Side‐effects of carbetocin to prevent postpartum hemorrhage: A systematic review and meta‐analysis of randomized controlled trials

Background and Purpose: The dapagliflozin’s safety profile in insulin-treated adult type-1 diabetes mellites (T1DM) patients remains poorly explored. Therefore, this systematic review and meta-analysis compared the risk of all-cause side effects, study discontinuation of participants due to side effects, urinary tract infection (UTI), diabetic ketoacidosis, and hypoglycemia between dapagliflozin 10 mg and dapagliflozin 5 mg, dapagliflozin 10 mg and placebo, and dapagliflozin 5 mg and placebo.Materials and Methods: Parallel-arm randomized controlled trials juxtaposing the above outcomes between the afore-mentioned interventions were eligible for inclusion in this study and were searched in PubMed, Embase, and Scopus. Utilizing the Cochrane tool, the risk of bias was assessed in the recruited trials. Finally, by random-effect meta-analysis, each outcome was compared among the above interventions, and the risk ratio was estimated.Results: Four trials of varying length (1-52 weeks) sourcing data from almost 1760 participants from about 32 nations were reviewed. Overall, the trials had a low or unclear risk of bias, and only one was at a high risk of bias. Compared to the placebo, the risk of side effects was higher in those treated with dapagliflozin 5 mg (RR=1.10; 95% CI=1.02-1.18; p=0.014; I2=0%). UTI risk was less with the 10mg dapagliflozin than its lower dose (RR=0.50; 95% CI=0.32-0.79; p-value=0.003; I2=0%). All the remaining comparisons were statistically not significantly different between the juxtaposed intervention pairs.Conclusion: In contrast to placebo, dapagliflozin 5mg increased the risk of overall adversities in insulin-treated type-1 diabetes, and dapagliflozin 10 mg had a reduced risk of UTI than its 5mg preparation.

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Preoperative Oral Gabapentin in the Management of Postoperative Catheter-Related Bladder Discomfort in Adults: A Systematic Review and Meta-Analysis

Frontiers in Surgery ◽

10.3389/fsurg.2021.755497 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yu-Ting Wang ◽

Chong Xiao ◽

Hong Liu ◽

Xi Fu ◽

Yi-Feng Ren ◽

...

Keyword(s):

Systematic Review ◽

Side Effects ◽

Postoperative Pain ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Surgical Patients ◽

Controlled Trials ◽

Assessment Development ◽

Randomized Controlled ◽

Short Time

Objective: To evaluate the efficacy and safety of preoperative oral gabapentin in preventing postoperative Catheter-Related Bladder Discomfort (CRBD) in surgical patients.Methods: Randomized controlled trials in which gabapentin was used for the prevention of CRBD in surgical patients with transurethral catheterization were evaluated. The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 2, and 6 h after surgery, and secondary outcomes included the incidence of any grade CRBD, postoperative pain, and adverse events. Pooled risk ratios (RRs) and mean difference (MD), 95% confidence intervals (CIs), and P values were estimated using fixed and random effects statistical models. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the levels of certainty for key results.Results: A total of 6 randomized controlled trials involving 679 participants were included in the meta-analysis. Gabapentin significantly reduced the risk of moderate-to-severe CRBD at 0, 1, 2, and 6 h (0 h: RR = 0.19, 95% CI: 0.11 to 0.31, p < 0.00001; 1 h: RR = 0.40, 95% CI: 0.25 to 0.66, p < 0.001; 2 h: RR = 0.38, 95% CI: 0.26 to 0.56, p < 0.00001; 6 h: RR = 0.20, 95% CI: 0.11 to 0.38, p < 0.00001). The overall incidence of CRBD at 1 h showed no statistical difference between the two groups (RR = 0.55, 95% CI: 0.30 to 1.00, p = 0.05). The risk of CRBD was significantly reduced in the gabapentin group at 0, 2, and 6 h after surgery (0 h: RR = 0.59, 95% CI: 0.46 to 0.74, p < 0.0001; 2 h: RR = 0.62, 95% CI: 0.51 to 0.75, p < 0.00001; 6 h: RR = 0.66, 95% CI: 0.52 to 0.83, p < 0.001). In addition, gabapentin was associated with low postoperative pain intensity without significant side effects.Conclusion: Preoperative oral gabapentin as an adjunct to surgery is effective in decreasing the risk and severity of CRBD over a short time after surgery, and it can decrease postoperative pain without significant side effects. Overall, the level of certainty was moderate to low.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42021228171.

