Current practice and resource utilisation in men diagnosed with premature ejaculation.

OBJECTIVES: To compare the healthcare resource utilisation of men diagnosed with premature ejaculation (PE) with that of age-matched men without a PE diagnosis, through a retrospective analysis of US medical claims data. METHODS: Data were from the PHARMetrics Database. Records of patients > or = 18 years of age diagnosed with PE (n = 1245) and age-matched controls (n = 3915) were compared with regard to number of physician encounters, concomitant medical diagnoses, drug therapies and treatment costs. RESULTS: Men diagnosed with PE visited their physicians twice as frequently in the year before their diagnosis as men in the control group. Men diagnosed with PE were more likely to receive a prescription for a selective serotonin reuptake inhibitor or a phosphodiesterase-5 inhibitor after their diagnosis than before and used more of these compared with controls. Prior to their PE diagnosis, patients received more (and more frequent) comorbid diagnoses than controls, and their mean yearly diagnosis and prescription costs were $1320 (vs. $447 for controls). In the year after the PE diagnosis, diagnosis and prescription costs fell by 24% (to $998), primarily because of a reduction in physician visits. CONCLUSIONS: Compared with controls, men with PE who sought help from a healthcare professional consumed more medical resources, primarily because of a higher number of physician visits and greater use of prescription drugs. Further research is warranted to determine if the observed associations between PE and other diagnoses indicate genuine aetiological factors or reporting bias.

Costs of opioid therapy for chronic nonmalignant pain in Germany: an economic model comparing transdermal fentanyl (Durogesic) with controlled-release morphine.

The fentanyl transdermal therapeutic system (fentanyl-TTS;Durogesic) has a distinct route of administration and safety profile compared with other opioids used in the treatment of moderate to severe pain.These aspects are likely to have an impact on patient acceptance and functioning as well as efficacy. We compared the cost-utility of fentanyl-TTS and controlled-release morphine (cr-morphine) in the treatment of moderate to severe nonmalignant pain in outpatients in Germany. A 1-year, three-phased decisionanalytic model was constructed, incorporating estimates of a variety of aspects of pain control.Use of fentanyl-TTS was predicted to incur higher costs than cr-morphine over 1 year of treatment (DM 6950 vs.DM 6186, respectively) but was associated with a higher number of quality-adjusted life days (234 vs. 216, respectively), thus achieving an incremental cost-utility ratio of DM 15,960 per quality-adjusted life-year gained.The results of the decision-analytic model support the use of fentanyl-TTS as a favorable cost-effective option for the treatment of moderate to severe nonmalignant pain.

A 1-year cost-effectiveness model for the treatment of chronic schizophrenia with acute exacerbations in Belgium.

OBJECTIVE: A 1-year semi-Markov model was constructed to simulate the cost-effectiveness of atypical and typical antipsychotic treatments for schizophrenia. METHODS: The core model comprised nine 6-week cycles and includes events such as survival, response, adverse events, and compliance. The nature, duration, intensity, and timing of adverse events were incorporated. Compliance was modeled as a function of health state, time, and adverse events. Three first-line treatments were considered (risperidone, olanzapine, and haloperidol oral) and the transition probabilities of switching between five different therapies (haloperidol oral, haloperidol depot, risperidone, olanzapine and clozapine) were included. Effectiveness was modeled based on a modified method of TWiST (time without symptoms and toxicity). The direct costs of utilization of medical resources are taken into account, including five different patient care settings, consultations, neuroleptic medication, laboratory tests, and treatment of side-effects. RESULTS: This paper reports the methodology used to construct the model and the results obtained when it was applied to the treatment of patients with schizophrenia in the Belgian health care system. CONCLUSIONS: Over the study period, risperidone and olanzapine were more cost-effective than haloperidol and of the two major atypical drugs, risperidone was the more cost-effective.

The assessment of biomarkers to detect nephrotoxicity using an integrated database.

