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Biomedical subjects

John M Kane

Publications and source records attributed to John M Kane.

At least 19 recordsLinked to original sources
PubMed2026

Characterization of local tolerability of TV-46000, a long-acting subcutaneous formulation of risperidone for the treatment of schizophrenia.

TV-46000 is a long-acting injectable antipsychotic (LAI) approved for the treatment of adults with schizophrenia and bipolar I disorder. LAIs like TV-46000 can improve adherence and reduce relapse in patients with schizophrenia; however, injection site reactions (ISRs) can contribute to LAI discontinuation. ISRs with TV-46000 treatment were characterized using data from two phase 3 trials of patients with schizophrenia (RISE [NCT03503318], SHINE [NCT03893825]) and a phase 1 study of patients with schizophrenia or schizoaffective disorder. Patients in the pooled safety population (aged 16-67 years) from RISE and SHINE (n = 525 TV-46000, n = 179 placebo) received 4554 TV-46000 injections and 2721 placebo injections. ISRs were reported in 19 % (n = 102) of patients who received TV-46000, corresponding to an exposure-adjusted event rate (EAER)/100 patient-years of 48.67. ISRs led to 9 (1.7 %) treatment discontinuations of TV-46000. The most frequently reported ISR adverse events were injection site pain (EAER, 15.38, n = 36 [7 %]) and injection site nodule (EAER, 12.01, n = 35 [7 %]). ISR frequency and pain and nodule adverse event frequency decreased after the first injection. In the phase 1 study (n = 99), mean injection site pain scores were highest immediately after injection, showed a notable decrease within 10 min of injection, and further decreased within 1 h after injection. In conclusion, for >4500 injections evaluated, ISR rates with TV-46000 were modest. Most ISRs were mild or moderate and rarely led to treatment discontinuation. Results support the favorable tolerability of TV-46000 as a treatment for schizophrenia in adults.

Humans↗
PubMed2006

Does antipsychotic polypharmacy increase the risk for metabolic syndrome?

OBJECTIVE: To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome. METHODS: 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses. RESULTS: Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models. CONCLUSIONS: Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.

Adult↗
PubMed2006

Disrupted in schizophrenia 1 genotype and positive symptoms in schizophrenia.

BACKGROUND: Converging evidence has demonstrated an association between the Disrupted in Schizophrenia 1 (DISC1) gene and schizophrenia (SZ). Within the DISC1 gene, a single nucleotide polymorphism (SNP), Ser704Cys, has been associated with the structure and function of the hippocampus. Because positive symptoms in SZ have also been associated with hippocampal structure and function, we hypothesized that variation in a DISC1 haplotype containing Ser704Cys would be significantly associated with positive symptomatology in SZ. METHODS: We tested for an association between variation in a haplotype block within the DISC1 gene containing Ser704Cys and lifetime history of positive symptoms in 199 Caucasian patients with SZ. RESULTS: We detected significant associations between a DISC1 haplotype containing Ser704Cys and Ser704Cys genotype and lifetime severity of delusions in SZ. CONCLUSIONS: These data suggest that that the effect of DISC1 genetic variation might be associated with positive symptoms in patients with SZ.

Cysteine↗
PubMed2006

Remission and cognitive ability in a cohort of patients with schizophrenia.

INTRODUCTION: Patients with schizophrenia were studied regarding their ability of achieving symptomatic remission. It was found that only approximately one-third of the patients fulfilled the criteria for remission. The importance of cognitive performance was studied to decide whether cognitive ability is a contributing factor for achieving remission. MATERIALS AND METHODS: A homogeneous cohort of 211 patients, of whom 76 patients attained remission (36%), and 135 patients (64%) failed to, was studied. Remission was decided by the use of eight items from the PANSS in which none of these items should have a score above three points. The patients were also tested on a comprehensive battery of cognitive tests including vigilance, working memory, long-term memory, executive functioning, learning performance, visuomotor speed/efficacy, cognitive flexibility and pre-morbid functioning. RESULTS: Marked differences were exhibited in the cognitive abilities in all domains of patients who had attained remission in comparison with those who had not. DISCUSSION: This study highlights the importance of cognitive performance as one possible predictor of remission. Patients without remission had lower cognitive ability and may have more difficulty in benefiting from, or complying with their treatment. As a consequence, various forms of supportive treatment might increase the likelihood of remission.

