Evidence-based medicine gaining supporters.
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Biomedical subjects
Publications and source records attributed to A Levin.
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MOTIVATION: With the main focus of the Human Genome Project shifting to sequencing, bioinformatics support for constructing large-scale genomic maps of other organisms is still required. We attempt to provide for this with our work, aimed at the delivery of robust and user-friendly contig-building software on the WWW. RESULTS: We present a prototype distributed analytical environment for molecular biologists working in the area of genomic mapping. It consists of the WWW server for constructing contigs from users' data with a hypertext output connected to Java-based map visualization software. AVAILABILITY: Freely available on http://www.mpimg-berlin-dahlem.mpg. de/ approximately andy/server/ CONTACT: andy@rag3.rz-berlin.mpg.de
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UNLABELLED: Ropivacaine has less potential for central nervous system and cardiovascular toxicity than bupivacaine; in pregnant patients and volunteers, it produces less motor block in equianalgesic doses than bupivacaine. We compared two doses of intrathecal ropivacaine combined with sufentanil with a standard dose of intrathecal bupivacaine plus sufentanil for labor analgesia using a combined spinal-epidural (CSE) technique. In a prospective, randomized, double-blind fashion, 48 patients requesting labor analgesia received either 2.5 mg of intrathecal bupivacaine plus sufentanil 10 microg (B), 2 mg of intrathecal ropivacaine plus sufentanil 10 microg (R2), or 4 mg of intrathecal ropivacaine plus sufentanil 10 microg (R4). Duration of analgesia and side effects, such as motor block, pruritus, hypotension, ephedrine requirements and fetal bradycardia, were recorded. Duration of analgesia (mean +/- SD) was 79+/-30 min for R2, 98+/-19 min for R4, and 92+/-38 min for B (P = not significant). No differences in motor block or side effects were detected among the groups. We conclude that ropivacaine, when combined with sufentanil, is effective for providing CSE labor analgesia and offers no advantage over bupivacaine in the studied doses. IMPLICATIONS: In this study, we compared a standard dose of intrathecal bupivacaine with sufentanil for combined spinal epidural analgesia with two doses of the new local anesthetic ropivacaine. Both local anesthetics provided similar labor analgesia duration with equivalent side effect profiles in the doses studied.
Sibutramine is a serotonin and norepinephrine reuptake inhibitor that has shown efficacy as a weight loss and weight maintenance agent. Because of the abuse liability and physical dependence potential of amphetamines and related antiobesity agents, this study evaluated the abuse potential of sibutramine and compared it with that of dextroamphetamine and placebo in recreational stimulant users. Thirty-one male recreational stimulant users participated in this single-site, Latin square crossover study that compared the effects of two doses of sibutramine (20 mg and 30 mg) to dextroamphetamine (20 mg and 30 mg) and placebo, using a series of validated subjective scales or questionnaires. For scales measuring stimulation and euphoria, there was a greater mean response for dextroamphetamine 30 mg versus 20 mg, with both doses having a significantly greater stimulant and euphoric effect than placebo at the majority of time points (p < 0.05); responses for both doses of sibutramine were statistically indistinguishable from placebo at all time points. Responses to "street value" and "most enjoyed study session" questions confirmed that sibutramine lacks abuse potential; mean cash value estimates of street value were significantly greater for both dextroamphetamine doses than for placebo or either sibutramine doses (p < 0.05), and the rank order of session enjoyment placed both doses of sibutramine last. Together with the relatively late Tmax of the active metabolites (3-4 hours), this short-term, single-dose study provides strong evidence that sibutramine does not have the potential for abuse that is characteristic of amphetamines and that it is indistinguishable from placebo in abuse potential.
