Meta-analysis Of Placebo-controlled Trials Research Articles

Influence of Corticosteroid Use on Short- and Long-Term Outcomes of Biologic Therapy for Inflammatory Bowel Diseases.

Corticosteroids (CS) are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC), but are not recommended as maintenance therapy. Biologic drugs are widely used as an alternative to or in conjunction with CS to induce and maintain remission. This meta-analysis tested the hypothesis that CS use is associated with differential response to biologics. We identified published placebo-controlled clinical trials of biologic drugs approved for the treatment of CD or UC. Pooled estimates of the risk difference (RD) and 95% confidence intervals were derived from random effects models for induction of response and remission and maintenance of remission comparing biologic with CS versus biologic alone. Heterogeneity of response was estimated using I2. Fifteen studies met the inclusion criteria. Pooled estimates of the RD and I2 comparing biologic plus CS versus biologic alone were as follows: induction of UC response 0.15 (0.05, 0.25), I2 = 57.29% and CD response 0.02 (- 0.03, 0.06), I2 = 0.01%; induction of UC remission 0.03 (- 0.01, 0.08), I2 = 0.00% and CD remission 0.08(0.02, 0.14), I2 = 7.81%; and maintenance of UC remission - 0.06 (- 0.13, 0.01), I2 = 0.00% and CD remission - 0.06 (- 0.14, 0.03), I2 = 11.24%. Patients in the placebo arm of CD trials who were receiving CS were less likely to achieve remission during the induction phase (pooled RD - 0.05 (- 0.09, - 0.00), I2 = 0.00%). In this meta-analysis of placebo-controlled trials, CS use was associated with higher biologic response rates for UC and remission rates for CD during the induction phase, but were not associated with improved maintenance of remission.

Meta-Analysis of Placebo-Controlled Trials of Levosimendan in Acute Myocardial Infarction

The treatment of acute myocardial infarction is early revascularization. Heart failure and cardiogenic shock may complicate acute myocardial infarction despite applying the best available strategy. Levosimendan is a relatively new drug to treat heart failure with a peculiar mechanism of action: calcium sensitization of myocardial fibres. Levosimendan has a direct inotropic effect but also pleiotropic effects; through the K+ATP channel’s opening, it also has a vasodilator effect which may participate concretely in the global effects of the drug. The focus of the literature is on the anti-heart failure and anti-cardiogenic shock properties of Levosimendan, but it may have effects also preventing the development of myocardial insufficiency in acute myocardial infarction. The aim of the meta-analysis is to evaluate the effect of Levosimendan on acute myocardial infarction in placebo-controlled trials. Based on the eight studies selected, we found a beneficial effect of Levosimendan on acute and long-term mortality of patients affected by acute myocardial infarction. With caution in interpreting the results of this meta-analysis, our data support the idea that Levosimendan may already have a role in the treatment of acute ischemic heart disease. Further studies specifically designed to investigate the early role in the treatment of ischemic heart failure are needed.

Impact of Biological Agents on Imaging and Biomarkers of Cardiovascular Disease in Patients with Psoriasis: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

The effect of biologics on the risk for cardiovascular disease in patients with psoriasis is still unclear despite their widespread use. The objective of this study was to examine the impact of licensed biological therapies on imaging and biomarkers of cardiovascular disease risk in patients with psoriasis by a systematic review and meta-analysis of placebo-controlled trials. A comprehensive search of studies published before 1 June 2020 was performed in Medline-Ovid, EMBASE, and CENTRAL using a predefined strategy to identify relevant articles. Five studies were included for the final examination, and two studies were included in the meta-analysis. We did not find a significant reduction in aortic vascular inflammation in patients treated with adalimumab compared with those who received placebo at weeks 12-16. There was no beneficial effect on imaging biomarkers (aortic vascular inflammation or flow-mediated dilatation) of cardiovascular disease risk in patients exposed to biological therapies (adalimumab and secukinumab) compared with those exposed to placebo, except for ustekinumab showing a reduction in aortic vascular inflammation at week 12 but not at week 52 after the open-label extension period. The strongest reduction in blood-based cardiometabolic risk biomarkers was observed with adalimumab (CRP, TNF-α, IL-6, and GlycA) and phototherapy (CRP and IL-6) compared with that observed with placebo. Randomized controlled trials show that ustekinumab reduces aortic vascular inflammation and that TNF-α inhibitors and phototherapy reduce CRP and IL-6. These surrogate marker findings require randomized controlled trials evaluating cardiovascular events to inform clinical practice.

