Lower urinary tract symptoms and depression.

UNLABELLED: Study Type--Symptom prevalence (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Depression plays an important role in pathogenesis of BPH. Our study shows that prostatic symptoms can be helpful in the screening for depression. OBJECTIVE: • To evaluate the relationship between lower urinary tract symptoms (LUTS) and depression in men through validated questionnaires. PATIENTS AND METHODS: • Healthy male workers (n = 673) were invited to a free health check-up. • Patients underwent a detailed medical examination. • All participants completed the International Prostate Symptom Score (IPSS) questionnaire and the Beck Depression Inventory (BDI). RESULTS: • Under multiple logistic regression analysis (adjusted for total testosterone and age), a significant effect of IPSS on BDI score was observed: mild depression (BDI score >9): odds ratio (OR) 1.092, 95% confidence interval (CI) 1.056-1.129; P < 0.001; moderate-to-severe depression (BDI score >19): OR 1.093, 95% CI 1.031-1.159; P = 0.003; and severe depression (BDI score >29): OR 1.176, 95% CI 1.048-1.320; P = 0.006. CONCLUSIONS: • In healthy men, LUTS are significantly associated with depression. • The treatment of LUTS is very important for the mental health of older men.

Are there symptom-specific testosterone thresholds in aging men?

OBJECTIVE: • To study the association between specific clinical symptoms (e.g. low libido and erectile dysfunction) and testosterone levels and age in order to define symptom-specific testosterone thresholds. MATERIALS AND METHODS: • Serum samples for testosterone determination were obtained from 675 healthy men. • Participants underwent urological examination and completed the Aging Males Symptoms scale, the Beck Depression Index and the International Index of Erectile Function. Overall scores and those from individual questions from the questionnaires were evaluated. • Testosterone levels in men with symptoms were compared with those in men without symptoms. • The risks of clinical symptoms were evaluated using univariate, multiple multinomial regression analyses and Bonferroni correction. RESULTS: • Significant associations between testosterone levels and a number of androgen deficiency symptoms were seen at testosterone levels of 13.5-14.4 nmol/L, but multiple logistic regression analysis revealed confounding effects with age. • Symptoms such as loss of libido, lack of vigour and sexual dysfunction were associated with age rather than with testosterone. • Erectile dysfunction was reported at testosterone levels between 14.65 nmol/L and 14.8 nmol/L, but was again significantly associated with age rather than testosterone levels. • The severity of symptoms significantly increased with decreasing testosterone levels using univariate analysis, but only the relationship with psychological symptoms remained significant after Bonferroni correction. CONCLUSION: • In aging males, androgen deficiency symptoms were reported at normal levels of testosterone, but age was an important confounder. Symptom-specific testosterone thresholds could not be defined.

Endocrine therapy plus zoledronic acid in premenopausal breast cancer.

BACKGROUND: Ovarian suppression plus tamoxifen is a standard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer. Aromatase inhibitors are superior to tamoxifen in postmenopausal patients, and preclinical data suggest that zoledronic acid has antitumor properties. METHODS: We examined the effect of adding zoledronic acid to a combination of either goserelin and tamoxifen or goserelin and anastrozole in premenopausal women with endocrine-responsive early breast cancer. We randomly assigned 1803 patients to receive goserelin (3.6 mg given subcutaneously every 28 days) plus tamoxifen (20 mg per day given orally) or anastrozole (1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every 6 months) for 3 years. The primary end point was disease-free survival; recurrence-free survival and overall survival were secondary end points. RESULTS: After a median follow-up of 47.8 months, 137 events had occurred, with disease-free survival rates of 92.8% in the tamoxifen group, 92.0% in the anastrozole group, 90.8% in the group that received endocrine therapy alone, and 94.0% in the group that received endocrine therapy with zoledronic acid. There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups (hazard ratio for disease progression in the anastrozole group, 1.10; 95% confidence interval [CI], 0.78 to 1.53; P=0.59). The addition of zoledronic acid to endocrine therapy, as compared with endocrine therapy without zoledronic acid, resulted in an absolute reduction of 3.2 percentage points and a relative reduction of 36% in the risk of disease progression (hazard ratio, 0.64; 95% CI, 0.46 to 0.91; P=0.01); the addition of zoledronic acid did not significantly reduce the risk of death (hazard ratio, 0.60; 95% CI, 0.32 to 1.11; P=0.11). Adverse events were consistent with known drug-safety profiles. CONCLUSIONS: The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer. (ClinicalTrials.gov number, NCT00295646.)

