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Biomedical subjects

Chris Robertson

Publications and source records attributed to Chris Robertson.

At least 19 recordsLinked to original sources
PubMed2006

Preliminary results on safety and activity of a randomized, double-blind, 2 x 2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention in premenopausal women.

PURPOSE: To determine whether low-dose tamoxifen and fenretinide have a synergistic effect on surrogate biomarkers, including circulating insulin-like growth factor I (IGF-I) and mammographic density, in premenopausal women at risk for breast cancer and to study drug safety. PATIENTS AND METHODS: Premenopausal women (n = 235) were randomly assigned in a double-blind four-arm trial to receive tamoxifen 5 mg/d, fenretinide 200 mg/d, both agents, or placebo for 2 years. The present analysis refers to preliminary data on safety, IGF-I, and breast cancer events. RESULTS: Patients were included if they had an excised ductal carcinoma-in-situ (57%), lobular carcinoma-in-situ (13%), minimal invasive breast cancer (7%), or a 5-year Gail risk > or = 1.3% (23%). After a median follow-up of 40 months, there was a reduction of 13%, 2%, 20%, and 1% in IGF-I levels for patients on tamoxifen, fenretinide, tamoxifen plus fenretinide, and placebo, respectively. Recruitment was stopped based on the lack of an interaction on IGF-I levels, which was a primary end point for the study. Thirty-six patients have dropped out of the study, 17 because of adverse events and 19 for various other reasons. One stage I endometrial cancer occurred in a patient on fenretinide, and one optic nerve ischemia and one deep venous thrombosis occurred on tamoxifen. There was no difference in menopausal symptoms, endometrial thickness, polyps, or ovarian cysts among treatment arms. To date, 24 breast cancers have been observed, without differences among arms. CONCLUSION: The combination of low-dose tamoxifen and fenretinide is safe but not synergistic in lowering IGF-I levels in premenopausal women. The clinical implications require further follow-up.

Adult↗
PubMed2005

Screening for prostate cancer: updated experience from the Tyrol study.

OBJECTIVES: The aim of this study was to monitor the impact of prostate cancer screening in a natural experiment by comparing prostate cancer mortality in Tyrol, Austria, where prostate-specific antigen (PSA) testing was made available at no charge, with the rest of Austria, where this screening was not introduced. METHODS: In 1993, PSA testing was made freely available to men aged 40 to 79 years old living in the Federal State of Tyrol, Austria. In the first 10 years of this study, at least 70% of all men in this age range had PSA tests done at least once. Initially, only total PSA was measured, but free PSA measurement was added in 1995, and complexed PSA was added in 2001. Digital rectal examination (DRE) was not part of the screening examination. RESULTS: Significant migration to lower clinical as well as pathological prostate cancer stages has been observed in patients undergoing radical prostatectomy since the introduction of this screening program. A reduction in mortality rates from prostate cancer in Austria occurred from 1993 onward, with a much greater reduction in Tyrol; mortality remained fairly constant between 1993 and 1995 and subsequently fell. From 1993 to 2000 (the most recent data), there was a significantly greater decrease in the rate of prostate cancer mortality in Tyrol compared to the rest of Austria (P value = 0.006). Based on age-specific death rates for men aged 40 to 79, the difference between the number of expected and observed deaths from prostate cancer in Tyrol was 22 in 1998 (a 42% decrease), 18 in 1999 (a 33% decrease) and 25 in 2000 (a 44% decrease). CONCLUSIONS: These findings are consistent with the hypothesis that a policy of making PSA testing freely available, and wide acceptance by men in the population, is associated with a reduction in prostate cancer mortality in an area in which urology services and radiotherapy are available freely to all patients. It is our opinion that most of this decline in mortality is likely to be due to aggressive downstaging and successful treatment and that any contribution from detecting and treating early cancers will only become apparent in the years to come.

Adult↗
PubMed2004

Beyond classical meta-analysis: can inadequately reported studies be included?