Therapeutic Safety and Efficacy of Gabapentin on Pain Intensity, Mood States, and Quality of Life of Patients with Neuropathic Pain: A Meta-Analysis of Placebo-Controlled Trials

Therapeutic Safety and Efficacy of Gabapentin on Pain Intensity, Mood States, and Quality of Life of Patients with Neuropathic Pain: A Meta-Analysis of Placebo-Controlled Trials

Systematic review and meta-analysis of placebo-controlled invasive interventions for the management of chronic stable angina

Abstract Background The benefits of invasive therapies for chronic stable angina are in large part supported by open label studies comparing invasive procedures to medical therapy alone. Placebo effects are frequently unaccounted for as control arms rarely receive placebo (sham) interventions. This review pools studies comparing invasive therapies for chronic stable angina to placebo interventions and aims to measure the true effects of different invasive interventions. Methods We performed a systematic review and meta-analysis of double blinded randomized placebo-controlled trials of invasive therapies for the management of chronic stable angina. The outcomes of interest were change in exercise tolerance time, change in Canadian cardiovascular society angina grade and rate of post-procedural complications including myocardial infarction and all-cause mortality. Results Six randomized placebo-controlled trials were included, with a total of 742 participants. Median follow-up ranged from 6 weeks to 16 months. Contrary to data reported in individual studies, pooled analysis favored invasive therapies over placebo procedures: exercise tolerance time was higher (standard mean difference (SMD) 35.2 seconds [4.4- 66.0]), angina scores were more likely to improve by ≥1 class (Odds Ratio (OR) 2.16 [1.05- 4.46]) and by ≥2 classes (OR 1.76 [1.13- 2.74]). There was no difference in post-procedural myocardial infarction (incidence rate ratio (IRR) 2.91 [0.61–13.93]) and all-cause mortality (IRR 0.39 [0.35–4.27]). Conclusions This meta-analysis of placebo-controlled trials for chronic stable angina found a beneficial effect from invasive therapies. This favorable effect has not been seen in individual studies. Our findings suggest that sample sizes should be adjusted upwards in placebo-controlled studies to detect true treatment effects independent of the placebo effect. Funding Acknowledgement Type of funding source: None

Phosphodiesterase-5 Inhibitors for Premature Ejaculation: Systematic Review and Meta-Analysis of Placebo-Controlled Trials.

The purpose of this analysis is to assess the efficacy and safety of phosphodiesterase-5 inhibitors (PDE5Is) for the treatment of premature ejaculation (PE). A comprehensive search was performed to ascertain from trials about PDE5Is for the treatment of PE and compare the results, including intravaginal ejaculatory latency time (IVELT), score of sexual satisfaction scale, and side effects, between the group treated with PDE5Is and that treated with placebo. Seven studies involving a total of 471 patients were included in this meta-analysis. This analysis showed that patients who were treated with PDE5Is had significantly increased IVELT (mean difference [MD] 2.60; 95% CI [1.85, 3.36]; p < .00001) and score of sexual satisfaction scale (MD 2.04; 95% CI [0.78, 3.30]; p = .002) compared with the group on placebo. More patients had side effects while taking PDE5Is, such as headache, dizziness, flushing, and nasal congestion. PDE5Is were significantly more effective than placebo in the treatment of PE. Side effects were more common among patients who were treated with PDE5Is.

