The Annals of pharmacotherapy
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N-nitrosodimethylamine (NDMA) is a hepatotoxic agent and carcinogen contaminant in commonly used medications such as valsartan, losartan, irbesartan, and ranitidine. NDMA can be produced during manufacture, introduced from contaminated ingredients procured elsewhere, or introduced from contaminated solvents and catalysts. The Food and Drug Administration has established a maximum dose of NDMA that is permissible per tablet and guidance for manufacturers. However, many unanswered questions about NDMA contamination need rigorous investigation.
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Background: Vasopressin decreases vasopressor requirements in patients with septic shock. However, the optimal norepinephrine dose for initiation or cessation of vasopressin is unclear. Objective: Analyze monthly intensive care unit (ICU) mortality rates 1 year preimplementation and postimplementation of a guideline suggesting a norepinephrine dose of 50 µg/min or more for initiation of vasopressin and early cessation of vasopressin. ⋯ Postguideline, fewer patients were initiated on vasopressin (305 [53.2%] vs 217 [37.7%], absolute difference -15.5% [95% CI -21.2% to -9.8%]), and the norepinephrine dose at vasopressin initiation was higher (median 25 [interquartile range 18, 40] µg/min vs 40 [22, 52] µg/min; median difference 15 [95% CI 11 to 19] µg/min; P < 0.01). After guideline implementation, there was no evidence for a difference in ICU mortality rate slope (slope change 0.07% [95% CI -0.8% to 1.0%] per month; P 0.87), but the vasoactive cost level decreased by US$183 (95% CI -US$327 to -US$39) per patient immediately after implementation. Conclusion and Relevance: Implementation of a guideline suggesting a high norepinephrine dose threshold for vasopressin initiation and early vasopressin cessation in patients with septic shock appears to be safe and may decrease vasoactive costs.
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Comparative Study
Rivaroxaban Versus Warfarin for Stroke Prevention and Venous Thromboembolism Treatment in Extreme Obesity and High Body Weight.
Background: Limited clinical data exist describing the use of direct-acting oral anticoagulants (DOACs) in patients with body mass index (BMI) >40 kg/m2 or body weight >120 kg. Thus, DOAC therapy in this population remains controversial. Objectives: To investigate rivaroxaban as a safe and effective alternative to warfarin for venous thromboembolism (VTE) treatment and prevention of stroke in patients with atrial fibrillation identified as extremely obese or of high body weight. ⋯ LOS was significantly shorter in the rivaroxaban arm (2 days [1-3] vs 4 days [2-7], P < 0.0001). Percentage of bleeding complications was higher in the rivaroxaban arm but not statistically significant (8% vs 2%, P = 0.06). Conclusion and Relevance: Although not statistically significant, rivaroxaban trended toward a lower incidence of clinical failure while demonstrating a significantly shorter LOS when compared with warfarin for VTE treatment or atrial fibrillation in morbidly obese or high-body-weight patients.
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Randomized Controlled Trial Multicenter Study
Is Benzodiazepine Use Associated With the Risk of Dementia and Cognitive Impairment-Not Dementia in Older Persons? The Canadian Study of Health and Aging.
Background: The use of benzodiazepines in relation to cognitive decline remains an area of controversy in aging populations. Objective: This study aims to evaluate the risk of cognitive impairment-not dementia (CIND), Alzheimer disease (AD), and all-cause dementia with benzodiazepine use. The effect modification by sex was also investigated. ⋯ All these effects were similar between men and women. Conclusion and Relevance: Benzodiazepine use in older people from the general population is related to subsequent occurrence of cognitive dysfunction but not implicated in the pathogenesis of dementia or AD. Caution should be exercised when prescribing benzodiazepines to preserve global cognitive function.
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Background: The use of extracorporeal membrane oxygenation (ECMO) sometimes requires deep levels of sedation (Richmond Agitation Sedation Scale [RASS] -5) in patients with acute respiratory distress syndrome (ARDS). The role of obesity in opioid and sedative requirements remains unclear in patients receiving ECMO. Objective: This study sought to determine whether obesity increases midazolam and opioid requirements in patients receiving venovenous (vv)-ECMO up to the first 7 days after initiation. ⋯ There were no differences in duration of ECMO, length of stay, or mortality. Conclusion and Relevance: Daily midazolam requirements were not significantly different, and opioid requirements were only significantly higher in the obese group on day 3 despite similar levels of sedation. The impact of obesity with the addition of ECMO and how to adapt doses of medications remains elusive.