OBJECTIVE: The purpose of this study was to assess the lifetime rates of occurrence of a full range of DSM-III-R axis I disorders in a group of patients with criteria-defined borderline personality disorder and comparison subjects with other personality disorders. METHOD: The axis I comorbidity of 504 inpatients with personality disorders was assessed by interviewers who were blind to clinical diagnosis and who used a semistructured research interview of demonstrated reliability. RESULTS: Four new findings emerged from this study. First, anxiety disorders were found to be almost as common among borderline patients (N=379) as mood disorders but far more discriminating from axis II comparison subjects (N=125). Second, posttraumatic stress disorder (PTSD) was found to be a common but not universal comorbid disorder among borderline patients, a finding inconsistent with the view that borderline personality disorder is actually a form of chronic PTSD. Third, male and female borderline patients were found to differ in the type of disorder of impulse in which they "specialized." More specifically, substance use disorders were significantly more common among male borderline patients, while eating disorders were significantly more common among female borderline patients. Fourth, a lifetime pattern of complex comorbidity (i.e., met DSM-III-R criteria for both a disorder of affect and a disorder of impulse at some point before the patients' index admission) was found to have strong positive predictive power for the borderline diagnosis as well as a high degree of sensitivity and specificity. CONCLUSIONS: These results suggest that the lifetime pattern of axis I comorbidity characteristic of borderline patients and distinguishing for the disorder is a particularly good marker for borderline personality disorder.
PURPOSE: The median survival of well-selected patients with single-brain metastases treated with whole-brain irradiation and resection or radiosurgery is comparable, although a randomized trial of these two modalities has not been performed. In this era of cost containment, it is imperative that health-care professionals make fiscally prudent decisions. The present environment necessitates a critical appraisal of apparently equi-efficacious therapeutic modalities, and it is within this context that we present a comparison of the actual costs of resection and radiosurgery for brain metastases. METHODS AND MATERIALS: Survival and quality of life outcome data for radiation alone or with surgery were obtained from two randomized trials, and radiosurgical results were obtained from a multiinstitutional analysis that specifically evaluated patients meeting surgical criteria. Only linear accelerator radiosurgery data were considered. Cost analysis was performed from a societal view point, and the following parameters were evaluated: actual cost, cost ratios, cost effectiveness, incremental cost effectiveness, cost utility, incremental cost utility, and national cost burden. The computerized billing records for all patients undergoing resection or radiosurgery for single-brain metastases from January 1989 to July 1994 were reviewed. A total of 46 resections and 135 radiosurgery procedures were performed. During the same time period, 454 patients underwent whole-brain radiation alone. An analysis of the entire bill was performed for each procedure, and each itemized cost was assigned a proportionate figure. The relative cost ratios of resection and radiosurgery were compared using the Wilcoxon rank sum test. Cost effectiveness of each modality, defined as the cost per year of median survival, was evaluated. Incremental cost effectiveness, defined as the additional cost per year of incremental gain in median survival, compared to the next least expensive modality, was also determined. To calculate the societal or national impact of these practices, the proportion of patients potentially eligible for aggressive management was estimated and the financial impact was determined using various utilization ratios for radiosurgery and surgery. RESULTS: Both resection and radiosurgery yielded superior survival and functional independence, compared to whole brain radiotherapy alone, with minor differences in outcome between the two modalities; resection resulted in a 1.8-fold increase in cost, compared to radiosurgery. The latter modality yielded superior cost outcomes on all measures, even when a sensitivity analysis of up to 50% was performed. A reversal estimate indicated that in order for surgery to yield equal cost effectiveness, its cost would have to decrease by 48% or median survival would have to improve by 108%. The average cost per week of survival was $310 for radiotherapy, $524 for resection plus radiation, and $270 for radiosurgery plus radiation. CONCLUSIONS: For selected patients, aggressive strategies such as resection or radiosurgery are warranted, as they result in improved median survival and functional independence. Radiosurgery appears to be the more cost-effective procedure.
