Early vs Late Use of Anti-TNFa Therapy in Adult Patients With Crohn Disease: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 26 (12) ◽  
pp. 1808-1818
Author(s):  
Shadi Hamdeh ◽  
Muhammad Aziz ◽  
Osama Altayar ◽  
Mojtaba Olyaee ◽  
Mohammad Hassan Murad ◽  
...  

Abstract Objectives While anti-tumor necrosis factor alpha (anti-TNFa) therapies for Crohn disease (CD) were initially introduced in 1998 for biologic therapies are often introduced after a minimum of 6 years after diagnosis. The benefit of anti-TNFa early in the course of CD is still controversial, with some studies showing better outcomes but others not. To determine whether earlier introduction of anti-TNFa therapy improves efficacy in clinical trials or clinical series, we aimed to perform a meta-analysis comparing early vs late anti-TNFa use in the management of CD. Methods A comprehensive search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database’s inception to November 3, 2019. We included comparative studies of early vs late use of anti-TNFa therapy in adult patients with CD. Results Eleven studies were included in the analysis, with a total of 2501 patients. Meta-analysis demonstrated that the early use of anti-TNFa was associated with a statistically significant decrease in the need for surgery (relative risk [RR] = 0.43; 95% confidence interval [CI], 0.26–0.69; I2 = 68%) and disease progression (RR = 0.51; 95% CI, 0.35–0.75; I2 = 61%). Early use also showed an increase in early remission (RR = 1.94; 95% CI, 1.54–2.46; I2 = 0%) and clinical response. There was no statistically significant difference in achieving late remission (RR = 1.39; 95% CI, 0.94–2.05; I2 = 65%) or mucosal healing (RR = 1.10; 95% CI, 0.63–1.91; I2 = 0%). Conclusion This systematic review suggests that using anti-TNFa earlier in the treatment of CD (within 3 years) may improve clinical outcomes compared to late administration in terms of achieving early clinical remission, clinical response, disease progression, and the need for surgery.

2021 ◽  
Vol 49 (1) ◽  
pp. 23-34
Author(s):  
Katherine P Hooper ◽  
Matthew H Anstey ◽  
Edward Litton

Reducing unnecessary routine diagnostic testing has been identified as a strategy to curb wasteful healthcare. However, the safety and efficacy of targeted diagnostic testing strategies are uncertain. The aim of this study was to systematically review interventions designed to reduce pathology and chest radiograph testing in patients admitted to the intensive care unit (ICU). A predetermined protocol and search strategy included OVID MEDLINE, OVID EMBASE and the Cochrane Central Register of Controlled Trials from inception until 20 November 2019. Eligible publications included interventional studies of patients admitted to an ICU. There were no language restrictions. The primary outcomes were in-hospital mortality and test reduction. Key secondary outcomes included ICU mortality, length of stay, costs and adverse events. This systematic review analysed 26 studies (with more than 44,00 patients) reporting an intervention to reduce one or more diagnostic tests. No studies were at low risk of bias. In-hospital mortality, reported in seven studies, was not significantly different in the post-implementation group (829 of 9815 patients, 8.4%) compared with the pre-intervention group (1007 of 9848 patients, 10.2%), (relative risk 0.89, 95% confidence intervals 0.79 to 1.01, P = 0.06, I2 39%). Of the 18 studies reporting a difference in testing rates, all reported a decrease associated with targeted testing (range 6%–72%), with 14 (82%) studies reporting >20% reduction in one or more tests. Studies of ICU targeted test interventions are generally of low quality. The majority report substantial decreases in testing without evidence of a significant difference in hospital mortality.


2019 ◽  
Vol 119 (10) ◽  
pp. 1686-1694 ◽  
Author(s):  
Bavand Bikdeli ◽  
Renuka Visvanathan ◽  
David Jimenez ◽  
Manuel Monreal ◽  
Samuel Z. Goldhaber ◽  
...  

