Standardized Risk Ratio Research Articles

Duration of Symptom Relief and Early Trajectory of Adverse Events for Oral Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

Despite an extensive body of research on nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis. We searched MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. Randomized controlled trials assessing the efficacy and/or safety of Federal Drug Administration-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95% CIs). We included 72 randomized controlled trials (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [95% CI -0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of gastrointestinal (GI) AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [95% CI 1.21, 1.57]). The incidence of cardiovascular (CV) AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity. NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen.

New hepatitis C diagnoses in Ontario, Canada are associated with the local prescription patterns of a controlled-release opioid.

Increases in acute hepatitis C virus (HCV) incidence may be a result of the rising prevalence of injection drug use and the opioid epidemic. Among persons who inject drugs, sharing of needles/syringes is less common and leads to a smaller proportion of incident cases than does sharing of injection drug preparation equipment. In Canada and Europe, hydromorphone controlled release has been associated with frequent reuse and sharing of IDPE. Drug excipients within HCR have been shown to preserve virus survival within IDPE. We hypothesized that regional differences in HCV incidence would mirror regional differences in HCR prescribing. We reviewed HCV incidence data across Ontario, Canada for 2016. Opioid prescribing patterns in each Health Unit were reviewed. Multivariable Poisson regression analyses were performed to test the strength of hydromorphone controlled release dispensing patterns in explaining HCV incidence compared to all opioids. Less vehicle access, lack of education, lower income, less population density, higher white race/ethnicity and more opioid substitution therapy recipients remained significant positive predictors of hepatitis C incidence in the Ontario model. Higher hydromorphone controlled release dispensing rate was a stronger predictor of HCV incidence than all opioid prescriptions (standardized risk ratio=1.17, P<.0001 vs sRR=1.11, P=.02). When hydromorphone controlled release was excluded from the opioid prescription variable, dispensing patterns of all other opioids no longer remained a significant predictor (sRR=1.042, P=.34). The observed relationship between HCV incidence and hydromorphone controlled release dispensing suggests that the type of opioid prescribed locally may contribute to variations in HCV incidence. These data add support to evidence that hydromorphone controlled release use is contributing to HCV spread in Ontario.

Systematic review and meta-analysis of femtosecond laser-enabled keratoplasty versus conventional penetrating keratoplasty.

The aim of this meta-analysis is to compare femtosecond laser-enabled keratoplasty with conventional penetrating keratoplasty regarding postoperative astigmatism, visual functions, graft rejection, graft failure, and complications. Eligible studies were retrieved from five mainstream electronic databases, including PubMed, Embase, Ovid MEDLINE, Cochrane Library, and ClinicalTrial.gov. Postoperative topographic astigmatism was set as the primary outcome, and best-corrected visual acuity, spherical equivalent, endothelial cell density, graft rejection, graft failure, and complications were chosen as the secondary outcomes. Standard mean difference and risk ratio were the size effects for continuous data and binomial data, respectively. The data were pooled through either the random-effects model or the fixed-effects model based on data heterogeneity. Moreover, subgroup analyses were conducted when the heterogeneity occurred distinctly (I2 > 50%). A total of seven comparative studies were included. The pooled standard mean difference (-0.32, 95% confidence interval: -0.74 to 0.10) showed that femtosecond laser-enabled keratoplasty was not superior over conventional penetrating keratoplasty to decrease postoperative topographic astigmatism (p = 0.14). However, best-corrected visual acuity after femtosecond laser-enabled keratoplasty was significantly better than that after conventional penetrating keratoplasty (p = 0.00, standard mean difference: -0.23, 95% confidence interval: -0.37 to -0.10). Furthermore, endothelial cell density after femtosecond laser-enabled keratoplasty was preserved significantly better (p = 0.03, standard mean difference: 0.63, 95% confidence interval: 0.07-1.20). Moreover, spherical equivalent, graft rejection, graft failure, and complications represented no distinct differences between femtosecond laser-enabled keratoplasty and conventional penetrating keratoplasty (p > 0.05). Femtosecond laser-enabled keratoplasty may not be superior over conventional penetrating keratoplasty in decreasing postoperative topographic astigmatism, but might have advantages to achieve best-corrected visual acuity and endothelial cell density preservation. In addition, the two techniques seem to be comparable regarding spherical equivalent, graft rejection/failure, and complications.

A Meta-analysis-Based Assessment of Intense Pulsed Light for Treatment of Melasma.