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Demand for dialysis for patients with end-stage renal disease is growing, as is the comorbidity of dialysis patients. Accurate prediction of those destined to die quickly despite dialysis could be useful to patients, providers, and society in making decisions about starting dialysis. To determine whether age and comorbidity accurately predict death within 6 months of first dialysis for end-stage renal disease, a prospective cohort study of 822 patients starting dialysis at one of 11 Canadian centers was performed. Patient characteristics were recorded at first dialysis. Follow-up continued until death or study end (at least 6 months after enrollment). One hundred thirteen of 822 (13.7%) patients died within 6 months. Although an existing scoring system predicted prognosis, adverse scores greater than 9 were found in only 9.7% of those who died; only 52% of those who scored higher than 9 died within 6 months. No score cutoff point combined high true-positive and low false-positive rates for predicting early death. Age, severity of heart failure or peripheral vascular disease, arrhythmias, malnutrition, malignancy, or myeloma were independent prognostic factors identified in multivariate models. However, the best fit discriminant and logistic models were also unable to accurately predict death within 6 months. Clinicians were very accurate in assigning patients to prognostic groups up to a 50% risk of death by 6 months, above which they tended to overestimate risk. However, clinicians were only marginally better than the predictive models in determining whether a given high-risk patient would die. The inability of a scoring system or clinical intuition to accurately predict death soon after starting dialysis for end-stage renal disease suggests that limiting access to dialysis on the basis of likely short survival may be inappropriate in Canada.
A 1993 National Institutes of Health Consensus statement stressed the importance of early medical intervention in predialysis populations. Given the need for evidence-based practice, we report the outcomes of predialysis programs in two major Canadian cities. The purpose of this report was to determine whether the institution of a multidisciplinary predialysis program is of benefit to patients, and to analyze those factors that are important in actualizing those benefits. Data from two different studies is presented: (1) a prospective, nonrandomized cohort study comparing patients who were or were not exposed to an ongoing multidisciplinary predialysis team (St Paul's Hospital) and (2) a retrospective review of outcomes before and after the institution of a predialysis program (The Toronto Hospital). Although created independently in major academic centers in Canada, the programs both aimed to reduce urgent dialysis starts, improve preparedness for dialysis, and improve resource utilization. The Vancouver study was able to demonstrate significantly fewer urgent dialysis starts (13% v 35%; P < 0.05), more outpatient training (76% v 43%; P < 0.05), and less hospital days in the first month of dialysis (6.5 days v 13.5 days; P < 0.05). Cost savings of the program patients in 1993 are conservatively estimated to be $173,000 (Canadian dollars) or over $4,000 per patient. The Toronto study demonstrated success in predialysis access creation (86.3% of patients), but could not realize any benefit in terms of elective dialysis initiation due to well-documented hemodialysis resource constraints. We conclude that an approach to predialysis patients involving a multidisciplinary team can have a positive impact on quantitative outcomes, but essential elements for success include (1) early referral to a nephrology center, (2) adequate resources for dedicated predialysis program staff and infrastructure, and (3) available resources for patients with end-stage renal disease (ESRD) (dialysis stations). In times of economic constraints, objective data are necessary to justify resource-intensive proactive programs for patients with ESRD. Future studies should confirm and extend our observations so that optimum and cost-effective care for patients approaching ESRD is uniformly available.
OBJECTIVE: The purpose of this study was to assess a full range of pathological childhood experiences reported by patients with criteria-defined borderline personality disorder and comparison patients with other personality disorders. METHOD: The pathological childhood experiences reported by 467 inpatients with personality disorders were assessed by interviewers who used a semistructured research interview and were blind to clinical diagnosis. RESULTS: Of the 358 patients with borderline personality disorder, 91% reported having been abused, and 92% reported having been neglected, before the age of 18. The borderline patients were significantly more likely than the 109 patients with other personality disorders to report having been emotionally and physically abused by a caretaker and sexually abused by a noncaretaker. They were also significantly more likely to report having a caretaker withdraw from them emotionally, treat them inconsistently, deny their thoughts and feelings, place them in the role of a parent, and fail to provide them with needed protection. The borderline patients with a childhood history of sexual abuse were significantly more likely than those without such a history to report having experienced all but one of the types of abuse and neglect studied. When all significant risk factors were considered together, four were found to be significant predictors of a borderline diagnosis: female gender, sexual abuse by a male noncaretaker, emotional denial by a male caretaker, and inconsistent treatment by a female caretaker. CONCLUSIONS: The results suggest that sexual abuse is neither necessary nor sufficient for the development of borderline personality disorder and that other childhood experiences, particularly neglect by caretakers of both genders, represent significant risk factors.
