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PubMed2005

Coronary and aortic calcification in women with a history of major depression.

BACKGROUND: Although depression is a well-documented risk factor for clinical heart disease, its association with subclinical atherosclerosis is unclear. We hypothesized that middle-aged women with a history of recurrent major depression would show evidence of atherosclerosis. METHODS: Coronary and aortic calcification was measured by electron beam tomography in 58 African American and 152 white healthy middle-aged women. Women were administered the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and a self-report measure of current depressive symptoms. RESULTS: Coronary calcification was found in 103 women (49%) and aorta calcification in 144 women (54%); high calcification scores were set at approximately 75% of the sample distribution (ie, at >/=10 for the coronary calcium score [n = 49 women] and at >100 for the aorta calcium score [n = 53 women]). Women with a history of recurrent major depression (n = 53) were more likely to have any coronary calcification or calcification in the high category at either site compared with women with a history of a single episode of depression or no depression. After stepwise forward adjustment for cardiovascular risk factors and sociodemographic characteristics, a history of recurrent major depression, compared with a single episode or no history, was associated with odds ratios (ORs) of 2.46 (95% confidence interval [CI], 1.06-5.67) for any coronary calcification, 2.71 (95% CI, 1.08-6.81) for high coronary calcification, and 3.39 (95% CI, 1.34-8.63) for high aortic calcification. Further adjustments for waist-hip ratio reduced the association between history of recurrent depression and any calcification (OR, 2.24; 95% CI, 0.94-5.32) and high calcification (OR, 2.31; 95% CI, 0.89-5.99). CONCLUSIONS: In this sample of asymptomatic middle-aged women without known coronary disease, recurrent major depression was independently associated with coronary and aortic calcification. Waist-hip ratio in part mediated the association. Our findings suggest that recurrent major depression may be a risk factor for early atherosclerosis in women.

Adult↗

PubMed2006

Prediction of recurrent spontaneous pneumothorax: CT scan findings versus management features.

OBJECTIVE: To assess the association between primary spontaneous pneumothorax (PSP) recurrence and pulmonary CT scan findings, and other variables pertaining to clinical presentation and management. METHODS: Consecutive patients hospitalized for the first episode of PSP and treated by various strategies including chest tube or pleurocatheter drainage and, in persistent pneumothorax, by chemical or surgical pleurodesis. All patients had a pulmonary CT scan examination in the week following hospital discharge in order to calculate a score combining distribution, number and size of dystrophic pulmonary abnormalities. This score as well as other pertinent clinical and therapeutic parameters were compared between patients who ultimately experienced PSP recurrence and those who did not. RESULTS: Eighty patients (mean age: 27+/-7 yr) were admitted for PSP and had a chest drainage with either a drain or pleurocatheter. Chest drainage and hospitalization durations were 4.7+/-3.2 and 6.2+/-3.5 days, respectively. Sixteen patients required chemical pleurodesis. Dystrophic bullae were present in CT scans in 72.5% patients. After a mean follow up of 34+/-20 months, 15 out of the 80 patients (19%) had a PSP recurrence. Multivariate statistical analysis disclosed the use of pleurocatheter (OR=5; 95% CI: 1.4-20; P=0.02) and of chemical pleurodesis (OR=8; 95% CI: 1.5-47; P=0.015) as independent predictors of PSP recurrence. The severity of dystrophic lesions inferred from the dystrophic score was not statistically associated with the risk of recurrence. CONCLUSION: Dystrophic lesions are frequently present in PSP. They are not associated with an increased risk of recurrence.

Adolescent↗

PubMed1999

Type 2 diabetes: evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs.

We are conducting a genome scan at an average resolution of 10 centimorgans (cM) for type 2 diabetes susceptibility genes in 716 affected sib pairs from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, chi = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q (chi = 57 cM, recurrence risk,lambda(s) = 1. 25, P = 0.009). Weighted logarithm of odds scores of 2.00 (chi = 69.5 cM, P = 0.010) and 1.92 (chi = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes-related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour glucose levels in offspring of diabetic individuals gave a MLS of 2. 12 (P = 0.0018) at 9.5 cM. Evidence from this and other studies suggests at least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity-onset diabetes of the young 1, hepatic nuclear factor 4-a (HNF-4alpha) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20q. We found no evidence that sequence changes in this gene accounted for the linkage results we observed.

