Treatment patterns in metastatic bladder cancer in Japan: results of the CancerMPact® survey 2020.

Aim: To assess physician-reported treatment of metastatic bladder cancer in Japan. Methods: 76 physicians completed the CancerMPact® survey in July 2020, considering patients treated within 6 months. Results: Physicians treated a mean of 38.1 patients per month. Of cisplatin-eligible and -ineligible patients, 97.6 and 89.3%, respectively, received first-line platinum-based therapy, most commonly cisplatin plus gemcitabine (72.9%) and carboplatin plus gemcitabine (59.7%). 1.6 and 5.6% received first-line immune checkpoint inhibitors, respectively. 48.4 and 45.0%, respectively, progressed and received second-line therapy, most commonly with pembrolizumab (61.7%). Conclusion: In 2020, most patients with metastatic bladder cancer in Japan received first-line platinum-based chemotherapy; however, >50% received no subsequent treatment, highlighting the need for new treatment regimens to improve outcomes and maximize first-line treatment benefits.

In 2020, researchers surveyed 76 Japanese doctors who specialized in bladder and urinary system disorders about how they treated people with bladder cancer. Cisplatin, a type of chemotherapy drug, was the most common first treatment. For people who were unable to receive cisplatin, doctors often prescribed a similar chemotherapy drug called carboplatin. Just under half of the people received a second treatment for their cancer. New treatments are now available for bladder cancer, including the immunotherapy drug avelumab, which is given to people whose cancer stops growing or shrinks with their first chemotherapy treatment. More research is needed to better understand how bladder cancer is treated in Japan, including how new treatments are used.

Physician reported treatment patterns and outcomes in metastatic bladder cancer in the USA: the CancerMPact® Survey 2020.

Aim: This study assessed physician-reported treatment patterns for metastatic bladder cancer. Materials & methods: A total of 106 USA-based physicians were surveyed in 2020 using the CancerMPact® online survey. Results: Among cisplatin-eligible patients, 86.1% received first-line (1L) platinum-containing chemotherapy, most commonly cisplatin plus gemcitabine, and 9.8% received immune checkpoint inhibitor monotherapy. Among cisplatin-ineligible patients, 46.5% received 1L platinum-containing chemotherapy, most commonly carboplatin plus gemcitabine and 46.2% received 1L immune checkpoint inhibitor therapy. Approximately 44% of patients who received 1L treatment received second-line (2L) therapy after progression. Conclusion: Platinum-containing chemotherapy was the most widely reported 1L treatment approach. A high proportion of patients received no 2L therapy. Validation in an updated dataset is warranted following the practice-changing approvals of avelumab 1L maintenance and additional 2L options.

In 2020, researchers surveyed 106 US doctors about how they treated people with advanced bladder cancer. Cisplatin, a chemotherapy drug, was the most common first treatment that was given to patients with advanced bladder cancer. For people who were unable to receive cisplatin, doctors preferred to prescribe a similar chemotherapy drug called carboplatin or an immunotherapy drug. Immunotherapies help the body's immune system to fight cancer cells. Most people treated by the surveyed doctors did not receive a second treatment if their cancer got worse. New treatments are now available for bladder cancer, such as the immunotherapy, avelumab. Avelumab is given after chemotherapy to try and stop the cancer from getting worse or coming back. More research is needed to further understand how bladder cancer is treated.

O impacto da pandemia da COVID-19 nos exames de rastreamento do câncer no Brasil: um estudo comparativo dos cânceres de mama, próstata e colo de útero / The impact of the COVID-19 pandemic on cancer screening tests in Brazil: a comparative study of breast, prostate, and cervical cancers

