Explore the vast range of titles available.

Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer. In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal-related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed. 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12·2 months (IQR 5·9–18·5) for patients on denosumab and 11·2 months (IQR 5·6–17·4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20·7 months (95% CI 18·8–24·9) with denosumab compared with 17·1 months (15·0–19·4) with zoledronic acid (hazard ratio 0·82, 95% CI 0·71–0·95; p=0·0002 for non-inferiority; p=0·008 for superiority). Adverse events were recorded in 916 patients (97%) on denosumab and 918 patients (97%) on zoledronic acid, and serious adverse events were recorded in 594 patients (63%) on denosumab and 568 patients (60%) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab group (121 [13%]) than in the zoledronic acid group (55 [6%]; p<0·0001). Osteonecrosis of the jaw occurred infrequently (22 [2%] vs 12 [1%]; p=0·09). Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer. Amgen.

Bone metastases are a major cause of morbidity and mortality in men with prostate cancer. Preclinical studies suggest that osteoclast inhibition might prevent bone metastases. We assessed denosumab, a fully human anti-RANKL monoclonal antibody, for prevention of bone metastasis or death in non-metastatic castration-resistant prostate cancer. In this phase 3, double-blind, randomised, placebo-controlled study, men with non-metastatic castration-resistant prostate cancer at high risk of bone metastasis (prostate-specific antigen [PSA] ≥8·0 μg/L or PSA doubling time ≤10·0 months, or both) were enrolled at 319 centres from 30 countries. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous denosumab 120 mg or subcutaneous placebo every 4 weeks. Randomisation was stratified by PSA eligibility criteria and previous or ongoing chemotherapy for prostate cancer. Patients, investigators, and all people involved in study conduct were masked to treatment allocation. The primary endpoint was bone-metastasis-free survival, a composite endpoint determined by time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death from any cause. Efficacy analysis was by intention to treat. The masked treatment phase of the trial has been completed. This trial was registered at ClinicalTrials.gov, number NCT00286091. 1432 patients were randomly assigned to treatment groups (716 denosumab, 716 placebo). Denosumab significantly increased bone-metastasis-free survival by a median of 4·2 months compared with placebo (median 29·5 [95% CI 25·4–33·3] vs 25·2 [22·2–29·5] months; hazard ratio [HR] 0·85, 95% CI 0·73–0·98, p=0·028). Denosumab also significantly delayed time to first bone metastasis (33·2 [95% CI 29·5–38·0] vs 29·5 [22·4–33·1] months; HR 0·84, 95% CI 0·71–0·98, p=0·032). Overall survival did not differ between groups (denosumab, 43·9 [95% CI 40·1–not estimable] months vs placebo, 44·8 [40·1–not estimable] months; HR 1·01, 95% CI 0·85–1·20, p=0·91). Rates of adverse events and serious adverse events were similar in both groups, except for osteonecrosis of the jaw and hypocalcaemia. 33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none on placebo. Hypocalcaemia occurred in 12 (2%) patients on denosumab and two (<1%) on placebo. This large randomised study shows that targeting of the bone microenvironment can delay bone metastasis in men with prostate cancer. Amgen Inc.

