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Background and objectives: Burnout results from chronic workplace stress leading to emotional exhaustion, negativity, and decreased professional efficiency. In the healthcare system, this can have consequences like increased medical errors, absenteeism, substance abuse, depression, and suicide among health professionals, adversely affecting patient care. Various individual-directed measures like the mindfulness-based stress reduction program (MBSR), one of the most studied and widely adopted techniques, and physical activity, like aerobics or sports, have shown to be effective against burnout. With this study, we intend to increase awareness regarding this public health issue among the residents and the faculty. Our aim is to define a successful intervention that can be incorporated as a yearly requirement for the completion of residency programs. Methodology: This study will be a phase III, multicentric, open-label, placebo (waiting list) controlled trial. Our sample size will be 720 residents sampled from 6 university hospitals from across the world, randomized into 3 parallel arms (1:1:1 ratio stratified according to site and specialty). Residents, diagnosed with burnout based on baseline Maslach Burnout Inventory score (MBI) and having no prior physical or mental health issues, will be included. The first group will undergo the MBSR program for 8 weeks, the second group will undergo a supervised aerobics program for 8 weeks, and the third group will be put into a waiting list for any of the interventions. The primary outcome will be the change in MBI scores after the intervention. The secondary outcomes will be the change in MBI score 3 months after the intervention, and changes in measures like heart rate, blood pressure, glycated hemoglobin, cortisol levels, quality of sleep and quality of life after the intervention and 3 months later. We also plan to do a subgroup analysis to see the difference based on specialty and gender. Study impact: The residency training period is considered one of the most stressful phases in medical education. Higher rates of burnout are noted in the residents, and this can negatively impact patient care and the progression of their careers. This trial will look at multiple interventions to combat burnout recruiting residents of different specialties in different work environments across the world. We hope to remove the stigma surrounding burnout in the healthcare system. This study will show the short and long term benefits of these interventions and would help us recommend their inclusion in various residency programs.

Introduction: In recent years, the number of patients with end-stage renal disease has rapidly increased worldwide. In Brazil, recent surveys have undisclosed a trend towards an increase in the prevalence of this condition. Aims and Objectives: This study aimed at describing the prevalence of patients with end-stage renal disease (ESRD) receiving publicly funded dialysis in Brazil. Methods asnd Materials: Data concerning the prevalence and mortality of patients with ESRD being provided renal replacement therapy by the SUS from 2008 to 2013 were collected at the DATASUS databank (www2.datasus.gov.br), the Authorization System for High Complexity/Cost Procedures (APAC) database, the SUS Ambulatory Information System (SIA) and the Mortality Information System (SIM) database. Results: From 2008 to 2013 there was a 25% increase in the absolute number of hemodialysis sessions (10,022,962; 12,561,623). This resulted in an estimated overall increase of 18% in the ratio of patients on hemodialysis per million population (352 pmp; 416 pmp). There were considerable differences among Brazilian States regarding the prevalence of patients with ESRD on hemodialysis. In 2013, the prevalence ranged from 173 pmp (State of Amazonas) to 531 pmp (State of Minas Gerais). The leading Brazilian States, in absolute number of patients, were São Paulo (19,301), Minas Gerais (10,940) and Rio de Janeiro (8,510), all of them in the southeast region. In 2013, the overall mean mortality rate was 18.4%. From 2008 to 2013, the renal transplantation rate increased from 35.2 to 41.6 transplants per year per million inhabitants. In 2013, hemodialysis was the most frequent modality of therapy, corresponding to 87.1% of the cases, followed by CAPD (9.2%) and APD (3.7%). Conclusion: In Brazil, chronic kidney disease is steadily increasing in prevalence and rapidly becoming a major public health concern. Therefore, policies towards prevention and strategies to avoid underdiagnose and assure broad access to renal replacement therapy should be strengthened nationwide.