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Side Effects Associated with Probiotic Use in Adult Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Nutrients ◽

10.3390/nu11122913 ◽

2019 ◽

Vol 11 (12) ◽

pp. 2913 ◽

Cited By ~ 4

Author(s):

Maria Pina Dore ◽

Stefano Bibbò ◽

Gianni Fresi ◽

Gabrio Bassotti ◽

Giovanni Mario Pes

Keyword(s):

Systematic Review ◽

Inflammatory Bowel Disease ◽

Side Effects ◽

Randomized Controlled Trials ◽

Bowel Disease ◽

Meta Analysis ◽

Adult Patients ◽

Controlled Trials ◽

Randomized Controlled ◽

Inflammatory Bowel

Probiotics demonstrated to be effective in the treatment of inflammatory bowel disease (IBD). However, the safety profile of probiotics is insufficiently explored. In the present systematic review and meta-analysis, we examined the occurrence of side effects related to probiotic/synbiotic use in randomized controlled trials (RCTs) of IBD patients as compared with placebo. Eligible RCTs in adult patients with IBD were identified by accessing the Medline database via PubMed, EMBASE, CENTRAL and the Cochrane central register of controlled trials up to December 2018. Occurrence of side effects was retrieved and recorded. Data were pooled and the relative risks (RRs) with their 95% confidence intervals (CIs) were calculated. The low-moderate study heterogeneity, assessed by the I2 statistic, allowed to use of a fixed-effects modelling for meta-analysis. Nine RCTs among 2337, including 826 patients (442 treated with probiotics/symbiotic and 384 with placebo) were analyzed. Eight were double-blind RCTs, and six enrolled ulcerative colitis (UC) patients. Although the risk for the overall side effects (RR 1.35, 95%CI 0.93–1.94; I2 = 25%) and for gastrointestinal symptoms (RR 1.78, 95%CI 0.99–3.20; I2 = 20%) was higher in IBD patients taking probiotics than in those exposed to placebo, statistical significance was achieved only for abdominal pain (RR 2.59, 95%CI 1.28–5.22; I2 = 40%). In conclusion, despite the small number of RCTs and the variety of probiotic used and schedule across studies, these findings highlight the level of research effort still required to identify the most appropriate use of probiotics in IBD.

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A systematic review and meta-analysis of randomized controlled trials to evaluate the risk of fatigue and pain among patients treated with ibrutinib.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.31_suppl.213 ◽

2017 ◽

Vol 35 (31_suppl) ◽

pp. 213-213

Author(s):

Myo Zaw ◽

Kyaw Zin Thein ◽

Myat M. Han ◽

Ruth D’Cunha ◽

Hassan Kaleem ◽

...

Keyword(s):

Systematic Review ◽

Back Pain ◽

Side Effects ◽

Randomized Controlled Trials ◽

B Cell ◽

Meta Analysis ◽

Cell Receptor ◽

Muscle Spasm ◽

Controlled Trials ◽

Randomized Controlled

213 Background: Bruton’s tyrosine kinase (BTK), a kinase downstream of the B-cell receptor, involves in the B cell survival and proliferation and has become an attractive therapeutic target. Ibrutinib is an oral potent, covalent inhibitor of BTK and hence employed in many hematologic malignancies. We performed a systematic review and pooled analysis of randomized controlled trials (RCTs) to determine the risk of fatigue and pain among patients treated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts through December 31, 2016. RCTs that mention fatigue, arthralgia, muscle spasm, back pain, pain in extremity and myalgia as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: Four phase 3 RCTs with a total of 1505 patients were eligible for the analysis. Studies compared Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B)+ rituximab (R) vs placebo + B+ R and I vs temsirolimus were included in the analysis. The relative risks (RR) of all-grade side effects were as follows: fatigue, 0.87 (95% CI: 0.74- 1.03, p = 0.11); arthralgia, 1.97 (95% CI: 1.11- 3.50, p = 0.02); muscle spasm, 1.92 (95% CI: 1.22- 3.02, p = 0.005); back pain, 1.56 (95% CI: 1.02- 2.37, p = 0.03); pain in extremity, 2.47 (95% CI: 1.14- 5.36, p = 0.02); and myalgia, 2.68 (95% CI: 1.18- 6.05, p = 0.01). The RR of high-grade side effects were as follows: fatigue, 0.70 (95% CI: 0.37- 1.33, p = 0.28); arthralgia, 3.62 (95% CI: 0.74- 17.66, p = 0.11); back pain, 2.80 (95% CI: 0.42- 18.35, p = 0.28); pain in extremity, 2.96 (95% CI: 0.31- 28.4, p = 0.34); and myalgia, 2.96 (95% CI: 0.31- 28.44, p = 0.34). Conclusions: Our meta-analysis demonstrated that the risk of all-grade arthralgia, muscle spasm, back pain, pain in extremity and myalgia with ibrutinib was high. Pain is a major determinant of quality of life in cancer patients undergoing chemotherapy and recognizing these may help clinicians in delivering proper supportive care.