AbstractAlthough prophylaxis for venous thromboembolism (VTE) is recommended after many surgeries, evidence base for use of VTE prophylaxis after foot or ankle surgery has been elusive, leading into varying guidelines recommendations and notable practice variations. We conducted a systematic review of the literature to determine if use of VTE prophylaxis decreased the frequency of subsequent VTE, including deep vein thrombosis (DVT) or pulmonary embolism (PE), compared with control. We searched PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through May 2018, for randomized controlled trials (RCTs) or prospective controlled observational studies of VTE prophylaxis in patients undergoing foot and ankle surgery. Our search retrieved 263 studies, of which 6 were finally included comprising 1,600 patients. Patients receiving VTE prophylaxis had lower risk for subsequent DVT (risk ratio [RR]: 0.72; 95% confidence interval [CI]: 0.55–0.94) and subsequent VTE (RR: 0.72; 95% CI: 0.55–0.94). There was only one case of nonfatal PE, no cases of fatal PE, and no change in all-cause mortality (RR: 3.51; 95% CI: 0.14–84.84). There was no significant difference in the risk for bleeding (RR: 2.12; 95% CI: 0.53–8.56). Very few RCTs exist regarding the efficacy and safety of VTE prophylaxis in foot and ankle surgery. Prophylaxis appears to reduce the risk of subsequent VTE, but the event rates are low and symptomatic events are rare. Future studies should determine the subgroups of patients undergoing foot or ankle surgery in whom prophylaxis may be most useful.


2013 ◽  
Vol 16 (5) ◽  
pp. 1173-1181 ◽  
Author(s):  
Marcelo T. Berlim ◽  
Hannah J. Broadbent ◽  
Frederique Van den Eynde

Abstract Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depression (MD). However, the perceived lack of a suitable sham rTMS condition might have compromised the success of blinding procedures in clinical trials. Thus, we conducted a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials (RCTs) on high frequency (HF-), low frequency (LF-) and bilateral rTMS for MD. We searched the literature from January 1995 to July 2012 using Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and Scopus. The main outcome measure was participants' ability to correctly guess their treatment allocation at study end. We used a random-effects model and risk difference (RD). Overall, data were obtained from seven and two RCTs on HF- and bilateral rTMS, respectively. No RCT on LF-rTMS reporting on blinding success was found. HF- and bilateral rTMS trials enrolled 396 and 93 depressed subjects and offered an average of approximately 13 sessions. At study end, 52 and 59% of subjects receiving HF-rTMS and sham rTMS were able to correctly guess their treatment allocation, a non-significant difference (RD = −0.04; z = −0.51; p = 0.61). Furthermore, 63.3 and 57.5% of subjects receiving bilateral and sham rTMS were able to correctly guess their treatment allocation, also a non-significant difference (RD = 0.05; z = 0.49; p = 0.62). In addition, the use of angulation and sham coil in HF-rTMS trials produced similar results. In summary, existing sham rTMS interventions appear to result in acceptable levels of blinding regarding treatment allocation.


2020 ◽  
pp. 089686082091871
Author(s):  
Guo Xieyi ◽  
Tang Xiaohong ◽  
Wu Xiaofang ◽  
Li Zi

An increasing number of studies have focused on whether peritoneal dialysis (PD) can be used for the urgent initiation of dialysis in patients with chronic kidney disease (CKD). We performed this systematic review and meta-analysis to evaluate the feasibility and safety of urgent-start PD compared with those of planned PD and urgent-start hemodialysis (HD) in this population. PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), clinicaltrials.gov , and China National Knowledge Infrastructure (CNKI) were searched for relevant studies. Conference abstracts were also searched in relevant websites. The meta-analysis was performed using RevMan 5.3 software. A total of 15 trials involving 2426 participants were identified. The quality of the included studies was fair, but the quality of evidence was very low. Unadjusted meta-analysis showed that urgent-start PD had significantly higher mortality than planned PD, while adjusted meta-analysis did not show a significant difference. Higher incident of leakage and catheter mechanical dysfunction were observed in urgent-start PD. However, peritonitis, exit-site infection, or PD technique survival were comparable between urgent-start and planned PD. The all-cause mortality was comparable in urgent-start PD and urgent-start HD. Bacteremia was significantly lower in the urgent-start PD group than with urgent-start HD. Based on limited evidences, PD may be a viable alternative to HD for CKD patients requiring urgent-start dialysis. Because of the inconsistent results and the low quality of evidence, a definitive conclusion could not be drawn for whether urgent-start PD was comparable with planned PD. Therefore, high-quality and large-scale studies are needed in the future.