How much physical activity is needed to maintain erectile function? Results of the Androx Vienna Municipality Study.

OBJECTIVE: To assess the correlation of erectile function (EF) and physical activity (PhA) by using standardized, validated instruments in healthy men. METHODS: A urologist examined 674 men aged 45-60 yr at their place of work. That included a urological physical examination, medical history, and assessment of testosterone (T) and sex hormone-binding globulin; all men completed the 5-item International Index of Erectile Function (IIEF-5) as well as the Paffenbarger score. PhA was assessed in kilojoules per week (4.2 kJ=1 kcal). RESULTS: A positive correlation between the IIEF-5 and the Paffenbarger score (r=0.164, p<0.001) was found. The IIEF-5 score increased with an increasing Paffenbarger score up to a level of 4000 kcal/wk. T revealed a trend to a significant impact on the IIEF-5 score, but showed no association with the Paffenbarger score. The risk of severe erectile dysfunction (ED) was decreased by 82.9% for males with PhA of at least 3000 kcal/wk compared with males with PhA under 3000 kcal/wk (OR=0.171, p=0.018). CONCLUSION: Increasing PhA from 1000 to 4000 kcal/wk may reduce the risk of ED.

Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a.

BACKGROUND: Clinical trial data have shown that among breast cancer patients who were disease free after 5 years of adjuvant treatment with tamoxifen, further extended treatment with the nonsteroidal aromatase inhibitor letrozole reduces breast cancer recurrence. We examined the efficacy and tolerability of extended adjuvant therapy with another aromatase inhibitor, anastrozole, for 3 years among women who had completed 5 years of adjuvant therapy. METHODS: Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6a is an extension of ABCSG Trial 6, in which hormone receptor-positive postmenopausal patients received 5 years of adjuvant tamoxifen, with or without the aromatase inhibitor aminoglutethimide, for the first 2 years of therapy. For ABCSG Trial 6a, patients who were disease free at the end of Trial 6 were randomly assigned to receive either 3 years of anastrozole or no further treatment. Efficacy data were analyzed with the use of a Cox proportional hazards regression model with two-sided P values and Kaplan-Meier curves, and tolerability data were estimated using logistic regression analysis with odds ratios and 95% confidence intervals (CIs). RESULTS: ABCSG Trial 6a included 856 patients. At a median follow-up of 62.3 months, women who received anastrozole (n = 387) had a statistically significantly reduced risk of recurrence (locoregional recurrence, contralateral breast cancer, or distant metastasis) compared with women who received no further treatment (n = 469; hazard ratio = 0.62; 95% CI = 0.40 to 0.96, P = .031). Anastrozole was well tolerated, and no unexpected adverse events were reported. CONCLUSIONS: These data confirm the benefit of extending adjuvant tamoxifen therapy beyond 5 years with anastrozole compared with no further treatment. Further research is required to define the optimum length of extended adjuvant therapy and to investigate the possibility of tailoring this period to suit different disease types.

Mood changes, body mass index and bioavailable testosterone in healthy men: results of the Androx Vienna Municipality Study.