Classical meta-analysis requires the same data from each clinical trial, thus data-reporting must be of a high-quality. Imputation methods are used to include studies that provide incomplete information on variability and the fixed and random effects of a drug. Regression models can be used to include studies other than randomized placebo-controlled studies. In the example outlined here, the use of non-randomized single-arm studies and studies against comparator treatments has little influence on the estimation of the treatment effect in comparison with placebo, an effect that is based on the randomized placebo-controlled studies. The inclusion of other studies serves to increase the precision of the effect of the treatment compared with baseline. Although multiple imputation techniques enable a larger number of studies to be included, which will typically increase the precision of the estimated effect, a careful sensitivity analysis is also required.

Clinical Trials as Topic↗
PubMed2004

Breast carcinoma in elderly women: features of disease presentation, choice of local and systemic treatments compared with younger postmenopasual patients.

BACKGROUND: Aging remains one of the single greatest risk factors for the development of new breast carcinoma. The aim of the study was to evaluate the relation between biologic features at first diagnosis of breast carcinoma and treatment choice for postmenopausal women > or = 50 years to optimize treatment in the elderly. METHODS: The sample included 2999 consecutive postmenopausal patients referred for surgery at the European Institute of Oncology (Milan, Italy) from April 1997 to February 2002. The patients were grouped according to age: young postmenopausal (YPM; 50-64 years, n = 2052), older postmenopausal (OPM; 65-74, n = 801), and elderly postmenopausal (EPM; > or = 75, n = 146). RESULTS: EPM patients referred to surgery had larger tumors compared with YPM patients (pT4: 6.7% vs. 2.4%) as well as greater lymph node involvement (lymph node positive: 62.5% vs. 51.3%). EPM patients showed a higher degree of estrogen and progesterone receptor expression (P < 0.01), less peritumoral vascular invasion (P < 0.01), and less HER-2/neu expression (P < 0.01) than YPM patients. Comorbidities were more often recorded for elderly patients (72% EPM vs. 45% YPM; P < 0.001), did not influence surgical choices, and were similar across groups (breast conservation: 73.9%, 76.9%, and 72.9%, respectively). No systemic therapy (either chemotherapy or endocrine therapy) was recommended for 19.1% of the EPM compared with 5.4% and 4.7% of the two other groups. CONCLUSIONS: In spite of larger tumor size at presentation, older patients had tumors with more favorable biologic characteristics, when compared with younger postmenopausal patients. Reluctance to prescribe systemic treatments was due to the complexity of evaluation for these patients. Taking into account the data from the current study and given the climate of uncertainty regarding optimal treatment, the authors decided to individualize care on the basis of biologic characteristics, comorbidity, social support, functional status, and patient preferences. Trials of tailored adjuvant therapy should be a health care priority.

Aged↗
PubMed2004

The impact of meningococcal serogroup C conjugate vaccine in Scotland.

The increasing number of cases of serogroup C meningococcal disease in Scotland in the late 1990s coincided with the availability of a new meningococcal conjugate serogroup C (MCC) vaccine that, from 1999 onwards, was offered to all individuals aged <20 years. Annual incidence rates between 1994 and 2003 were calculated in 3 age groups (<5 years old; 5-19 years old; and >or=20 years old), and Poisson regression models were used to verify disease trends over time. Dramatic reductions (P<.05) in the incidence of serogroup C meningococcal disease were seen in target age groups: from 15.8 incidents per 100,000 subjects in 1999 (95% confidence interval [CI], 11.3-20.3) to 0.7 incidents per 100,000 subjects in 2001 (95% CI, -0.3 to 1.6), for subjects <5 years old, and from 6.7 incidents per 100,000 subjects in 1999 (95% CI, 5.1-8.3) to 1.5 incidents per 100,000 subjects in 2001 (95% CI, 0.7-2.3), for subjects 5-19 years old. An increasing incidence of serogroup B meningococcal disease in individuals 5-19 years old was clearly established before the campaign began. A 30% decrease in the case-fatality rate for individuals <20 years old was not significant (P=.1598). The MCC vaccine program has been highly effective in Scotland, leading to substantial reductions in serogroup C meningococcal disease and meningococcal mortality, with no adverse effects on other groups.

