scholarly journals Safety and adverse effect profile of colchicine in renal impairment: a systematic review of randomised trials

2020 ◽  
Vol 9 (4) ◽  
pp. e28-e28
Author(s):  
Julian Yaxley ◽  
William Yaxley ◽  
Tahira Scott
Keyword(s):  
Systematic Review ◽  
Adverse Effect ◽  
Side Effects ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Randomised Trial ◽  
Gastrointestinal Symptoms ◽  
Adverse Effect Profile ◽  
Randomised Trials ◽  
Increased Risk

Introduction: Colchicine is an anti-inflammatory drug prescribed for numerous medical conditions. Side effects are frequently encountered, particularly gastrointestinal symptoms. Caution and dose reduction are advised in patients with renal impairment because of a presumed increased risk of side effects. This systematic review intends to summarise the available literature to define the adverse effect profile of colchicine used in patients with kidney disease. Methods: We conducted a systematic review of randomised clinical trials seeking to evaluate the association between renal impairment and colchicine toxicity. We limited our search to randomised studies in humans in the English language. We allowed colchicine prescribed for any duration, dose or indication. Results: Our literature search identified a total of 7707 records. Only a single randomised trial was ultimately identified as meeting the inclusion criteria and addressing our research question. In patients with renal impairment, colchicine was not associated with an increased risk of dialysis, time until dialysis, or the incidence of liver function test derangement. We found no data for adverse events such as leukopenia, thrombocytopenia or diarrhoea in the kidney disease subgroup. Data was sparse and of poor quality. Conclusion: It is widely recommended that colchicine dose be reduced in patients with renal impairment due to an increased risk of drug accumulation and side effects. In our study, we failed to identify any robust clinical research substantiating this association. This is the first systematic review of randomised trials to investigate this link. Further research is required before the safety and tolerability of colchicine in renal disease can be confirmed.

scholarly journals P0275SCOPE AND CONSISTENCY OF OUTCOME MEASURES FOR PHYSICAL FITNESS IN TRIALS IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dev Jegatheesan ◽  
Richard Modderman ◽  
Rathika Krishnasamy ◽  
Allison Tong ◽  
Jeff Coombes ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Physical Fitness ◽  
Exercise Capacity ◽  
Outcome Measures ◽  
Cochrane Library ◽  
Randomised Trials ◽  
Increased Risk ◽  
Patient Reported

Abstract Background and Aims Impaired physical fitness is prevalent across the spectrum of kidney disease and is associated with an increased risk of mortality, progression to end-stage kidney disease, falls and hospitalisation. Physical fitness outcomes have been extensively reported in randomised trials involving patients with kidney disease. This study aimed to assess the scope and consistency of physical fitness outcomes and outcome measures reported in kidney disease trials. Method A systematic review of randomised trials reporting physical fitness outcomes in adults with chronic kidney disease not requiring kidney replacement therapy, receiving maintenance haemodialysis or peritoneal dialysis, and kidney transplant recipients was conducted. The scope, frequency and characteristics of physical fitness outcome measures were categorised and analysed. Trials were identified from MEDLINE, Embase and the Cochrane Library from March 2000 to March 2019. Results From 115 relevant trials, 171 outcome measures for 32 outcomes were identified and categorised into five domains of physical fitness: exercise capacity (reported in 83% of trials), physiological-metabolic (57%), neuromuscular fitness (52%), body composition (45%) and cardiorespiratory fitness (19%). Exercise capacity had 53 different outcome measures and at 15 separate time points. The most common outcome measures were the 6-minute walk test (29%), peak oxygen uptake (20%), 1-repetition maximum (19%) and hand-grip strength (11%), with marked inconsistency in the reporting of outcomes between trials. Outcomes were assessed by field-based tests (65%), lab-based tests (31%) and patient-reported measures (4%). Conclusion There is large heterogeneity in the reporting of physical fitness outcomes, with inconsistencies in the use of validated, relevant and patient-important outcome measures.

scholarly journals Tinzaparin in Cancer and Renal Impairment: A Systematic Review Focusing on Safety

2020 ◽  
Author(s):  
Ioannis Vathiotis ◽  
Nikolaos Syrigos ◽  
Evangelos Dimakakos
Keyword(s):  
Systematic Review ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Severe Renal Impairment ◽  
Vitamin K Antagonists ◽  
Bleeding Events ◽  
Increased Risk ◽  
Therapeutic Doses

