Response rates to sequential trials of antipsychotic medications according to algorithms or treatment guidelines in psychotic disorders. A systematic review and meta-analysis.

BACKGROUND: There is a relative lack of research evaluating the outcomes when treatment guidelines or algorithms for psychotic disorders are followed. This systematic review and meta-analysis determined the response rates to antipsychotic medications at different stages of these algorithms and whether these response rates differ in first episode cohorts. METHODS: Data sources: A systematic search strategy was conducted across four databases PubMed, EMBASE, PsycINFO (Ovid) and CINAHL. Studies that had sequential trials of different antipsychotic medications were included. A meta-analysis of proportions was performed using random effects models and sub-group analysis in first episode psychosis studies. RESULTS: Of the 4078 unique articles screened, fourteen articles, from nine unique studies, were eligible and included 2522 participants. The proportion who experienced a response to any antipsychotic in the first stage of an algorithm was 0.53 (95 % C.I.:0.38,0.68) and this decreased to 0.26 (95 % C.I.:0.15,0.39) in the second stage. When clozapine was used in the third stage, the proportion that achieved a response was 0.43 (95 % C.I. 0.19, 0.69) compared to 0.26 (95 % C.I.:0.05,0.54) if a different antipsychotic was used. Four studies included 907 participants with a first episode of psychosis and the proportions that achieved a response were: 1st stage: 0.63 (95 % C.I.: 0.45, 0.79); 2nd stage: 0.34 (95 % C.I.:0.16,0.55); clozapine 3rd stage: 0.45 (95 % C.I.:0.0,0.97), different antipsychotic 3rd stage: 0.15 (95 % C.I.,0.01,0.37). DISCUSSION: These findings support the recommendation to have a trial of clozapine after two other antipsychotic medications have been found to be ineffective.

A systematic review and meta-analysis of health, functional, and cognitive outcomes in young people who use methamphetamine.

Methamphetamine use typically starts in adolescence, and early onset is associated with worse outcomes. Yet, health, functional, and cognitive outcomes associated with methamphetamine use in young people are not well understood. The aim of this study was to comprehensively assess the evidence on health, functional, and cognitive outcomes in young people (10-25 years-old) who use methamphetamine. Sixty-six studies were included. The strongest association observed was with conduct disorder, with young people who use methamphetamine some 13 times more likely to meet conduct disorder criteria than controls. They were also more likely to have justice system involvement and to perpetrate violence against others. Educational problems were consistently associated with youth methamphetamine use. The cognitive domain most reliably implicated was inhibitory control. Key limitations in the literature were identified, including heterogenous measurement of exposure and outcomes, lack of adequate controls, and limited longitudinal evidence. Outcomes identified in the present review - suggesting complex and clinically significant behavioural issues in this population - are informative for the development of future research and targeted treatments.

Neonatal sepsis definitions from randomised clinical trials.

INTRODUCTION: Neonatal sepsis is a leading cause of infant mortality worldwide with non-specific and varied presentation. We aimed to catalogue the current definitions of neonatal sepsis in published randomised controlled trials (RCTs). METHOD: A systematic search of the Embase and Cochrane databases was performed for RCTs which explicitly stated a definition for neonatal sepsis. Definitions were sub-divided into five primary criteria for infection (culture, laboratory findings, clinical signs, radiological evidence and risk factors) and stratified by qualifiers (early/late-onset and likelihood of sepsis). RESULTS: Of 668 papers screened, 80 RCTs were included and 128 individual definitions identified. The single most common definition was neonatal sepsis defined by blood culture alone (n = 35), followed by culture and clinical signs (n = 29), and then laboratory tests/clinical signs (n = 25). Blood culture featured in 83 definitions, laboratory testing featured in 48 definitions while clinical signs and radiology featured in 80 and 8 definitions, respectively. DISCUSSION: A diverse range of definitions of neonatal sepsis are used and based on microbiological culture, laboratory tests and clinical signs in contrast to adult and paediatric sepsis which use organ dysfunction. An international consensus-based definition of neonatal sepsis could allow meta-analysis and translate results to improve outcomes.

Longitudinal Assessment Using Optical Coherence Tomography in Patients with Friedreich's Ataxia.

Ocular abnormalities occur frequently in Friedreich's ataxia (FRDA), although visual symptoms are not always reported. We evaluated a cohort of patients with FRDA to characterise the clinical phenotype and optic nerve findings as detected with optical coherence tomography (OCT). A total of 48 patients from 42 unrelated families were recruited. Mean age at onset was 13.8 years (range 4-40), mean disease duration 19.5 years (range 5-43), mean disease severity as quantified with the Scale for the Assessment and Rating of Ataxia 22/40 (range 4.5-38). All patients displayed variable ataxia and two-thirds had ocular abnormalities. Statistically significant thinning of average retinal nerve fibre layer (RNFL) and thinning in all but the temporal quadrant compared to controls was demonstrated on OCT. Significant RNFL and macular thinning was documented over time in 20 individuals. Disease severity and visual acuity were correlated with RNFL and macular thickness, but no association was found with disease duration. Our results highlight that FDRA is associated with subclinical optic neuropathy. This is the largest longitudinal study of OCT findings in FRDA to date, demonstrating progressive RNFL thickness decline, suggesting that RNFL thickness as measured by OCT has the potential to become a quantifiable biomarker for the evaluation of disease progression in FRDA.

Neurophysiological and ophthalmological findings of SPG7-related spastic ataxia: a phenotype study in an Irish cohort.

BACKGROUND: Mutations in SPG7 are increasingly identified as a common cause of spastic ataxia. We describe a cohort of Irish patients with recessive SPG7-associated phenotype. METHODS: Comprehensive phenotyping was performed with documentation of clinical, neurophysiological, optical coherence tomography (OCT) and genetic data from individuals with SPG7 attending two academic neurology units in Dublin, including the National Ataxia Clinic. RESULTS: Thirty-two symptomatic individuals from 25 families were identified. Mean age at onset was 39.1 years (range 12-61), mean disease duration 17.8 years (range 5-45), mean disease severity as quantified with the scale for the assessment and rating of ataxia 9/40 (range 3-29). All individuals displayed variable ataxia and spasticity within a spastic-ataxic phenotype, and additional ocular abnormalities. Two had spasmodic dysphonia and three had colour vision deficiency. Brain imaging consistently revealed cerebellar atrophy (n = 29); neurophysiology demonstrated a length-dependent large-fibre axonal neuropathy in 2/27 studied. The commonest variant was c.1529C > T (p.Ala510Val), present in 21 families. Five novel variants were identified. No significant thinning of average retinal nerve fibre layer (RNFL) was demonstrated on OCT (p = 0.61), but temporal quadrant reduction was evident compared to controls (p < 0.05), with significant average and temporal RNFL decline over time. Disease duration, severity and visual acuity were not correlated with RNFL thickness. CONCLUSIONS: Our results highlight that recessive SPG7 mutations may account for spastic ataxia with peripheral neuropathy in only a small proportion of patients. RNFL abnormalities with predominant temporal RNFL reduction are common and OCT should be considered part of the routine assessment in spastic ataxia.