Effect of Concomitant Therapy With Steroids and Tumor Necrosis Factor Antagonists for Induction of Remission in Patients With Crohn's Disease: A Systematic Review and Pooled Meta-analysis.

BACKGROUND & AIMS: It is not clear whether concomitant therapy with corticosteroids and anti-tumor necrosis factor (TNF) agents is more effective at inducing remission in patients with Crohn's disease (CD) than anti-TNF monotherapy. We aimed to determine whether patients with active CD receiving corticosteroids during induction therapy with anti-TNF agents had higher rates of clinical improvement than patients not receiving corticosteroids during induction therapy. METHODS: We systematically searched the MEDLINE, Embase, and CENTRAL databases, through January 20, 2016, for randomized trials of anti-TNF agents approved for treatment of CD and identified 14 trials (5 of adalimumab, 5 of certolizumab, and 4 of infliximab). We conducted a pooled meta-analysis of individual patient and aggregated data from these trials. We compared data from participants who continued oral corticosteroids during induction with anti-TNF therapy to those treated with anti-TNF agents alone. The endpoints were clinical remission (CD activity index [CDAI] scores <150) and clinical response (a decrease in CDAI of 100 points) at the end of induction (weeks 4-14 of treatment). RESULTS: We included 4354 patients who received induction therapy with anti-TNF agents, including 1653 [38.0%] who were receiving corticosteroids. The combination of corticosteroids and an anti-TNF agent induced clinical remission in 32.0% of patients, whereas anti-TNF monotherapy induced clinical remission in 35.5% of patients (odds ratio [OR], 0.93; 95% CI, 0.74-1.17). The combination of corticosteroids and an anti-TNF agent induced a clinical response in 42.7% of patients, whereas anti-TNF monotherapy induced a clinical response in 46.8% (OR 0.84; 95% CI, 0.73-0.96). These findings did not change with adjustment for baseline CDAI scores and concurrent use of immunomodulators. CONCLUSIONS: Based on a meta-analysis of data from randomized trials of anti-TNF therapies in patients with active CD, patients receiving corticosteroids during induction therapy with anti-TNF agents did not have higher rates of clinical improvement compared with patients not receiving corticosteroids during induction therapy. Given these findings and the risks of corticosteroid use, clinicians should consider early weaning of corticosteroids during induction therapy with anti-TNF agents for patients with corticosteroid-refractory CD.

Pregnancy Outcomes After Liver Transplantation: A Systematic Review and Meta-Analysis.

INTRODUCTION: Liver transplantation (LT) remains the gold standard for treatment of end-stage liver disease. Given the increasing number of liver transplantation in females of reproductive age, our aim was to conduct a systematic review and meta-analysis evaluating pregnancy outcomes after LT. METHODS: MEDLINE, Embase, and Scopus databases were searched for relevant studies. Study selection, quality assessment, and data extraction were conducted independently by 2 reviewers. Estimates of pregnancy-related outcomes in LT recipients were generated and pooled across studies using the random-effects model. RESULTS: A comprehensive search identified 1,430 potential studies. Thirty-eight studies with 1,131 pregnancies among 838 LT recipients were included in the analysis. Mean maternal age at pregnancy was 27.8 years, with a mean interval from LT to pregnancy of 59.7 months. The live birth rate was 80.4%, with a mean gestational age of 36.5 weeks. The rate of miscarriages (16.7%) was similar to the general population (10%-20%). The rates of preterm birth, preeclampsia, and cesarean delivery (32.1%, 12.5%, and 42.2%, respectively) among LT recipients were all higher than the rates for the general US population (9.9%, 4%, and 32%, respectively). Most analyses were associated with substantial heterogeneity. DISCUSSION: Pregnancy outcomes after LT are favorable, but the risk of maternal and fetal complications is increased. Large studies along with consistent reporting to national registries are necessary for appropriate patient counseling and to guide clinical management of LT recipients during pregnancy.

Changing epidemiology of immune-mediated inflammatory diseases in immigrants: A systematic review of population-based studies.

BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are systemic diseases of multifactorial etiology that share aberrant immune responses as the common final pathway. With rising globalization, their incidence is increasing in developing countries and among immigrants. Our primary objective was to systematically review the epidemiology of IMIDs in immigrants and conduct a meta-analysis to estimate the risk of IMIDs in immigrant populations according to their origin and destination countries. METHODS: We systematically searched five biomedical databases and reviewed population-based studies, from inception through August 2018, that reported incidence or prevalence data of inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS) or psoriasis and psoriatic arthritis (PPA) among immigrants and the host population. RESULTS: The incidence and prevalence of IMIDs among immigrants differ from host populations, and evolve over subsequent generations. The risk of IBD among immigrants approximates that in hosts, especially among South Asians, with ulcerative colitis incidence changing prior to Crohn's disease incidence. MS risk is highest in Iranian immigrants, T1D in African immigrants and SLE in African and Iraqi immigrants. Data on other IMIDs are sparse. Significant heterogeneity between the studies precluded meta-analysis. CONCLUSION: Based on our systematic review, the epidemiology of IMIDs among immigrants varies according to native and host countries, immigrant generation, and IMID type. The rapid evolution suggests a role for non-genetic factors and gene-environment interactions. Future studies should focus on these pattern shifts, given implications of rising global burden of IMIDs and immigration.

Serum antigliadin antibodies in cerebellar ataxias: a systematic review and meta-analysis.

BACKGROUND: Gluten sensitivity refers to prominent immunological responses to gluten, usually in conjunction with elevated levels of serum antigliadin antibody (AGA). The association between AGA and cerebellar ataxias has been inconsistently reported. METHODS: We performed a systematic literature search and a meta-analysis to study the weighted pooled OR of idiopathic cerebellar ataxia (IDCA) cases to controls or to hereditary ataxia (HA) for AGA seropositivity using fixed effect model. RESULTS: Eleven studies were included, with a total of 847 IDCA cases, 1654 controls and 445 HA cases. IDCA cases had fourfold higher odds than controls (OR 4.28, 95% CI 3.10 to 5.90) and twofold higher odds than HA cases (OR 2.23, 95% CI 1.45 to 3.44) of having AGA seropositivity. Sensitivity analysis excluding the most weighted study, which accounted for 69% of the total weight, still showed similar associations (IDCA vs controls, OR 3.18, 95% CI 1.79 to 5.67 and IDCA vs HA, OR 1.72, 95% CI 1.03 to 2.86, respectively). The subgroup analysis showed that, when compared with controls, IDCA cases of both East Asian and Western countries had approximately threefold to fourfold higher odds to have AGA seropositivity (OR 3.41, 95% CI 1.67 to 6.97 and OR 4.53, 95% CI 3.16 to 6.49, respectively), suggesting the lack of ethnic heterogeneity. The odds of AGA seropositivity for HA cases was not significantly higher than controls (OR 1.41, 95% CI 0.82 to 2.44). CONCLUSION: Our study indicates the association between AGA and IDCA, across different geographic regions.

The prognostic importance of duration of AKI: a systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI), as defined by peak increase in serum creatinine, is independently associated with increased risk of mortality and length of stay. Studies have suggested that the duration of AKI may be an important additional or independent prognostic marker of increased mortality in patients with AKI across clinical settings. We performed a systematic review and meta-analysis of published studies to assess the impact of duration of AKI on outcomes. METHODS: Various bibliographic databases (MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science) were searched through database inception to December 2015. Human, longitudinal studies with patients aged 18 or above describing outcomes of duration of AKI were included. Duration of AKI categorized as "Short" if AKI duration was ≤2 days or labeled as "transient AKI"; "Medium" for AKI durations 3-6 days and "Long" for AKI duration of ≥7 days or "non-recovered". Various outcomes looked at were Long term mortality, cardiovascular events, chronic kidney disease (CKD). RESULTS: Eighteen studies were deemed eligible for the systematic review. The outcome of long-term mortality with duration of AKI was reported in 8 studies. The pooled Risk Ratio (RR) for long-term mortality generally was higher for longer duration of AKI: short duration of AKI (n = 8 studies, RR 1.42, 95% CI 1.21-1.66), medium duration (n = 4 studies, RR 1.92, 95% CI 1.34-2.75), and long duration (n = 8 studies, RR 2.28, 95% CI 1.77-2.94) duration of AKI. Further, Duration of AKI was independently associated with higher risk of cardiovascular outcomes and incident CKD Stage 3 when stratified within each stage of AKI. CONCLUSION: Duration of AKI was independently associated with long term mortality, cardiovascular(CV) events, and development of incident CKD Stage 3.

Transfusion-associated necrotizing enterocolitis in preterm infants: an updated meta-analysis of observational data.

