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Two similarly designed extension studies evaluated the long-term safety and tolerability of desvenlafaxine for the treatment of children and adolescents with major depressive disorder (MDD). Efficacy was evaluated as a secondary objective.
Both 6-month, open-label, flexible-dose extension studies enrolled children and adolescents who had completed one of two double-blind, placebo-controlled, lead-in studies. One lead-in study included a 1-week transition period prior to the extension study. Patients received 26-week treatment with flexible-dose desvenlafaxine (20–50 mg/d). Safety assessments included comprehensive psychiatric evaluations, vital sign assessments, laboratory evaluations, 12-lead electrocardiogram, physical examination with Tanner assessment, and Columbia-Suicide Severity Rating Scale. Adverse events (AEs) were collected throughout the studies. Efficacy was assessed using the Children’s Depression Rating Scale–Revised (CDRS-R).
A total of 552 patients enrolled (completion rates: 66.4 and 69.1%). AEs were reported by 79.4 and 79.1% of patients in the two studies; 8.9 and 5.2% discontinued due to AEs. Treatment-emergent suicidal ideation or behavior was reported for 16.6 and 14.1% of patients in the two studies. Mean (SD) CDRS-R total score decreased from 33.83 (11.93) and 30.92 (10.20) at the extension study baseline to 24.31 (7.48) and 24.92 (8.45), respectively, at week 26.
Desvenlafaxine 20 to 50 mg/d was generally safe and well tolerated with no new safety signals identified in children and adolescents with MDD who received up to 6 months of treatment in these studies. Patients maintained the reduction in severity of depressive symptoms observed in all treatment groups at the end of the lead-in study.
New collaborative care models with an emphasis on primary care are required for long-term management of patients with severe and enduring mental illness (SMI). We conducted a descriptive evaluation of clinical outcomes of the first 3 years of a novel enhanced primary care (EPC) service. Data from 2818 patients and staff survey results were analysed.
2310 patients were discharged to EPC (508 not assessed as clinically suitable or patients/general practitioners declined the transfer); mean length of stay with secondary care service of the cohort was 9.8 years (range 0–24). 717 patients (31%) have been discharged to primary care only out of the EPC services and 233 patients (10%) have been transferred back to secondary care. Patient and staff satisfaction with the new EPC model was high. No severe untoward incidents were recorded.
The data suggest that EPC can be safely provided for a significant proportion of patients with SMI, who traditionally received long-term secondary care support. The novel EPC model can be utilised as a template for the provision of cost-effective, recovery-oriented and non-stigmatising care in the community.
We consider the Bayesian over-dispersed Poisson (ODP) model for claims reserving in general insurance. We choose two different types of prior distributions for the parameters and then study the different Bayesian predictors. This study leads, on the one hand, to the classical chain ladder predictor and, on the other hand, to Bornhuetter & Ferguson predictors. We highlight (either analytically or numerically) how these predictors are obtained and how their prediction uncertainty can be determined.
Highly variable DNA polymorphisms called microsatellites are rapidly becoming the marker of choice in population genetic studies. Until now, microsatellites have not been utilized for Drosophila studies. We have identified eight polymorphic microsatellite loci in Drosophila melanogaster and used them to characterize the genetic variation in a wild population from the Tyrrell's winery in Australia. Microsatellites were isolated from a partial genomic DNA library. All microsatellites consist of (AC)n repeats ranging from n = 2 to n = 24. Six loci were assigned to chromosomal location by genetic mapping, with three loci on chromosome II, one locus on chromosome III and two loci on the X chromosome. Up to four microsatellite loci were multiplexed in the same reaction. Microsatellite variation is substantially greater than allozyme variation in the Tyrrell's Drosophila population. 80% of the microsatellite loci examined are polymorphic, compared with 28% of allozymes. The mean number of alleles per polymorphic locus is 5·2 in microsatellites compared with 30 in allozymes. The average observed heterozygosity of polymorphic microsatellites is 47% compared with 26% for allozymes. Microsatellite variation in Drosophila melanogaster is similar to that reported for other insects. Higher variability commends microsatellites over allozymes for genetic studies in Drosophila melanogaster.
