Aripiprazole and Other Third-Generation Antipsychotics as a Risk Factor for Impulse Control Disorders: A Systematic Review and Meta-Analysis.

BACKGROUND: Increasing evidence suggests an association between third-generation antipsychotics (TGAs) and impulse control disorders (ICDs). This is thought to be due to their partial agonism of dopamine receptors. However, neither the relative nor absolute risks of ICDs in those prescribed TGAs are well established. To inform clinical practice, this systematic review and meta-analysis summarizes and quantifies the current evidence for an association. METHODS: An electronic search of Medline, PsychINFO, EMBASE, and the Cochrane Clinical Trials Database was undertaken from database inception to November 2022. Three reviewers screened abstracts and reviewed full texts for inclusion. A random-effects meta-analysis was conducted with eligible studies. RESULTS: A total of 392 abstracts were retrieved, 214 remained after duplicates were removed. Fifteen full texts were reviewed, of which 8 were included. All 8 studies found that TGAs were associated with increased probability of ICDs. Risk of bias was high or critical in 7 of 8 studies. Three studies were included in the pooled analysis for the primary outcome, 2 with data on each of aripiprazole, cariprazine, and brexpiprazole. Exposure to TGAs versus other antipsychotics was associated with an increase in ICDs (pooled odds ratio, 5.54; 2.24-13.68). Cariprazine and brexpiprazole were significantly associated with ICDs when analyzed individually. Aripiprazole trended toward increased risk, but very wide confidence intervals included no effect. CONCLUSIONS: Third-generation antipsychotics were associated with increased risk of ICDs in all studies included and pooled analysis. However, the risk of bias is high, confidence intervals are wide, and the quality of evidence is very low for all TGAs examined.

Epistaxis duration predicts bleeding in immune thrombocytopenia: a cohort study.

OBJECTIVE: To test for an association between duration of epistaxis and clinically relevant bleeding in the following 12 months in children with immune thrombocytopenia (ITP). DESIGN: Prospective cohort study. SETTING: The national UK Paediatric ITP registry, a multicentre prospective clinical registry of new cases of ITP between 2006 and February 2020. PATIENTS: All children aged between 2 months and 16 years in participating UK centres. EXPOSURE: Epistaxis at presentation defined as none, <10 min, 10-30 min and >30 min. MAIN OUTCOME MEASURES: Incident severe bleeds, combined moderate and severe bleeds and drop in haemoglobin (Hb) by ≥20 g/L. RESULTS: The sample included 1793 patients, of which 334 had epistaxis <10 min, 88 lasting 10-30 min and 97 >30 min. In the 12 months following presentation, 19 had a severe bleed, 140 had a moderate bleed and 54 had a drop in Hb ≥2 g/dL. Epistaxis >30 min duration was associated with increased odds of severe bleeds (OR 1.43-15.67), moderate or severe bleeding (OR 1.33-4.2) and drop in Hb (OR 1.23-6.91). Shorter duration epistaxis was not associated with increased odds of any outcome. A trend for increased odds with longer duration epistaxis was significant for all outcomes. CONCLUSIONS: The longer the duration of epistaxis at presentation with ITP, the higher the risk of a clinically significant bleeding event in the 12 months following. This should inform clinical severity ratings and treatment decisions.

Does the association between cognition and education differ between older adults with gradual or rapid trajectories of cognitive decline?

Education is associated with improved baseline cognitive performance in older adults, but the association with maintenance of cognitive function is less clear. Education may be associated with different types of active cognitive reserve in those following different cognitive trajectories. We used data on n = 5642 adults aged >60 from the English Longitudinal Study of Aging (ELSA) over 5 waves (8 years). We used growth mixture models to test if the association between educational attainment and rate of change in verbal fluency or immediate recall varied by latent class trajectory. For recall, 91.5% (n = 5164) of participants were in a gradual decline class and 8.5% (n = 478) in a rapid decline class. For fluency, 90.0% (n = 4907) were in a gradual decline class and 10.0% (n = 561) were in a rapid decline class. Educational attainment was associated with improved baseline performance for both verbal fluency and recall. In the rapidly declining classes, educational attainment was not associated with rate of change for either outcome. In the verbal fluency gradual decline class, education was associated with higher (an additional 0.05-0.38 words per 2 years) or degree level education (an additional 0.04-0.42 words per 2 years) when compared to those with no formal qualifications. We identified no evidence of a protective effect of education against rapid cognitive decline. There was some evidence of active cognitive reserve for verbal fluency but not recall, which may reflect a small degree of domain-specific protection against age-related cognitive decline.

Barriers to and Facilitators of Evidence-Based Practice in Psychiatry Core Trainees in Northwest England.

