Methotrexate and Adverse Events in CIRT Secondary Analysis

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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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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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

Addiction ◽

10.1111/add.15440 ◽

2021 ◽

Author(s):

Emma Beard ◽

Sarah E. Jackson ◽

Robert M. Anthenelli ◽

Neal L. Benowitz ◽

Lisa St. Aubin ◽

...

Keyword(s):

Adverse Events ◽

Nicotine Patch ◽

Secondary Analysis ◽

Bayes Factors ◽

Analysis Of Results ◽

Estimation Of Risk

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The role of endoscopy and findings in COVID-19 patients, an early North American Cohort

BMC Gastroenterology ◽

10.1186/s12876-021-01796-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gabriela Kuftinec ◽

◽

B. Joseph Elmunzer ◽

Sunil Amin

Keyword(s):

Adverse Events ◽

North American ◽

Secondary Analysis ◽

Gastrointestinal Manifestations ◽

Endoscopic Procedures ◽

Systematic Assessment ◽

The North ◽

The Usa ◽

Enteral Access

Abstract Background and aims Gastrointestinal manifestations in patients with COVID-19 are common but the role of endoscopy in this patient population remains unclear. We investigated the need for endoscopic procedures, their findings, and impact on patient care in a systematic and geographically diverse sample of patients hospitalized with COVID-19. Methods As part of the North American Alliance for the Study of Digestive Manifestations of COVID-19, we identified consecutive patients hospitalized with COVID-19 at 36 medical centers in the USA and Canada. We performed a secondary analysis of patients who underwent endoscopy, collecting information on endoscopic indications, findings, interventions, staffing, procedure location, anesthesia utilization, and adverse events. Results Data were collected on 1992 patients; 24 (1.2%) underwent 27 endoscopic procedures (18 upper endoscopies, 7 colonoscopies, 2 endoscopic retrograde cholangiopancreatographies). The most common indications were: gastrointestinal bleeding (13) and enteral access (6). The most common findings were erosive or inflammatory changes. Ten patients underwent an endoscopic intervention for hemostatic therapy (2), enteral access (6), or biliary obstruction (2). Half of cases employed anesthesiology support; no sedation-related adverse events were reported. One-third of cases were performed in the intensive care setting and one quarter in the endoscopy unit. Conclusions In this large, systematic, geographically diverse cohort of patients hospitalized with COVID-19 in North America, very few patients underwent endoscopy despite a high prevalence of gastrointestinal manifestations. Almost all endoscopic findings and interventions were thought related to critical illness rather than direct viral injury. This systematic assessment of endoscopic necessity and outcomes may help guide resource allocation in the event of ongoing and future surges.

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Cost-Effectiveness Evaluation for the US of Fondaparinux Compared to Argatroban in the Management of Suspected HIT

Blood ◽

10.1182/blood.v126.23.4727.4727 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4727-4727

Author(s):

Ahmed Aljabri ◽

Mahdi Gharaibeh ◽

Yvonne Huckleberry ◽

Hussam Kutbi ◽

Yuval Raz ◽

...

Keyword(s):

Sensitivity Analysis ◽

Cost Effectiveness ◽

Adverse Events ◽

Wholesale Price ◽

Secondary Analysis ◽

Case Analysis ◽

Base Case ◽

Base Case Analysis ◽

Off Label ◽

Primary Base

Abstract Introduction. The relative efficacy and safety of fondaparinux and argatroban in the management of suspected heparin-induced thrombocytopenia (HIT) have been documented. We conducted a cost-effectiveness analysis of both agents in terms of cost and adverse events averted. Methods. We developed a two-armed decision tree model to simulate a cohort of patients with suspected or confirmed HIT managed with argatroban or fondaparinux, using published efficacy data and probabilities of developing HIT-related VTE or major bleeding. The primary base case analysis considered our institutional cost while the secondary analysis used the Average Wholesale Price. Probabilistic sensitivity analysis (PSA) was performed to confirm findings and one-way sensitivity analysis to evaluate additional scenarios. Results. In the primary base case analysis, fondaparinux dominated argatroban treatment as it was less expensive in managing suspected HIT ($154 vs. $2,064) and more effective in terms of adverse events averted (0.998878 vs. 0.995739). This was confirmed in PSA in terms of both cost ($154 vs. $1,999) and adverse events averted (0.9988711 vs. 0.9957212). Sensitivity analysis showed that the total costs of argatroban would never be less than fondaparinux based on our assumptions. In the secondary analysis, fondaparinux was less expensive ($362 vs. $3722) and more effective in terms of adverse event averted (0.998878 vs. 0.995739). The PSA confirmed these findings both in terms of cost ($343 vs. $3477) adverse events averted. (0.9988711 vs. 0.9957212). Conclusions. The cost savings from a once-daily SC fondaparinux injection with limited laboratory monitoring are more advantageous than IV argatroban infusion that requires continuous titration. Disclosures Off Label Use: Fondaparinux is used as "off-label" for the management of patients with suspected or confirmed HIT.

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