Objetivo: Analisar a influência da pandemia da COVID-19 na execução dos exames de rastreamento e diagnóstico dos cânceres de próstata, mama e colo uterino na população brasileira. Métodos: Estudo analítico transversal e quantitativo com levantamento do número desses exames realizados pelo SUS (Sistema Único de Saúde). Os dados foram extraídos do Datasus nos períodos de pré-pandemia (março/2019 a fevereiro/2020) e pandemia (março/2020 a fevereiro/2021). Foram extraídos os números de exames realizados mês a mês e comparados os períodos pré-pandemia com o de pandemia. Foi realizada uma análise estatística descritiva, e as médias mensais de exames realizados nos dois períodos foram comparadas usando o teste t de Student. Resultados: Na comparação entre os períodos pré-pandemia e de pandemia, houve diminuição de média de 45,2% no número de exames citopatológicos, (194.978 exames por mês a menos; p < 0,00001), de 44,4% nos exames de mamografia (142.015 mamografias a menos por mês; p < 0,00001) e de 24,4% nos exames de antígeno prostático específico (PSA) (148.815 exames a menos por mês; p = 0,0012). Conclusão: A influência da pandemia gerou uma diminuição considerável no número de exames de rastreamento, mamografia, dosagem de PSA e citopatológico, o que deverá se traduzir em aumento nos casos de doença avançada, com graves consequências negativas para os pacientes e para o sistema de saúde.

Objective: To analyze the impact of COVID-19 pandemic on the number of screening and diagnostic cancer tests performed for prostate, breast and cervical cancer in the Brazilian population. Methods: This was a transversal analytical and quantitative study on the number of screening and diagnostic cancer tests performed in the public Brazilian health care system SUS (Sistema Único de Saúde). Data were collected from the Datasus (online SUS database) during pre-pandemic (March/2019 to February/2020) and pandemic periods (March/2020 to February/2021). We obtained the number of tests performed monthly for each of the tests and compared the two periods. Descriptive statistics were employed and the monthly average number of tests performed in each period were compared using the T Student test. Results: Comparing the pre-pandemic levels with pandemic levels, we found that there was a 45.2% decrease in the number of Papanicolaou (PAP smear) tests (194,978 less exams per month, p < 0,00001), 44.4% decrease in mammograms (142,015 less tests per month, p < 0,00001), and a reduction of 24.4% in the number of prostate specific antigen (PSA) tests per month (minus 148,815 exams performed, p < 0.0012). Conclusion: There was a statistically significant reduction in the number of screening/diagnostic mammograms, PAP smears and PSA performed during the pandemic period, compared to the period before COVID-19. This reduction may result in an increase in the number of cases diagnosed at an advanced stage, with grave consequences for the patients and for the sustainability of the healthcare system.

Patterns of Care and Outcomes for Non-Metastatic Prostate Cancer in the United States: Results of the CancerMPact® Survey 2018.

PURPOSE: We describe patterns of care and treatment outcomes for non-metastatic PCa (nmPCA), either hormone-sensitive or castration-resistant, in the United States of America (USA) in 2018. METHODS: A survey (CancerMPact®) recruited physicians nationwide to answer an online questionnaire about how they treated patients with nmPCA. Questions covered aspects of treatment at all disease stages. Board-certified urologists and oncologists with at least five years of clinical practice and who treated at least 30 PCa patients monthly were included. RESULTS: The survey included responses from ninety-four physicians with an average of 17.5 years of clinical practice, who had treated a combined average of 4415 patients with nmPCA per month in 2018. Approximately 40% of patients in stage I were managed with either active surveillance or observation/no therapy, decreasing to 20%, 8% and 6% in stages II, III and IV(M0), respectively. Intensity-modulated radiotherapy was favored over other radiotherapy modalities, with rates of use ranging between 60% and 69% depending on disease stage. Leuprolide as monotherapy or in combination with enzalutamide, abiraterone or bicalutamide were the most common systemic treatment options for non-metastatic hormone-sensitive PCa (nmHSPC) patients with the first or second recurrence. Only 16.5% of non-metastatic castration-resistant PCa (nmCRPC) patients did not relapse within five years of initial therapy for nmCRPC. CONCLUSION: While PCa treatment recommendations are rapidly changing due to advances in treatment, we observed great concordance between their most current versions and real-world data treatment patterns reported by US physicians.

