Physician's perceptions regarding the pharmaceutical industry: a Brazilian national study.

OBJECTIVE: The objective of this study was to investigate the newly graduated physicians' attitudes and perceptions regarding the medical relationship with the pharmaceutical industry and identify the sociodemographic patterns related to such thinking. METHODS: A structured questionnaire was administered to 4,601 participants selected from a pool of 16,323 physicians who were registered with one of the 27 Regional Medical Councils of Brazil in 2015. Answers were analyzed using two stratification variables: type of medical school (public vs. private) and the sex of the respondents. RESULTS: Out of the participants, 61.8% believed that industry funding could support medical conferences and education, and 48.4% felt that small gifts and conference travel funding were acceptable. Conversely, 64.7% disagreed with industry-sponsored social events. Views on whether pharmaceutical representatives' visits influenced prescriptions were divided. Statistically significant differences were observed between genders and medical school types, with men and private school graduates being more accepting of certain industry interactions. CONCLUSION: The study highlights the nuanced attitudes of new doctors toward industry relationships, indicating the need for clearer ethical guidelines and education in medical schools to align practice with evolving societal values.

Physician's perceptions regarding the pharmaceutical industry: a Brazilian national study

OBJECTIVE: The objective of this study was to investigate the newly graduated physicians' attitudes and perceptions regarding the medical relationship with the pharmaceutical industry and identify the sociodemographic patterns related to such thinking. METHODS: A structured questionnaire was administered to 4,601 participants selected from a pool of 16,323 physicians who were registered with one of the 27 Regional Medical Councils of Brazil in 2015. Answers were analyzed using two stratification variables: type of medical school (public vs. private) and the sex of the respondents. RESULTS: Out of the participants, 61.8% believed that industry funding could support medical conferences and education, and 48.4% felt that small gifts and conference travel funding were acceptable. Conversely, 64.7% disagreed with industry-sponsored social events. Views on whether pharmaceutical representatives' visits influenced prescriptions were divided. Statistically significant differences were observed between genders and medical school types, with men and private school graduates being more accepting of certain industry interactions. CONCLUSION: The study highlights the nuanced attitudes of new doctors toward industry relationships, indicating the need for clearer ethical guidelines and education in medical schools to align practice with evolving societal values.

N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline, the major bioactive compound from Sideroxylon obtusifolium, attenuates pilocarpine-induced injury in cultured astrocytes.

Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 µg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.

N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline, the major bioactive compound from Sideroxylon obtusifolium, attenuates pilocarpine-induced injury in cultured astrocytes

Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 μg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.

Relação das alterações vestibulares em indivíduos com disfunção temporomandibular: um estudo piloto / Relationship of vestibular changes in individuals with temporomandibular dysfunction: a pilot study

Objetivo: Objetivou-se investigar as possíveis relações entre as Disfunções Temporomandibulares com alterações do Sistema Vestibular (SV). Métodos: Estudo descritivo com abordagem quantitativa realizado em 09 pacientes com idade média entre 18 e 40 anos. Os participantes foram recrutados no grupo de estudo e pesquisa em Fisioterapia e Odontologia na Dor Orofacial (FISIODOF) da Universidade de Fortaleza. O presente estudo foi aprovado pelo comitê de ética, com parecer N° 1.310.583. Resultados: De acordo com o RDC/TMD, 3 casos são do grupo G1, 1 caso é do grupo G2, 1 casos é do grupo G1 e G2, e os outros 4 casos como grupos G1 e G3. Todos os pacientes apresentaram resultados negativo no teste de Fukuda. Já na Manobra de Dix-Hallpike 3 pacientes apresentaram resultado positivo. Discussão: A hipertonia muscular é descrita como principal responsável pelos sintomas auditivos e vestibulares de pacientes com DTM. Entretanto, não existe uma relação precisa descrita na literatura entre DTM e disfunção do sistema vestibular. Conclusão: A DTM pode causar alterações no sistema vestibular, explicadas pelo fato das estruturas da articulação temporomandibular e sistema vestibular serem anatomicamente próximas. No entanto, outras pesquisas se fazem necessárias para caracterizar os achados vestibulares em portadores de disfunção temporomandibular(AU)

