Importance of open access to atypical antipsychotics for the treatment of schizophrenia and bipolar disorder: a European perspective.

OBJECTIVE: To assess European psychiatrists' prescribing behaviour and their perceived need for access to a wide range of atypical antipsychotics for patients with schizophrenia and bipolar disorder. METHODS: A blinded, internet survey of psychiatrists from the UK, Germany, Italy and the Netherlands occurred in 2007. Key inclusion criteria for psychiatrists: practising full time; practising for 5-35 years; prescribed atypical antipsychotics in prior 6 months to > or =20 patients with schizophrenia or bipolar disorder. Eligible psychiatrists selected records for four patients with schizophrenia or bipolar disorder for whom they prescribed > or =1 atypical antipsychotic since January 2004. RESULTS: Survey response rates were: UK, 14.8% (n = 107); Germany, 9.6% (n = 104); Italy, 8.9% (n = 101) and the Netherlands, 3.7% (n = 51); 363 psychiatrists reported on 1442 patients. Psychiatrists perceived a greater difference among atypical antipsychotics as a class (mean, 5.1 on a 7-point scale [7 = 'highly differentiated']) but not selective serotonin reuptake inhibitors (mean, 3.6). On average, psychiatrists used 6.8 different atypical antipsychotics across their patients with schizophrenia and 4.4 across their patients with bipolar disorder, with 2.5 and 2.4 changes required following first-line treatment to stabilise therapy, respectively. The most common reason for switching medication was lack of efficacy. Psychiatrists reported that expected consequences for patients should access to atypical antipsychotics be restricted would include illness deterioration, non-adherence and hospitalisation. CONCLUSIONS: Although this study is limited by potential selection biases, these data suggest that European psychiatrists tailor antipsychotic medications for patients with schizophrenia or bipolar disorder according to patients' needs and specific drug attributes.

Different approaches to valuing the lost productivity of patients with migraine.

OBJECTIVE: To calculate and compare the human capital approach (HCA) and friction cost approach (FCA) methods for estimating the cost of lost productivity of migraineurs after the initiation of sumatriptan from a US societal perspective. DESIGN: Secondary, retrospective analysis to a prospective observational study. SETTING: A mixed-model managed care organisation in western Pennsylvania, USA. PATIENTS: Patients with migraine using sumatriptan therapy. INTERVENTIONS: Patient-reported questionnaires collected at baseline, 3 and 6 months after initiation of sumatriptan therapy. OUTCOME MEASURES: The cost of lost productivity estimated with the HCA and FCA methods. RESULTS: Of the 178 patients who completed the study, 51% were full-time employees, 13% were part-time, 18% were not working and 17% changed work status. Twenty-four percent reported a clerical or administrative position. From the HCA, the estimated total cost of lost productivity for 6 months following the initiation of sumatriptan was $US117905 (1996 values). From the FCA, the six-month estimated total cost of lost productivity ranged from $US28329 to $US117905 (1996 values). CONCLUSIONS: This was the first study to retrospectively estimate lost productivity of patients with migraine using the FCA methodology. Our results demonstrate that depending on the assumptions and illustrations employed, the FCA can yield lost productivity estimates that vary greatly as a percentage of the HCA estimate. Prospective investigations are needed to better determine the components and the nature of the lost productivity for chronic episodic diseases such as migraine headache.

Effects of the dietary phytoestrogens daidzein and genistein on the incidence of vulvar carcinomas in 129/J mice.

The objective of this study was to determine the effect of dietary phytoestrogens on the incidence of spontaneous vulvar carcinomas in 129/J mice using three natural ingredient diets and two purified diets containing predetermined levels of daidzein and genistein. Eighty weanling female mice without clinical evidence of vulvar carcinomas were randomly assigned 16 per diet to each of 5 test diets. Mice were clinically examined for vulvar masses weekly for 3 months and at monthly intervals thereafter. Vulvar carcinomas in representative groups of mice were confirmed using routine histological procedures. The incidence of vulvar carcinomas increased sharply in mice on all test diets during the first 2 months with minor changes during the remainder of the study. Within one month, the incidence of vulvar carcinomas in mice fed the AIN-76A modified soy protein diet was significantly (P < .05) increased over those of mice fed the AIN-76A modified casein diet, the #5K96, or the # 5058 diet. At three months, the incidence of vulvar carcinomas in mice fed the soy protein diet was significantly (P < .05) increased over those of mice fed the NIH-31 diet or the PMI #5K96 diet. There was a marginally significant (P < .10) correlation between the total daidzein and genistein levels in the five test diets and the incidence of vulvar carcinomas in mice as determined by clinical examination. We concluded that dietary levels of daidzein and genistein were associated with an increase in the incidence of vulvar carcinomas in mice and that the 129/J mouse may provide an animal model for studying the development of vulvar carcinomas.