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Risk of gastrointestinal and hepatic toxicities in patients with metastatic solid tumors treated with cabozantinib: A systematic review and meta-analysis of randomized controlled trials.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.31_suppl.208 ◽

2017 ◽

Vol 35 (31_suppl) ◽

pp. 208-208

Author(s):

Myo Zaw ◽

Kyaw Zin Thein ◽

Myat M. Han ◽

Henry Palangdao Igid ◽

Fred L. Hardwicke ◽

...

Keyword(s):

Systematic Review ◽

Side Effects ◽

Randomized Controlled Trials ◽

Solid Tumors ◽

Tyrosine Kinases ◽

Meta Analysis ◽

Controlled Trials ◽

High Grade ◽

Randomized Controlled ◽

Relative Risks

208 Background: The vascular endothelial growth factor (VEGF) signaling pathways and the proto-oncogenes MET, KIT and RET were implied in cancer development and progression. Cabozantinib is an oral inhibitor of multiple tyrosine kinases and hence employed in many solid tumors. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities among patients with metastatic solid tumors treated with cabozantinib. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception to March 2017 were queried. Phase 3 RCTs that mention GI and elevation of liver enzymes as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Random effects model was applied. Results: We included 3 RCTs with a total of 1999 patients treated with cabozantinib for various solid tumors. The study arm used cabozantinib while the control arm utilized everolimus, placebo or prednisone. The relative risks (RR) of all-grade side effects were as follows: diarrhea, 2.39 (95% CI: 2.01 – 2.85, P < 0.0001); nausea, 1.86 (95% CI: 1.64 – 2.10, P < 0.0001); vomiting, 2.53 (95% CI: 1.60 – 3.99, P < 0.0001); stomatitis, 4.08 (95% CI: 0.55 – 30.01, P = 0.16); dysgeusia, 4.23 (95% CI: 2.30 – 7.76, P < 0.0001); elevated AST, 2.04 (95% CI: 1.12 – 3.73, P = 0.02); and elevated ALT, 1.61 (95% CI: 0.67 – 3.88, P = 0.28). The RR of high-grade side effects were as follows: diarrhea, 5.93 (95% CI: 3.43 – 10.25, P < 0.0001); nausea, 4.05 (95% CI: 1.99 – 8.23, P < 0.0001); vomiting, 2.37 (95% CI: 1.26 – 4.44, P = 0.007); stomatitis, 3.36 (95% CI: 0.45 – 24.98, P = 0.23); dysgeusia, 1.52 (95% CI: 0.15 – 14.57, P = 0.71); elevated AST, 1.70 (95% CI: 0.72 – 4.01, P = 0.22); and elevated ALT, 3.00 (95% CI: 0.60 – 14.93, P = 0.17). Conclusions: The risk of developing all-grade and high-grade diarrhea, nausea and vomiting with cabozantinib is high. Moreover, it is associated with all-grade elevated AST and dysgeusia. Timely recognition and providing good supportive care will enhance patients’ quality of life.

