Biomedical subjects
Publications and source records attributed to N Carson.
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PURPOSE: Recent evidence indicates that in a number of species detrusor relaxation is mediated through activation of the beta3-adrenergic receptor. We determined whether activation of the beta3-adrenergic receptor would be a useful therapeutic approach for bladder instability. We profiled in vitro activity of the beta3-adrenergic receptor agonist CL-616243 and the efficacy of this compound in experimental models of detrusor instability and bladder hyperreflexia. MATERIALS AND METHODS: Isolated rat detrusor strips were contracted by depolarizing the preparations with 20 mM. KCl. CL-316423 was added to the tissue bath in increasing concentrations and contraction inhibition was assessed. Efficacy against bladder instability was evaluated using the obstructed hypertrophied bladder model in the rat. The acetic acid bladder cystometry model was used to assess the efficacy of CL-316423 in bladder hyperreflexia. Isovolumetric contractions were evoked by electrical stimulation using a silver bipolar electrode. Data are expressed as the mean plus or minus standard error of mean. RESULTS: CL-316243 inhibited spontaneously contracting, isolated rat detrusor strips in a concentration dependent manner with a mean concentration inhibiting 50% of maximal response of 2.65 +/- 0.36 nM. Intrinsic activity relative to forskolin was 1. In vivo CL-316243 administered intravenously or orally significantly increased the voiding interval and bladder compliance. In addition, there was a decrease in the number of spontaneous contractions during the filling phase in a model of neurogenic and obstruction induced bladder instability. The amplitude of electrically evoked isovolumetric contractions was significantly smaller after CL-316243 exposure. CONCLUSIONS: These data suggest that activating the beta3-adrenergic receptor in rat bladder using CL-316243 may directly inhibit smooth muscle contractility, experimental hyperreflexia and detrusor instability, and be useful for urge urinary incontinence.
The medical community and general population have become aware that genetic testing is available to look for BRCA1 and BRCA2 mutations. However, criteria for who should be referred for genetic counseling and possible subsequent testing have yet to be determined, and many genetics centers have been overwhelmed by the demand for service. We set out to develop a family history assessment tool (FHAT) that could be used by physicians to select individuals for genetic counseling. Arbitrarily, we chose individuals who would have an approximate doubling of their lifetime risk for breast or ovarian cancer. The FHAT was then applied to 184 unrelated families, with an index patient who had breast or ovarian cancer and who had accepted the offer of BRCA1 BRCA2 testing. Data were compiled to compare the number of individuals who would have been referred for genetic counseling and the number of mutation-positive individuals who would have been screened out from counseling using FHAT, the tables from Claus, and the BRCAPRO system. In this population, FHAT was effective in minimizing both the number of referrals and the likelihood of missing women who were later found to be mutation-positive.
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BACKGROUND: The purpose of the present paper was (i) to identify trends in in-hospital mortality after transurethral resection of the prostate (TURP) in Victorian public hospitals; and (ii) to explore associations between in-hospital mortality after TURP and age, adverse events, type of admission (emergency/planned), location of the hospital (metropolitan/rural), teaching status of the hospital and length of stay. METHODS: Trends in in-hospital mortality after TURP and the associations between in-hospital mortality and the aforementioned variables were studied using International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) coded Victorian hospital morbidity data from public hospitals between 1987-88 and 1994-95. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) were based on univariate and multivariate logistic regression, respectively. RESULTS: After adjustment for age, comorbidity, and other confounding variables, the trend in mortality reduction over time was highly significant (P for trend < 0.0001, 95% CI for trend: 0.84-0.95). Highly significant associations with mortality were observed for emergency admissions (OR = 1.99, P < 0.0001), presence of adverse events (OR = 2.69, P < 0.0001), length of hospital stay (P for trend < 0.0001, 95% for trend: 1.88-2.15) and age (P for trend < 0.0001; 95% CI for trend: 1.26-1.48). CONCLUSIONS: Routinely collected data from hospitals can provide tentative evidence of improved effectiveness of a surgical treatment, provided analysis takes careful account of potential sources of bias, especially those related to possible changes in case selection over time. These kinds of data should stimulate a joint effort between clinicians, quality assurance experts and epidemiologists to confirm this attribution, and to locate the causative factors.
Models for strategic priority setting in public health and health services research typically lack coherence or omit key considerations. We propose a new model, the Seven 'I's, with seven components: innovation, identification, inequalities, incorporation, importance, influences, and interventions. It tests the 'relevance' of research, while 'excellence' will be evaluated using existing criteria for peer review. It should be used to set research priorities primarily on the basis of expected health benefits, with adjustments for other non-health benefits as necessary. We discuss each component and compare our approach to other models. We argue that our model helps ensure resource allocation is transparent and accountable, and encourages the link to population health gains. It is flexible, and is applicable to both commissioned and investigator-driven research. It may be applied to assess existing proposals, or to generate research ideas.