Adolescent↗
PubMed2004

A two-by-two factorial trial comparing oral with transdermal estrogen therapy and fenretinide with placebo on breast cancer biomarkers.

PURPOSE: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increase breast cancer risk, whereas the effect of transdermal estradiol (E2) and MPA is less known. Fenretinide may decrease second breast malignancies in premenopausal women but not in postmenopausal women, suggesting a hormone-sensitizing effect. We compared the 6 and 12-month changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), IGF-I:IGFBP-3 ratio, sex-hormone binding-globulin, and computerized mammographic percent density during oral CEE or transdermal E2 with sequential MPA and fenretinide or placebo. EXPERIMENTAL DESIGN: A total of 226 recent postmenopausal healthy women were randomly assigned in a two-by-two factorial design to either oral CEE 0.625 mg/day (n = 111) or transdermal E2, 50 microg/day (n = 115) and to fenretinide 100 mg/twice a day (n = 112) or placebo (n = 114) for 12 months. Treatment effects were investigated by the Kruskall-Wallis test and analysis of covariance. P values were two-sided. RESULTS: After 12 months, oral CEE decreased IGF-I by 26% [95% confidence interval (CI), 22-30%] and increased sex-hormone binding-globulin by 96% (95% CI, 79-112%) relative to baseline, whereas no change occurred with transdermal E2 (P < 0.001 between groups). Fenretinide decreased IGFBP-3 relative to placebo (P = 0.04). Percentage of breast density showed an absolute increase of 3.5% (95% CI, 2.5-4.6%) during hormone therapy without differences between groups (P = 0.39). CONCLUSIONS: Oral CEE has more favorable changes than transdermal E2 on circulating breast cancer risk biomarkers but gives similar effects on mammographic density. Fenretinide exerted little modulation on most biomarkers. The clinical implications of these findings require additional studies.

Administration, Cutaneous↗
PubMed2004

Tamoxifen and metabolite concentrations in serum and breast cancer tissue during three dose regimens in a randomized preoperative trial.

PURPOSE: Both therapeutic and adverse effects of tamoxifen may be related to its tissue concentrations. We investigated concentrations of tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and N-didesmethyltamoxifen in serum, normal breast, and breast cancer tissues during conventional dosage and two low-dose regimens. Furthermore we studied tamoxifen effects on the cancer proliferation marker Ki-67, and on sex hormone-binding globulin (SHBG). EXPERIMENTAL DESIGN: From September 1999 to August 2001, 120 breast cancer patients were randomized to 20-, 5-, or 1-mg tamoxifen daily. We measured serum and tissue concentrations of tamoxifen and three metabolites after 28 days of treatment, and the changes between baseline and post-treatment levels of SHBG and Ki-67. RESULTS: The median (range) tamoxifen concentrations (ng/ml) at doses of 1, 5, and 20 mg daily (n = 38, 37, and 36) were 7.5 (2.9-120.9), 25.2 (1.9-180.9), and 83.6 (8.7-134.4) in serum, and 78.2 (35.9-184), 272.3 (122-641), and 744.4 (208.6-2556) in breast cancer tissue, respectively. Tamoxifen levels followed a dose-concentration relationship. The concentrations of tamoxifen and metabolites were related to each other. Serum and tissue concentrations of tamoxifen were associated with corresponding changes of SHBG levels, whereas changes of Ki-67 levels were not related. CONCLUSIONS: Estrogen agonistic effects of tamoxifen on SHBG decreased with lower dosage, whereas tamoxifen effects on Ki-67 expression did not change. This together with a >10-fold variation in serum tamoxifen concentrations and a serum to tissue concentration relationship suggest that tamoxifen treatment may be improved by administration of lower doses and therapeutic drug monitoring.

Aged↗
PubMed2004

Screening for prostate cancer: updated experience from the Tyrol study.