P.160 The impact of antipsychotics on metabolic parameters in the treatment of schizophrenia: A systematic review and meta-analysis of placebo-controlled trials

A promising approach to repair significant organ and tissue damages is to incorporate tissue-engineered scaffolds which can closely mimic the heterogenous three-dimensional structure, physical and biological properties of extracellular matrix (ECM), and function of the native tissue. Nevertheless, regaining natural organ functionality remains a prime challenge in organ regeneration due to the lack of nanofibrous architectures, unique physical properties (e.g., electrical conductivity), mechanical properties of synthetic or natural biomaterials to create functional tissue grafts. Carbon-based nanomaterials such as graphene and carbon nanotubes have drawn an incomparable interest in the development of flexible electronic devices, supercapacitors, biosensors, and actuators for biomedical applications owing to their excellent mechanical and electrical properties and interesting nanoscale features such as large surface area and micropatterning capability. Endowed with nanoscale features, carbon-based structures can provide nanofibrous architectures and tunable physical properties such as porosity and degradability to compensate for the deficiencies of microporous scaffolds in providing tissue-specific engineered ECM. Recently, integration of such nanomaterials in bioengineered tissues has unveiled a new approach toward creating functional biomimetic tissues and organs. In this chapter, we have highlighted some of the most recent progresses in developing functional engineered tissues, namely, in the fields of cardiac, neural, bone, and muscle tissue regeneration. Lastly, we discuss prospective applications of hybrid carbon-based engineered tissues in organ reparation and regeneration.

Efficacy and Safety of Tamsulosin in the Medical Expulsion Therapy for Distal Ureteral Calculi: A Systematic Review and Meta-Analysis of Placebo-Controlled Trials.

Tamsulosin, a medical expulsive therapy (MET), was always recommended for patients with distal ure-teral calculi less than 10 mm. The aim of the systematic review was to assess the efficacy and safety of tamsulosin in MET compared with placebo. A comprehensive search was conducted in the databases PubMed, EMBASE and Web of Science for relevant articles, covering all the literatures published until April 2018. All placebo controlled trails were identified in which patients were randomized to receive either tamsulosin or placebo for distal ureteral calculi. A total of seven placebo controlled studies including 4135 patients met the inclusion criteria and were involved in the review. We found that tamsulosin was associated with a significantly higher expulsion rate (ESR) [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.00-1.21] than placebo in patients with distal ureteral stones less than 7 mm. The ESR ranged from 67.0%-90.7%. But the significant difference was better seen in pa-tients with distal ureteral stones less than 10 mm (OR = 1.11, 95% CI = 1.01-1.21). Even though tamsulosin has a higher incidence of retrograde ejaculation than placebo, no significant difference was observed in the incidence of other adverse events. The results of the current meta-analysis indicated that tamsulosin was superior to placebo in its effi-cacy for distal ureteral stones though retrograde ejaculation was worse with tamsulosin use. It should be a safe and effective medical expulsive therapy choice for distal ureteral stones when stone sizes are less than 10 mm.

Mo1904 – Concomitant Steroid Therapy with Anti-TNF Therapy is Not More Effective Than Anti-TNF Monotherapy in Inducing Remission in Crohn’s Disease: A Systematic Review and Pooled Meta-Analysis of Placebo-Controlled Trials

Mo1904 – Concomitant Steroid Therapy with Anti-TNF Therapy is Not More Effective Than Anti-TNF Monotherapy in Inducing Remission in Crohn’s Disease: A Systematic Review and Pooled Meta-Analysis of Placebo-Controlled Trials

Efficacy and safety of probiotics in adults with ulcerative colitis: A meta-analysis of placebo-controlled trials

Efficacy and safety of probiotics in adults with ulcerative colitis: A meta-analysis of placebo-controlled trials

Poly (ADP-Ribose) Polymerase Inhibition for Chemotherapy-Induced Peripheral Neuropathy: A Meta-Analysis of Placebo-Controlled Trials.