In the LATITUDE trial, addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) improved overall survival compared with placebos plus ADT in patients with newly diagnosed, high-risk, metastatic castration-naive prostate cancer. Understanding the effects of treatments on patient-reported outcomes (PROs) and health-related quality of life (HRQOL) is important for treatment decisions; therefore we aimed to analyse the effects of ADT plus abiraterone acetate and prednisone versus ADT plus placebos on PROs and HRQOL in patients in the LATITUDE study. In the multicentre, international, randomised, phase 3 LATITUDE trial, eligible patients were aged 18 years or older, had newly diagnosed, high-risk, metastatic castration-naive prostate cancer confirmed by bone scan (bone metastases) or by CT or MRI (visceral, soft tissue, or nodal metastases), and an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less. Patients from 235 clinical sites in 34 countries were randomly assigned (1:1) following a country-by-country scheme done by permuted block randomisation (with two blocks) and stratified by the presence of visceral metastasis and ECOG performance status to receive ADT plus 1000 mg oral abiraterone acetate and 5 mg oral prednisone once daily or ADT plus placebos. Selection of ADT, chemical or surgical, was at the investigator's discretion. The co-primary endpoints of the trial, overall survival and radiographic progression-free survival, have been published. PRO data were collected directly on electronic tablet devices at the clinical sites during screening and before any other visit procedure on day 1 of cycles 1–3, monthly during cycles 4–13, and then every 2 months until the end of treatment, by use of the Brief Pain Inventory—Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy Prostate scale (FACT-P), and the EuroQol (EQ-5D-5L) questionnaires. PRO analyses were an exploratory endpoint. Analyses were by intention-to-treat. Results from the first pre-planned interim analysis (Oct 31, 2016), are presented here. This ongoing study is registered with Clinicaltrials.gov, number NCT01715285. Between Feb 12, 2013, and Dec 11, 2014, 1199 patients were randomly assigned: 597 to ADT plus abiraterone acetate and prednisone and 602 to ADT plus placebos. Median follow-up was 30·9 months (IQR 21·2–33·2) in the ADT plus abiraterone acetate and prednisone group versus 29·7 months (1·4–43·5; 16·1–31·3) in the ADT plus placebos group. Median time to worst pain intensity progression assessed by the BPI-SF score was not reached in either group (ADT plus abiraterone acetate and prednisone, not reached [95% CI not reached to not reached]; 25th percentile 11·07 months [95% CI 9·23–18·43]; ADT plus placebos group, not reached [95% CI not reached to not reached]; 25th percentile 5·62 [95% CI 4·63–7·39]; hazard ratio [HR] 0·63 [95% CI 0·52–0·77]; p<0·0001). Median time to worst fatigue intensity was not reached in either the ADT plus abiraterone acetate and prednisone group (not reached [95% CI not reached to not reached]; 25th percentile 18·4 months [95% CI 12·9–27·7]) or the ADT plus placebos group (not reached [95% CI not reached to not reached]; 25th percentile 6·5 months [95% CI 5·6–9·2]; HR 0·65 [95% CI 0·53–0·81], p=0·0001). Median time to deterioration of functional status assessed by the FACT-P total score scale was 12·9 months (95% CI 9·0–16·6) in the ADT plus abiraterone acetate and prednisone group versus 8·3 months (7·4–11·1) in the ADT plus placebos group (HR 0·85 [95% CI 0·74–0·99]; p=0·032). The addition of abiraterone acetate plus prednisone to ADT in patients with newly diagnosed, high-risk metastatic castration-naive prostate cancer improved overall PROs by consistently showing a clinical benefit in the progression of pain, prostate cancer symptoms, fatigue, functional decline, and overall HRQOL. Janssen Research & Development.

Over the years, the paper and cellulose industry in Alto Tietê community kept the eucalypt production system in partners with local farmers. However, the costs of the integrated systems were very higher, and contribute to the industry adopted the new strategy like investment in production mechanization in areas plains and most far. This hit the local market with eucalyptus devaluation. Thus, this paper aims to analyze the strategy applied by local farmers to reduce eucalypt production costs. The case study was carried out in the Salesópolis community, São Paulo, as an exploratory research to comprehend the impact of paper and cellulose industry change made in the local community. The results showed that the total cost estimated to first production cycle was 1.8 most than the second cycle and the rentability in 6.5 years was de 1,92% less than other cycles. The third production cycle showed downs in land rentability, almost 18.5% less than the second cycle and 16.5% less than the first cycle. Therefore, the eucalypt production in the Alto Tietê community already was a big business and income source to local farmers and with eucalypt market devaluation and the cost increase of production and operation, the farmers had opted by the maintenance of the third cycle of production even not being the most profitable.