The aim of the Tyrol study was to monitor the impact of screening in a natural experiment by comparing prostate cancer mortality in Tyrol, where prostate-specific antigen (PSA) testing was introduced at no charge, with the rest of Austria, where it was not strictly organized and not free of charge. In 1993, PSA testing was made freely available to men between the ages of 45 and 75 years in the Federal State of Tyrol, Austria. At least 70% of all of the men in this age range have been tested at least once during the first 10 years of the study. Initially, only total PSA was measured, but free PSA measurement was added in 1995. Since 2001, complexed PSA also has been measured. Digital rectal examination was not part of the screening examination. Significant migration to lower clinical and pathological stages has been observed since the introduction of this screening program. These findings are consistent with the hypothesis that the policy of making PSA testing freely available, and the wide acceptance by men in the population, is associated with a reduction in prostate cancer mortality in an area in which urology services and radiotherapy are available freely to all patients. It is our opinion that most of this decline is likely a result of aggressive downstaging and successful treatment and that any contribution from detecting and treating early cancers will become apparent in the years to come.

Aged↗
PubMed2004

Objective assessment of speech after surgical treatment for oral cancer: experience from 196 selected cases.

In 1992, a personal computer-based workstation for speech-digitized analysis was developed in conjunction with Canniesburn Hospital and Edinburgh University to measure all dispersion in speech after surgery for oral cancer. The voices of 196 patients with tumor of the oral cavity were recorded preoperatively and postoperatively. Surgical resection was carefully mapped out on standard diagrams of the oral cavity. Patients' recordings were assessed for conversational understandability by two referees. Patients also self-scored their speech using the Functional Intraoral Glasgow Scale self-questionnaire. Many patients had similar if not identical resections; therefore, 12 homogeneous groups were identified. Functional outcome for speech was correlated with the site and size of resected tissue and with the reconstruction modalities. The original association of an objective, computer-based tool and two subjective assessment tools proved to be the most suitable investigation method for speech. The general pattern was for consistently better speech quality with smaller excisions. The reconstruction modalities did not seem to influence the overall speech quality, as it was related mainly to the extent of surgical demolition. The authors present a detailed correlation between site and size of excision and functional outcome using color multiple-view diagrams for immediate appreciation. Positive and negative prognostic factors were identified in surgery for oral cancer.

Adult↗
PubMed2004

The prevalence of urinary incontinence in community-dwelling married women: a matter of definition.

OBJECTIVE: To determine the prevalence of female urinary incontinence (UI) and its impact on quality of life. SUBJECTS AND METHODS: In a Dutch national postal questionnaire survey, 1460 spouses of 1771 men in the town of Boxmeer, age-stratified and randomly selected, were asked to participate. The prevalence of UI in the women was assessed in two ways. First, a total score on a short UI-specific questionnaire differentiated them into three groups, i.e. no symptoms (score 0-2), minimally (3-6) or severely incontinent (7-14). Second, a self-reported UI prevalence was calculated by asking respondents if they ever had urine loss. To conform to the International Continence Society standard definition, spouses were also asked to complete a general (Short Form-12) and lower urinary tract disease-specific quality-of-life questionnaire, and were asked about their need to seek help. RESULTS: The questionnaires were returned by 1071 women (mean age 57 years, range 29-79; response rate 73%); 34% were regarded as minimally and 12% as severely incontinent. The self-reported UI rate was 40%. Disease-specific and general quality of life was significantly lower for women with UI than for those with minimal or no urine loss; 38% of incontinent respondents had consulted a physician for their UI, and among respondents with minimal complaints this was 28%. CONCLUSIONS: Up to 46% of the married female population had some degree of UI, and severe UI significantly compromised their quality of life.

Adult↗
PubMed2003

A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer.