Abstract Purpose: Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin sodium, prescribed either as a prophylactic or as a therapeutic regimen for VTE in cancer patients and individuals suffering from renal impairment. Method: We identified and studied clinical studies from 2000 until 2020, reporting safety outcomes for cancer patients and individuals with renal impairment receiving either prophylactic or therapeutic doses of tinzaparin. Results: In patients with cancer major bleeding rates fluctuate between 0.8% and 7%; reported major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 2.3% of cases; major bleeding rates were higher for cancer patients with renal impairment receiving therapeutic doses of tinzaparin (4.3 to 10%). Patients on tinzaparin exhibit significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin is not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin does not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Conclusion: Tinzaparin is safe and can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a thoroughly studied and safe choice for special populations at increased risk for thrombosis and bleeding.

scholarly journals Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis

BMJ ◽  
2021 ◽  
pp. n2321
Author(s):  
Bruno R da Costa ◽  
Tiago V Pereira ◽  
Pakeezah Saadat ◽  
Martina Rudnicki ◽  
Samir M Iskander ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Event ◽  
Adverse Events ◽  
Meta Analysis ◽  
Hip Osteoarthritis ◽  
Randomised Trials ◽  
Increased Risk ◽  
Inflammatory Drugs ◽  
Topical Nsaids ◽  
Topical Diclofenac

Abstract Objective To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. Design Systematic review and network meta-analysis of randomised trials. Data sources Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. Eligibility criteria for selecting studies Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. Outcomes and measures The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. Review methods Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. Results 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). Conclusions Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. Systematic review registration PROSPERO number CRD42020213656

scholarly journals Patiromer Acetate Induced Hypercalcemia: An Unreported Adverse Effect

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Shreeyukta Bhattarai ◽  
Stephen Pupillo ◽  
Gulshan Man Singh Dangol ◽  
Erdal Sarac
Keyword(s):  
Adverse Effect ◽  
Chronic Kidney Disease ◽  
Clinical Trials ◽  
Side Effects ◽  
Kidney Disease ◽  
Cation Exchange ◽  
Stage Iv ◽  
Theoretical Possibility ◽  
Chronic Therapy

Hyperkalemia, a potential life threating condition, is a commonly encountered problem in chronic kidney disease (CKD) patients. Patiromer acetate, a nonabsorbable cation exchange polymer, is a gastrointestinal agent for chronic therapy in patients with persistent hyperkalemia. Patiromer is generally well tolerated in patients; common side effects are gastrointestinal, such as diarrhea, constipation, flatulence, and vomiting. Hypercalcemia, although a theoretical possibility, has not been reported in any major clinical trials. We present a case of hypercalcemia associated with patiromer acetate used for treatment of hyperkalemia in a stage IV CKD patient. Clinicians should be aware of the possibility of hypercalcemia while taking patiromer.

Risk of Intestinal Necrosis With Sodium Polystyrene Sulfonate: A Systematic Review and Meta-analysis

2021 ◽  
Vol 16 (8) ◽  
Author(s):  
Jürgen L Holleck ◽  
Andrea E Roberts ◽  
Elizabeth A Marhoffer ◽  
Alyssa A Grimshaw ◽  
Craig G Gunderson
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Cochrane Library ◽  
Selective Reporting ◽  
Sodium Polystyrene Sulfonate ◽  
Composite Outcome ◽  
Polystyrene Sulfonate ◽  
Intestinal Necrosis ◽  
Increased Risk ◽  
Gastrointestinal Side Effects

BACKGROUND: Reports of severe gastrointestinal side effects associated with sodium polystyrene sulfonate (SPS), particularly intestinal necrosis, have led some to recommend costlier alternative medications. No prior systematic review has included studies with controls reporting intestinal necrosis rates associated with SPS. METHODS: A systematic literature search was conducted using Cochrane Library, Embase, Medline, Google Scholar, PubMed, Scopus, and Web of Science Core Collection from database inception through October 4, 2020. We included any clinical trial, cohort, or case-control study reporting an association between SPS and intestinal necrosis or severe gastrointestinal side effects. RESULTS: Six studies including 26,716 patients treated with SPS with controls met inclusion criteria. The pooled odds ratio (OR) of intestinal necrosis was 1.43 (95% CI, 0.39-5.20). The pooled hazard ratio (HR) for intestinal necrosis from the two studies that performed survival analysis was 2.00 (95% CI, 0.45-8.78). The pooled HR for the composite outcome of severe gastrointestinal adverse events was 1.46 (95% CI, 1.01-2.11). CONCLUSION: Based on our review of six studies, the risk of intestinal necrosis with SPS is not statistically greater than controls, although there was a statistically significantly increased risk for the composite outcome of severe gastrointestinal side effects based on two studies. Because of the risk of bias from potential confounding and selective reporting, the overall strength of evidence to support an association between SPS and intestinal necrosis or other severe gastrointestinal side effects is low. PROSPERO registration CRD42020213119.

Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: systematic review and meta-analysis

2013 ◽  
Vol 44 (11) ◽  
pp. 2255-2269 ◽  
Author(s):  
T. Kishi ◽  
H. Y. Meltzer ◽  
Y. Matsuda ◽  
N. Iwata
Keyword(s):  
Systematic Review ◽  
Major Depressive Disorder ◽  
Side Effects ◽  
Depressive Disorder ◽  
Partial Agonist ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Cochrane Library ◽  
Number Needed To Treat ◽  
Major Depressive

BackgroundA meta-analysis of the serotonin1A (5-HT1A) receptor partial agonist of the azapirone class as an anxiolytic drug for the treatment of major depressive disorder (MDD) has not previously been reported.MethodWe carried out a systematic review of the literature available in PubMed, the Cochrane Library database and PsycINFO up to 12 October 2013, and conducted a meta-analysis of randomized controlled trials (RCTs) comparing 5-HT1A agonists with placebo and RCTs of 5-HT1A agonist augmentation therapies for MDD treatment. We calculated the risk ratio (RR), number needed to treat (NNT)/number needed to harm (NNH) and 95% confidence intervals (CIs).ResultsFifteen RCTs comparing 5-HT1A agonists with placebo (total n = 2469, four studies with buspirone, seven with gepirone, three with ipsapirone and one with zalospirone) were identified. Pooled 5-HT1A agonists had significantly more responders (RR 0.74, 95% CI 0.65–083, p < 0.00001, NNT = 6, 12 trials, n = 1816) than placebo. Pooled 5-HT1A agonists were superior to placebo in discontinuation due to inefficacy (RR 0.49, p = 0.02, NNH = 16, p = 0.03, 10 trials, n = 1494) but were inferior to placebo in discontinuation due to side-effects (RR 1.88, p < 0.0001, NNH = 17, p = 0.001, 13 trials, n = 2196). However, all-cause discontinuation was similar in both groups (RR 0.99, p = 0.85, 14 trials, n = 2402). Four 5-HT1A agonist augmentation studies were identified (total n = 365, three buspirone studies and one tandospirone study). There were no statistically significant effects of 5-HT1A agonist augmentation therapies on response rate (RR 0.98, p = 0.85, four trials, n = 341). 5-HT1A agonist-related side-effects including gastrointestinal symptoms, dizziness, insomnia, palpitation, paresthesia and sweating were greater than with placebo (p < 0.00001 to p = 0.03).ConclusionsOur results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.

scholarly journals Effect of COVID-19 on Mortality of Pregnant and Postpartum Women: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-33
Author(s):  
Leila Karimi ◽  
Somayeh Makvandi ◽  
Amir Vahedian-Azimi ◽  
Thozhukat Sathyapalan ◽  
Amirhossein Sahebkar
Keyword(s):  
Systematic Review ◽  
Cesarean Section ◽  
Pregnant Women ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Severe Illness ◽  
Postpartum Women ◽  
Presenting Symptoms ◽  
Increased Risk ◽  
Adverse Pregnancy

Background. Based on what is known at this time, pregnant women are at an increased risk of severe illness from COVID-19 compared to nonpregnant women. Additionally, pregnant women with COVID-19 might have an increased risk of adverse pregnancy outcomes. To investigate the effects of coronavirus disease 2019 (COVID-19) on mortality of pregnant and postpartum women, we performed a systematic review of available published literature on pregnancies affected by COVID-19. Methods. Web of Science, SCOPUS, and MEDLINE- databases were searched for original studies concerning the effect of COVID-19 on mortality of pregnant and postpartum women published by July 10, 2020. Meta-analyses of proportions were used to combine data and report pooled proportions. Results. 117 studies with a total of 11758 pregnant women were included. The age ranged between 15 and 48 years. Most subjects were infected with SARS-CoV-2 in the third trimester. Disease severity was not reported in 1125 subjects. Maternal mortality was 1.3%. In 100% of fatal cases with adequate data, fever alone or with cough was one of the presenting symptoms. Also, dyspnea (58.3%) and myalgia (50%) were the most common symptoms. Sore throat (8.3%) and gastrointestinal symptoms (anorexia, nausea) (8.3%) were rare. The rate of comorbidities was 20% among COVID-19 deaths. The majority of COVID-19-infected women who died had cesarean section (58.3%), 25% had a vaginal delivery, and 16.7% of patients were not full term. Conclusion. COVID-19 infection in pregnant women was associated with higher rates (and pooled proportions) of cesarean section and mortality. Because new data are continuously being generated and published, the findings of this study can be complete and updated with new researches. The results of this study can guide and improve prenatal counseling of COVID-19-infected pregnant women.