OBJECTIVE: To determine whether sex hormones alone or in combination with body mass index (BMI) influence mood in men. SUBJECTS AND METHODS: Blood samples were taken from 669 manual workers (aged 43-67 years) to measure sex hormone levels, in particular bioavailable testosterone (BAT). At the same time BMI was calculated. All participants completed the Beck's Depression Inventory (BDI) for the evaluation of depression. Then BMI and BAT were correlated to the BDI scores, to determine a possible interaction. RESULTS: There was a quadratic main effect for BAT on the BDI scores, i.e. an increased risk of depression with an odds ratio of 1.871 (P = 0.029) for hypo- and hypergonadal men. Also, there was an interaction between BAT and BMI, which was mainly detected in underweight and obese men. This U-shaped effect for underweight and obese men was not detected in men with a 'normal' weight, who had a significantly linear decrease in the risk of depression by changing from the hypogonadal to the eugonadal subgroup, as well as for changing from the eugonadal to the hypergonadal subgroup, with a mean odds ratio of 0.513 (P = 0.032). CONCLUSIONS: Depression depends on BAT and BMI; in men of normal weight, an increase in BAT reduces the risk of depression, which is not the case in underweight and obese men. Consequently eugonadal men with normal testosterone levels have the lowest risk of depression.

Intra- and extrauterine maturation of amplitude-integrated electroencephalographic activity in preterm infants younger than 30 weeks of gestation.

OBJECTIVE: To prospectively investigate the longitudinal changes of amplitude-integrated electroencephalographic (aEEG) activity in preterm infants <30 weeks gestational age (GA). METHODS: Infants (GA <30 weeks) without evidence of neurological abnormalities had weekly aEEG recordings performed. The relative duration of the three aEEG patterns (discontinuous low voltage, discontinuous high voltage and continuous) was determined and the influence of GA and postnatal age (PNA) on the occurrence of each pattern was assessed. RESULTS: Ninety-eight infants (median GA 26 weeks; range 23-29 weeks) were studied. With higher GA (OR 1.68, 95% CI 1.33-2.13) and PNA (OR 1.91, 95% CI 1.53-2.38), the likelihood for the occurrence of continuous activity increased. The discontinuous low-voltage pattern was less likely to occur with increasing GA (OR 0.68, 95% CI 0.55-0.83) and PNA (OR 0.70, 95% CI 0.61-0.81). CONCLUSION: Maturation of aEEG activity in preterm infants is influenced by both GA and PNA.

The impact of age, body mass index and testosterone on erectile dysfunction.

PURPOSE: Erectile dysfunction (ED) may be associated with low serum total testosterone (T), low serum bioavailable testosterone (BAT) and high body mass index (BMI) in aging men. MATERIALS AND METHODS: A total of 675 workers (age range 45 to 60 years old) were entered into this study. Investigations were performed directly at their place of work. Exclusion criteria were abnormal urogenital status, antihypertensive drugs, medication possibly affecting the endocrine function and a history of previous pelvic trauma. T and sex hormone-binding globulin were measured with commercially available assays, and BAT was calculated from T and sex hormone-binding globulin. BMI was assessed and every individual completed a self-administrated questionnaire for erectile function (International Index of Erectile Function [IIEF-5]). RESULTS: T and BAT showed a significantly negative correlation with age and BMI. Each additional year of increase in age caused a decrease in the IIEF-5 score of 0.195 (p <0.001). Increase in BMI by 1 kg/m reduced IIEF-5 by 0.141, independent of age (p =0.005). Multiple logistic regression analyses confirmed the influence of increased age and higher BMI on the risk of ED. The corresponding odds ratio for ED was 1.082 (p <0.001) and 1.076 (p <0.001), respectively. These data indicate an increase in ED risk by 8.2% per year and by 7.6% per kg/m BMI. Severe cases of ED (IIEF-5 score 7 or less) were significantly associated with a decrease in T and BAT. Individuals with low BAT (1 ng/ml or less) had a 3 times higher risk of severe ED compared with men with BAT greater than 1 ng/ml (odds ratio 3.045, 95% CI 1.088 to 8.522, p =0.034). The result of the multiple logistic regression analysis was adjusted to age and BMI, and did not show a significant influence on the incidence of severe ED. CONCLUSIONS: BMI contributes strongly to ED. Low T or BAT are only relevant if IIEF-5 questionnaire results in severe ED.