PURPOSE: To determine whether breast conservation and prolonged neoadjuvant chemotherapy have efficacy in locally advanced breast cancer (LABC), as measured by survival and rate of breast conservation. MATERIALS AND METHODS: Eighty-nine patients with stage III disease were enrolled at the University of Michigan (UM) onto a prospective nonrandomized trial. Patients received nine 21-day cycles of neoadjuvant chemohormonal therapy that consisted of doxorubicin 30 mg/m2 and cyclophosphamide 750 mg/m2 intravenously on day 1, conjugated estrogens 0.625 mg orally twice daily on days 6 to 8, methotrexate 40 mg/m2 and fluorouracil 500 mg/m2 intravenously on day 8, and tamoxifen 10 mg orally twice daily on days 9 to 14. Patients with a negative biopsy received radiation only, while those with residual disease underwent mastectomy and postoperative radiotherapy. Eight more cycles of chemohormonal therapy were administered after local-regional therapy. RESULTS: The clinical response rate to neoadjuvant therapy was 97%, 28% of patients had a complete pathologic response evaluated at biopsy. Five-year overall and disease-free survival probabilities were 54% and 44%, respectively. The median disease-free survival time was 2.4 years. The 5-year actuarial rates of local-regional control with local failure as only first failure were 82% and 78% following radiotherapy, and mastectomy and radiotherapy, respectively (P = .99). CONCLUSION: Prolonged neoadjuvant chemohormonal therapy and biopsy-driven local therapy have efficacy in LABC, with 28% of patients being candidates for breast conservation and a 5-year overall survival rate of 54%.
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There has been considerable debate regarding the use of pediatric donor kidneys in adults with end-stage renal disease. These small kidneys may not be able to deal with the metabolic demands of the large adult size, and thus pediatric kidneys may be at higher risk of loss due to hyperperfusion injury. To study the impact of small kidney size on renal outcome, we studied two groups of patients. This retrospective review of patients at a single institution compared recipients of pediatric renal transplants (age < 7 years, n = 37) to a matched group of adult-kidney recipients (1:2 ratio, n = 74). The groups were matched for age, sex, diabetic status, HLA type, and duration of follow-up. Primary outcomes of interest were: calculated creatinine clearance at 6 months, 1 year, 2 years, and 3 years after transplantation and evidence of hyperperfusion damage as determined by proteinuria, graft biopsy, and late graft loss due to chronic rejection. This study demonstrates no significant difference in calculated creatinine clearance between pediatric and adult transplants at 6 months (43.8 vs. 50.7 ml/min, respectively) or at 3 years after transplantation (56.3 vs. 56.2 ml/min), nor was there any evidence of increased proteinuria or late graft loss in the pediatric-kidney recipients compared with adult-kidney recipients. Our data do not demonstrate the detrimental effects of small kidney size relative to recipient on subsequent renal outcomes, and thus support the practice of pediatric donor kidneys being used in adult recipients when pediatric recipients are not available.
Left ventricular hypertrophy is very prevalent among patients with renal insufficiency. Known hypertrophic factors, such as systemic hypertension, do not adequately account for the prevalence of left ventricular hypertrophy in these patients. Circulating growth factors may stimulate cardiomyocyte growth and contribute to the development of left ventricular hypertrophy. The effects of sera from patients with (n = 30) and without (n = 5) chronic renal insufficiency on the growth of cultured adult cardiomyocytes were compared. An adult rat cardiomyocyte primary culture system was established with a high purity of cardiomyocyte population as confirmed by immunocytochemical staining of cardiac contractile proteins. Myocytes responded with increased [3H]thymidine incorporation when treated with angiotensin II, epidermal growth factor, hydrocortisone and insulin, and with increased [3H]phenylalanine incorporation when treated with parathormone, isoproterenol, phenylephrine and insulin. Renal insufficiency serum stimulated [3H]thymidine incorporation was 1.5 times that of the control (P < 0.02) and also tended to increase incorporation of [3H]phenylalanine compared to the control (P = N.S.). Increased [3H]thymidine incorporation by renal insufficiency serum did not correlate with serum insulin, parathormone or glucose in the renal insufficiency patients. A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) method was used to measure renal insufficiency serum-induced atrial natriuretic peptide mRNA expression in cultured cardiomyocytes. Atrial natriuretic peptide (ANP) mRNA was increased 1-3-fold in cardiomyocytes treated with renal insufficiency sera in comparison to control sera. These data suggest that circulating growth factor(s) may contribute to the development of cardiac hypertrophy in patients with renal insufficiency.
