Comparative Safety of Smoking Cessation Pharmacotherapies During a Government-Sponsored Reimbursement Program

2020 ◽  
Author(s):  
Greg Carney ◽  
Malcolm Maclure ◽  
Suzanne Malfair ◽  
Ken Bassett ◽  
James M Wright ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Relative Risk ◽  
Adverse Events ◽  
Primary Outcome ◽  
Randomized Clinical Trials ◽  
Boxed Warning ◽  
Serious Adverse Events ◽  
Adjusted Risk ◽  
Relative Safety ◽  
Comparative Safety

Abstract Introduction The British Columbia Ministry of Health launched a Smoking Cessation Program on September 30, 2011, providing financial coverage for smoking cessation pharmacotherapies. Although pharmacotherapies have been shown to have a moderate short-term benefit as a quitting aid, substantial cardiovascular and neuropsychiatric safety concerns have been identified in adverse-reporting databases, leading to prescription label warnings by Health Canada and the U.S. Food and Drug Administration. However, recent studies indicate these warnings may be without merit. This study examined the comparative safety of medications commonly used to aid smoking cessation. Aims and Methods Population-based retrospective cohort study using B.C. administrative data to assess the relative safety between varenicline, bupropion, and nicotine replacement therapies (NRTs). The primary outcome was a composite of cardiovascular hospitalizations. Secondary outcomes included mortality, a composite of neuropsychiatric hospitalizations, and individual components of the primary outcome. Statistical analysis used propensity score-adjusted log-binomial regression models. A sensitivity analysis excluded patients with a history of cardiovascular disease. Results The study included 116 442 participants. Compared with NRT, varenicline was associated with a 10% 1-year relative risk decrease of cardiovascular hospitalization (adjusted risk ratio [RR] = 0.90, 95% confidence interval (CI): 0.82 to 1.00), a 20% 1-year relative risk decrease of neuropsychiatric hospitalization (RR: 0.80, CI: 0.7 to 0.89), and a 19% 1-year relative risk decrease of mortality (RR: 0.81, CI: 0.71 to 0.93). We found no significant association between NRT and bupropion for cardiovascular hospitalizations, neuropsychiatric hospitalizations, or mortality. Conclusions Compared with NRT, varenicline is associated with fewer serious adverse events and bupropion the same number of serious adverse events. Implications This study addresses the need for comparative safety evidence in a real-world setting of varenicline and bupropion against an active comparator. Compared with NRT, varenicline was associated with a decreased risk of mortality, serious cardiovascular events, and neuropsychiatric events during the treatment, or shortly after the treatment, in the general population of adults seeking pharmacotherapy to aid smoking cessation. These results provide support for the removal of the varenicline boxed warning for neuropsychiatric events and add substantively to the cardiovascular safety findings of previous observational studies and randomized clinical trials.

scholarly journals A Perioperative Smoking Cessation Intervention with Varenicline

2012 ◽  
Vol 117 (4) ◽  
pp. 755-764 ◽  
Author(s):  
Jean Wong ◽  
Amir Abrishami ◽  
Yiliang Yang ◽  
Amna Zaki ◽  
Zeev Friedman ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Relative Risk ◽  
Adverse Events ◽  
Odds Ratio ◽  
Controlled Trial ◽  
Smoking Cessation Intervention ◽  
Point Prevalence ◽  
Serious Adverse Events ◽  
Cessation Intervention ◽  
Point Prevalence Abstinence

