Metafor Package Research Articles

Is Buprenorphine Effective for Chronic Pain? A Systematic Review and Meta-analysis.

The objective was to perform a systematic review and meta-analysis of the literature on the effects of buprenorphine on chronic pain outcomes (i.e., patient-reported pain intensity) in patients with and without opioid use disorder (OUD). Ovid/Medline, PubMed, Embase, and the Cochrane Library were searched for studies that explored the effectiveness (in reducing pain) of buprenorphine treatment for chronic pain patients with and without a history of OUD. Randomized controlled trials and observational studies were included in the review. Two separate searches were conducted to identify buprenorphine trials that included chronic pain patients either with or without OUD. Five studies used validated pain report measures and included a chronic pain population with OUD. Nine studies used validated report measures and included chronic pain patients without OUD. Meta-analysis was performed using the R, version 3.2.2, Metafor package, version 1.9-7. The meta-analysis revealed that buprenorphine has a beneficial effect on pain intensity overall, with a small mean effect size in patients with comorbid chronic pain and OUD and a moderate- to large-sized effect in chronic pain patients without OUD. Our results indicate that buprenorphine is modestly beneficial in reducing pain intensity in patients without OUD. Although informative, these findings should be carefully interpreted due to the small amount of data available and the variation in study designs.

RSA-tested TKA Implants on Average Have Lower Mean 10-year Revision Rates Than Non-RSA-tested Designs

The number of revisions after TKA is expected to rise because of aging populations in many countries and because patients are undergoing TKA at younger ages. Aseptic loosening is a major reason for late revision, which can be predicted by radiostereometric analysis (RSA) of small groups of patients at 2 years of follow-up. RSA is therefore an ideal tool to assess new TKA designs before they are introduced to the market, although not every TKA design has been studied with RSA. If RSA-tested TKA designs have lower 10-year revision rates in national registries than non-RSA-tested TKA designs, RSA testing of all new designs could be advocated. In this study, we asked: Is there a difference in the all-cause revision rate between non-RSA-tested and RSA-tested TKA designs registered in national knee arthroplasty registries at 5 and 10 years of follow-up? Knee arthroplasty registries were identified through the European Federation of National Associations of Orthopaedics and Traumatology webpage and through a manual internet search. Inclusion criteria were a minimum follow-up duration of 10 years and available revision or survival data per TKA design. Twenty-six registries were identified; seven were included comprising 339 TKA designs, of which 236 designs were classified as RSA-tested and 103 as non-RSA-tested. Six registries were excluded because no report was published. One registry was excluded because no fixation method was mentioned (79 TKA designs). Another registry was excluded because there was no 10-year data available (22 non-RSA-tested designs; 10 RSA-tested designs). Eleven registries were excluded because they did not provide revision rates per design and had not reached 10 years follow-up. The revision rates with their standard errors were extracted per design. We used the data from a recent meta-analysis to identify whether a TKA design was previously tested with RSA. This meta-analysis found 53 RSA studies comprising 70 different TKA designs. The prosthesis model, fixation method and insert type were extracted from these RSA-studies. The design characteristics of the TKA reported in the knee arthroplasty registries were also extracted, and if possible, matched to the TKA designs reported in the RSA-studies. At 5 years of follow-up, 191 TKA designs were identified as non-RSA-tested and 92 were identified as RSA-tested. At 10 years of follow-up, 154 TKA designs and 74 TKA designs were classified as non-RSA-tested and RSA-tested, respectively. A random-effects model using the Metafor Package in R statistics was used to estimate the pooled revision rate at 5 and 10 years of follow-up for both groups. The difference in revision rates between groups at 5 and 10 years of follow-up was estimated by including RSA as a factor in the random-effects model. Mean all-cause revision rates at 5 years for non-RSA-tested and RSA-tested implants were 3.6% (95% CI 3.4 to 3.8) and 2.9% (95% CI 2.7 to 3.0), with a mean difference of 0.6% favoring RSA-tested implants (95% CI 0.4 to 0.8; p < 0.001). Mean all-cause revision rates at 10 years for non-RSA-tested and RSA-tested implants were 5.5% (95% CI 5.2 to 5.9) and 4.4% (95% CI 4.1 to 4.7), with a mean difference of 0.9% favoring RSA-tested implants (95% CI 0.4 to 1.3; p < 0.001). Although there are exceptions, across registries, TKA designs that have been tested in an RSA setting have a slightly lower (about 1%) mean all-cause revision rate at 5-year and 10-year follow-up than those tested in a non-RSA setting. Acknowledging the inherent limitations of this observational study, a risk difference of 1% could potentially translate into an approximate 20% decrease in revision burden up to 10 years, which may have a profound impact on patient morbidity and health-related costs. Level III, therapeutic study.