BACKGROUND: Although numerous studies have shown that the status of the sentinel node is an accurate predictor of the status of the axillary nodes in breast cancer, the efficacy and safety of sentinel-node biopsy require validation. METHODS: From March 1998 to December 1999, we randomly assigned 516 patients with primary breast cancer in whom the tumor was less than or equal to 2 cm in diameter either to sentinel-node biopsy and total axillary dissection (the axillary-dissection group) or to sentinel-node biopsy followed by axillary dissection only if the sentinel node contained metastases (the sentinel-node group). RESULTS: The number of sentinel nodes found was the same in the two groups. A sentinel node was positive in 83 of the 257 patients in the axillary-dissection group (32.3 percent), and in 92 of the 259 patients in the sentinel-node group (35.5 percent). In the axillary-dissection group, the overall accuracy of the sentinel-node status was 96.9 percent, the sensitivity 91.2 percent, and the specificity 100 percent. There was less pain and better arm mobility in the patients who underwent sentinel-node biopsy only than in those who also underwent axillary dissection. There were 15 events associated with breast cancer in the axillary-dissection group and 10 such events in the sentinel-node group. Among the 167 patients who did not undergo axillary dissection, there were no cases of overt axillary metastasis during follow-up. CONCLUSIONS: Sentinel-node biopsy is a safe and accurate method of screening the axillary nodes for metastasis in women with a small breast cancer.

Adult↗
PubMed2003

A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers.

BACKGROUND: Tamoxifen reduces the risk of breast cancer in women at high risk for the disease but increases the risk for endometrial tumors and venous thromboembolisms, possibly in a dose-dependent fashion. We compared the effects of tamoxifen at 1 mg/day and 5 mg/day with those of the standard dose of 20 mg/day on breast cancer proliferation using a surrogate endpoint marker (Ki-67 expression) and blood biomarkers associated with breast cancer, cardiovascular disease, and bone fracture risk. METHODS: We randomly assigned 120 women with estrogen receptor (ER)-positive breast cancer to tamoxifen at 1, 5, or 20 mg/day for 4 weeks. Expression of the tumor proliferation marker Ki-67 and of biomarkers of breast cancer (insulin-like growth factor-I, sex hormone-binding globulin), cardiovascular disease (cholesterol, triglycerides, ultrasensitive C-reactive protein, fibrinogen, antithrombin-III), and bone fracture (type I collagen C-telopeptide) risk were determined before (baseline) and after treatment. All levels were compared with those in two nonrandomized control groups (34 women with ER-negative breast cancer and 29 additional women with ER-positive breast cancer). Data were analyzed by analysis of covariance. All statistical tests were two-sided. RESULTS: Expression of Ki-67 decreased in all three tamoxifen groups, with no difference in the magnitude of reduction among groups (P =.81). Relative to baseline, Ki-67 expression decreased by a median of 15.0% (95% confidence interval = 0.0% to 24.1%) among the tamoxifen groups but increased by 12.8% (95% confidence interval = 0.0% to 19.6%) among the nonrandomized control groups. Several blood biomarkers showed dose-response relationships with tamoxifen, including decreased insulin-like growth factor-I, increased sex hormone-binding globulin, and decreased low-density lipoprotein-cholesterol, ultrasensitive C-reactive protein, fibrinogen, and antithrombin-III levels. CONCLUSIONS: The effects on Ki-67 expression of lower doses of tamoxifen were comparable to those achieved with the standard dose, although the effects on blood biomarkers were variable. The effects of lower doses of tamoxifen should be assessed further in randomized trials.

Adult↗
PubMed2003

Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women.