Objective: The objective was to investigate the possible relationships between Temporomandibular Disorders with changes in the Vestibular System (SV). Methods: Descriptive study with a quantitative approach conducted in 09 patients with a mean age between 18 and 40 years. Participants were recruited from the study and research group in Physiotherapy and Dentistry in Orofacial Pain at the University of Fortaleza. This study was approved by the ethics committee, No. 1,310,583. Results: According to the RDC / TMD, 3 cases are from the G1 group, 1 case is from the G2 group, 1 case are from the G1 and G2 group, and the 4 other cases are from the G1 and G3 groups. All patients had a negative Fukuda test result. In the Dix-Hallpike maneuver, 3 patients had a positive result. Discussion: Muscular hypertonia is described as the main responsible for the auditory and vestibular symptoms of patients with TMD. However, there is no precise relationship described in the literature between TMD and vestibular system dysfunction. Conclusion: TMD can cause changes in the vestibular system, explained by the fact that the structures of the temporomandibular joint and the vestibular system are anatomically close. However, further research is necessary to characterize vestibular findings in patients with temporomandibular disorders(AU)

Potency and Selectivity Optimization of Tryptophanol-Derived Oxazoloisoindolinones: Novel p53 Activators in Human Colorectal Cancer.

To search for novel p53 activators, four series of novel (S)- and (R)-tryptophanol-derived oxazoloisoindolinones were synthesized in a straightforward manner and their antiproliferative activity was evaluated in the human colorectal cancer HCT116 cell line. Structural optimization of the hit compound SLMP53-1 led to the identification of a (R)-tryptophanol-derived isoindolinone that was found to be six-fold more active, with increased selectivity for HCT116 cells with p53 and with low toxicity in normal cells. Binding studies with MDM2 showed that the antiproliferative activity of tryptophanol-derived isoindolinones does not involve inhibition of the main negative regulator of the p53 protein. Molecular docking simulations showed that although these molecules establish hydrophobic interactions with MDM2, they do not possess the required features to bind MDM2.

Análise da terapia craniossacral na disfunção temporomandibular associada a cefaleia tensional / Analysis of craniosacral therapy in temporomandibular dysfunction associated with tensional headache

Resumo Introdução Ocorrendo de forma branda e não invasiva, a terapia craniossacral é uma técnica de manipulação na qual o terapeuta exerce leve pressão sobre estrutura óssea, sendo utilizada como tratamento para diversos problemas de saúde, como cefaleias e DTM. Objetivo Analisar os efeitos da terapia craniossacral em indivíduos com disfunção temporomandibular associada a cefaleia do tipo tensional. Material e método Estudo descritivo, intervencionista com abordagem quantitativa, realizado no núcleo de atenção médica integrado, no período de fevereiro a setembro de 2018. Foram inclusos no estudo indivíduos com disfunção temporomandibular e que apresentaram cefaleia dentre os sintomas. Foram exclusos aqueles que não compareceram ao atendimento ou não apresentaram a sintomatologia. Previamente, foi realizada uma avaliação para identificar a dor na crise de cefaleia, a mensuração da amplitude de movimento mandibular e a palpação dos músculos da mastigação, para classificar a dor em leve, moderada ou forte. Após oito atendimentos, sendo duas vezes por semana com duração de 15 minutos cada, todos foram reavaliados. Resultado Participaram do estudo 31 indivíduos, sendo 90,3% do sexo feminino. Na classificação do RDC/TMD, houve prevalência dos grupos G1 e G1G3. Quanto a mobilidade mandibular, houve ganho para os movimentos de abertura, com 45,6 mm (±7,5) antes da terapia e, na reavaliação, 47,4 mm (±8,4); desvios laterais antes da terapia (lado direito - 7,0 ±2,8) e (lado esquerdo - 7,7±3,0), e após a terapia (8,0±3,0) e (8,6±2,9), respectivamente; o movimento de protusão, antes com média 5,03 ±2,5 e, na reavaliação, com 4,8 ±1,9. Na palpação muscular, destacamos redução do quadro álgico no músculo pterigoideo medial com média 2,2 (±1,05) antes da terapia e 1,5 (±1,02) após a terapia. Conclusão Concluímos que a terapia se mostrou eficaz no tratamento de pacientes com disfunção temporomandibular associada a cefaleia do tipo tensional.