Revisão sistemática e análise de custo- minimização de lipegfilgrastim na profilaxia da neutropenia e da neutropenia febril relacionadas à quimioterapia citotóxica / Systematic review and cost-minimization analysis of lipegfilgrastim in the prophylaxis of neutropenia and febrile neutropenia related to cytotoxic chemotherapy

Objetivo: Realizar avaliação econômica de lipegfilgrastim, fator de crescimento de longa duração (G-CSF), com os demais medicamentos da classe terapêutica disponíveis para a diminuição da duração da neutropenia grave (NG) e da incidência de neutropenia febril (NF), em pacientes adultos tratados com quimioterapia citotóxica para neoplasias malignas. Métodos: Revisão sistemática da literatura de evidências científicas sobre a eficácia e a segurança de lipegfilgrastim e análise de custo-minimização em comparação com pegfilgrastim ou filgrastim sob a perspectiva do Sistema Suplementar no Brasil. A análise incluiu tempo de tratamento de estudos clínicos, custo de infusão/ honorários médicos e custo com aquisição de medicamentos, distribuídos em três perspectivas: cenário 1 (conservador), cenário 2 (moderado) e cenário 3 (mundo real). Resultados: Seis estudos foram incluídos na análise, sendo três estudos randomizados e três revisões sistemáticas. O lipegfilgrastim resultou numa duração média de NG significativamente menor ao placebo e não inferior ao pegfilgrastim. Um estudo que comparou indiretamente lipegfilgrastim com filgrastim não encontrou diferenças estatisticamente significativas em redução de duração de NG e incidência de NF. O lipegfilgrastim apresentou redução de custos diretos de -R$ 3.673,50/paciente comparado com pegfilgrastim em todos os cenários avaliados e, na comparação com filgrastim, observou-se redução de -R$ 57.403,40; -R$ 19.183,67 e de -R$ 42,50/paciente nos cenários 1, 2 e 3, respectivamente. Conclusões: Lipegfilgrastim apresentou perfil de custo-minimização favorável em comparação com pegfilgrastim ou filgrastim, e surge como uma importante alternativa para o tratamento da redução da duração da neutropenia e da incidência da neutropenia febril durante a realização de tratamento quimioterápico, que pode representar economia de recursos para o Sistema de Saúde Suplementar.

jective: To develop an economic evaluation of lipegfilgrastin, long acting G-CSF, compared to other available G-CSF to reduce the duration of severe neutropenia (SN) and the incidence of febrile neutropenia (FN) in adult patients treated with cytotoxic chemotherapy for cancer in the Brazilian private Health System. Methods: Systematic literature review of scientific evidence evaluating the efficacy and safety of lipegfilgrastin and cost-minimization analysis comparing to pegfilgrastin or filgrastin in the Brazilian private Health System. The analysis includes time of treatment with filgrastin from clinical trials (scenario 1) or real world data (scenario 2 and 3) and considers direct medical costs. Results: Six studies were included in the analysis: three randomized controlled trials and three systematic reviews. Lipegfilgrastin resulted in a statistically significant reduction of median SN duration compared to placebo and non-inferior compared to pegfilgrastin. A study that performed an indirect comparison of lipegfilgrastin and filgrastin did not find any difference statistically significant reduction of SN duration and FN incidence. Lipefilgrastin resulted in a cost-difference of -R$ 3.673,50/patient compared to pegfilgrastin in all scenarios and -R$ 57.403,40; -R$ 19.183,67 and -R$ 42,50/patient compared to filgrastin in scenario 1, 2 and 3 respectively. Conclusions: Lipegfilgrastim showed a favorable cost-minimization profile compared to pegfilgrastin or filgrastin and is an important alternative treatment in reducing the duration of neutropenia and the incidence of febrile neutropenia during the course of chemotherapy, and may result in resource savings for the Brazilian Private Health System.

Amino acid formula as a new strategy for diagnosing cow's milk allergy in infants: is it cost-effective?

