The patient's choice of androgen-deprivation therapy in locally advanced prostate cancer: bicalutamide, a gonadotrophin-releasing hormone analogue or orchidectomy

OBJECTIVE: To investigate patient preference for three established androgen-deprivation therapies for locally advanced prostate cancer; the patient's capacity to decide his therapy; the reasons for selecting a certain mode of therapy; and patient satisfaction with the chosen therapy 3 months after initiation. PATIENTS AND METHODS: In all, 150 patients (mean age 75 years, range 57-89) with previously untreated locally advanced prostate cancer from 13 hospitals were consecutively given the chance to choose between the antiandrogenic oral drug bicalutamide, a gonadotrophin-releasing hormone analogue (GnRH) by injection, or surgical orchidectomy. After discussing the nature of their disease the patients took home written information about prostate cancer and the three different treatment options. After 1 week they were assessed using a questionnaire for biographical data, their attitude towards the different treatment alternatives and their choice of therapy. Three months later the patients completed a questionnaire about the treatment they had undergone. RESULTS: Sixty-three patients (42%) chose bicalutamide, 51 (34%) the GnRH analogue and 36 (24%) orchidectomy; 87% of those choosing bicalutamide, 84% GnRH and 94% orchidectomy, respectively, were sure about their choice but 12%, 17% and 3% of the patients, respectively, had some difficulty in deciding. The most important reasons for the therapy chosen were avoidance of injections and surgery, and a lower risk of impotence (bicalutamide), negative attitude to surgery and tablets (GnRH), and avoidance of injections and tablets (orchidectomy). Almost all patients (98%, 98% and 97%, respectively) were satisfied with their choice after 3 months of treatment. CONCLUSION: There are three equally effective forms of androgen deprivation for locally advanced prostate cancer without known metastases. There are major differences among these treatments in the mode of application and the likelihood and impact of side-effects. When patients are fully informed and play an active role in the treatment decision they are satisfied with their decision 3 months later.     

The effect of plaque control and surgical pocket elimination on the establishment and maintenance of periodontal health. A longitudinal study of periodontal therapy in cases of advanced disease

Abstract The present clinical study was initiated in 1969 to test the hypothesis that microbial plaque is the cause of periodontal disease and that hence even advanced cases of periodontitis can be cured in patients willing to exercise optimal plaque control. The material consisted of 75 patients with severe destruction of the periodontal tissues. The patients were selected for the study because of their ability to maintain plaque-free dentition. Following an initial examination, a preliminary treatment plan was presented to the patients. This plan included detailed instructions in plaque control measures, scaling, root planing and emergency dental care, including endodontic therapy and extractions. Three to six months after the termination of the so-called presurgical treatment, surgical elimination of pathologically deepened pockets was performed. The patients were recalled every 3 to 6 months after the end of the treatment. At these reexaminations the following parameters were assessed: Plaque Index, Gingival Index, Pocket Depths, Marginal alveolar bone topography and height. The results demonstrate that it is possible to treat periodontal disease successfully, even in advanced stages, in patients willing to maintain plaque-free dentition.     

Non-word repetition and non-word discrimination in Swedish preschool children

By looking at data on expressive phonology, non-word repetition, non-word discrimination and phonological sensitivity in two groups of Swedish children, the common basis for tasks tapping into different levels of phonological processing is discussed. Two studies were performed, one including children with language impairment (LI) and one including children with normal language development (NL). A discrimination task consisting of non-word pairs differing in one phoneme was developed. In both groups there was a significant correlation between non-word repetition and phoneme identification. In children with LI phoneme identification was significantly correlated with expressive phonology. In children with NL non-word repetition correlated significantly with non-word discrimination, which was linked both to rhyme recognition and phoneme identification. Non-word discrimination might be equally useful as non-word repetition as an early screening tool and would circumvent the confounding factor of an expressive phonological impairment as well as decrease the amount of complicating factors involved in scoring procedures.     