Abstract Introduction Occurring in a mild and non-invasive way, craniosacra therapy is a manipulation technique that the therapist exerts light pressure on the bone structure, being used as a treatment for several health problems, such as headaches and TMD. Objective To analyze the effects of craniosacra therapy in individuals with temporomandibular disorders associated with tension-type headache. Material and method Descriptive, interventional study with a quantitative approach, carried out in the integrated medical care center from February to September 2018. Individuals with temporomandibular disorder and who presented headache among the symptoms were included in the study. And those who did not attend the service or did not present symptoms were excluded. Previously, an assessment was carried out to identify pain during headache attacks, measurement of mandibular range of motion and palpation of mastication muscles, to quantify pain as mild, moderate and severe. After 8 consultations, twice a week lasting 15 minutes each, all were reassessed. Result 31 individuals participated in the study, being 90.3% female. In the classification of the RDC/TMD, there was a prevalence of groups G1 and G1G3. Regarding mandibular mobility, there was a gain for opening movements with 45.6mm (±7.5) before therapy and 47.4mm (±8.4) in the reassessment; lateral deviations before therapy (right side - 7.0 ±2.8) and (left side - 7.7±3.0) and after (8.0±3.0) and (8.6±2.9); and the protrusion movement before with an average of 5.03 ± 2.5 and in the reassessment with 4.8 ± 1.9. And in muscle palpation, we highlight a reduction in pain in the medial pterygoid muscle with a mean of 2.2 (±1.05) before therapy and 1.5 (±1.02) after. Conclusion We conclude that the therapy has been shown to be effective in treating patients with temporomandibular disorders associated with tension-type headache.

Laser terapia no tratamento da perimplantite, mito ou realidade / Laser therapy in the treatment of periimplantitis, myth or reality

O presente trabalho faz uma revisão de literatura abordando o uso dos diversos tipos de lasers de alta intensidade no tratamento da perimplantite como terapia única ou coadjuvante aos métodos tradicionalmente usados, como mecânico e químico. A busca por novos recursos de tratamento, que sejam menos invasivos, mais seguros e de maior alcance em regiões remotas, impulsiona as pesquisas usando terapias com os diversos tipos delasers e sua aplicação no campo da implantodontia. Evidências de baixa confiabilidade, custo elevado dos equipamentos ainda são um obstáculo a ser vencido na realidade do uso do laser como terapia única. Com futuro promissor no tratamento coadjuvante às tradicionais terapias o uso do laser segue como aliado importante no complexo horizonte da perimplantite.

This paper reviews the literature addressing the use of different types ofhigh-intensity laser in the treatment of perimplantitis as a single therapy or as an adjunct to traditionally used methods, such as mechanical and chemical. The search for new treatment resources, which are less invasive, safer and with greater reach in remote regions, boosts research using therapies with different types of lasers and its application in the field of implantology. Evidence of low reliability and high cost of equipment are still an obstacle to be overcome in the reality of using lasers as the only therapy. With a promising future in adjunctive treatment to traditional therapies, the use of laser continues to be an important ally in the complex horizon of perimplantitis.

Implementation of a systematic comprehensive geriatric assessment for elderly patients suspected of pulmonary hypertension.

BACKGROUND: The phenotype of patients seen for a suspicion of pulmonary hypertension has changed, with an increasing age and frequency of comorbidities. Selection of elderly patients, in whom a classical work-up is mandatory, is challenging. Comprehensive geriatric assessment (CGA) has modified the management of elderly patients with cancer. Pulmonary hypertension (PH) shares with cancer a functional impact and may evolve rapidly, depending on the group of PH. We assessed the impact of a systematic CGA in patients over 70 years old referred for a suspicion of PH. METHODS: A standardised CGA was performed on every patient older than 70 years old, referred for a PH suspicion, before considering invasive tests for diagnosis and treatment, between July 2014 and May 2019. Our primary aim was to describe the impact of CGA on the decision to stop or pursue the recommended diagnostic work-up for PH. RESULTS: Among the thirty-one patients evaluated [mean age 81,5 (72-91) years], a negative CGA leads to stop the diagnostic work-up in eleven patients. Among the nineteen remaining patients, sixteen had confirmed PH, with half being chronic thromboembolic pulmonary hypertension. CONCLUSIONS: Our study indicates that comprehensive geriatric assessment could be an excellent first screen for elderly patients referred for a PH suspicion. Involving a geriatric physician stopped the investigations in one third of patients. In patients with a favourable CGA, PH was confirmed in most of the cases, with chronic thromboembolic pulmonary hypertension being the first cause of PH.

DLNO/DLCO ratio evolution under targeted therapy in patients with pulmonary hypertension.

