Effect of Clinical Decision Support on Cardiovascular Risk Among Adults With Bipolar Disorder, Schizoaffective Disorder, or Schizophrenia: A Cluster Randomized Clinical Trial.

IMPORTANCE: Adults with schizophrenia, schizoaffective disorder, or bipolar disorder, collectively termed serious mental illness (SMI), have shortened life spans compared with people without SMI. The leading cause of death is cardiovascular (CV) disease. OBJECTIVE: To assess whether a clinical decision support (CDS) system aimed at primary care clinicians improves CV health for adult primary care patients with SMI. DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized clinical trial conducted from March 2, 2016, to September 19, 2018, restricted randomization assigned 76 primary care clinics in 3 Midwestern health care systems to receive or not receive a CDS system aimed at improving CV health among patients with SMI. Eligible clinics had at least 20 patients with SMI; clinicians and their adult patients with SMI with at least 1 modifiable CV risk factor not at the goal set by the American College of Cardiology/American Heart Association guidelines were included. Statistical analysis was conducted on an intention-to-treat basis from January 10, 2019, to December 29, 2021. INTERVENTION: The CDS system assessed modifiable CV risk factors and provided personalized treatment recommendations to clinicians and patients. MAIN OUTCOMES AND MEASURES: Patient-level change in total modifiable CV risk over 12 months, summed from individual modifiable risk factors (smoking, body mass index, low-density lipoprotein cholesterol level, systolic blood pressure, and hemoglobin A1c level). RESULTS: A total of 80 clinics were randomized; 4 clinics were excluded for having fewer than 20 eligible patients, leaving 42 intervention clinics and 34 control clinics. A total of 8937 patients with SMI (4922 women [55.1%]; mean [SD] age, 48.4 [13.5] years) were enrolled. There was a 4% lower rate of increase in total modifiable CV risk among intervention patients relative to control patients (relative rate ratio [RR], 0.96; 95% CI, 0.94-0.98). The intervention favored patients who were 18 to 29 years of age (RR, 0.89; 95% CI, 0.81-0.98) or 50 to 59 years of age (RR, 0.93; 95% CI, 0.90-0.96), Black (RR, 0.93; 95% CI, 0.88-0.98), or White (RR, 0.96; 95% CI, 0.94-0.98). Men (RR, 0.96; 95% CI, 0.94-0.99) and women (RR, 0.95; 95% CI, 0.92-0.97), as well as patients with any SMI subtype (bipolar disorder: RR, 0.96; 95% CI, 0.94-0.99; schizoaffective disorder: RR, 0.94; 95% CI, 0.90-0.98; schizophrenia: RR, 0.92; 95% CI, 0.85-0.99) also benefited from the intervention. Despite treatment effects favoring the intervention, there were no significant differences in individual modifiable risk factors. CONCLUSIONS AND RELEVANCE: This CDS intervention resulted in a rate of change in total modifiable CV risk that was 4% lower among intervention patients compared with control patients. Results were driven by the cumulative effects of incremental and mostly nonsignificant changes in individual modifiable risk factors. These findings emphasize the value of using CDS to prompt early primary care intervention for adults with SMI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02451670.

Associations between CES1 variants and dosing and adverse effects in children taking methylphenidate.

