Diabetes mellitus among outpatients receiving clozapine: prevalence and clinical-demographic correlates

BACKGROUND: Treatment with antipsychotic drugs has been associated with increased risk for developing diabetes mellitus. Recent consensus statements suggest that clozapine may pose an especially high risk. The purpose of this study is to examine the prevalence and clinical-demographic correlates of diabetes among outpatients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder receiving clozapine. METHOD: One hundred one outpatients receiving clozapine at the University of Rochester Department of Psychiatry, Rochester, N.Y., were evaluated between September 2002 and September 2003. Demographic data were collected from medical records, and body mass index (BMI) and body fat measurements were conducted. Diagnosis of diabetes was established through review of medical records and fasting blood glucose testing. Associations between clinical and demographic variables and diabetes were examined using t tests, Fisher exact tests, and logistic regression. RESULTS: Mean (SD) age of patients was 40.4 (9.5) years, and 79% were white. Mean (SD) dose and duration of clozapine treatment were 426 (164) mg/day and 5.7 (3.6) years, respectively. Point prevalence of diabetes was 25.7%. Mean (SD) BMI was 32.6 (8.0) kg/m(2), and mean (SD) body fat was 34.0% (11.0%). Logistic regression revealed significant associations between diabetes and nonwhite race/ethnicity and family history of diabetes (p = .02 and .002, respectively). No significant associations were found between diabetes prevalence and BMI or body fat. CONCLUSION: Patients receiving clozapine are at substantial risk for developing diabetes, although the level of risk relative to other antipsychotic medications has not been fully determined. Clinicians should monitor all severely mentally ill patients receiving antipsychotic drugs for diabetes, with closer monitoring of patients with established demographic risk factors.     

Holding American hospitals accountable: rhetoric and reality

Assessing the vast arena that continues to grow in pursuit of accountability in American hospitals, this paper raises the following question: Is this enterprise geared toward making hospitals better or toward making them only look better? ‘Accountability’ has become an umbrella concept to signal the need to demonstrate — to others — that performance is being measured and perfected. The author asserts that there is an imperfect fit between health‐care and the industrial model being used to measure quality of care due to four problematic issues: the nature of contemporary patient care, the overstating and overselling of accountability proposals, inflated expectations placed upon ‘rationalization’, and insufficient attention afforded accident and error. The paper concludes with a plea for reconsideration of the tilt toward a business approach to health‐care, asking if, in our zeal to hold hospitals accountable, we are measuring what is important or simply making important what we can measure.     

Neurons in hippocampal afferent zones of rat striatum parse routes into multi-pace segments during maze navigation

Hippocampal 'place' neurons discharge when rats occupy specific regions within an environment. This finding is a cornerstone of the theory of the hippocampus as a cognitive map of space. But for navigation, representations of current position must be implemented by signals concerning where to go next, and how to get there. In recordings in hippocampal output structures associated with the motor system (nucleus accumbens and ventromedial caudate nucleus) in rats solving a plus-maze, neurons fired continuously from the moment the rat left one location until it arrived at the next goal site, or at an intermediate place, such as the maze centre. While other studies have shown discharges during reward approach behaviours, this is the first demonstration of activity corresponding to the parsing of complex routes into sequences of movements between landmarks, similar to the lists of instructions we often employ to communicate directions to follow between points on a map. As these cells fired during a series of several paces or re-orientation movements, perhaps this is homologous to 'chunking'. The temporal overlaps in the activity profiles of the individual neurons provide a possible substrate to successively trigger movements required to arrive at the goal. These hippocampally informed, and in some cases, spatially selective responses support the view of the ventral striatum as an interface between limbic and motor systems, permitting contextual representations to have an impact on fundamental action sequences for goal-directed behaviour.     