The ratio of the diffusing capacity of the lung for carbon monoxide (DLCO) and for nitric oxide (DLNO) measured simultaneously is modified in patients with precapillary pulmonary hypertension (PH). The potential impact of targeted therapy on the DLCO/DLNO ratio is unknown. Simultaneous measurements of DLNO and DLCO were performed at baseline, 3-4 month follow-up (first evaluation) and 12-month follow-up (second evaluation) after initiation of targeted PH therapies in incident cases of precapillary PH. The main outcome was the change in DLNO/DLCO ratio under treatment between baseline and the first evaluation. Twenty-nine patients were included (mean age: 66.8 years, 62.1% female). No significant change in the DLNO/DLCO ratio was found between baseline and the first evaluation. Similarly, no significant differences were noted with regard to changes in Dm or Vc, the DLNO/DLCO ratio in different patient subgroups, or in the 20 patients evaluated at the second follow-up. Within the limitations of this study, the DLNO/DLCO ratio is not useful in monitoring the response to treatment in PH.

Outcomes of Acute Stroke Patients Requiring Mechanical Ventilation: Study Protocol for the SPICE Multicenter Prospective Observational Study.

BACKGROUND: Care pathways and long-term outcomes of acute stroke patients requiring mechanical ventilation have not been thoroughly studied. METHODS AND RESULTS: Stroke Prognosis in Intensive Care (SPICE) is a prospective multicenter cohort study which will be conducted in 34 intensive care units (ICUs) in the Paris, France area. Patients will be eligible if they meet all of the following inclusion criteria: (1) age of 18 years or older; (2) acute stroke (i.e., ischemic stroke, intracranial hemorrhage, or subarachnoid hemorrhage) diagnosed on neuroimaging; (3) ICU admission within 7 days before or after stroke onset; and (4) need for mechanical ventilation for a duration of at least 24 h. Patients will be excluded if they meet any of the following: (1) stroke of traumatic origin; (2) refusal to participate; and (3) privation of liberty by administrative or judicial decision. The primary endpoint is poor functional outcome at 1 year, defined by a score of 4 to 6 on the modified Rankin scale (mRS), indicating severe disability or death. Main secondary endpoints will include decisions to withhold or withdraw care, mRS scores at 3 and 6 months, and health-related quality of life at 1 year. CONCLUSIONS: The SPICE multicenter study will investigate 1-year outcomes, ethical issues, as well as care pathways of acute stroke patients requiring invasive ventilation in the ICU. Gathered data will delineate human resources and facilities needs for adequate management. The identification of prognostic factors at the acute phase will help to identify patients who may benefit from prolonged intensive care and rehabilitation. TRIAL REGISTRATION: NCT03335995.

Amniotic band syndrome with double encephalocele: A case report.

BACKGROUND: Amniotic band syndrome (ABS) is a rare condition of controversial etiology that is associated with varying degrees of anomalies. This study reports a case of a newborn with ABS associated with double encephalocele in the frontal region. CASE DESCRIPTION: A 29-year-old primiparous woman with no history of prenatal infection or consanguineous marriage had a cesarean section at gestational week 38, giving birth to a newborn who was well but had limb anomalies (constriction rings, amputations, and syndactyly) and craniofacial anomalies, mainly double frontal encephalocele. The patient underwent surgical repair and subsequent placement of a ventriculoperitoneal shunt. CONCLUSION: Studies clarifying this uncommon association with double encephalocele are limited. ABS associated with double encephalocele is rare and even more complex when associated with other anomalies. Thus, the conditions in such children are severe and require multidisciplinary monitoring.

Sentimentos dos Estudantes de Medicina e Médicos Residentes ante a Morte: uma Revisão Sistemática / Feelings of Medical Students and Resident Doctors Facing Death: a Systematic Review