AIMS: To estimate the cost-effectiveness of a new strategy that uses an amino acid formula in the elimination diet of infants with suspected cow's milk allergy (CMA). MATERIALS AND METHODS: This pharmacoeconomic study was developed from the perspective of the Brazilian Public Healthcare System. The new strategy proposes using an amino acid formula in the diagnostic elimination diet of infants (≤24 months) with suspected CMA. The rationale is that infants who do not respond to the amino acid formula do not suffer from CMA. Patients with a positive oral challenge test receive a therapeutic elimination diet based on Brazilian Food Allergy Guidelines. This approach was compared to the current recommendations of the Brazilian Food Allergy Guidelines. A decision model was constructed using TreeAge Pro 2012 software. Model inputs were based on a literature review and the opinions of a panel of experts. A univariate sensitivity analysis of incremental cost-effectiveness ratios was performed. RESULTS: The mean cost per patient of the new amino acid formula strategy was R$3,341.57, while the cost of the current Brazilian guidelines strategy was R$3,641.08. The mean number of symptom-free days per patient, which was used as an indicator of effectiveness, was 900.6 and 875.7 days, respectively. The new strategy is, therefore, dominant. In the sensitivity analysis, the dominance was maintained with parameter variation. LIMITATIONS: In the absence of information in the literature, some premises were defined by a panel of specialists. CONCLUSIONS: The new strategy, which uses an amino acid formula in the elimination diagnostic diet followed by an oral food challenge, is a dominant pharmacoeconomic approach that has a lower cost and results in an increased number of symptom-free days.

Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA) and Western Europe. Androgen-deprivation therapy alone (ADT) remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT) that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel) for metastatic hormone-naive prostate cancer (mHNPC). METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (95% CI). RESULTS: The final analysis included 3 trials comprising 2,264 patients (mHNPC). Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001), and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%). The biochemical progression-free survival (bPFS) also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001), also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%). Finally, the combination of ADT with docetaxel showed a superior overall survival (OS) compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001), with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%). A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002). In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003). Regarding adverse events and severe toxicity (grade ≥3), the group receiving the combined therapy had higher rates of neutropenia, febrile neutropenia and fatigue. CONCLUSION: The combination of ADT with docetaxel improved the clinical progression-free survival, bPFS and OS of patients with mHNPC. A superior OS was seen especially for patients with metastatic and high-volume disease. This contemporary combination therapy may now be offered as a first-line treatment for selected patients.

Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Prostate cancer is the most common cancer in older men in the United States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most cases, the first-line of treatment for these cases. The negative impact of CAD in quality of life, secondary to the adverse events of sustained hormone deprivation, plus the costs of this therapy, motivated the intermittent treatment approach. The objective of this study is to to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), cancer-specific survival (CSS), time to progression (TTP) and adverse events. We performed a meta-analysis (MA) of the published data. The results were expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% Confidence Intervals (CI 95%). RESULTS: The final analysis included 13 trials comprising 6,419 patients with hormone-sensitive prostate cancer. TTP was similar in patients who received intermittent androgen deprivation (IAD) or continuous androgen deprivation (CAD) (fixed effect: HR = 1.04; CI 95% = 0.96 to 1.14; p = 0.3). OS and CSS were also similar in patients treated with IAD or CAD (OS: fixed effect: HR = 1.02; CI 95% = 0.95 to 1.09; p = 0.56 and CSS: fixed effect: HR = 1.06; CI 95% = 0.96 to 1.18; p = 0.26). CONCLUSION: Overall survival was similar between IAD and CAD in patients with locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. Data on CSS are weak and the benefits of IAD on this outcome remain uncertain. Impact in QoL was similar for both groups, however, sexual activity scores were higher and the incidence of hot flushes was lower in patients treated with IAD.