Background: Chemotherapy-induced peripheral neuropathy is characterized by pain, numbness, and tingling in the hands and feet and by diminished quality of life. Multiple previous studies, mostly preclinical, suggest that poly (ADP-ribose) polymerase (PARP) inhibitors may help with these symptoms. Objective: To assess the relationship between PARP inhibition and prevention/palliation of peripheral neuropathy in a clinical setting. Design: Meta-analysis of placebo-controlled clinical trials with PARP inhibitors. Setting/Subjects: We conducted 9 literature searches that included PubMed and other sources to compile fully published placebo-controlled clinical trials that tested PARP inhibitors and that reported on peripheral neuropathy. Measurements: The relative risks for neuropathy of all grades based on PARP inhibition were calculated for each trial. Each trial was weighted by its respective sample size. A forest plot was constructed. Results: Five trials, inclusive of 843 patients, met this study's eligibility criteria. Four included a concomitant PARP inhibitor (either olaparib or veliparib) and paclitaxel, a neuropathy-causing chemotherapy agent; the remaining trial evaluated long-term monotherapy with olaparib. The pooled overall relative risk for the development of neuropathy with PARP inhibition was 1.06 (95% confidence interval: 1-1.4). Conclusions: PARP inhibition does not appear to reduce the risk of chemotherapy-induced peripheral neuropathy. Whether PARP inhibitors may palliate (rather than prevent) neuropathy remains an area in need of further investigation.

Exam 1: Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti–Tumor Necrosis Factor Therapy for Crohn's Disease: A Meta-analysis of Placebo-controlled Trials

Exam 1: Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti–Tumor Necrosis Factor Therapy for Crohn's Disease: A Meta-analysis of Placebo-controlled Trials

Statin therapy and plasma coenzyme Q10 concentrations—A systematic review and meta-analysis of placebo-controlled trials

Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: −0.44μmol/L, 95%CI: −0.52, −0.37, p<0.001). The pooled effect size was robust and remained significant in the leave-one-out sensitivity analysis. Subgroup analysis suggested that the impact of statins on plasma CoQ10 concentrations is significant for all 4 types of statins studied i.e. atorvastatin (WMD: −0.41μmol/L, 95%CI: −0.53, −0.29, p<0.001), simvastatin (WMD: −0.47μmol/L, 95% CI: −0.61, −0.33, p<0.001), rosuvastatin (WMD: −0.49μmol/L, 95%CI: −0.67, −0.31, p<0.001) and pravastatin (WMD: −0.43μmol/L, 95%CI: −0.69, −0.16, p=0.001). Likewise, there was no differential effect of lipophilic (WMD: −0.43μmol/L, 95%CI: −0.53, −0.34, p<0.001) and hydrophilic statins (WMD: −0.47μmol/L, 95%CI: −0.62, −0.32, p<0.001). With respect to treatment duration, a significant effect was observed in both subsets of trials lasting <12 weeks (WMD: −0.51μmol/L, 95%CI: −0.64, −0.39, p<0.001) and ≥12 weeks (WMD: −0.40μmol/L, 95%CI: −0.50, −0.30, p<0.001). The meta-analysis showed a significant reduction in plasma CoQ10 concentrations following treatment with statins. Further well-designed trials are required to confirm our findings and elucidate their clinical relevance.

Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti–Tumor Necrosis Factor Therapy for Crohn’s Disease: A Meta-analysis of Placebo-controlled Trials

There is debate over whether patients with Crohn's disease who start anti-tumor necrosis factor (TNF) therapy after failed immunomodulator therapy should continue to receive concomitant immunomodulators. We conducted a meta-analysis of subgroups from randomized controlled trials (RCTs) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy vs anti-TNF monotherapy. We performed a systematic review of literature published from 1980 through 2008 and identified 11 RCTs of anti-TNF agents in patients with luminal or fistulizing Crohn's disease. We excluded RCTs of patients who were naive to anti-TNF and immunomodulator therapy. The primary end points were clinical response at weeks 4-14 and 24-30 and remission at weeks 24-30. Secondary end points included infusion site or injection site reactions and selected adverse events. A priori subgroup analyses were performed to evaluate fistula closure and the efficacy and safety of combination therapy with different anti-TNF agents. Overall, combination therapy was no more effective than monotherapy in inducing 6-month remission (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.80-1.31), inducing a response (OR, 1.08; 95% CI, 0.79-1.48), maintaining a response (OR, 1.53; 95% CI, 0.67-3.49), or inducing partial (OR, 1.25; 95% CI, 0.84-1.88) or complete fistula closure (OR, 1.10; 95% CI, 0.68-1.78). In subgroup analyses of individual anti-TNF agents, combination therapy was not more effective than monotherapy in inducing 6-month remission in those treated with infliximab (OR, 1.73; 95% CI, 0.97-3.07), adalimumab (OR, 0.88; 95% CI, 0.58-1.35), or certolizumab (OR, 0.93; 95% CI, 0.65-1.34). Overall, combination therapy was not associated with an increase in adverse events, but inclusion of infliximab was associated with fewer injection site reactions (OR, 0.46; 95% CI, 0.26-0.79.) On the basis of a meta-analysis, continued use of immunomodulator therapy after starting anti-TNF therapy is no more effective than anti-TNF monotherapy in inducing or maintaining response or remission. RCTs are needed to adequately assess the efficacy of continued immunomodulator therapy after anti-TNF therapy is initiated.