Adult↗

PubMed2006

Effect of nonviral factors on hepatitis C recurrence after liver transplantation.

OBJECTIVE: Hepatitis C (HCV) is now the most common indication for orthotopic liver transplantation (OLT). While graft reinfection remains universal, progression to graft cirrhosis is highly variable. This study examined donor, recipient, and operative variables to identify factors that affect recurrence of HCV post-OLT to facilitate graft-recipient matching. METHODS: Retrospective review of 307 patients who underwent OLT for HCV over a 10-year period at our center. Recurrence of HCV was identified by the presence of biochemical graft dysfunction and concurrent liver biopsy showing diagnostic pathologic features. Time to recurrence was the endpoint for statistical analysis. Five donor, 6 recipient, and 2 operative variables that may affect recurrence were analyzed by univariate comparison and Cox proportional hazard regression models. RESULTS: Recurrence-free survival in the 307 study patients was 69% and 34% at 1 and 5 years, respectively. Four predictive variables related to either donor or recipient characteristics were identified. Advanced donor age, prolonged donor hospitalization, increasing recipient age, and elevated recipient MELD scores were found to increase the relative risk of HCV recurrence. Examination of HLA disparity between donors and recipients demonstrated no correlation between class I or class II mismatches and recurrence-free survival. CONCLUSIONS: We have identified donor and recipient characteristics that significantly predict hepatitis C recurrence following liver transplantation. These factors are identifiable before transplant and, if considered when matching donors to HCV recipients, may decrease the incidence of HCV recurrence after OLT. A change in the current national liver allocation system would be needed to realize the full value of this benefit.

Adult↗

PubMed2006

Early results for new lightweight mesh in laparoscopic totally extra-peritoneal inguinal hernia repair.

Prosthetic mesh reinforcement is now routine in the management of inguinal hernia but can cause considerable pain and stiffness around the groin. The aim of this study was to compare the outcome after laparoscopic TEP inguinal repair using new lightweight or traditional heavyweight mesh performed in a single unit. Between November 2004 and March 2005, 113 patients underwent laparoscopic TEP inguinal repair using either lightweight (28 g/m(2)) or heavyweight (85 g/m(2)) mesh. Follow-up data was obtained using case note review and telephone-based questionnaire in April 2005. Follow-up information was obtained for 93 (83%) out of 113 patients. There was no difference between the two groups in the incidence of pain/discomfort at mean 3-month follow-up (45 vs 41%, Mann-Whitney U, P=0.641). However, there was a significant inverse correlation between the length of time since operation and severity of pain/discomfort in the lightweight group (P=0.001, Pearson test), suggesting a faster speed of recovery with lightweight mesh. Laparoscopic TEP inguinal hernia repair with lightweight mesh yields promising early results. Whilst there was no significant difference in pain or recurrence in the short term, post-operative pain scores improved earlier in patients with lightweight mesh compared to heavyweight mesh. This merits further study, with larger cohorts and longer follow-up, to determine the benefits of lightweight mesh.

Adult↗

PubMed2004

Treatment outcomes of three-dimensional conformal radiotherapy for localized prostate carcinoma: a large community-based experience.