Tamoxifen improves outcome in women with breast cancer and reduces the incidence of estrogen receptor-positive (ER+) breast tumors in prevention trials. Tamoxifen use is associated with an increased risk of potentially serious adverse events, principally endometrial cancer and venous thromboembolic events and, therefore, detailed knowledge of the effects of tamoxifen is important. With more cases of breast cancer being found as the follow-up time increases, it is now possible to perform more detailed analysis of the Italian Randomized Trial of Tamoxifen. Women with hysterectomy (N = 5408) were randomly assigned to receive 20 mg tamoxifen per day (N = 2700) or placebo (N = 2708). After a median of 81.2 months of follow-up, 79 case subjects (34 in the tamoxifen arm and 45 in the placebo arm) were diagnosed with breast cancer. We were able to identify a group of women at increased risk of ER+ breast cancers (high-risk group) on the basis of baseline as well as reproductive and hormonal characteristics (height, age at menarche, parity, age at first birth, and oophorectomy). Tamoxifen administered to women in the high-risk group showed statistically significantly reduced incidence of breast cancer (tamoxifen, 3 and placebo, 15; P =.003), but no such effect was seen in the low-risk group (tamoxifen, 31 and placebo, 30; P =.89). The positive effect of tamoxifen on breast cancer among high-risk women is most marked for ER+ tumors (tamoxifen, 1 and placebo, 11; P =.002). Chemoprevention of breast cancer with tamoxifen appears to be effective in women at high risk of ER+ tumors but not among women at low risk, who may well be protected naturally by late age at menarche or early first pregnancy, or artificially by removal of the ovaries. Tamoxifen could be offered as a preventive agent to women identified at high-risk of breast cancer because of hormone-related risk factors. Such a strategy would greatly reduce the numbers of women who would need to take tamoxifen to obtain the same absolute reduction in breast cancer. These findings are exploratory and need to be confirmed in other randomized trials.

Antineoplastic Agents, Hormonal↗
PubMed2003

Comparison of outcomes in women and men treated with coronary stent implantation.

Worse outcomes have been observed in women after PTCA. The present study was undertaken to compare clinical and angiographic results of coronary stenting among women and men. We retrospectively analyzed acute and 6-month results in a consecutive series of 940 men and 160 women undergoing coronary stent implantation between May 1992 and January 1998. Women were older (63 vs. 57 years; P = 0.001), more often hypertensive (46.9% vs. 31.4%; P < 0.001) and diabetic (13.2% vs. 8.3%; P = 0.05), and less often smokers than men (32.5% vs. 70.5%; P < 0.001). A previous history of Q-wave MI was less frequently present in women (28.2% vs. 40.2%; P = 0.003) who more often underwent coronary revascularization because of unstable angina (37.5% vs. 27.1%; P = 0.027). No difference was observed in coronary artery disease extension, lesion complexity, and stented vessel between the sexes. Bailout stenting was more frequently needed in women (28% vs. 17.8%; P = 0.001). No difference was observed in the number of stent implanted per vessel and per patient and average maximal inflation pressure used for stent postdilation. However, a smaller final balloon size was used in women. Procedural and clinical success was achieved in 94.4% and 92.5% of women and 96.7% and 94.5% of men (P = NS), respectively, without differences regarding in-hospital major adverse cardiac events. Bleeding complications occurred more often in women when anticoagulation was used (OR = 2.87; 95% CI = 1.38-5.74). At 6-month clinical follow-up, TLR was similar between the sexes and event-free survival was 75.5% in women and 81.5% in men (P = NS). Angiographic follow-up, performed in 71% of the patients, showed that restenosis was 64% higher in women (OR = 1.64; 95% CI = 1.02-2.61). Despite older age, higher incidence of comorbidities, and more unstable presentation, women treated with coronary stenting showed acute and mid-term clinical results similar to those observed in men. However, they were significantly more likely to develop angiographic restenosis.

Age Factors↗
PubMed2003

Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7).