Adult↗
PubMed2006

Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.

PURPOSE: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. PATIENTS AND METHODS: Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. RESULTS: The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively). CONCLUSION: In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

Adult↗
PubMed2006

The FEZ1 gene shows no association to schizophrenia in Caucasian or African American populations.

Schizophrenia is a complex psychiatric disorder with both genetic and environmental components and is thought to be in part neurodevelopmental in origin. The DISC1 gene has been linked to schizophrenia in two independent Caucasian populations. The DISC1 protein interacts with a variety of proteins including FEZ1, the mammalian homolog of the Caenorhabditis elegans unc-76 protein, which is involved in axonal outgrowth. Variation at the FEZ1 gene has been associated with schizophrenia in a large Japanese cohort. In this study, nine SNP markers at the FEZ1 locus were genotyped in two populations. A North American Caucasian cohort of 212 healthy controls, 178 schizophrenics, 79 bipolar disorder, and 58 with schizoaffective disorder, and an African American cohort of 133 healthy controls, 162 schizophrenics, and 28 with schizoaffective disorder. No association to schizophrenia, bipolar disorder or schizoaffective disorder was found for any of the nine markers typed in these populations at the allelic or the genotypic level. Additionally no association was found in either population between specific haplotypes and any of the psychiatric disorders. Variation at the FEZ1 locus does not play a significant role in the etiology of schizophrenia, bipolar disorder or schizoaffective disorder in North American Caucasian or African American populations.Neuropsychopharmacology (2007) 32, 190-196. doi:10.1038/sj.npp.1301177; published online 16 August 2006.

Adaptor Proteins, Signal Transducing↗
PubMed2006

COMT genotype and manic symptoms in schizophrenia.

Inconsistencies in the relation between COMT variation and schizophrenia may be clarified by careful delineation of a target phenotype. The present study reports a significant association between a COMT haplotype and the severity of manic symptoms in 162 patients with schizophrenia or schizoaffective disorder (SZ). These data suggest that the effect of COMT variation may be associated with comorbid manic symptoms in SZ.

Adult↗
PubMed2006

Linking the PANSS, BPRS, and CGI: clinical implications.

To understand what given scores of the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) mean from a clinical point of view is important for the translation of research results into practice. We therefore (a) compared the absolute change of the BPRS/PANSS with the Clinical Global Impressions Ratings (CGI) -improvement score and the change of the CGI severity score, (b) analyzed whether the severity of illness at baseline had an impact on the latter association, and (c) attempted to replicate previous BPRS findings using a completely different data set based upon the PANSS-derived BPRS. The method used was equipercentile linking of BPRS and CGI ratings from 14 drug trials in acutely ill patients with schizophrenia (n=5970). An absolute reduction of the BPRS/PANSS by approximately 10/15 points corresponded to a CGI change of 'minimally improved' and to a change of the CGI severity score by one severity step. However, the latter associations depended on the severity of symptoms at baseline. Less severely ill patients required less BPRS/PANSS total score reduction to achieve the same CGI-improvement score than more severely ill patients. This effect of initial severity was attenuated using percentage rather than absolute BPRS/PANSS reduction scores. The linking analysis between the absolute BPRS/PANSS reduction and the CGI may have an implication for the interpretation of efficacy differences found in clinical trials, and for sample size estimations. Clinicians seem to base CGI ratings on relative change rather than on absolute change of symptoms.

Adult↗
PubMed2006

Ziprasidone-induced cognitive enhancement in schizophrenia: specificity or pseudospecificity?

OBJECTIVE: Ziprasidone may improve cognition in schizophrenia; however, this could be related to clinical symptom improvement, reflecting "pseudospecificity". We tested the hypothesis that ziprasidone improves cognition in the absence of clinical improvement. METHODS: We conducted a 12-week, open-label study of ziprasidone in 10 schizophrenia patients who met non-response criteria (<20% reduction in BPRS scores over 12 weeks). We conducted comprehensive cognitive testing and assessed change from baseline to end of study. RESULTS: We detected significant improvement on three measures of episodic memory (p<0.01) in these clinically non-responsive patients. Trend-level improvements were noted on tests involving processing speed and executive function. CONCLUSIONS: These data suggest that ziprasidone has cognitive benefits unrelated to an influence on other disease parameters.

