Randomized, double-blind, clinical trial of the use of mirtazapine versus megestrol for the control of anorexia-cachexia in cancer patients in palliative care

INTRODUÇÃO: A anorexia-caquexia associada ao câncer é uma síndrome insidiosa que tem um impacto importante sobre a qualidade de vida do paciente, mas também está associada a uma redução significativa da sobrevida. Apesar da sua importância clínica, permanece como uma condição amplamente subestimada e não tratada. Faz-se necessário o investimento em estudos que possam contribuir para o tratamento racional e eficaz dessa condição clínica. A mirtazapina tem um especial potencial terapêutico por ser um fármaco bem tolerado, com poucos efeitos adversos e com ação orexígena bem conhecida na prática clínica. OBJETIVO: O objetivo deste estudo foi avaliar o efeito da mirtazapina em comparação ao megestrol como medida farmacológica no manejo da síndrome anorexia-caquexia relacionada ao câncer em pacientes em cuidados paliativos. MÉTODOS: Trata-se de um ensaio clínico randomizado, duplo-cego, controlado, que envolveu 52 pacientes oncológicos com síndrome anorexia-caquexia em cuidados paliativos. Os voluntários foram randomizados para receber mirtazapina 30 mg ao dia ou megestrol 320 mg ao dia e foram avaliados longitudinalmente por um período de oito semanas. O desfecho primário foi o efeito da mirtazapina comparada ao megestrol sobre a anorexia e ganho ponderal e os desfechos secundários foram a tolerância e segurança da mirtazapina e seu efeito sobre a composição corporal, capacidade funcional, nível de atividade física, consumo alimentar e qualidade de vida dos voluntários envolvidos. Em todas as comparações, a probabilidade de erro de primeira espécie (alfa) foi mantida em 5% (p<0,05). RESULTADOS: Foram elegíveis 239 pacientes, dos quais 52 foram randomizados. A média de idade dos voluntários foi de 65,8±8,4 anos e houve um discreto predomínio de homens (51,9%). Com relação aos desfechos primários, houve melhora do apetite em 92% dos voluntários do grupo megestrol e em apenas 56% do grupo mirtazapina em 60 dias após a intervenção (p=0,007). Porém, em 30 dias, não houve diferença entre os grupos em relação ao apetite (p=0,236), com melhora do apetite em 72% dos voluntários do grupo megestrol e em 67% dos voluntários do grupo da mirtazapina. Na avaliação do peso, houve melhora em 52% dos voluntários do grupo megestrol e em apenas 38% dos voluntários do grupo mirtazapina em 30 dias após a intervenção (p=0,040). Porém, essa diferença não se manteve após 60 dias, com manutenção ou melhora do peso em 50% dos voluntários de ambos os grupos (p=0,166). Na subanálise realizada por sexo, observou-se diferença na resposta terapêutica. Apesar da melhora no apetite ter sido mais evidente com o megestrol em ambos os sexos, somente as mulheres apresentaram benefício com o uso da mirtazapina (OR 25,09, IC95% 7,05- 89,31, p<0,01 em 30 dias; OR 51,93, IC95% 8,74-308,39, p<0,01 em 60 dias). Além disso, houve ganho de peso no grupo de mulheres que recebeu mirtazapina (diferença estimada 1,92kg, IC95% 0,31-3,54, p=0,02 em 30 dias; diferença estimada 2,48kg, IC95% 0,81-4,15, p<0,01 em 60 dias), que não foi observado nos homens. A adesão terapêutica foi melhor no grupo megestrol (RR 1,31; IC95% 1,05-1,64, p=0,02), sendo observada maior perda de seguimento no grupo mirtazapina (RR 0,18; IC 95% 0,03-0,99, p=0,04). CONCLUSÕES: O megestrol parece ser superior à mirtazapina na melhora do peso em 30 dias e na melhora do apetite em 60 dias em pacientes oncológicos portadores de síndrome anorexia-caquexia em cuidados paliativos. Entretanto, pode haver uma diferença entre os sexos quanto à resposta terapêutica e as mulheres parecem se beneficiar do uso da mirtazapina.INTRODUCTION: Cancer-associated anorexia-cachexia is an insidious syndrome that has an important impact on the patient\'s quality of life, but is also associated with a significant reduction in survival. Despite its clinical importance, it remains a largely underestimated and untreated condition. It is necessary to invest in studies that can contribute to the rational and effective treatment of this clinical condition. Mirtazapine has a special therapeutic potential as it is a well-tolerated drug, with few adverse effects and with a well-known orexigenic action in clinical practice. OBJECTIVE: The aim of this study was to evaluate the effect of mirtazapine compared to megestrol as a pharmacological measure in the management of cancer-related anorexia-cachexia syndrome in palliative care patients. METHODS: This is a randomized, double-blind, controlled clinical trial involving 52 cancer patients with anorexia-cachexia syndrome in palliative care. Participants were randomized to receive mirtazapine 30 mg daily or megestrol 320 mg daily and were longitudinally evaluated over a period of eight weeks. The primary end point was the effect of mirtazapine compared to megestrol on anorexia and weight gain and the secondary end points were the tolerance and safety of mirtazapine and its effect on body composition, functional capacity, physical activity level, food consumption and quality of life of the participants involved. In all comparisons, the probability of type I error (alpha) was maintained at 5% (p<0.05). RESULTS: 239 patients were eligible, of which 52 were randomized. The mean age of the participants was 65.8±8.4 years and there was a slight predominance of men (51.9%). Regarding the primary outcomes, there was improvement in appetite in 92% of the participants in the megestrol group and in only 56% of the mirtazapine group at 60 days after the intervention (p=0.007). However, at 30 days, there was no difference between the groups in terms of appetite (p=0.236), with improvement in appetite in 72% of the participants in the megestrol group and in 67% of the participants in the mirtazapine group. In the weight assessment, there was improvement in 52% of the participants in the megestrol group and in only 38% of the participants in the mirtazapine group at 30 days after the intervention (p=0.040). However, this difference was not maintained after 60 days, with weight maintenance or improvement in 50% of the participants in both groups (p=0.166). In the sub analysis performed by sex, there was a difference in the therapeutic response. Although the improvement in appetite was more evident with megestrol in both sexes, only women showed benefit with the use of mirtazapine (OR 25.09, 95%CI 7.05-89.31, p<0.01 in 30 days; OR 51.93, 95%CI 8.74-308.39, p<0.01 at 60 days). In addition, there was weight gain in the group of women who received mirtazapine (estimated difference 1.92kg, 95%CI 0.31-3.54, p=0.02 at 30 days; estimated difference 2.48kg, 95%CI 0, 81- 4.15, p<0.01 at 60 days), which was not observed in men. Therapeutic adherence was better in the megestrol group (RR 1.31; 95%CI 1.05-1.64, p=0.02), with greater loss to follow-up being observed in the mirtazapine group (RR 0.18; CI 95 % 0.03-0.99, p=0.04). CONCLUSIONS: Megestrol appears to be superior to mirtazapine in improving 30-day weight and 60-day appetite in cancer patients with anorexia-cachexia syndrome in palliative care. However, there may be a difference between the sexes in the therapeutic response and women seem to benefit from the use of mirtazapine