Groups of industrial workers exposed to heavy metals (cadmium, mercury, and lead) or solvents were studied together with corresponding control groups. The cohorts were collected from several European centers (countries). Eighty-one measurements were carried out on urine, blood, and serum samples and the results of these analyses together with questionnaire information on each individual were entered into a central database using the relational database package Rbase. After the completion of the database construction phase, the data were exported in a format suitable for analysis by the statistical package SAS. The potential value of each test as an indicator of nephrotoxicity was then assessed. Rigorous exclusion criteria were applied which resulted in the elimination of some tests and samples from the dataset. The measurable contributions of smoking, gender, metal exposure, and site were either singly or in combination assessed by biomarkers for nephrotoxicity. The parameters measured included three urinary enzymes, six specific proteins, total protein, two extracellular matrix markers, four prostaglandins and anti-GBM antibodies, and beta 2-microglobulin in serum. The most sensitive renal tests included the urinary enzymes N-acetyl-beta-D-glucosaminidase (NAG) and intestinal alkaline phosphatase (IAP), brush border antigens, and urinary low-molecular-weight proteins. Of the newer tests investigated the prostaglandins were the most promising. Different patterns of biomarker excretion were observed following exposure to lead, cadmium, or mercury. The dataset provides a unique repository of data which could provide the basis of an enlarging source of information on normal human reference ranges and on the effects of exposure to toxins and the use of biomarkers for monitoring nephrotoxicity.

Development and validation of new screening tests for nephrotoxic effects.

Within the framework of an European Commission-funded project, groups of industrial workers exposed to heavy metals (cadmium, mercury and lead) or solvents were studied together with corresponding control groups. Eighty-one measurements were carried out on urine and serum samples and the scientific results together with individual questionnaire information were entered into a central database. Data obtained was assessed centrally and individually in subsidiary studies. The measurable contributions were assessed either singly or in combination, of smoking, gender, metal exposure and site, to nephrotoxicity. The potential value of each test as an indicator of nephrotoxicity was then assessed on the basis of sensitivity and specificity. A number of new tests including prostaglandins and for extracellular matrix components were investigated as well as established tests for renal damage and dysfunction. The data obtained from this comprehensive study emphasises the value of noninvasive biomarkers for the early detection of nephrotoxicity due to environmental toxins. The urinary profile varied with the type of environmental/occupational toxin. By careful selection of a small panel of markers they can be used to indicate the presence of renal damage, the principal region affected, and to monitor the progress of disease and damage. Biomarkers were also used to confirm and tentatively establish safe exposure levels to nephrotoxins.

Occupational renal diseases.

There is no doubt that particular occupational exposures may induce acute renal effects. The role of occupational exposure in the development or progression of chronic renal failure, however, is still not clear. Recent epidemiological studies point towards a contributive role of particular occupational exposures in the progression of renal disease. Furthermore, some observations in the 1994-1995 literature suggest a primary or secondary role, or both, of new substances such as silicon-containing compounds in the development of anti-neutrophil cytoplasmic antibody-positive rapidly progressive glomerulonephritis and Wegener's granulomatosis. Finally, studies suggesting a particular sensitivity of the diabetic kidney towards the damaging effects of certain occupational exposures deserve confirmation.

Significance of elevated urinary human intestinal alkaline phosphatase in Japanese people exposed to environmental cadmium.

Urinary human intestinal alkaline phosphatase (IAP), beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) were analyzed in 40 Japanese environmental-cadmium (Cd)-exposed and 40 non-exposed subjects to evaluate early biological markers for Cd-induced renal damage. All urinary indicators were significantly higher in the Cd-exposed subjects than non-exposed subjects. A fourth-order function was fitted for the relationship between beta 2-MG and IAP or NAG. The beta 2-MG concentration corresponding to the inflexion point for IAP was smaller than that for NAG. This result may support the contention that the cells containing IAP are damaged earlier than those containing NAG, and that IAP is a useful marker for detecting renal tubular dysfunction in people moderately exposed to Cd. However, in the stage of severe renal damage, the combination of IAP and beta 2-MG is considered to be more useful.

New occupational risk factors for chronic renal failure.