Hormesis, hotspots and emissions trading

Instrument choice--the comparison of technology standards, performance standards, taxes and tradable permits--has been a major topic in environmental law and environmental economics. Most analyses assume that emissions and health effects are positively and linearly related. If they are not, this complicates the instrument choice analysis. This article analyses the effects of a nonlinear dose-response function on instrument choice. In particular, it examines the effects of hormesis (high-dose harm but low-dose benefit) on the choice between fixed performance standards and tradable emissions permits. First, the article distinguishes the effects of hormesis from the effects of local emissions. Hormesis is an attribute of the dose-response or exposure-response relationship. Hotspots are an attribute of the emissions-exposure relationship. Some pollutants may be hormetic and cause local emissions-exposure effects; others may be hormetic without causing local emissions-exposure effects. It is only the local exposure effects of emissions that pose a problem for emissions trading. Secondly, the article shows that the conditions under which emissions trading would perform less well or even perversely under hormesis, depend on how stringent a level of protection is set. Only when the regulatory standard is set at the nadir of the hormetic curve would emissions trading be seriously perverse (assuming other restrictive conditions as well), and such a standard is unlikely. Moreover, the benefits of the overall programme may justify the risk of small perverse effects around this nadir. Thirdly, the article argues that hotspots can be of concern for two distinct reasons, harmfulness and fairness. Lastly, the paper argues that the solution to these problems may not be to abandon market-based incentive instruments and their cost-effectiveness gains, but to improve them further by moving from emissions trading and emissions taxes to risk trading and risk taxes. In short, the article argues that hormesis does not pose a general obstacle to emissions trading or emissions taxes, but that in those cases where hormesis does pose such a problem, a shift toward risk trading or risk taxes would be the superior route.     

Choices in the management of asymptomatic lung nodules in the elderly

More than half of all lung cancer cases are diagnosed in patients older than 65 years of age. Risk of death after thoracotomy also increases over the age of 65. As a result, surgical intervention for lung cancer is often considered too risky in elderly patients, leaving the caregiver with a treatment dilemma when confronted with an abnormal radiographic finding. Advances in preoperative risk assessment, surgical and anesthetic techniques, radiation oncology, and locally ablative techniques have resulted in improved survival with a significant decrease in post-procedure mortality and morbidity for the aged population. On this basis, we believe treatment options for incidental pulmonary nodules found on chest roentgenograms should be discussed with patients and interventional work up pursued. It is no longer reasonable to deny elderly patients the benefits of surgical intervention simply on the basis of age. Every effort should be made to assess risk and optimize treatment for this large and growing segment of the population.     

Rhabdomyosarcoma and undifferentiated sarcoma in the first two decades of life: a selective review of intergroup rhabdomyosarcoma study group experience and rationale for Intergroup Rhabdomyosarcoma Study V

PURPOSE: To review the importance of prognostic factors in developing new protocols for children with rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Four studies conducted by the Intergroup Rhabdomyosarcoma Study (IRS) Group from 1972 through 1991. RESULTS: Favorable prognostic factors are: (1) undetectable distant metastases at diagnosis; (2) primary sites in the orbit and nonparameningeal head/neck and genitourinary nonbladder/prostate regions; (3) grossly complete surgical removal of localized tumor at the time of diagnosis; (4) embryonal/botryoid histology; (5) tumor size < or = 5 cm; and (6) age younger than 10 years at diagnosis. The IRS-V protocols are risk-based and refine therapy by reducing exposure to cyclophosphamide and radiation therapy (XRT) in patients at low risk while adding new, active agents such as topotecan or irinotecan to the standard therapy of vincristine, actinomycin D, and cyclophosphamide (VAC) plus XRT for patients with unfavorable histology or advanced disease. Collection of biologic specimens from patients with newly diagnosed disease continues to identify other factors that may distinguish patients with favorable features from those who need more intensive therapy. A new protocol that takes into account their previous treatment is needed for patients with recurrent disease. This program (being planned) does not include bone marrow/stem cell reconstitution because this strategy has thus far failed to improve survival rates of patients with metastases at diagnosis. CONCLUSION: Better understanding of biologic differences and new, active agents are needed to improve outcome of patients with unfavorable features at presentation.