Mental health nurses can increase capability and capacity in primary care by educating practice nurses: an evaluation of an education programme in England.

Most people with a mental health problem in England are cared for by clinicians in primary care who may have had little or no training in this area. Our aim was to develop an accessible education programme which was appropriate to the learning needs of this workforce. A survey of the mental health and well-being training needs and preferred learning methods of practice nurses was undertaken, then a programme of education was developed by a primary care mental health expert. Teaching was delivered by mental health nurses who were trained as educators. Both the practice nurses and mental health nurses felt their clinical practice would improve as a result of being involved in this programme. To sustain the learning, mental health nurses were supported by attending and then leading their own action learning sets. This model of education can be adapted and used by health organizations both nationally and internationally. Research is required to find out whether training practice nurses using this programme has an impact on patients.

Pilot of BRAF mutation analysis in indeterminate, suspicious and malignant thyroid FNA cytology.

BACKGROUND: BRAF V600E mutation has been reported to show a high specificity for papillary thyroid carcinoma (PTC). Using this marker to upgrade 'indeterminate' or 'suspicious' thyroid fine needle aspiration (FNA) cytology to 'malignant' could potentially allow one-stage therapeutic total thyroidectomy. METHODS: For a 14-month period, FNA cytology specimens in the Thy3-5 categories, which are the UK equivalents of indeterminate (Thy3a, atypical; Thy3f, follicular), suspicious for malignancy (Thy4) and malignant (Thy5) in the Bethesda System, underwent BRAF mutation testing by melt curve analysis. The results were correlated with histology. RESULTS: We tested 123 cytology specimens of which 12 (9.8%) failed. The BRAF mutation rate in the remainder was 16.2% (18/111), with 93 showing the wild-type. Seventeen mutations were V600E and one was non-V600E. The rate of mutation increased significantly (P < 0.0001 if Thy3a and Thy3f were combined) with the cytology category: 1/42 Thy3a (2.4%), 1/36 Thy3f (2.8%), 4/15 Thy4 (26.7%), 12/18 Thy5 (66.7%). All BRAF mutations correlated with PTC on histology, except for one recurrent PTC without histology. One mutation-positive case with Thy3a cytology showed the target lesion to be a 10-mm follicular adenoma on histology with an immediately adjacent 4-mm micro-PTC, in a patient who did not require total thyroidectomy. CONCLUSION: BRAF mutational analysis by melt curve analysis is feasible in routine thyroid cytology, and in our series had a 100% specificity for PTC in subsequent histology. The application of BRAF analysis could be useful for indeterminate cytology, but we suggest that it would be most appropriate and cost-effective for Thy4/suspicious cases, for which it could enable one-stage therapeutic surgery in the context of multidisciplinary discussion. In contrast, the sensitivity is low and there is no role for avoiding diagnostic thyroid surgery if wild-type BRAF is found.

Comparison of five clustering algorithms to classify phytoplankton from flow cytometry data.

BACKGROUND: Artificial neural networks (ANNs) have been shown to be valuable in the analysis of analytical flow cytometric (AFC) data in aquatic ecology. Automated extraction of clusters is an important first stage in deriving ANN training data from field samples, but AFC data pose a number of challenges for many types of clustering algorithm. The fuzzy k-means algorithm recently has been extended to address nonspherical clusters with the use of scatter matrices. Four variants were proposed, each optimizing a different measure of clustering "goodness." METHODS: With AFC data obtained from marine phytoplankton species in culture, the four fuzzy k-means algorithm variants were compared with each other and with another multivariate clustering algorithm based on critical distances currently used in flow cytometry. RESULTS: One of the algorithm variants (adaptive distances, also known as the Gustafson--Kessel algorithm) was found to be robust and reliable, whereas the others showed various problems. CONCLUSIONS: The adaptive distances algorithm was superior in use to the clustering algorithms against which it was tested, but the problem of automatic determination of the number of clusters remains to be addressed.

A double-blind, placebo-controlled trial of nefazodone in the treatment of patients hospitalized for major depression.