Kinetics of tyrosine transport and cognitive functioning in schizophrenia

BACKGROUND: Tyrosine supplementation in humans has been shown to improve cognitive functioning. Several studies have demonstrated a decreased maximal transport capacity of tyrosine (Vmax) across the cell membrane and an increased affinity (Km) of tyrosine to membrane binding sites in schizophrenic patients. A lack of tyrosine for dopamine synthesis with impairment of dopaminergic transmission could impair cognitive functioning. Aberrant tyrosine kinetics in patients with schizophrenia might therefore be associated with cognitive dysfunction--a core feature of schizophrenia. METHODS: Tyrosine kinetics was determined in cultured fibroblasts from 36 schizophrenic patients. The kinetic parameters Vmax and Km were calculated and then the patients were divided into two groups according to the median of the kinetic parameters. A comprehensive neuropsychological test battery was used to evaluate cognitive functioning. RESULTS: Patients with low Km (below the median) had poorer cognitive performance than patients with high Km (above the median). Vmax did not discriminate schizophrenic patients with cognitive dysfunction to the same extent. CONCLUSIONS: Changes in tyrosine transport probably influence cognitive functioning via the dopamine system. However, our findings of a relation between low Km and cognitive dysfunction may have a more complex background. It is suggested that the connection is related to genetically determined membrane factors that disturb communication/transmission among neurons.     

Renal artery stenosis evaluated with 3D-Gd-magnetic resonance angiography using transstenotic pressure gradient as the standard of reference. A multireader study

PURPOSE: To evaluate 3D-Gd-magnetic resonance angiography (MRA) in detecting hemodynamically significant renal artery stenosis (RAS). MATERIAL AND METHODS: Thirty patients evaluated for atherosclerotic RAS by MRA and digital subtraction angiography (DSA) were retrospectively included. Standard of reference for hemodynamically significant RAS was a transstenotic gradient of 15 mmHg. DSA visualized 60 main renal arteries and 9 accessory arteries. Pressure gradient measurement (PGM) was available from 61 arteries. Three radiologists evaluated all examinations independently in a blinded fashion. RESULTS: RAS was present in 26 arteries. On MRA, each reader identified 4 of 9 accessory renal arteries, a detection rate of 44%. The three readers correctly classified 22/25/22 of the 26 vessels with a significant gradient as > or =60% RAS and 31/25/32 of the 35 with no significant gradient as < 60% RAS on MRA. Interobserver agreement was substantial. MRA image quality was adequate for RAS evaluations in all patients. ROC curves indicated that MRA is an adequate method for evaluating RAS. When screening for RAS, a 50% diameter reduction cut-off is better than 60%. RAS with 40-80% diameter reductions accounted for 65% of discrepancies. CONCLUSION: MRA is an adequate method for evaluating RAS limited mainly by poor detection rate for accessory renal arteries.     

Gadolinium contrast media are more nephrotoxic than a low osmolar iodine medium employing doses with equal X-ray attenuation in renal arteriography: an experimental study in pigs

RATIONALE AND OBJECTIVES: To investigate in a unilaterally nephrectomized porcine model whether gadolinium contrast media (Gd-CM) are less nephrotoxic than iodine media (I-CM) in x-ray arteriography of a kidney made temporarily ischemic by arterial balloon occlusion. MATERIALS AND METHODS: In a noncrossover design, 3 mL of each test solution were injected in eight pigs (mean weight 19 kg) at a rate of 20 mL/min into the right renal artery at the start of a 10-minute period of ischemia. In group 1 (40 pigs) we injected 0.5 M gadopentetate, 0.5 M gadodiamide, 0.5 M iohexol (190 mg I/mL), 0.18 M iohexol (70 mg I/mL; with an x-ray attenuation equal to that of 0.5 M Gd-CM at 80 kV), and saline. In group 2 (24 pigs), we tested 0.18 M iohexol with ischemia and saline with and without ischemia. Gd- and iodine contrast media functioned as markers of glomerular filtration rate (GFR). When saline was tested, a low dose of iohexol (3 mL per pig; 300 mg I/mL) was injected as GFR marker intravenously in group 1 and into the renal artery in group 2. The plasma half-life elimination times of the CM 1-3 hours after injection were used to compare the effects of the different test solutions on GFR. Longer half-life means lower GFR. RESULTS: Group 1: median plasma half-life elimination time of the GFR marker was 3 340 minutes after injection of 0.5 M gadopentetate, 256 after 0.5 M gadodiamide, 179 after 0.5 M iohexol, 143 after 0.18 M iohexol, and 133 minutes after saline. All differences except that between 0.18 M iohexol and saline were statistically significant (P < .01). Group 2: median plasma half-life was 174 minutes after 0.18 M iohexol with ischemia, 196 minutes after saline with ischemia, and 195 minutes after saline without ischemia. There were no significant differences between the test solutions in group 2 (P > .05). CONCLUSION: In pigs, 0.5 M Gd-CM were more nephrotoxic than both equal-attenuating (70 mg I/mL) and equimolar (190 mg I/mL) concentrations of the I-CM iohexol. These results do not support the "off-label" use of Gd-CM for renal x-ray arteriography in man instead of commercially available concentrations of iodine contrast media at 140, 150 and 180 mg I/mL or diluted to 70 mg I/mL.     