Background The efficacy of perioperative tobacco interventions on long-term abstinence and the safety of smoking cessation less than 4 weeks before surgery is unclear. Our objective was to determine the efficacy and safety of a perioperative smoking cessation intervention with varenicline to reduce smoking in elective surgical patients. Methods In a prospective, multicenter, double-blind, placebo-controlled trial, 286 patients were randomized to receive varenicline or placebo. Both groups received in-hospital and telephone counseling during 12 months. The primary outcome was the 7-day point prevalence abstinence rate 12 months after surgery. Secondary outcomes included abstinence at 3 and 6 months after surgery. Multivariable logistic regression was used to identify independent variables related to abstinence. Results The 7-day point prevalence abstinence at 12 months for varenicline versus placebo was 36.4% versus 25.2% (relative risk: 1.45; 95%: CI: 1.01-2.07; P = 0.04). At 3 and 6 months, the 7-day point prevalence abstinence was 43.7% versus 31.9% (relative risk: 1.37; 95% CI: 1.01 to 1.86; P = 0.04), and 35.8% versus 25.9% (relative risk: 1.43; 95%: CI 1.01-2.04; P = 0.04) for varenicline versus placebo, respectively. Treatment with varenicline (odds ratio: 1.76; 95% CI: 1.03-3.01; P = 0.04), and preoperative nicotine dependence (odds ratio: 0.82, 95% CI: 0.68 to 0.98; P = 0.03) predicted abstinence at 12 months. The adverse events profile in both groups was similar except for nausea, which occurred more frequently for varenicline versus placebo (13.3% vs. 3.7%, P = 0.004). Conclusions A perioperative smoking cessation intervention with varenicline increased abstinence from smoking 3, 6, and 12 months after elective noncardiac surgery with no increase in serious adverse events.

Successful Use of Intravenous Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Pediatric Patients

2021 ◽  
Author(s):  
Kimberly P. Mills ◽  
Christopher C. McPherson ◽  
Ahmed S. Said ◽  
Michael A. Lahart
Keyword(s):  
Adverse Events ◽  
Critically Ill ◽  
Primary Outcome ◽  
Pediatric Patients ◽  
Case Series ◽  
Opioid Withdrawal ◽  
Limited Data ◽  
Serious Adverse Events ◽  
Patient Response ◽  
Hospital Patients

Abstract Objectives Methylnaltrexone is U.S. Food and Drug Administration (FDA) approved as a subcutaneous injection for adults with opioid-induced constipation (OIC). Case series have described the use of methylnaltrexone for OIC in the pediatric oncology population. There are limited data describing its intravenous use in critically ill pediatric patients. Methods We conducted a retrospective observational study at St. Louis Children's Hospital. Patients less than 18 years old who received at least one dose of intravenous methylnaltrexone while admitted to an intensive care unit between January 2016 and August 2019 were included. The primary outcome was documented laxation within 24 hours of methylnaltrexone administration. Results Sixteen patients received a total of 34 doses of intravenous methylnaltrexone. Patients received a median of 1.69 (interquartile range [IQR], 0.9–4.86) morphine milligram equivalents per kilogram per 24 hours, over a median of 14 days (IQR, 11–30), before methylnaltrexone administration. The median dose of methylnaltrexone was 0.15 mg/kg (IQR, 0.15–0.16). Ten patients (63%) responded to the first dose of methylnaltrexone, and 14 patients (88%) responded to at least one dose. Overall, 26 doses (76%) led to patient response. Four patients (25%) experienced adverse events (emesis, abdominal pain) after methylnaltrexone administration. No signs or symptoms of opioid withdrawal were documented. Conclusions Intravenous methylnaltrexone appears to be safe and effective in treating OIC in critically ill pediatric patients. No serious adverse events or signs of opioid withdrawal were observed after single and repeat dosing. Patients responded to methylnaltrexone with varying opioid dosing and durations prior to administration.

Abstract 104: Disability After Minor Stroke and TIA in the POINT Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Brett L Cucchiara ◽  
Jordan Elm ◽  
J Donald Easton ◽  
Shelagh Coutts ◽  
Joshua Willey ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Adverse Events ◽  
Antiplatelet Therapy ◽  
Primary Outcome ◽  
Dual Antiplatelet Therapy ◽  
Recurrent Stroke ◽  
Primary Outcome Measure ◽  
Minor Stroke ◽  
Serious Adverse Events ◽  
Index Event

Background and Purpose: To assess the effect of combination antiplatelet therapy with aspirin and clopidogrel versus aspirin alone on disability following TIA or minor stroke and to identify factors associated with disability. Methods: The POINT trial randomized patients with TIA or minor stroke (NIHSS≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, MI, or vascular death. We performed a post-hoc exploratory analysis to examine the effect of treatment on overall disability (defined as mRS>1) at 90 days as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results: At 90 days, 188/1964 (9.6%) of patients enrolled with TIA and 471/2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% vs. 14.3%, OR 0.97, 95%CI 0.82-1.14, p=0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% vs. 4.0%, OR 0.73, 95%CI 0.53-1.01, p=0.06), and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% vs. 7.4%, OR 0.78, 95% CI 0.62-0.99, p=0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% vs. 6.0%, OR 0.74 95% CI 0.57-0.96, p=0.02). In multivariate analysis of patients enrolled with TIA, disability was significantly associated with age, subsequent ischemic stroke, serious adverse events, and major bleeding. In patients enrolled with stroke, disability was associated with female sex, hypertension, diabetes, NIHSS score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events. Conclusions: In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, dual antiplatelet therapy might reduce stroke-related disability.