3-D ultrasonographic imaging of the cerebral ventricular system in very low birth weight infants.

The purpose of the study was to assess reference ranges for lateral ventricular volume of very low birth weight (VLBW) infants using 3-D ultrasound (US). A total of 108 patients with birth weights < or =1500 g or mother's postmenstrual age < or =32 weeks were examined prospectively in a longitudinal study. Infants in conditions considered being potential confounders such as intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL) were not included in the calculations. Hence, 77 subjects remained for final statistical analysis. Mean postmenstrual age at birth was 194.5 (27 weeks and 5.5 days) +/- 14 SD days, mean birth weight was 972.5 +/- 236.3 SD g. Reference ranges for lateral ventricle volume were established from serial images. The exponential regression analyses revealed a weekly increase in volume of 6.3% (95% CI 4.4%-8.3%) and 6.6% (95% CI 4.7%-8.6%) in respect to the left and the right ventricle (p < 0.001). Postmenstrual age correlated significantly (p < or = 0.015) with ventricle volume. No significant association to head circumference could be determined. Establishment of reference values for the lateral ventricle volume of VLBW infants should facilitate application of 3-D US in routine diagnostics in neonatal intensive care units and detection of ventricular enlargement as a prediction of risk for poor neurodevelopmental outcome in high-risk cohorts.

Monitoring of serum Her-2/neu predicts response and progression-free survival to trastuzumab-based treatment in patients with metastatic breast cancer.

PURPOSE: The present pilot study was performed to elucidate whether early changes in serum Her-2/neu extracellular domain (ECD) levels during trastuzumab-based treatment would predict the clinical course of disease in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Sera from 55 patients with Her-2/neu-overexpressing metastatic breast cancer obtained immediately before each weekly administration of trastuzumab were analyzed by a serum Her-2/neu ELISA. RESULTS: Whereas response rates were significantly higher in patients with elevated (>or=15 ng/ml) ECD levels before initiation of treatment (35% versus 7%, P = 0.045), progression-free and overall survival did not differ significantly between patients with normal and elevated ECD levels. In patients responding to treatment, ECD levels decreased significantly as early as from day 8 of treatment onwards (all P for weekly measurements versus baseline <0.001). In contrast, no significant change in ECD levels was observed in patients with progressive disease. Multiple logistic regression analyses identified kinetics of ECD levels as the only factor that allowed for the accurate prediction of response likelihood as early as from day 8 of trastuzumab-based treatment onwards (P = 0.020). In addition, determination of serial ECD levels allowed for the prediction of the risk for disease progression within the observed period as early as day 15 of treatment (P = 0.010). CONCLUSIONS: Serial monitoring of the ECD may represent a valuable tool for early prediction of the probability of response and progression-free survival to trastuzumab-based treatment and is thus likely to contribute to an optimization of treatment and resource allocation.

Reference values for amplitude-integrated electroencephalographic activity in preterm infants younger than 30 weeks' gestational age.