Maps showing depth to the Moho, the 6 km/s and 7 km/s isovelocity surfaces and the thickness of the crust with a velocity greater than 7.0 km/s for the UK and surrounding continental crust have been generated from a compilation of wide-angle/refraction data. The data show that the crust beneath northwestern Scotland is thinner and of higher velocity than that beneath southern Britain. The lower crust beneath the East Irish Sea and parts of the southern North Sea is formed from thick layers of high velocity rock. The lateral extent of these layers cross-cuts the downward projection of major structures mapped at the surface. This suggests that the major structures do not bound regions of lower crust with contrasting properties at depth. Instead these structures may be overprinted by modification of the lower crust, for example, by magmatic underplating, which is not observed directly at the surface. Mapped variations in crustal thickness do not mirror the variations in surface topography, which appears to contradict the view that the crust is in Airy isostatic equilibrium.
This paper jointly models a landowner's decision to develop a parcel and the option to enroll that parcel in a current use assessment program. The analytical results highlight different factors that influence the effectiveness of a current use program in delaying development. The results also underscore the difficulty a local government might have in influencing the behavior of the landowner. Except for altering eligibility rules, a local government employing current use assessment has but two policy tools: a penalty for development and the property tax rate.
Single locus neutralist models predict that population size bottlenecks will reduce genetic variation and increase inbreeding, thereby reducing evolutionary potential. However, experimental evaluations of the effects of bottlenecks on quantitative genetic variation do not always follow predictions, especially for characters related to reproductive fitness. Populations of Drosophila melanogaster were subjected to population bottlenecks of a single pair for one or three generations, and their ability to tolerate increasing concentrations of NaCl was compared with those of their outbred base populations, and related highly inbred lines. Bottlenecked populations became extinct at significantly lower concentrations of NaCl than their non-bottlenecked base populations. Population bottlenecks should be avoided in managing species of conservation concern.
To investigate a cluster of cases of legionnaires' disease among patients at a hospital.
A university hospital that is a regional transplant center.
Retrospective review of microbiology and serology data from the hospital laboratories and prospective surveillance via the radiology department; a case-control study and environmental sampling within the hospital and from nearby cooling towers.
Diagnosis of seven cases of legionnaires' disease in the first 9 months of 1996 led to recognition of a nosocomial outbreak that may have begun as early as 1979. Review of charts from 1987 through September 1996 identified 25 culture-confirmed cases of nosocomial or possibly nosocomial legionnaires' disease, including 18 in bone marrow and heart transplant patients. Twelve patients (48%) died. During the first 9 months of 1996, the attack rate was 6% among cardiac and bone marrow transplant patients. For cases that occurred before 1996, intubation was associated with increased risk for disease. High-dose corticosteroid medication was strongly associated with the risk for disease, but other immunosuppressive therapy or cancer chemotherapy was not. Several species and serogroups of Legionella were isolated from numerous sites in the hospital's potable water system. Six of seven available clinical isolates were identical and were indistinguishable from environmental isolates by pulsed-field gel electrophoresis. Initial infection control measures failed to interrupt nosocomial acquisition of infection. After extensive modifications to the water system, closely monitored repeated hyperchlorinations, and reduction of patient exposures to aerosols, transmission was interrupted. No cases have been identified since September 1996.
Legionella can colonize hospital potable water systems for long periods of time, resulting in an ongoing risk for patients, especially those who are immunocompromised. In this hospital, nosocomial transmission possibly occurred for more than 17 years and was interrupted in 1996, after a sudden increase in incidence led to its recognition. Hospitals specializing in the care of immunocompromised patients (eg, transplant centers) should prioritize surveillance for cases of legionnaires' disease. Aggressive control measures can interrupt transmission of this disease successfully.