scholarly journals Adverse events of exercise therapy in randomised controlled trials: a systematic review and meta-analysis

2019 ◽  
Vol 54 (18) ◽  
pp. 1073-1080 ◽  
Author(s):  
Andre Niemeijer ◽  
Hans Lund ◽  
Signe Nilssen Stafne ◽  
Thomas Ipsen ◽  
Cathrine Luhaäär Goldschmidt ◽  
...  
Keyword(s):  
Systematic Review ◽  
Relative Risk ◽  
Adverse Events ◽  
Exercise Therapy ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Control Group ◽  
Controlled Trials ◽  
Serious Adverse Events ◽  
Randomised Controlled

ObjectiveTo evaluate the relative risk (RR) of serious and non-serious adverse events in patients treated with exercise therapy compared with those in a non-exercising control group.DesignSystematic review and meta-analysis.Data sourcesPrimary studies were identified based on The Cochrane Database of Systematic Reviews investigating the effect of exercise therapy.Eligibility criteriaAt least two of the authors independently evaluated all identified reviews and primary studies. Randomised controlled trials were included if they compared any exercise therapy intervention with a non-exercising control. Two authors independently extracted data. The RR of serious and non-serious adverse events was estimated separately.Results180 Cochrane reviews were included and from these, 773 primary studies were identified. Of these, 378 studies (n=38 368 participants) reported serious adverse events and 375 studies (n=38 517 participants) reported non-serious adverse events. We found no increase in risk of serious adverse events (RR=0.96 (95%CI 0.90 to 1.02, I2: 0.0%) due to exercise therapy. There was, however, an increase in non-serious adverse events (RR=1.19 (95%CI 1.09 to 1.30, I2: 0.0%). The number needed to treat for an additional harmful outcome for non-serious adverse events was 6 [95%CI 4 to 11).ConclusionParticipating in an exercise intervention increased the relative risk of non-serious adverse events, but not of serious adverse events. Exercise therapy may therefore be recommended as a relatively safe intervention.PROSPERO registration numberCRD42014014819.

scholarly journals Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis

2017 ◽  
Vol 43 (4) ◽  
pp. 302-312 ◽  
Author(s):  
Israel Silva Maia ◽  
Mariângela Pimentel Pincelli ◽  
Victor Figueiredo Leite ◽  
João Amadera ◽  
Anna Maria Buehler
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Therapeutic Effects ◽  
Muscarinic Antagonists ◽  
Serious Adverse Events ◽  
Exacerbation Rate ◽  
Copd Exacerbations ◽  
Long Acting

ABSTRACT Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

scholarly journals Influence of Cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar

2021 ◽  
Author(s):  
Leyre Pernaute-Lau ◽  
Ulrika Morris ◽  
Mwinyi Msellem ◽  
Andreas Mårtensson ◽  
Anders Björkman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cytochrome P450 ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Plasmodium Falciparum Malaria ◽  
Serious Adverse Events ◽  
Exact Test ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
Minor Alleles