Response Rates in Online Surveys With Affective Disorder Participants

Abstract. A meta-analysis was performed to determine whether response rates to online psychology surveys have decreased over time and the effect of specific design characteristics (contact mode, burden of participation, and incentives) on response rates. The meta-analysis is restricted to samples of adults with depression or general anxiety disorder. Time and study design effects are tested using mixed-effects meta-regressions as implemented in the metafor package in R. The mean response rate of the 20 studies fulfilling our meta-analytic inclusion criteria is approximately 43%. Response rates are lower in more recently conducted surveys and in surveys employing longer questionnaires. Furthermore, we found that personal invitations, for example, via telephone or face-to-face contacts, yielded higher response rates compared to e-mail invitations. As predicted by sensitivity reinforcement theory, no effect of incentives on survey participation in this specific group (scoring high on neuroticism) could be observed.

Meta-analysis of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy.

Various imaging modalities have been used to explore pathogenic mechanisms and stratify the severity of hepatic encephalopathy (HE). The hypothesis of this meta-analysis was that there is a progressive identifiable derangement of imaging measures using magnetic resonance spectroscopy (MRS) related to the severity of the HE. Studies with more than 10 cases and HE diagnosis were identified from the electronic databases PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Literatura Latino Americana em Ciências da Saúde (LILACS), and Cochrane Central Register of Controlled Trials (CENTRAL) through July 25, 2018. Participants were stratified into healthy controls and patients with non-HE (NHE) (cirrhosis without HE), minimal HE (MHE), and overt HE (OHE). Analyses were organized by metabolite studied and brain region examined. Statistical meta-analysis was performed using the metafor package in R (v3.4.1). Pooled standardized mean differences between patient groups were calculated using a random effects model. We identified 31 studies (1,481 patients) that included data for cirrhosis-related HE. We found the parietal region to be the most reliable in differentiating between patients with and without MHE, with standard mean differences of +0.82 (95% confidence interval [CI] +0.49 to +1.15, p < 0.0001, I 2 = 37.45%) for glutamine/glutamate, -0.36 (95% CI -0.61 to -0.10, p = 0.007, I 2 = 20.00%) for choline, and-0.77 (95% CI -1.19 to -0.34, p = 0.0004, I 2 = 67.48%) for myo-inositol. We also found that glutamine/glutamate was the metabolite that reliably correlated with HE grade in all brain regions. The meta-analysis reveals that MRS changes in glutamine/glutamate, choline, and myo-inositol, particularly in the parietal lobe, correlate with the severity of HE. MRS may be of value in the assessment of HE.

Association between moral cognition, moral emotion and prosocial behavior: Evidence from meta-analysis

Moral competence plays an important role in social, family, and peer relationships, and thus has received extensive attention. A large number of studies on children and adults have found that the cognitive and emotional components of moral competence can have a certain degree of impact on social interaction and social behaviors. Among these outcomes, prosocial behavior, or “behaviors aimed at benefiting others”, is considered important in moral development. Yet, relationship between moral cognition, moral emotion and prosocial behavior still needs to be further clarified. Especially, the large body of research on prosocial behavior has provided only limited direct comparison as to how the influences from moral cognition and moral emotion are similar and different. Therefore, the current meta-analysis was conducted to compare the roles of moral cognition and moral emotion in prosocial behavior. In addition, because maturation of moral cognition and moral emotion with age might moderate their relationship with prosocial behavior, age of participant was included as a potential moderator of interest. Empirical studies with typically developing participants at or over the age 3 years were selected. Then, results were systematically pooled to show how the roles of moral cognition and moral emotion might differ. Effect sizes describing the relationship between moral competence and prosocial behavior were extracted/calculated from the data. Altogether, 39 independent effect sizes (9960 participants) for moral cognition and 29 independent effect sizes (6946 participants) for moral emotion were retained for meta-analysis. All data were analyzed in R (3.6.1) with the Metafor package. The results showed that both moral cognition ( r = 0.22) and moral emotion ( r = 0.27) were positively associated with prosocial behavior. There were significant differences across studies in the strength of the relationship between moral competence and prosocial behavior, but the current meta-analysis did not yield evidence of statistical difference that age could explain these differences. Further analysis revealed that moral emotion and moral cognition played the same role overall. In most age groups, the two predictors had similar effect sizes on prosocial behavior, and only in adolescents, moral emotion had a stronger association with prosocial behavior at marginal significance than moral cognition had. One explanation is that individual hormone levels and brain structures are developing rapidly in adolescence, which may make adolescents more sensitive to information conveyed by moral emotion than that by moral cognition and greatly strengthen the influences of moral emotion on their social behaviors. Further studies are desired to examine the finer differences between the roles of moral emotion and moral cognition in relation to the developmental characteristics at different stages from preschool to adulthood. Overall, the findings provided evidence that both moral cognition and moral emotion were associated with prosocial behavior, and played similar roles despite a trend toward difference at certain development stages.

Systematic review and meta-analysis of the anatomical variants of the left colic artery.