BACKGROUND: The current study documented the implementation of three-dimensional conformal radiotherapy and assessed the tumor control and toxicity of such treatment in a large, multisite community practice. METHODS: The authors retrospectively reviewed their first 222 consecutive patients with clinically localized (N0) prostate carcinoma treated with a 6-field conformal technique from October 1993 through March 2000. Standardized target definitions, dose planning constraints, and gantry angles were utilized to develop the treatment plan. Patients were categorized by low, intermediate, and high risk. Low risk was defined as T1a-T2a disease, a Gleason score < 7, and prostate-specific antigen (PSA) level </= 10.0 ng/mL (n = 47 [21%]). Intermediate risk was defined as T2b disease, a Gleason score > 6, or PSA level > 10.01 ng/mL (n = 60 [27%]). High risk was defined as 2 of the above risk factors or as T3 disease, a Gleason score > 7, or a PSA level > 20 (n = 115 [52%]). Biochemical disease recurrence was defined in accordance with the American Society for Therapeutic Radiology and Oncology definition. Urinary and bowel toxicity were graded using the Radiation Therapy Oncology Group morbidity scoring system. RESULTS: The median follow-up after radiotherapy for surviving patients was 47 months (range, 0-99 months). The 2 and 5-year actuarial biochemical control rates for all patients were 84% and 78%, respectively. Using logistic regression analysis, lower dose (< 75.6 gray [Gy] vs. 75.6 Gy; P = 0.006), higher risk group (P = 0.033), higher stage (P = 0.045), and higher PSA level (P = 0.001) were significantly associated with biochemical disease recurrence. Toxicity was not significantly correlated with a higher radiotherapy dose. CONCLUSIONS: Dose escalation to 75.6 Gy using a 6-field conformal technique was feasible in the authors' community practice and resulted in acceptable toxicity and early biochemical outcomes.

Adult↗

PubMed2003

Timing of cholecystectomy for acute biliary pancreatitis: outcomes of cholecystectomy on first admission and after recurrent biliary pancreatitis.

Biliary stones are the leading cause of acute pancreatitis. Although cholecystectomy and selective endoscopic retrograde cholangiography (ERC) comprise the current treatment in patients with acute biliary pancreatitis (ABP), the time of intervention is still controversial. In this study we evaluated the outcomes of cholecystectomy on first admission for ABP and in patients with recurrent biliary pancreatitis. A series of 43 patients with ABP between January 1997 and November 2000 were evaluated retrospectively. Patients were classified into two groups. Group I included 27 patients who underwent cholecystectomy on first admission before discharge from the hospital. Group II comprised 16 patients who had recurrent biliary pancreatitis and then underwent cholecystectomy. The severity of the pancreatitis was determined by Ranson's criteria. Age, gender, length of hospital stay, severity of pancreatitis, amylase level, and complications of cholecystectomy were evaluated in both groups. Patients in group I underwent cholecystectomy during the original hospital admission and patients in group II during an admission for a recurrence. There were 24 patients with a Ranson's score </= 3 in group I and 12 in group II. The mean hospital stays were 15.29 days (range 4-48 days) and 36.66 days (range 15-123 days) in groups I and II, respectively ( p = 0.006). Morbidity was 11% without mortality in group I and 43% with one mortality in group II ( p = 0.023). Definitive treatment of ABP can be accomplished effectively and safely by cholecystectomy following clinical improvement, with selective ERC performed during the first admission (delayed cholecystectomy). Waiting to perform cholecystectomy (interval cholecystectomy) may result in recurrent biliary pancreatitis, which may increase morbidity and the length of the hospital stay.

Acute Disease↗

PubMed2004

[Microwave coagulation therapy for liver metastases from colorectal cancer].

Hepatic resection has gained acceptance as the most effective therapy for liver metastases from colorectal cancer. Microwave coagulation therapy (MCT) and radiofrequency ablation as well as resection are also reported as effective therapies. We analyzed the prognosis of 52 patients with liver metastases from colorectal cancer treated with MCT as the first radical therapy. A total of 4 percutaneous MCT's (3 cases with interruption of hepatic blood flow), 23 MCT's with laparotomy, and 25 with hepatic resection + MCT with laparotomy were performed. Thirty-three MCT's performed as a second therapy for recurrence in the liver were also analyzed. Clinical risk scoring as reported by Fong, et al was used in our cases. The indication for percutaneous MCT with interruption of hepatic blood flow is solitary tumor less than 20 mm in diameter. The 5-year survival rate for the 4 percutaneous MCT's, 23 MCT's with laparotomy, and 25 hepatic resection + MCT's with laparotomy and 68 hepatic resections were 20, 24 and 24%, respectively. No significant difference was found among them. The 5-year survival rate for the 17 MCT's and 12 hepatic resections with recurrence in the liver were 20% and 24%, respectively. There was no significant difference found between them. The 5-year survival rate for the 28 CRS3 was 17%, almost equal to the rate, 20%, reported by Fong, et al for hepatic resections only. MCT is effective therapy for liver metastases from colorectal cancer, recurrence in the liver, and hepatic resections.

