scholarly journals Systematic review and meta-analysis of drug induced liver injury secondary to biologic medications in inflammatory bowel disease

2021 ◽  
Vol 5 (1) ◽  
pp. 005-012
Author(s):  
Gadour Eyad ◽  
Hassan Zeinab

Introduction: Drug-induced Hepatotoxicity and biologic drugs have historically been challenging in IBD. We aim to study the prevalence of hepatotoxicity in adult patients using biologic medications. Methodology: With the guidelines described by PRISMA-P, a detailed search strategy for each electronic database was developed based on PubMed, Medline, and Embase. We include RCTs that assessed the efficacy and hepatotoxicity of biologics in IBD patients. Hepatotoxicity was defined as AST and/or ALT >2x upper limit of normal or cholestasis. The Odds ratio (OR) was calculated with a 95% confidence interval (CI). Heterogeneity was assessed using the Chi2 test and the I2 statistic. Results: 862 records identified in total. After removing the duplicates 564 records were left for review. Four studies did not report on how participants were randomized to treatment groups or how allocation concealment was achieved, we rated these studies at unclear risk of bias for these domains. There was no presence of any heterogeneity among studies by (Chi2= 2.21, df = 6, p = 0.90, and I2 = 0%). Our meta-analysis was conducted on the fixed effects model, with the (0.770, 95% CI [-0.630, 0.957], and p = 0.02). Hepatotoxicity was not related to any TNF-α antagonist. Thiopurine induced liver injury occurred more frequently within the first months of treatment, 50% of cases within the first 3 months (11.4% vs. 2.3%, p < 0.05). Conclusion: When hepatotoxicity occurred, the treatment was withdrawn in thirty one percent of patients. This group of patients had a dose-dependent hepatotoxicity rather than an immunologic hepatitis.

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e027940 ◽  
Author(s):  
Seungwon Yang ◽  
Se Jung Hwang ◽  
Jung Yun Park ◽  
Eun Kyoung Chung ◽  
Jangik I Lee

ObjectivesThe objective of this study was to investigate the association between genetic polymorphisms of N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), glutathione S-transferase (GST) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) and the risk of anti-tuberculosis drug-induced liver injury (ATDILI).DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Web of Science and Cochrane Reviews databases were searched through April 2019.Eligibility criteriaWe included case-control or cohort studies investigating an association between NAT2, CYP2E1, GST or SLCO1B1 polymorphisms and the ATDILI risk in patients with tuberculosis.Data extraction and synthesisThree authors screened articles, extracted data and assessed study quality. The strength of association was evaluated for each gene using the pooled OR with a 95% CI based on the fixed-effects or random-effects model. Sensitivity analysis was performed to confirm the reliability and robustness of the results.ResultsFifty-four studies were included in this analysis (n=26 for CYP2E1, n=35 for NAT2, n=19 for GST, n=4 for SLCO1B1). The risk of ATDILI was significantly increased with the following genotypes: CYP2E1 RsaI/PstI c1/c1 (OR=1.39, 95% CI 1.06 to 1.83), NAT2 slow acetylator (OR=3.30, 95% CI 2.65 to 4.11) and GSTM1 null (OR=1.30, 95% CI 1.12 to 1.52). No significant association with ATDILI was found for the genetic polymorphisms of CYP2E1 DraI, GSTT1, GSTM1/GSTT1, SLCO1B1 388A>G and SLCO1B1 521T>C (p>0.05).ConclusionsATDILI is more likely to occur in patients with NAT2 slow acetylator genotype, CYP2E1 RsaI/PstI c1/c1 genotype and GSTM1 null genotype. Close monitoring may be warranted for patients with these genotypes.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Wei Huang ◽  
Ruiyun Zhou ◽  
Jianfeng Li ◽  
Jianjun Wang ◽  
Hongwei Xiao