This is an observational transversal cohort study in which we aim to analyze the Brazilian penis length and compare the penis size of the men self-declared as white (SDW) or black (SDB) skin color. Subjects were asked for self-declare according to their skin color, after that they have been invited to participate in a semi-structured interview so as to have their perception evaluated regarding their penis size and their self-esteem as well. Eventually, their penis length was measured with an anthropometric ruler. The men´s mean penis length who declared themselves as black skin color was 16.5 ± 1.7 cm (penis length in real fully-stretched flaccid length) and the men´s mean penis length who declared themselves as white skin color was 15.8 ± 1.6 cm (p < 0.001).The majority of either SDB (94.0%) or SDW (89.4%) are satisfied with their penis size (p = 0.464). We have shown that the man´s mean penis length who identifies himself as black is just a little bit bigger than the one who identifies himself as white. However, there were no significant difference between groups regarding self-assessment of genital body image.

Purpose To assess influence of penile biometric characteristics on surgical outcome of tubularized incised plate (TIP) repair for hypospadias. Methods We prospectively studied 42 boys with distal hypospadias that underwent TIP urethroplasty. Biometric assessment prior to surgery consisted of classifying glans shape, urethral plate (UP) length and width, prepuce vascularization and penile size, using a caliper rule, according to previous definitions. Surgical outcome was assessed according to the occurrence of dehiscence, fistula or urethral stricture. Results There was no statistical difference among groups concerning postoperative complications. Glans shape: grooved (24/57 %), shallow (9/21 %) and conical (9/21 %). UP width: <10 mm (26/62 %) and ≥10 mm (16/38 %). UP length was evaluated in 29 patients: <10 mm in (12/41 %) and ≥10 mm (17/59 %). Prepuce vascularization: one predominant blood vessel (17/41 %), two predominant blood vessels (8/19 %), H-like form with communication between two well-developed blood vessels (6/14 %) and net-like form with no predominant blood vessels (11/26 %). Penile size was measured in 28 patients under 50th percentile (25/89 %). Conclusion Glans shape, UP width, UP length, prepuce vascularization and penile size do not significantly affect the complication rate of TIP repair in distal hypospadias. Most of the patients with distal hypospadias presented with penile size under mean length for age suggesting some form of mild hypogonadism.

Purpose The use of minilaparoscopic instruments has gained interest in recent years, permitting a less invasive treatment for many surgical procedures. Its application in urological surgeries has not been established yet. Methods Between November 2012 and December 2014, 32 patients underwent minilaparoscopic surgeries, using 3.5-mm instruments. The procedures performed included pyeloplasties (16 cases), radical nephrectomies (2), simple nephrectomies (4), renal cyst decortication (5), ureterolithotomy (2) ureteral reimplantation (2) and partial ureterectomy (1). Results All the procedures were performed minilaparoscopically, except for one simple nephrectomy and one renal cyst decortication that were converted to a standard laparoscopic approach, due to intensive perioperative bleeding. One pyeloplasty had to be reoperated for a urinary fistula repair. All the patients had good-to-excellent cosmetic outcomes, except for one patient who developed keloids at her scars. Functional results were comparable to the ones described in the literature. Conclusion Minilaparoscopy is a feasible option for patients and physicians searching for a even less invasive procedure compared with the laparoscopic approach, with better cosmetic and the same functional and oncologic outcomes.

Purpose To investigate whether ultrasonographic bladder wall thickness (BWT) correlates with urodynamic parameters in patients with spinal cord injury (SCI). Methods Two hundred and seventy-two patients with SCI were enrolled in the study. All of the patients underwent bladder ultrasonography and urodynamic study. The anterior bladder wall was measured and compared to urodynamic data. Results The mean age of the patients was 37.4 years. The mean BWT was 3.9 mm. BWT was significantly higher in the patients with neurogenic detrusor overactivity associated with detrusor sphincter dyssynergia (NDO/DSD) compared to those without sphincter dyssynergia (4.2 vs. 3.6 mm, respectively, p  < 0.001) and in those with compliance <20 ml/cm H 2 O. Nevertheless, ROC curve analysis [ROC = 0.624, 95 % CI (0.530, 0.718), p  = 0.011] showed that no meaningful BWT measurement cutoff could be made to predict an elevated detrusor pressure in the storage phase. Conclusions Increased BWT was present in patients with low bladder compliance and NDO/DSD. No BWT cutoff value to predict an elevated detrusor pressure was found. Therefore, the measurement of BWT has no clinical role in patients with SCI and cannot replace urodynamic evaluation.