To provide a comprehensive evidence-based assessment of the anatomical variations of the left colic artery (LCA). A thorough systematic search of the literature up until 1 April 2019 was conducted on the electronic databases PubMed, SCOPUS and Web of Science (WOS) to identify studies eligible for inclusion. Data were extracted and pooled into a meta-analysis using the Metafor package in R. The primary outcomes of interest were the absence of the LCA and the anatomical variants of its origin. The secondary outcomes were the distance (mean±SD) between the origin of the inferior mesenteric artery (OIMA) and the origin of the left colic artery (OLCA). A total of 19 studies (n=2040 patients) were included. The pooled prevalence estimate (PPE) of LCA absence was 1.2% (95% CI 0.0-3.6%). Across participants with either a Type I or Type II LCA, the PPE of a Type I LCA was 49.0% (95% CI 40.2-57.8%). The PPE of a Type II LCA was therefore 51.0%. The pooled mean distance from the OIMA to the OLCA was 40.41mm (95 CI% 38.69-42.12mm). The pooled mean length of a Type I LCA was 39.12mm (95% CI 36.70-41.53mm) while the pooled mean length of a Type IIa and Type IIb LCA was 41.43mm (95% CI 36.90-43.27mm) and 39.64mm (95% CI 37.68-41.59mm), respectively. Although the absence of the LCA is a rare occurrence (PPE 1.2%), it may be associated with an important risk of anastomotic leakage as a result of insufficient vascularization of the proximal colonic conduit. It is also necessary to distinguish variants I and II of Latarjet, the frequency of which is identical, with division of the LCA being technically more straightforward in variant I of Latarjet. Surgeons should be aware that technical difficulties are likely to be more common with variant II of Latarjet, as LCA ligation may be more difficult due to its close proximity to the inferior mesenteric vein (IMV).

Outcomes After Cervical Disc Arthroplasty Versus Stand-Alone Anterior Cervical Discectomy and Fusion: A Meta-Analysis.

Study Design:Systemic review and meta-analysis.Objectives:To review and compare surgical outcomes for patients undergoing stand-alone anterior cervical discectomy and fusion (ACDF) versus cervical disc arthroplasty (CDA) for the treatment of cervical spine disease.Methods:A systematic search was performed on PubMed, Medline, and the Cochrane Library. Comparative trials measuring outcomes of patients undergoing CDA and stand-alone ACDF for degenerative spine disease in the last 10 years were selected for inclusion. After data extraction and quality assessment, statistical analysis was performed with R software metafor package. The random-effects model was used if there was heterogeneity between studies; otherwise, the fixed-effects model was used.Results:In total, 12 studies including 859 patients were selected for inclusion in the meta-analysis. Patients undergoing stand-alone ACDF had a statistically significant increase in postoperative segmental angles (mean difference 0.85° [95% confidence interval = 0.35° to 1.35°], P = .0008). Patients undergoing CDA had a decreased rate of developing adjacent segmental degeneration (risk ratio = 0.56 [95% confidence interval = −0.06 to 1.18], P = .0745). Neck Disability Index, Japanese Orthopedic Association score, Visual Analogue Scale of the arm and neck, as well as postoperative cervical angles were similar between the 2 treatments.Conclusions:When compared with CDA, stand-alone ACDF offers similar clinical outcomes for patients and leads to increased postoperative segmental angles. We encourage further blinded randomized trials to compare rates of adjacent segmental degeneration and other postoperative outcomes between these 2 treatments options.

B Cell Maturation Antigen-Specific CAR T Cells for Relapsed or Refractory Multiple Myeloma: A Meta-Analysis