A safe and effective treatment for melasma, an acquired refractory pigmented skin disease, remains a problem, although numerous clinical trials have explored the possibility of combined therapy involving intense pulsed light. To date, little is known regarding the efficacy of this treatment. The current study, therefore, sought to explore the effectiveness of intense pulsed light. We used published studies from literature databases, based on established inclusion criteria, to calculate standardized mean differences (SMDs) and risk ratio (RRs), and evaluated the effectiveness of combined therapy with intense pulsed light in melasma patients. We performed data analysis using the Review Manager 5.3 software at 95% confidence interval. We obtained a total of 8 studies, involving 215 patients, from the databases and found a significant effect on efficacy following combined therapy with intense pulsed light. Specifically, the melasma area and severity index (MASI) score was significantly low (SMD = 0.61, CI [0.42, 0.80] P < 0.0001 for a fixed-effects model), while a four-point scoring scale self-assessment by patients was significantly high (RR = 1.44, CI [1.17, 1.76] P = 0.0004 for a fixed-effects model). Our meta-analysis showed that IPL-based combination therapy for melasma can effectively reduce the MASI score and result in higher satisfaction among patients, indicating an effective method for treatment of the condition. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Effects of enteral nutritional rich in n-3 polyunsaturated fatty acids on the nutritional status of gastrointestinal cancer patients: a systematic review and meta-analysis.

Postoperative malnutrition is a major issue among gastrointestinal cancer patients. Because n-3 polyunsaturated fatty acids (n-3 PUFAs) have immunological benefits, n-3 PUFAs are widely used in oral nutritional supplements (ONS). However, n-3 PUFAs in ONS reduced patients' compliance with ONS and affected the role of ONS in maintaining the postoperative nutritional status of patients. The aim of this study was to systematically explore the benefits of enteral nutrition rich in n-3 PUFAs in maintaining the nutritional status of patients after gastrointestinal surgery. Databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP databases were searched through March 16, 2019. The references of related reviews and studies were assessed up to March 16, 2019. The effect sizes from individual studies were calculated as the standardized mean difference (SMD), mean difference (MD), and risk ratio (RR) with 95% confidence intervals (95% CIs). A total of 11 studies (n = 977) were included. In this systematic review and meta-analysis, we observed that enteral supplementation of n-3 PUFAs had no significant effect on weight (MD, 1.09; 95% CI, -0.90, 3.08), body mass index (MD, 0.55; 95% CI, -1.45, 2.54), albumin (SMD, 0.39; 95% CI, -0.10, 0.87), wound infections (RR, 0.87, 95% CI, 0.57, 1.33), or pneumonia (RR, 0.98; 95% CI, 0.60, 1.59) in gastrointestinal cancer patients. Thus, compared with enteral nutritional without n-3 PUFAs, enteral nutritional rich in n-3 PUFAs has no significant effects on nutritional status, incidence of pneumonia, or wound infections among gastrointestinal cancer patients during postoperative convalescence.

Failure to Rescue as an Outcome Metric for Pediatric and Congenital Cardiac Catheterization Laboratory Programs: Analysis of Data From the IMPACT Registry.

BackgroundRisk‐adjusted adverse event (AE) rates have been used to measure the quality of pediatric and congenital cardiac catheterization laboratories. In other settings, failure to rescue (FTR) has demonstrated utility as a quality metric.Methods and ResultsA multicenter retrospective cohort study was performed using data from the IMPACT (Improving Adult and Congenital Treatment) Registry between January 2010 and December 2016. A modified FTR metric was developed for pediatric and congenital cardiac catheterization laboratories and then compared with pooled AEs. The associations between patient‐ and hospital‐level factors and outcomes were evaluated using hierarchical logistic regression models. Hospital risk standardized ratios were then calculated. Rankings of risk standardized ratios for each outcome were compared to determine whether AEs and FTR identified the same high‐ and low‐performing centers. During the study period, 77 580 catheterizations were performed at 91 hospitals. Higher annual hospital catheterization volume was associated with lower odds of FTR (odds ratio: 0.68 per 300 cases; P=0.0003). No association was seen between catheterization volume and odds of AEs. Odds of AEs were instead associated with patient‐ and procedure‐level factors. There was no correlation between risk standardized ratio ranks for FTR and pooled AEs (P=0.46). Hospital ranks by catheterization volume and FTR were associated (r=−0.28, P=0.01) with the largest volume hospitals having the lowest risk of FTR.ConclusionsIn contrast to AEs, FTR was not strongly associated with patient‐ and procedure‐level factors and was significantly associated with pediatric and congenital cardiac catheterization laboratory volume. Hospital rankings based on FTR and AEs were not significantly correlated. We conclude that FTR is a complementary measure of catheterization laboratory quality and should be included in future research and quality‐improvement projects.