Attacking the system: Next-generation auto-immune therapies target pathways rather than symptoms.

Auto‐immune diseases are a major health problem in both developed and developing countries: They cause as many deaths as the leading infectious diseases and exact an even greater toll on patients’ quality of life given their chronic nature (Box 1). Reliable data for all auto‐immune diseases are hard to collect, but a 2011 study by the American Autoimmune Related Diseases Association (AARDA) reported that the total annual cost of just seven leading auto‐immune diseases (Crohn's disease, ulcerative colitis, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), psoriasis, and scleroderma) was somewhere between US$51.8 billion and US$70.6 billion in the USA alone (http://www.diabetesed.net/page/_ files/autoimmune-diseases.pdf). The AARDA report also drew attention to the indirect societal toll with one example being sufferers from RA in the USA, who experienced a decline in average earnings from US$18,409 to US$13,900 per year, and the number of jobs they were able to perform dropped from 11.5 to 2.6 million. It was also found that approximately 50 percent of RA patients were unable to work at all within ten years after disease onset. ### Box 1: Some common auto‐immune diseases #### Graves’ Disease The most common auto‐immune disease in which the body produces antibodies to the receptor for thyroid‐stimulating hormone (TSH). It usually attacks the thyroid, frequently causing it to enlarge to twice its size or more (goiter) and become overactive, with related hyperthyroid symptoms such as increased heartbeat, muscle weakness, disturbed sleep, and irritability. No ideal cure but it can be controlled, with last resort surgical excision of the gland. Other treatments include anti‐thyroid drugs, which reduce the production of thyroid hormone, and radioiodine to shrink the gland and reduce its activity. #### Hashimoto's thyroiditis Another auto‐immune disease of the thyroid gland that involves a variety of cell‐ and antibody‐mediated immune processes. It was the first disease to be recognized as auto‐immune in 1912. In this case, the …

Efficacy of tumour necrosis factor antagonists on remission, colectomy and hospitalisations in ulcerative colitis: Meta-analysis of placebo-controlled trials

BackgroundThe potential for disease modification of tumour necrosis factor antagonists in ulcerative colitis remains debated. MethodsWe searched MEDLINE, the Cochrane Library and EMBASE. Clinical response/remission, mucosal healing, colectomy, disease-related hospitalisations, and adverse events were analysed by the methods of Peto and Der Simonian and Laird. ResultsFive trials enrolled 3654 patients (anti-tumour necrosis factor=2338). Anti-tumour necrosis factor therapy was more effective than placebo to induce and maintain clinical remission, with a number needed to treat of 12 (95% confidence interval [CI], 7–35) and 6 (95% CI, 4–12) for adalimumab and infliximab, respectively. Anti-tumour necrosis factor therapy was more effective than placebo to induce and maintain mucosal healing, with number needed to treat of 9 (95% CI, 5–48), 7 (95% CI, 5–17), 4 (95% CI, 3–6) for adalimumab, golimumab and infliximab, respectively. Only infliximab was associated with a reduced need for colectomy. Both infliximab and adalimumab were associated with less hospitalisations. Anti-tumour necrosis factor therapy did not increase the risk of adverse events. ConclusionsAnti-tumour necrosis factor therapy is more effective than placebo to induce and maintain clinical remission and mucosal healing. Both infliximab and adalimumab are associated with less hospitalisations. Infliximab reduces the need for colectomy. Anti-tumour necrosis factor therapy does not increase the risk of adverse events.

