Estimation of risk of neuropsychiatric adverse events from varenicline, bupropion and nicotine patch versus placebo: secondary analysis of results from the EAGLES trial using Bayes factors

Abstract Background: Frailty is common in older patients with lymphoma. However, it remains unknown whether frailty is prevalent in patients included in clinical trials of lymphoma, as those with frailty may meet inclusion criteria of a trial which do not include functional information beyond performance status (PS). Understanding the prevalence and impact of frailty in clinical trials is important to direct future stratification criteria, as well as to have robust data to counsel frail patients on their potential outcomes. Methods: We conducted a secondary analysis using data from the phase III LY.12 clinical trial in which patients with relapsed aggressive non-Hodgkin lymphoma were randomized to gemcitabine-dexamethasone-cisplatin or dexamethasone-high dose cytarabine-cisplatin chemotherapy prior to autologous stem cell transplant. The primary objective of our study was to construct a lymphoma clinical trials specific frailty index (FI) using previously described methods (Searle. BMC Geriatr. 2008;8:24). Secondary objectives were to describe the association of frailty (binary variable) with overall survival (OS), event-free survival (EFS), hospitalization, adverse events (AE), serious adverse events (SAE), and proceeding to transplant, and to describe the association of frailty with these outcomes, controlling for important covariates (age, sex, immunophenotype, revised international prognostic index score (rIPI), Eastern Cooperative Oncology Group (ECOG) PS, stage, and response to previous chemotherapy). Results: 619 patients in the LY12 trial were used to construct the frailty index (Table 1). Using a binary cut-off for frailty (<0.2), 15% (N=93) of patients were classified as frail. There were no differences in age or sex between frail and non-frail patients; however they differed in terms of other lymphoma-related characteristics (Table 2). Frailty was strongly associated with OS (HR 2.012, 95% CI 1.57-2.58), EFS (HR 1.94, 95% CI 1.53-2.46), frequency of the worst overall Grade >3 AE (OR 2.65 (15% vs. 6%), p=0.003), and likelihood of proceeding to ASCT (OR 0.26, 95% CI 0.15-0.43), but not hospitalization (OR 1.52, 95% CI 0.97-2.40) or SAE (6% vs. 4%, p=0.3). In multivariable analysis, frailty was not significantly associated with OS, EFS, likelihood of proceeding to ASCT, nor hospitalization (Table 3), though there was a trend to significance for ASCT. However, rIPI remained significantly associated with OS and EFS, ECOG remained significantly associated with OS (Table 3) Conclusion: A potentially broadly applicable lymphoma clinical trials specific FI was constructed through secondary analysis of LY12 data. 15% of patients were classified as frail. Frailty was significantly associated with OS, EFS, frequency of grade >3 AE and likelihood of proceeding to transplant. However, this relationship no longer was significant when controlling for lymphoma-related prognostic variables, suggesting that the impact of poor prognostic features of lymphoma supersede the impact of frailty alone in this younger clinical trial population. Interestingly, rIPI and ECOG demonstrated their value as simple predictors that are highly associated with OS and/or EFS even when controlling for other important covariates including frailty. These findings require further testing in an external data set, and would be particularly valuable to test in an older population. Calibration of the FI against clinical frailty assessment (e.g. Clinical Frailty Scale, Comprehensive Geriatric Assessment) would also be meaningful to confirm its ability to classify frail versus non-frail patients. Figure 1 Figure 1. Disclosures Crump: Epizyme: Research Funding; Roche: Research Funding; Kyte/Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Hay: Merck: Research Funding; Roche: Research Funding; Abbvie: Research Funding; Amgen: Research Funding; Karyopharm: Research Funding; Seattle Genetics: Research Funding. Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria.

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Preliminary Estimates of Change in Physical Function After Targeted Kyphosis Exercise Intervention in Older Adults With Low Function: A Secondary Analysis of The SCOR Trial

10.21203/rs.3.rs-111481/v1 ◽

2020 ◽

Author(s):

Amy Gladin ◽

Wendy Katzman ◽

Yoshimi Fukuoka ◽

Neeta Parimi ◽

Shirley Wong ◽

...