Adjunctive minocycline for major mental disorders: A systematic review

This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of minocycline for three major mental disorders: schizophrenia, bipolar disorder and major depressive disorder (MDD). A systematic literature search of major electronic databases was conducted. Meta-analysis of clinical efficacy as defined by the respective studies, all-cause discontinuation, adverse drug reactions (ADRs) with standardized mean difference (SMD) and risk ratios (RRs) and their 95% confidence intervals (CI) was conducted using random-effects model. Quality assessment was performed with the Jadad scale and Cochrane risk of bias. Sixteen RCTs (n=1357) on minocycline (50-300 mg/day) for schizophrenia (13 RCTs, n=1196), bipolar depression (1 RCT, n=49), and MDD (2 RCTs, n=112) were analyzed separately by diagnosis. Twelve RCTs mentioned randomized allocation specifically; the weighted Jadad scores were 4.0. Adjunctive minocycline outperformed placebo in improving total psychopathology [SMD: -0.45 (95%CI: -0.73, -0.16), p=0.002; I2=77%], positive [SMD: -0.15 (95%CI: -0.28, -0.02), p=0.02; I2=0%], negative [SMD: -0.62 (95%CI: -0.95, -0.28), p=0.0003; I2=85%] and general psychopathology scores [SMD: -0.28 (95%CI: -0.53, -0.03), p=0.03; I2=59%] in schizophrenia. Minocycline showed no significant effect on depressive and manic symptoms in both bipolar depression and MDD. Minocycline caused significantly less headache (p=0.02, number-needed-to-harm=14, 95%CI=5-14) than placebo in schizophrenia. All-cause discontinuation and other ADRs were similar between minocycline and placebo in each diagnostic category. In this meta-analysis, adjunctive minocycline appeared to be efficacious and safe for schizophrenia. However, the efficacy of adjunctive minocycline for bipolar depression or MDD could not be demonstrated. PROSPERO: CRD42018102483.

Statins significantly reduce mortality in patients receiving clopidogrel without affecting platelet activation and aggregation: a systematic review and meta-analysis

BackgroundCombination of statins and clopidogrel is frequently administered in patients with coronary artery disease (CAD). They are mainly activated and eliminated in the liver by cytochrome P450 isoenzyme 3A4 (CYP3A4). The aim was to clarify whether the coadministration of clopidogrel and statins attenuate respective efficacy.MethodsPubMed, Embase, the Cochrane Library, Web of Science and Clinical Trials. gov were searched for until August 2018. Randomized controlled trials (RCTs) and cohort studies were taken into quality evaluation. Data were pooled using random effect models to estimate standard mean difference (SMD) or risk ratio (RR) with 95% confidence interval (CI).ResultsIn total, 28 studies representing 25,267 participants were included. Statins reduce the mortality of patients administered clopidogrel (RR 0.54; 95% CI 0.40,0.74; p = 0.000), no differences were found in platelet aggregation (PA) (SMD 0.02; 95% CI -0.38,0.42; p = 0.920) and the expressions of P-selectin (SMD -0.04; 95% CI -0.14,0.05; p = 0.346), CD40L (SMD 0.09; 95% CI -0.29,0.48; p = 0.633), CD63 (SMD 0.09; 95% CI -0.01,0.19; p = 0.079) and PAC-1 (SMD 0.03; 95% CI -0.08,0.13; p = 0.633). Furthermore, CYP3A4 metabolized or non-CYP3A4 metabolized statins have no discrepancies in PA (SMD 0.13; 95% CI -0.31,0.58; p = 0.556), P-selectin (SMD 0.17; 95% CI -0.16,0.51; p = 0310), death (RR 0.89; 95% CI 0.38,2.07; p = 0.791), except for triglyceride (TG) (SMD -0.19; 95% CI –0.33,-0.06; p = 0.005).ConclusionsThis meta-analysis confirmed that statins reduce mortality in patients undergoing clopidogrel treatment without affecting platelet activation and aggregation.