Background: Methylphenidate is the most prescribed stimulant to treat attention deficit-hyperactivity disorder (ADHD). Despite its widespread usage, a fair proportion of children are classified as non-responders to the medication. Variability in response and occurrence of adverse events with methylphenidate use may be due to several factors, including drug-drug interactions as well as pharmacogenetic differences resulting in pharmacokinetic and/or pharmacodynamic variances within the general population. The objective of this study was to analyze the effect of carboxylesterase 1 (CES1) variants on the frequency of adverse effects and dosing requirements of methylphenidate in children with ADHD. Methods: This was a retrospective cohort study of children and adolescents who met the inclusion criteria and had a routine visit during the enrollment period were invited to participate. Inclusion criteria included: ADHD diagnosis by a healthcare provider, between 6 and 16 years of age at the time of permission/assent, had not previously been prescribed methylphenidate, and treatment with any methylphenidate formulation for at least three consecutive months. Three months of records were reviewed in order to assess changes in dose and frequency of discontinuing methylphenidate. Participants' ADHD symptoms, medication response, adverse effects, select vitals, and dose were extracted from the electronic health record. Saliva samples were collected by trained study coordinators. Haplotypes were assigned based on copy number in different portions of the CES1 gene. Due to limited numbers, diplotypes (combinations of two haplotypes) were grouped for analysis as CES1A1/CES1A1, CES1A1/CES1A1c and CES1A1c/CES1A1c. Results: A total of 99 participants (n = 30 female; n = 69 male) had both clinical data and CES1 sequencing data, with an average age of 7.7 years old (range 3-15 years). The final weight-based dose in all individuals was 0.79 mg/kg/day. The most common adverse effects reported were decreased appetite (n = 47), weight loss (n = 24), and sleep problems (n = 19). The mean final weight-based dose by haplotype was 0.92 mg/kg for CES1A2/CES1A2, 0.81 mg/kg for CES1A2/CES1P1, and 0.78 mg/kg for CES1P1/CES1P1. After correction for multiple hypothesis testing, only one SNV, rs114119971, was significantly associated with weight-based dosing in two individuals. The individuals with the rs114119971 SNV had a significantly lower weight-based dose (0.42 mg/kg) as compared to those without (0.88 mg/kg; p < 0.001). Discussion: Variation in CES1 activity may impact dose requirements in children who are prescribed methylphenidate, as well as other CES1 substrates. Although intriguing, this study is limited by the retrospective nature and relatively small sample size.

Pragmatic trial design of an intervention to reduce cardiovascular risk in people with serious mental illness.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of death for people with serious mental illness (SMI), but clinicians are often slow to address this risk. METHODS/DESIGN: 78 Midwestern primary care clinics were randomized to receive or not receive access to a clinical decision support (CDS) tool. Between March 2016 and September 2018, primary care clinicians (PCPs) received CDS alerts during visits with adult patients with SMI who met minimal inclusion criteria and had at least one CV risk factor not at goal. The PCP CDS included a summary of six modifiable CV risk factors and patient-specific treatment recommendations. Psychiatrists received CDS alerts during their next visit with an eligible patient with SMI that alerted them to an elevated body mass index or recent weight gain and the presence of an obesogenic SMI medication. Study outcomes include total modifiable CV risk, six modifiable CV risk factors, and use of obesogenic SMI medications. DISCUSSION: This cluster-randomized pragmatic trial allowed PCPs and psychiatrists the opportunity to improve CV risk in a timely manner for patients with SMI. Effectiveness will be assessed using an intent-to-treat analysis, and outcomes will be assessed largely through electronic health record data harvested by the CDS tool itself. In total, 10,347 patients with SMI had an index primary care visit in a randomized clinic, and 8937 patients had at least one follow-up visit. Analyses are ongoing, and trial results are expected in mid-2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02451670.

Primary Care Clinicians Attitudes and Knowledge of Pharmacogenetics in a Large, Multi-state, Healthcare System.