OBJECTIVE: Barriers and facilitators of evidence-based practice (EBP) in psychiatrists in training have only been researched with reference to prescribing decisions. We sought to quantitatively describe general EBP barriers and facilitators perceived by psychiatry core trainees (CTs) in England. METHODS: A cross-sectional survey of CTs from a single English region in their 1st to 3rd year of specialist training (CT1-3) uses the EBP inventory, a 26-item questionnaire subdivided into the domains of attitudes, social norms, perceived behavioral control (PBC), decision-making preferences, and intention and behavior. This was analyzed using a multiple indicators multiple causes model. RESULTS: The response rate was 42.9% (72/168 CTs). In all, domain's responses overall tended to be positive toward EBP. The most commonly reported barriers were rarely discussing research literature, feeling incapable of staying up to date, aversion to statistics, a preference for intuition or experience, and a perception that EBP disregards the individual differences between patients. Attitudes, norms, and behavior all loaded onto their intended factors. The decision-making factor was not present and PBC subdivided into 2 factors: clinical and knowledge self-efficacy. Regression coefficients for predicting behavior from the other factors were attitudes - 0.16 (p = 0.34), norms 0.34 (p = 0.24), clinical PBC - 0.28 (p = 0.10), and knowledge PBC 0.613 (p = 0.01). Additionally, question 5 (EBP respects individual patients) and question 13 (discusses research literature with colleagues) independently predicted behavior (ß = 0.388; p = 0.05 and ß = 0.433; p = 0.01). CONCLUSIONS: EBP intention and behavior were associated with perceiving EBP as relevant to individual patients, discussion about research with colleagues, and knowledge self-efficacy.

Cognitively stimulating activities and risk of probable dementia or cognitive impairment in the English Longitudinal Study of Ageing.

OBJECTIVES: To examine the association between cognitive stimulating activities (CSA) in later life (internet/email use, employment, volunteering, evening classes, social club membership and newspaper reading) and risk of cognitive impairment or dementia using marginal structural models to account for time-varying confounding affected by prior exposure. METHODS: Data were used from the English Longitudinal Study of Ageing waves 1 (2002) to 7 (2014), a nationally representative sample of adults in England aged ≥50. Self-reported participation in CSAs were measured as binary exposures from waves 2 (2004) to 6 (2012), with final sample sizes between n = 3937 and n = 2530 for different CSAs. Baseline exposure and covariates were used to create inverse probability of treatment and censoring weights (IPTCW). IPTCW repeated measures Poisson and linear regression were used to estimate each CSAs effect on risk of probable cognitive impairment or dementia at wave 7 (defined as a score of ≤11/27 on a modified telephone interview for cognitive status (TICS-27)). Results were compared to standard regression adjustment. RESULTS: Internet use at any wave (Risk ratios between 0.62 and 0.69) and volunteering in waves 3 to 6 (RRs between 0.516 and 0.633) were associated with reduced risk of cognitive impairment in IPTCW models. Standard estimates were similar for both internet use and volunteering.Newspaper reading (RR 95% Confidence interval 0.74-0.99) and social club membership (RR 95% CI 0.54-0.86) at wave 6 were significantly associated with risk of cognitive impairment in standard models, but not in the IPTCW models (RR 95% CI 0.82-1.11 and 0.60-1.08 respectively). Employment and evening classes were not associated with cognitive impairment in either model. CONCLUSIONS: We found that volunteering and internet use were associated with reduced risk of cognitive impairment. Associations between newspaper reading or social club membership and cognitive impairment may be due to time-varying confounding affected by prior exposure.

An application of Bayesian measurement invariance to modelling cognition over time in the English Longitudinal Study of Ageing.

OBJECTIVES: Recommended cut-off criteria for testing measurement invariance (MI) using the comparative fit index (CFI) vary between -0.002 and -0.01. We compared CFI results with those obtained using Bayesian approximate MI for cognitive function. METHODS: We used cognitive function data from Waves 1-5 of the English Longitudinal Study of Ageing (ELSA; Wave 1 n = 11,951), a nationally representative sample of English adults aged ≥50. We tested for longitudinal invariance using CFI and approximate MI (prior for a difference between intercepts/loadings ~N(0,0.01)) in an attention factor (orientation to date, day, week, and month) and a memory factor (immediate and delayed recall, verbal fluency, and a prospective memory task). RESULTS: Conventional CFI criteria found strong invariance for the attention factor (CFI + 0.002) but either weak or strong invariance for the memory factor (CFI -0.004). The approximate MI results also supported strong MI for attention but found 9/20 intercepts or thresholds were noninvariant for the memory factor. This supports weak rather than strong invariance. CONCLUSIONS: Within ELSA, the attention factor is suitable for longitudinal analysis but not the memory factor. More generally, in situations where the appropriate CFI criteria for invariance are unclear, Bayesian approximate MI could alternatively be used.