Faculty Bibliography

Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance, we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and quantitative methylation specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage design consisting of discovery and prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (κ = 0.64), HOXA9 (κ = 0.60), NID2 (κ = 0.60), and EDNRB (κ = 0.60) had a moderate to substantial agreement with clinical diagnosis in the discovery screen. HOXA9 had 68% sensitivity, 100% specificity, and a 0.81 Area Under the Curve (AUC). NID2 had 71% sensitivity, 100% specificity, and a 0.79 AUC. In the prevalence screen, HOXA9 (κ = 0.82) and NID2 (κ = 0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity, and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity, and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity, and a 0.97 AUC. In saliva, from OSCC cases and controls, HOXA9 had 75% sensitivity, 53% specificity, and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity, and a 0.73 AUC. This phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.

BACKGROUND: This study aimed to characterize the inpatient utilization of depot antipsychotics. METHOD: The characteristics of adults with schizophrenia or schizoaffective disorder, hospitalized for at least 28 days, and who were prescribed depot antipsychotics were examined from 2004 to 2006 using a database from a large state-operated psychiatric hospital system. Demographic and clinical characteristics of patients receiving depot fluphenazine or haloperidol were compared to those prescribed depot risperidone. RESULTS: We identified 2210 unique patients who initiated treatment with a depot antipsychotic (after receiving oral antipsychotics). Of these, 1484 (67.1%) received depot fluphenazine or haloperidol, and 726 (32.9%) received risperidone as their initial depot antipsychotic. Patients who received depot risperidone did not differ from those receiving depot fluphenazine or haloperidol with regard to demographics, diagnosis of schizoaffective disorder, number of comorbid psychiatric or medical diagnoses, or diagnosis of substance abuse. Patients started on depot risperidone during the observation period had a longer length of stay prior to initiation of depot than those started on depot fluphenazine or haloperidol (583 days vs. 237 days, t=5.489, p<.001). Patients who started on depot risperidone were less likely to be discharged on that medication than were patients who started on depot fluphenazine or haloperidol (odds ratio from Cox regression model=0.846 [95% CI 0.745-0.960]). CONCLUSIONS: Patients initiated on depot risperidone had a longer length of stay prior to their first injection and were less likely to be discharged on that medication compared to patients initiated on depot fluphenazine or haloperidol, possibly indicating that patients initiating depot risperidone had a more severe or treatment-resistant course of illness and/or that there were reimbursement barriers for the outpatient utilization of depot risperidone, or that efficacy differences exist between the depot antipsychotics at the doses used in this population

BACKGROUND: The purpose of this article is to review the utilization and dosing of ziprasidone in a state hospital system and to compare the dosing to dosing recommendations contained in product labeling that suggest a starting dose of 40 mg/day and a target dose range of 40 to 160 mg/day for schizophrenia. METHOD: Dosing of ziprasidone was examined from the time when it was first marketed in 2001 up to and including calendar year 2006 using a database that contains patient information and drug prescription information for every inpatient within the adult civil facilities of the New York State psychiatric hospital system operated by the New York State Office of Mental Health. Supporting evidence for a therapeutic dose response for ziprasidone was examined by conducting a PubMed search for the period January 1, 1990, to June 1, 2008, identifying English-language articles related to ziprasidone dose in schizophrenia using the search terms ziprasidone, dose, and schizophrenia. RESULTS: Although the highest efficacious dose of ziprasidone recommended in the manufacturer's product label is 160 mg/day, the mean dose of ziprasidone prescribed among patients hospitalized in New York State in calendar year 2006 and receiving antipsychotic medication (N = 7154) was 179 mg/day (N = 709), with 51.6% receiving doses in excess of 160 mg/day (N = 366). Patients discharged on treatment with ziprasidone (N = 189) received a mean dose of 206 mg/day. Patients with schizophrenia with a history of prior state hospital admission were more likely to receive doses greater than 160 mg/day. Clinicians in hospitals with the highest prescribing rates for ziprasidone were more likely to prescribe ziprasidone in excess of 160 mg/day. The initial dose on the first day for new starts on treatment with ziprasidone was 91 mg/day (N = 112). Published anecdotal reports describe the use of ziprasidone in excess of 160 mg/day and up to 640 mg/day among patients not responding to lower doses, but, currently, there are no published reports from double-blind randomized clinical trials establishing the utility of this high-dose treatment strategy. CONCLUSIONS: Dosing of ziprasidone in a large state hospital system is higher than what has been established in the registration program for schizophrenia. Although there is anecdotal evidence describing the use of ziprasidone in excess of 160 mg/day, controlled clinical trials are needed to determine if these higher doses are more effective