BACKGROUND: There are few published placebo-controlled clinical trials demonstrating the efficacy of the newer antidepressants in markedly or severely depressed hospitalized patients. This study demonstrates the efficacy of nefazodone compared with placebo in the treatment of patients hospitalized for major depression. METHOD: Nefazodone and placebo treatment were compared in a 6-week trial of 120 patients hospitalized for DSM-III-R diagnosed major depression (without psychosis) at 2 study centers. Efficacy was evaluated using standard psychiatric rating scales, and patients were monitored for safety. RESULTS: Nefazodone treatment resulted in a significant reduction (p < .01) of the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score compared with placebo from the end of the first treatment week through the end of the study (-12.2 nefazodone vs. -7.7 placebo). At the end of the trial, significantly more nefazodone-treated patients (50%) than placebo-treated patients (29%) had responded, as indicated by their Clinical Global Impressions-Improvement score (p = .021) or by a > or = 50% reduction in their HAM-D-17 scores (p = .017). Significantly more patients treated with nefazodone (36%) than placebo-treated patients (14%) had a HAM-D-17 score < or = 10 at the end of treatment (p = .004). Significant treatment differences (p < .01) in favor of nefazodone were also seen in the Montgomery-Asberg Depression Rating Scale; the HAM-D retardation, anxiety, and sleep disturbance factors; and HAM-D item 1 (depressed mood). Patients with dysthymia in addition to major depression also showed significant improvement (p < .05) when treated with nefazodone, with significant differences in response rates seen as early as week 2 and through the end of the trial. The mean nefazodone dose was 491 mg/day at the end of week 2 and 503 mg/day at the end of treatment. Nefazodone was well tolerated, and the number of patients discontinuing owing to adverse events was small, with no significant safety issues noted in either treatment group. Fewer nefazodone-treated than placebo-treated patients discontinued owing to lack of efficacy. CONCLUSION: Nefazodone was superior to placebo in the treatment of marked to severe major depression in patients requiring hospitalization. The clinical benefit of nefazodone was evident as early as the first week of treatment as judged by several measures of efficacy, with significant differences from placebo sustained throughout the trial.

Survey of the diet of Pima Indians using quantitative food frequency assessment and 24-hour recall. Diabetic Renal Disease Study.

OBJECTIVE: A dietary survey was conducted in the Gila River Indian Community in Arizona using two methods of dietary assessment--24-hour recall and quantitative food frequency (QFF) assessment--to determine the usual intake of the population. DESIGN: Interviews were conducted by Pima women who were trained and monitored by a research dietitian. Energy and nutrient intake were calculated using a computerized dietary database that included specific Pima foods. SUBJECTS: An age- and sex-stratified sample of 575 Pima Indians (273 men, 302 women) aged 18 to 74 years participated in the study. STATISTICAL ANALYSES: Spearman correlations were used to compare the results of the two survey methods for energy and each nutrient. Intraclass correlations were used to measure reproducibility. RESULTS: According to the 24-hour recall, mean reported energy intakes within decades of age were 95% to 112% of those in the US population for Pima women, and 76% to 94% of those in the US population for Pima men. Total energy intake assessed using QFF was 30% higher in men and 33% higher in women than the intake assessed using the 24-hour recall method. CONCLUSIONS: A large dietary survey conducted using lay interviewers in a Native-American community was as reproducible as studies conducted in the general US population. The Pima diet was distributed among the major nutrients in a proportion similar to the US diet.

Therapeutic dose range of nefazodone in the treatment of major depression.

The therapeutic dose range of nefazodone for treatment of major depression was examined in a series of placebo-controlled efficacy studies carried out during phase 2 and 3 premarketing clinical evaluation. Nefazodone is a new antidepressant drug with pharmacologic effects on both serotonin and norepinephrine neurotransmitters. The usual starting dose of nefazodone for depressed patients, unless they are being switched from a serotonin selective reuptake inhibitor (SSRI), is 100 mg. b.i.d. A lower starting dose is recommended for elderly patients or patients being treated with an SSRI. Following assessment of the patient's clinical response after the first week of therapy, the daily dose should be adjusted upward for most patients. In the efficacy studies, the majority of patients were being maintained on a dose of 300 to 500 mg daily at the end of the acute treatment period. The side effects of nefazodone most often related to dosage were sedation, nausea, and visual symptoms. Imipramine-treated patients, on the other hand, had a high incidence of dry mouth, constipation, and asthenia. In these studies, nefazodone was found to be effective and well tolerated by patients, the majority of whom were being maintained at a 300- to 500-mg/day dose, following an initial starting dose of 100 mg b.i.d.

