Comparative study between sodium stibogluconate BP 88R and meglumine antimoniate for cutaneous leishmaniasis treatment : I. Efficacy and safety

A eficácia e segurança do antimoniato de meglumina e do estibogluconato de sódio BP 88R foram comparadas no tratamento da leishmaniose cutânea em Corte de Pedra, Bahia, área endêmica de leishmaniose causada por Leishmania (Viannia) braziliensis. Realizou-se um estudo quase-experimental que incluiu 127 pacientes cujo diagnóstico baseou-se na observação clínica e a intradermorreação de Montenegro. Cinqüenta e oito pacientes receberam antimoniato de meglumina e 69 estibogluconato de sódio. Utilizou-se a dose de 20 mg/Sbv/kg/dia por 20 dias, em ambos os grupos. Os pacientes foram acompanhados a cada dez dias durante o tratamento e mensalmente por três meses. Observou-se a cura em 62% dos pacientes tratados com antimoniato de meglumina e em 55% daqueles tratados com estibogluconato de sódio (p = 0,42). A cefaléia foi mais freqüente na primeira metade do tratamento no grupo tratado com estibogluconato de sódio (p = 0,026). Na segunda metade do tratamento, os pacientes tratados com estibogluconato de sódio apresentaram maior freqüencia de mialgia/artralgia (p = 0,004) e dor abdominal/anorexia (p = 0,004). Três pacientes tratados com o estibogluconato de sódio apresentaram efeitos colaterais graves.Efficacy and safety of meglumine antimoniate and sodium stibogluconate BP88R were compared in cutaneous leishmaniasis treatment in Corte de Pedra, Bahia, an endemic area of leishmaniasis due to Leishmania (Viannia) braziliensis. An open trial was developed with one hundred twenty seven patients who were diagnosed based on clinical criteria and Montenegro´s skin test. Fifty eight patients were treated with meglumine antimoniate and 69 received sodium stibogluconate. Both groups received 20 mg/Sbv/kg/day for 20 days. Patients were followed every ten days during treatment and every month thereafter for three months. Sixty two percent patients cured with meglumine antimoniate and 55% cured with sodium stibogluconate (p = 0,42). Headache was more frequent during the first half of treatment in patients receiving sodium stibogluconate (p = 0,026). During the second half, patients treated with sodium stibogluconate showed a greater frequency of myalgia/arthralgia (p = 0,004) and abdominal pain/anorexia (p = 0,004). Three patients treated with sodium stibogluconate had severe side effects

Endometriose: fisiopatologia e manejo terapêutico: Endometriosis: pathophysiology and therapeutic management

A endometriose é definida como a presença anormal de tecido endometrial fora da cavidade uterina, manifestando-se como uma condição inflamatória crônica, benigna, estrogênio-dependente e grande causadora de dor e infertilidade. Essa afecção atinge cerca de 10% das mulheres em idade reprodutiva e afeta mais de 170 milhões de mulheres no mundo, apresentando seu pico de incidência entre 25 e 45 anos de idade e a sua prevalência aumenta em mulheres com dismenorreia, infertilidade e/ou dor pélvica. Os mecanismos dessa condição não são completamente conhecidos, mas entre eles, coexistem fatores etiológicos, congênitos, ambientais, genéticos, autoimunes, imunológicos e endócrinos. A sintomatologia da endometriose é diversa, porém, destaca-se dor pélvica crônica, dismenorreia e infertilidade. A anamnese e o exame físico dessa patologia revelam queixa principal de dor, em suas mais variadas durações, formas e localidades, sendo primariamente citadas dor pélvica cíclica, dismenorreia, dor periovulatória, dor pélvica crônica não cíclica, dispareunia posicional ou permanente, disquezia e disúria. Os fatores genéticos mais comuns relacionados ao risco de endometriose estão localizados em sequências reguladoras de DNA, que acabam por alterar a regulação da transcrição gênica. A ultrassonografia transvaginal é um exame básico no diagnóstico da endometriose, sendo uma ferramenta investigativa e técnica de imagem de primeira linha em pacientes com suspeita de tal afecção. A tomografia computadorizada não detém papel na avaliação de rotina da endometriose, exceto em poucos e particulares cenários. A laparoscopia com confirmação simultânea no exame histopatológico é o padrão ouro para o diagnóstico. As terapêuticas possíveis são o controle de sintomas, melhora da qualidade de vida das pacientes, manutenção da fertilidade, redução da recorrência e das abordagens cirúrgicas. A abordagem cirúrgica, ainda que não seja a indicação primária, tem extrema valia e o método usado varia conforme a clínica do paciente, sendo a videolaparoscopia o método preferencial de tratamento

Criptococose pulmonar: Pulmonary cryptococcosis

Introdução: A criptococose é uma micose sistêmica causada pela inalação de esporos viáveis do fungo Cryptococcus spp. As principais espécies em humanos são Cryptococcus neoformans e Cryptococcus gattii, que se associam, respectivamente, às condições de imunodepressão celular e à infecção primária de indivíduos imunocompetentes. O pulmão é o sítio primário mais comum, logo após o sistema nervoso central.  Apresentação do caso: JMF, masculino, 39 anos, apresentava queixa de tosse produtiva associada a desconforto respiratório aos moderados esforços, há cerca de 04 meses. Portador de HIV, sem outras comorbidades. Ao exame físico, sinais vitais estáveis, ausculta pulmonar com diminuição do murmúrio vesicular à direita. Na tomografia computadorizada (TC) de tórax evidenciou-se múltiplas opacidades nodulares difusas e de tamanhos variados, com presença de broncograma aéreo. Paciente foi submetido a biópsia por agulha percutânea e a análise do anatomopatológico constatou Criptococose Pulmonar. Discussão: A Criptococose pulmonar era considerada uma afecção rara, quando a prevalência de imunossuprimidos aumentou consideravelmente no século XX, sobretudo devido a Síndrome da Imunodeficiência Adquirida (SIDA). As manifestações clínicas são inespecíficas, variam desde infecção autolimitada até a disseminada, com meningoencefalite. O estado imunológico do paciente é o fator de risco e de prognóstico mais importante, influenciando tanto na evolução clínica quanto na abordagem terapêutica. Conclusão: Tendo em vista a similaridade dos sinais e sintomas com outras infecções pulmonares e ao potencial de gravidade da doença, principalmente em portadores de imunodeficiência, é de suma importância o diagnóstico precoce e o uso apropriado dos agentes antifúngicos para a redução da morbimortalidade