Adolescent↗
PubMed2006

Electrophysiological indices of automatic and controlled auditory information processing in first-episode, recent-onset and chronic schizophrenia.

BACKGROUND: Deficits in amplitudes of auditory event-related potentials (ERP) indexing preattentive, automatic (mismatch negativity, MMN) and controlled, attention-dependent (N2, P3) auditory information processing have been well described in chronic schizophrenia. Normal MMN, but deficient N2 and P3 have been reported in first-episode patients. No study has investigated these ERPs concurrently in first-episode patients; thus, reported differences in MMN, N2 and P3 generation may reflect differences in patient samples rather than genuine differences in abnormal generation of these ERPs. METHODS: We recorded MMN, N2 and P3 in 26 first-episode patients, 25 recent-onset patients within 1.5 to 5 years after first admission, 25 chronic patients and 39 healthy controls. RESULTS: Recent-onset and chronic, but not first-episode patients showed reduced MMN. However, among first-episode patients those with low premorbid educational achievement demonstrated significantly reduced MMN. All patient groups showed pronounced N2 deficits and, to a variable extent, abnormalities in P3 generation. CONCLUSIONS: Abnormalities in N2 and P3 generation appear to reflect premorbid neuropathology, whereas MMN deficits may index both ongoing disease processes associated with illness progression as well as premorbid neurocognitive impairment. ERPs may provide tools to assess static and progressive neuropathology in schizophrenia. These findings need confirmation in longitudinal studies.

Acoustic Stimulation↗
PubMed2006

American Joint Committee on Cancer clinical stage as a selection criterion for sentinel lymph node biopsy in thin melanoma.

BACKGROUND: A significant proportion of newly diagnosed melanomas are thin lesions (< or = 1.00 mm). Because tumor thickness correlates with the risk for nodal metastases, sentinel lymph node (SLN) biopsy in this subset is controversial. Incorporating other prognostic factors (Clark level and ulceration), we evaluated the 6th edition American Joint Committee on Cancer (AJCC) clinical stage as a simple and widely applicable guideline for offering SLN biopsy for thin melanoma. METHODS: This study was a review of a prospective melanoma SLN database from 1993 to 2003 with emphasis on SLN positivity rates based on the 6th edition AJCC primary tumor thickness intervals and clinical stage. RESULTS: Three hundred five patients underwent SLN biopsy, with an overall positivity rate of 17.7%. By the 6th edition AJCC, lesions < or = 1.00 mm had an SLN positivity rate of 6.6%. By 6th edition clinical stage, SLN positivity rates were 4.9% for stage IA and 10.4% for stage IB. By using stage IA as the criterion for not offering SLN biopsy, this procedure would have been avoided in 46% (39 of 85) of < or = 1.00-mm melanoma patients with a negative SLN. CONCLUSIONS: Sixth edition AJCC clinical stage IB as a selection criterion for performing SLN biopsy in thin melanoma identifies most patients with a positive SLN while also avoiding a negative SLN biopsy in many patients. Until additional widely accepted and validated selection criteria are available, SLN biopsy for clinical stage IB, but not stage IA, thin melanomas is a reasonable approach.

Adult↗
PubMed2006

Genetic variation in DTNBP1 influences general cognitive ability.

Human intelligence is a trait that is known to be significantly influenced by genetic factors, and recent linkage data provide positional evidence to suggest that a region on chromosome 6p, previously associated with schizophrenia, may be linked to variation in intelligence. The gene for dysbindin-1 (DTNBP1) is located at 6p and has also been implicated in schizophrenia, a neuropsychiatric disorder characterized by cognitive dysfunction. We report an association between DTNBP1 genotype and general cognitive ability (g) in two independent cohorts, including 213 patients with schizophrenia or schizo-affective disorder and 126 healthy volunteers. These data suggest that DTNBP1 genetic variation influences human intelligence.

Adult↗
PubMed2006

Utilization of long-acting antipsychotic medication in patient care.