Background Cellular immunotherapies represent an enormously promising strategy for relapsed/refractory multiple myeloma (RRMM). Chimeric antigen receptor (CAR) T cells targeting B cell maturation antigen (BCMA) have shown impressive results in early-phase clinical studies. Here, we summarize the current body of evidence on the role of anti-BCMA CAR T cell therapy for RRMM. Methods We performed a systematic literature review to identify all publicly available prospective studies. We searched Medline, Cochrane trials registry, and www.clinicaltrials.gov. To include the most recent evidence, meeting abstracts from international hematology congresses were added. A conventional meta-analysis was conducted using meta and metafor packages in R statistical software. Pooled event rates and 95% confidence intervals (CIs) were calculated using the inverse variance method within a random-effects framework. Main efficacy outcomes were overall response, complete response (CR), and minimal residual disease (MRD). Furthermore, relapse rates, progression-free survival, and overall survival were evaluated. In terms of safety, outcomes were cytokine release syndrome (CRS), neurotoxicity, and hematologic toxic effects. Results Fifteen studies comprising a total of 285 patients with heavily pretreated RRMM were included in quantitative analyses. Patients received a median of seven prior treatment lines (such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, stem cell transplantation) which included autologous stem cell transplantation in 90% of patients. The median age of patients was 59 years and median follow-up duration ranged from 1.1 to 11.3 months. Most studies used 4-1BB (or CD137), a member of the TNF receptor superfamily, as an activation-induced T-cell costimulatory molecule. Most studies used fludarabine and cyclophosphamide for lymphodepletion while one study used busulfan and cyclophosphamide and one study used cyclophosphamide only. Most studies used the former Lee criteria for CRS grading. Anti-BCMA CAR T cells resulted in a pooled overall response of 82% (95% CI, 74-88%). The pooled proportion of CR in all evaluable patients was 36% (95% CI, 24-50%). Within responders, the pooled proportion of MRD negativity was 77% (95% CI, 67-85%). Higher dose levels of infused CAR+ cells were associated with higher overall response rates resulting in a pooled proportion of 88% (95% CI, 78-94%). In addition, peak CAR T cell expansion appeared to be associated with responses.The presence of high-risk cytogenetics appeared to be associated with lower overall response rates resulting in a pooled proportion of 68% (95% CI, 47-83%). The presence of extramedullary disease at time of infusion did not influence outcome and was associated with similar response rates compared with RRMM patients who did not have extramedullary disease, resulting in a pooled proportion of 78% (95% CI, 47-93%). The pooled relapse rate of all responders was 45% (95% CI, 27-64%) and the median progression-free survival was 10 months. In terms of overall survival, pooled survival rates were 84% (95% CI, 60-95%) at last follow-up (median, 11 months). In terms of safety, the pooled proportion of CRS of any grade was 69% (95% CI, 51-83%). Notably, the pooled proportions of CRS grades 3-4 and neurotoxicity were 15% (95% CI, 10-23%) and 18% (95% CI, 10-31%). Peak CAR T cell expansion appeared to be more likely in the setting of more severe CRS in three studies. Most hematologic toxic effects of grade 3 or higher were neutropenia (85%), thrombocytopenia (70%), and leukopenia (60%). Conclusion Anti-BCMA CAR T cells showed high response rates, even in high-risk features such as high-risk cytogenetics and extramedullary disease at time of CAR T cell infusion. Toxicity was manageable across all early-phase studies. However, almost half of the patients who achieved a response eventually relapsed. Larger studies with longer follow-up evaluating the association of response and survival are needed. Disclosures Ayuk: Novartis: Honoraria, Other: Advisory Board, Research Funding. Kroeger:Medac: Honoraria; Sanofi-Aventis: Honoraria; Neovii: Honoraria, Research Funding; Riemser: Research Funding; JAZZ: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; DKMS: Research Funding.

FIRST FAILED MACULAR HOLE SURGERY OR REOPENING OF A PREVIOUSLY CLOSED HOLE: Do We Gain by Reoperating?-A Systematic Review and Meta-analysis.

To evaluate repeated surgery for idiopathic full-thickness macular hole that failed to close (FTC) after first surgery or reopened (RO) once originally closed. Systematic review and meta-analysis. Pubmed.gov and Cochrane Library were searched for studies in English presenting outcomes of idiopathic full-thickness macular hole that FTC or RO (case reports/series of <5 cases excluded). Anatomical closure, postoperative best-corrected visual acuity, intraoperative/postoperative complications, and patient-reported outcomes. Meta-analysis was performed on aggregate and available individual participant data sets using the metafor package in R. Twenty-eight eligible studies were identified. After reoperation, pooled estimates for anatomical closure were 78% (95% confidence interval 71-84%) and 80% (95% confidence interval 66-89%) for FTC and RO groups, respectively. On average, best-corrected visual acuity improved in both groups. However, only 15% (28 of 189 eyes) of FTC eyes achieved best-corrected visual acuity of ≥6/12. The pooled estimated probability of ≥2-line best-corrected visual acuity improvement was 58% in the FTC group (95% confidence interval 45-71%); meta-analysis was not possible in the RO group. The most common complication was cataract. Reoperation for FTC or RO idiopathic full-thickness macular hole achieved a clinically meaningful visual acuity improvement in more than half of patients; high levels of vision (≥6/12), however, were uncommon.

Abstract 616: Literature review and meta-analyses of the prevalence of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) for colorectal (CRC), gastric (GC), endometrial (EC) and ovarian cancers (OC) in Chinese population

Abstract Purpose Given the high prevalence of MSI-H/dMMR in gastrointestinal and gynecologic cancers we systematically collected published studies and investigated its’ prevalence for Chinese CRC, GC, EC, OC subjects to better understand the size of potential target population available for pembrolizumab treatment in China. Experimental Design Both Chinese and English literature were searched in WanFang and PubMed database respectively. Studies were included if they assessed prevalence of MSI-H by PCR based method investigating 5 markers from NCI or Promega panel, and/or dMMR by immunohistochemistry (IHC) for all 4 MMR proteins. Studies focusing only on hereditary or sporadic cancer were filtered out. Among eligible studies, meta-analyses (DerSimonian Laird random effect model) were performed on the proportion of MSI-H/dMMR for each tumor type by R metafor package. Prevalence for advanced stage (III/IV) were also extracted if the data were available. Results For CRC, the prevalence of MSI-H estimated from 11 studies (13.7% [10.2-17.6%]) was similar as that of dMMR from 22 studies (14.6% [12.3-17.1%]). Pooled prevalence of MSI-H/dMMR from 32 studies (12,341 subjects) was estimated at 14.1% (12.2-16.1%), and 9.7% (7.2-12.5%) from 17 studies (3,933 subjects) for advanced stage CRC. The prevalence estimation for GC, EC and OC were 18.5%, 26% and 12.9% respectively. Further, the prevalence in advanced stage cancer, regardless of the cancer type, tended to be numerically lower than the all-stage combined prevalence. Conclusions This was the first study comprehensively integrating published studies to estimate prevalence of MSI-H/dMMR across 4 main tumor types for Chinese subjects. The meta-analysis indicated the prevalence of MSI-H/dMMR for all or advanced stage Chinese cancer patients might be similar as that for western population. Citation Format: Xiaoqiao Liu, Jiaqi Fan, Kai-Li Liaw, Mo Xu, Yu Zhou, Mayur Amonkar, Gefei Zeng. Literature review and meta-analyses of the prevalence of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) for colorectal (CRC), gastric (GC), endometrial (EC) and ovarian cancers (OC) in Chinese population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 616.

