Using EHR data to identify coronavirus infections in hospitalized patients: Impact of case definitions on disease surveillance.

PURPOSE: To evaluate the number, characteristics, and outcomes of patients identified hospitalized with coronavirus disease 2019 (COVID-19) using two different case definitions. PROCEDURES: Electronic Health Record data were evaluated from patients hospitalized with COVID-19 through May 2020 at 52 health systems across the United States. Characteristics of inpatients with positive laboratory tests for SARS-CoV-2 were compared with those with clinical diagnosis of COVID-19 but without a confirmatory lab result. FINDINGS: Of 14,371 inpatients with COVID-19, 6623 (46.1 %) had a positive laboratory result, and n = 7748 (52.9 %) had only a clinical diagnosis of COVID-19. Compared with clinically diagnosed cases, those with laboratory-confirmed COVID were similar in age and sex, but differed by race, ethnicity, and insurance status. Laboratory-confirmed cases were more likely to receive certain COVID-19 therapies including hydroxychloroquine, anti-IL6 agents and antivirals (p < 0.001). Those with laboratory-confirmed COVID-19 had lower rates of most complications such as myocardial infarction, but higher overall mortality (p < 0.001). CONCLUSION: We observed a two-fold difference in the number of patients hospitalized with COVID-19 depending on whether the case definition required laboratory confirmation. Variations in case definitions also led to differences in cohort characteristics, treatments, and outcomes.

Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders.

OBJECTIVE: Adults with attention-deficit/hyperactivity disorder (ADHD) have higher rates of alcohol and drug use disorders than adults without ADHD. The study aim was to determine if atomoxetine was superior to placebo in improving ADHD and alcohol use in recently abstinent adults with ADHD and comorbid alcohol use disorder. METHODS: Adults with DSM-IV diagnoses of ADHD and alcohol abuse and/or dependence were abstinent from alcohol at least 4 days (maximum 30 days) before study randomization. Participants received atomoxetine (25-100mg daily) or placebo for 12 weeks. ADHD symptoms were assessed using ADHD Investigator Symptom Rating Scale (AISRS) total score. Time-to-relapse to heavy alcohol use was analyzed using a 2-sided log-rank test based on Kaplan-Meier estimates and cumulative heavy drinking events over time were evaluated post hoc with recurrent-event analysis. RESULTS: Subjects received atomoxetine (n=72) or placebo (n=75) and 80 subjects completed the 12-week double-blind period (n=32 and 48, respectively). ADHD symptoms were significantly improved in the atomoxetine cohort compared to placebo (AISRS total score mean [S.D.], atomoxetine: -13.63 [11.35], P<.001; placebo: -8.31 [11.44], P<.001, difference: P=.007; effect size=0.48). No significant differences between treatment groups occurred in time-to-relapse of heavy drinking (P=.93). However, cumulative heavy drinking days were reduced 26% in atomoxetine-treated subjects versus placebo (event ratio=0.74, P=.023). There were no serious adverse events or specific drug-drug reactions related to current alcohol use. CONCLUSIONS: This 3-month, double-blind, placebo-controlled study of atomoxetine in adults with ADHD and comorbid alcohol use disorder demonstrates clinically significant ADHD improvement, and inconsistent effects on drinking behavior.

Functional outcomes in the treatment of adults with ADHD.

OBJECTIVE: ADHD is associated with significant functional impairment in adults. The present study examined functional outcomes following 6-month double-blind treatment with either atomoxetine or placebo. METHOD: Patients were 410 adults (58.5% male) with DSM-IV-defined ADHD. They were randomly assigned to receive either atomoxetine 40 mg/day to 80 mg/day (n = 271) or placebo (n = 139). The primary functional outcome measure was the Endicott Work Productivity Scale (EWPS), and the secondary measure was the Adult ADHD Quality of Life (AAQoL). Patients were seen for four visits in 6 months. RESULTS: At 6 months, both groups had nonsignificantly different improvements in EWPS total scores. Atomoxetine-treated patients showed significantly greater improvement than placebo-treated patients on the AAQoL after controlling for baseline severity of ADHD. Both treatment groups had low 6-month study completion rates. CONCLUSION: Following 6-month treatment with atomoxetine, adults with ADHD showed significantly greater improvement in functioning on disease-specific measures of quality of life than patients treated with placebo.

