Twice-daily versus once-daily lisinopril and losartan for hypertension: Real-world effectiveness and safety.

BACKGROUND: Lisinopril and losartan manufacturer labels recommend twice-daily dosing (BID) if once-daily (QDay) is insufficient to lower blood pressure (BP). METHODS AND RESULTS: Retrospective cohort study of patients taking QDay lisinopril and losartan who experienced a dose-doubling (index date). A text-processing tool categorized BID and QDay groups at the index date based on administration instructions. We excluded: pregnant/hospice, regimens other than BID/QDay, and without BP measurements -6 months/+12 months of the index date. The most proximal BP measurements -6 months and +2 weeks to 12 months of the index date were used to evaluate BP differences. Propensity scores were generated, and differences in BP and adverse events (angioedema, acute kidney injury, hyperkalemia) between BID/QDay groups were analyzed within dosing cohorts using inverse propensity of treatment-weighted regression models. Of 11,210 and 6,051 patients who met all criteria for lisinopril and losartan, 784 (7.0%) and 453 (7.5%) were taking BID, respectively. BID patients were older and had higher comorbidity and medication burdens. There were no differences in systolic/diastolic BP between BID and QDay, with absolute differences in mean systolic BP ranging from -1.8 to 0.7 mmHg and diastolic BP ranging from -1.1 to 0.1 mmHg (all 95% confidence intervals [CI] cross 0). Lisinopril 10mg BID was associated with an increased odds of angioedema compared to lisinopril 20mg QDay (odds ratio 2.27, 95%CI 1.13-4.58). CONCLUSIONS: Adjusted models do not support improved effectiveness or safety of BID lisinopril and losartan.

Risk Factors for Utilization of Acute Care Services for Lithium Toxicity.

OBJECTIVE: This study evaluated risk factors for utilization of acute care services (ACS) (hospitalization or emergency department or urgent care visit) for lithium toxicity and the prevalence of lithium toxicity in a large, ambulatory population. METHODS: A nested case-control study compared lithium users with ACS utilization for lithium toxicity (case group) to lithium users without toxicity (control group) by using data from Kaiser Permanente Colorado for patients with at least one lithium prescription purchase. Patients in the case group were matched 1:5 with patients in the control group who had purchased lithium within 39 days of the ACS encounter. Possible lithium toxicity, identified by lithium level or diagnosis, was confirmed by chart review. Multivariable, conditional logistic regression analysis was used to identify patient and prescription characteristics associated with ACS utilization for lithium toxicity. The prevalence of lithium toxicity was determined. RESULTS: Of 3,115 individuals who took lithium, 70 experienced lithium toxicity, with or without ACS utilization, for a prevalence of 2.2%. Identified risk factors for ACS utilization for lithium toxicity included a newly initiated potentially interacting medication (odds ratio [OR]=30.30, 95% confidence interval [CI]=2.32-394.95), a higher number of treated chronic diseases (OR=1.28, CI=1.12-1.45), older age (OR=1.05, CI=1.02-1.09), and higher total daily lithium dose (OR=1.00, CI=1.00-1.00). CONCLUSIONS: Newly initiated, potentially interacting medications are a major preventable driver of ACS use for lithium toxicity, whereas age, chronic disease, and total daily lithium dose are small but significant factors. Clinicians should use extra caution when initiating a potentially interacting medication.

Design and implementation of population-based specialty care programs.

PURPOSE: The development, implementation, and scaling of 3 population-based specialty care programs in a large integrated healthcare system are reviewed, and the role of clinical pharmacy services in ensuring safe, effective, and affordable care is highlighted. SUMMARY: The Kaiser Permanente (KP) integrated healthcare delivery model allows for rapid development and expansion of innovative population management programs involving pharmacy services. Clinical pharmacists have assumed integral roles in improving the safety and effectiveness of high-complexity, high-cost care for specialty populations. These roles require an appropriate practice scope and are supported by an advanced electronic health record with disease registries and electronic surveillance tools for care-gap identification. The 3 specialty population programs described were implemented to address variation or unrecognized gaps in care for at-risk specialty populations. The Home Phototherapy Program has leveraged internal partnerships with clinical pharmacists to improve access to cost-effective nonpharmacologic interventions for psoriasis and other skin disorders. The Multiple Sclerosis Care Program has incorporated clinical pharmacists into neurology care in order to apply clinical guidelines in a systematic manner. The KP SureNet program has used clinical pharmacists and data analytics to identify opportunities to prevent drug-related adverse outcomes and ensure timely follow-up. CONCLUSION: Specialty care programs improve quality, cost outcomes, and the patient experience by appropriating resources to provide systematic and targeted care to high-risk patients. KP leverages an integration of people, processes, and technology to develop and scale population-based specialty care.

Medication adherence and its effect on relapse among patients discharged from a Veterans Affairs posttraumatic stress disorder treatment program.

BACKGROUND: Clinical outcomes in patients with posttraumatic stress disorder (PTSD) can be affected by several factors, including medication adherence. PTSD is associated with an increased likelihood of missed appointments, medication underuse or abuse, and treatment nonadherence. OBJECTIVE: To evaluate medication adherence and its effect on relapse following discharge of veterans from a PTSD residential rehabilitation program (PRRP). METHODS: A retrospective evaluation of drug adherence and relapse in the 12 months following discharge of patients from a PRRP was performed. All veterans who were discharged from January 1, 2005, to December 31, 2006, and were receiving antidepressant therapy were included. Adherence to antidepressant therapy was assessed by electronic prescription claims and defined as a medication possession ratio of at least 0.8 in the year following discharge. Relapse was defined as a hospitalization for psychiatric symptomatology. Predictive factors of adherence were also explored. RESULTS: Twenty-eight of the 82 (34%) veterans included in our study were adherent to medication during the 12 months following discharge. Seventeen (20.7%) veterans were rehospitalized for psychiatric symptoms, but nonadherence was not significantly associated with relapse (p = 0.91). The total number of drugs that a veteran received was related to adherence; patients who had a higher median number of medications were more adherent (p = 0.014). Age, comorbid substance abuse, combat service, and service connection were not associated with drug adherence. CONCLUSIONS: The majority of patients who were discharged from a residential PTSD treatment program were nonadherent to antidepressant drug therapy. One in 5 veterans with PTSD was rehospitalized within 1 year; however, medication adherence did not affect this outcome.

High vulnerability to acute dystonic reactions: a case of antipsychotic exposure and uncontrolled seizure activity.

Antipsychotic-induced extrapyramidal side effects have a negative impact on treatment for mental illness. Acute dystonic reactions are uncomfortable and frightening to the patient, and often lead to early discontinuation of drug therapy and worsened long-term outcome. The lower propensity of the atypical antipsychotic agents to cause extrapyramidal symptoms (EPS) has been associated with multiple benefits, including improved adherence. The authors describe a 57-year-old male patient who was in the treatment refractory unit. This patient exhibited extreme sensitivity to antipsychotic agents, experiencing acute dystonic reactions with quetiapine and olanzapine, in addition to older typical antipsychotic agents. The patient has not experienced acute EPS since therapy with aripiprazole was initiated. Further complicating this patient's course is his unusual sensitivity to experiencing dystonic reactions. We have observed acute dystonias in the absence of antipsychotic treatment and in the context of seizure activity (or paroxysmal dyskinetic activity). The true etiology of the latter dystonic activity has not been completely determined due to the patient's unwillingness to cooperate with invasive testing. None of the gene variations tested (CYP2D6 phenotype, two dopamine D2 receptor variants and one D3 receptor variant) appeared to explain the patient's vulnerability to acute dystonic reactions.