Change of ROCK1 Gene Expression Level in Patients with Acute Lymphoblastic Leukemia and Its Clinical Significance

To investigate the expression change of ROCK1 gene in patients with acute lymphoblastic leukemia (ALL) and its prognostic significance. Sixty patients with ALL were selected in our hospital from April 2017 to April 2018, and 60 healthy persons subjected to physical examination were selected as control. The venous blood was taken from the subjects, and then the mononuclear cells were separated. The ROCK1 gene expression level in the samples was detected by RT-PCR, and the expression level of ROCK1 protein was detected by Western blot. The correlation between ROCK1 gene expression and clinical characteristics of ALL patients was analyzed by using statistical methots. The RT-PCR showed that the relative expression level of ROCK1 gene in ALL patients was 1.37 (1.28-1.46), which was significantly higher than that in the control group (P<0.05). Western blot showed that the protein expression level of ROCK1 in ALL patients was higher than that in the control group (P<0.05). The expression level of ROCK1 gene correlated with age, WBC count, lactate dehydrogenase (LDH) level, peripheral blood immature cell count, and risk stratification of ALL patients (P<0.05). The expression level of ROCK1 gene did not correlate with sex, hemoglobin (Hb) level, platelet count and immunophenotype in ALL patients (P>0.05). The standard risk ratio of B-ALL and T-ALL patients with low ROCK1 expression was significantly higher than that in patients with high ROCK1 expression (P<0.05). The high risk ratio of B-ALL and T-ALL patients with low ROCK1 expression was significantly lower than those with high ROCK1 expression (P<0.05). The ratio of CR in the group with low ROCK1 expression patients was significantly higher than that in patients with high ROCK1 expression (P<0.05). The Relapse rate of the group with low ROCK1 expression was significantly lower than that of the group with high ROCK1 expression (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in ALL patients with low ROCK1 expression were superior to those in ALL patients with high ROCK1 expression (P<0.05). Multiple factor Cox regression analysis showed that age and ROCK1 gene were independent influencing factors for OS (P<0.05); leukocyte count and ROCK1 gene were independent influencing factors for DFS (P<0.05). The expression level of ROCK1 gene in ALL patients is high, which may stimulate the genesis of ALL, and the down-regulation of ROCK1 gene expression may help improve the therapeutic effect for ALL patients.

Efficacy and safety of paricalcitol in patients undergoing hemodialysis: a meta-analysis.

BackgroundThe elevated calcium and phosphorus levels in patients undergoing hemodialysis may increase the risk of all-cause mortality. Paricalcitol, as a new vitamin D receptor activator (VDRA), seemed to be effective in reducing the calcium and phosphorus levels.ObjectivesThe aim of this study was to compare the efficacy and safety of paricalcitol with other VDRAs in patients undergoing hemodialysis.MethodsPubMed, Embase, and Web of Science database were systematically reviewed.Selection criteriaStudies that focused on the use of paricalcitol for hemodialysis patients were eligible for inclusion.Data collection and analysisTwo independent investigators performed the literature search, data extraction, and assessment of methodological quality. The outcomes were expressed with standard mean difference (SMD), HR, or risk ratio (RR) with 95% CI.ResultsThirteen studies involving 112,695 patients were included in this meta-analysis. Among these studies, four studies were cohort studies and nine studies were randomized controlled trials (RCTs). For cohort studies, they were regarded as being of high quality; for RCTs, only one was classified as being at low risk of bias; and the remaining eight studies were at being unclear risk of bias. Compared with other VDRAs, paricalcitol significantly improved the overall survival (HR =0.86, 95% CI: 0.80, 0.92; P<0.001) and reduced the intact parathyroid hormone (iPTH) (SMD =−0.53, 95% CI: −0.90, −0.17; P=0.004). Paricalcitol offered similar effect with other VDRAs in the control of calcium (SMD =0.32, 95% CI: −0.04, 0.67; P=0.078) and phosphorus (SMD =0.06, 95% CI: −0.26, 0.37; P=0.727) levels. However, the serum change in calcium phosphate product was greater in the paricalcitol group than in the other VDRA group (SMD =2.13, 95% CI: 0.19, 4.07; P=0.031). There was no significant difference in the incidence of adverse events between the two groups (RR =1.02, 95% CI: 0.93, 1.12; P=0.674).ConclusionParicalcitol was crucial in reducing the mortality in patients undergoing hemodialysis. Moreover, both paricalcitol and other VDRAs were effective in control of the serum iPTH, calcium, and phosphorus levels. Given the potential limitations in this study, more prospective large-scale, well-conducted RCTs are needed to confirm these findings.

Marginal Structural Models for Risk or Prevalence Ratios for a Point Exposure Using a Disease Risk Score.