OBJECTIVE: To prospectively investigate the development of amplitude-integrated electroencephalographic (aEEG) activity during the first 2 weeks of life in neurologically normal and clinically stable preterm infants <30 weeks' gestational age (GA). PATIENTS AND METHODS: Infants with a GA of <30 weeks admitted to the neonatal intensive care unit of the Vienna University Children's Hospital (Vienna, Austria) were studied prospectively by using aEEG and cranial ultrasound. Clinically stable infants without clinical or sonographic evidence of neurologic abnormalities were eligible for inclusion in the reference group. The distribution of 3 background aEEG activity patterns (discontinuous low-voltage, discontinuous high-voltage, and continuous), presence of sleep-wake cycles, and number of bursts per hour in the reference group were determined by visual analysis. RESULTS: Seventy-five infants (median GA: 27 weeks; range: 23-29 weeks) were eligible for inclusion in the reference group and had aEEG recordings during the first 2 weeks of life available. Analysis of aEEG background activity showed that with higher GA the relative amount of continuous activity increased while discontinuous patterns decreased. The number of bursts per hour decreased with increasing GA. Cyclical changes in aEEG background activity resembling early sleep-wake cycles were observed in all infants. CONCLUSIONS: Normal values for aEEG background activity were determined in preterm infants <30 weeks' GA. Clinically stable and neurologically normal preterm infants exhibit at least 2 different patterns of aEEG activity. There is a correlation between the GA and the relative duration of continuous aEEG activity.

Body mass index, follicle-stimulating hormone and their predictive value in in vitro fertilization.

PURPOSE: The objective was to explore whether body mass and day 3 follicle-stimulating hormone have predictive value on odds of pregnancy after in vitro fertilisation. Few studies show that obesity produces a variety of alterations in the reproductive system, and that women with an elevation of day 3 FSH have declining ovarian function. METHODS: The data of one-hundred-seventy-one women who underwent a standard regime of controlled ovarian hyperstimulation was analyzed with particular reference to variations in body mass and hormone levels. RESULTS: By raising BMI and FSH (mIU/mL) by one unit, the odds for pregnancy were decreased by the respective factors 0.84 (95% confidence interval 0.73-0.97) and 0.77 (95% confidence interval 0.59-1.00). CONCLUSIONS: The results demonstrate that for the purpose of raising the odds of pregnancy BMI should be reduced. A low FSH value may cause the same effect. Nontheless, obesity and hormonal function may be independent risk factors for failure in assisted reproduction.

Percutaneous saline-enhanced radiofrequency ablation of unresectable hepatic tumors: initial experience in 26 patients.

OBJECTIVE: The purpose of our study was to evaluate the safety and efficacy of percutaneous saline-enhanced radiofrequency ablation for unresectable primary or metastatic hepatic tumors. SUBJECTS AND METHODS: Twenty-six patients with 15 hepatocellular carcinomas and 33 hepatic metastases (maximum diameter < or = 8.6 cm) were treated; of these, seven tumors in five patients were treated twice. Thus, 44 radiofrequency treatments were performed. Saline-enhanced and impedance-controlled radiofrequency ablation (0.5-1.1 mL/min of saline, 15-mm conductive portion of the electrode tip, 25-60 W, 5-43 min) was performed using MR imaging guidance. Coagulation necrosis, volume indexes, morbidity, and complications were assessed. RESULTS: The volume of coagulation necrosis 1-7 days after radiofrequency ablation was 1.6-126.6 cm(3) (median, 18.9 cm(3)), corresponding to coagulation diameters of 1.5-6.2 cm (median, 3.2 cm). The coagulation volume was significantly larger if there were more than four radiofrequency applications (p = 0.006). Tumors of 3 cm or less in diameter were eight times as likely to be successfully completely ablated (p = 0.01) and volume indexes of lesions treated with the patient under general anesthesia were significantly larger than those treated with the patient under conscious sedation (p < 0.001). Major complications occurred in four patients (15%). Incomplete ablation in 19 (35%) of 54 radiofrequency lesions was due to cooling by a large vessel nearby (n = 2) or to low power applied in painful (n = 11) or critical (n = 6) locations. Residual tumor was observed in 14 (58%) of 24 tumors evaluated 6-8 months after radiofrequency ablation. CONCLUSION: Percutaneous saline-enhanced and impedance-controlled radiofrequency ablation can be effective in the treatment of unresectable hepatic tumors and minimizes potential carbonization. A greater number of radiofrequency applications, general anesthesia, and increasing experience provide significantly better results.