Characterizing and dating the onset of symptoms in psychotic illness: the Symptom Onset in Schizophrenia (SOS) inventory

Prodromal symptoms, including disturbances of perceptions, beliefs, cognition, affect, and behavior, are often the first symptoms of schizophrenia. Little is understood about the initial, prodromal stage of schizophrenia, despite the compelling research and clinical need. The development and psychometric properties of a new, time-efficient instrument to characterize and date the initial symptoms of a psychotic illnesses, the Symptom Onset in Schizophrenia (SOS) scale, is described in this paper. The SOS rates the presence and dates the onset of 16 general prodromal, positive, negative, and disorganizational symptoms, as well as a clinician, family, and patient global rating of onset of illness. Inter-rater reliability for the presence of each symptom in 35 patients with schizophrenia, schizoaffective, or schizophreniform disorder was good to excellent, with kappa coefficient >0.7 for 12 items, and >0. 5 for all items. Agreement on symptom duration was good to excellent for individual items (ICC=0.7-1.0) and for global rating of duration of illness (ICC=0.97). Our data indicate that the SOS is a reliable, valid, time-efficient tool useful to retrospectively assess the onset of schizophrenia and related psychotic disorders. Further study is underway to evaluate other psychometric properties of the SOS, including test-retest reliability and predictive validity.     

Electrocardiographic ST-segment changes during acute, severe isovolemic hemodilution in humans

BACKGROUND: Controversy exists regarding the lowest blood hemoglobin concentration that can be safely tolerated. The authors studied healthy resting humans to test the hypothesis that acute isovolemic reduction of blood hemoglobin concentration to 5 g/dl would produce an imbalance in myocardial oxygen supply and demand, resulting in myocardial ischemia. METHODS: Fifty-five conscious healthy human volunteers were studied. Isovolemic removal of aliquots of blood reduced blood hemoglobin concentration from 12.8 +/- 1.2 to 5.2 +/- 0.5 g/dl (mean +/- SD). Removed blood was replaced simultaneously with intravenous fluids to maintain constant isovolemia. Hemodynamics and arterial oxygen content (Cao2) were measured before and after removal of each aliquot of blood. Electrocardiographic (ECG) changes were monitored continuously using a Holter ECG recorder for detection of myocardial ischemia. RESULTS: During hemodilution, transient, reversible ST-segment depression developed in three subjects as seen on the electrocardiogram during hemodilution. These changes occurred at hemoglobin concentrations of 5-7 g/dl while the subjects were asymptomatic. Two of three subjects with ECG changes had significantly higher heart rates than those without ECG changes at the same hemoglobin concentrations. When evaluating the entire study period, the subjects who had ECG ST-segment changes had significantly higher maximum heart rates than those without ECG changes, despite having similar baseline values. CONCLUSION: With acute reduction of hemoglobin concentration to 5 g/dl, ECG ST-segment changes developed in 3 of 55 healthy conscious adults and were suggestive of, but not conclusive for, myocardial ischemia. The higher heart rates that developed during hemodilution may have contributed to the development of an imbalance between myocardial supply and demand resulting in ECG evidence of myocardial ischemia. However, these ECG changes appear to be benign because they were reversible and not accompanied by symptoms.     

Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study.

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicities, and clinical effect of tipifarnib, a farnesyltransferase (FTase) inhibitor, in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs (EIAEDs). This study compares the pharmacokinetics and pharmacodynamics of tipifarnib at MTD in patients on and off EIAEDs. PATIENTS AND METHODS: Recurrent malignant glioma patients were treated with tipifarnib using an interpatient dose-escalation scheme. Pharmacokinetics and pharmacodynamics were assessed. RESULTS: Twenty-three assessable patients taking EIAEDs received tipifarnib in escalating doses from 300 to 700 mg bid for 21 of 28 days. The dose-limiting toxicity was rash, and the MTD was 600 mg bid. There were significant differences in pharmacokinetic parameters at 300 mg bid between patients on and not on EIAEDs. When patients on EIAEDs and not on EIAEDs were treated at MTD (600 and 300 mg bid, respectively), the area under the plasma concentration-time curve (AUC)(0-12 hours) was approximately two-fold lower in patients on EIAEDs. Farnesyltransferase inhibition was noted at all tipifarnib dose levels, as measured in peripheral-blood mononuclear cells (PBMC). CONCLUSION: Toxicities and pharmacokinetics differ significantly when comparing patients on or off EIAEDs. EIAEDs significantly decreased the maximum concentration, AUC(0-12 hours), and predose trough concentrations of tipifarnib. Even in the presence of EIAEDs, the levels of tipifarnib were still sufficient to potently inhibit FTase activity in patient PBMCs. The relevance of these important findings to clinical activity will be determined in ongoing studies with larger numbers of patients.     

The Impact of Comprehensive Care for Joint Replacement Bundled Payment Program on Care Delivery

Background

Comprehensive Care for Joint Replacement (CJR) is a Medicare initiative to test the impact of holding a hospital accountable for services provided during an episode of care for a lower extremity joint arthroplasty on costs and quality. This study examines whether hospital participation in CJR is associated with having programs focused on improving posthospitalization care or reducing costs using a survey of orthopedic surgeons.

Labial Adhesion with Acute Urinary Retention Secondary to Bartholin's Abscess

Labial adhesions are usually seen in early childhood or in the postmenopausal years, but this clinical entity is rarely seen in the reproductive years. We report a case of labial adhesion with acute urinary retention secondary to Bartholin's abscess in a reproductive‐aged woman with normal menstrual periods. We emphasize the possible occurrence of labial adhesion following Bartholin's abscess in the reproductive years with normal estrogen levels.     

Local Tobacco Control: Application of the Essential Public Health Services Model in a County Health Department’s Efforts to Put It Out Rockland

In 2000, Rockland County, a small suburban county north of New York City, dedicated $1 million of its Master Settlement Agreement funds to a comprehensive tobacco control program, Put It Out Rockland. Developed and implemented by the county health department, this program used an essential public health services model and an ongoing financial investment, within the context of strong statewide tobacco control efforts, to lower adult smoking rates to 9.7% and to reduce both smoking among youths and exposure to secondhand smoke over the ensuing decade. By combining state funds and local dollars for a total of $6.75 cost per capita, this comprehensive effort yielded 11 000 fewer smokers and translated to a potential savings of more than $24 million for the county.