The disease risk score is a summary score that can be used to control for confounding with a potentially large set of covariates. While less widely used than the exposure propensity score, the disease risk score approach might be useful for novel or unusual exposures, when treatment indications or exposure patterns are rapidly changing, or when more is known about the nature of how covariates cause disease than is known about factors influencing propensity for the exposure of interest. Focusing on the simple case of a binary point exposure, we describe a marginal structural model for estimation of risk (or prevalence) ratios. The proposed model incorporates the disease risk score as an offset in a regression model, and it yields an estimate of a standardized risk ratio where the target population is the exposed group. Simulations are used to illustrate the approach, and an empirical example is provided. Confounder control based on the proposed method might be a useful alternative to approaches based on the exposure propensity score, or as a complement to them.

Epidemiological investigation of sudden cardiac death in multiethnic Xinjiang Uyghur autonomous region in Northwest China

BackgroundThe epidemiological characteristics of sudden cardiac death (SCD) in the autonomous region of Xinjiang Uygur have been largely unknown. This study aimed to evaluate the incidence and demographic risk factors of SCD in Xinjiang, China.MethodsThis retrospective study reviewed medical records from 11 regions in Xinjiang with different geography (north and south of the Tian Shan mountain range), gross domestic product, and ethnicity (Han, Uyghur, Kazakh, and Hui). SCD was defined as unexpected death due to cardiac reasons within 1 hour after the onset of acute symptoms, including sudden death, unexpected death, and nonviolent death. Monitoring was conducted throughout 2015. Demographic and mortality data were recorded and age-adjusted standardized risk ratio (SRR) was analyzed.ResultsAmong 3,224,103 residents, there were 13,308 all-cause deaths and 1244 events of SCD (784 men and 460 women; overall incidence 38.6 per 100,000 residents). SCD was associated with age (χ2 = 2105.3), but not geography. Men had an increased risk of SCD compared with women (SRR: 1.75, 95% CI: 1.10–2.79). The risk of SCD was highest in residents of the Uyghur (SRR: 1.59, 95% CI: 1.05–2.42) and Kazakh (SRR: 1.92, 95% CI: 1.29–2.87) compared with those of the Han. Poor economic development was associated with elevated risk of SCD (SRR: 1.55, 95% CI: 1.02–2.38).ConclusionSCD is an important public health issue in China. Our understanding of the demographic differences on SCD in Xinjiang, China may improve the risk stratification and management to reduce the incidence and lethality of SCD.

Utility of Real-Time and Retrospective Continuous Glucose Monitoring in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.

In the present study, we aimed to investigate the effects of continuous glucose monitoring (CGM) on blood glucose levels, body weight, blood pressure, and hypoglycaemia in patients with type 2 diabetes mellitus using a meta-analysis of randomized controlled trials (RCTs). A literature search was performed using MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov. RCTs using CGM in patients with type 2 diabetes mellitus were then selected. Statistical analysis included calculation of the standardized mean difference (SMD) or risk ratio and 95% confidence intervals (CIs) using a random effects model. After literature search, seven RCTs (669 patients) satisfied the eligibility criteria established herein and were included into the meta-analysis. Compared with the self-monitoring blood glucose group, the CGM group exhibited significantly lower HbA1c levels (SMD, −0.35; 95% CI, −0.59–−0.10; P = 0.006) and shorter time spent with hypoglycaemia (SMD, −0.42; 95% CI, −0.70–−0.13; P = 0.004). Conversely, no differences in body weight and blood pressure were observed between the groups. CGM in patients with type 2 diabetes mellitus could reduce HbA1c levels and time spent with hypoglycaemia. However, because few RCTs were included in this present study and heterogeneity was also noted, care should be taken when interpreting the results.

Hidradenitis Suppurativa: A Systematic Review and Meta-analysis of Therapeutic Interventions.

Hidradenitis suppurativa is a chronic inflammatory condition that affects skin regions bearing apocrine glands. Although hidradenitis suppurativa is difficult to treat and cure, the currently available treatments are directed toward managing the lesions and associated symptoms. This review presents an evidence-based outline of the available treatment options. We searched four electronic databases and extracted data from retrieved studies for qualitative or quantitative analysis. Meta-analysis was conducted using the comprehensive meta-analysis software to generate pooled standardized mean differences or risk ratios. Numerous medical treatments are available for hidradenitis suppurativa such as antibiotics, retinoids, antiandrogens, immunosuppressive and anti-inflammatory agents and radiotherapy for early lesions. Adalimumab, an anti-tumor necrosis factor antibody, was superior to placebo in reducing Sartorius score (standardized mean difference = -0.32, confidence interval [-0.46, -0.18], P < 0.0001) and pain (risk ratio = 1.42, confidence interval [1.07, 1.9], P = 0.02), when given weekly (not every other week). Combination therapies (such as antibiotics and hyperbaric oxygen therapy) have been tested, which have shown promising results that are yet to be confirmed. Based on the quality of evidence, the most recommended treatments for hidradenitis suppurativa include adalimumab and laser therapy. Surgery (either by simple excision or complete local excision followed by skin graft) is the first choice for intractable disease presenting in the late stages. However, the evidence on most of these treatments is deficient and further randomized trials are needed to establish the most efficient therapies for hidradenitis suppurativa management.