We report a case of Farber lipogranulomatosis in a girl with hepatosplenomegaly, macular cherry-red spot, and subcutaneous nodules who developed liver dysfunction with jaundice and ascites, and myelophthisic anaemia because of infiltration of bone marrow with storage cells. Acid ceramidase assay confirmed the diagnosis. We conclude that the bone marrow dysfunction and cherry-red spot are features of type IV Farber lipogranulomatosis that have not been previously recognized, and should be added to the clinical phenotypic description.
Left ventricular hypertrophy (LVH) is present in over 70% of patients commencing dialysis. It is an independent risk factor for cardiac death, which is the cause of death in approximately 45% of patients in dialysis. The prevalence of LVH in patients earlier in the course of renal insufficiency is unknown. As part of a prospective longitudinal study evaluating the progression of comorbid diseases in patients with progressive renal disease, we evaluated LVH. In 175 consecutive patients attending a renal insufficiency clinic we obtained technically adequate echocardiograms and estimated left ventricular mass index (LVMI) using two-dimensional targeted M-mode echocardiography. We calculated LVMI using the American Society of Echocardiography cube formula method regressed to anatomic validation. The population consisted of 115 men and 60 women ranging in age from 20 to 82 years (mean age, 51.5 years). The mean creatinine was 403 +/- 207 micro mol/L (+/-SD), representing a creatinine clearance (Ccr) of 25.5 +/- 17 mL/min. Left ventricular hypertrophy was defined as LVMI greater than 131 g/m(2) in men and greater than 100 g/m(2) in women, and was present in 38.9% of the population studied. We demonstrate that the prevalence of LVH increased with progressive renal decline: 26.7% of patients with Ccr greater than 50 mL/min had LVH, 30.8% of those with Ccr between 25 and 49 mL/min had LVH, and 45.2% of patients with severe renal impairment (Ccr <25 L/min) had LVH (P = 0.05). The mean LVMI was significantly different among the three groups (97.5 g/m(2) v 114.4 g/m(2), respectively; P < 0.001). Univariate analyses revealed that age, hemoglobin, systolic blood pressure and Ccr were significantly different between the groups with and without LVH. The logistic regression model confirmed the findings of the univariate analysis: an increase in age of 5 years was associated with an increase of 3% in risk of LVH (P = 0.0094), as was an increase in systolic blood pressure of 5 mm Hg (P = 0.0018). For each 10 g/L decrease in hemoglobin, the risk of LVH increased by 6% (P = 0.0062), and for each 5 mL/min decline in Ccr the risk increased by 3% (P = 0.0168). We demonstrate the high prevalence of LVH in patients with renal insufficiency prior to the need for dialysis, which is associated with severity of renal impairment, and identify two modifiable factors (systolic blood pressure and anemia) as important predictors of LVH. We suggest that future studies should focus on interventions aimed at attenuating the impact of these factors.
Of 54 milk samples from 54 healthy nursing women analysed for volatile N-nitrosamines, 42 appeared negative. Trace amounts (below the detection limit 0.5 microgram l-1) of N-nitrosodimethylamine were detected in the milk of 10 mothers and two samples contained this compound at 1.1 and 1.2 micrograms 1-1 respectively. Almost all samples investigated contained nitrate (mean 2.9 +/- 2.3 mg1-1 and nitrate reducing microorganisms (mean 4.2 +/- 1.0 log ml-1). The recent finding of N-nitrosodimethylamine in human milk gives evidence of the continuous endogenous formation of N-nitrosamines.