Abstract The aim of the present study was to investigate the association of TNF-α-308 and TNF-α-238 gene polymorphisms with the risk of bone-joint and spinal tuberculosis (TB) by meta-analysis. By searching PubMed, Web of Science, Wanfang databases, CNKI, Medline, and Cochrane Library, the published articles about studies of the association of the TNF-α-308, TNF-α-238 gene polymorphisms with risk of bone-joint and spinal tuberculosis were collected by two reviewers. Begg’s and Egger’s tests were performed to assess publication bias. Stata 12.0 software was used for data analysis. The symmetry of the funnel plot indicated no significant publication bias in the Begg’s test (A: P=1.00, B: P=0.764), and the results of the Egger’s test showed no evidence of publication bias (A: P=0.954, B: P=0.626). Seven studies assessed the relationship between TNF-α-308 gene polymorphisms and risk of bone-joint and spinal tuberculosis risk. The heterogeneity (I2) of GG vs. AA or AG was 0% and there was no heterogeneity (χ2 = 0.06 and P=0.944) in a fixed-effects model. There was also a lack of association between TNF-α-308 polymorphism and bone-joint and spinal tuberculosis risk under the recessive model. The remaining models of the TNF-α-308 genotype and further studies of TNF-α-238 did not show a noteworthy association. Overall, there was no significant association between TNF-α-308, TNF-α-238 gene polymorphisms and bone-joint and spinal tuberculosis risk. Our study suggests that tumor necrosis factor α (TNF-α) gene polymorphisms may not contribute to bone-joint and spinal tuberculosis based on the current evidence.


2020 ◽  
Vol 20 (13) ◽  
pp. 1604-1612
Author(s):  
Congcong Wu ◽  
Hua Jiang ◽  
Jianghua Chen

Background: Although the adjuvant therapy of bisphosphonates in prostate cancer is effective in improving bone mineral density, it is still uncertain whether bisphosphonates could decrease the risk of Skeletal- Related Event (SRE) in patients with prostate cancer. We reviewed and analyzed the effect of different types of bisphosphonates on the risk of SRE, defined as pathological fracture, spinal cord compression, radiation therapy to the bone, surgery to bone, hypercalcemia, bone pain, or death as a result of prostate cancer. Methods: A systemic literature search was conducted on PubMed and related bibliographies. The emphasis during data extraction was laid on the Hazard Ratio (HR) and the corresponding 95% Confidence Interval (CI) from every eligible Randomized Controlled Trial (RCT). HR was pooled with the fixed effects model, and preplanned subgroup analyses were performed. Results: 5 RCTs (n = 4651) were included and analyzed finally after screening 51 articles. The meta-analysis of all participants showed no significant decrease in the risk of SRE when adding bisphosphonates to control group (HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536) with low heterogeneity (I2 = 0.0% (d.f. = 4) p = 0.679). There was no significant improvement on SRE neither in the subgroups with Metastases (M1) or Castration-Sensitive Prostate Cancer (CSPC) (respectively HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536, I2 = 0.0% (d.f. = 4) p = 0.679; HR = 0.954, 95% CI = 0.837 - 1.088, p = 0.484, I2 = 0.0% (d.f. = 3) p = 0.534). Conclusion: Our study demonstrated that bisphosphonates could not statistically significantly reduce the risk of SRE in patients with prostate cancer, neither in the subgroups with M1 or CSPC.


2021 ◽  
pp. postgradmedj-2020-139172
Author(s):  
Rimesh Pal ◽  
Mainak Banerjee ◽  
Urmila Yadav ◽  
Sukrita Bhattacharjee

PurposeObservations studies have shown that prior use of statins is associated with a reduced risk of adverse clinical outcomes in patients with COVID-19. However, the available data are limited, inconsistent and conflicting. Besides, no randomised controlled trial exists in this regard. Hence, the present meta-analysis was conducted to provide an updated summary and collate the effect of statin use on clinical outcomes in COVID-19 using unadjusted and adjusted risk estimates.MethodsPubMed, Scopus and Web of Science databases were systematically searched using appropriate keywords till December 18 2020, to identify observational studies reporting clinical outcomes in COVID-19 patients using statins versus those not using statins. Prior and in-hospital use of statins were considered. Study quality was assessed using the Newcastle-Ottawa Scale. Unadjusted and adjusted pooled odds ratio (OR) with 95% CIs were calculated.ResultsWe included 14 observational studies pooling data retrieved from 19 988 patients with COVID-19. All the studies were of high/moderate quality. Pooled analysis of unadjusted data showed that statin use was not associated with improved clinical outcomes (OR 1.02; 95% CI 0.69 to 1.50, p=0.94, I2=94%, random-effects model). However, on pooling adjusted risk estimates, the use of statin was found to significantly reduce the risk of adverse outcomes (OR 0.51; 95% CI 0.41 to 0.63, p<0.0005, I2=0%, fixed-effects model).ConclusionsStatin use is associated with improved clinical outcomes in patients with COVID-19. Individuals with multiple comorbidities on statin therapy should be encouraged to continue the drug amid the ongoing pandemic.