Adult↗

PubMed2000

The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making.

CONTEXT: Patients with unstable angina/non-ST-segment elevation myocardial infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk for death and cardiac ischemic events. OBJECTIVE: To develop a simple risk score that has broad applicability, is easily calculated at patient presentation, does not require a computer, and identifies patients with different responses to treatments for UA/NSTEMI. DESIGN, SETTING, AND PATIENTS: Two phase 3, international, randomized, double-blind trials (the Thrombolysis in Myocardial Infarction [TIMI] 11B trial [August 1996-March 1998] and the Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI trial [ESSENCE; October 1994-May 1996]). A total of 1957 patients with UA/NSTEMI were assigned to receive unfractionated heparin (test cohort) and 1953 to receive enoxaparin in TIMI 11B; 1564 and 1607 were assigned respectively in ESSENCE. The 3 validation cohorts were the unfractionated heparin group from ESSENCE and both enoxaparin groups. MAIN OUTCOME MEASURES: The TIMI risk score was derived in the test cohort by selection of independent prognostic variables using multivariate logistic regression, assignment of value of 1 when a factor was present and 0 when it was absent, and summing the number of factors present to categorize patients into risk strata. Relative differences in response to therapeutic interventions were determined by comparing the slopes of the rates of events with increasing score in treatment groups and by testing for an interaction between risk score and treatment. Outcomes were TIMI risk score for developing at least 1 component of the primary end point (all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization) through 14 days after randomization. RESULTS: The 7 TIMI risk score predictor variables were age 65 years or older, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50% or more, ST-segment deviation on electrocardiogram at presentation, at least 2 anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac markers. Event rates increased significantly as the TIMI risk score increased in the test cohort in TIMI 11B: 4.7% for a score of 0/1; 8.3% for 2; 13. 2% for 3; 19.9% for 4; 26.2% for 5; and 40.9% for 6/7 (P<.001 by chi(2) for trend). The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation groups (P<.001). The slope of the increase in event rates with increasing numbers of risk factors was significantly lower in the enoxaparin groups in both TIMI 11B (P =.01) and ESSENCE (P =.03) and there was a significant interaction between TIMI risk score and treatment (P =. 02). CONCLUSIONS: In patients with UA/NSTEMI, the TIMI risk score is a simple prognostication scheme that categorizes a patient's risk of death and ischemic events and provides a basis for therapeutic decision making. JAMA. 2000;284:835-842

Aged↗

PubMed1983

Pathologic features of nerve sheath tumors with respect to prognostic signs.

Clinicopathologic evaluation of primary and recurrent nerve sheath tumors was performed for 87 fully documented cases treated in the National Oncological Institute (Budapest) between 1955 and 1976. Morphologic features of all tumors, i.e., of both nonrecurring and recurring tumors with and without malignant transformation, were evaluated according to a uniform scoring system. Scores of the primary tumors showed good correlation with their further course; in case of recurring tumors, the scores permitted some conclusions regarding their expectable behavior. Neurofibromas and neurinomas displayed similar courses, but the clinical courses of typical and cellular tumors were not the same. Cellular tumors with high scores were more disposed to recur and undergo malignant transformation. Recurrences in cases of late malignant transformation were more frequent than in those showing no transformation.

Adult↗

PubMedDate not supplied

Quality of life assessments in epithelial ovarian cancer patients during and after chemotherapy.

