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INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

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We analyze how the structure of complex networks of non-identical oscillators influences synchronization in the context of the Kuramoto model. The complex network metrics assortativity and clustering coefficient are used in order to generate network topologies of Erdös-Rényi, Watts-Strogatz, and Barabási-Albert types that present high, intermediate, and low values of these metrics. We also employ the total dissonance metric for neighborhood similarity, which generalizes to networks the standard concept of dissonance between two non-identical coupled oscillators. Based on this quantifier and using an optimization algorithm, we generate Similar, Dissimilar, and Neutral natural frequency patterns, which correspond to small, large, and intermediate values of total dissonance, respectively. The emergency of synchronization is numerically studied by considering these three types of dissonance patterns along with the network topologies generated by high, intermediate, and low values of the metrics assortativity and clustering coefficient. We find that, in general, low values of these metrics appear to favor phase locking, especially for the Similar dissonance pattern.

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PURPOSE: To generate and present the survey results on critical issues relevant to screening, diagnosis, and staging tools for prostate cancer (PCa) focused on developing countries. METHODS: A total of 36 of 300 questions concern the main areas of interest of this paper: (1) screening, (2) diagnosis, and (3) staging for various risk levels of PCa in developing countries. A panel of 99 international multidisciplinary cancer experts voted on these questions to create recommendations for screening, diagnosing, and staging tools for PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support the screening, diagnosis, and staging of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for screening, diagnosis, and staging of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

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PURPOSE: A group of international urology and medical oncology experts developed and completed a survey on prostate cancer (PCa) in developing countries. The results are reviewed and summarized, and recommendations on consensus statements for very low-, low-, and intermediate-risk PCa focused on developing countries were developed. METHODS: A panel of experts developed more than 300 survey questions of which 66 questions concern the principal areas of interest of this paper: very low, low, and intermediate risk of PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up for very low-, low-, and intermediate-risk PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support management for very low, low, and intermediate risk of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment for very low, low, and intermediate risk of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

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Radical prostatectomy is a commonly adopted treatment for localized/locally advanced prostate cancer in men with a life expectancy of ten years or more. Robotic-assisted radical prostatectomy (RARP) is comparable to open radical prostatectomy on cancer control and complication rates; however, new evidence suggests that RARP may have better functional outcomes, especially with respect to urinary incontinence and erectile dysfunction. Some of the surgical steps of RARP are not adequately described in published literature and, as such, may have an impact on the final outcomes of the procedure. We organized a Brazilian experts' panel to evaluate best practices in RARP. The confection of the recommendations broadly involved: selection of the experts; establishment of working groups; systematic review of the literature and elaboration of a questionnaire; and construction of the final text with the approval of all participants. The participants reviewed the publications in English from December 2019 to February 2020. A one-round Delphi technique was employed in 188 questions. Five reviewers worked on the final recommendations using consensual and non-consensual questions. We found 59.9% of questions with greater than 70% agreement that were considered consensual. Non-consensual questions were reported according to the responses. The recommendations were based on evidence-based literature and individual perceptions adapted to the Brazilian reality, although some issues remain controversial. We believe that these recommendations may help urologists involved in RARP and hope that future discussions on this surgical procedure may evolve over the ensuing years.

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Heart rate variability (HRV) is a non-invasive alternative to analyze the role of the autonomic nervous system (ANS) on heart functioning. Many tools have been developed to analyze collected cardiac data. Among them, the Central Tendency Measure (CTM) is a quantitative method for variability analysis of RR intervals. The values of the CTM must be between 0 and 1 (inclusive) for different radius, which follows the intrinsic characteristics of each time series. Using the conventional CTM, the successive differences of the time series may be calculated, and it can classify and differentiate the disturbances in the ANS involving HRV. This method was extended (e-CTM) to analyze the differences between RR interval time series. In this extension, a new parameter is added, which allows analysis of long time intervals, instead of successive and adjacent RR intervals. The ability of the e-CTM to differentiate the groups of the RR interval time series was verified with 145 RR interval time series divided into three groups: subjects with congestive heart failure, healthy subjects, and nurses during one hour of their workday. Results evidence that the new parameter added differentiates the group with pathology (and subsequent impairment of ANS) and group under stress at work (temporary impairment of ANS). These results suggest that the e-CTM is capable of detection long-term variations in the HRV according to the ANS impairment.