Efficacy and safety of atomoxetine in adolescents with attention-deficit/hyperactivity disorder and major depression.

This double-blind study examined efficacy and safety of atomoxetine (ATX; < or =1.8mg/kg per day) in adolescents aged 12-18 with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses of both attention-deficit/hyperactivity disorder (ADHD) and co-morbid major depressive disorder (MDD). Diagnoses were confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version and persistently elevated scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Parent version, Investigator-administered and -scored (ADHDRS-IV-Parent:Inv, > or =1.5 standard deviations above age and gender norms) and Children's Depression Rating Scale-Revised (CDRS-R, > or = 40). Patients were treated for approximately 9 weeks with ATX (n = 72) or placebo (n = 70). Mean decrease in ADHDRS-IV-Parent:Inv total score was significantly greater in the ATX group (-13.3 +/- 10.0) compared with the placebo group (-5.1 +/- 9.9; p < 0.001). Mean CDRS-R score improvement was not significantly different between groups (ATX, -14.8 +/- 13.3; placebo, -12.8 +/- 10.4). Rates of treatment-emergent mania did not differ between groups (ATX, 0.0%; placebo, 1.5%). ATX treatment was associated with significantly more nausea and decreased appetite (p = 0.002; p = 0.003). No spontaneously reported adverse events involving suicidal ideation or suicidal behavior occurred in either group. ATX was an effective and safe treatment for ADHD in adolescents with ADHD and MDD. However, this trial showed no evidence for ATX of efficacy in treating MDD.

Transition from methylphenidate or amphetamine to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder--a preliminary tolerability and efficacy study.

BACKGROUND: The primary treatment for attention-deficit/hyperactivity disorder (ADHD) has been psychostimulants. Recently developed nonpsychostimulant treatments have allowed certain patients to switch from a psychostimulant to a nonpsychostimulant. However, the outcomes of such switches have not been systematically studied. OBJECTIVE: The purpose of this pilot study was to assess treatment tolerance and efficacy during a cross-taper transition from methylphenidate or amphetamine to atomoxetine among children and adolescents with ADHD. METHODS: This pilot study was conducted in patients (aged 6-17 years) with incomplete responses (failure to obtain full reduction/elimination of symptoms) or intolerance of adverse events (AEs) during psychostimulant treatment. Patients continued ongoing psychostimulant treatment during the first week of the study. Transition to atomoxetine began by administering atomoxetine 0.5 mg/kg . d plus full-dose psychostimulant for 1 week, followed in the second week by 1.2 mg/kg . d atomoxetine plus half-dose psychostimulant. Patients remained on 1.2 mg/kg . d atomoxetine monotherapy for the remaining 5 weeks. This stepwise transition was enacted due to the difference in pharmacodynamics between the psychostimulants and atomoxetine. Applying a stepwise cross-titration allowed for better control of ADHD symptoms during the intervening period. Change in ADHD symptoms, as measured by the mean change in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-administered and -scored (ADHDRS-IV-Parent:Inv), was assessed from baseline to end point. RESULTS: Of the 62 subjects enrolled in the study, 39 (62.9%) were diagnosed as ADHD-combined type. Similar proportions were receiving methylphenidate (51.6%) and amphetamine (48.4%). Slightly more wished to switch due to inadequate response (53.2%) than intolerability (46.8%). Nine subjects discontinued at various times during the course of the study (patient or parent/caregiver decision [4], AE [2], protocol violation [2], and lack of efficacy [1]). Mean (SD) ADHDRS-IV-Parent:Inv total scores (n = 59, last-observation-carried-forward) improved significantly from baseline (visit 2) to an end point (32.1 [10.5] vs 22.6 [14.0]; P < 0.001). Of the 58 subjects answering in the atomoxetine monotherapy phase, 38 (65.5%) reported a preference for atomoxetine treatment over their previous psychostimulant. Tolerability results were as follows: 26 (44.1%) of 59 patients reported >or=1 AE, the most common being somnolence (4 [6.8%]), fatigue (3 [5.1%]), decreased appetite (3 [5.1%]), cough (3 [5.1%]), headache (3 [5.1%]), and contact dermatitis (2 [3.4%]). No clinically severe AEs were reported. Both mean (SD) diastolic (2.4 [7.8] mm Hg; P = 0.031) and systolic (2.4 [7.9] mm Hg; P = 0.029) blood pressures increased significantly from baseline to end point. Electrocardiography revealed a significant increase in mean (SD) heart rate (9.2 [11.6] bpm; P < 0.001) and a corresponding decrease in mean (SD) RR interval (-77.8 [98.2] ms; P < 0.001). Statistically significant, but mild, increases in diastolic pressure and heart rate were observed. CONCLUSION: These children and adolescent patients were successfully switched from methylphenidate or amphetamine to atomoxetine treatment, with resulting improvement in ADHD symptom severity from baseline in this pilot study.