2021 ◽  
Author(s):  
Naomi Algeo ◽  
Kathleen Bennett ◽  
Deirdre Connolly

Abstract Background Research recommends the development and evaluation of interventions to support women with breast cancer in returning to, or managing, work. Despite this, there has historically been a paucity of rehabilitation interventions to support women with breast cancer to maintain or return to their work role. The aim of this systematic review was to examine key characteristics of rehabilitation interventions, and their effectiveness on work outcomes for women with breast cancer, compared to usual care. Methods A systematic review was conducted of controlled studies of rehabilitation interventions with work outcomes for women with breast cancer. Six databases were systematically searched: EMBASE, Web of Science, MEDLINE (OVID), CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL). Results are presented either as pooled odds ratio (OR) or pooled effect size (hedges g) between groups, with 95% confidence intervals (CI). Narrative synthesis was conducted on intervention outcomes not suitable for meta-analysis. Results Five thousand, five hundred and thirty-five studies were identified. Nine out of 28 abstracts met inclusion criteria. Heterogeneity of interventions and outcomes precluded meta-analysis for most outcomes. Of the interventions included in meta-analysis, no significant differences compared to usual care were found for sick leave (2 studies (12 months); OR 1.11 (95% CI: 0.66 to 1.87), number of sick days taken (2 studies (six months); difference in effect: -0.08, (95% CI: -0.48 to 0.38) or working hours (2 studies (12 months); 0.19, (95% CI: -0.20 to 0.64). Only one study, with a multidisciplinary intervention, showed a significant difference for work outcomes when compared to usual care. Work-specific content featured in three interventions only, none of which provided conclusive evidence for improvement in work outcomes. Enhanced physical and psychological sequalae, and quality of life was observed in some studies. Conclusion There remains a lack of effective and methodologically rigorous rehabilitation intervention studies for breast cancer survivors. The development and evaluation of effective rehabilitation interventions to support return to work is warranted.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S516-S517
Author(s):  
M Khorshid Fasge ◽  
M Alboraie ◽  
W Abbas ◽  
Z E Sayed ◽  
M El-Nady

Abstract Background To perform a systematic review and meta-analysis discussing the efficacy and safety of vedolizumab (VDZ) treatment in patients with active moderate to severe ulcerative colitis (UC). Methods Using relevant keywords, we searched PubMed, Web of Science, Scopus, and Cochrane Central databases, until June 2020. We included interventional and observational cohort studies which assessed the safety and effectiveness of VDZ 300 mg intravenous infusion, in patients with active moderate to severe UC. We used the Cochrane risk of bias assessment tool and the Newcastle-Ottawa scale to assess the quality of included interventional and cohort studies, respectively. Dichotomous outcomes were pooled as proportion, 95% Confidence interval (CI), and p-value under the random-effects model in the open meta-analyst software. Results We found 10 interventional studies and 35 cohort studies, including 4,794 patients eligible for our review. Most of the included citations were single-arm studies. Our meta-analysis showed that VDZ therapy could induce a significant clinical response in UC patients up to 54 weeks (proportion 0.516, 95% CI [0.453, 0.578], p < 0.001). VDZ was associated with clinically significantly clinical remission and steroid-free clinical remission after 54 weeks (p < 0.0001). Durable clinical remission, histological remission, and endoscopic response rates were maintained in UC patients taking VDZ at the 52nd week. There was no significant difference between VDZ and placebo regarding the incidence of drug-related serious adverse events (p = 0.113) and death rates (p = 0.085). Conclusion Our systematic review and meta-analysis showed that the use of VDZ in patients with active moderate to severe UC was associated with high percentages of clinical response and remission rates in induction and maintenance treatment stages. VDZ seems to be well tolerated in UC patients, apart from some infections and inflammations. Future RCTs should compare VDZ to active treatments for longer follow-up periods with larger sample size.


BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e026752
Author(s):  
Mahmoud Tawfik KhalafAllah ◽  
Ahmed Basiony ◽  
Ahmed Salama

ObjectiveTopical steroids are the cornerstone in controlling the inflammation after cataract surgery. Prednisolone acetate and difluprednate are the two main products for this purpose. However, it is unclear which one should be used in terms of effectiveness and safety.DesignSystematic review and meta-analysis.Data sourcesMedline via PubMed, Cochrane Central Register of Controlled Trials, Web of science and clinicaltrials.gov were searched through 10 January 2018, and updated on 20 July 2019, in addition to researching the references’ lists of the relevant articles.Eligibility criteriaRandomised-controlled trials (RCTs) comparing difluprednate and prednisolone acetate regardless of the dosing regimen used.Data extraction and synthesisTwo independent authors assessed the included RCTs regarding the risk of bias using the Cochrane tool. Relevant data were extracted, and meta-analysis was conducted using a random-effects model. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to appraise the evidence quality.ResultsWe included six RCTs with 883 patients: 441 received difluprednate and 442 received prednisolone acetate. The evidence quality was graded as moderate for corneal oedema and intraocular pressure and low for anterior chamber (AC) clearance. After small incision cataract surgery, difluprednate was superior in clearing AC cells at 1 week (OR=2.5, p>0.00001) and at 2 weeks (OR=2.5, p=0.04), as well as clearing the AC flare at 2 weeks (OR=6.7, p=0.04). After phacoemulsification, difluprednate was superior in terms of corneal clarity at 1 day (OR=2.6, p=0.02) and 1 week after surgery (OR=1.96, p=0.0007). No statistically significant difference was detected between both agents at 1 month in effectiveness. Also, both agents were safe, evaluated by the ocular hypertension (OR=1.23, p=0.8).ConclusionWith low-to-moderate certainty, difluprednate and prednisolone acetate are safe agents for controlling the inflammation after cataract surgery. Difluprednate showed significant superiority in terms of AC cells and AC flare at 2 weeks postoperatively.


Author(s):  
Jiawen Deng ◽  
Zachary Silver ◽  
Emma Huang ◽  
Elena Zheng ◽  
Kyra Kavanagh ◽  
...  

Abstract Objective To perform a network meta-analysis (NMA) on the efficacy of antiosteoporotic interventions in the prevention of vertebral and non-vertebral fractures in adult patients taking glucocorticoids (GCs). Methods We performed NMAs based on a prospectively developed protocol. A librarian-assisted database search of MEDLINE, EMBASE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), the Cochrane Central Register of Controlled Trials (CENTRAL) and Chinese databases was conducted for randomized controlled trials (RCTs) comparing antiosteoporotic interventions in adult patients taking GCs. Outcomes were vertebral and non-vertebral fracture incidences. Results We included 56 RCTs containing 6479 eligible patients in our analysis. We found that alendronate and teriparatide were associated with decreased odds of both vertebral and non-vertebral fractures. Denosumab and risedronate were associated with decreased odds of vertebral fractures, while etidronate, ibandronate and alfacalcidol were associated with decreased odds of non-vertebral fractures. We observed low network heterogeneity as indicated by the I2 statistic, and we did not detect evidence of publication bias. All outcomes were based on a moderate quality of evidence according to GRADE. Conclusion Bisphosphonates, teriparatide and denosumab are associated with decreased odds of fracture in patients undergoing GC therapy. Vitamin D metabolites and analogues (e.g. alfacalcidol) may have greater anti-fracture efficacy compared with plain vitamin D. Systematic Review Registration The International Prospective Register of Systematic Reviews (PROSPERO)—CRD42019127073


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yihua Fan ◽  
Xinyan Wen ◽  
Qiang Zhang ◽  
Fangyuan Wang ◽  
Qing Li ◽  
...  