Síndrome de Adie: Adie's Syndrome

Introdução: A Síndrome de Adie-Homes é uma doença caracterizada pela presença de pupila tônica associada à diminuição ou ausência dos reflexos tendíneos profundos. É uma doença considerada típica de adultos jovens e apresenta uma etiologia comumente idiopática.A presença de alteração no tamanho das pupilas é uma das queixas mais comuns.  Apresentação do caso: Paciente do sexo feminino, 28 anos, admitida em Hospital Geral de Goiânia, apresentou há 1 mês quadro de cefaleia fronto-orbital a direita, associada a vesículas em mesma região, dolorosas, em queimação, com diagnóstico de herpes zóster. Após 2 semanas, notou que sua acuidade visual à direita para perto estava diminuída associado a fotofobia. Ao avaliar pupilas com lâmpada de fenda, observou-se anisocoria à direita. Ao instilar pilocarpina 0,125% em ambos os olhos, apenas a pupila direita contraiu.. Discussão: Embora a etiologia da doença não esteja totalmente elucidada, acredita-se que possa ocorrer processos imunomediado e infecções por vírus da herpes-zoster, parvovírus B19, Treponema pallidum. Atualmente, o tratamento ainda se baseia no uso de Pilocarpina 0,125% para diminuir o desconforto do paciente, podendo ser usado 2-4 vezes ao junto, em associação ao uso de óculos escuros em ambientes muito iluminados. Conclusão: A síndrome de Adie é rara e encontramos em sua apresentação clínica singularidades que difere de paciente a paciente. Nota-se que a síndrome tem correlação com diversas áreas médicas, o que faz com que seu diagnóstico ocorra através do oftalmologista, podendo ter sua suspeição diagnóstica através de outros especialistas como reumatologistas, infectologistas e até mesmo dermatologistas

Statement of Second Brazilian Congress of Mechanical Ventilarion : part I

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Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

© 2018 The Author(s). Background: Assessments of age-specifc mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Afairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specifc mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in diferent components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings: Globally, 18·7% (95% uncertainty interval 18·4-19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2-59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5-49·6) to 70·5 years (70·1-70·8) for men and from 52·9 years (51·7-54·0) to 75·6 years (75·3-75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5-51·7) for men in the Central African Republic to 87·6 years (86·9-88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3-238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6-42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2-5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation: This analysis of age-sex-specifc mortality shows that there are remarkably complex patterns in population mortality across countries. The fndings of this study highlight global successes, such as the large decline in under-5 mortality, which refects signifcant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Comparative study between sodium stibogluconate BP 88R and meglumine antimoniate in cutaneous leishmaniasis treatment. II. Biochemical and cardiac toxicity

Foi avaliada a toxicidade de dois antimoniais pentavalentes em 111 pacientes com leishmaniose cutânea. Quarenta e sete pacientes receberam antimoniato de meglumina (Grupo I) e 64 pacientes, estibogluconato de sódio BP 88R (Grupo II), 20mg SbV/kg/dia por 20 dias. Realizou-se a avaliação de aminotransferases, fosfatase alcalina, amilase, creatinina, uréia, exame de urina e eletrocardiograma, antes do tratamento e no décimo e vigésimo dias. Observou-se maior freqüência de valores anormais de aminotransferases no décimo e vigésimo dias de tratamento no grupo II (p < 0,001) e maior proporção de valores anormais de amilase no décimo dia no mesmo grupo (p < 0,001). Houve maior variação dos níveis de aminotransferases, fosfatase alcalina e amilase nos primeiros dez dias no grupo II (p < 0,01). No vigésimo dia observou-se maior variação nos níveis de aminotransferases no grupo II (p = 0,02 e p = 0,03, respectivamente). Quarenta e três porcento dos pacientes do grupo I e 54% dos pacientes do grupo II apresentaram alterações eletrocardiográficas (p = 0,30).Toxicity of two antimonial pentavalents were evaluated in 111 patients with cutaneous leishmaniasis. Forty seven patients received meglumine antimoniate (Group I) and 64 patients, sodium stibogluconate BP 88R (Group II), 20mg SbV/kg/day for 20 days. Evaluation of aminotransferases, alkaline phosphatase, amilase, creatinine, urea, urine analysis and electrocardiogram were performed at baseline, on the tenth and twentieth day of treatment. Greater frequency of aminotransferase abnormal levels were observed on the tenth and twentieth days in group II (p < 0,001) and a greater proportion of amilase abnormal levels at the tenth day in the same group (p < 0,001). There was a greater variation of aminotransferases, alkaline phosphatase and amilase in the first ten days of treatment in group II (p < 0,01). On the twentieth day there was a greater variation of aminotransferase levels in group II (p = 0,02 and p = 0,03, respectively). Forty three percent of group I and 54% of group II showed electrocardiographic abnormalities (p = 0,30)