The economics of medical therapy for lower urinary tract symptoms associated with benign prostatic hyperplasia

Medical therapy is currently the most popular treatment choice for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Because medical therapy of BPH-related LUTS is considered a life-long strategy, short- and long-term cost considerations should play a major role in therapeutic decision-making. The effectiveness in terms of long and short amelioration of symptoms, flow rate, and quality of life are well documented for 5α-blockers and 5α-reductase inhibitors as well as for the gold standard treatment for BPH, transurethral resection of the prostate and minimally invasive therapies. Short-and long-term safety concerns also are well documented for these various treatment options. On the contrary, short- and long-term costs have been less well studied and comparisons depend on the model or analyses undertaken in the few studies available. However, the economic studies based on prospective clinical trial data that have become available throughout the past several decades allow us to rationalize our use of α-blockers, 5α -reductase inhibitors, and combination therapy, taking into consideration age, severity of symptoms, prostate volume, prostate-specific antigen, and the differential response of the various medications (and combination) in selected patients. Based on current studies, 5α -blockers generally provide cost-effective therapy for most patients, whereas 5α-reductase therapy and combination therapy provide cost-effective treatment for patients with larger prostate glands or higher baseline prostate-specific antigen levels.     

CAR2 displays unique ligand binding and RXRalpha heterodimerization characteristics.

The constitutive androstane receptor (CAR; NR1I3) regulates the expression of genes involved in xenobiotic metabolism. Alternative splicing of the human CAR gene yields an array of mRNAs that encode structurally diverse proteins. One form of CAR, termed CAR2, contains an additional four amino acids (SPTV) that are predicted to reshape the ligand-binding pocket. The current studies show a marked, ligand-independent, CAR2-mediated transactivation of reporters containing optimal DR-3, DR-4, and DR-5 response elements, and reporters derived from the natural CYP2B6 and CYP3A4 gene promoters. Overexpression of the RXRalpha ligand binding domain was critical for achieving these effects. CAR2 interaction with SRC-1 was similarly dependent on the coexpression of RXRalpha. Mutagenesis of Ser233 (SPTV) to an alanine residue yielded a receptor possessing higher constitutive activity. Alternatively, mutating Ser233 to an aspartate residue drastically reduced the transactivation capacity of CAR2. The respective abilities of these mutagenized forms of CAR2 to transactivate a DR-4 x 3 reporter element correlated with their ability to interact with RxRalpha and to recruit SRC-1 in a ligand-regulated manner. Together, these results demonstrate a robust RXRalpha-dependent recruitment of coactivators and transactivation by CAR2. In addition, CAR2 displays novel dose responses to clotrimazole and androstanol compared with the reference form of the receptor while at the same time retaining the ability to bind CITCO. This result supports a hypothesis whereby the four-amino-acid insertion in CAR2 structurally modifies its ligand binding pocket, suggesting that CAR2 is regulated by a set of ligands distinct from those governing the activity of reference CAR.     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

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Serum ferritin in haemodialysis patients: is there a relationship to 'haemochromatosis alleles' HLA A3, B7, B14?

Serum ferritin levels were measured in 57 patients on maintenance haemodialysis to determine if patients who possessed 1 or more of the histocompatibility antigens associated with idiopathic haemochromatosis (HLA A3, B7 or B14) were at increased risk of iron overload. There was no significant difference in the mean serum ferritin levels between those patients with HLA A3, B7 or B14 (357.9 +/- 522.6 ng/1; n = 19) and those without these antigens (393.7 + 556.2 ng/1; n = 38). Iron overload in haemodialysis patients is not a histocompatibility-linked disorder.     

Geographic Benefit from Decentralized Medical Education: Student and Preceptor Practice Patterns

The performance of area health education center (AHEC)-stimulated programs and decentralized education for medicine is not well understood. The Statewide Education Activities for Rural Colorado's Health (SEARCH)/AHEC project at the University of Colorado School of Medicine was examined to determine if the program had an effect on the practice location of its graduates. Practice location and specialty of graduates of the University of Colorado School of Medicine (UCSOM) classes 1980-1985 were compared for students who had participated in decentralized SEARCH/AHEC experiences versus students who had not. The majority of the graduates were practicing out of state in 1990. Non-Colorado doctors were more often practicing in rural (non-metropolitan statistical area [MSA]) counties and in towns of fewer than 2,500, 5,000 and 10,000 residents, respectively. In addition, of the 251 active patient care physicians practicing in Colorado communities of fewer than 10,000 in non-MSA counties in 1986, those who precepted UCSOM students on SEARCH rotations were more likely to have remained in their same practice location in 1992 (77.8% versus 62.1% for those who had not precepted students). This analysis of both student and preceptor practice patterns documents the value of decentralized medical education in addressing the geographic and specialty maldistribution of physicians. These results have important policy implications for funding medical education programs.     

Mode of onset of simple phobia subtypes: further evidence of heterogeneity

Previous research has demonstrated heterogeneity of the simple phobia diagnostic category. As a further test of the notion of heterogeneity of the DSM-III-R simple phobia diagnostic category, mode of onset was examined in a sample of simple phobic outpatients. Patients were separated into one of four subtypes: animal or insect, blood and injury, situational, and choking-vomit phobias. Careful study yielded five distinct mode-of-onset categories. Two researchers independently determined the mode of onset for the patients studied: direct trauma, spontaneous, vicarious learning, gradual, and lifelong. Significant mode of onset differences were observed across groups. Situational phobics reported a preponderance of spontaneous onsets as compared to the other groups studied. These results offer further evidence of the heterogeneity of the simple phobia diagnostic category and also support the contention that situational simple phobias are closely related to agoraphobia.     

The patient''s view of general practice in an urban area

The paper reviews evidence from the health care professionsabout the quality and accessibility of general practice in London,which suggests that inner London is less well served than elsewhere,and recommends changes to the organization and equipment ofinner London practice. Results from a community survey in north-eastLondon are presented to show how the views about general practiceamong residents in a typical inner city district compared withthose in a suburban area. The results suggest that while therespondents were generally satisfied with their doctor's practice,a significant minority were dissatisfied, particularly in theinner city. Some of the respondents' views seemed to differfrom the model of desirable general practice suggested by thepolicy literature. In particular, single-handed practice wasmore popular with patients than group practice. The resuitsreflect the importance to patients of good personal rapportand communication with their doctor, which seemed to them themost significant quality of general practice. The implicationsfor policies to improve inner city practice are considered.     

Integrating disability management into strategic plans: creating healthy organizations.

The integration of disability management into the strategic planning of a corporation ensures a work environment is created that motivates employees to consistently meet customer expectations. Disability management strategies can achieve significant decreases to the human and financial cost of workers' compensation, sick leave or short term disability, and long-term disability. The business case for disability management including effective return to work programs clearly supports program implementation to enhance employee engagement, delivery of corporate priorities, and improvement to the company's bottom line.