Adjunctive Metformin for Antipsychotic-Induced Dyslipidemia: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Background: Antipsychotic-induced dyslipidemia could increase the risk of cardiovascular diseases. This is a meta-analysis of randomized double-blind placebo-controlled trials (RCTs) to examine the efficacy and safety of adjunctive metformin for dyslipidemia induced by antipsychotics in schizophrenia. Methods: The standardized mean differences (SMDs) and risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated using the random-effects model with the RevMan 5*3 version software. The primary outcome was the change of serum lipid level. Results: Twelve studies with 1,215 schizophrenia patients (592 in metformin group and 623 in placebo group) were included and analyzed. Adjunctive metformin was significantly superior to placebo with regards to low density lipoprotein cholesterol [SMD: -0*37 (95%CI:-0*69, -0*05), P=0*02; I2=78%], total cholesterol [SMD: -0*47 (95%CI:-0*66, -0*29), P<0*00001; I2=49%], triglyceride [SMD: -0*33 (95%CI:-0*45, -0*20), P<0*00001; I2=0%], and high density lipoprotein cholesterol [SMD: 0*29 (95%CI:0*02, 0*57), P=0*03; I2=69%]. The superiority of metformin in improving LDL-C level disappeared in a sensitivity analysis and 80% (8/10) of subgroup analyses. Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P=0*002 to 0*01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P=0*07 to 0*33). The rates of discontinuation due to any reason [RR: 0*97 (95%CI: 0*66, 1*43), P=0*89; I2=0%] was similar between the two groups. Conclusions: Adjunctive metformin could be useful to improve total cholesterol and triglyceride levels, but it was not effective in improving LDL-C level in schizophrenia. Funding Statement: The study was supported by the National Key and Development Plan Precision Medical Research 2016 Project (2016YFC0906302) and Science and Technology Program of Guangzhou (201807010064). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Review registration: CRD42019125861.

New vertebral fractures after osteoporotic vertebral compression fracture between balloon kyphoplasty and nonsurgical treatment PRISMA

Because of aging of population, osteoporotic vertebral compression fracture (OVCF) appears an increasing incidence rate. Conservative therapy (CT) and balloon kyphoplasty (BKP) have been used to treat OVCFs. However, an increase in new vertebral compression fractures at nontreated levels following BKP is of concern. It is still not clear whether new fractures were a result of BKP and the purpose of this meta-analysis was to evaluate the new fractures risk after BKP compared with CT. An exhaustive literature search of PubMed, EMBASE, and the Cochrane Library was conducted to identify randomized controlled trials and prospective nonrandomized controlled study that compared BKP with CT for patients suffering OVCF. A random-effect model was used. Results were reported as standardized mean difference or risk ratio with 95% confidence interval. Twelve studies were included and there was no significant difference in total new fractures (P = .33) and adjacent fractures (P = .83) between 2 treatments. Subgroup analyses did not demonstrate significant differences in follow-up period, mean age, anti-osteoporosis therapy, and the proportion of women. Our systematic review revealed that an increased risk of fracture of vertebral bodies was not associated with BKP compared with CT.

Bias caused by sampling error in meta-analysis with small sample sizes.

BackgroundMeta-analyses frequently include studies with small sample sizes. Researchers usually fail to account for sampling error in the reported within-study variances; they model the observed study-specific effect sizes with the within-study variances and treat these sample variances as if they were the true variances. However, this sampling error may be influential when sample sizes are small. This article illustrates that the sampling error may lead to substantial bias in meta-analysis results.MethodsWe conducted extensive simulation studies to assess the bias caused by sampling error. Meta-analyses with continuous and binary outcomes were simulated with various ranges of sample size and extents of heterogeneity. We evaluated the bias and the confidence interval coverage for five commonly-used effect sizes (i.e., the mean difference, standardized mean difference, odds ratio, risk ratio, and risk difference).ResultsSampling error did not cause noticeable bias when the effect size was the mean difference, but the standardized mean difference, odds ratio, risk ratio, and risk difference suffered from this bias to different extents. The bias in the estimated overall odds ratio and risk ratio was noticeable even when each individual study had more than 50 samples under some settings. Also, Hedges’ g, which is a bias-corrected estimate of the standardized mean difference within studies, might lead to larger bias than Cohen’s d in meta-analysis results.ConclusionsCautions are needed to perform meta-analyses with small sample sizes. The reported within-study variances may not be simply treated as the true variances, and their sampling error should be fully considered in such meta-analyses.