Intravenous sotalol for the termination of supraventricular tachycardia and atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled study. Sotalol Multicenter Study Group.

Sotalol is an antiarrhythmic agent with combined beta-blocking and class III antiarrhythmic properties. This study was designed to assess the safety and efficacy of sotalol in terminating supraventricular tachycardia (SVT), atrial fibrillation (AFib), and atrial flutter (AFl). Ninety-three patients with spontaneous or induced SVT (n = 45) or AF (AFib or AFl; n = 48) with a ventricular rate of > or = 120 beats/min were studied. In the first phase, the double-blind phase, patients were randomly assigned to receive placebo or intravenous (i.v.) sotalol, 1.0 or 1.5 mg/kg. If SVT or AF did not convert to sinus rhythm or if the ventricular rate did not slow to < 100 beats/min within 30 minutes, patients then entered the second phase, the open-label phase, which also lasted 30 minutes, and were given 1.5 mg/kg iv sotalol. In the SVT group, during the double-blind phase conversion to sinus rhythm occurred in 2 (14%) of 14 of patients who received placebo, 10 (67%) of 15 who received sotalol, 1.0 mg/kg (p < 0.05 vs placebo), and 10 (67%) of 15 who received 1.5 mg/kg sotalol (p < 0.05 vs placebo); during the open-label phase, 1.5 mg/kg i.v. sotalol converted 7 (41%) of 17 of patients. In the AF group, during the double-blind phase conversion to sinus rhythm occurred in 2 (14%) of 14 of patients who received placebo, 2 (11%) of 18 who received 1.0 mg/kg sotalol (p not significant [NS] vs placebo), and 2 (13%) of 16 who received 1.5 mg/kg sotalol (p = NS vs placebo); in these groups, a > 20% reduction of ventricular rate without conversion to sinus rhythm occurred in 0 (0%) of 14, 13 (72%) of 18 (p < 0.05 vs placebo), and 12 (75%) of 16 of patients (p < 0.05 vs placebo), respectively; during the open-label phase, 1.5 mg/kg i.v. sotalol converted 7 (30%) of 23 of patients. The most common adverse events were hypotension and dyspnea. During the double-blind phase they occurred in 10% of patients who received placebo, 9% of those who received 1.0 mg/kg i.v. sotalol (p = NS vs placebo), and 10% of those who received 1.5 mg/kg i.v. sotalol (p = NS vs placebo). Most of these events were mild to moderate, but all were transient and clinically manageable.(ABSTRACT TRUNCATED AT 400 WORDS)

Glomerular function in Pima Indians with noninsulin-dependent diabetes mellitus of recent onset.

Differential solute clearances were used to characterize glomerular function in 20 Pima Indians with noninsulin-dependent diabetes mellitus (NIDDM) of less than 3 yr duration. 28 Pima Indians with normal glucose tolerance served as controls. In the diabetic group, the glomerular filtration rate (GFR, iothalamate clearance) exceeded the control value by 15% (140 +/- 6 vs. 122 +/- 5 ml/min, P less than 0.01). A corresponding 12% increase in renal plasma flow (RPF) was not statistically significant and did not account fully for the observed hyperfiltration, suggesting a concomitant elevation of the ultrafiltration pressure or coefficient. The median albumin excretion ratio in NIDDM exceeded control by almost twofold (10.1 vs. 5.8 mg/g creatinine), a trend which just failed to achieve statistical significance (P = 0.06). Fractional clearances of dextrans of broad size distribution were also elevated in diabetic subjects, significantly so for larger dextrans of between 48 and 60 A radius. A theoretical analysis of dextran transport through a heteroporous membrane revealed glomerular pores in NIDDM to be uniformly shifted towards pores of larger size than in controls. We conclude that an impairment of barrier size selectivity combined with high GFR elevates the filtered protein load in NIDDM of recent onset. We propose that enhanced transglomerular trafficking of protein may predispose to sclerosis of glomeruli in those Pima Indians with NIDDM who ultimately develop diabetic nephropathy.