Targeted therapy in triple-negative metastatic breast cancer: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of randomized controlled trials that compared the efficacy of targeted therapy to conventional chemotherapy (CT) in patients with metastatic triple-negative breast cancer (TNBC). METHODS: Several databases were searched, including Medline, Embase, LILACS, and CENTRAL. The primary end point was progression-free survival (PFS). We performed a meta-analysis of the published data. The results are expressed as hazard ratio (HR) or risk ratio, with their corresponding 95% confidence intervals (95% CIs). RESULTS: The final analysis included twelve trials comprising 2,054 patients with TNBC, which compared conventional CT alone against CT combined with targeted therapy (bevacizumab [Bev], sorafenib [Sor], cetuximab, lapatinib, and iniparib). PFS was superior in previously untreated patients with TNBC who received Bev plus CT compared to CT alone (fixed effect, HR 0.62, 95% CI 0.51-0.75; P<0.00001). Also, PFS was higher in one study that tested Bev plus CT combination in previously treated patients (HR 0.49, 95% CI 0.33-0.74; P=0.0006). Sor plus CT was also tested as first-line and second-line treatments. The pooled data of PFS favored the combination CT plus Sor (fixed effect, HR 0.69, 95% CI 0.49-0.98; P=0.04). Comparisons of iniparib plus CT also had a better PFS than CT alone (fixed effect, HR 0.75, 95% CI 0.62-0.90; P=0.002). CONCLUSION: Targeted therapy, when associated with conventional CT, demonstrated gains in the PFS of patients with TNBC.

Systematic review and meta-analysis of target terapies for the treatment of metastatic renal cancer

Objectives At present there are several drugs for the treatment of advanced renal cell carcinoma (ARCC). The main objective of this work was to perform a systematic review (SR) and meta-analysis (MA) of clinical randomized studies that compared target cell therapies (TCT). Materials and Methods SR identified clinical randomized trials that compared TCT versus interferon-alpha in the treatment of patients with ARCC. In order to analyze efficiency, it was evaluated free-survival progression (FSP), total survival (TS) and response rate (RR). Results In relation to first line treatment, seven studies of TCT were identified using sunitinib, sorafenib, bevacizumab and temsirolimus; and two studies with sorafenib and everolimus for second line treatment. Relative risk (RRi) of MA for FSP of first line therapies was: 0.83, CI = 0.78-0.87, I2 = 94% and p < 0.00001. Best results of RR of specific FSP among studies were: 0.38, sunitinib, CI = 0.25-0.58, bevacizumab, 0.62, CI = 0.47-0.83; and temsirolimus, 0.78, CI = 0.70-0.87. MA didn't show any benefit regarding TS of first line treatment of all analyzed drugs. As for RR significant results were: sunitinib, 3.83 CI = 2.86-5.12; bevacizumab, 2.52 CI = 1.78-3.57 and bevacizumab, 1.97 CI = 1.43-2.71. Conclusions: For first line treatment, sunitinib was the most effective TCT in relation to FPS; there was no alteration of TS and RR was small but significant for sunitinib and bevacizumab. Available studies could not conclude any results for second line treatments. .

Decision tree cnnstruction and cost-effectivenes analysis of treatment of ulceerative colitis with pentasa® mesalazine 2 g sachet / Construcao de arvore de decisao e analise de custo-efetividade do tratamento da retocolite ulcerativa com Pentasa (mesalazina) 2 g sache

Context Unspecified Ulcerative Rectocolitis is a chronic disease that affects between 0.5 and 24.5/105 inhabitants in the world. National and international clinical guidelines recommend the use of aminosalicylates (including mesalazine) as first-line therapy for induction of remission of unspecified ulcerative rectocolitis, and recommend the maintenance of these agents after remission is achieved. However, multiple daily doses required for the maintenance of disease remission compromise compliance with treatment, which is very low (between 45% and 65%). Use of mesalazina in granules (2 g sachet) once daily - Pentasa® sachets 2 g - can enhance treatment adherence, reflecting in an improvement in patients' outcomes. Objective To evaluate the evidence on the use of mesalazine for the maintenance of remission in patients with unspecified ulcerative rectocolitis and its effectiveness when taken once versus more than once a day. From an economic standpoint, to analyze the impact of the adoption of this dosage in Brazil's public health system, considering patients' adherence to treatment. Methods A decision tree was developed based on the Clinical Protocol and Therapeutic Guidelines for Ulcerative Colitis, published by the Ministry of Health in the lobby SAS/MS n° 861 of November 4 th, 2002 and on the algorithms published by the Associação Brasileira de Colite Ulcerativa e Doença de Crohn, aiming to get the cost-effectiveness of mesalazine once daily in granules compared with mesalazine twice daily in tablets. Results The use of mesalazine increases the chances of remission induction and maintenance when compared to placebo, and higher doses are associated with greater chance of success without increasing the risk of adverse events. Conclusion The use of a single daily dose in the maintenance of remission is effective and related to higher patient compliance when compared to the multiple daily dose regimens, ...

