Effect of stroke location on the laryngeal cough reflex and pneumonia risk

Abstract Background The purpose of this study was to evaluate the risk of developing pneumonia in acute stroke patients comparing the early anatomical stroke location and laryngeal cough reflex (LCR) testing. Methods A prospective study of 818 consecutive acute stroke patients utilizing a reflex cough test (RCT), which assesses the neurological status of the LCR compared to magnetic resonance imaging or computerized tomography for stroke location and subsequent pneumonia outcome. Stroke diagnosis and stroke location were made by a neurologist and clinical radiologist, respectively; both were blinded to the RCT results. Results Brainstem (p-value < .007) and cerebral strokes (p-value < .005) correlated with the RCT results and pneumonia outcome. Of the 818 patients, 35 (4.3%) developed pneumonia. Of the 736 (90%) patients who had a normal RCT, 26 (3.5%) developed pneumonia, and of the 82 (10%) patients with an abnormal RCT, 9 (11%) developed pneumonia despite preventive interventions (p-value < .005). The RCT had no serious adverse events. Conclusion The RCT acted as a reflex hammer or percussor of the LCR and neurological airway protection and indicated pneumonia risk. Despite stroke location, patients may exhibit "brainstem shock," a global neurological condition involving a transient or permanent impairment of respiratory drive, reticular activating system or LCR. Recovery of these functions may indicate emergence from brainstem shock, and help predict morbidity and mortality outcome.Peer Reviewe

Functional development in clinical high risk youth: Prediction of schizophrenia versus other psychotic disorders

This study evaluates premorbid social and academic functioning in clinical high-risk individuals as predictors of transition to schizophrenia versus another psychotic disorder. Participants were 54 individuals enrolled in phase one of the North American Prodrome Longitudinal Study who over two and a half years of follow-up met criteria for schizophrenia/schizophreniform disorder (n=28) or another psychotic disorder (n=26). Social and academic functioning in childhood, early adolescence, and late adolescence was assessed at baseline using the Cannon-Spoor Premorbid Adjustment Scale. Social maladjustment in late adolescence predicted significantly higher odds of transition to schizophrenia versus another psychotic disorder independent of childhood and early adolescent adjustment (OR = 4.02) and conveyed unique risk over academic maladjustment (O R= 5.64). Premorbid academic maladjustment was not associated with psychotic disorder diagnosis. Results support diagnostic specificity of premorbid social dysfunction to schizophrenia in clinical high-risk youth and underscore an important role for social maladjustment in the developmental pathology of schizophrenia and its prediction. (C) 2013 Elsevier Ireland Ltd. All rights reserved

An Individualized Risk Calculator for Research in Prodromal Psychosis

About 20–35% of individuals aged 12–30 years who meet criteria for a prodromal risk syndrome convert to psychosis within two years. However, this estimate ignores the fact that clinical high-risk (CHR) cases vary considerably in risk. Here we sought to create a risk calculator that can ascertain the probability of conversion to psychosis in individual patients based on profiles of risk indicators. The high risk category predicted by this calculator can inform research criteria going forward

Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis

Objective: This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia. Method: This randomized trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received olanzapine (5–15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period. Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores. Results: During the treatment year, 16.1% of olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg, SD=4.24). Conclusions: A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is warrante

Severity of thought disorder predicts psychosis in persons at clinical high-risk

BACKGROUND: Improving predictive accuracy is of paramount importance for early detection and prevention of psychosis. We sought a symptom severity classifier that would improve psychosis risk prediction. METHODS: Subjects were from two cohorts of the North American Prodrome Longitudinal Study. All subjects met Criteria of Psychosis-Risk States. In Cohort-1 (n=296) we developed a classifier that included those items of the Scale of Psychosis-Risk Symptoms that best distinguished subjects who converted to psychosis from nonconverters, with performance initially validated by randomization tests in Cohort-1. Cohort-2 (n=592) served as an independent test set. RESULTS: We derived 2-Item and 4-Item subscales. Both included unusual thought content and suspiciousness; the latter added reduced ideational richness and difficulties with focus/concentration. The Concordance Index (C-Index), a measure of discrimination, was similar for each subscale across cohorts (4-Item subscale Cohort-2: 0.71, 95% CI=[0.64, 0.77], Cohort-1: 0.74, 95% CI=[0.69, 0.80]; 2-Item subscale Cohort-2: 0.68, 95% CI=[0.3, 0.76], Cohort-1: 0.72, 95% CI=[0.66-0.79]). The 4-Item performed better than the 2-Item subscale in 742/1000 random selections of 80% subsets of Cohort-2 subjects (p-value=1.3E-55). Subscale calibration between cohorts was proportional (higher scores/lower survival), but absolute conversion risk predicted from Cohort-1 was higher than that observed in Cohort-2, reflecting the cohorts\u27 differences in 2-year conversion rates (Cohort-2: 0.16, 95% CI=[0.13, 0.19]; Cohort-1: 0.30, 95% CI=[0.24, 0.36]). CONCLUSION: Severity of unusual thought content, suspiciousness, reduced ideational richness, and difficulty with focus/concentration informed psychosis risk prediction. Scales based on these symptoms may have utility in research and, assuming further validation, eventual clinical applications