Resumo: Introdução: Como os profissionais da área médica terão que lidar com a questão da morte, este trabalho teve como objetivos identificar os sentimentos dos estudantes de Medicina e dos médicos residentes do Brasil ante o morrer e a morte, e compreender como eles vivenciam a própria formação durante a graduação e a especialização para esse enfrentamento. Método: Trata-se de uma revisão sistemática da literatura feita com base na metodologia PRISMA. A revisão foi conduzida entre agosto e dezembro de 2019 com os descritores "estudantes de medicina", "medical students", "morte" e "death", pesquisados na Biblioteca Virtual de Saúde (BVS). Resultados: Dos 372 artigos identificados na busca, 18 estudos publicados atendiam a todos os critérios de inclusão e exclusão estabelecidos. Quanto à análise dos artigos em relação aos sentimentos dos estudantes de Medicina e dos médicos residentes perante situações de morte, percebeu-se que a maioria dos estudos relatou experiências negativas, como medo, insegurança, tristeza, raiva e culpa. Apesar de ainda serem incipientes as disciplinas e estratégias institucionalizadas, parece que, com o decorrer do curso e da prática profissional, os sentimentos negativos são amenizados, porque se vivenciam com mais frequência contextos de terminalidade e morte, oportunizando, assim, o aprendizado por meio da observação e postura perante essas situações práticas, visto que a morte e suas interfaces fazem parte do cotidiano médico. Conclusões: Os estudantes de Medicina e os médicos residentes do Brasil apresentam desconforto e dificuldade em lidar com os processos de morte e do morrer. Para modificar esse cenário de despreparo, é consenso entre eles a necessidade de incluir disciplinas teórico-práticas de Tanatologia, Cuidados Paliativos e Psicologia Médica no currículo das faculdades de Medicina e reformular o conteúdo delas de forma a abordar mais profundamente o processo de morte no contexto prático.

Abstract: Introduction: Most professionals in the medical field will have to deal with the issue of death. This paper aims to describe the feelings of Brazilian medical students and resident doctors regarding end of life and death, as well as to understand how they experience their undergraduate training and specialization in dealing with this process. Method: This is a systematic literature review based on the PRISMA methodology, conducted between August and December 2019 with the descriptors "medical students" and "death," in both English and Portuguese, in papers indexed in the Virtual Health Library (VHL). Results: 372 papers were identified in the search; 18 were published studies that met all the established inclusion and exclusion criteria. Analysis of the articles concerning the feelings of medical students and resident doctors facing situations involving death revealed that most studies reported negative experiences, such as fear, insecurity, sadness, anger, and guilt. Despite the subjects and institutionalized strategies still being relatively new, it would seem that as their training and professional practice progress, the young doctors' negative feelings are attenuated as they experience end-of-life and death situations more frequently, thus learning through observation and posture in these practical situations, seeing as death and dealing with it is part of everyday medical work. Conclusions: Medical students and medical residents in Brazil experience discomfort and difficulty in dealing with the processes of death and dying. To improve their preparedness in this respect, there is a consensus among them about the need to include the theoretical/practical disciplines of Thanatology, Palliative Care and medical psychology in the medical curriculum and to reformulate the content in order to approach the subject of death in a more practical context.

Chronic thromboembolic pulmonary hypertension suspicion after pulmonary embolism in cancer patients.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe condition which should be screened in patient with persistent dyspnea after pulmonary embolism (PE). After PE, CTEPH incidence was estimated between 0.1 and 9.1% in overall patients. Although cancer is associated with an increased risk of CTEPH, CTEPH incidence is still unknown in cancer patients with PE. We aimed to estimate the frequency CTEPH-likely patients after PE, in cancer patients. MATERIALS: We individualized cancer patients of a monocentric prospective registry including consecutive patients with symptomatic PE. The primary outcome was the frequency of "CTEPH-likely" patients defined by the European Respiratory Society (ERS) guidelines (an accelerated tricuspid regurgitation more than 2.8m/s and at least 1-2 segmental or larger-sized defects, after more than 3 months of therapeutic anticoagulation). RESULTS: We included 129 cancer patients with PE. Colorectal cancer (19%), breast cancer (17%) and prostate cancer (15%) were the most frequent cancers. PE occurred after surgery or medical immobilization in 17% of patients, while 26% of patients had history of venous thromboembolism. During the follow-up, 2 patients (1.5%) had a clinical suspicion of CTEPH and only 1 patient with ovarian cancer (0.75% 95%CI [0.0%-2.2%]) was classified as "CTEPH-likely", 6 months after PE. CONCLUSION: The frequency of screening for CTEPH seems negligible in PE patients with cancer. Concomitant cancer may affect the clinical suspicion of CTEPH.

