Serious Bleeding in Patients With Atrial Fibrillation Using Diltiazem With Apixaban or Rivaroxaban.

Importance: Diltiazem, a commonly prescribed ventricular rate-control medication for patients with atrial fibrillation, inhibits apixaban and rivaroxaban elimination, possibly causing overanticoagulation.

Objective: To compare serious bleeding risk for new users of apixaban or rivaroxaban with atrial fibrillation treated with diltiazem or metoprolol.

Design, Setting, And Participants: This retrospective cohort study included Medicare beneficiaries aged 65 years or older with atrial fibrillation who initiated apixaban or rivaroxaban use and also began treatment with diltiazem or metoprolol between January 1, 2012, and November 29, 2020.

Antipsychotic Medications and Mortality in Children and Young Adults.

Importance: Dose-related effects of antipsychotic medications may increase mortality in children and young adults.

Objective: To compare mortality for patients aged 5 to 24 years beginning treatment with antipsychotic vs control psychiatric medications.

Design, Setting, And Participants: This was a US national retrospective cohort study of Medicaid patients with no severe somatic illness or schizophrenia or related psychoses who initiated study medication treatment.

Concurrent Gabapentin and Opioid Use and Risk of Mortality in Medicare Recipients with Non-Cancer Pain.

Gabapentin is prescribed for pain and is perceived as safe generally. However, gabapentin can cause respiratory depression, exacerbated by concomitant central nervous system depressants (e.g.

Risk for Bleeding-Related Hospitalizations During Use of Amiodarone With Apixaban or Rivaroxaban in Patients With Atrial Fibrillation : A Retrospective Cohort Study.

Background: Amiodarone, the most effective antiarrhythmic drug in atrial fibrillation, inhibits apixaban and rivaroxaban elimination, thus possibly increasing anticoagulant-related risk for bleeding.

Objective: For patients receiving apixaban or rivaroxaban, to compare risk for bleeding-related hospitalizations during treatment with amiodarone versus flecainide or sotalol, antiarrhythmic drugs that do not inhibit these anticoagulants' elimination.

Design: Retrospective cohort study.

Duloxetine, Gabapentin, and the Risk for Acute Myocardial Infarction, Stroke, and Out-of-Hospital Death in Medicare Beneficiaries With Non-Cancer Pain.

Objective: Duloxetine is a serotonin-norepinephrine reuptake inhibitor prescribed for musculoskeletal and other forms of chronic pain. Its dual pharmacologic properties have the potential to either raise or lower cardiovascular risk: adrenergic activity may increase the risk for acute myocardial infarction (AMI) and stroke, but antiplatelet activity may decrease risk. Gabapentin is another nonopioid medication used to treat pain, which is not thought to have adrenergic/antiplatelet effects.

Association of Rivaroxaban vs Apixaban With Major Ischemic or Hemorrhagic Events in Patients With Atrial Fibrillation.

Importance: The comparative effectiveness of rivaroxaban and apixaban, the most frequently prescribed oral anticoagulants for ischemic stroke prevention in patients with atrial fibrillation, is uncertain.

Objective: To compare major ischemic and hemorrhagic outcomes in patients with atrial fibrillation treated with rivaroxaban or apixaban.

Design, Setting, And Participants: Retrospective cohort study using computerized enrollment and claims files for US Medicare beneficiaries 65 years or older.

Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study.

Background: Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients.

Individual short-acting opioids and the risk of opioid-related adverse events in adolescents.

Purpose: Hydrocodone, codeine, oxycodone, and tramadol are frequently prescribed to adolescents for moderate pain related to minor trauma or dental, surgical, or medical procedures. Pharmacokinetic and pharmacodynamic differences between these opioids could affect their relative safety. We aimed to compare occurrence of opioid-related adverse events in adolescents without cancer or other severe conditions taking hydrocodone, codeine, oxycodone, and tramadol.

Association of Antipsychotic Treatment With Risk of Unexpected Death Among Children and Youths.

Importance: Children and youths who are prescribed antipsychotic medications have multiple, potentially fatal, dose-related cardiovascular, metabolic, and other adverse events, but whether or not these medications are associated with an increased risk of death is unknown.

Objective: To compare the risk of unexpected death among children and youths who are beginning treatment with antipsychotic or control medications.

Design, Setting, And Participants: This retrospective cohort study was conducted from 1999 through 2014 and included Medicaid enrollees aged 5 to 24 years in Tennessee who had no diagnosis of severe somatic illness, schizophrenia or related psychoses, or Tourette syndrome or chronic tic disorder.

Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding.

Importance: Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment.