2021 ◽  
Vol 164 ◽  
pp. 105404
Author(s):  
Hao Niu ◽  
Judith Sanabria-Cabrera ◽  
Ismael Alvarez-Alvarez ◽  
Mercedes Robles-Diaz ◽  
Simona Stankevičiūtė ◽  
...  

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e043956
Author(s):  
Guizuo Wang ◽  
Dong Han ◽  
Zhengdong Jiang ◽  
Manxiang Li ◽  
Shumei Yang ◽  
...  

ObjectiveEarly life bronchiolitis has been hypothesised to be associated with the subsequent risk of persistent wheezing or asthma. However, the link remains controversial. The objective of our study was to evaluate the association between bronchiolitis before 2 years of age and the late-onset wheezing/asthma.DesignSystematic review and meta-analysis.MethodsPubMed, Embase and Web of Science databases were systematically searched for studies published between 1955 and January 2020. Meanwhile, we also checked through the reference lists of relevant articles to see whether these references included reports of other studies that might be eligible for the review. Cohort and case–control studies assessing the association between early-life bronchiolitis and late-onset wheezing/asthma were included in this meta-analysis. Data were extracted by two independent reviewers. Results were pooled using a random-effects model or fixed-effects model according to the heterogeneity among studies.Results32 original articles with 292 844 participants, which met the criteria, were included in this meta-analysis. Bronchiolitis before 2 years of age was associated with an increased risk of subsequent wheezing/asthma (relative risk=2.46, 95% CI 2.14 to 2.82, p<0.001). After categorising studies into different groups based on age at the end of follow-up, geographical region and study quality, the association still remained significant.ConclusionsThe meta-analysis indicates an association between bronchiolitis before 2 years of age and the wheezing/asthma in later life. Well-designed and highly standardised prospective studies that better address bias due to potential confounding factors are needed to validate the risk identified in our meta-analysis.PROSPERO registration numberCRD42018089453.


2020 ◽  
Vol 52 (12) ◽  
pp. 841-849
Author(s):  
Chunmei Xu ◽  
Ping Wang ◽  
Huikai Miao ◽  
Tianyue Xie ◽  
Xiaojun Zhou ◽  
...  

AbstractA potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mostafa K Fouad ◽  
Ashraf M Hazem ◽  
Kareem M Elnaghy