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Does the assignment order of a fixed collection of slightly distinct subsystems into given communication channels influence the overall ensemble behavior? We discuss this question in the context of complex networks of nonidentical interacting oscillators. Three types of connection configurations are considered: Similar, Dissimilar, and Neutral patterns. These different groups correspond, respectively, to oscillators alike, distinct, and indifferent relative to their neighbors. To construct such scenarios we define a vertex-weighted graph measure, the total dissonance, which comprises the sum of the dissonances between all neighbor oscillators in the network. Our numerical simulations show that the more homogeneous a network, the higher tend to be both the coupling strength required for phase locking and the associated final phase configuration spread over the circle. On the other hand, the initial spread of partial synchronization occurs faster for Similar patterns in comparison to Dissimilar ones, while neutral patterns are an intermediate situation between both extremes.

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We study the Deserter Hubs Model: a Kuramoto-like model of coupled identical phase oscillators on a network, where attractive and repulsive couplings are balanced dynamically due to nonlinearity of interactions. Under weak force, an oscillator tends to follow the phase of its neighbors, but if an oscillator is compelled to follow its peers by a sufficient large number of cohesive neighbors, then it actually starts to act in the opposite manner, i.e., in anti-phase with the majority. Analytic results yield that if the repulsion parameter is small enough in comparison with the degree of the maximum hub, then the full synchronization state is locally stable. Numerical experiments are performed to explore the model beyond this threshold, where the overall cohesion is lost. We report in detail partially synchronous dynamical regimes, like stationary phase-locking, multistability, periodic and chaotic states. Via statistical analysis of different network organizations like tree, scale-free, and random ones, we found a measure allowing one to predict relative abundance of partially synchronous stationary states in comparison to time-dependent ones.

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A new approach based on the dual-tree complex wavelet transform is introduced for phase assignment to non-linear oscillators, namely, the Discrete Complex Wavelet Approach-DCWA. This methodology is able to measure phase difference with enough accuracy to track fine variations, even in the presence of Gaussian observational noise and when only a single scalar measure of the oscillator is available. So, it can be an especially interesting tool to deal with experimental data. In order to compare it with other phase detection techniques, a testbed is introduced. This testbed provides time series from dynamics similar to non-linear oscillators, such that a theoretical phase choice is known in advance. Moreover, it allows to tune different types of phase synchronization to test phase detection methods under a variety of scenarios. Through numerical benchmarks, we report that the proposed approach is a reliable alternative and that it is particularly effective compared with other methodologies in the presence of moderate to large noises.

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PURPOSE: Little is known about the effects of literacy levels on prostate cancer screening. This study evaluates the association between literacy, compliance with screening, and biopsy findings in a large Brazilian screening study. MATERIALS AND METHODS: We analyzed 17,571 men screened for PCa with digital rectal examination (DRE) and total and free prostate-specific antigen (PSA) from January 2004 to December 2007. Of those, 17,558 men had information regarding literate status. Full urological evaluation in a specialized cancer center was recommended in the case of: a) suspicious DRE, b) PSA > 4.0 ng/mL, or c) PSA 2.5-3.9 ng/mL and free/total PSA (f/tPSA) ratio 15%. Transrectal ultrasound guided prostate biopsy (14 cores) was performed upon confirmation of these findings after the patient's consent. Patients' compliance with screening recommendations and biopsy results were evaluated according to literacy levels. RESULTS: an abnormal PSA, a suspicious DRE, or both were present in 73.2%, 19.7%, and 7.1% of those men who underwent biopsy, respectively. PCa was diagnosed in 652 men (3.7%). Previous PSAs or DREs were less common among illiterate men (p < 0.0001). Additionally, illiterate men were less prone to attend to further evaluations due to an abnormal PSA or DRE (p < 0.0001). PSA levels > 10 mg/mL (p = 0.03), clinical stage > T2a (p = 0.005), and biopsy Gleason > 7 (p = 0.02) were more common among illiterate men. CONCLUSIONS: In a screened population, literacy levels were associated with prior PCa evaluations and with compliance with screening protocols. Illiterate men were at higher risk of being diagnosed with more advanced and aggressive PCa.