Occupational pollutants may have a role in development of chronic renal failure (CRF). Most epidemiological studies have been cross-sectional, limited to certain renal diagnoses, or concentrated on early transient renal effects. In a case-control study, we examined the association between CRF and occupational exposure. Occupational histories of 272 men and women with CRF (of all types) were compared with those of 272 controls matched for age, sex, and region of residence. Exposures were assessed and degree and frequency were scored independently by three industrial hygienists unaware of case/control status. Significantly increased risks of CRF were found for exposure to lead (odds ratio 2.11 [95% CI 1.23-4.36]), copper (2.54 [1.16-5.53]), chromium (2.77 [1.21-6.33]), tin (3.72 [1.22-11.3]), mercury (5.13 [1.02-25.7]), welding fumes (2.06 [1.05-4.04]), silicon-containing compounds (2.51 [1.37-4.60]), grain dust (2.96 [1.24-7.04]), and oxygenated hydrocarbons (5.45 [1.84-16.2]). The frequencies of various occupational exposures were high among patients with diabetic nephropathy. This epidemiological study confirms previously identified risk factors and suggests that additional occupational exposures, for which there is some other experimental evidence, may be important in the development of CRF. The role of grain dust and the association between occupational exposure and diabetic nephropathy merit further investigation.

Wegener granulomatosis is associated to exposure to silicon compounds: a case-control study.

Wegener granulomatosis is a rare disease of unknown aetiology. In the majority of these patients the kidney is involved in the disease process. We performed a case-control study to evaluate the role of occupational exposure in the development of Wegener granulomatosis with renal involvement. The occupational histories of 16 cases with clearly established diagnosis of Wegener granulomatosis with renal involvement were compared with those of 32 age- and sex-matched controls. It was observed that inhalation of silicon-containing compounds such as silica and grain dust gave a nearly sevenfold risk for Wegener granulomatosis. Further epidemiological and experimental work needs to be performed in order to corroborate these findings.

Early urinary markers of target nephron segments as studied in cadmium toxicity.

A number of chemicals may adversely affect one or more of the anatomical structures of the kidney, such as the glomerulus, the tubular apparatus, the medullary, or interstitial cells. To recognize subclinical renal dysfunction, a battery of new, non-invasive tests was applied in comparison to established ones. The study on cadmium exposed subjects, performed within the framework of a collaborative European research project, exemplifies the concept of target selectivity within a nephron. One hundred seventy-two subjects were classified according to urinary cadmium excretion as controls (< 1.5 micrograms/g creatinine), or subjects with moderate or high cadmium body burden (1.5 to 5 micrograms/g creatinine, > 5 micrograms/g creatinine). Twenty-six urinary analytes (such as serum derived proteins, tubular enzymes, eicosanoids) and four plasma markers, related to the function or integrity of specific nephron segments, were investigated in a cross-sectional study. The group with the moderate cadmium body burden showed alterations of proximal tubular integrity, that is, increased excretion of tubular brush-border antigens. The group with higher cadmium body burden revealed an involvement of the whole nephron. The most prominent quantitative changes were found for the glomerular markers high molecular weight proteins, and thromboxane B2 and for the proximal tubular markers retinol binding protein, alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, and the intestinal alkaline phosphatase. A diagnostic approach to screen for nephrotoxicity due to environmental hazards like cadmium should include proximal tubular markers (alpha 1-microglobulin and tubular enzymes, that is, intestinal alkaline phosphatase) but the measurement of glomerular markers is also advisable.

Human urinary intestinal alkaline phosphatase as an indicator of S3-segment-specific alterations in incipient diabetic nephropathy.

Urinary enzymes were determined in a controlled study including 28 type I diabetes mellitus patients. Fifteen patients had persistent microalbuminuria and were compared to 13 normoalbuminuric patients with comparable age and sex distribution. All patients had normal renal function as measured by serum creatinine. Human intestinal alkaline phosphatase (hIAP), a specific marker of the proximal tubular S3 segment, was elevated in the urine of microalbuminuric patients while human tissue non-specific alkaline phosphatase (hTNAP), indicating effects mainly at the S1-S2 segments, was not. Urinary hIAP was correlated with serum glycated haemoglobin. These results suggest that tubular alterations are present at an early stage of diabetic nephropathy, especially at the S3 segment, and that hIAP may have promise as an early marker.

luxAB gene fusions with the arsenic and cadmium resistance operons of Staphylococcus aureus plasmid pI258.

pC101, a novel shuttle vector between Escherichia coli and Staphylococcus aureus carrying the lux genes encoding luciferase from Vibrio harveyi, selectable ampicillin and chloramphenicol markers and origins of replication for Gram-negative and Gram-positive bacteria has been constructed. The inducibility of the arsenic and cadmium operon from S. aureus plasmid pI258 to different ions has been tested in E. coli and in S. aureus with two fusions in pC101: an arsB-luxAB and a cadA-luxAB transcriptional gene fusion. Patterns of induction are influenced by the host strain and are slightly different from previous reports using the blaZ gene as reporter gene.

