Antipsychotic prescribing practices in Connecticut's public mental health system: rates of changing medications and prescribing styles

We characterized prescribing in Connecticut's State public mental health system to assess the feasibility of implementing an evidence-based medication algorithm. Medication records for a random sample of outpatients with diagnoses of schizophrenia spectrum disorders showed prescribing patterns similar to the entire United States. The base rate of changing antipsychotic medications was moderate. Over half of patients received decanoate medications, polypharmacy was nontrivial, and there was variability in prescribing patterns across physicians. Caucasian patients were more likely to receive an atypical antipsychotic and less likely to have a decanoate medication, and Latino patients were less likely to change medications. Because the base rate of changing medications was moderate and a considerable proportion of patients were prescribed newer antipsychotic medications, introducing a research-derived medication algorithm with newer atypical antipsychotics as first line agents may fit well with current practice. Further, implementing such an algorithm may reduce racial and ethnic disparities in prescribing patterns.     

Grafting assay distinguishes promotion sensitive from promotion resistant JB6 cells

The JB6 mouse epidermal cell system has been used extensively as an in vitro transformation model for the study of tumor promotion. The standard JB6 cell assay for promotion of transformation is carried out in soft agar or other anchorage independent conditions. The present study was directed to the development of an in vivo model to distinguish the promotion resistant (P-) and promotion sensitive (P+) progression phenotypes. Results indicate that the grafting assay distinguishes P- and P+ cells in vivo with P+ but not P- cells forming tumors within 7-9 weeks. Expression of dominant negative mutant jun TAM67 blocks both anchorage independent transformation response and graft bed tumor formation by P+ cells, suggesting that the requirement for AP-1 activation in transformation now applies in vivo. Expression of mutated p53 produced a gain of P+ phenotype in P- cells in vitro, but not in vivo. Histochemical and Northern blot analysis for expression of various keratinocyte markers revealed no evidence for expression, suggesting a loss of keratinocyte markers following establishment in culture. In summary, the skin-grafting assay described in this study appears to be a valid in vivo assay for distinguishing the preneoplastic progression phenotypes represented by JB6 P- and P+ cells.      

Fiber orientation in hypertrophied canine left ventricle.

Myocardial fiber orientation was examined in transmural specimens obtained at the maximum diameter of the left ventricle from five dogs with pressure-overload hypertrophy produced by aortic stenosis, six dogs with volume-overload hypertrophy due to an arteriovenous fistula, and six exercise-hypertrophied greyhounds trained for racing. Hearts arrested in diastole were fixed in situ while the operating end-diastolic pressure was maintained. Fiber orientation changed smoothly from about +60 degrees (with respect to the equator) at the endocardium to about -69 degrees at the epicardium. The majority of fibers near the midwall were oriented circumferentially. These findings are quite similar to those previously reported for normal dogs. In comparison to normals, the left ventricles from dogs with pressure-overload had an increase in longitudinally oriented fibers, i.e. fiber angles between -67.5 degrees and -90 degrees and between +67.5 degrees and +90 degrees; these fibers comprised 10.4 +/- 1.8% of the total fibers in dogs with aortic stenosis vs. 2.9 +/- 1.8% of total fibers in normal dogs (P less than 0.001). Neither the dogs with volume-overload hypertrophy nor exercise-trained animals were significantly different from normals.     

Differential effectiveness of clozapine for patients nonresponsive to or intolerant of first generation antipsychotic medications

This report examines whether the gains associated with changing to clozapine are greater for people who have been intolerant of first generation antipsychotic medications versus those who have been treatment-nonresponsive to previous agents. We examined data from an open-label, randomized trial that compared clozapine to usual care with first generation agents (n = 227). While most patients (n = 173, 76%) entered that study because they were nonresponsive to at least two first generation antipsychotic medications (treatment nonresponsive [TNR]), 24 percent (n = 54) were eligible because they experienced intolerable side effects (treatment intolerant [TI]). Significantly more TI patients discontinued their clozapine trial during the 2-year study compared to TNR patients, and TI patients taking clozapine were more likely to develop agranulocytosis or severe leukopenia. However, TI patients who remained on clozapine showed significant reductions in problematic behaviors and greater movement toward independent living situations than TNR patients. Clinicians should give serious consideration to offering clozapine and other second generation antipsychotic medications to patients who have demonstrated intolerance to first generation antipsychotic medications.     