Introduction: Congenital megaureter constitutes the second most frequent cause of hydronephrosis in children. There is still much debate on what extent environmental or genetic factors are involved in the pathogenesis of congenital megaureter. Objectives: This study aimed at investigating a pair of monozygotic twins discordant for the expression of bilateral congenital megaureter using the whole exome sequencing technique. Methods: Peripheral blood DNA was extracted and then sequenced using the whole exome technique from a pair of twins discordant for the presence of bilateral congenital refluxing unobstructed megaureter, his parents and a set of 11 non-related individuals with confirmed diagnosis of congenital megaureter. The DNA of the set of 11 non-related individuals was pooled in three groups. The monozygotic twins and their parents had DNA samples sequenced separately. Sanger validation was performed after data was filtered. Results: In the proband were identified 256 candidate genes, including TBX3, GATA6, DHH, LDB3, and HNF1, which are expressed in the urinary tract during the embryonic period. After Sanger validation, the SNVs found in the genes TBX3, GATA6, DHH and LDB3 were not confirmed in the proband. The SNV chr17:36104650 in the HNF1b gene was confirmed in the proband, his twin brother and the mother, however was not found in the pool of 11 non-related individuals with congenital megaureter. Conclusion: Due to the possible complex causative network of genetic variations and the challenges regarding the use of the whole exome sequencing technique we could not unequivocally associate the genetic variations identified in this study with the development of the congenital megaureter.

The early era of evidence-based medicine (EBM) saw the emergence of a cohort of leaders who applied the concepts of clinical expertise, best available evidence and patient preferences to healthcare. Yet, with time, these core components of EBM have become distorted, misinterpreted and hijacked.1 The EBM Manifesto provided a roadmap for tackling the core issues related to the practice and application of EBM.2 One of the important items in the manifesto is to ‘ Encourage the next generation of leaders in evidence-based medicine ’.2 Achieving improvements in healthcare globally requires building and sustaining early and mid-career researchers (EMCRs).3 Yet, there are big gaps in both critical appraisal and research capacity, particularly in low-income and middle-income countries (LMICs), and this hinders development in these regions.4 At the 2019 EBMLive conference (see box 1), we wanted to better understand the problems and challenges that EMCRs encounter. In particular, we focused on EMCRs in those LMICs undergoing major health system transformations, such as Brazil and India. We asked the six recipients of the Building Capacity Bursaries (all co-authors of this commentary) to describe the challenges that they have encountered individually and among their peers, along with potential solutions (see box 2). Their responses reflect healthcare professionals who practice in South America, Africa, the Middle East and Asia. While some challenges are specific to certain settings, we tried to identify, highlight and describe broad overarching themes. Box 1 ### The EBMLive Conference

Science is conceptually dynamic and constantly trying to re-inventing itself. Since the beginning humankind has always been struggling on whether to go more general in its beliefs or to acknowledge diversity, allowing the construction of different solutions tailored to local particularities. Currently, it seems that researchers, patients, the pharmaceutical industry, governments, other stakeholders, are in midst of a debate where social, cultural and environmental characteristics have been historically overlooked as factors to be considered in the art of research and decision making. For decades we have built a framework where patients are being deliberately forced to fulfill a standard and reproduce the results of a study published elsewhere. Shouldn’t it be the other way around? This failure to navigate between the search for universal truths and personalized healthcare has taken the patient from the center of the driving force of innovation. This dynamic allowed too much power in the hands of a few which have deliberately been trying to dictate the standards on how we behave and consume healthcare resources, opening the doors to incoherence, bias, conflicts of interests and frustration. Hopefully, in the near future, this search for truths, which forcibly must be applied to all, will be acknowledged as an oversimplified approach especially in the scenario of a world full of inequities and economic disparities. In this context, science is being called to shift its paradigms and acknowledge the complexity and diversity of humans. The overemphasized appeal of international publications, the irrational sophistication of the p.

Congenital anomalies of the kidney and urinary tract (CAKUT) represent a broad range of disorders that result from abnormalities of the urinary collecting system, abnormal embryonic migration of the kidneys, or abnormal renal parenchyma development. These disorders are commonly found in humans, accounting for 20-30% of all genetic malformations diagnosed during the prenatal period. It has been estimated that CAKUT are responsible for 30-50% of all children with chronic renal disease worldwide and that some anomalies can predispose to adult-onset diseases, such as hypertension. Currently, there is much speculation regarding the pathogenesis of CAKUT. Common genetic background with variable penetrance plays a role in the development of the wide spectrum of CAKUT phenotypes. This review aims to summarize the possible mechanisms by which genes responsible for kidney and urinary tract morphogenesis might be implicated in the pathogenesis of CAKUT.