Association Between Neck Circumference and Coronary Heart Disease: A Meta-analysis.

Aims: Neck circumference (NC) was found to be related to the risk factors for coronary heart disease (CHD). However, the effects of NC on CHD are still controversial. To evaluate the relationship between NC and CHD, a meta-analysis of observational studies was performed. Method: Eligible studies on the association between NC and CHD were searched in Medline, Embase, Ovid, and Web of Science databases published in English from January 1980 to December 2016. Moreover, studies published in Chinese in Wanfang and China Hospital Knowledge databases were also searched. Random effects models in the metafor package in statistical analysis software R 3.3.3 were used for the meta-analysis. Heterogeneity was analyzed with Q statistics. Results: Eight studies were selected for the meta-analysis. A larger NC was associated with a higher prevalence of CHD (OR = 1.18, 95% CI 1.04–1.34, p = 0.0108). The eight studies were further divided into three subgroups according to the criteria for diagnosing CHD. In the subgroup of coronary angiography, NC was also found to be associated with the prevalence of CHD with low heterogeneity (OR = 1.17, 95% CI 1.07–1.28, p = 0.0007, I2 = 17.02%). However, in the subgroup of computed tomography or past history, no association between NC and CHD was found. In addition, subgroup analyses were also conducted according to the regions of the study. No association between NC and CHD was identified in either Chinese studies or Brazil studies (OR = 1.20, 95% CI 0.96–1.49; OR = 1.31, 95% CI 0.82–2.09, respectively). Conclusion: Larger NC is associated with increased risk of CHD, especially when coronary angiography was taken to diagnose CHD.

Efficacy and Safety of Pioglitazone Monotherapy in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Pioglitazone, the only thiazolidinedione drug in clinical practice is under scrutiny due to reported adverse effects, it’s unique insulin sensitising action provides rationale to remain as a therapeutic option for managing type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis comparing pioglitazone monotherapy with monotherapies of other oral antidiabetic drugs for assessing its efficacy and safety in T2DM patients. Mean changes in glycated haemoglobin (HbA1c), and mean changes in fasting blood sugar (FBS) level, body weight (BW) and homeostasis model assessment-insulin resistance (HOMA-IR) were primary and secondary outcomes, respectively. Safety outcomes were changes in lipid parameters, blood pressure and incidences of adverse events. Metafor package of R software and RevMan software based on random-effects model were used for analyses. We included 16 randomised controlled trials. Pioglitazone monotherapy showed equivalent efficacy as comparators in reducing HbA1c by 0.05% (95% CI: −0.21 to 0.11) and greater efficacy in reducing FBS level by 0.24 mmol/l (95% CI: −0.48 to −0.01). Pioglitazone showed similar efficacy as comparators in reducing HOMA-IR (WMD: 0.05, 95% CI: −0.49 to 0.59) and increasing high-density lipoprotein level (WMD: 0.02 mmol/l, 95% CI: −0.06 to 0.10). Improved blood pressure (WMD: −1.05 mmHg, 95% CI: −4.29 to 2.19) and triglycerides level (WMD: −0.71 mmol/l, 95% CI: −1.70 to 0.28) were also observed with pioglitazone monotherapy. There was a significant association of pioglitazone with increased BW (WMD: 2.06 kg, 95% CI: 1.11 to 3.01) and risk of oedema (RR: 2.21, 95% CI: 1.48 to 3.31), though the risk of hypoglycaemia was absolutely lower (RR: 0.51, 95% CI: 0.33 to 0.80). Meta-analysis supported pioglitazone as an effective treatment option for T2DM patients to ameliorate hyperglycaemia, adverse lipid metabolism and blood pressure. Pioglitazone is suggested to prescribe following individual patient’s needs. It can be a choice of drug for insulin resistant T2DM patients having dyslipidaemia, hypertension or history of cardiovascular disease.