Disease-related outcomes influence prevalence of falls in people with rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of falls, with potential adverse outcomes. There is a considerable variation across studies regarding the prevalence of falls and its correlation with clinical data, disease-related outcomes and physical performance tests. OBJECTIVE: The aim of this study was to evaluate the prevalence of falls and its association with clinical data, disease-related outcomes and physical performance tests. METHODS: In this cross-sectional study, 113 RA patients were divided into 3 groups - "non-fallers", "sporadic fallers" and "recurrent fallers" - and compared in terms of clinical data, Clinical Disease Activity Index (CDAI), lower-limb tender and swollen joint count, disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), Foot Function Index (FFI), Berg Balance Scale (BBS), Timed-up-and-go Test (TUG) and 5-Time Sit Down-To-Stand Up Test (SST5). Logistic regression analysis was performed to analyze the associations between the studied variables and the occurrence of falls, estimating odds ratios (ORs). We also analyzed the correlation between disease outcome measures (HAQ-DI and CDAI) and physical tests (BBS, TUG, SST5). RESULTS: Falls and fear of falling were reported by 59 (52.21%) and 71 (64.5%) patients, respectively. Significant associations were found between "recurrent fallers" and vertigo (OR=3.42; P=0.03), fear of falling (OR=3.44; P=0.01), low income (OR=2.02; P=0.04), CDAI (OR=1.08; P<0.01), HAQ-DI (OR=3.66; P<0.01), Lower-limb HAQ (OR=3.48; P<0.01), FFI-pain (OR=1.24; P=0.03), FFI-total (OR=1.23; P=0.04), lower-limb tender joint count (OR=1.22; P<0.01), BBS score (OR=1.14; P<0.01), TUG score (OR=1.13; P=0.03) and SST5 score (OR=1.06; P=0.02). On multivariate analysis, CDAI was the only significant predictor of recurrent falls (OR=1.08; P<0.01). Physical performance test scores (BBS, TUG, SST5) were correlated with the CDAI and HAQ-DI. CONCLUSION: The prevalence of falls in RA is high, most influenced by disease-related outcomes and linked to worse performance on physical tests (BBS, TUG and SST5).

Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5-fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC). These combinations have resulted in increased progression-free survival (PFS) in patients with mCRC; however, there are remaining concerns over the extent of their effect on overall survival (OS). Published studies to date suggest no major differences between the three currently available monoclonal antibodies (MoAbs); however, there are differences in costs. In addition, there is rising litigation in Brazil in order to access these medicines as they are currently not reimbursed. OBJECTIVE: The aim was to investigate the comparative effectiveness and safety of three MoAbs (bevacizumab, cetuximab and panitumumab) associated with fluoropyrimidine-based chemotherapy regimens and compared to fluoropyrimidine-based chemotherapy alone in patients with mCRC, through an updated systematic review and meta-analysis of concurrent or non-concurrent observational cohort studies, to guide authorities and the judiciary. METHOD: A systematic review and meta-analysis was performed based on cohort studies published in databases up to November 2017. Effectiveness measures included OS, PFS, post-progression survival (PPS), Response Evaluation Criteria In Solid Tumors (RECIST), response rate, metastasectomy and safety. The methodological quality of the studies was also evaluated. RESULTS: A total of 21 observational cohort studies were included. There were statistically significant and clinically relevant benefits in patients treated with bevacizumab versus no bevacizumab mainly around OS, PFS, PPS and the metastasectomy rate, but not for the disease control rates. However, there was an increase in treatment-related toxicities and concerns with the heterogeneity of the studies. CONCLUSION: The results pointed to an advantage in favor of bevacizumab for OS, PFS, PPS, and metastasectomy. Although this advantage may be considered clinically modest, bevacizumab represents a hope for increased survival and a chance of metastasectomy for patients with mCRC. However, there are serious adverse events associated with its use, especially severe hypertension and gastrointestinal perforation, that need to be considered.

Portuguese consensus document for the management of alpha-1-antitrypsin deficiency.

Alpha-1-antitrypsin deficiency (AATD) is a genetic autosomal codominant disorder caused by mutations in SERPINA1 gene. It is one of the most prevalent genetic disorders, although it remains underdiagnosed. Whereas at international level there are several areas of consensus on this disorder, in Portugal, inter-hospital heterogeneity in clinical practice and resources available have been adding difficulties in reaching a diagnosis and in making therapeutic decisions in this group of patients. This raised a need to draft a document expressing a national consensus for AATD. To this end, a group of experts in this field was created within the Portuguese Pulmonology Society - Study group on AATD, in order to elaborate the current manuscript. The authors reviewed the existing literature and provide here general guidance and extensive recommendations for the diagnosis and management of AATD that can be adopted by Portuguese clinicians from different areas of Medicine. This article is part of a supplement entitled "Portuguese consensus document for the management of alpha-1-antitrypsin deficiency" which is sponsored by Sociedade Portuguesa de Pneumologia.