Socioeconomic disparities are suspected to play an important role in the development of non-communicable chronic diseases and increase the risk for mortality and morbidity among patients with end-stage renal disease. This study aimed to investigate a possible association between educational levels, monthly per capita income and prevalence of clinical comorbidities found in patients at the initiation of the hemodialysis therapy. A sample of 214 patients was analyzed. Patients were stratified according to their educational level in two groups: ≤ 4 and > 4 years of formal education. For the monthly per capita income the following groups were considered: < US$300.00, ≥ US$300.00 and < US$450.00 and ≥ US$450.00. There was no statistical significant difference regarding the prevalence of comorbidities when comparing different educational levels. Similar results were found when monthly per capita income was analysed. In spite of that, there was an elevated frequency of patients with ≤ 4 years of formal education (73.36%, p

IntroductionOpen repair was considered for several years the gold standard therapy for the treatment of peripheral artery aneurysms (PAAs). However, with advancements in endovascular technology increasing attention has been directed toward repairing PAAs using an endovascular stent graft.MethodsThis retrospective study evaluated a cohort of patients after the correction of PAAs with Viabahn. Patients treated from January 2011 to January 2018 were assessed for all-cause mortality, amputation and the need for re-intervention. Data were extracted from an administrative database from a healthcare organization in Belo Horizonte, Brazil.ResultsFifty-two patients were included in the study (median age 69.1 years, range 15 to 90 years; male 63.5 percent), three of whom also received Viabahn for contralateral PAAs. In total, 84 devices were used (average 1.5 per PAA); distribution: popliteal and tibial arteries (n = 30; 57 percent), femoral and iliac arteries (n = 19; 37 percent), axillary artery (n = 1; 2 percent), splenic artery (n = 1; 2 percent), abdominal aorta (n = 1; 2 percent). After a mean follow up time of 1.98 ± 1.68 years, we observed death (n = 3; 5.8 percent), amputation (n = 3; 5.8 percent) and the need for re-intervention (n = 17; 32.6 percent) in 23 patients (44.2 percent). The combined overall survival for the first, second and third year of follow up was 70.2 percent (Confidence Interval [95% CI]: 58.9 - 83.6); 63 percent (95% CI: 51.0 - 78.0) and 57.3 percent (95% CI 44.6 - 73.6).ConclusionsThere are still several unanswered questions regarding the best approach for patients with PAAs. In the absence of well-designed clinical studies, the assessment of databanks on real-world patients may contribute to improve our understanding of treatment alternatives and provide guidance to improve current clinical results.

IntroductionMany patients presenting with arrhythmias are treated with antiarrhythmic drug therapy. However, for some patients, usually survivors of previous serious ventricular arrhythmias, treatment implies the use of implantable cardioverter defibrillators (ICDs) and/or Cardiac Resynchronization Therapy (CRT) devices.MethodsThis retrospective study evaluated a cohort of patients with arrhythmia requiring the use of ICDs, CRT or ICDs + CRT from January 2004 to March 2018. Data from a private healthcare organization in Belo Horizonte, Brazil were used to assess all-cause mortality and the need for replacement of the device. Continuous variables were expressed as mean and standard deviation. Cox proportional regression model and Log-Rank test were used to adjust the survival curve.ResultsFive hundred and ninety-three patients were included in the study (median age 67.6 years, range 23 to 89 years; male 62 percent). According to the type of device used to treat these patients, the distribution was 338 (57.0 percent), 169 (28.5 percent), 86 (14.5 percent), for ICDs, ICDs + CRT, CRT, respectively. After a mean follow-up time of 3.12 years (range 0 to 13.6 years), 283 devices were replaced (ICDs n = 140; ICDs + CRT n = 90; CRT n = 53) and 284 deaths occurred (median survival of 6.9 years). The median survival was 7.3, 5.8, 4.8, 5.5 years for ICDs single-chamber, ICDs dual-chamber, ICDs + CRT, CRT, respectively.ConclusionsRandomized trials are often criticized for their enrollment of highly selected patients. Studies on real-word data can provide reliable information regarding the use of ICDs and/or CRT devices in the treatment of patients with serious ventricular arrhythmias.