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PURPOSE: Simple diversions are underutilized, mostly for unfit, bedridden, and very self-limited patients requiring palliative surgical management due to life-threatening conditions. Experience with cutaneous ureterostomy (CU) as palliative urinary diversion option for unfit bladder cancer patients is reported. METHODS: We retrospectively reviewed clinical and operative parameters of 41 patients who underwent CU following RC in three specialized Cancer Centers from July/2005 to July/2010. Muscle-invasive disease (clinical Stage T2/worse), multifocal high-grade tumor, and carcinoma in situ refractory to intravesical immunotherapy were the main indications for RC. Double-J ureteral stents were used in all patients and replaced every 6 months indefinitely. Peri-operative morbidity and mortality were evaluated. RESULTS: Median age was 69 years (interquartile range--IQR 62, 76); 30 (73%) patients were men. Surgery in urgency setting was performed in 25 (61%) of patients, most due to severe bleeding associated with hemodynamic instability; 14 patients (34%) showed an American Society of Anesthesiologists score 4. Median operative time was 180 minutes (IQR 120, 180). Peri-operative complications occurred in 30 (73%) patients, most Clavien grade I and II (66.6 %). There was no per-operative death. Re-intervention was necessary in 7 (17%) patients. Overall survival was 24% after 9.4 months follow-up. CONCLUSIONS: CU with definitive ureteral stenting represents a simplified alternative for urinary diversion after palliative cystectomy in unfit patients. It can be performed quickly, with few early and late postoperative complications allowing RC in a group of patients otherwise limited to suboptimal alternatives. Future studies regarding the quality of life are warranted.

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UNLABELLED: What's known on the subject? and What does the study add? In spite of its low specificity, PSA is the most widely used screening test for prostate cancer (PCa), and is considered the main cause of the stage migration recently observed. The ratio of free to total PSA (%fPSA) has been shown to increase PSA accuracy in cancer detection; however, few screening studies have systematically evaluated its role in cancer detection rates in men with PSA levels <4.0 ng/mL and normal DRE. The present study supports a possible role of %fPSA as an adjunct to screening in men with total PSA 2.5-4.0 ng/mL and normal DRE, with a marked increase in cancer detection rates in a large Brazilian PCa screening study. We believe that %fPSA maybe a useful refinement to biopsy indications in men with low PSA levels. OBJECTIVE: • To evaluate the role of the free to total prostate-specific antigen ratio (%fPSA) in identifying prostate cancer (PCa) in men with a prostate-specific antigen (PSA) level of 2.5-3.9 ng/mL and a normal digital rectal examination (DRE). PATIENTS AND METHODS: • A prospective PCa screening study was conducted, which included 17571 men aged ≥ 45 years, across six Brazilian states, where men were recalled for further evaluation in the case of either a suspicious DRE and/or PSA ≥ 4.0 ng/mL, or PSA 2.5-3.9 ng/mL and %fPSA ≤ 15. • We evaluated the impact of a %fPSA ≤ 15 on cancer detection rates and the clinical and pathological stage of tumours in men with a normal DRE and PSA 2.5-3.9 ng/mL. RESULTS: • When suspicious DRE and/or PSA ≥ 4.0 ng/mL were considered as criteria to prompt further evaluation, the cancer detection rate was 3.1%. When %fPSA ≤ 15 in men with total PSA levels of 2.5-3.9 ng/mL were considered as criteria, the PCa detection rate increased to 3.7%. Considering %fPSA ≤ 15 in men with PSA 2.5-3.9 ng/mL and normal DRE, the positive predictive value of biopsy was 31.1%. • Clinical stage was more favourable among men with PSA 2.5-3.9 ng/mL, normal DRE, and %fPSA ≤ 15 compared with men with normal DRE and PSA ≥ 4.0 ng/mL (P= 0.02). • Among those who underwent radical prostatectomy, pathological stage and the proportion of insignificant tumours were similar between men with PSA 2.5-3.9 ng/mL, normal DRE findings and %fPSA ≤ 15, and men with PSA ≥ 4.0 ng/mL. CONCLUSIONS: • The use of %fPSA ≤ 15 as a biopsy indication in men with normal DRE and PSA 2.5-4.0 ng/mL in a PCa screening programme, increased cancer detection rates. Tumours in this subset of patients had similar pathological characteristics. • Using %fPSA ≤ 15 to indicate biopsy in men with PSA 2.5-3.9 ng/mL is a useful adjunct to PCa screening.

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Baseado em anotaçöes, reminiscências do autor e valiosos documentos, constitui-se em valiosa contribuiçäo ao conhecimento da saúde pública no Brasil. Ao relato dos acontecimentos científicos somam-se fatos pitorescos testemunhados pelo sanitarista.

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Relato de episódios de passadas campanhas sanitárias, apresentando casos, situaçöes, a experiência vivida e até frustraçöes de médicos sanitaristas e de guardas sanitários.

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Relembra alguns episódios marcantes ocorridos na vivência do trabalho de prevençäo da peste, tracoma, doença de Chagas e outras endemias. Mostra, de um lado, a dura realidade de país subdesenvolvido e, do outro, o humor com que o autor soube enfrentar as situaçöes mais difíceis de sua carreira de sanitarista.

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