Keyword(s):

Older Adults ◽

Adverse Events ◽

Physical Function ◽

High Intensity ◽

Exercise Intervention ◽

Secondary Analysis ◽

Community Dwelling ◽

Spinal Curvature ◽

Targeted Interventions ◽

Function Group

Abstract Background: Hyperkyphosis is common in older adults and associated with low physical function and reduced health related quality of life (HrQol). Improved kyphosis has been previously established in kyphosis-targeted interventions in randomized controlled trials in older adults with hyperkyphosis however evidence for improved physical function is conflicting. Few studies have investigated change in physical function after a targeted kyphosis intervention in older adults with low physical function. The primary aim in this descriptive study was to explore change in physical function after a progressive high intensity 3-month targeted kyphosis exercise and posture training intervention in older adults with low physical function and hyperkyphosis. Secondary aims were to explore change in HrQol, spinal strength and spinal curvature, and adherence and safety of the intervention in older adults with low physical function and hyperkyphosis.Methods: In this secondary analysis of the Specialized Center of Research (SCOR) Kyphosis randomized trial, 101 community dwelling older men and women with hyperkyphosis who completed the intervention were divided into a low function group (LFG) and high function group (HFG). Baseline characteristics were compared between LFG and HFG. Physical function, HrQol, spinal strength and spinal curvature (kyphosis and lordosis) pre/post intervention change scores were explored within and between groups. Adherence and adverse events were examined in the LFG and HFG. Results:Twenty-six (26%) older adults were LFG, mean SPPB 9.62 (SD=1.17) points. At baseline, the LFG was older than HFG (p=0.005), endorsed more pain, (p=0.060), had worse physical function and HrQol (p≤0.001), and comparable kyphosis (p=0.640). SPPB increased 0.62 (95% CI: -0.20 to 1.44) points in the LFG and decreased 0.04 (95%CI: -0.28 to 0.19) points in the HFG, p=0.020. Gait speed improved 0.04 (95%CI: -0.02 to 0.10) m/s in the LFG. Kyphosis improved equally in both groups. Adherence was similar and there were no adverse events in the LFG or HFG. Conclusions:Older adults with low physical function and hyperkyphosis may improve physical function after a kyphosis targeted intervention. Older adults with low physical function may safely participate in targeted high-intensity kyphosis exercise and posture training. This observation needs to be confirmed in larger adequately powered studies. Clinicaltrials.gov dentifier: NCT01766674

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Impact of strategic planning, organizational culture imprint and care bundles to reduce adverse events in the ICU

International Journal for Quality in Health Care ◽

10.1093/intqhc/mzy198 ◽

2018 ◽

Vol 31 (6) ◽

pp. 480-484

Author(s):

Pablo Álvarez-Maldonado ◽

Arturo Reding-Bernal ◽

Alejandro Hernández-Solís ◽

Raúl Cicero-Sabido

Keyword(s):

Organizational Culture ◽

Strategic Planning ◽

Adverse Events ◽

Usual Care ◽

Care Center ◽

Tertiary Care ◽

Secondary Analysis ◽

Healthcare Personnel ◽

Cross Sectional ◽

Care Bundles

Abstract Objective To evaluate the occurrence of adverse events during a multifaceted program implementation. Design Cross-sectional secondary analysis. Setting The respiratory-ICU of a large tertiary care center. Participants Retrospectively collected data of patients admitted from 1 March 2010 to 28 February 2014 (usual care period) and from 1 March 2014 to 1 March 2017 (multifaceted program period) were used. Interventions The program integrated three components: (1) strategic planning and organizational culture imprint; (2) training and practice and (3) implementation of care bundles. Strategic planning redefined the respiratory-ICU Mission and Vision, its SWOT matrix (strengths, weaknesses, opportunities, threats) as well as its medium to long-term aims and planned actions. A ‘Wear the Institution's T-shirt’ monthly conference was given in order to foster organizational culture in healthcare personnel. Training was conducted on hand hygiene and projects ‘Pneumonia Zero’ and ‘Bacteremia Zero’. Finally, actions of both projects were implemented. Main outcome measures Rates of adverse events (episodes per 1000 patient/days). Results Out of 1662 patients (usual care, n = 981; multifaceted program, n = 681) there was a statistically significant reduction during the multifaceted program in episodes of accidental extubation ([Rate ratio, 95% CI] 0.31, 0.17–0.55), pneumothorax (0.48, 0.26–0.87), change of endotracheal tube (0.17, 0.07–0.44), atelectasis (0.37, 0.20–0.68) and death in the ICU (0.82, 0.69–0.97). Conclusions A multifaceted program including strategic planning, organizational culture imprint and care protocols was associated with a significant reduction of adverse events in the respiratory-ICU.