Risk of bias and brand explain the observed inconsistency in trials on glucosamine for osteoarthritis:a meta-analysis of placebo-controlled trials

Purpose: the aim of this study was to determine whether study sponsor, chemical formulation, brand of glucosamine, and/or risk of bias explain observed inconsistencies in trial findings of glucosamine’s efficacy for treating pain in osteoarthritis (OA) clinical trials. Furthermore, we determined the effect of glucosamine on pain in OA and how the aforementioned factors play a role in regards to the efficacy of the preparation on pain in OA. Methods: A systematic review and stratified meta-analysis of randomized placebo-controlled trials (RCTs) were conducted. Inclusion criteria consisted of RCTs testing glucosamine compounds vs. placebo in humans with combined treatment regimens as an exclusion criterion (i.e. glucosamine combined with other intervention vs. placebo). Random effects models were applied with inconsistency (I-squared) and heterogeneity (Tau-squared) using Review Manager and SAS, respectively. The major outcome measure was reduction of pain. Selecting outcome-measuring scale for data extraction was done after a predefined verified hierarchy of pain scales; the standardized mean difference (SMD and [95%CI]) served as effect size. Results: The inclusion criteria yielded 25 trials (3,458 patients). Compared with a placebo, glucosamine reduced pain (SMD = -0.51 [-0.72 to -0.30]), although expected high level of between-trial inconsistency was observed (I-sq=88%). The single most important explanation (i.e., covariate) was brand (reducing heterogeneity by 41%, p=(0.00032): Twelve trials (1,437) using the Rottapharm|Madaus product apparently resulted in significant pain reduction (-1.05 [-1.43 to -0.68],), with a large amount of inconsistency(I-sq=92%); whereas 13 trials (1,963 patients) using non-Rottapharm|Madaus products consistently failed to show a reduction in pain when compared with placebo (-0.11 [-0.46 to 0.24], I-sq=10%) - Tau-sq reduced from 0.601 to 0.359 (p<0.001). The second most important explanation was overall risk of bias (reducing Tau-sq by 32%). Conclusions: Trials using the Rottapharm|Madaus glucosamine product had a superior outcome on pain in OA compared to other preparations of glucosamine, though Rottapharm|Madaus trial showed large inconsistency in their results and therefore confidence in the results in limited. We did not find an effect of other brands of glucosamine. Most of the observed heterogeneity in trials on glucosamine for (OA) can be explained by brand and risk of bias.Tabled 1Stratified meta-analysisVariableTrialsEffect size95%CItau-squaredp-value for interactionAll trials25−0.58(−0.90 to −0.26)0.601Label:0.3590.00032Other label13−0.11(−0.46 to 0.24)Rottapharm|Madaus12−1.05(−1.43 to −0.68)Chemical structure:0.54670.082HCl40.03(−0.72 to 0.77)SO421-0.7(−1.04 to −0.36)Risk of bias (overall)0.40790.004Low RoB8−0.09(−0.54 to 0.36)Unclear RoB7−0.39(−0.90 to 0.12)High RoB10−1.14(−1.59 to −0.69)Industry funding0.54990.0767Yes14−0.83(−0.41 to 1.24)No11−0.26(−0.73 to 0.20) Open table in a new tab

Efficacy of second generation antipsychotics in treating acute mixed episodes in bipolar disorder: A meta-analysis of placebo-controlled trials