IntroductionBariatric surgery has become one of the fastest growing operative procedures due to its sustained results and the increasing prevalence of obesity worldwide. Despite this fact, bariatric surgery carries the usual risks and threats of surgical interventions and therefore its benefits might be undermined by its mid and long-term complications.MethodsThis retrospective study included obese patients requiring bariatric surgery from January 2004 to December 2017 provided by a private healthcare organization in Belo Horizonte, Brazil. Data regarding healthcare utilization were extracted from an administrative database (software Oracle Business Intelligence). Continuous variables were expressed as mean and standard deviation. Log-Rank test was used to adjust the survival curve (software STATA 13.1, Stata Corp, USA). This historical cohort resulted in no interventions, neither during the instituted treatment nor after the observed outcome. Privacy of subjects and the confidentiality of their personal information were handled in accordance with the ethical principles of the Declaration of Helsinki.ResultsIn total, 16,786 patients were included in the study (mean age 37.2 ± 10.2 years; female 79.2 percent; mean body mass index 42.4 ± 5.5 kg/m2). Patients were followed for up to seven years before and after surgery (total of 78,113 patients/year). For this group, the hospitalization rate was 0.099 / patients-year before versus 0.151 / patients-year after the bariatric surgery (p ConclusionsBariatric surgery has been an increasingly popular choice in the management of obesity. In our sample, it did not reduce the overall mid-term healthcare utilization rate.

Claudia Kimie Suemoto,1,2 Sherine Ismail,1,3 Paulo César Rodrigues Pinto Corrêa,1,4,5 Faiza Khawaja,1,6 Teodoro Jerves,1 Laura Pesantez,1 Ana Claudia Camargo Gonçalves Germani,1,7 Fabio Zaina,1,8 Augusto Cesar Soares dos Santos Junior,1,9,10 Ricardo Jorge de Oliveira Ferreira,1,11 Priyamvada Singh,1,12 Judy Vicente Paulo,1,13 Suely Reiko Matsubayashi,1,14 Liliane Pinto Vidor,1,15 Guilherme Andretta,1,16 Rita Tomás,1,17 Ben MW Illigens,1,18 Felipe Fregni1,18,19 1Collaborative Learning in Clinical Research Program, Principles and Practice of Clinical Research (PPCR), Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 2Discipline of Geriatrics, Department of Internal Medicine, University of São Paulo Medical School, São Paulo, Brazil; 3King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Pharmaceutical Care Department, King Khalid Hospital, NGHA, Jeddah, Saudi Arabia; 4Discipline of Internal Medicine and Medical Semiology, Department of Internal Medicine, Federal University of Ouro Preto (UFOP) Medical School, Ouro Preto, Brazil; 5Discipline of Pneumology, Department of Internal Medicine, Centro Universitário de Belo Horizonte (Uni-BH), Belo Horizonte, Brazil; 6Canadian Centre for Advanced Eye Therapeutics, Mississauga, ON, Canada; 7Department of Preventive Medicine, University of São Paulo Medical School, São Paulo, Brazil; 8Italian Scientific Spine Institute (ISICO), Milan, Italy; 9Hospital Osvaldo Rezende Franco, Betim, Brazil; 10Nucleo de Avaliação de Tecnologia em Saude, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; 11Department of Rheumatology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 12Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA, USA; 13Portuguese Institute of Oncology, Coimbra, Portugal; 14Acupuncture Center, Orthopedics and Traumatology Institute, University of Sao Paulo Medical School, São Paulo, Brazil; 15Department of Medical Science, Faculty of Medicine, University Federal of Rio Grande do Sul, Porto Alegre, Brazil; 16Quintiles Transnational, São Paulo, Brazil; 17Department of Physical Medicine and Rehabilitation, Hospital de Curry Cabral, Centro Hospitalar de Lisboa Central, EPE, Lisbon, Portugal; 18Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; 19Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Boston, MA, USA Abstract: The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008–2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background. Keywords: education, distance learning, biomedical research, critical thinking, e-learning