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Quitting Failure and Success With and Without Using Medication: Latent Classes of Abstinence and Adherence to Nicotine Monotherapy, Combination Therapy, and Varenicline

Nicotine & Tobacco Research ◽

10.1093/ntr/nty157 ◽

2018 ◽

Vol 21 (11) ◽

pp. 1488-1495 ◽

Cited By ~ 1

Author(s):

Danielle E McCarthy ◽

Mark V Versella

Keyword(s):

Combination Therapy ◽

Repeated Measures ◽

Latent Class ◽

Interactive Voice Response ◽

Nicotine Patch ◽

Secondary Analysis ◽

Comparative Trial ◽

Smoking History ◽

Latent Classes ◽

Increased Risk

Abstract Introduction Nonadherence to pharmacotherapies complicates studies of comparative pharmacotherapy effectiveness. Modeling adherence and abstinence simultaneously may facilitate analysis of both treatment acceptability and effectiveness. Methods Secondary analyses of a three-arm randomized comparative trial of nicotine patch, varenicline, and combination nicotine patch and lozenge among adult daily smokers (N = 1086) were conducted. Adherence rates collected via interactive voice response systems during the first 27 days of quitting were compared across treatment conditions. Repeated measures latent class analyses of adherence and abstinence in 3-day parcels through 27 days of a quit attempt were conducted with treatment, demographic, and smoking history covariates. Results Adherence varied across treatments and was lowest for nicotine lozenge use in combination nicotine replacement therapy (NRT). Five latent classes that differed significantly in 6-month abstinence rates were retained, including three subgroups of adherent participants varying in treatment response and two nonadherent groups varying in abstinence probabilities. Nonadherence was more likely among those receiving varenicline and combination NRT, relative to patch monotherapy. Varenicline and combination NRT did not promote abstinence among adherent latent classes but did promote abstinence among those partially adherent, relative to patch alone. Combination therapy attenuated increased risk of treatment disengagement with more years smoking. Minority smokers, those high in dependence, and those with shorter past abstinence were at increased risk for low-adherence and low-abstinence latent classes. Conclusions Varenicline and combination nicotine patch and lozenge are less likely to be used as directed and may not increase first-month abstinence better than patch alone when taken adherently. Implications This secondary analysis of adherence and abstinence in a comparative effectiveness trial shows that adherence is highest for the nicotine patch, next highest for varenicline, and lowest for combination nicotine patch and lozenge therapy due to low lozenge use. Distinct latent classes were found that varied in both first-month abstinence and adherence. Varenicline and combination NRT may not enhance abstinence over patch alone among smokers who take medication adherently. Adherent use of medication especially benefits those who are low in dependence and have positive quitting histories; it is less beneficial to at-risk smokers and members of racial minorities.

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Cortrak-Assisted Feeding Tube Insertion: A Comprehensive Review of Adverse Events in the MAUDE Database

American Journal of Critical Care ◽

10.4037/ajcc2017369 ◽

2017 ◽

Vol 26 (2) ◽

pp. 149-156 ◽

Cited By ~ 23

Author(s):

Annette M. Bourgault ◽

Lillian Aguirre ◽

Joseph Ibrahim

Keyword(s):

Adverse Events ◽

Secondary Analysis ◽

Left Lung ◽

Feeding Tube ◽

Tube Placement ◽

Tube Insertion ◽

Electromagnetic Devices ◽

User Expertise ◽

User Facility ◽

Feeding Tube Placement

Background Electromagnetic devices to guide feeding tube placement such as the CORTRAK Enteral Access System have shown promising results; however, researchers in recent studies have expressed concern that a higher level of user expertise may be required for safe use. Objectives To review adverse events related to CORTRAK-assisted feeding tube insertion reported in the Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database. Methods A retrospective, secondary analysis of the MAUDE database was performed to evaluate adverse events (ie, injury or death of patient) related to CORTRAK. Results Fifty-four adverse events between January 1, 2006 and February 29, 2016 were identified and reviewed. Most events (98%) involved feeding tube placement in the lungs (37%, left lung; 46%, right lung; 15%, not specified). Lung complications included pneumothorax (77%) and pneumonitis (21%). Death occurred in 17% of lung placements. Clinicians failed to recognize placement in 89% of CORTRAK insertion tracings reviewed. Conclusions Lung placement is not unique to CORTRAK and is an inherent risk of all feeding tube insertions. In known or suspected lung placement, feeding tubes should be removed and radiography performed to assess for pneumothorax. Clinicians must observe closely for lung placement and discriminate lung from gastric placement on insertion tracings. Clinicians require specialized training and experience to develop competency in using the CORTRAK device, although the exact amount of experience needed is unknown.

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