Abstract P1-12-11: Exercise interventions for breast cancer (BC) patients in rural areas: The Northern New England (NNE) experience

Abstract Background: Women in rural areas are less likely to engage in physical activity (PA) compared with their urban counterparts. It can be even more challenging for BC patients due to the sequelae of their cancer and treatment. A quality improvement project in our cancer center evaluating leisure time activity among BC patients identified that about half the responders were sedentary or insufficiently active. Only one third were aware of the recommendation to achieve 150 active minutes per week while more than half reported not meeting the goal. Lack of motivation was quoted as the main reason for not meeting the goal by one-third of the responders. Goal setting has been an integral part of cardiac rehabilitation and behavior change techniques. It has shown to increase participation and motivation. We performed a combined analysis of collaborative interventions in NNE to identify if effective goal setting can overcome the barriers to PA among BC survivors. Methods: 5 IRB-approved interventions promoting PA among BC patients across 3 states were included. Studies were stratified according to the stages of treatment, the types of intervention and whether goal-setting was used. Pooled effects were calculated using Comprehensive Meta-Analysis software and R package metafor (v.2.0.0) with the maximum-likelihood configuration. Subgroup analyses were conducted based on the goal-setting criteria. Results: The 5 studies examining 4 exercise interventions are shown in the table below. The studies evaluating exercise interventions in BC patientsStudy nameIWEB/ W12051D12030D1032D12110UVM (STW)RegionVT/ MA/ NHVT/ NHVT/ NHVT/NHVTUrban/ Rural MixedMixedRuralRuralRuralUrbanRandomizedNoYesNoYesNoMeasurement Type of interventionIntermittent (Web-based)Pedometer Phone callSelf-reportedSelf-reportedSelf-reportedFinal goal defined as &amp;gt;150 min of PA weeklyYesNoNoNoYesGoal-settingYesYesYesYesNoBMI eligibilityYesNoNoNoNoPA eligibilityNoYesNoNoNoEnrolled50282359407Completed intervention3441724279Completed/ Assigned to intervention (%)10014734168.6Completed + change PA (%)41.3100697580.4 D12030 included patients on chemotherapy with the aim to increase activity by 10MET/week, while the W12051, UVM, D1032 and D12110 studies included patients who were post-chemotherapy. Home-based programs were used in W12051 and D12030. Goal-setting was used in all the studies except for the UVM study which used a supervised program with self-reporting. Weighing by percentage of patients completing the program, the pooled change in PA was 56.6% (95% CI=24.2-89.1%). Pooled PA for the goal-setting subgroup was nearly twice as high as the without-goal-setting subgroup (74.3% and 39.5%, respectively). Conclusion: Cancer centers with large catchment areas need to design creative approaches to encourage PA among the BC survivors. With the lack of motivation as the most common barrier to achieving the recommended PA, goal-directed programs can be helpful by creating attainable targets as well as providing emotional and psychological support. In addition, geographical barriers need to be addressed through interventions like internet-based programs, personal tracking devices, and small-group social activities. Citation Format: Batukbhai B, Stannard MG, Donovan AM, Lyons KD, Dittus K, Stoedefalke K, Chamberlin MD. Exercise interventions for breast cancer (BC) patients in rural areas: The Northern New England (NNE) experience [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-11.

Risk of Pneumonitis and Pneumonia Associated With Immune Checkpoint Inhibitors for Solid Tumors: A Systematic Review and Meta-Analysis.

Background: We performed a systematic review and meta-analysis to evaluate the risk of pneumonitis and pneumonia associated with immune checkpoint inhibitors (ICIs) for solid tumors.Methods: The following keywords were used in searching the Embase and PubMed database: pneumonitis, pneumonia, and immune checkpoint inhibitors. The data was analyzed by using the R software and Metafor package.Results: Among 3,436 studies, 23 randomized clinical trials (RCTs) met our selection criteria which included data from 12,876 patients. Compared with chemotherapy, PD-1 inhibitors showed significant increase in grade 1-5 and grade 3-5 pneumonitis (RR, 5.17, 95% CI: 2.82–9.47, p < 0.001; RR, 4.14, 95% CI: 1.82–9.42, p < 0.001), but not in pneumonia. PD-L1 inhibitors showed significant increase in grade 1-5 pneumonitis and pneumonia (RR, 3.25, 95% CI: 1.61–6.57, p < 0.001; RR, 2.11, 95% CI: 1.20–3.70, p < 0.001). There was no significant difference in any grade pneumonitis and pneumonia in cytotoxic T lymphocyte-associated protein 4 (CTLA4) inhibitors subgroup. Programmed cell death protein 1 (PD-1) inhibitor (nivolumab and pembrolizumab) both showed significant increase in grade 1-5 pneumonitis, and pembrolizumab specially tended to increase grade 3-5 pneumonitis. (RR, 5.64 95% CI: 1.94–16.38, p < 0.001). Compared with PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab) monotherapy, PD-1 inhibitor, and CTLA-4 inhibitor (nivolumab plus ipilimumab) combination therapies showed significant increase in grade 1-5 and grade 3-5 pneumonitis (RR 3.47, 95%CI:1.76–6.83, p < 0.001; RR 3.48, 95%CI: 1.10–11.02, p < 0.001).Conclusions: PD-1/PD-L1 inhibitors treatment could increase the risk of all-grade pneumonitis. CTLA4 inhibitor ipilimumab treatment alone could not increase the risk of pneumonitis but could augment the risk of pneumonitis in PD-1/PD-L1 inhibitor treated patients. There was no significant increase in the risk of pneumonia after either PD-1/PDL-1inhibitor or CTLA4 inhibitor treatment alone or in combination.