Schizophrenia is a complex disorder characterized by a broad spectrum of psychopathology. Aggressive efforts to bring the patient into remission should begin immediately after the first episode. Consequences of non-remission include poor prognosis, psychiatric and general medical complications, treatment resistance, and death from medical comorbidities and suicide. Prevention of relapse following remission is critical to the well-being and optimal functioning of patients with schizophrenia. The key to optimizing patients' outcomes is to ensure a patient's long-term continuation on medication. As treatment discontinuation can greatly impact the progression of the illness and the patient's ultimate outcome, selecting a treatment with maximum treatment effectiveness is optimal. Nonadherence to treatment is extremely prevalent among patients with schizophrenia, due to such factors as impaired cognition, lack of insight, and side effects associated with antipsychotic treatment. Atypical antipsychotics have shown some advantages over conventional antipsychotics in terms of reducing positive and negative symptoms of schizophrenia, preventing relapse, and incidence of tardive dyskinesia. Injectables and long-acting formulations of antipsychotics offer additional benefits in terms of ensuring treatment adherence.

Antipsychotic Agents↗
PubMed2006

Cognitive development in schizophrenia: follow-back from the first episode.

Despite consensus that schizophrenia is a neurodevelopmental disorder characterized by cognitive deficits, objective data documenting the course of cognitive development remain sparse. We conducted a follow-back study of patients ascertained at the time of their initial episode of schizophrenia or schizoaffective disorder, and a group of demographically matched healthy volunteers. We obtained school records containing standardized achievement test scores from the 1st through 12th grades, and scholastic aptitude test results from the 11th and 12th grades, and examined the developmental trajectories of cognitive performance with respect to prospective examinations conducted following participants' enrollment in our study. We found significant differences in academic achievement tests as early as the first grade, with scores from participants who would later develop schizophrenia lagging behind their peers by 0.8 to 1.1 grade equivalents. This gap widened resulting in a difference between groups of 1.5 to 1.8 grade equivalents by the 12th grade. In the subset of patients for whom SAT scores were available, we found that WAIS-R Full Scale IQ was 11.5 points lower than predicted from earlier SAT scores, suggesting a substantial decline in cognitive ability accompanying the initial episode of illness. These findings suggest that schizophrenia is marked by substantial cognitive deficits in the first grade, that there may be additional subtle decline preceding the overt onset of psychotic symptoms, and that the initial episode of illness is marked by additional decline. These observations may help advance concepts of premorbid cognitive ability in the schizophrenia syndrome and constrain models of pathophysiology.

Adolescent↗
PubMed2006

Efficacy and tolerability of ziprasidone in patients with treatment-resistant schizophrenia.

This multicentre, parallel-group study compared the efficacy and tolerability of ziprasidone and chlorpromazine in treatment-resistant schizophrenia (at least three treatment periods of at least 6 weeks each with two or more antipsychotic agents during the past 5 years without significant response) that was unresponsive to 6 weeks of open-label haloperidol (</=30 mg/day). Haloperidol nonresponders were randomized to ziprasidone 80-160 mg/day (n=152) or chlorpromazine 200-1200 mg/day (n=154) for up to 12 weeks. The primary efficacy measures were the Brief Psychiatric Rating Scale (BPRSd) total score derived from the Positive and Negative Syndrome Scale (PANSS), BPRSd core psychotic symptoms, and Clinical Global Impression-Severity (CGI-S). Secondary efficacy variables included PANSS total score, PANSS Negative Subscale, and the Montgomery-Asberg Depression Rating Scale. Results were assessed at baseline and week 6 of haloperidol treatment (n=415) and at weeks 0, 3, 6, 9 and 12 of randomized treatment (n=306). Improvements in efficacy variables were greater with ziprasidone at weeks 3 and 6, reaching statistical significance versus chlorpromazine (P<0.05) at week 6 for CGI-S and week 12 for PANSS Negative Subscale. Improvements in BPRSd total and core items and PANSS total scores were comparable at weeks 9 and 12. Ziprasidone was associated with a greater decrease in median prolactin levels and a lower incidence of clinically significant weight change. Neither agent caused any clinically important changes in QTc interval.

Adult↗