Assessment of the impact of changes in temperature in Biomphalaria glabrata (Say, 1818) melanic and albino variants infected with Schistosoma mansoni (Sambon, 1907) / Avaliação de impacto de alterações na temperatura em Biomphalaria glabrata variantes melânica e albina infectadas com Schistosoma mansoni

Abstract Fluctuations in population density of planorbid hosts of S. mansoni are influenced by climatic factors. The knowledge about interference from changes in water temperature in these populations is an important aspect of the epidemiology of schistosomiasis. In this experiment, it is explored the influence of different temperatures on the development of Schistosoma mansoni in Biomphalaria glabrata melanic and albino variants. The results indicated an intrinsic relationship between temperature and development of the parasite in the intramollusc phase, independent of the pigmentation of the mantle of the molluscs. The higher the temperature, the shorter the period necessary for the development of the parasite was while the higher the mortality of infected mollusks. It is concluded that, in the presence of climate change, the increasement of temperature in cold and flooded regions may encourage the establishment of new foci of transmission of schistosomiasis by changing the geographic extent and extending the epidemiological transmission potential. In warm climates, higher temperatures, however, could compromise the transmission of the disease because of biological stress suffered by parasite and host. Under these conditions, it can result in the death of the parasite or a change in their ability to infect new host species of molluscs in new areas. Mantle pigmentation patterns in molluscs have not shown significant interference in the development of the parasite.

Resumo Flutuações na densidade populacional de planorbídeos hospedeiros do S. mansoni são influenciadas por fatores climáticos. O conhecimento sobre a interferência de alterações na temperatura da água nestas populações é um aspecto importante da epidemiologia da esquistossomose. Neste experimento avaliou-se a influência de diferentes temperaturas no desenvolvimento de Schistosoma mansoni em Biomphalaria glabrata variantes melânica e albina. Os resultados indicaram uma relação intrínseca entre temperatura e desenvolvimento do parasito na fase intramolusco, independente da pigmentação do manto dos moluscos. Quanto mais elevada a temperatura, menor o período necessário para desenvolvimento do parasito e maior mortalidade dos moluscos infectados. Conclui-se que, na presença de alterações climáticas, o aumento da temperatura em regiões frias e alagadas poderá favorecer o estabelecimento de novos focos de transmissão da esquistossomose alterando a extensão geográfica e ampliando o potencial epidemiológico da transmissão. Em regiões de clima quente, o aumento da temperatura, por sua vez, poderá comprometer a transmissão da doença em virtude do estresse biológico sofrido por parasito e hospedeiro. Nestas condições, poderá ocorrer a morte do parasito ou uma alteração na sua habilidade de infectar novas espécies de moluscos hospedeiros em novas áreas. Padrões de pigmentação do manto nos moluscos não demonstraram interferência significativa no desenvolvimento do parasita.

Susceptibility of Biomphalaria glabrata submitted to concomitant infection with Angiostrongylus costaricensis and Schistosoma mansoni / Suscetibilidade de Biomphalaria glabrata submetida à infecção concomitante com Angiostrongylus costaricensis e Schistosoma mansoni

Abstract The easy adaptation of Angiostrongylus costaricensis, nematode responsible for abdominal angiostrongyliasis to several species of terrestrial and freshwater molluscs and the differences observed in the interactions of trematodes with their intermediate hosts have induced us to study the concomitant infection of Biomphalaria glabrata with Schistosoma mansoni and A. costaricensis. Prior exposure of B. glabrata to A. costaricensis (with an interval of 48 hours), favored the development of S. mansoni, observing higher infection rate, increased release of cercariae and increased survival of molluscs, when compared to molluscs exposed only to S. mansoni. Prior exposure of B. glabrata to A. costaricensis and then to S. mansoni also enabled the development of A. costaricensis since in the ninth week of infection, higher amount of A. costaricensis L3 larvae was recovered (12 larvae / mollusc) while for molluscs exposed only to A. costaricensis, the number of larvae recovered was lower (8 larvae / mollusc). However, pre-exposure of B. glabrata to S. mansoni (with an interval of 24 hours), and subsequently exposure to A. costaricensis proved to be very harmful to B. glabrata, causing extensive mortality of molluscs, reduced pre-patent period to release cercariae and greater recovery of L3 A. costaricensis larvae.