Objectives: To compare the incidence of hospitalization for upper gastrointestinal tract bleeding in patients using individual anticoagulants with and without PPI cotherapy, and to determine variation according to underlying gastrointestinal bleeding risk.

Design, Setting, And Participants: Retrospective cohort study in Medicare beneficiaries between January 1, 2011, and September 30, 2015.

Outpatient Opioid Prescriptions for Children and Opioid-Related Adverse Events.

Background And Objectives: Little is known about opioid prescribing for children without severe conditions. We studied the prevalence of and indications for outpatient opioid prescriptions and the incidence of opioid-related adverse events in this population.

Methods: This retrospective cohort study between 1999 and 2014 included Tennessee Medicaid children and adolescents aged 2 to 17 without major chronic diseases, prolonged hospitalization, institutional residence, or evidence of a substance use disorder.

Comparative out-of-hospital mortality of long-acting opioids prescribed for non-cancer pain: A retrospective cohort study.

Purpose: Despite significant growth of opioid prescriptions, only limited data are available regarding the comparative safety of long-acting opioids for chronic non-cancer pain. Recent data suggest that transdermal fentanyl and oxycodone CR may have greater toxicity than morphine SR in patients with non-cancer pain. Thus, we compared the risk of out-of-hospital deaths in patients with non-cancer pain filling prescriptions for transdermal fentanyl or oxycodone CR with that for morphine SR.

High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death.

Objective: Studies demonstrating that higher doses of citalopram (> 40 mg) and escitalopram (> 20 mg) prolong the corrected QT interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these selective serotonin reuptake inhibitors (SSRIs) to that for equivalent doses of fluoxetine, paroxetine, and sertraline.

Methods: The Tennessee Medicaid retrospective cohort study included 54,220 persons 30-74 years of age without cancer or other life-threatening illness who were prescribed high-dose SSRIs from 1998 through 2011.

Association of Proton Pump Inhibitors With Reduced Risk of Warfarin-Related Serious Upper Gastrointestinal Bleeding.

Background & Aims: Proton pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding.

Methods: This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow-up.

Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain.

Importance: Long-acting opioids increase the risk of unintentional overdose deaths but also may increase mortality from cardiorespiratory and other causes.

Objective: To compare all-cause mortality for patients with chronic noncancer pain who were prescribed either long-acting opioids or alternative medications for moderate to severe chronic pain.

Design, Setting, And Participants: Retrospective cohort study between 1999 and 2012 of Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care.

Development of an algorithm to identify serious opioid toxicity in children.

Background: The use of opioids is increasing in children; therefore, opioid toxicity could be a public health problem in this vulnerable population. However, we are not aware of a published algorithm to identify cases of opioid toxicity in children using administrative databases. We sought to develop an algorithm to identify them.

Out-of-hospital mortality among patients receiving methadone for noncancer pain.

Importance: Growing methadone use in pain management has raised concerns regarding its safety relative to other long-acting opioids. Methadone hydrochloride may increase the risk for lethal respiratory depression related to accidental overdose and life-threatening ventricular arrhythmias.

Objective: To compare the risk of out-of-hospital death in patients receiving methadone for noncancer pain with that in comparable patients receiving sustained-release (SR) morphine sulfate.

Genotype and risk of major bleeding during warfarin treatment.

Aim: To determine whether genetic variants associated with warfarin dose variability were associated with increased risk of major bleeding during warfarin therapy.

Materials & Methods: Using Vanderbilt's DNA biobank we compared the prevalence of CYP2C9, VKORC1 and CYP4F2 variants in 250 cases with major bleeding and 259 controls during warfarin therapy.

Results: CYP2C9*3 was the only allele that differed significantly among cases (14.

Performance of time-dependent propensity scores: a pharmacoepidemiology case study.

Purpose: Pharmacoepidemiologic studies of acute effects of episodic exposures often must control for many time-dependent confounders. Marginal structural models permit this and provide unbiased estimates when confounders are on the causal pathway. However, if causal pathway confounding is minimal, analyses with time-dependent propensity scores, calculated for time periods defined by individual drug prescriptions, may have better efficiency.

Brief report: Risk of adverse fetal outcomes associated with immunosuppressive medications for chronic immune-mediated diseases in pregnancy.

Objective: To assess the risk of adverse fetal outcomes following exposure to individual immunosuppressive drugs in pregnant women with chronic immune-mediated diseases.

Methods: Health plan data were obtained from the Tennessee Medicaid and Kaiser Permanente Northern California and Southern California claims databases, with linkage to both vital records and medical records. Women with inflammatory arthropathies, those with systemic lupus erythematosus, and those with inflammatory bowel disease who filled prescriptions for immunosuppressive treatments during pregnancy were included.