OBJECTIVES: Lower urinary tract symptoms (LUTS), which are often caused by benign prostatic hypertrophy (BPH), and sexual dysfunction are common in older men, with an overall prevalence of >50% in men aged > or =50 years. Men with LUTS have been reported to experience sexual dysfunction, including ejaculatory loss, painful ejaculation, and erectile dysfunction. This study was conducted to investigate the relationship between LUTS and sexual problems in aging men. METHODS: A large-scale, multinational survey was conducted in the US and six European countries to systematically investigate the relationship between LUTS and sexual dysfunction in older men. Detailed questionnaires were mailed to a national representative sample of men aged 50 to 80 years in each country. Selection was made on the basis of age, occupation, geographic region, and population density. LUTS and sexual function were assessed by validated symptom scales, including the International Prostate Symptom Score, the Danish Prostatic Symptom Score, and the International Index of Erectile Function. Subjects also completed a health and demographics questionnaire. RESULTS: A total of 34,800 surveys were mailed out, 14,254 were completed and returned, and 12,815 were deemed evaluable and included in the analysis. Results were consistent from one country to another. Although 90% of the men had LUTS, only 19% had sought medical help for urinary problems and only 11% were medically treated. Sexual activity was reported by 83% of the sample, with 71% reporting at least one episode of sexual activity during the previous 4 weeks. Sexual disorders and their bothersomeness were strongly related to both age and severity of LUTS. The relationship between sexual problems and LUTS is independent of comorbidities such as diabetes, hypertension, cardiac disease, and hypercholesterolemia. CONCLUSIONS: Sexual activity is common in a majority of men over age 50 and is an important component of overall quality of life. The presence and severity of LUTS are independent risk factors for sexual dysfunction in older men. These results highlight the clinical importance of evaluating LUTS in patients with sexual dysfunction, and the need to consider sexual issues in the management of patients with benign prostatic hypertrophy.

Age Distribution↗
PubMed2002

Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy women.

BACKGROUND: The increase in C-reactive protein (CRP) during oral conjugated equine estrogen (CEE) may explain the initial excess of cardiovascular disease observed in clinical studies. Because the effect of transdermal estradiol (E2) on CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a randomized 2x2 retinoid-placebo trial. METHODS AND RESULTS: A total of 189 postmenopausal women were randomized to 50 microg/d transdermal E2 and 100 mg BID of the retinoid fenretinide (n=45), 50 microg/d transdermal E2 and placebo (n=49), 0.625 mg/d oral CEE and 100 mg BID fenretinide (n=46), or 0.625 mg/d oral CEE and placebo (n=49) for 1 year. Sequential medroxyprogesterone acetate was added in each group. Relative to baseline, CRP increased by 10% (95% CI -9% to 33%) and by 48% (95% CI 22% to 78%) after 6 months of transdermal E2 and oral CEE, respectively. The corresponding figures at 12 months were 3% (95% CI -14% to 23%) for transdermal E2 and 64% (95% CI 38% to 96%) for oral CEE. Fenretinide did not change CRP levels at 6 and 12 months relative to placebo. Relative to oral CEE, the mean change in CRP after 12 months of transdermal E2 was -48% (95% CI -85% to -7%, P=0.012), whereas fenretinide was associated with a mean change of -1% (95% CI -34% to 40%, P=0.79) compared with placebo. CONCLUSIONS: In contrast to oral CEE, transdermal E2 does not elevate CRP levels up to 12 months of treatment. The implications for early risk of coronary heart disease require further studies.

Administration, Oral↗
PubMed2002

A method for estimating within-patient variability in maximal urinary flow rate adjusted for voided volume.

OBJECTIVES: To investigate whether volume adjustment can be used to reduce the within-patient variability of the maximal urinary flow rate (Qmax) without affecting the variability between patients. METHODS: We analyzed 2049 urinary flow curves of 208 men with lower urinary tract symptoms suggestive of bladder outlet obstruction and studied the relation between Qmax and voided volume (VV) in individual patients using multilevel regression analysis. RESULTS: In agreement with most previous studies, we found a hyperbolic relation between the VV and Qmax. Although hyperbolic on average, the slope of the regression line relating the VV to Qmax differed substantially across individual patients. In some patients, Qmax even tended to be lower with an increased VV. CONCLUSIONS: The reproducibility of Qmax is poor, in part because of its dependence on the VV. The current methods to adjust Qmax for VV, such as the Siroky nomogram, minimize between-patient dependency, whereas our findings emphasize the importance of within-patient variability. A common approach to adjust Qmax for VV, however, is not feasible, because the relation of Qmax to VV differs substantially across patients. The only valid, although impractical option, remains to record a large number of urinary flow curves for each patient.

Diagnostic Techniques, Urological↗