To study the immediate and long-term effects of chemotherapy on quality of life (QoL) of advanced ovarian cancer patients. All consecutive patients undergoing chemotherapy for metastatic ovarian cancer and those presenting for follow-up post chemotherapy were recruited. Participants were asked to fill out a short QoL questionnaire (Functional Assessment Cancer Therapy-Ovarian) during each clinic visit. Two-factor analysis of variance analyses were used to examine the effects of chemotherapy treatment and current disease status on QoL scores. Ninety-four patients on chemotherapy and 159 follow-up patients participated. Patients on chemotherapy for recurrent disease had a significantly worsened overall, emotional, and ovarian cancer-specific concerns QoL scores compared to those receiving first-line chemotherapy. There were favorable significant differences between those on follow-up compared to those on chemotherapy in the mean overall QoL scores and in the means of physical, functional, and concern scores. There were significant differences favoring patients with complete response compared to those with partial response or progressive disease in the mean overall QoL scores as well as the physical, emotional, functional, and concern domains mean scores. There were improvements in most QoL measures after completion of chemotherapy. Complete disease remission remained important in maintaining improved QoL.

Female↗

PubMed1995

Radiological evidence of constipation in urinary tract infection.

Little objective evidence has been published to support the claim that constipation is an important contributory factor in recurrent urinary tract infection (UTI) in childhood. Using a radiological scoring system, two observers assessed faecal loading from abdominal radiographs of children with proved UTIs. There was a significant increase in the degree of faecal loading in children with UTI when compared with controls (r = 0.237). This difference was mainly accounted for by girls with recurrent (greater than five) UTIs. This study confirms an association between recurrent UTI and faecal loading. Further studies are needed to establish if there is a causal relationship and benefits from treatment.

Adolescent↗

PubMed2004

Early carotid surgery in acute stroke: a multicentre randomised pilot study.

BACKGROUND: Standard practice has been to delay carotid endarterectomy (CEA) for 2 months following acute stroke to avoid a perceived risk of cerebral haemorrhage. We investigated whether early CEA reduces early recurrent stroke and improves outcome in partial anterior circulation infarction (PACI). METHODS: Patients with PACI and a Barthel score of >18 before stroke underwent carotid duplex and CT imaging within 7 days of stroke. Forty consenting patients fit for surgery with greater than 70% ipsilateral carotid stenosis were randomised, 19 to 'early' (within 24 h) and 21 to 'delayed' surgery (at 8 weeks). Modified Rankin and Barthel scores were recorded at 1 week, 2 months, 6 and 12 months. RESULTS: Rankin scores improved more rapidly following 'early' surgery to a score of 1 (0-4) at 2 and 6 months compared with 2.5 and 2 (1-4), respectively, for delayed surgery (p < 0.05). Barthel scores were also significantly improved following 'early' CEA at 7 days but both groups reached a median score of 20 by 2 months. Four 'delayed' and 3 'early' patients suffered extension or recurrence of neurological deficits with 1 death in each group. CONCLUSIONS: Early CEA within 7 days of ischaemic stroke improved functional outcome with earlier hospital discharge. A large multicentre study is needed to exclude the possibility that 'early' CEA increases the risk of cerebral haemorrhage or death.

Activities of Daily Living↗

PubMed2003

Percent of prostate needle biopsy cores with cancer is significant independent predictor of prostate specific antigen recurrence following radical prostatectomy: results from SEARCH database.

PURPOSE: Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy. MATERIALS AND METHODS: A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. RESULTS: On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p <0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p <0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score. CONCLUSIONS: Percent of positive cores in the prostate needle biopsy was a significant predictor of adverse pathology and biochemical failure following radical prostatectomy, and the cut points of less than 34%, 34% to 50% and greater than 50% can be used to risk stratify patients preoperatively. The finding that percent of positive cores from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome.

Biopsy, Needle↗

PubMed2000

Menstrual cycle symptom variation in a community sample of women using and not using oral contraceptives.