Resumo A facilidade de adaptação do Angiostrongylus costaricensis, nematódeo responsável pela angiostrongiliase abdominal, a diversas espécies de moluscos terrestres e dulciaquícolas e as divergências observadas nas interações dos trematódeos com seus hospedeiros intermediários nos induziu a estudar a infecção concomitante de Biomphalaria glabrata com Schistosoma mansoni e A. costaricensis. A exposição prévia de B. glabrata ao A. costaricensis (com intervalo de 48 horas), favoreceu o desenvolvimento do S. mansoni observando-se elevação da taxa de infecção, maior liberação de cercárias e maior sobrevivência dos moluscos, quando comparado com os moluscos expostos somente ao S. mansoni. A exposição de B. glabrata previamente ao A. costaricensis e posteriormente ao S. mansoni também facilitou o desenvolvimento do A. costaricensis uma vez que na nona semana de infecção foi recuperada maior quantidade de larvas L3 de A. costaricensis, enquanto nos moluscos expostos somente ao A. costaricensis, o número de larvas recuperadas foi menor . Entretanto a pré-exposição de B. glabrata ao S. mansoni (com intervalo de 24 horas), e posteriormente a exposição ao A. costaricensis mostrou-se muito prejudicial à B. glabrata provocando grande mortalidade dos moluscos, redução do período pré-patente para liberação de cercárias e maior recuperação de larvas L3 de A. costaricensis.

Susceptibility of Biomphalaria glabrata submitted to concomitant infection with Angiostrongylus costaricensis and Schistosoma mansoni

Abstract The easy adaptation of Angiostrongylus costaricensis, nematode responsible for abdominal angiostrongyliasis to several species of terrestrial and freshwater molluscs and the differences observed in the interactions of trematodes with their intermediate hosts have induced us to study the concomitant infection of Biomphalaria glabrata with Schistosoma mansoni and A. costaricensis. Prior exposure of B. glabrata to A. costaricensis (with an interval of 48 hours), favored the development of S. mansoni, observing higher infection rate, increased release of cercariae and increased survival of molluscs, when compared to molluscs exposed only to S. mansoni. Prior exposure of B. glabrata to A. costaricensis and then to S. mansoni also enabled the development of A. costaricensis since in the ninth week of infection, higher amount of A. costaricensis L3 larvae was recovered (12 larvae / mollusc) while for molluscs exposed only to A. costaricensis, the number of larvae recovered was lower (8 larvae / mollusc). However, pre-exposure of B. glabrata to S. mansoni (with an interval of 24 hours), and subsequently exposure to A. costaricensis proved to be very harmful to B. glabrata, causing extensive mortality of molluscs, reduced pre-patent period to release cercariae and greater recovery of L3 A. costaricensis larvae.

Resumo A facilidade de adaptação do Angiostrongylus costaricensis, nematódeo responsável pela angiostrongiliase abdominal, a diversas espécies de moluscos terrestres e dulciaquícolas e as divergências observadas nas interações dos trematódeos com seus hospedeiros intermediários nos induziu a estudar a infecção concomitante de Biomphalaria glabrata com Schistosoma mansoni e A. costaricensis. A exposição prévia de B. glabrata ao A. costaricensis (com intervalo de 48 horas), favoreceu o desenvolvimento do S. mansoni observando-se elevação da taxa de infecção, maior liberação de cercárias e maior sobrevivência dos moluscos, quando comparado com os moluscos expostos somente ao S. mansoni. A exposição de B. glabrata previamente ao A. costaricensis e posteriormente ao S. mansoni também facilitou o desenvolvimento do A. costaricensis uma vez que na nona semana de infecção foi recuperada maior quantidade de larvas L3 de A. costaricensis, enquanto nos moluscos expostos somente ao A. costaricensis, o número de larvas recuperadas foi menor . Entretanto a pré-exposição de B. glabrata ao S. mansoni (com intervalo de 24 horas), e posteriormente a exposição ao A. costaricensis mostrou-se muito prejudicial à B. glabrata provocando grande mortalidade dos moluscos, redução do período pré-patente para liberação de cercárias e maior recuperação de larvas L3 de A. costaricensis.