OBJECTIVE: To compare crude and adjusted in-hospital mortality rates after prostatectomy between hospitals using routinely collected hospital discharge data and to illustrate the value and limitations of using comparative mortality rates as a surrogate measure of quality of care. METHODS: Mortality rates for non-teaching hospitals (n = 21) were compared to a single notional group of teaching hospitals. Patients age, disease (comorbidity), length of stay, emergency admission, and hospital location were identified using ICD-9-CM coded Victorian hospital morbidity data from public hospitals collected between 1987/88 and 1994/95. Comparisons between hospitals were based on crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) derived using univariate and multivariate logistic regression. Model fit was evaluated using receiver operating characteristic curve i.e. statistic, Somer's D, Tau-a, and R2. RESULTS: The overall crude mortality rates between hospitals achieved borderline significance (alpha2=31.31; d.f.=21; P=0.06); these differences were no longer significant after adjustment (chi2=25.68; P=0.21). On crude analysis of mortality rates, four hospitals were initially identified as 'low' outlier hospitals; after adjustment, none of these remained outside the 95% CI, whereas a new hospital emerged as a 'high' outlier (OR=4.56; P= 0.05). The adjusted ORs between hospitals compared to the reference varied from 0.21 to 5.54, ratio = 26.38. The model provided a good fit to the data (c=0.89; Somer's D= (0.78; Tau-a = 0.013; R2= 0.24). CONCLUSIONS: Regression adjustment of routinely collected data on prostatectomy from the Victorian Inpatient Minimum Database reduced variance associated with age and correlates of illness severity. Reduction of confounding in this way is a move in the direction of exploring differences in quality of care between hospitals. Collection of such information over time, together with refinement of data collection would provide indicators of change in quality of care that could be explored in more detail as appropriate in the clinical setting.
BACKGROUND: A retrospective analysis of data from the Victorian Inpatient Minimum Database (VIMD) was conducted to analyse trends in prostatectomy rates in Victorian public acute-care hospitals from 1989/90 to 1994/95. The study also sought to identify predictors of adverse events (AE) after prostatectomy, and to compare in-hospital complications between open prostatectomy and transurethral resection of prostate (TURP). METHODS: All patients who had undergone any prostatectomy were identified according to the relevant ICD-9-CM procedure codes (60.2-60.4) documented in the VIMD. The main outcome measures, AE, were identified using the ICD-9-CM supplementary classification of external cause of injury (E850-858, E870-876, E878-879, E930-949). The variables used as predictors were year of prostatectomy, type of admission (planned, emergency), location of the hospital (rural, metropolitan), type of procedure (TURP, open), and teaching status of the hospital. Crude and adjusted odds ratios (OR) were based on univariate and multivariate logistic regression. RESULTS: The rates of prostatectomies have significantly increased over the 6-year study period (P for trend < 0.0001). The percentage of AE after prostatectomy increased simultaneously from 6.1 to 12.9% (P < 0.0001). During the same period, the in-hospital mortality rate after prostatectomy decreased from 1.2 to 0.5%, and length of stay decreased from 10.3 to 6.1 days (Kruskal-Wallis P < 0.0001). The significant predictors of outcome were year of prostatectomy (P for trend < 0.0001), emergency admissions (OR = 1.57; P < 0.0001), metropolitan hospitals (OR = 0.81; P = 0.0003), non-teaching hospitals (OR = 0.78; P < 0.0001), and open prostatectomy (OR = 1.52; P = 0.04). More in-hospital complications were associated with open prostatectomy than with TURP. CONCLUSIONS: The rise in AE rate after prostatectomy is unlikely to reflect poor quality of care, because in the same period there was a significant decrease in in-hospital mortality after prostatectomy. A more likely explanation is heightened awareness of AE with a lower threshold for reporting such events. Important factors other than variations in quality of care can result in an increase in AE. Hence the reported increase should be interpreted with caution before attempting to conclude that changes in clinical practice could have a direct impact on these rates.
This study determined effects of surgical dissection and chronic stimulation on degeneration of the latissimus dorsi muscle (LDM), the muscle used for contractile assistance in cardiomyoplasty. LDMs from 10 goats were allocated into four groups: N-LDM (normal), D-LDM (dissected muscle and collateral vessels ligated, muscle remained in original anatomic location), S-LDM (electrically stimulated for 65-75 days), and DS-LDM (dissected and stimulated). S-LDM had nearly a complete transformation to type I fibers throughout the lengths of the muscle. Both groups of dissected muscles (D-LDM and DS-LDM) showed lesser transformation and significant damage. Type I myosin heavy chain and citrate synthase activity were less in the distal compared with the proximal LDM. Morphology of the N-LDM and S-LDM was normal, whereas dramatic morphological abnormalities were observed in the D-LDM and DS-LDM, including lipid-containing ghostlike fibers, atrophied and hypertrophied fibers within the same fascicle. In conclusion, muscle degeneration associated with the cardiomyoplasty procedure was caused by surgical dissection, which was exacerbated by chronic stimulation but was not caused by stimulation alone.
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