This study aimed to retrospectively evaluate a cohort of patients with prostate cancer and persistent urinary incontinence after radical prostatectomy. From January 2004 to December 2015, eighty-six individuals were identified to have received an AUS implant, provided by a private nonprofit HMO operating in Belo Horizonte, Brazil. On total, there were 91 AUS implants, with a median interval between radical prostatectomy and AUS implant of 3.6 years (IQR 1.9 to 5.5). The rate of AUS cumulative survival, after a median follow-up of 4.1 years (IQR 1.7-7.2 years), was 44% (n=40). The median survival of AUS implants was 2.9 years (IQR 0.5-7.9 years). Thirty-seven AUS implants (40.7%) resulted in grade III surgical complications. There were 5 deaths at 2.1, 4.7, 5.7, 5.7 and 6.5 years of follow-up, but none due to causes directly associated to the AUS implant. Persistent severe incontinence was documented in 14 (15.3%) additional patients. From the 51 AUS implants which resulted in grade III surgical complications or persistent severe incontinence, 24 (47.1%) underwent surgical revisions. Explantation of the sphincter or its components was observed in 6 cases (25.0%). Mechanical failure, described as fluid loss and/or inability to recycle the AUS device, was observed in 4 devices (16.7%). In conclusion, although AUS implants are recommended as the gold-standard treatment of severe urinary incontinence after prostatectomy, the observed high rates of malfunction and grade III adverse events are a matter of concern warranting further assessment on the safety and efficacy of these devices.

Congenital anomalies of the kidney and urinary tract (CAKUT) represent a broad range of disorders that result from abnormalities of the urinary collecting system, abnormal embryonic migration of the kidneys, or abnormal renal parenchyma development. These disorders are commonly found in humans, accounting for 20-30% of all genetic malformations diagnosed during the prenatal period. It has been estimated that CAKUT are responsible for 30-50% of all children with chronic renal disease worldwide and that some anomalies can predispose to adult-onset diseases, such as hypertension. Currently, there is much speculation regarding the pathogenesis of CAKUT. Common genetic background with variable penetrance plays a role in the development of the wide spectrum of CAKUT phenotypes. This review aims to summarize the possible mechanisms by which genes responsible for kidney and urinary tract morphogenesis might be implicated in the pathogenesis of CAKUT.

This study aimed to retrospectively evaluate a cohort of patients with prostate cancer and persistent urinary incontinence after radical prostatectomy. From January 2004 to December 2015, eighty-six individuals were identified to have received an AUS implant, provided by a private nonprofit HMO operating in Belo Horizonte, Brazil. On total, there were 91 AUS implants, with a median interval between radical prostatectomy and AUS implant of 3.6 years (IQR 1.9 to 5.5). The rate of AUS cumulative survival, after a median follow-up of 4.1 years (IQR 1.7-7.2 years), was 44% (n=40). The median survival of AUS implants was 2.9 years (IQR 0.5-7.9 years). Thirty-seven AUS implants (40.7%) resulted in grade III surgical complications. There were 5 deaths at 2.1, 4.7, 5.7, 5.7 and 6.5 years of follow-up, but none due to causes directly associated to the AUS implant. Persistent severe incontinence was documented in 14 (15.3%) additional patients. From the 51 AUS implants which resulted in grade III surgical complications or persistent severe incontinence, 24 (47.1%) underwent surgical revisions. Explantation of the sphincter or its components was observed in 6 cases (25.0%). Mechanical failure, described as fluid loss and/or inability to recycle the AUS device, was observed in 4 devices (16.7%). In conclusion, although AUS implants are recommended as the gold-standard treatment of severe urinary incontinence after prostatectomy, the observed high rates of malfunction and grade III adverse events are a matter of concern warranting further assessment on the safety and efficacy of these devices.