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Risk of infectious, hematological, and gastrointestinal side effects in patients treatedwith ibrutinib: A systematic review and meta-analysis of randomized controlled trials.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18265 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18265-e18265

Author(s):

Myo Zaw ◽

Kyaw Zin Thein ◽

Aung Tun ◽

Lukman Tijani ◽

Elizabeth Guevara

Keyword(s):

Systematic Review ◽

Side Effects ◽

Adverse Effects ◽

Randomized Controlled Trials ◽

Chemokine Receptors ◽

Meta Analysis ◽

Controlled Trials ◽

High Grade ◽

Randomized Controlled ◽

Gastrointestinal Side Effects

e18265 Background: Bruton’s tyrosine kinase (BTK) is essential for signaling of B-cell and chemokine receptors. Ibrutinib targets BTK and has become frontier in many hematologic malignancies. We undertook systematic review and pooled analysis of randomized controlled trials (RCTs) to determine infectious, hematological and gastrointestinal risks associated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts through December 31, 2016. The RCTs that mention infectious, hematological and gastrointestinal side effects as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: Four RCTs with a total of 1505 patients were eligible for the analysis. Studies compared Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B)+ rituximab (R) vs placebo + B+ R and I vs temsirolimus were included in the analysis. The relative risks (RR) of all-grade side effects were as follows: infection, 1.34 (95% CI: 1.04 – 1.74; p = 0.02); pneumonia, 1.16 (95% CI: 0.82–1.66; p = 0.38); anemia, 0.77 (95% CI: 0.64 – 0.93; p = 0.007); neutropenia, 0.99 (95% CI: 0.87 – 1.14; p = 0.98); thrombocytopenia, 0.86 (95% CI: 0.71 – 1.04; p = 0.12); diarrhea, 1.74 (95% CI: 1.48 – 2.05; p < 0.0001); nausea, 0.94 (95% CI: 0.80 – 1.10; p = 0.45); and vomiting, 0.98 (95% CI 0.74 – 1.30; p = 0.93). The RR of high-grade adverse effects were as follows: febrile neutropenia, 1.32 (95% CI: 0.84 – 2.08; p = 0.21); infection, 1.20 (95% CI: 0.73 – 1.98; p = 0.45); pneumonia, 1.22 (95% CI: 0.76–1.95; p = 0.39); anemia, 0.48 (95% CI: 0.33 – 0.71; p < 0.0001); neutropenia, 0.99 (95% CI: 0.86 – 1.15; p = 0.94); thrombocytopenia, 0.61 (95% CI: 0.47 – 0.81; p = 0.001); diarrhea, 1.72 (95% CI: 0.88 – 3.34;p = 0.10); nausea, 2.56 (95% CI: 0.59 – 10.99; p = 0.20); and vomiting, 0.42 (95% CI 0.11 – 1.63; p = 0.21). Conclusions: Ibrutinib increased the risk of all-grade diarrhea and infection whereas the risks of all-grade anemia, high-grade anemia and thrombocytopenia were significantly lower in the study arm, favoring ibrutinib.

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EPR19-74: Risk of Cabozantinib-Associated Gastrointestinal and Hepatic Toxicities in Patients With Metastatic Solid Tumors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2018.7155 ◽

2019 ◽

Vol 17 (3.5) ◽

pp. EPR19-74

Author(s):

Anita Sultan ◽

Sriman Swarup ◽

Francis Mogollon-Duffo ◽

Ye Aung ◽

Yin M. Myat ◽

...

Keyword(s):