Contexto A retocolite ulcerativa inespecífica é uma doença crônica que atinge entre 0,5 e 24,5/105 habitantes no mundo. Diretrizes clínicas nacionais e internacionais recomendam o emprego de aminosalicilatos (entre eles, a mesalazina) como terapia de primeira linha na indução da remissão da retocolite ulcerativa inespecífica, com manutenção destes agentes após a remissão. Mas as múltiplas doses diárias necessárias comprometem a adesão ao tratamento, que é muito baixa (entre 45% e 65%). A utilização de mesalazina em grânulos (sachê 2 g) dose única diária - Pentasa® sachê 2 g - pode aumentar a aderência ao tratamento, refletindo numa melhora nos desfechos dos pacientes. Objetivo Avaliar as evidências sobre o uso de mesalazina para a manutenção da remissão em pacientes com retocolite ulcerativa inespecífica e sua eficácia quando tomada uma vez versus mais de uma vez ao dia. Do ponto de vista econômico, avaliar o impacto que a adoção desta posologia teria para o sistema público de saúde do país, comparada ao tratamento padrão atual, considerando a adesão dos pacientes. Métodos Foi elaborada uma árvore de decisão construída a partir do Protocolo Clínico e Diretrizes Terapêuticas de Colite Ulcerativa, publicado pelo Ministério da Saúde na portaria SAS/MS n° 861, de 04 de novembro de 2002, e de algoritmos publicados pela Associação Brasileira de Colite Ulcerativa e Doença de Crohn, objetivando-se obter o custo-efetividade da mesalazina dose única diária em grânulos comparado com mesalazina duas vezes ao dia em comprimidos. Resultados O emprego de mesalazina aumenta as chances de indução da remissão e sua manutenção, quando comparado a ...

Lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in the treatment of HER-2-overexpressing locally advanced or metastatic breast cancer: systematic review and meta-analysis.

BACKGROUND: This paper reports a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in human epidermal growth factor receptor 2-overexpressing (HER-2+) locally advanced or metastatic breast cancer. METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were progression-free survival and overall survival. The side effects of each treatment were analyzed. The data extracted from the studies were combined by using the hazard ratio or risk ratio with their corresponding 95% confidence interval (CI). RESULTS: A total of 113 references were identified and screened. The final analysis included four trials comprising 1,073 patients with HER-2+. The overall response rate was higher in patients who received the combination of CET plus lapatinib (risk ratio 0.78; 95% CI 0.71-0.85; P < 0.00001) but with significant heterogeneity (χ(2) = 15.61, df = 3; P = 0.001; I(2) = 81%). This result remained favorable to the use of lapatinib when a random-effects model analysis was performed (risk ratio 0.76; 95% CI 0.62-0.94; P = 0.01). Progression-free survival was also higher in patients who received CET plus lapatinib (hazard ratio 0.57; 95% CI 0.49-0.66; P < 0.00001) with no heterogeneity detected on this analysis (χ(2) = 3.05; df = 3; P = 0.38; I(2) = 1%). Overall survival was significantly longer in patients who received CET plus lapatinib (hazard ratio 0.80; 95% CI 0.69-0.92; P = 0.002) without heterogeneity on this analysis (χ(2) = 1.26; df = 3; P = 0.74; I(2) = 0%). Regarding adverse events and severe toxicities (grade ≥3), the group receiving CET plus lapatinib had higher rates of neutropenia (risk ratio 2.08; 95% CI 1.64-2.62; P < 0.00001), diarrhea (risk ratio 4.82; 95% CI 3.14-7.41; P < 0.00001), and rash (risk ratio 8.03; 95% CI 2.46-26.23; P = 0.0006). CONCLUSION: The combination of CET plus lapatinib increased the overall response rate, progression-free survival, and overall survival in patients with HER-2+ locally advanced or metastatic breast cancer.

