The impact of adjunctive aripiprazole on QT interval: A 12-week open label study in patients on olanzapine, clozapine or risperidone.

OBJECTIVE: To evaluate the effect of adjunct aripiprazole on QT of patients clinically stabilized on atypical antipsychotics. METHODS: The dataset was from an open-label 12-week prospective trial that evaluated adjunctive use of 5 mg/day of aripiprazole on metabolic profile in patients with schizophrenia, or schizoaffective disorder stabilized on olanzapine, clozapine, or risperidone. Bazett-corrected QT (QTc) was manually calculated from ECGs measured at baseline (before aripiprazole) and week 12, by two doctors blind to the diagnosis and atypical antipsychotic. The change in QTc (∆QTc: baseline QTc-week 12 QTc) and the number of participants in normal, borderline, prolonged, and pathological groups after 12 weeks were analyzed. RESULTS: Fifty-five participants, mean age of 39.3 (SD 8.2) years, were analyzed. The ∆QTc after 12 weeks was 5.9 ms (p = 0.143) for the whole sample; 16.4 ms (p = 0.762), 3.7 ms (p = 0.480) and 0.5 ms (p = 0.449), for the clozapine, risperidone and olanzapine group, respectively. There was no significant statistical difference comparing the change in QTc overall, and between atypical antipsychotic groups, when evaluating from baseline to endpoint. However, stratifying the sample based on sex-dependent QTc cut-offs showed a 45% decrease in abnormal QTc readings (p = 0.049) after aripiprazole initiation; 20 subjects had abnormal QTc at baseline, while only 11 subjects had abnormal QTc at 12 weeks. 25.5% of participants showed a reduction in at least one QTc severity group, while 65.5% had no change and 9.0% worsened in QTc group, after 12 weeks of adjunct aripiprazole. CONCLUSION: Low-dose adjunctive aripiprazole did not prolong QTc in patients stabilized on either olanzapine, risperidone, or clozapine. More controlled studies evaluating the QTc effect of adjunctive aripiprazole should be done to confirm and support these findings.

Validity of the patient health questionnaire 9-item in autistic youths: a pilot study.

BACKGROUND: Autistic adolescents have greater predisposition to depression and suicidality than neurotypical adolescents. Early detection is essential for timely treatment. The Patient Health Questionnaire 9-item (PHQ-9) is a brief screen for depression. The study examines the validity of the PHQ-9 for detecting major depressive disorder (MDD) in autistic youths. METHODS: English speaking youths aged 10-18 years, with DSM-IV/DSM-5/ICD-10 diagnosis of Autism Spectrum Disorder (ASD), and their parents presenting to a child psychiatric service were invited to participate between May 2018 to August 2020. Participants completed the respective self- and parent-rated PHQ-9 independently. MDD was verified using the MINI-Kid (Mini-International Neuropsychiatric Interview, Kid version). RESULTS: One hundred one youth, mean (SD) age 14.6 (2.3), were enrolled. 27 (27%) met criteria for current MDD. Mean total PHQ-9 scores, percentage ratings for severity of symptoms of depression, functional impairment, dysthymia and suicidality were compared. Areas under the ROC curve and statistically optimal cutoffs were determined. Parents rated depressive symptoms severity lower than their children. The PHQ-9 displayed low sensitivity with high false negative rates at conventional, adjusted and proposed cutoffs. CONCLUSIONS: Future studies should improve on the validity and reliability of existing depression screening tools, or develop more appropriate screening methods of depression, for autistic youths.

Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies.

Inherited peripheral neuropathies are a genetically heterogeneous group of disorders characterized by distal muscle weakness and sensory loss. Mutations in genes encoding aminoacyl-tRNA synthetases have been implicated in peripheral neuropathies, suggesting that these tRNA charging enzymes are uniquely important for the peripheral nerve. Recently, a mutation in histidyl-tRNA synthetase (HARS) was identified in a single patient with a late-onset, sensory-predominant peripheral neuropathy; however, the genetic evidence was lacking, making the significance of the finding unclear. Here, we present clinical, genetic, and functional data that implicate HARS mutations in inherited peripheral neuropathies. The associated phenotypic spectrum is broad and encompasses axonal and demyelinating motor and sensory neuropathies, including four young patients presenting with pure motor axonal neuropathy. Genome-wide linkage studies in combination with whole-exome and conventional sequencing revealed four distinct and previously unreported heterozygous HARS mutations segregating with autosomal dominant peripheral neuropathy in four unrelated families (p.Thr132Ile, p.Pro134His, p.Asp175Glu and p.Asp364Tyr). All mutations cause a loss of function in yeast complementation assays, and p.Asp364Tyr is dominantly neurotoxic in a Caenorhabditis elegans model. This study demonstrates the role of HARS mutations in peripheral neuropathy and expands the genetic and clinical spectrum of aminoacyl-tRNA synthetase-related human disease.

Ad Hoc Modifications to a High Dependency Psychiatric Unit for People With Dementia During the COVID-19 Period.

The COVID-19 pandemic led to behavioral exacerbations in people with dementia. Increased hospitalizations and lack of bed availability in specialized dementia wards at a tertiary psychiatric hospital in Singapore resulted in lodging people with dementia in the High Dependency Psychiatric Unit (HDPCU). Customizations to create a dementia-friendly environment at the HDPCU included: (1) environmental modifications to facilitate orientation and engender familiarity; (2) person-centered care to promote attachment, inclusion, identity, occupation, and comfort; (3) risk management for delirium; and (4) training core competencies. Such practical solutions can also be implemented elsewhere to help overcome resource constraints and repurpose services to accommodate increasing populations of people living with dementia.