scholarly journals Carfilzomib Based Regimens for Treatment of Newly Diagnosed Multiple Myeloma: A Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5588-5588
Author(s):  
Maimoona Khan ◽  
Asma Waheed ◽  
Rida Ul Jannat ◽  
Arafat Ali Ali Farooqui ◽  
Muhammad Saad Farooqi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Effect ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Induction Therapy ◽  
Drug Combination ◽  
Alkylating Agents ◽  
Adverse Effect Profile ◽  
Newly Diagnosed ◽  
Grade 3

Background: Carfilzomib (Car), a second-generation proteasome inhibitor (PI), has been approved by the US Food and Drug Administration (FDA) as therapy for relapsed and /or refractory multiple myeloma (RRMM), either as a single agent or in combination with other agents. It has proven to be superior in many ways compared to the the first generation PI, bortezomib, both in terms of superior efficacy and neuropathy related adverse effect profile. Carfilzomib has lower rate of peripheral neuropathy. In this review, we gathered data from trials which studied Carfilzomib for newly diagnosed MM (NDMM). Carfilzomib based two and three drug combination as induction regimens for the management of NDMM is an emerging approach. Through this systematic review, we explore efficacy, adverse effect profile of Car based regimens for NDMM. Methods: Per PRISMA guidelines, a thorough database search was conducted on 06/24/2019 using the following search engines; PubMed, EMBASE, Cochrane library, Scopus, Web of Science, CINAHL, and Clinicaltrials.gov. We included all published trials that used carfilzomib as an induction agent in NDMM patients and had at least response rates after induction. Results: The total number of articles identified with initial search were 1131, out of which 19 articles met our selection / eligibility criteria (n=2286). The overall response rates (ORR) after induction therapy with carfilzomib based regimens was very impressive (range: 84.3% - 100%). Two drug combination using carfilzomib and dexamethasone (n=72) had an ORR of 90% and a greater than very good partial response rate (>VGPR) of 84%. Three drug combinations used for induction therapy included carfilzomib/dexamethasone with immunomodulators (n=391) and alkylating agents (n=308). The combination of carfilzomib/dexamethasone with lenalidomide (n=189, ORR: 97% - 98%, >VGPR: 69% - 98%) and thalidomide (n=202, ORR: 90% - 94%, >VGPR: 66% - 68%) showed the best response. Alkylating agents used in combination with carfilzomib were melphalan (n=98, ORR: 90% - 93%, >VGPR: 58% - 70%), cyclophosphamide (n=192, ORR: 87% - 95%, >VGPR: 39% - 71%) and bendamustine (n=18, ORR; 100%, >VGPR: 89%). Four drug combinations with carfilzomib used were daratumumab/lenalidomide/dexamethasone (n=22, ORR: 100%, >VGPR: 90%, 12m PFS: 95%) and cyclophosphamide / thalidomide / dexamethasone (n=64, ORR; 91%, >VGPR: 69%, 24m PFS: 76%). One trial directly compared carfilzomib/melphalan/dexamethasone (n=478, ORR: 84%, >VGPR: 61%, PFS: 22.3m) with bortezomib/melphalan/dexamethasone (n=477, ORR: 79%, >VGPR: 49%, PFS: 22.1m). Another trial compared the combination of carfilzomib / dexamethasone with lenalidomide (n=315) or cyclophosphamide (n=159) that showed similar ORR (97% vs 91%) though >VGPR rate was better with lenalidomide (75% vs 60%). Efficacy data including progression free survival (PFS) for carfilzomib based regimens is reported in table 1. Most common >grade 3 hematological adverse effects reported were anemia (2% - 35%), lymphopenia (5% - 76%), thrombocytopenia (4% - 28%) and neutropenia (1% - 38%). Most Common >grade 3 non-hematological adverse events included cardiac events (5% - 10%), respiratory disorders (8% - 16%), infections (2% - 9%), hypertension (6% - 17%), renal events (9% - 10%) and hyperglycemia (6% - 23%). (Table 1) Conclusion: The overall efficacy and favorable adverse effect profile of Carfilzomib-based induction regimens seem very promising for the treatment of NDMM. Car is now approved for weekly dosing which is convenient. Due to cardiovascular toxicity seen in upto 10% cases, Car should be used very judiciously in patients with cardiovascular risk factors and heart failure. Several ongoing phase 3 clinical trials are studying Carfilzomib in various combinations will help to establish foundation for future standard therapy as well as next phase of drug development through clinical trials. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

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