Safety of baclofen versus tizanidine for older adults with musculoskeletal pain.

BACKGROUND: Baclofen and tizanidine are both muscle relaxants that carry the risk for neuropsychiatric events in older adults but there is a lack of data directly comparing their safety. This study aimed to investigate the relative risk between these two medications in causing injury and delirium in older adults. METHODS: This was a retrospective cohort study that was completed in an integrated healthcare system in the United States and included patients aged 65 years or older who started baclofen or tizanidine for the treatment of musculoskeletal pain from January 2016 through December 2018. Outcomes included new incidence of injury (concussion, contusion, dislocation, fall, fracture, or other injuries) and delirium. The cohort was followed from the initiation of therapy until the first occurrence of any of the following events: end of the index drug exposure, end of health plan membership, death, or the study end date of December 31st, 2019. Descriptive statistics were used to compare baseline patient characteristics between baclofen and tizanidine treatment groups. Cox proportional hazards model was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals. RESULTS: The final study cohort included 12,101 and 6,027 older adults in the baclofen and tizanidine group respectively (mean age 72.2 ± 6.2 years old, 59% female). Older adults newly started on baclofen had a greater risk of injury (HR = 1.54, 95% CI = 1.21-1.96, P = < 0.001) and delirium (HR = 3.33, 95% CI = 2.11-5.26, p = <0.001) compared to those started on tizanidine. CONCLUSION: The results of this study suggest that baclofen is associated with higher incidences of injury and delirium compared to tizanidine when used for the treatment of musculoskeletal pain. Future studies should investigate if these risks are dose-related and include a comparison group not exposed to either drug.

The Risk of Pneumonia in Older Adults Using Nonbenzodiazepine Hypnotics.

BACKGROUND: Previous studies have shown an increased risk of pneumonia with benzodiazepines (BZD) and an increased risk of any infection with non-BZD hypnotics, but no analysis has specifically investigated the risk of pneumonia with non-BZD hypnotic use. OBJECTIVE: To evaluate the risk of pneumonia associated with non-BZD hypnotic use in the elderly. METHODS: This was a retrospective case-control study of members aged 65 years and older enrolled in an integrated health care system. Cases were identified as patients aged 65 years and older with a diagnosis of pneumonia from January 2011 to December 2012. Controls were matched in a 4:1 ratio to cases based on age, gender, and active enrollment. Non-BZD hypnotic exposure was evaluated for all cases and controls 1 year before the index date. Proximity of exposure to index date and duration of use were analyzed. Conditional logistic regression adjusted for covariates was performed. RESULTS: We identified 51,029 cases with pneumonia and matched 188,391 controls without pneumonia. Of the cases with pneumonia, 5.5% (2,790) of cases had exposure to a non-BZD hypnotic, compared with 3.4% (6,345) of controls. Non-BZD hypnotic exposure was associated with an increased risk of pneumonia (OR = 1.14; 95% CI = 1.08-1.20). When exposure was stratified by proximity to index date, only current exposure was associated with an increased risk of pneumonia (OR = 1.27; 95% CI = 1.18-1.36). Short-term exposure was associated with a relatively higher risk of pneumonia (OR = 1.57; 95% CI = 1.39-1.77) compared with long-term use (OR = 1.16; 95% CI = 1.06-1.25). CONCLUSIONS: Current use of non-BZD hypnotics in older adults is associated with an increased risk of pneumonia. The findings of this study provide additional support for reducing the use of non-BZD hypnotics in older adults and for pursuing safer alternatives for treating insomnia. DISCLOSURES: No outside funding supported this study. At the time of this study, Jung was a PGY2 resident in drug information at Kaiser Permanente Drug Information Services. All authors are employed by Kaiser Permanente and report no other potential financial conflicts of interest. Study concept and design were contributed by Jung, Spence, Lee, and Gibbs. Jung, Spence, and Hui were responsible for data collection, and data interpretation was performed by Jung and Spence, with assistance from Escasa, Lee, and Hui. The manuscript was primarily written by Jung, along with Spence and Escasa, and revised by Spence, Escasa, and Lee, along with the other authors.

Risk of Injury in Older Adults Using Gastrointestinal Antispasmodic and Anticholinergic Medications.