Pharmacological interventions for apathy in Alzheimer's disease.

Despite the high prevalence of apathy in Alzheimer's disease (AD), and its harmful effects, there are currently no therapies proven to treat this symptom. Recently, a number of pharmacological therapies have been investigated as potential treatments for apathy in AD. Objective 1: To assess the safety and efficacy of pharmacotherapies for the treatment of apathy in Alzheimer's disease (AD).Objective 2: To assess the effect on apathy of pharmacotherapies investigated for other primary outcomes in the treatment of AD. We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), MEDLINE, Embase, CINAHL, PsycINFO, LILACS, ClinicalTrials.gov and the World Health Organization (WHO) portal, ICTRP on 17 May 2017. Eligible studies were double-blind, randomized, placebo-controlled trials (RCTs) investigating apathy as a primary or secondary outcome in people with AD. Three review authors extracted data. We assessed the risks of bias of included studies using Cochrane methods, and the overall quality of evidence for each outcome using GRADE methods. We calculated mean difference (MD), standardized mean difference (SMD) or risk ratio (RR) with 95% confidence intervals on an intention-to-treat basis for all relevant outcome measures. We included 21 studies involving a total of 6384 participants in the quantitative analyses. Risk of bias is very low to moderate. All studies reported appropriate methods of randomization and blinding. Most studies reported appropriate methods of allocation concealment. Four studies, three with methylphenidate and one with modafinil, had a primary aim of improving apathy. In these studies, all participants had clinically significant apathy at baseline. Methylphenidate may improve apathy compared to placebo. This finding was present when apathy was assessed using the apathy evaluation scale (AES), which was used by all three studies investigating methylphenidate: MD -4.99, 95% CI -9.55 to -0.43, n = 145, 3 studies, low quality of evidence, but not when assessed with the neuropsychiatric inventory (NPI)-apathy subscale, which was used by two of the three studies investigating methylphenidate: MD -0.08, 95% CI -3.85 to 3.69, n = 85, 2 studies, low quality of evidence. As well as having potential benefits for apathy, methylphenidate probably also slightly improves cognition (MD 1.98, 95% CI 1.06 to 2.91, n = 145, 3 studies, moderate quality of evidence), and probably improves instrumental activities of daily living (MD 2.30, 95% CI 0.74 to 3.86, P = 0.004, n = 60, 1 study, moderate quality of evidence), compared to placebo. There may be no difference between methylphenidate and placebo in the risk of developing an adverse event: RR 1.28, 95% CI 0.67 to 2.42, n = 145, 3 studies, low quality of evidence. There was insufficient evidence from one very small study of modafinil to determine the effect of modafinil on apathy assessed with the FrSBe-apathy subscale: MD 0.27, 95% CI -3.51 to 4.05, n = 22, 1 study, low quality of evidence. In all other included studies, apathy was a secondary outcome and participants were not selected on the basis of clinically significant apathy at baseline. We considered the evidence on apathy from these studies to be indirect and associated with publication bias. There was low or very low quality of evidence on cholinesterase inhibitors (ChEIs) (six studies), ChEI discontinuation (one study), antipsychotics (two studies), antipsychotic discontinuation (one study), antidepressants (two studies), mibampator (one study), valproate (three studies) and semagacestat (one study). Methylphenidate may demonstrate a benefit for apathy and may have slight benefits for cognition and functional performance in people with AD, but this finding is associated with low-quality evidence. Our meta-analysis is limited by the small number of studies within each drug class, risk of bias, publication bias, imprecision and inconsistency between studies. Additional studies should be encouraged targeting people with AD with clinically significant apathy which investigate apathy as a primary outcome measure, and which have a longer duration and a larger sample size. This could increase the quality of evidence for methylphenidate, and may confirm whether or not it is an effective pharmacotherapy for apathy in AD.

