Clinical utility of the Prostate Health Index (phi) for biopsy decision management in a large group urology practice setting.

BACKGROUND: Deciding when to biopsy a man with non-suspicious DRE findings and tPSA in the 4-10 ng/ml range can be challenging, because two-thirds of such biopsies are typically found to be benign. The Prostate Health Index (phi) exhibits significantly improved diagnostic accuracy for prostate cancer detection when compared to tPSA and %fPSA, however only one published study to date has investigated its impact on biopsy decisions in clinical practice. METHODS: An IRB approved observational study was conducted at four large urology group practices using a physician reported two-part questionnaire. Physician recommendations were recorded before and after receiving the phi test result. A historical control group was queried from each site's electronic medical records for eligible men who were seen by the same participating urologists prior to the implementation of the phi test in their practice. 506 men receiving a phi test were prospectively enrolled and 683 men were identified for the historical control group (without phi). Biopsy and pathological findings were also recorded for both groups. RESULTS: Men receiving a phi test showed a significant reduction in biopsy procedures performed when compared to the historical control group (36.4% vs. 60.3%, respectively, P < 0.0001). Based on questionnaire responses, the phi score impacted the physician's patient management plan in 73% of cases, including biopsy deferrals when the phi score was low, and decisions to perform biopsies when the phi score indicated an intermediate or high probability of prostate cancer (phi ≥36). CONCLUSIONS: phi testing significantly impacted the physician's biopsy decision for men with tPSA in the 4-10 ng/ml range and non-suspicious DRE findings. Appropriate utilization of phi resulted in a significant reduction in biopsy procedures performed compared to historical patients seen by the same participating urologists who would have met enrollment eligibility but did not receive a phi test.

A review of treatment-emergent adverse events during olanzapine clinical trials in elderly patients with dementia.

OBJECTIVE: Olanzapine and other antipsychotics are not approved by the U.S. Food and Drug Administration to treat behavioral disturbances associated with dementia, but they are often prescribed to these patients. Although antipsychotics may be efficacious in this population, elderly patients with dementia may be particularly vulnerable to adverse events. This article reviews the safety of olanzapine in elderly patients with dementia. DATA SOURCES: Data from 6 studies comparing olanzapine to placebo, risperidone, or conventional antipsychotics in elderly patients with dementia were analyzed for mortality, cerebrovascular adverse events (CVAEs), and other adverse events. These trials represent all Lilly olanzapine-comparator trials in this population. The data included integration of 5 double-blind, placebo-controlled studies (olanzapine, N = 1184; placebo, N = 478; median age = 79 years; 1 study also compared olanzapine with risperidone, N = 196) and an open-label study comparing olanzapine (N = 150) with conventional antipsychotics (N = 143). DATA SYNTHESIS: Incidence of mortality was significantly higher in olanzapine- (3.5%) than in placebo-treated patients (1.5%; p = .024). There were no significant differences in the crude incidence of mortality between olanzapine- (2.9%) and risperidone- (2.0%) or olanzapine- (14.8%) and conventional antipsychotic-treated patients (16.1%; p = .871). Risk factors associated with mortality in olanzapine-treated patients included age >/= 80, concurrent benzodiazepine use, treatment-emergent sedation, or treatment-emergent pulmonary conditions. Incidence of CVAEs was approximately 3 times higher in olanzapine- (1.3%) than in placebo-treated patients (0.4%). There were no significant differences in the incidence of CVAEs between olanzapine- (2.5%) and risperidone- (2.0%; p = 1.0) or olanzapine- (3.4%) and conventional antipsychotic-treated patients (4.3%; p = .765). CONCLUSION: These findings should be considered if prescribers elect to treat behavioral disturbances associated with dementia in the elderly with olanzapine or other antipsychotics.

Comparison of treatment-emergent extrapyramidal symptoms in patients with bipolar mania or schizophrenia during olanzapine clinical trials.

BACKGROUND: Previous research on pharmacotherapy with conventional antipsychotics has suggested that patients with affective disorders have higher rates of treatment-emergent extrapyramidal symptoms (EPS) than patients with schizophrenia. It is not known whether this differential vulnerability holds true for treatment with atypical antipsychotics such as olanzapine. The present analysis retrospectively examined olanzapine clinical trial data for incidence of treatment-emergent EPS in patients with either schizophrenia or bipolar disorder. METHOD: Study participants were 4417 patients meeting DSM-III or DSM-IV criteria for either schizophrenia or bipolar mania participating in olanzapine clinical trials through July 31, 2001. Data were pooled across haloperidol-controlled trials and separately across placebo-controlled trials. Measures of EPS included rates of treatment-emergent EPS adverse event by type (i.e., dystonic, parkinsonian, or residual), Simpson-Angus Scale score mean change, rates of treatment-emergent parkinsonism, and rates of anticholinergic use. RESULTS: Consistent with prior research, haloperidol-treated patients with bipolar disorder appeared to be more vulnerable to the development of EPS than those with schizophrenia. However, olanzapine-treated patients with bipolar disorder were no more likely to develop EPS than those with schizophrenia. CONCLUSION: Results support previous research regarding conventional antipsychotics and suggest that olanzapine therapy does not increase the risk of EPS for patients with bipolar disorder.