OBJECTIVES: To determine the risk of injury associated with gastrointestinal (GI) antispasmodic and anticholinergic use in elderly adults. DESIGN: Retrospective case-control study. SETTING: Integrated healthcare system. PARTICIPANTS: Healthcare system members aged 65 and older (N = 260,010; 54,152 cases, 205,858 controls). MEASUREMENTS: Cases were identified as individuals with an injury resulting in a hospitalization, emergency department, or urgent care visit (index date) from January 2009 through December 2010. Cases and controls were matched in a 1:4 ratio based on age and sex. GI antispasmodic and anticholinergic current and past exposure for cases and controls was evaluated. Individuals were classified as current users if the days' supply of the GI prescription overlapped the index date and past users if the days' supply ended more than 60 days before the index date. Duration of use for current users was analyzed for short- and long-term use. Conditional logistic regression produced adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Of the total population, 1,068 (0.4%) had current exposure to a GI antispasmodic or anticholinergic (302 (0.6%) cases, 766 (0.4%) controls). Current users had a small but significantly greater risk of injury than nonusers (OR = 1.16, 95% CI = 1.01-1.34, P = .03). Past use was not significantly different from no use. Short-term users had a significantly greater risk of injury (OR = 1.31, 95% CI = 1.01-1.70, P = .04) than nonusers. Long-term use was associated with greater risk, but the difference was not statistically significant. CONCLUSION: Older adults using GI antispasmodic and anticholinergic drugs have greater risk of injury. These findings support recommendations to limit the prescribing of GI antispasmodics and anticholinergics in elderly adults.

Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death.

Treatment regimens for acute myeloid leukemia (AML) continue to offer weak clinical outcomes. Through a high-throughput cell-based screen, we identified avocatin B, a lipid derived from avocado fruit, as a novel compound with cytotoxic activity in AML. Avocatin B reduced human primary AML cell viability without effect on normal peripheral blood stem cells. Functional stem cell assays demonstrated selectivity toward AML progenitor and stem cells without effects on normal hematopoietic stem cells. Mechanistic investigations indicated that cytotoxicity relied on mitochondrial localization, as cells lacking functional mitochondria or CPT1, the enzyme that facilitates mitochondria lipid transport, were insensitive to avocatin B. Furthermore, avocatin B inhibited fatty acid oxidation and decreased NADPH levels, resulting in ROS-dependent leukemia cell death characterized by the release of mitochondrial proteins, apoptosis-inducing factor, and cytochrome c. This study reveals a novel strategy for selective leukemia cell eradication based on a specific difference in mitochondrial function.

Risk of injury associated with skeletal muscle relaxant use in older adults.

BACKGROUND: The use of skeletal muscle relaxants (SMRs) among older adults is associated with sedation and confusion, which may lead to an increased risk of falls and injuries. SMRs continue to be used among older adults, although they are on the Beers list as drugs to avoid in the elderly. OBJECTIVE: To investigate the relationship between SMR use and subsequent risk of injury. METHODS: This was a retrospective case-control study of members aged 65 years or older enrolled in an integrated health care system. Cases were defined as patients with a documented injury resulting in either a hospitalization or an emergency department or urgent care visit from January 2009 through December 2010. Cases were matched to controls in a 1:4 ratio by age and sex. Patients had to be enrolled and alive on the date of an injury (index date). SMR exposure for all cases and controls was evaluated within 60 days prior to the index date. Conditional logistic regression adjusted for covariates was performed, with risk estimates presented as odds ratios with 95% confidence intervals. RESULTS: From a base population of 322,806 older adults, we identified 27,974 cases of injury and 104,303 matched controls. Among the cases, 365 (1.30%) used an SMR; among the controls, 801 (0.77%) used an SMR in the 60 days prior to the index date. After adjustment for demographic and clinical covariates, risk of injury was significantly increased for patients using an SMR compared to no use (OR 1.32, 95% CI 1.16-1.50; p < 0.001). Carisoprodol was associated with an increased risk of injury (OR 1.73, 95% CI 1.04-2.88; p = 0.036), as were methocarbamol (OR 1.42, 95% CI 1.16-1.75; p = 0.001) and cyclobenzaprine (OR 1.22, 95% CI 1.02-1.45; p = 0.029). CONCLUSIONS: Older adults using SMRs have an increased risk of injury. These findings provide evidence to support current recommendations to avoid the use of SMRs in elderly patients.