Phytoestrogen content of purified, open- and closed-formula laboratory animal diets.

BACKGROUND AND PURPOSE: Phytoestrogens exert estrogenic effects on the central nervous system, induce estrus, and stimulate growth of the genital tract of female animals. Over 300 plants and plant products, including some used in laboratory animal diets, contain phytoestrogens. Therefore, the source and concentration of phytoestrogens in rodent diets were determined. METHODS: Twelve rodent diets and six major dietary ingredients were assayed for phytoestrogens (daidzein, genistein, formononetin, biochanin A, and coumestrol), using high-performance liquid chromatography. Three rodent diets recently formulated to reduce phytoestrogen content also were assayed. RESULTS: Formononetin, biochanin A, and coumestrol were not detected. Soybean meal was the major source of daidzein and genistein; their concentrations were directly correlated to the percentage of soybean meal in each diet. CONCLUSIONS: High, variable concentrations of daidzein and genistein are present in some rodent diets, and dietary phytoestrogens have the potential to alter results of studies of estrogenicity. Careful attention should be given to diet phytoestrogen content, and their concentration should be reported. A standardized, open-formula diet in which estrogenic substances have been reduced to levels that do not alter results of studies that are influenced by exogenous estrogens is recommended.

Efficacy of various therapeutic regimens in eliminating Pasteurella pneumotropica from the mouse.

Pasteurella pneumotropica, a gram-negative opportunistic pathogen, can be isolated from the oropharynx, intestinal tract, and reproductive tract of clinically normal mice and has been associated with various clinical syndromes, including conjunctivitis, infections of the reproductive tract, otitis, and subcutaneous abscess formation. Enrofloxacin, a fluoroquinolone bactericidal antimicrobial, has been shown to be effective in eliminating P. multocida from rabbits. We sought to determine whether enrofloxacin would eliminate P. pneumotropica from mice known to be asymptomatically infected with the agent. Pasteurella pneumotropica-positive (culture and immunofluorescence assay) male (n = 55) and female (n = 55) C57BL/6N mice were randomly assigned to one of seven treatment groups or to a control group. These groups were designed to evaluate the efficacy of enrofloxacin administered orally via the drinking water or parenterally at three dosages (8.5, 25.5, and 85.0 mg/kg of body weight per day) over a 14-day treatment period. A tetracycline-treated group (60 mg/kg per day) and an untreated control group were included for comparisons. Repeated oropharyngeal swab and fecal specimens were obtained for culture through posttreatment day 30, and specimens from numerous enteric and reproductive organs collected during necropsy were used to evaluate group differences. Enrofloxacin eliminated evidence of P. pneumotropica from all sites when administered at 25.5 or 85 mg/kg but not at 8.5 mg/kg by either route for at least 30 days after treatment. Tetracycline-treated and control groups remained consistently culture-positive throughout the study. We concluded that the oral route may be a more practical method for treating large numbers of mice. Enrofloxacin may be a practical and inexpensive alternative to cesarian rederivation or embryo transfer for the elimination of P. pneumotropica in mice.

A standard procedure for measuring pellet hardness of rodent diets.

A Chatillon Model TCM-200 test stand with exchangeable flat horizontal or concave receptacle bases and a DFI-200 gauge load cell with multiple types of upper exchangeable test jaws (large round-flat, medium round-flat, chisel, bullet, and cone-shaped) were compared by using preautoclaved and autoclaved NIH-31 rodent diet pellets to determine which type of hardness testing system would give the most accurate and reproducible results for measuring pellet hardness. The type and size of the contact area of the upper jaws significantly affected the force required to break the pellets. Significant differences were observed between the flat-horizontal and concave receptacle bases in the force required to break the pellets when using the two round-flat upper jaws. In contrast, similar results were obtained with both bases when the bullet, chisel, or cone-shaped upper jaws were used. Autoclaved pellets were 69.4% (range, 49 to 94%) harder than preautoclaved pellets. These results suggest that different testing systems can be used for measuring pellet hardness and that a standard procedure must be used in order to compare pellet hardness results between different testing laboratories. It was concluded that the flat-horizontal base and the larger round-flat end upper jaw gave the most reproducible results for measuring pellet hardness.