This systematic review and meta-analysis aimed at evaluating the effect of traditional Chinese medicine (TCM) Bufei granule on stable chronic obstructive pulmonary disease (COPD). We retrieved data from PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials, CNKI, Wanfang, and WeiPu (VIP) for studies focusing on whether the TCM Bufei granule would be effective in treating stable COPD. No language restriction and blinding were used. All trials involved were examined based on the standards of the Cochrane Handbook, and Review Manager 5.3 software was applied for analyzing data. We included four studies involving 599 patients with stable COPD. When compared to placebo treatment, TCM Bufei granule intervention exhibited improvement in the forced expiratory volume in one second (FEV1) (standardized mean difference (SMD) = 0.70; range, 0.50–0.91; I2 = 0%), forced vital capacity (FVC) (SMD = 0.43; range, 0.23–0.62; I2 = 0%), FEV1 percentage of predicted value (FEV1%) (SMD = 0.57; range, 0.38–0.76; I2 = 4%), and FEV1/FVC (SMD = 0.69; range, 0.50–0.87; I2 = 0%). There was a statistically significant difference in St George’s Respiratory Questionnaire scores between the TCM Bufei granule and placebo treatments (SMD = −1.29; range, −2.32 to −0.26, I2 = 97%). None of the studies reported any adverse events. Therefore, TCM Bufei granule intervention could help in improving the lung function and quality of life in patients with stable COPD.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043751
Author(s):  
Lorraine Lau ◽  
Jamie L Benham ◽  
Patricia Lemieux ◽  
Jennifer Yamamoto ◽  
Lois E Donovan

ObjectiveTo evaluate the effect of levothyroxine therapy on pregnancy outcomes compared with placebo or no treatment in women without overt hypothyroidism with presence of thyroid peroxidase antibodies (TPOAb) and/or thyroglobulin antibodies (TgAb).DesignSystematic review and meta-analysis of randomised controlled trialsStudy eligibility criteriaPrespecified criteria for inclusion were: randomised trials of levothyroxine versus control (placebo or no treatment) among women with positive TPOAb or TgAb who were pregnant or considering conception.Data sourcesOvid MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials were searched from 1980 to 5 November 2020.Outcome measuresPrespecified data elements were extracted and where appropriate, meta-analyses were conducted. Main outcomes include pregnancy achieved, miscarriage, preterm delivery and live birth.Risk of bias assessmentCochrane Risk of Bias Tool for Quality Assessment of Randomised Controlled Trials.ResultsFrom 3023 citations, 79 citations were identified for full-text review. Of these, six trials (total of 2263 women) were included for qualitative and quantitative analyses. Risk of bias was deemed low for only one trial. There was no significant difference in the relative risk (RR) of pregnancy achieved (RR 1.03; 95% CI 0.93 to 1.13), miscarriage (RR 0.93; 95% CI 0.76 to 1.14), preterm delivery (RR 0.66; 95% CI 0.39 to 1.10) or live births (RR 1.01; 95% CI 0.89 to 1.16) in thyroid autoimmune women treated with levothyroxine compared with controls. Sensitivity analyses of preterm birth identified study quality and timing of levothyroxine initiation as sources of heterogeneity.ConclusionsAmong pregnant women or women planning conception, with thyroid autoimmunity, there is a lack of evidence of benefit for levothyroxine use (moderate to high Grading of Recommendations, Assessment, Development and Evaluations). Recommendations to use levothyroxine in this setting need to be reconsidered.PROSPERO registration numberCRD42019130459.


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