BackgroundThe literature on the treatment mixed episodes in Bipolar Disorder [BD] is sparse. Second generation antipsychotics [SGA] have documented efficacy in mania, but not mixed episodes. The objective of this meta-analysis was to ascertain the efficacy of SGA, either as mono- and/or adjunctive therapy, in the treatment of acute mixed episodes of BD, compared to placebo. MethodsA MEDLINE search for English language publications of randomized controlled trials [RCTs] comparing SGA with placebo in the treatment of an acute manic/mixed episode of BD, during the period 1990–2012, was performed using the terms ‘atypical antipsychotics’, ‘SGA’, ‘mixed episodes’, ‘dysphoric mania’ and each SGA independently. 9 RCTs reporting data on 1289 mixed episode patients treated with aripiprazole, asenapine, olanzapine, paliperidone-ER, risperidone, and ziprasidone, either as monotherapy or as adjunctive therapy, versus placebo, for 3–6 weeks, were included in the meta-analysis. We extracted data on the number of patients, SGA, duration of study and mean change in mania and depression scores from baseline to endpoint. Standardized mean difference between SGA and placebo for the mean baseline-to-endpoint change in mania and depression rating scores was calculated, with a 95% confidence limit. ResultsSGA, either alone or in combination with mood stabilizers, had superior efficacy in treating manic symptoms of mixed episodes compared to placebo (−0.41, 95% CI −0.53, −0.30; overall effect p<0.00001). SGA were equally effective for manic symptoms in mixed episodes and pure mania (p=0.99). SGA had superior efficacy in treating depressive symptoms of mixed episodes (−0.30, 95% CI −0.47, −0.13; p<0.001) compared to placebo in two trials reporting this information. LimitationsThirteen relevant studies could not be included as data for mixed-episodes were not presented separately. ConclusionsSGA are effective in treating acute mixed episodes of BD, with predominant manic symptoms. Their efficacy in treating depressed mixed episodes remains unclear.

Effect of l-Arginine Supplementation on Blood Pressure in Pregnant Women: A Meta-Analysis of Placebo-Controlled Trials

Objective. A meta-analysis of placebo-controlled trials was conducted to evaluate the effect of l-arginine supplementation on blood pressure (BP) in pregnancy. Methods. Trials were searched in PubMed, Embase, and Cochrane Library. A total of five trials were included in the meta-analysis. Results. l-Arginine supplementation exhibited a mean decrease of 3.07 mmHg (p = 0.004) for diastolic blood pressure and a mean increase of 1.23 weeks (p = 0.002) for gestation age at delivery in pregnancy, but did not reduce systolic BP (p = 0.19) as compared to placebo. Conclusion. l-Arginine supplementation had a significant effect of lowering diastolic blood pressure and prolonging gestation age in pregnancy.

Effects on Lipid Profile of Dipeptidyl Peptidase 4 Inhibitors, Pioglitazone, Acarbose, and Sulfonylureas: Meta-analysis of Placebo-Controlled Trials

Lipid profile is an important determinant of cardiovascular risk in type 2 diabetes. It is well known that patients with type 2 diabetes are more likely to be dyslipidemic than the general population. Given the observed connection between glucose and lipid metabolism in patients with type 2 diabetes, it is conceivable that different glucose-lowering agents can have a varying impact on the lipid profile. When metformin monotherapy fails, other drugs can be added to achieve sufficient glycemic control. Available oral agents include pioglitazone, acarbose, dipeptidyl peptidase 4 (DPP-4) inhibitors, and insulin secretagogs. The present meta-analysis was designed to assess the effect of DPP-4 inhibitors, pioglitazone, insulin secretagogs, and acarbose on blood lipids when compared to placebo. An extensive search (any date up to November 1, 2011) was performed for all trials performed on the following classes of drugs: gliptin, insulin secretagogs, pioglitazone, and acarbose. The following endpoints were considered: endpoint total, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) and triglycerides. The difference in mean total cholesterol values at endpoint versus baseline was significantly higher in patients on pioglitazone, sulfonylureas, and DPP-4 inhibitor treatment (but not on acarbose) than those on placebo, demonstrating that treatment with these drugs (except acarbose) is associated with a significant reduction in total cholesterol. With respect to triglycerides, a significant reduction could be observed with acarbose, pioglitazone, and DPP-4 inhibitors, but not with sulfonylureas. HDL-C appeared to be increased by treatment with acarbose and pioglitazone, and decreased by sulfonylureas. The present meta-analysis shows that available glucose-lowering drugs may have varying effects on the lipid profile. DPP-4 inhibitors, acarbose, and pioglitazone seem to have a more favorable effect on the lipid profile than sulfonylureas.