The impact of olanzapine, risperidone, or haloperidol on the cost of schizophrenia care in a medicaid population.

OBJECTIVE: The objective of this study was to assess the impact of medication treatment on Medicaid costs for persons with schizophrenia. METHODS: Michigan Medicaid claims from January 1995 through September 1998 were analyzed for persons with schizophrenia diagnoses who initiated olanzapine (n = 458), risperidone (n = 481), or haloperidol (n = 252) treatment between January 1996 and September 1997. Total and component Medicaid payments were compared for the year after treatment initiation, with simultaneous adjustment for patient demographics, comorbid conditions, prior medication use, prior service use, and prior year costs. RESULTS: Significant baseline differences existed between the groups in prior medication and service use. Adherence to index medication varied between the groups (O = 60%; R = 54%; H = 37%; P < =.01 for each pairwise comparison). Average postperiod costs were US dollars 14512 per subject. After baseline adjustment, there were no significant differences in mean total cost. Excluding index medication costs, the olanzapine group's average cost was significantly lower than risperidone (-US dollars 1791, P =.002) and haloperidol (-US dollars 2080, P =.003), whereas the risperidone and haloperidol groups were not significantly different. The differences were driven by significantly lower cost for inpatient services for other medications among the olanzapine group. CONCLUSION: Total costs of schizophrenia care associated with olanzapine, risperidone, or haloperidol were similar, but component costs differed. Relative to risperidone or haloperidol, olanzapine may have a higher acquisition cost, but may decrease inpatient costs and be associated with more optimal medication use patterns. Use of risperidone may also increase pharmacy costs and be associated with greater persistence, relative to haloperidol.

Outpatient use of major antipsychotic drugs in ambulatory care settings in the United States, 1997-2000.

OBJECTIVE: To describe the prescription of antipsychotic agents in the United States and to investigate the association between demographic characteristics, clinical diagnosis, and antipsychotic prescribed. METHODS: Four years (1997-2000) of data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Care Survey (NHAMCS) were combined for analysis. Distributions for patient age, race, gender, primary diagnosis, and provider's medical specialty were assessed. Logistic regression models were developed to estimate the probability of receiving either (1) a second-generation vs a first-generation antipsychotic, or (2) olanzapine vs risperidone, given differences in gender, race, age, and primary diagnosis. RESULTS: Nearly 35.9 million ambulatory healthcare visits resulted in antipsychotic prescription during 1997-2000, or nearly 1% of all healthcare visits for the period. Nearly 30% of these visits were to nonpsychiatric physicians. The use of first-generation antipsychotics declined during this period, while the use of second-generation antipsychotics increased. Risperidone and olanzapine accounted for the majority of second-generation antipsychotic use. While the mean ages of patients using risperidone and olanzapine were similar, the age distributions differed, with risperidone showing more frequent use among the young (< 18 years) and the old (> 65 years). Patients of nonwhite race were more likely to receive olanzapine than risperidone. CONCLUSION: Results from this national survey indicate that second-generation antipsychotics are being used with increasing frequency and are widely used outside of the psychiatric specialty. Differences in age distribution, racial representation, and diagnostic representation are associated with drug selection, reinforcing the importance of accounting for case-mix factors when researching these antipsychotics in observational studies.