BACKGROUND: The prevalence of significant symptom change (symptom cyclicity) prospectively rated over multiple menstrual cycles has not been established in a non-clinical population. METHODS: Seventy-three women charted 57 symptoms over 2-6 menstrual cycles each. Symptoms, and summarized symptom scores within seven symptom groups, were tested for changes between the follicular phase and the luteal phase of each cycle. Recurrent symptom cyclicity over multiple cycles within individuals was ascertained and the stability between cycles of mean symptom scores for both the follicular phase and the luteal phase. RESULTS: Forty-five percent of the participants experienced cyclicity over multiple cycles in at least one symptom and 23% in at least one symptom group. Eighteen percent of the participants consistently reported a higher symptom score during the luteal phase compared to the follicular phase (a PMS-like pattern) in all symptoms in which they experienced a change. The remaining 27% experienced a varying direction of change in the same symptom between cycles, or consistently experienced a lower symptom score during the luteal phase (a reverse PMS-like pattern) of the cycles they charted. Recurrent cyclicity was experienced by 16% of the participants in one symptom; in two symptoms by 15%; in 3 8 symptoms by 14%; in one symptom group by 19% and in two symptom groups by only 4% of participants. Average symptom severity did not vary significantly between cycles. CONCLUSION: Due to the varied direction of symptom severity change over multiple cycles, prospective daily ratings are necessary to achieve a true picture of menstrual related symptom cyclicity in the general population.

Adult↗

PubMed1990

Treatment of aggressive keratoacanthomas by radiotherapy.

Keratoacanthomas infrequently are treated by radiotherapy. However, keratoacanthomas that are recurrent after surgical excision or whose resection would result in cosmetic deformity may benefit from radiotherapy. Between January 1970 and June 1988, 29 such keratoacanthomas in 18 patients were irradiated. Doses ranged from 3500 cGy in 15 fractions to 5600 cGy in 28 fractions. Measured end points of therapy were (1) initial response, (2) freedom from recurrence, and (3) quality of the subsequent cosmetic appearance (scored as good, fair, or poor). No lesion progressed and all eventually regressed completely. Cosmetic results generally were considered good by both the patient and the referring dermatologist; none of the results was considered poor. Our results demonstrate that radiation is an effective means of treating keratoacanthomas.

Adult↗

PubMed2003

The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. METHODS: We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. RESULTS: The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

5-alpha Reductase Inhibitors↗

PubMed2000

A neural network predicts progression for men with gleason score 3+4 versus 4+3 tumors after radical prostatectomy.

OBJECTIVES: To determine the significance of Gleason scores 3+4 (GS3+4) versus 4+3 (GS4+3) with respect to biochemical recurrence in a retrospective review of a series of men with clinically localized prostate cancer who underwent radical retropubic prostatectomy (RRP) and to develop and test an artificial neural network (ANN) to predict the biochemical recurrence after surgery for this group of men using the pathologic and clinical data. METHODS: From 1982 to 1998, 600 men had pathologic Gleason score 7 disease without lymph node or seminal vesicle involvement. We analyzed the freedom from biochemical (prostate-specific antigen) progression after RRP on 564 of these men on the basis of their GS3+4 versus GS4+3 (Gleason 7) status. The Cox proportional hazards model was used to determine the importance of Gleason 7 status as an independent predictor of progression. In addition, an ANN was developed using randomly selected training and validation sets for predicting biochemical recurrence at 3 or 5 years. Different input variable subsets, with or without Gleason 7 status, were compared for the ability of the ANN to maximize the prediction of progression. Standard logistic regression was used concurrently on the same random patient population sets to calculate progression risk. RESULTS: A significant recurrence-free survival advantage was found in men who underwent RRP for GS3+4 compared with those with GS4+3 disease (P <0.0001). The ANN, logistic regression, and proportion hazard models demonstrated the importance of Gleason 7 status in predicting patient outcome. The ANN was better than logistic regression in predicting patient outcome, in terms of prostate-specific antigen progression, at 3 and 5 years. CONCLUSIONS: A simple modification of the Gleason scoring system for men with Gleason 7 disease revealed a difference in the patient outcome after RRP. ANN models can be developed and used to better predict patient outcome when pathologic and clinical features are known.

Disease Progression↗