Avanços no tratamento da leishmaniose tegumentar do novo mundo nos últimos dez anos: uma revisão sistemática da literatura

INTRODUÇÃO: O arsenal terapêutico contra a leishmaniose tegumentar é muito restrito. Os antimoniais pentavalentes permanecem como as drogas de escolha para seu tratamento há mais de 50 anos. Apesar da sua eficácia, necessita de injeções diárias, apresenta muitos efeitos colaterais e tempo de cura prolongado. OBJETIVO: Realizar uma revisão sistemática da literatura sobre os avanços no tratamento da leishmaniose tegumentar do novo mundo nos últimos dez anos. METODOLOGIA: Realizou-se em junho de 2009 uma busca eletrônica nas bases de dados Pubmed, LILACS e na biblioteca eletrônica Scielo. As palavras de busca em inglês foram: "cutaneous", "leishmaniasis" e "treatment". Foram incluídos apenas ensaios clínicos randomizados, duplo-cegos, placebo controlados. Utilizou-se a escala de Jadad para avaliar a qualidade dos estudos selecionados. RESULTADOS: Segundo os critérios de inclusão e exclusão, apenas 8 artigos foram selecionados. As drogas avaliadas nos estudos selecionados foram Glucantime®, miltefosine, imunoterapia, imiquimod, rhGM-CSF, pentoxifilina e paramomicina. CONCLUSÃO: Apesar de a leishmaniose tegumentar ser um importante problema de saúde pública, os dados publicados sobre o uso de novas drogas para o tratamento da leishmaniose tegumentar em nosso meio ainda são bastante limitado

Eficácia da combinação tópica de peróxido de benzoíla 5% e clindamicina 1% para o tratamento da hipomelanose macular progressiva: um estudo randomizado, duplo-cego, placebo-controlado

FUNDAMENTOS: A hipomelanose macular progressiva é uma dermatose sem etiologia definida. Não há consenso ou medicação de primeira linha para o seu tratamento e os tratamentos utilizados são pouco eficazes. OBJETIVO: Avaliar a eficácia terapêutica da combinação tópica de peróxido de benzoíla 5% e clindamicina 1% associada à exposição solar para o tratamento da hipomelanose macular progressiva. MATERIAIS E MÉTODOS: Trata-se de um estudo randomizado, duplo-cego, placebo-controlado, no qual os pacientes foram divididos em dois grupos: o Grupo A utilizou a combinação tópica de peróxido de benzoíla 5% e clindamicina 1% e o Grupo B usou um creme gel como placebo. Os pacientes foram orientados à exposição solar diária, avaliados e fotografados sistematicamente. Os dados coletados foram inseridos e analisados pelo software Epi Info. Definiu-se a significância estatística por valor de p<0,05. RESULTADOS: Dos 23 pacientes incluídos, 13 foram do Grupo A e 10, do Grupo B. Onze pacientes do primeiro grupo (85%) obtiveram melhora clínica importante e apenas dois (20%) do segundo grupo obtiveram uma melhora clínica equivalente (p=0,003). Os efeitos colaterais foram mais frequentes nos pacientes do Grupo A (p=0,003). CONCLUSÃO: A combinação tópica de peróxido de benzoíla 5% e clindamicina 1% é eficaz no tratamento da hipomelanose macular progressiva

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit