Reducing the duration of untreated first-episode psychosis: effects on clinical presentation

CONTEXT: Most studies on first-episode psychosis show an association between a long duration of untreated psychosis (DUP) and poorer short-term outcome, but the mechanisms of this relationship are poorly understood. OBJECTIVE: To determine whether it is possible to reduce the DUP for first-episode patients in a defined health care area through the introduction of an early detection (ED) program, compared with parallel health care areas without an ED program (No-ED). SETTING AND PATIENTS: We included consecutive patients with a DSM-IV diagnosis of nonorganic, nonaffective psychosis coming to their first treatment in the study health care areas between January 1, 1997, and December 31, 2000. A total of 281 patients (76% of the total) gave informed consent. INTERVENTIONS: The ED and No-ED health care areas offered an equivalent assessment and treatment program for first-episode psychosis. The ED area also carried out an intensive ED program. RESULTS: The DUP was significantly shorter for the group of patients coming from the ED area, compared with patients from the No-ED areas (median, 5 weeks [range, 0-1196 weeks] vs 16 weeks [range, 0-966 weeks]). Clinical status measured by the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale was significantly better for patients from the ED area at start of treatment and, with the exception of Positive and Negative Syndrome Scale positive subscale, at 3 months. Multiple linear regression analyses gave no indication that confounders were responsible for these differences. CONCLUSIONS: It is possible to reduce the DUP through an ED program. The reduction in DUP is associated with better clinical status at baseline that is maintained after 3 months.     

Insulin stimulated glucose disposal in peripheral tissues studied with microdialysis and stable isotope tracers

BACKGROUND & AIMS: Methods to study glucose kinetics in vivo in specific tissues or tissue beds in humans are often not feasible due to invasiveness or costs of equipment needed. Here we investigate whether the loss (fractional extraction) of 2H7-glucose infused via a microdialysis catheter can be used to study glucose disposal in skeletal muscle and subcutaneous adipose tissue. METHODS AND RESULTS: A perfusion period of 2 h was needed to ensure an isotopic steady state in the microdialysis catheters in skeletal muscle and adipose tissue. In six healthy volunteers the fractional extraction increased during a hyperinsulinemic euglycemic clamp in both skeletal muscle and adipose tissue. Following 48 h of starvation in the same subjects, insulin was not able to increase the fractional extraction of 2H7-glucose from the microdialysis in comparison with a baseline measurement. CONCLUSIONS: In response to insulin infusion, the fractional extraction of 2H7-glucose from a microdialysis catheter increases in skeletal muscle and subcutaneous adipose tissue and this increase is blunted during insulin resistance induced by starvation. These results validate that the fractional extraction of a glucose tracers infused via microdialysis can be used as an index of glucose disposal in peripheral tissues or tissue beds.     

Spinal substance P release in vivo during the induction of long-term potentiation in dorsal horn neurons

Long-term potentiation (LTP) in wide dynamic range (WDR) neurons in the dorsal horn has been suggested to contribute to central sensitization and the development of chronic pain. Indirect experimental evidence indicates an involvement of substance P (SP), in this respect. The aim of the present study was to monitor the extracellular level of substance P-like immunoreactivity (SP-LI) in the dorsal horn of the rat during and after induction of LTP in WDR neurons in vivo. Electrophysiological recordings of single (WDR) neurons were performed in parallel with microdialysis in the dorsal horn under urethane-anaesthesia. The amount of SP-LI in the microdialysate was determined by radioimmunoassay. As previously shown, high frequency conditioning stimulation of the sciatic nerve induced an increased firing response of WDR neurons. An increased response to C-fibre stimulation, but not A-fibre stimulation, could be determined. A significant increase of the extracellular level of SP-LI in the dorsal horn was detected during, but not after, induction of LTP. These data suggest that SP may be involved in the induction of LTP by high frequency stimulation. However, the maintenance of spinal LTP following high frequency peripheral nerve stimulation does not seem to depend on an increased release of SP.     

Post systolic shortening in nonobstructive hypertrophic cardiomyopathy with delayed emptying of the apex: a Doppler flow,tissue Doppler and strain rate imaging case study

We report a case of a 92-year-old woman with syncope and exertional dyspnea, who on echocardiographic examination proved to have hypertrophic cardiomyopathy. Doppler flow revealed delayed emptying of the apex, extending into the early filling phase. Tissue Doppler and strain rate imaging illustrated postsystolic shortening corresponding to the apical ejection, demonstrating that the apical flow was due to wall thickening resulting in active ejection. The imaging methods and mechanics of post-systolic shortening are discussed.     

Low levels of mannose-binding lectin do not affect occurrence of severe infections or duration of fever in acute myeloid leukaemia during remission induction therapy

PURPOSE: To estimate the clinical significance of low serum concentrations of mannose-binding lectin (MBL) in patients with acute myeloid leukaemia (AML) during initial cancer chemotherapy. PATIENTS AND METHODS: 80 consecutive, newly diagnosed, and unselected AML patients (age 18-77 yr) undergoing remission induction chemotherapy. The patients were examined for 28 d. MAIN FINDINGS: Low levels of serum MBL (<1,000 microg/L) were found in 16/80 patients at diagnosis. This frequency is similar to what is found in the general population. In the remaining 64 patients, MBL concentrations were significantly higher than in controls and showed only a slight rise during the period of antineoplastic chemotherapy with its associated infectious complications. Low levels of MBL did not affect overall survival or morbidity in terms of incidence or duration of fever, or occurrence of septicaemia or pneumonia. Long-term survival was likewise independent of MBL concentration. CONCLUSION: MBL levels have no discernible influence on the occurrence or course of infections in AML patients during the initial hospitalisation. The predominant immunodeficiency during this phase is the profound granulocytopenia, which also compromises important effector functions of MBL. The finding in most AML patients of elevated MBL concentrations on admission is most likely because of the role of MBL as an acute phase reactant.     