Abstract BackgroundThe antimalarial drug amodiaquine, a commonly used long acting partner drug in artemisinin-based combination therapy, is metabolized to active desethyl-amodiaquine (DEAQ) by cytochrome P450 2C8 (CYP2C8). The CYP2C8 gene carries several polymorphisms including the more frequent minor alleles CYP2C8*2 and CYP2C8*3. These minor alleles have been associated with decreased enzymatic activity, slowing the amodiaquine biotransformation towards DEAQ. This study aimed to assess the influence of these CYP2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment for uncomplicated Plasmodium falciparum malaria in Zanzibar.MethodsWe analysed data from 618 children under 5 years of age with uncomplicated P. falciparum malaria enrolled in two randomized clinical trials comparing artesunate-amodiaquine and artemether-lumefantrine in 2002-2005 in Zanzibar. CYP2C8*2 and CYP2C8*3 genotype frequencies were determined by PCR-restriction fragment length polymorphism. Statistical associations between CYP2C8*2 and/or CYP2C8*3 allele carriers and treatment outcome or occurrence of adverse events were assessed by Fisher’s Exact test.ResultsThe allele frequencies of CYP2C8*2 and CYP2C8*3 were 17.5% (95% CI 15.4-19.7%) and 2.7% (95% CI 1.8-3.7%), respectively. There was no significant difference in the proportion of subjects carrying either CYP2C8*2 or CYP2C8*3 alleles amongst those with reinfections (44.1%; 95% CI 33.8-54.8) or those with recrudescent infections (48.3%; 95% CI 29.4-67.5), compared to those with an adequate clinical and parasitological response (36.7%; 95% CI 30.0-43.9) (P = 0.25 and P = 0.31, respectively). However, patients carrying either the CYP2C8*2 or CYP2C8*3 alleles were significantly associated with an increased occurrence of non-serious adverse events, when compared with CYP2C8 *1/*1 wildtype homozygotes (44.9%; 95% CI 36.1-54.0 versus 28.1%; 95% CI 21.9-35.0, respectively; P = 0.003). ConclusionsCYP2C8 genotypes did not influence treatment efficacy directly, but the tolerability to AS-AQ may be reduced in subjects carrying the CYP2C8*2 and CYP2C8*3 alleles. The importance of this non-negligible association with regards to amodiaquine-based malaria chemotherapy warrants further investigation.

Pain and functional outcomes of the sacroiliac joint after platelet-rich plasma injection: a descriptive review

2021 ◽  
Vol 16 (1) ◽  
pp. 87-100
Author(s):  
Joshua B Rothenberg ◽  
Keshav Godha ◽  
David M Civitarese ◽  
Gerard Malanga ◽  
Jaspal Ricky Singh ◽  
...  
Keyword(s):  
Sacroiliac Joint ◽  
Functional Outcomes ◽  
Primary Outcome ◽  
Randomized Clinical Trials ◽  
Platelet Rich Plasma ◽  
Review Of The Literature ◽  
Serious Adverse Events ◽  
Plasma Injection ◽  
The Status ◽  
Double Blinded

The purpose of this manuscript is to highlight and review the status of literature regarding efficacy of platelet-rich plasma (PRP) in the treatment of sacroiliac joint (SIJ) dysfunction. A review of the literature on PRP interventions on the SIJ or ligaments was performed. Seven studies had improvements in their respective primary end point and demonstrated a strong safety profile without any serious adverse events. Only five articles demonstrated clinical efficacy of >50% in their primary outcome measures. There appears to be inconsistent and insufficient evidence for a conclusive recommendation for or against SIJ PRP. There is a need for adequately powered well-designed, standardized, double-blinded randomized clinical trials to determine the effectiveness of PRP in SIJ-mediated pain.

A Randomized Trial of Dabigatran Versus Warfarin in the Treatment of Acute Venous Thromboembolism (RE-COVER II)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 205-205 ◽  
Author(s):  
Sam Schulman ◽  
Ajay K Kakkar ◽  
Sebastian M Schellong ◽  
Samuel Z. Goldhaber ◽  
Eriksson Henry ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Adverse Events ◽  
Primary Outcome ◽  
Warfarin Dose ◽  
Hazard Ratio ◽  
Bleeding Events ◽  
Serious Adverse Events ◽  
Coronary Syndrome ◽  
Recurrent Vte ◽  
Acute Venous Thromboembolism