Establishing connections between microarray expression data and chemotherapeutic cancer pharmacology

We have investigated three different microarray datasets of approximately 6 K gene expressions across the National Cancer Institute's panel of 60 tumor cell lines. Initial assessments of reproducibility for gene expressions within each dataset, as derived from sequence analysis of full-length sequences as well as expressed sequence tags (EST), found statistically significant results for no more than 36% of those cases where at least one replicate of a gene appears on the array. Filtering the data based only on pairwise comparisons among these three datasets creates a list of approximately 400 significant concordant expression patterns. The expression profiles of these smaller sets of genes were used to locate similar expression profiles of synthetic agents screened against these same 60 tumor cell lines. A correspondence was found between mRNA expression patterns and 50% growth inhibition response patterns of screened agents for 11 cases that were subsequently verifiable from ligand-target crystallographic data. Notable amongst these cases are genes encoding a variety of kinases, which were also found to be targets of small drug-like molecules within the database of protein structures. These 11 cases lend support to the premise that similarities between expression patterns and chemical responses for the National Cancer Institute's tumor panel can be related to known cases of molecular structure and putative cellular function. The details of the 11 verifiable cases and the concordant gene subsets are provided. Discussions about the prospects of using this approach as a data mining tool are included.     

Effects of aging on event-related neural activity related to prospective memory

The neural foundation of age-related declines in prospective memory was explored using event-related brain potentials (ERPs). Consistent with previous research, a decline in the efficiency of prospective memory was observed in older adults that reflected a decrease in veridical prospective responses and an increase in false prospective responses. The neurophysiological data revealed an age-related reduction in the amplitude of modulations of the ERPs related to prospective remembering, but not visual information processing, and are consistent with the hypothesis that a reduction in the efficiency of a frontally mediated neural system contributes to prospective memory failure in older adults.     

北京崇文区中老年原发性骨质疏松症的发生及其影响因素：分层多阶段整群抽样调查

目的:了解北京市崇文区中老年人原发性骨质疏松症患病情况及其影响因素。方法:①调查对象:选择1998-06/09居住在北京市崇文区具有正式户口的常住男女人群,按照分层多阶段整群抽样方法抽取年龄在40～85岁中老年人为调查对象。②实验方法和评估指标:骨密度测量采用双能X线骨密度测定仪测量308名中老年人腰椎(L2～L4)前后位及股骨上端的骨股颈、三角区(Ward's)和大粗隆的骨密度;问卷调查分为一般情况、月经和生育史、药物应用史、饮食习惯和体格检查情况。结果:308名中老年人接受调查,其中男140名,女168名。年龄40～85岁,平均(60.80±10.12)岁。①各年龄段不同性别中老年人腰椎和股骨上端骨密度测量结果:大粗隆、骨股颈和三角区骨密度无论男女均随着年龄的增长有下降趋势。②各年龄段不同性别中老年人原发性骨质疏松症患病率情况:腰椎、大粗隆和三角区部位的患病率女性高于男性,股骨颈部位的患病率男性高于女性。男性以股骨颈原发性骨质疏松症检出率最高,女性以三角区检出率最高。原发性骨质疏松症患病率随着年龄的增加有增高的趋势。③Ward's三角区骨密度单因素分析:年龄、绝经后年限、生育次数与Ward's三角区骨密度呈负相关(P<0.05);居住环境采光条件、每周蛋类摄入量、身高和体质量与Ward's三角区骨密度呈正相关(P<0.05)。男性和女性、服用钙剂组和未服用钙剂组、服用避孕药物组和未服用避孕药物组、受背痛困扰组和未受背痛困扰之间差异有显著性(P<0.05)。④Ward's三角区骨密度多因素分析:年龄、体质量、绝经年限(女性)是引起骨密度降低的3个重要因素。结论:对于男性人群腰椎骨密度正常,但有明显骨质增生者应参考股骨上端骨密度方能作出正确评价。绝经后高龄妇女、低体质量的人群是原发性骨质疏松的高危人群。     

Distress with Medication Side Effects among Persons with Severe Mental Illness

We examined prevalence and perceived distress resulting from self-reported side effects (SEs) attributed to psychotropic medications among individuals with severe mental illness participating in a study of consumer-operated services. We examined gender and racial differences using logistic regression, conducted factor analyses of SEs, and examined correlations between distress and self-reported symptoms. Over 90% reported at least one SE, and nearly two-thirds reported a high level of distress with at least one SE. The most distressing SEs reported were embarrassment from weight gain, weight gain, dry mouth, and sedation. The likelihood of distress by particular SEs varied by gender and race. Preliminary results of this work were presented as a poster at the 44th annual meeting of the New Clinical Drug Evaluation Unit of the National Institute of Mental Health, Phoenix, AZ, 2004.