Reduced mortality in treating acutely sick,frail older patients in a geriatric evaluation and management unit. A prospective randomized trial

OBJECTIVES: Documentation of treatment effects in acutely sick frail older patients in geriatric evaluation and management units (GEMUs) is scarce. The present study evaluated whether treatment in a GEMU would reduce mortality as compared to traditional treatment delivered in the Department of Internal Medicine. DESIGN: Prospective randomized trial. SETTING: GEMU or general medical ward. PARTICIPANTS: Acutely sick frail patients aged 75 and older who had been admitted to the Department of Internal Medicine were randomly assigned to treatment in the GEMU (n = 127) or to the general medical wards (n = 127). The following inclusion criteria were used to target frail patients: chronic disability, acute impairment of single activity of daily living, mild/moderate dementia, confusion, depression, imbalance/dizziness, falls, impaired mobility, urinary incontinence, malnutrition, polypharmacy, vision or hearing impairment, social problems, or prolonged bedrest. INTERVENTION: In the GEMU, the treatment strategy emphasized interdisciplinary assessment of all relevant disorders, prevention of complications and iatrogenic conditions, early mobilization/rehabilitation, and comprehensive discharge planning. The control group received treatment as usual from the Department of Internal Medicine. After discharge neither group received specific follow-up. MEASUREMENTS: Mortality and causes of death. RESULTS: Mortality in the intervention and control groups, respectively, was 12% and 27% at 3 months (P =.004), 16% and 29% (P =.02) at 6 months, and 28% and 34% (P =.06) at 12 months. The hazard ratio was 0.39 (95% confidence interval = 0.21-0.72) at 3 months. The main cause of death was cardiovascular disease. CONCLUSION: Treatment of acutely sick, frail, older patients in a GEMU substantially reduced mortality.     

Comparison of procedures for evaluating laboratory performance in external quality assessment schemes for lead in blood and aluminum in serum demonstrates the need for common quality specifications

BACKGROUND: The different scoring methods used by eight European External Quality Assessment Schemes (EQASs) for occupational and environmental laboratory medicine were compared to develop suitable quality specifications as a step toward harmonization. METHODS: Real results for blood lead and serum aluminum assays, reported by participants in Italian and United Kingdom EQASs, were evaluated according to individual scheme scoring criteria. The same results were then used to produce z scores using scheme-based between-laboratory SDs as the estimate of variability to determine whether simple performance-derived quality specifications produced better agreement among schemes. RESULTS: The schemes gave conflicting assessments of participants' performance, and participants judged to be successful by one scheme could be defined as performing inadequately by another. An approach proposed by Kenny et al. (Scand J Clin Lab Invest 1999;59:585), which uses clinical inputs to set targets for analytical imprecision, bias, and total error allowable, was then used to elaborate quality specifications. CONCLUSIONS: We suggest that the CLIA '88 recommendations for blood lead (+/- 40 micro g/L or +/- 10% of the target concentration, whichever is the greater) could be used as a quality specification, although a revision to +/- 30 micro g/L or +/- 10% is recommended. For serum aluminum, a suitable quality specification of +/- 5 micro g/L or +/- 20% of the target concentration, whichever is the greater, is suggested. These specifications may be used to compare laboratory performance across schemes.     

Successful open reduction of a 5-month-old hip dislocation associated with a femoral head fracture

The long-term prognosis after open reduction of neglected posterior hip dislocations is poor; as such, primary arthroplasty is recommended by a number of authors. We present a patient with a 5-month-old posterior hip dislocation with concomitant paralysis of the sciatic nerve who had an open reduction. At a follow-up of 3.5 years, the patient has normal function with no signs of arthrosis. Magnetic resonance imaging scans, however, revealed partial avascular necrosis of the femoral head. A discussion based on the literature shows the uniqueness of this case.     

Brachytherapy for prostate cancer: a systematic review of clinical and cost effectiveness

OBJECTIVES: Brachytherapy is emerging as a new treatment option for prostate cancer, and is increasingly being used in Europe and North America. METHODS: A systematic review of studies that compared clinical or cost effectiveness of prostate brachytherapy with radical prostatectomy or external beam radiation for patients with localised prostate cancer. RESULTS: No randomised controlled trials were identified, but five observational studies with comparable patient groups were included in the review. There were no valid data on overall or disease-free survival. There was no difference in disease-free survival based on PSA as a surrogate measure, or in rates of complications. No cost effectiveness studies were found. Based on Norwegian data, the one-year cost of the three treatment options seem fairly similar, while long term cost data are lacking due to lack of data on long term clinical outcome. CONCLUSION: The evidence on the clinical effectiveness of therapies for localised prostate cancer is scarce, but the outcome appears to be comparable for radical prostatectomy, external beam radiotherapy and brachytherapy.