Frailty syndrome and cognitive impairment in older adults: systematic review of the literature.

Objective:to synthesize the knowledge about the association of frailty syndrome and cognitive impairment in older adults.Method:the Joanna Briggs Institute’s systematic review of etiology and risk factors was adopted. The search for the studies was conducted by two independent reviewers in the databases MEDLINE, Embase, CINAHL and LILACS and by manual search was performed by tow reviewers independently. The measures of association Odds Ratio and Relative Risk were used in the meta-analysis. The software R version 3.4.3 and the meta-analysis package Metafor 2.0 were used for figure analysis.Results:three studies identified the association of frailty syndrome and cognitive impairment through Odds Ratio values show that frail older adults are 1.4 times more likely to present cognitive impairment than non-frail older adults. Four studies analyzed the association through the measure of Relative Risk and found no statistical significance, and four studies used mean values.Conclusion:despite of the methodological differences of the studies and the lack of definition of an exact proportion in the cause and effect relationship, most studies indicate Frailty Syndrome as a trigger for Cognitive decline.

A systematic literature mapping and meta-analysis of animal-based traits as indicators of production diseases in pigs

The choice of animal-based traits to identify and deal with production diseases is often a challenge for pig farmers, researchers and other related professionals. This systematic review focused on production diseases, that is, the diseases that arise from management practices, affecting the digestive, locomotory and respiratory system of pigs. The aim was to classify all traits that have been measured and conduct a meta-analysis to quantify the impact of diseases on these traits so that these can be used as indicators for intervention. Data were extracted from 67 peer-reviewed publications selected from 2339 records. Traits were classified as productive (performance and carcass composition), behavioural, biochemical and molecular traits. A meta-analysis based on mixed models was performed on traits assessed more than five times across studies, using the package metafor of the R software. A total of 524 unique traits were recorded 1 to 31 times in a variety of sample material including blood, muscle, articular cartilage, bone or at the level of whole animal. No behavioural traits were recorded from the included experiments. Only 14 traits were measured on more than five occasions across studies. Traits within the biochemical, molecular and productive trait groups were reported most frequently in the published literature and were most affected by production diseases; among these were some cytokines (interleukin (IL) 1-β, IL6, IL8 and tumour necrosis factor-α), acute phase proteins (haptoglobin) and daily weight gain. Quantification of the influence of factors relating to animal characteristics or husbandry practices was not possible, due to the low frequency of reporting throughout the literature. To conclude, this study has permitted a holistic assessment of traits measured in the published literature to study production diseases occurring in various stages of the production cycle of pigs. It shows the lack of consensus and common measurements of traits to characterise production diseases within the scientific literature. Specific traits, most of them relating to performance characteristics or immunological response of pigs, are proposed for further study as potential tools for the prognosis and study of production diseases.

Short communication: Meta-analysis of dairy cows fed conventional sorghum or corn silages compared with brown midrib sorghum silage

A meta-analysis was conducted to compare the effects of feeding dairy cows conventional sorghum silage (CSS) or conventional corn silage (CCS) compared with brown midrib sorghum silage (BMRSS) diets on dry matter intake (DMI), milk production, and milk composition. Data from 9 published articles (1984 to 2015) were used to contrast diets with CSS (7 means comparisons; 104 cows) or CCS (13 means comparisons; 204 cows) versus BMRSS diets. Statistical analysis was performed using fixed or random effects models with the Metafor package of R (https://www.R-project.org). The degree of heterogeneity was measured with the I2 statistic, and publication bias was determined with funnel plots and Egger's regression test. Other sources of heterogeneity of response were analyzed through meta-regression. Estimated effect size was calculated for DMI, milk production, and milk composition. No evidence of publication bias was observed for any variable tested. The highest degree of heterogeneity (I2 = 41.5 and 72.6%) was observed for DMI among dependent variables tested in both comparisons, indicating that intake responses to silage type are rather inconsistent; in contrast, milk production had the lowest degree of heterogeneity (I2 = 0%), supporting the idea that the responses of this variable to silage type were very consistent across studies. Compared with BMRSS diets, cows fed CSS diets exhibited decreased milk production (1.64 kg/d), milk fat concentration (0.09%), milk fat yield (0.08 kg/d), milk protein yield (0.04 kg/d), and milk lactose yield (0.16 kg/d) and tended to decrease DMI (0.83 kg/d). Compared with CCS diets, cows fed BMRSS diets increased milk fat concentration (0.10%), but decreased milk protein concentration (0.06%) and tended to increase lactose yield (0.08 kg/d). Meta-regression indicated that days in milk affected DMI and milk production when CSS diets were compared with BMRSS diets, and DMI when CCS diets were compared with BMRSS diets. Additionally, the inclusion rate of silage in the diet and dietary neutral detergent fiber affected yields of milk fat and lactose, respectively, when CCS and BMRSS diets were compared. Overall, lactation performance improved when cows were fed diets formulated with BMRSS compared with CSS, but performance was not different for cows fed BMRSS and CCS diets. However, the small sample size may have influenced these results by increasing the margin of the error and, concurrently, the power of the meta-analysis. Results of this analysis suggest that additional research is needed to explore the effects of days in milk and the inclusion rates of silages in the diets when comparing BMRSS with CSS or CCS.