O11.5. EFFECTIVENESS OF COORDINATED SPECIALTY CARE FOR EARLY PSYCHOSIS

BackgroundThe value of early intervention in psychosis and allocation of public resources has long been debated since outcomes in people with schizophrenia-spectrum disorders have remained suboptimal. Several research programs for early psychosis yielded promising results for team-based, multi-element coordinated specialty care (CSC).MethodsSystematic literature search of PubMed/PsycInfo/Embase/clinicaltrials.gov without language restrictions until 06/06/2017. Random effects meta-analysis of randomized trials comparing CSC versus Treatment as Usual (TAU) in in first episode psychosis or early-phase schizophrenia-spectrum disorders (schizophrenia, psychotic disorder not otherwise specified, schizoaffective disorder, schizophreniform disorder, delusional disorder), calculating standardized mean differences (SMDs) and risk ratios (RRs) for continuous and categorical outcomes as well as prespecified subgroup and meta-regression analyses.Co-primary outcomes were all-cause treatment discontinuation and ≥1 psychiatric hospitalization during the treatment period. Key secondary outcomes were total symptom improvement, functioning, and work or school involvement.ResultsAcross 10 trials (n=2,176; age=27.5 ± 4.6 years; male=62.3%; trial duration=16.2 ± 7.4 (range=9–24) months), CSC outperformed TAU at the end of treatment regarding all meta-analyzable outcomes. This included all-cause discontinuation (studies=10, n=2,173, RR=0.70, 95% confidence interval (CI)=0.61–0.80, p<0.001; number-needed-to-treat (NNT)=12.4), ≥1 hospitalization (studies=10, n=2,105, RR=0.74, 95%CI=0.61–0.90, p=0.003; NNT=10.1), total symptom severity (studies=8, n=1,179, SMD=-0.32, 95%CI=-0.47, -0.17, p<0.001), positive symptoms (studies=10, n=1,532, SMD=-0.22, 95%CI=-0.32, -0.13, p<0.001), negative symptoms (studies=10, n=1,432, SMD=-0.28, 95%CI=-0.42, -0.14, p<0.001), general symptoms (studies=8, n=1,118, SMD=-0.30, 95%CI=-0.47, -0.13, p=0.001), depressive symptoms (studies=5, n=874, SMD=-0.19, 95%CI=-0.35, -0.03, p=0.017), functioning (studies=7, n=1,005, SMD=0.21, 95%CI=0.09–0.34, p=0.001), involvement in school/work (studies=6, n=1,743, RR=1.13, 95%CI=1.03–1.24, p=0.012; NNT=17.8), and quality of life (studies=4, n=505, SMD=0.23, 95%CI=0.004–0.456, p=0.046). Superiority of CSC regarding all outcomes was also evident at 6, 9–12, and 18–24 months of treatment (except general symptoms and depression at 18–24 months).DiscussionIn early psychosis, CSC is superior to TAU across all meta-analyzable, highly relevant outcomes with small-to-medium effect sizes. These results support the need for funding and utilization of CSC in patients with early-phase psychosis.

Efficacy of curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis

PurposeThe unfavorable safety profiles of commonly prescribed knee osteoarthritis (OA) treatments have led clinicians and patients to seek safer alternatives. Research has suggested that curcuminoid and boswellia formulations could moderate key inflammatory pathways that are associated with worsening symptoms and disease progression. We conducted a systematic review and meta-analysis to assess the efficacy and safety of these treatments vs. placebo or NSAIDs for knee OA. MethodsWe searched Medline, EMBASE, Google Scholar, Web of Science and the Cochrane database from inception to February 21, 2018. We also hand searched reference lists and reviewed conference proceedings. We included randomized clinical trials (RCTs) comparing curcuminoid or boswellia formulations with placebo or NSAIDs for knee OA. We calculated standardized mean differences (SMD) or risk ratios (RR) for all relevant outcomes. Meta-analyses were conducted using random effects models. Heterogeneity was assessed using the I2 statistic. ResultsEleven RCTs (N = 1009) were eligible for analysis. Study quality was low overall, and most included RCTs were conducted on fewer than 100 participants. Both curcuminoid and boswellia formulations were statistically significantly more effective than placebo for pain relief and functional improvement. There were no significant differences between curcuminoids or boswellia and placebo in safety outcomes. Curcuminoids showed no statistically significant differences in efficacy outcomes compared to NSAIDs; patients receiving curcuminoids were significantly less likely to experience gastrointestinal adverse events. No RCTs compared boswellia against approved NSAIDs. ConclusionsThe results of our study suggest that curcuminoid and boswellia formulations could be a valuable addition to the knee OA treatment regimens by relieving symptoms while reducing safety risks. The current body of evidence is not adequate in size or quality to make any meaningful clinical practice recommendations. Further research through large, high quality RCTs probably investigating the synergistic effect of these products with other OA treatments is warranted.