Adverse drug reactions (ADRs) are associated with increased morbidity, mortality, and resource utilization. Drug interactions (DDIs) are among the most common causes of ADRs, and estimates have cited that up to 22% of patients take interacting medications. DDIs are often due to the propensity for agents to induce or inhibit enzymes responsible for the metabolism of concomitantly administered drugs. However, this phenomenon is further complicated by genetic variants of such enzymes. The aim of this study is to quantify and describe potential drug-drug, drug-gene, and drug-drug-gene interactions in a community-based patient population.

A regional pharmacy with retail outlets in Arkansas provided deidentified prescription data from March 2020 for 4761 individuals. Drug-drug and drug-drug-gene interactions were assessed utilizing the logic incorporated into GenMedPro, a commercially available digital gene-drug interaction software program that incorporates variants of 9 pharmacokinetic (PK) and 2 pharmacodynamic (PD) genes to evaluate DDIs and drug-gene interactions. The data were first assessed for composite drug-drug interaction risk, and each individual was stratified to a risk category using the logic incorporated in GenMedPro. To calculate the frequency of potential drug-gene interactions, genotypes were imputed and allocated to the cohort according to each gene’s frequency in the general population. Potential genotypes were randomly allocated to the population 100 times in a Monte Carlo simulation. Potential drug-drug, gene-drug, or gene-drug-drug interaction risk was characterized as minor, moderate, or major.

Based on prescription data only, the probability of a DDI of any impact (mild, moderate, or major) was 26% [95% CI: 0.248-0.272] in the population. This probability increased to 49.6% [95% CI: 0.484-0.507] when simulated genetic polymorphisms were additionally assessed. When assessing only major impact interactions, there was a 7.8% [95% CI: 0.070-0.085] probability of drug-drug interactions and 10.1% [95% CI: 0.095-0.108] probability with the addition of genetic contributions. The probability of drug-drug-gene interactions of any impact was correlated with the number of prescribed medications, with an approximate probability of 77%, 85%, and 94% in patients prescribed 5, 6, or 7+ medications, respectively. When stratified by specific drug class, antidepressants (19.5%), antiemetics (21.4%), analgesics (16%), antipsychotics (15.6%), and antiparasitics (49.7%) had the highest probability of major drug-drug-gene interaction.

In a community-based population of outpatients, the probability of drug-drug interaction risk increases when genetic polymorphisms are attributed to the population. These data suggest that pharmacogenetic testing may be useful in predicting drug interactions, drug-gene interactions, and severity of interactions when proactively evaluating patient medication profiles.

Genomind, Inc.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

There is consensus about the importance of ‘recovery’ in mental health services, but the link between recovery orientation of mental health teams and personal recovery of individuals has been underresearched.

To investigate differences in team leader, clinician and service user perspectives of recovery orientation of community adult mental health teams in England.

In six English mental health National Health Service (NHS) trusts, randomly chosen community adult mental health teams were surveyed. A random sample of ten patients, one team leader and a convenience sample of five clinicians were surveyed from each team. All respondents rated the recovery orientation of their team using parallel versions of the Recovery Self Assessment (RSA). In addition, service users also rated their own personal recovery using the Questionnaire about Processes of Recovery (QPR).

Team leaders (n = 22) rated recovery orientation higher than clinicians (n = 109) or patients (n = 120) (Wald(2) = 7.0, P = 0.03), and both NHS trust and team type influenced RSA ratings. Patient-rated recovery orientation was a predictor of personal recovery (b = 0.58, 95% CI 0.31–0.85, P<0.001). Team leaders and clinicians with experience of mental illness (39%) or supporting a family member or friend with mental illness (76%) did not differ in their RSA ratings from other team leaders or clinicians.

Compared with team leaders, frontline clinicians and service users have less positive views on recovery orientation. Increasing recovery orientation may support personal recovery.

Blood pressure is elevated in most patients during acute ischemic stroke, but the prognostic significance of this is unclear as the current data yield conflicting results.

Admission blood pressure from the 1281 patients in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) was analyzed for prognostic significance as well as the risk of hemorrhagic transformation. We also examined weighted-average blood pressure over seven days, and the impact of a 30% change in blood pressure in 24 hours. Patients with severe hypertension were excluded from the TOAST trial.

Increasing systolic blood pressure (SBP) on admission, but not diastolic (DBP) or mean arterial pressure (MAP) was predictive of poor outcome, but this effect was not significant after adjustment for other know prognostic factors. Increasing weighted-average SBP and MAP over seven days were predictive for poor outcome, but a 30% change in blood pressure over 24 hours was not.

Admission blood pressure is not an independent prognostic factor in acute ischemic stroke, but the weighted-average of SBP and MAP over seven days probably does have predictive value with higher values having a worse prognosis. A prospective trial of blood pressure control during acute stroke is needed.

This prospective, case control study evaluates quality of life (QOL), depressive affect, and memory outcomes of epilepsy patients implanted with a vagus nerve stimulator (VNS).

Three groups of patients with epilepsy underwent assessment on two occasions: 1) patients with a VNS were tested before and 12 months after implantation (n = 16); 2) patients who underwent cerebral resective surgery were tested pre- and post-operatively (n = 10); and 3) patients under medical management (n = 9). Group means were compared on the QOLIE-89, Geriatric Depression Scale, Wechsler Memory Scale - III, and the Memory Observation Questionnaire. Secondary analyses calculated the reliable change index, providing information on change beyond measurement error and chance.

Mean ratings of QOL, depression, and memory complaints and objective memory scores remained stable or improved in all the groups. The QOL improved more after cerebral resective surgery than VNS or medication controls, but the VNS and medication control groups did not differ. In the VNS group, QOL was not related to seizure reduction. The percentage of cases showing real change in memory was equivalent across groups, except in one of eight indices (i.e., verbal recognition memory).

This first case controlled design found that vagus nerve stimulation as an adjunctive therapy for seizure control did not change QOL, depressive affect, or objective memory scores over one-year more so than medical management alone. We point out the need for larger case control, non-industry funded investigations.