Systematic Review ◽

Side Effects ◽

Randomized Controlled Trials ◽

Solid Tumors ◽

Meta Analysis ◽

Controlled Trials ◽

Growth Factor Signaling ◽

High Grade ◽

Phase 3 ◽

Randomized Controlled

Background: Cabozantinib is an oral inhibitor of multiple tyrosine kinases and is used in treatment of multiple solid tumors, targeting several pathways such as vascular endothelial growth factor signaling pathway and proto-oncogenes MET, KIT, RET. These pathways are implicated in several tumor development and progression. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities among patients with metastatic solid tumors treated with cabozantinib. Methods: MEDLINE, EMBASE databases, and meeting abstracts from inception to September 2018 were queried. Phase 3 RCTs that mention GI and elevation of liver enzymes as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% CI. Random effects model was applied. Results: We included 4 phase 3 RCTs with a total of 2,703 patients with various solid tumors. The study arm used cabozantinib while the control arm utilized everolimus or placebo or prednisone. The relative risks of all-grade side effects were as follows: diarrhea, 2.495 (95% CI: 2.149–2.897, P<.0001); nausea, 1.849 (95% CI: 1.649–2.072; P<.0001); vomiting, 2.335 (95% CI: 1.724–3.163; P<.0001); stomatitis, 4.541 (95% CI: 0.908–22.696; P=.065); dysgeusia, 4.428 (95% CI: 2.67–7.343; P<.0001); elevated AST, 2.002 (95% CI: 1.331–3.011; P=.001); and elevated ALT, 1.988 (95% CI: 0.936–4.222; P=.074). The RR of high-grade side effects were as follows: diarrhea, 5.913 (95% CI: 3.655–9.566; P<.0001); nausea, 3.098 (95% CI: 1.266–7.581; P=.013); vomiting, 1.298 (95% CI: 0.395–4.265; P=.668); stomatitis, 3.837 (95% CI: 0.749–19.665; P=.107); dysgeusia, 1.522 (95% CI: 0.159–14.574; P=.716); elevated AST, 1.733 (95% CI: 1.101–2.728; P=.018); and elevated ALT, 2.489 (95% CI: 1.164–5.326; P=.019). Conclusion: The risk of developing all grades of diarrhea, nausea, elevated AST, and any-grade vomiting, dysgeusia as well as high-grade elevated ALT, was high in cabozantinib group. Timely recognition and providing good supportive care will enhance patients’ quality of life.

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A Systematic Review and Meta-Analysis of Ayurvedic Herbal Preparations for Hypercholesterolemia

Medicina ◽

10.3390/medicina57060546 ◽

2021 ◽

Vol 57 (6) ◽

pp. 546

Author(s):

Dinesh Gyawali ◽

Rini Vohra ◽

David Orme-Johnson ◽

Sridharan Ramaratnam ◽

Robert H. Schneider

Keyword(s):

Systematic Review ◽

Side Effects ◽

Randomized Controlled Trials ◽

Total Cholesterol ◽

Meta Analysis ◽

P Value ◽

Controlled Trials ◽

Endocrine Disorders ◽

Black Cumin ◽

Randomized Controlled

Background and Objectives: Cardiovascular disease (CVD) is the leading cause of death globally and hypercholesterolemia is one of the major risk factors associated with CVD. Due to a growing body of research on side effects and long-term impacts of conventional CVD treatments, focus is shifting towards exploring alternative treatment approaches such as Ayurveda. However, because of a lack of strong scientific evidence, the safety and efficacy profiles of such interventions have not been well established. The current study aims to conduct a systematic review and meta-analyses to explore the strength of evidence on efficacy and safety of Ayurvedic herbs for hypercholesterolemia. Methods: Literature searches were conducted using databases including Medline, Cochrane Database, AMED, Embase, AYUSH research portal, and many others. All randomized controlled trials on individuals with hypercholesterolemia using Ayurvedic herbs (alone or in combination) with an exposure period of ≥ 3 weeks were included, with primary outcomes being total cholesterol levels, adverse events, and other cardiovascular events. The search strategy was determined with the help of the Cochrane Metabolic and Endocrine Disorders Group. Two researchers assessed the risk of each study individually and discrepancies were resolved by consensus or consultation with a third researcher. Meta-analysis was conducted using the inverse variance method and results are presented as forest plots and data summary tables using Revman v5.3. Results: A systematic review of 32 studies with 1386 participants found randomized controlled trials of three Ayurvedic herbs, Allium sativum (garlic), Commiphora mukul (guggulu), and Nigella sativa (black cumin) on hypercholesterolemia that met inclusion criteria. The average duration of intervention was 12 weeks. Meta-analysis of the trials showed that guggulu reduced total cholesterol and low-density lipoprotein levels by 16.78 mg/dL (95% C.I. 13.96 to 2.61; p-value = 0.02) and 18.78 mg/dL (95% C.I. 34.07 to 3.48; p = 0.02), respectively. Garlic reduced LDL-C by 10.37 mg/dL (95% C.I. −17.58 to −3.16; p-value = 0.005). Black cumin lowered total cholesterol by 9.28 mg/dL (95% C.I. −17.36, to −1.19, p-value = 0.02). Reported adverse side effects were minimal. Conclusion: There is moderate to high level of evidence from randomized controlled trials that the Ayurvedic herbs guggulu, garlic, and black cumin are moderately effective for reducing hypercholesterolemia. In addition, minimal evidence was found for any side effects associated with these herbs, positioning them as safe adjuvants to conventional treatments.

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