A theoretical analysis of long-term bisphosphonate effects on trabecular bone volume and microdamage

Bisphosphonates increase bone mass and reduce fracture risk, but their anti-resorptive action may lead to increases in fatigue microdamage. To investigate how bisphosphonate effects influence changes in bone volume and microdamage in the long term, a strain-adaptive model of bone remodeling and microdamage balance was developed for a continuum-level volume of postmenopausal trabecular bone by invoking Frost's mechanostat hypothesis. Both disuse and fatigue microdamage were assumed to stimulate the activation frequency of basic multicellular units (BMUs) such that bone remodeling served to remove excess bone mass and microdamage. Bisphosphonate effects were simulated as follows: low, intermediate, high, or complete suppression of BMU activation frequency either without a change in resorption by the BMU or with an independent decrease in resorption while the bone formation process was unaffected (i.e., formation initially exceeded resorption). Of the bisphosphonate effects, a reduction in resorption relative to formation dictated the long-term gain in bone volume while the potency of activation frequency suppression controlled the rate of gain. A plateau in the bone mass gain that typically occurs in clinical studies of bisphosphonate treatment was predicted by the model because the resultant reduction in strain forced bone formation by the BMU to decrease over time until it matched the reduction in BMU resorption. A greater suppression of activation frequency proportionally increased microdamage, but the accumulation was limited over the long term as long as remodeling was incompletely suppressed. The results of the model suggest creating bisphosphonates that provide minimal suppression of remodeling and a large decrease in BMU resorption because this would minimize damage accumulation and increase bone mass, respectively.     

The cost-effectiveness of anorexia nervosa treatment

OBJECTIVE: Anorexia nervosa (AN) is an expensive-to-treat illness with a high mortality rate. Some health care systems have limited the amount of treatment provided for AN despite the lack of clearly documented efficacy for these limited-intensity approaches. One method that can inform decisions about AN treatment is cost-effectiveness analysis. METHOD: Cost-modeling analysis was used to estimate the incremental cost-effectiveness of AN treatment. Modeling was chosen given the lack of primary data on costs and outcomes in AN treatment. Data for age of onset, life expectancy, and disease-associated mortality were taken from the literature. The costs of treatment used in the analysis were those in use at the University of Minnesota. RESULTS: Assuming an approach consisting of inpatient weight restoration, followed by treatment of gradually diminishing intensity (partial hospitalization, then outpatient psychotherapy plus medication management), incremental cost-effectiveness ratios were calculated and compared with a limited intensity, "usual care" model. These assumptions yielded a cost per year of life saved of 30,180 dollars. DISCUSSION: Relative to many other medical interventions, the comprehensive treatment of AN appears to be quite cost-effective in terms of cost per year of life saved. Such data may have an impact on payer decisions and underscore the serious nature of AN.     

Is 'moral hazard' inefficient? The policy implications of a new theory

"Moral hazard" refers to the additional health care that is purchased when persons become insured. Under conventional theory, health economists regard these additional health care purchases as inefficient because they represent care that is worth less to consumers than it costs to produce. A new theory, however, suggests that much of moral hazard is actually efficient. When the care that was deemed to be welfare-decreasing is reclassified as welfare-increasing, health insurance becomes much more valuable to consumers than health economists have hitherto thought it was. As a result, there is a new argument for national health insurance: efficiency.