Healthy worker effect in a cross-sectional study of lead workers.

To study the role lead may play in the development of renal disease, we performed a cross-sectional study of workers at a lead smelting plant. Renal function was defined based on calculated creatinine clearance using the prevalence of values under the 3rd percentile to compare groups. The prevalence of calculated creatinine clearance values under the 3rd percentile in these workers (n = 1782) as a whole was 2.81%, a result comparable to that which has to be expected for the general population. Closer analysis, however, showed significantly lower prevalence of calculated creatinine clearance under the 3rd percentile in certain subgroups of workers. These subgroups were workers between the ages of 30 and 39, workers over the age of 50, and Belgian workers who had worked in the plant for longer than 10 years. We conclude that these observations once more clearly demonstrate a "healthy worker effect" on the measurement of renal function in this work force, a major problem in epidemiologic cross-sectional studies.

Urinary enzymes in acute renal failure.

Intestinal-type alkaline phosphatase (IAP) has been localized to the S3 segment of the renal tubule in previous studies, a site believed to be particularly vulnerable to toxic and ischaemic damage. During a 17-month period a pilot study of the value of urinary enzyme measurements (IAP and tissue non-specific alkaline phosphatase--TNAP, using monoclonal antibody-based immunoassays, and N-acetyl-beta-glucosaminidase--NAG, using colorimetric assay) in 50 prospectively followed cases of acute renal failure (ARF) was performed. Urinary enzymes were measured at initial evaluation ('start'), and then each day for 14 days, with the highest enzyme value ('peak') also used for analysis. Patients were divided into prerenal (n = 16), renal (n = 28), postrenal (n = 6) categories according to standard criteria. Of the renal ARF patients 23 of 28 had acute tubular necrosis (ATN), 3 of 28 acute interstitial nephritis (AIN), and 2 of 28 acute glomerulonephritis (AGN); 18 of 50 had a fatal outcome and 1 of 50 was dialysis-dependent at discharge ('poor' prognosis group), while 31 of 50 survived hospital without becoming dialysis-dependent ('good' prognosis group). Median enzyme concentration were increased in 'poor' compared to 'good' prognosis patients: start IAP 3.2 versus 2.2 U/g creat (NS), start NAG 48.6 versus 13.7 (P < 0.01), start TNAP 3.5 versus 0.9 (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal alkaline phosphatase as an indicator of effects on the S3-segment of the human proximal tubule.

A specific monoclonal antibody (IAP250) raised against human intestinal alkaline phosphatase was used to study the expression of this isoenzyme in human renal tissue and its release into urine.

Immunoassay in urine of a specific marker for proximal tubular S3 segment.

Urinary intestinal alkaline phosphatase (EC 3.1.3.1; IAP) is a marker of the S3 segment of the human kidney proximal tubule. An accurate enzyme-antigen immunoassay (EAIA) with a high-affinity specific monoclonal antibody (IAP250) developed for this marker has a detection limit below the lowest IAP activity found in urine samples of normal subjects. The intra- and interassay CVs were less than 5%. Mean analytical recovery of pure IAP added to urine was 102% (SD 6%), and the EAIA results correlated well with immunoreactivity (measured by a sandwich ELISA), suggesting that the EAIA detected all of the IAP in urine. In healthy individuals (ages 20-80 years) the IAP concentrations, expressed as urinary creatinine ratios, ranged from 0.1 to 2.0 U/g (5-95 percentiles) without major differences related to sex and age. Workers exposed to mercury, which affects the S3 segment, showed an increased IAP elimination; abusers of analgesics, which affect more distal parts of the nephron, did not. As opposed to currently measured markers, the EAIA offers easy, accurate, and precise measurement of early alterations in the S3 segment.

Intestinal-type alkaline phosphatase in urine as an indicator of mercury induced effects on the S3 segment of the proximal tubule.

Intestinal-type alkaline phosphatase (IAP) is a specific and sensitive marker for alterations of the S3 segment of the human proximal tubule, the preferred part for several nephrotoxins. We studied IAP and other renal parameters in mercury-exposed workers and their controls. IAP excretion is clearly increased in the exposed workers, compared to other parameters, indicating that the determination of this enzyme can be a useful screening test of renal effects in occupational mercury exposure.