OBJECTIVE: This study describes the use of 'stat' medications for inpatients in a large state psychiatric hospital system, and examines the relationship between receipt of a 'stat' for agitation and subsequent hospital discharge. METHODS: Use of 'stat' medications in 2005 was retrospectively determined using a database that contains diagnosis and prescription information from 17 state-run adult civil facilities. A logistic regression model explored the relationship between receipt of a 'stat' order for intramuscular preparations of either antipsychotics or lorazepam within the first 30 days of hospitalization and likelihood of hospital discharge by 6 months. RESULTS: Among 7,202 patients who received antipsychotic medication in 2005, 3,240 (45%) also received a 'stat' psychotropic medication during that year. Among 40,651 stat orders, 19,142 (47%) were for intramuscular antipsychotics or lorazepam presumably given for the treatment of agitation. Among 1,673 patients admitted in the first 6 months of 2005, 415 (25%) received at least one such 'agitation stat.' The percent discharged at six months among 'agitation stat' receivers was 39%, compared to 69% among those who did not receive an 'agitation stat' (chi-square = 115, df = 1, P < .001). Regression analysis showed that receiving an 'agitation stat' in the first 30 days of hospitalization was associated with a 37% lower likelihood of being discharged by 6 months after admission (odds ratio .63, 95% CI: .46-.86). CONCLUSIONS: 'Stat' medications are commonly used. The use of 'agitation stat' medications can be used as a proxy for clinical stability and may prove to be a useful outcome measure for future pharmacoepidemiologic studies of comparative medication effectiveness

OBJECTIVE: The purpose of the study was to describe the incidence of newly treated diabetes mellitus, the prevalence of identified cases, and surveillance for new cases between 1997 and 2004 among inpatients in a large state psychiatric hospital system. METHODS: Prevalence was determined by ascertaining the number of individuals who received antidiabetic medication or had a diagnosis of diabetes mellitus for each calendar year in inpatient facilities operated by the New York State Office of Mental Health. Yearly incidence was calculated by identifying unique patients who received new prescriptions of antidiabetic medication among patients with no known history of receiving such medication and no recorded diagnosis of diabetes mellitus. Surveillance for abnormal plasma glucose levels was measured by calculating the number of plasma glucose tests completed per 100 patient-days among patients without diabetes mellitus. RESULTS: Prevalence of identified cases of diabetes increased from 6.9 percent of 10,091 patients in 1997 to 14.5 percent of 7,420 patients in 2004 (risk ratio [RR] = 2.11, 95 percent confidence interval [CI] = 1.93-2.31). Incidence of newly treated diabetes increased from .9 percent in 1997 to 1.8 percent in 2004 (RR = 2.03, CI = 1.51-2.73). The increase in incidence and prevalence was only partially explained by the increase in surveillance for new cases, which increased from 1.23 plasma glucose tests per 100 patient-days in 1997 to 1.80 in 2002 (RR = 1.46, CI = 1.43-1.50). CONCLUSIONS: The doubling of the treated incidence rate and the rise in prevalence of identified cases of diabetes among psychiatric inpatients mirrors the rise observed in the general population but with higher absolute rates