Putative Astroglial Dysfunction in Schizophrenia: A Meta-Analysis of 1H-MRS Studies of Medial Prefrontal Myo-Inositol.

Background: Several lines of evidence support a role for astroglial pathology in schizophrenia. Myo-inositol is particularly abundant in astroglia. Many small sized studies have reported on myo-inositol concentration in schizophrenia, but to date these have not been pooled to estimate a collective effect size.Methods: We reviewed all proton magnetic resonance spectroscopy (1H-MRS) studies reporting myo-inositol values for patients satisfying DSM or ICD based criteria for schizophrenia in comparison to a healthy controls group in the medial prefrontal cortex published until February 2018. A random-effects model was used to calculate the pooled effect size using metafor package. A meta-regression analysis of moderator variables was also undertaken.Results: The literature search identified 19 studies published with a total sample size of 585 controls, 561 patients with schizophrenia. Patients with schizophrenia had significantly reduced medial prefrontal myo-inositol compared to controls (RFX standardized mean difference = 0.19, 95% CI [0.05–0.32], z = 2.72, p = 0.0067; heterogeneity p = 0.09). Studies with more female patients reported more notable schizophrenia-related reduction in myo-inositol (z = 2.53, p = 0.011).Discussion: We report a small, but significant reduction in myo-inositol concentration in the medial prefrontal cortex in schizophrenia. The size of the reported effect indicates that the biological pathways affecting the astroglia are likely to operate only in a subset of patients with schizophrenia. MRS myo-inositol could be a useful tool to stratify and investigate such patients.

Anthropometric indices as surrogates for estimating abdominal visceral and subcutaneous adipose tissue: A meta-analysis with 16,129 participants

AimTo seek anthropometric indices that estimate visceral and subcutaneous adipose tissue (VAT and SAT) by meta-analysis and comparing the predictive efficacy based on different characteristics of participants. MethodsPubMed, PubMed Central, Web of Science, China National Knowledge Infrastructure and Wanfang databases were searched for publications containing correlation coefficients of VAT and/or SAT with waist circumference (WC) and/or body mass index (BMI). The overall or subgroup pooled results were analyzed by meta and metafor packages of R with random effects model. MedCalc software was used to compare the correlation coefficients between groups. ResultsTwenty-nine publications were included in this meta-analysis. The correlation coefficients of VAT-WC, VAT-BMI, SAT-WC and SAT-BMI for total studies were between 0.640 and 0.785. The correlation of VAT with WC was larger than that with BMI (Z = 11.664, P < 0.001). Meanwhile, the correlation coefficients of VAT-WC were statistically different among different age groups, areas, ethnicities, body shapes, scanning levels, units and instruments of measuring VAT (P < 0.05). The overall correlation of SAT with BMI was larger than that with WC (Z = 3.805, P < 0.001). The subgroups’ correlation coefficients of SAT-BMI showed statistical differences between genders, age groups, areas, ethnicities, body shapes, scanning levels, units (cm2 and cm3) and instruments of measuring SAT (P < 0.05). ConclusionsWC may be a common and simple surrogate for estimating VAT, and BMI for SAT, especially in Europeans, but not in the aged people.

Dengue infection in India: A systematic review and meta-analysis.

IntroductionDengue is the most extensively spread mosquito-borne disease; endemic in more than 100 countries. Information about dengue disease burden, its prevalence, incidence and geographic distribution is critical in planning appropriate control measures against dengue fever. We conducted a systematic review and meta-analysis of dengue fever in IndiaMethodsWe searched for studies published until 2017 reporting the incidence, the prevalence or case fatality of dengue in India. Our primary outcomes were (a) prevalence of laboratory confirmed dengue infection among clinically suspected patients, (b) seroprevalence in the general population and (c) case fatality ratio among laboratory confirmed dengue patients. We used binomial–normal mixed effects regression model to estimate the pooled proportion of dengue infections. Forest plots were used to display pooled estimates. The metafor package of R software was used to conduct meta-analysis.ResultsOf the 2285 identified articles on dengue, we included 233 in the analysis wherein 180 reported prevalence of laboratory confirmed dengue infection, seven reported seroprevalence as evidenced by IgG or neutralizing antibodies against dengue and 77 reported case fatality. The overall estimate of the prevalence of laboratory confirmed dengue infection among clinically suspected patients was 38.3% (95% CI: 34.8%–41.8%). The pooled estimate of dengue seroprevalence in the general population and CFR among laboratory confirmed patients was 56.9% (95% CI: 37.5–74.4) and 2.6% (95% CI: 2–3.4) respectively. There was significant heterogeneity in reported outcomes (p-values<0.001).ConclusionsIdentified gaps in the understanding of dengue epidemiology in India emphasize the need to initiate community-based cohort studies representing different geographic regions to generate reliable estimates of age-specific incidence of dengue and studies to generate dengue seroprevalence data in the country.