The relations of age and pubertal development with cortisol and daily stress in youth at clinical risk for psychosis

Prodromal syndromes often begin in adolescence – a period of neurodevelopmental changes and heightened stress sensitivity. Research has shown elevated stress and cortisol in individuals at clinical high risk (CHR) for psychosis. This cross-sectional study examined relations of age and pubertal status with cortisol and self-reported stress in healthy controls (HCs) and CHR adolescents. It was hypothesized that the relations of age and pubertal stage with cortisol and stress would be more pronounced in CHR youth

Sexual dimorphisms and prediction of conversion in the NAPLS psychosis prodrome

Sex differences in age at onset, symptomatology, clinical course (see Walker, Walder, Lewine and Loewy, 2002) and functional impairment (Thorup et al., 2007) are well documented in psychosis. The general pattern of findings is that males manifest an earlier onset, more severe symptoms and poorer prognosis than females. Limited studies examining individuals at clinical high-risk (CHR) suggest a similar pattern of sexual dimorphism (Holtzman et al., in review; Corcoran et al., 2011). As part of the North American Prodrome Longitudinal Study (NAPLS), the current study prospectively examined sexual dimorphisms differences in relationships among CHR symptoms, childhood (premorbid) academic and social functioning, baseline social and role functioning, and conversion to psychosis. Subjects included 276 (113F/163M) CHR NAPLS participants (ages 12–36.8 years). All measures/criteria were assessed at baseline except conversion status, assessed at 6-month intervals up to 30 months. Results show sex differences in baseline social and role functioning (though not in early childhood adjustment) that predate psychosis onset, with sexually dimorphic patterns in relation to prodromal symptoms. Among male (but not female) CHRs, baseline social functioning and positive prodromal symptoms predicted conversion. These findings help elucidate early course of vulnerability for, and maximally sensitive and specific etiological and prediction models of, psychosis conversion. Findings highlight the importance of considering sexually differentiated predictors of longitudinal course and outcome, in the context of emerging risk profiles. This may optimize efforts at early identification and individually tailored preventive interventions targeting different neurobiological markers/systems and/or cognitive-behavioral approaches. We speculate a contemporary, multidimensional model of psychosis risk that posits a role of sexually dimorphic, genetically linked influences that converge with a modulating role of gonadal hormones (see Walder et al., 2012) across a temporally sensitive neurodevelopmental trajectory towards conferring risk

The relation of antipsychotic and antidepressant medication with baseline symptoms and symptom progression: A naturalistic study of the North American Prodrome Longitudinal Sample

A substantial number of patients who meet criteria for a prodromal syndrome for first psychosis are treated with antipsychotic and/or antidepressant medications. There is suggestive evidence that both classes of medication may reduce prodromal symptoms. This longitudinal study examined the relation of antipsychotic and antidepressant medication with prodromal symptom severity at baseline and 6-month follow-up. Participants met Structured Interview for Prodromal Syndromes (SIPS) criteria for the prodrome, and were evaluated at eight centers as part of the North American Prodrome Longitudinal Study (NAPLS).Symptom ratings (positive, negative, disorganized and general) and data on antipsychotics, SSRIs, and other antidepressant medications were obtained at baseline and 6-month follow-up. Analyses revealed that all symptom dimensions declined in severity over time, but there were differences in the magnitude of the decline as a function of antipsychotic medication. Those never on antipsychotics showed less reduction in positive and disorganized symptoms over time. SSRIs and other antidepressants were not linked with declines in symptom severity. Consistent with findings from small-sample, clinical trials, the present results suggest that atypical antipsychotics may be effective in reducing the severity of attenuated positive symptoms associated with the prodrome to psychotic disorders. Limitations of the present study are noted, including the fact that it is not a randomized trial, and data on duration and dosage of medication and 2-year follow-up were not available for most participants. The results are discussed in light of the relative risks and benefits of preventive interventions, both medication and cognitive therapies, and the importance of future clinical trials

Functional Capacity Assessed by the Map Task in Individuals at Clinical High-Risk for Psychosis

Recent studies have recognized that signs of functional disability in schizophrenia are evident in early phases of the disorder, and, as a result, can potentially serve as vulnerability markers of future illness. However, functional measures in the psychosis prodrome have focused exclusively on real-world achievements, rather than on the skills required to carry-out a particular real-world function (ie, capacity). Despite growing evidence that diminished capacity is critical to the etiology of the established disorder, virtually no attention has been directed towards assessing functional capacity in the pre-illness stages. In the present study, we introduce the Map task, a measure to assess functional capacity in adolescent and young-adult high-risk populations