BACKGROUND: Considerable progress has been made in the way of pharmacogenetic research and the development of clinical recommendations; however, its implementation into clinical practice has been slower than anticipated. We sought to better understand its lack of clinical uptake within primary care. AIM: The primary objective of this survey was to ascertain primary care clinicians' perceptions of pharmacogenetic use and implementation in an integrated health system of metropolitan and rural settings across several states. METHODS: Primary care clinicians (including MDs, DOs, NPs, and PAs) were invited to participate in a survey via email. Questions about pharmacogenetics knowledge and perceptions were presented to assess current understanding and usage of pharmacogenetics in practice. RESULTS: The rate of response for the survey was 17%. Of the 90 respondents, 58% were female, 69% were MDs/DOs, 20% were NPs, and 11% were PAs. Fifty-eight percent of respondents received their clinical degree in or after 2000. Ninety percent of respondents noted that they were uncomfortable ordering a pharmacogenetics test, with 76% stating they were uncomfortable applying the results of a pharmacogenetic test. Notably, 78% of respondents were interested in having pharmacogenetic testing available through Medication Therapy Management (MTM) services, although PAs were significantly less interested as compared to NPs and MD/DOs. Ninety-five percent of respondents were interested in a clinical decision support tool relevant to pharmacogenetic results. CONCLUSIONS: As a whole, prescribing clinicians in primary care clinics are uncomfortable in the ordering, interpreting, and applying pharmacogenetic results to individual patients. However, favorable attitudes towards providing pharmacogenetic testing through existing MTM clinics provides the opportunity for pharmacists to advance existing practices.

Further examination of embedded performance validity indicators for the Conners' Continuous Performance Test and Brief Test of Attention in a large outpatient clinical sample.

OBJECTIVE: Assessing test performance validity is a standard clinical practice and although studies have examined the utility of cognitive/memory measures, few have examined attention measures as indicators of performance validity beyond the Reliable Digit Span. The current study further investigates the classification probability of embedded Performance Validity Tests (PVTs) within the Brief Test of Attention (BTA) and the Conners' Continuous Performance Test (CPT-II), in a large clinical sample. METHOD: This was a retrospective study of 615 patients consecutively referred for comprehensive outpatient neuropsychological evaluation. Non-credible performance was defined two ways: failure on one or more PVTs and failure on two or more PVTs. Classification probability of the BTA and CPT-II into non-credible groups was assessed. Sensitivity, specificity, positive predictive value, and negative predictive value were derived to identify clinically relevant cut-off scores. RESULTS: When using failure on two or more PVTs as the indicator for non-credible responding compared to failure on one or more PVTs, highest classification probability, or area under the curve (AUC), was achieved by the BTA (AUC = .87 vs. .79). CPT-II Omission, Commission, and Total Errors exhibited higher classification probability as well. CONCLUSION: Overall, these findings corroborate previous findings, extending them to a large clinical sample. BTA and CPT-II are useful embedded performance validity indicators within a clinical battery but should not be used in isolation without other performance validity indicators.

Implementation of the MEDFRAT to Promote Quality Care and Decrease Falls in Community Hospital Emergency Rooms.

ABSTRACTPURPOSE: To identify and implement an evidence-based fall-risk assessment tool for use in emergency departments at Essentia Health, a large, primarily rural health care delivery system with 12 emergency departments. METHODS: The Iowa Model of Evidence-Based Practice to Promote Quality Care was used to guide the process. The Memorial Emergency Department Fall-Risk Assessment Tool (MEDFRAT) was programmed into the electronic medical record, along with interventions that could be selected for 2 fall-risk levels. An education session was developed for emergency nurses about falls and MEDFRAT, with planned time for discussion about any concerns in the implementation of MEDFRAT. MEDFRAT was selected for implementation by nursing leadership because it is evidence based and appeared to be conducive to implementation in the diverse emergency departments across 12 sites in 3 states. RESULTS: Education sessions were presented to nurses at 11 of 12 emergency departments. Suggestions to support site-specific implementation were programmed into the electronic health record. Nurses expressed appreciation that they were consulted, and their feedback was incorporated into the tool before it was implemented. Resources needed at each site to implement recommended MEDFRAT interventions in the tool were identified. Needed resources were then provided to the emergency departments before implementation of MEDFRAT. CONCLUSIONS: The Iowa Model was a useful framework to select an evidence-based tool and then engage nurses in the process of implementing evidence-based practice changes in emergency departments across a diverse health care system serving a largely rural population. Ongoing follow-up will determine if this process results in fewer falls.