Abstract Abstract 205 Background: Dabigatran has been compared with warfarin for treatment of acute venous thromboembolism in one previous trial (RE-COVER). Based on the low rate of the primary outcome as the RE-COVER study was running, we undertook this replica study to confirm the results of RE-COVER, and to allow for more rigorous sub-group analyses. Methods: In a randomized, double-blind, double-dummy trial of 2568 patients with acute VTE, treated with low molecular weight or unfractionated heparin for 5 to 11 days, we compared dabigatran, 150 mg twice daily, with warfarin, dose-adjusted to an International Normalized Ratio of 2.0 and 3.0, each given for 6 months. Primary outcome was recurrent symptomatic, objectively confirmed venous thromboembolism and deaths related to venous thromboembolism during 6 months. Safety endpoints included bleeding events, acute coronary syndrome, elevated liver function tests, and adverse events. Results: Of 1279 patients randomized to dabigatran, 30 (2.4%) had recurrent VTE compared with 28 (2.2%) of 1289 patients randomized to warfarin; risk difference 0.2% (95% confidence interval [CI], −1.0 to 1.5); p<0.0001 for the pre-specified non-inferiority margin. The hazard ratio for dabigatran was 1.08 (95% CI, 0.64 to 1.80). Major bleeding occurred in 15 patients treated with dabigatran and 22 patients treated with warfarin (hazard ratio 0.69; 95% CI, 0.36 to 1.32) and any bleeding occurred in 200 versus 285 patients, respectively (hazard ratio 0.67, 95% CI, 0.56 to 0.81). The frequency of reported ACS events was less than 1% in the trial, with more cases in the dabigatran treatment group than those treated with warfarin. There were 25 deaths during each treatment, and serious adverse events were similar in the two groups. Analysis of outcomes based on demographic characteristics showed consistency of effects for both safety and efficacy. This included the analysis based on Asian race, which had been limited in RE-COVER. There were 537 Asian patients in RE-COVER II compared to only 65 in RE-COVER. The event rates of recurrent VTE and of any bleeding were similar in Asians and non-Asians. Conclusion: The study confirms that the efficacy of dabigatran is non-inferior to warfarin in the treatment of acute VTE and with a lower risk for bleeding. The safety of dabigatran is similar in the Asian population compared with non-Asians. Disclosures: Off Label Use: dabigatran for treatment of venous thromboembolism. Christiansen:Boehringer Ingelheim: Employment. Schnee:Boehringer Ingelheim: Employment.

scholarly journals Effectiveness and safety of 12-month certolizumab pegol treatment for axial spondyloarthritis in real-world clinical practice in Europe

Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 113-124
Author(s):  
Xenofon Baraliakos ◽  
Torsten Witte ◽  
Luc De Clerck ◽  
Bruno Frediani ◽  
Eduardo Collantes-Estévez ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Axial Spondyloarthritis ◽  
Certolizumab Pegol ◽  
Signs And Symptoms ◽  
Serious Adverse Events ◽  
The Mean ◽  
One Year

Abstract Objectives The efficacy and safety of certolizumab pegol (CZP), an Fc-free, PEGylated anti-TNF, in axial spondyloarthritis (axSpA) has been established in clinical trial settings. We report CZP effectiveness and safety in European clinical practice in patients with axSpA, including radiographic (r-) and non-radiographic (nr-) axSpA. Methods CIMAX (NCT02354105), a European non-interventional multicentre prospective study, observed CZP treatment response and safety over 12 months in a real-world axSpA cohort. The primary outcome was change from baseline in BASDAI to week 52, with additional outcomes pertaining to effectiveness and safety. Patients who received ≥1 dose CZP were followed up for adverse events, and those with baseline and ≥1 post-baseline BASDAI assessment were included in effectiveness analyses. Results A total of 672 patients (r-axSpA: 469; nr-axSpA: 201; unconfirmed diagnosis: 2) from 101 sites received ≥1 dose of CZP, of whom 564 (r-axSpA: 384; nr-axSpA: 179; unconfirmed: 1) were included in the effectiveness analyses. The mean baseline BASDAI was 6.1 in the overall axSpA population and r-axSpA and nr-axSpA subpopulations. At week 52, the mean (s.d.) change in BASDAI was −2.9 (2.3; n = 439); for r-axSpA and nr-axSpA, it was −2.9 (2.2; n = 301) and −2.8 (2.4; n = 137), respectively (P &lt;0.0001 for all). Similar improvements were seen across other axSpA disease measures. In total, 37.9% (255/672) patients experienced adverse events, and 1.8% (12/672) experienced ≥1 serious adverse events. Conclusion Improvements observed in signs and symptoms of axSpA following one year of CZP treatment in real-world clinical practice were similar to those from previous randomized clinical trials, with no new safety concerns.

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