BACKGROUND: The number of observational studies that report an association between packed red blood cell (PRBC) transfusions and necrotizing enterocolitis (NEC) has increased. The primary objective of this study was to evaluate the association between PRBC transfusions and NEC in observational studies. METHODS: Medline, Embase and Cochrane Library databases as well as the Pediatrics Academic Societies abstract archives were systematically searched to identify observational studies that investigated the association between PRBC transfusions and NEC. Key search terms included premature infant, blood transfusion and necrotizing enterocolitis. The generic inverse variance method with a random-effects model was used to meta-analyze selected studies. Odds ratios (ORs) and confidence intervals (CIs) were calculated. RESULTS: A meta-analysis of 17 observational studies that reported the association between PRBC transfusions and NEC was performed. The meta-analysis revealed no evidence of an association between PRBC transfusions and a higher risk of NEC (OR: 0.96; 95% CI: 0.53-1.71; P=0.88). The effect estimates that suggested an association between PRBC transfusion and NEC in matched case-control studies (OR: 1.20; 95% CI: 0.58-2.47; P=0.63) differed from those reported in cohort studies (OR: 0.51; 95% CI: 0.34-0.75; P=<0.01). CONCLUSIONS: This updated meta-analysis of predominantly low-to-moderate quality observational studies suggests that there is no significant association between PRBC transfusions and NEC. A higher quality of evidence on this topic is needed.

The Experience of Black Patients With Serious Illness in the United States: A Scoping Review.

CONTEXT: Black patients experience health disparities in access and quality of care. OBJECTIVE: To identify and characterize the literature on the experiences of Black patients with serious illness across multiple domains - physical, spiritual, emotional, cultural, and healthcare utilization. METHODS: We conducted a scoping review of US literature from the last ten years using the PRISMA-ScR framework. PubMed was used to conduct a comprehensive search, followed by recursive citation searches in Scopus. Two reviewers screened the resulting citations to determine eligibility for inclusion and extracted data, including study methods and sample populations. The included articles were categorized by topic and then further organized using the Social-Ecological Model. RESULTS: From an initial review of 433 articles, a final sample of 160 were included in the scoping review. The majority of articles used quantitative research methods and were published in the last four years. Articles were categorized into 20 topics, ranging from Access to Hospice and Utilization (42 articles) to Community Outreach and Services (three articles). Three-quarters (76.3%) of the included studies provided evidence that racial disparities exist in serious illness care, while less than one-quarter examined causes of disparities. The most common Model levels were the Health Care System (102 articles) and Individual (71 articles) levels. CONCLUSION: More articles focused on establishing evidence of disparities between Black and White patients than on understanding their root causes. Further investigation is warranted to understand how factors at the patient, provider, health system, and society levels interact to remediate disparities.

Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries.

BACKGROUND: Numerous studies have reported declines in semen quality and other markers of male reproductive health. Our previous meta-analysis reported a significant decrease in sperm concentration (SC) and total sperm count (TSC) among men from North America-Europe-Australia (NEA) based on studies published during 1981-2013. At that time, there were too few studies with data from South/Central America-Asia-Africa (SAA) to reliably estimate trends among men from these continents. OBJECTIVE AND RATIONALE: The aim of this study was to examine trends in sperm count among men from all continents. The broader implications of a global decline in sperm count, the knowledge gaps left unfilled by our prior analysis and the controversies surrounding this issue warranted an up-to-date meta-analysis. SEARCH METHODS: We searched PubMed/MEDLINE and EMBASE to identify studies of human SC and TSC published during 2014-2019. After review of 2936 abstracts and 868 full articles, 44 estimates of SC and TSC from 38 studies met the protocol criteria. Data were extracted on semen parameters (SC, TSC, semen volume), collection year and covariates. Combining these new data with data from our previous meta-analysis, the current meta-analysis includes results from 223 studies, yielding 288 estimates based on semen samples collected 1973-2018. Slopes of SC and TSC were estimated as functions of sample collection year using simple linear regression as well as weighted meta-regression. The latter models were adjusted for predetermined covariates and examined for modification by fertility status (unselected by fertility versus fertile), and by two groups of continents: NEA and SAA. These analyses were repeated for data collected post-2000. Multiple sensitivity analyses were conducted to examine assumptions, including linearity. OUTCOMES: Overall, SC declined appreciably between 1973 and 2018 (slope in the simple linear model: -0.87 million/ml/year, 95% CI: -0.89 to -0.86; P < 0.001). In an adjusted meta-regression model, which included two interaction terms [time × fertility group (P = 0.012) and time × continents (P = 0.058)], declines were seen among unselected men from NEA (-1.27; -1.78 to -0.77; P < 0.001) and unselected men from SAA (-0.65; -1.29 to -0.01; P = 0.045) and fertile men from NEA (-0.50; -1.00 to -0.01; P = 0.046). Among unselected men from all continents, the mean SC declined by 51.6% between 1973 and 2018 (-1.17: -1.66 to -0.68; P < 0.001). The slope for SC among unselected men was steeper in a model restricted to post-2000 data (-1.73: -3.23 to -0.24; P = 0.024) and the percent decline per year doubled, increasing from 1.16% post-1972 to 2.64% post-2000. Results were similar for TSC, with a 62.3% overall decline among unselected men (-4.70 million/year; -6.56 to -2.83; P < 0.001) in the adjusted meta-regression model. All results changed only minimally in multiple sensitivity analyses. WIDER IMPLICATIONS: This analysis is the first to report a decline in sperm count among unselected men from South/Central America-Asia-Africa, in contrast to our previous meta-analysis that was underpowered to examine those continents. Furthermore, data suggest that this world-wide decline is continuing in the 21st century at an accelerated pace. Research on the causes of this continuing decline and actions to prevent further disruption of male reproductive health are urgently needed.