Abstract Aim of the Work to provide cumulative data about the efficacy and safety of neuro-muscular electrical stimulation (NMES) combined with usual care (UC) versus usual care alone in ICU patients with Critical Illness Myopathy (CIM). Methodology The current systematic review was done on studies published between 2009 and 2019. The total number of patients in all the included studies was 1259 patients; 652 in NMES group, and 607 in UC group. Our data were divided into two groups: NMES (652 patients), and UC (607 patients). Metaanalysis study was done on 11 studies which described and compared the 2 different techniques for treatment of CIM; with overall number of patients (N = 1259). Results Regarding 1ry outcome measures, we found 8 studies reported critical Critical illness myopathy (CIM), critical illness polyneuropathy (CIP), and the overlap, critical care setting   MRC scale for muscle strength, with total number of patients (N = 968). The random-effects model of the meta-analysis study showed non-significant difference in mean MRC scale in NMES group compared to usual care group (p &gt; 0.05). We also found 11 studies reported ICU stay with total number of patients (N = 1259). The random-effects model of the meta-analysis study showed nonsignificant difference in mean ICU stay in NMES group compared to usual care group (p &gt; 0.05). We also found only 2 studies reported SF-36 scale for quality of life, with total number of patients (N = 270). The fixed-effects model of the metaanalysis study showed highly significant decrease in mean SF-36 scale in NMES group compared to usual care group (p = 0.003). Regarding 2ry outcome measure, we found 3 studies reported CIM incidence with total number of patients (N = 394). The fixed-effects model of the meta-analysis study showed marked decrease in CIM incidence in NMES group compared to usual care group, but not reaching statistical significance (p &gt; 0.05). We also found 9 studies reported mortality rate with total number of patients (N = 1044). The fixed-effects model of the meta-analysis study showed non-significant difference in mortality rate in NMES group compared to usual care. Our systematic review and meta-analysis showed that NMES combined with usual care was not associated with significant differences in global muscle strength, ICU stay, quality of life score, CIM incidence and mortality rate in comparison with usual care alone in critically ill patients. Conclusion NMES is not superior to usual care in management of CIM. Usual care remains the mainstay of management of CIM with significant better outcomes, in addition to preventive measures as early aggressive treatment of sepsis and MOF, blood glucose control, optimizing certain drugs use, early enteral nutrition, maintaining water, electrolyte and acidbase balance.


2005 ◽  
Vol 23 (34) ◽  
pp. 8606-8612 ◽  
Author(s):  
Stefanos Bonovas ◽  
Kalitsa Filioussi ◽  
Nikolaos Tsavaris ◽  
Nikolaos M. Sitaras

Purpose A growing body of evidence suggests that statins may have chemopreventive potential against breast cancer. Laboratory studies demonstrate that statins induce apoptosis and reduce cell invasiveness in various cell lines, including breast carcinoma cells. However, the clinical relevance of these data remains unclear. The nonconclusive nature of the epidemiologic data prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Patients and Methods A comprehensive search for articles published up until 2005 was performed; reviews of each study were conducted; and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed. Results Seven large randomized trials and nine observational studies (five case-control and four cohort studies) contributed to the analysis. We found no evidence of publication bias or heterogeneity among the studies. Statin use did not significantly affect breast cancer risk (fixed effects model: RR = 1.03; 95% CI, 0.93 to 1.14; random effects model: RR = 1.02; 95% CI, 0.89 to 1.18). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, the sensitivity analysis confirmed the stability of our results. Conclusion Our meta-analysis findings do not support a protective effect of statins against breast cancer. However, this conclusion is limited by the relatively short follow-up times of the studies analyzed. Further studies are required to investigate the potential decrease in breast cancer risk among long-term statin users.


Cephalalgia ◽  
2014 ◽  
Vol 35 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Amy A Gelfand ◽  
Peter J Goadsby ◽  
I Elaine Allen

Context Infant colic is a common and distressing disorder of early infancy. Its etiology is unknown, making treatment challenging. Several articles have suggested a link to migraine. Objective The objective of this article was to perform a systematic review and, if appropriate, a meta-analysis of the studies on the relationship between infant colic and migraine. Data sources Studies were identified by searching PubMed and ScienceDirect and by hand-searching references and conference proceedings. Study selection For the primary analysis, studies specifically designed to measure the association between colic and migraine were included. For the secondary analysis, studies that collected data on colic and migraine but were designed for another primary research question were also included. Data extraction Data were abstracted from the original studies, through communication with study authors, or both. Two authors independently abstracted data. Main outcomes and measures The main outcome measure was the association between infant colic and migraine using both a fixed-effects model and a more conservative random-effects model. Results Three studies were included in the primary analysis; the odds ratio for the association between migraine and infant colic was 6.5 (4.6–8.9, p < 0.001) for the fixed-effects model and 5.6 (3.3–9.5, p = 0.004) for the random-effects model. In a sensitivity analysis wherein the study with the largest effect size was removed, the odds ratio was 3.6 (95% CI 1.7–7.6, p = 0.001) for both the fixed-effects model and random-effects model. Conclusions In this meta-analysis, infant colic was associated with increased odds of migraine. If infant colic is a migrainous disorder, this would have important implications for treatment. The main limitation of this meta-analysis was the relatively small number of studies included.


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