analysis and overall RR of mortality was 3.82 (95% CI 3.41, 3.4.29) compared to the general population. Observations using data prior to 1971 had a much larger estimated RR (5.80 (95% CI 4.20, 8.01)) when compared to: data between; 1971 and 1980 (5.06 (95% CI 3.44, 7.45)); 1981–90 (3.59 (95% CI 3.15, 4.09)); and those after 1990 (3.11 (95% CI 2.47, 3.91)); suggesting mortality of Type 1 diabetes patients when compared to the general population have been improving over time. Similarly, females (4.54 (95% CI 3.79–5.45)) had a larger RR estimate when compared to males (3.25 (95% CI 2.82–3.73) and the meta-regression found evidence for temporal trends and sex (p<0.01) accounting for heterogeneity between studies.

Conclusions

Type 1 diabetes patients’ mortality has declined at a faster rate than the general population. However, the largest relative improvements have occurred prior to 1990. Emphasis on intensive blood glucose control alongside blood pressure control and statin therapy may translate into further reductions in mortality in coming years.     

Efficacy and Safety of Adding Clopidogrel to Aspirin on Stroke Prevention among High Vascular Risk Patients: A Meta-Analysis of Randomized Controlled Trials

Objectives

Whether clopidogrel should be added to aspirin for stroke prevention remained controversial for the risk of hemorrhagic complications. This meta-analysis was aimed to assess the efficacy and safety of adding clopidogrel to aspirin on stroke prevention in high vascular risk patients, and to provide evidence for a suitable duration of dual antiplatelet therapy.

Methods

We searched PubMed, EMBase, OVID and Cochrane Central Register of Controlled Trials (up to June, 2013) for randomized controlled trials evaluating the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in high vascular risk patients. Comparisons of stroke and hemorrhagic complications between treatment groups were expressed by the pooled Relative Risks (RRs) with 95% Confidence Intervals (CIs).

Results

Fifteen trials with a total of 97692 intention-to-treat participants were included with duration of follow-up ranging from 7 days to 3.6 years. Dual antiplatelet therapy reduced all stroke by 21% (RR: 0.79, 95% CI: 0.73–0.85) with no evidence of heterogeneity across the trials (P = 0.27, I ² = 17%).The effects were consistent between short-term subgroup (≤1 month, RR: 0.76, 95% CI: 0.67–0.85) and long-term subgroup (≥3 months, RR: 0.81, 95% CI: 0.73–0.89). The risk of major bleeding was not significantly increased by dual antiplatelet therapy in short-term subgroup (RR: 1.11, 95% CI: 0.91–1.36), while significantly increased in long-term subgroup (RR: 1.52, 95% CI: 1.36–1.69). Long-term dual antiplatelet therapy substantially increased the risk of intracranial bleeding (RR: 1.76, 95% CI: 1.22–2.54).

Conclusions

This meta-analysis demonstrates that short-term combination of clopidogrel and aspirin is effective and safe for stroke prevention in high vascular risk patients. Long-term combination therapy substantially increases the risk of major bleeding and intracranial bleeding.     

Memantine Monotherapy for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Background

We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer’s disease (AD).

Methods

The meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes.

Results

Nine studies including 2433 patients that met the study’s inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=−0.27, 95% confidence interval (CI)=−0.39 to −0.14, p=0.0001], behavioral disturbances (SMD=−0.12, 95% CI=−0.22 to −0.01, p=0.03), activities of daily living (SMD=−0.09, 95% CI=−0.19 to −0.00, p=0.05), global function assessment (SMD=−0.18, 95% CI=−0.27 to −0.09, p=0.0001), and stage of dementia (SMD=−0.23, 95% CI=−0.33 to −0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17¬ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups.

Conclusions

Memantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.     

A Meta Analysis of Lumbar Spinal Fusion Surgery Using Bone Morphogenetic Proteins and Autologous Iliac Crest Bone Graft

BackgroundBone morphogenetic protein (BMPs) as a substitute for iliac crest bone graft (ICBG) has been increasingly widely used in lumbar fusion. The purpose of this study is to systematically compare the effectiveness and safety of fusion with BMPs for the treatment of lumbar disease.MethodsCochrane review methods were used to analyze all relevant randomized controlled trials (RCTs) published up to nov 2013.Results19 RCTs (1,852 patients) met the inclusion criteria. BMPs group significantly increased fusion rate (RR: 1.13; 95% CI 1.05–1.23, P = 0.001), while there was no statistical difference in overall success of clinical outcomes (RR: 1.04; 95% CI 0.95–1.13, P = 0.38) and complications (RR: 0.96; 95% CI 0.85–1.09, p = 0.54). A significant reduction of the reoperation rate was found in BMPs group (RR: 0.57; 95% CI 0.42–0.77, p = 0.0002). Significant difference was found in the operating time (MD−0.32; 95% CI−0.55, −0.08; P = 0.009), but no significant difference was found in the blood loss, the hospital stay, patient satisfaction, and work status.ConclusionCompared with ICBG, BMPs in lumbar fusion can increase the fusion rate, while reduce the reoperation rate and operating time. However, it doesn’t increase the complication rate, the amount of blood loss and hospital stay. No significant difference was found in the overall success of clinical outcome of the two groups.