Chelation Therapy in Patients With Cardiovascular Disease: A Systematic Review.

Background EDTA is an intravenous chelating agent with high affinity to divalent cations (lead, cadmium, and calcium) that may be beneficial in the treatment of cardiovascular disease (CVD). Although a large randomized clinical trial showed benefit, smaller studies were inconsistent. We conducted a systematic review of published studies to examine the effect of repeated EDTA on clinical outcomes in adults with CVD. Methods and Results We searched 3 databases (MEDLINE, Embase, and Cochrane) from database inception to October 2021 to identify all studies involving EDTA treatment in patients with CVD. Predetermined outcomes included mortality, disease severity, plasma biomarkers of disease chronicity, and quality of life. Twenty-four studies (4 randomized clinical trials, 15 prospective before/after studies, and 5 retrospective case series) assessed the use of repeated EDTA chelation treatment in patients with preexistent CVD. Of these, 17 studies (1 randomized clinical trial) found improvement in their respective outcomes following EDTA treatment. The largest improvements were observed in studies with high prevalence of participants with diabetes and/or severe occlusive arterial disease. A meta-analysis conducted with 4 studies reporting ankle-brachial index indicated an improvement of 0.08 (95% CI, 0.06-0.09) from baseline. Conclusions Overall, 17 studies suggested improved outcomes, 5 reported no statistically significant effect of treatment, and 2 reported no qualitative benefit. Repeated EDTA for CVD treatment may provide more benefit to patients with diabetes and severe peripheral arterial disease. Differences across infusion regimens, including dosage, solution components, and number of infusions, limit comparisons across studies. Additional research is necessary to confirm these findings and to evaluate the potential mediating role of metals. Registration URL: https://www.crd.york.ac.uk/; Unique identifier: CRD42020166505.

The association of impaired lung function and nonalcoholic fatty liver disease: a systematic review.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) and impaired lung function share similar risk factors and phenotypes, such as obesity and type 2 diabetes. The study is an updated meta-analysis to evaluate the association between NAFLD and impaired lung function. METHODS: A total of 696 articles were identified with mention of NAFLD and lung function (or pulmonary function testing) in MEDLINE, EMBASE, and Scopus. After de-duplication, 455 articles were screened, 18 underwent full-text review. Five studies met our review and inclusion criteria with an interrater reliability kappa score of 1. RESULTS: Five studies with a total of 118 118 subjects (28.4% with NAFLD) were included. The cross-sectional studies supported a statistically significant relationship between decreased pulmonary function tests and NAFLD. There was no association observed with obstructive lung pattern. One of the longitudinal studies revealed an association with increased rate of decline in forced vital capacity in patients with NAFLD and FIB4 score ≥1.30 (-21.7 vs. -27.4 mL/year, P = 0.001 in males, -22.4 vs. -27.9 mL/year, P = 0.016 in females). The second longitudinal study revealed that patients with impaired pulmonary function had an increased hazard ratio of developing NAFLD dependent on the severity of pulmonary impairment. CONCLUSIONS: This is the first systematic review that supports an association of NAFLD with decreased (restrictive) lung function. The estimated severity of liver fibrosis correlates with the rate of progression of restrictive lung function. There are also data showing that patients with impaired lung function have a higher risk of developing NAFLD.