Pseudomonas aeruginosa infection in patients with cystic fibrosis: scientific evidence regarding clinical impact, diagnosis, and treatment.

Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO-an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group.

Implante transcateter de bioprótese valvular pulmonar: revisão sistemática da literatura / Transcatheter pulmonary valve implantation: systematic literature review

A correção cirúrgica de algumas cardiopatias congênitas complexas envolve a reconstrução da via de saída do ventrículo direito com a interposição de homoenxertos, biopróteses, enxertos de jugular bovina ou outros condutos valvulados entre o ventrículo direito e o tronco da artéria pulmonar. Apesar de essas cirurgias poderem ser realizadas com baixa mortalidade, a vida útil das válvulas ou dos condutos implantados é normalmente pequena (< 10 anos), seja por degeneração e/ou calcificação. Graus variáveis de estenose pulmonar na maioria das vezes associada a insuficiência pulmonar são consequências da degeneração dos condutos. Em 2000, Bonhoeffer et al. foram os primeiros a relatar o implante transcateter de bioprótese valvular pulmonar (ITVP) com um dispositivo que posteriormente foi denominado de válvula Melody® (Medtronic, Minneapolis, Estados Unidos). A técnica foi inicialmente desenvolvida para limitar a necessidade de múltiplos procedimentos cirúrgicos, substituindo, em última análise, uma nova troca cirúrgica valvular. Estudos subsequentes na Europa e Estados Unidos atestaram para a segurança e eficácia dessa técnica em um número maior de pacientes. Como a Agência Nacional de Vigilância Sanitária (Anvisa) concedeu a aprovação para o uso clínico da válvula biológica pulmonar transcateter Melody® em fevereiro de 2013, consideramos necessária e oportuna a avaliação judiciosa da utilização dessa nova tecnologia antes que ela fosse aplicada em larga escala em nosso país. O objetivo deste estudo foi realizar uma revisão sistemática da literatura sobre o ITVP em pacientes com disfunções de homoenxertos, condutos valvulados e biopróteses implantados cirurgicamente na via de saída do ventrículo direito.

Surgical repair of some complex congenital heart diseases involves reconstruction of the right ventricular outflow tract using homografts, bioprostheses, bovine jugular grafts or other valved conduits between the right ventricle and the main pulmonary artery. Although these surgical procedures may be performed with low mortality rates, the life span of these implanted valves or conduits is usually short (< 10 years) due to either degeneration and/or calcification. Variable degrees of pulmonary stenosis, often associated with pulmonary insufficiency, are consequences of conduit degeneration. In 2000, Bonhoeffer et al. were the first to report the transcatheter pulmonary valve implantation (TPVI) of a bioprosthetic pulmonary valve later named Melody® valve (Medtronic, Minneapolis, USA). The technique was initially developed to limit the need for multiple surgical procedures, and, ultimately, to work as a surrogate of a new surgical valve replacement. Subsequent clinical studies in Europe and the United States confirmed the safety and efficacy of this technique in a larger number of patients. Since the National Sanitary Surveillance Agency (Agência Nacional de Vigilância Sanitária - Anvisa) granted approval for clinical use of the Melody® transcatheter pulmonary biological valve in February 2103, we deemed that a judicious assessment of this new technology was timely and necessary before the widespread use in our country. The objective of this study was to perform a systematic literature review on the use of TPVI in patients with dysfunctional homografts, valved conduits and bioprostheses implanted surgically in the right ventricular outflow tract.

Pseudomonas aeruginosa infection in patients with cystic fibrosis: scientific evidence regarding clinical impact, diagnosis, and treatment / Infecção por Pseudomonas aeruginosa em pacientes com fibrose cística: evidências científicas sobre o impacto clínico, diagnóstico e tratamento

Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO–an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group. .

As técnicas de medicina baseada em evidências são cada vez mais utilizadas para a construção de diretrizes clínicas e recomendações para a prática médica. O uso de níveis de evidências permite que o leitor identifique a qualidade da informação científica que sustenta as recomendações feitas pelos especialistas. Esta revisão teve por objetivo abordar conceitos atuais sobre o impacto clínico, diagnóstico e tratamento das infecções por Pseudomonas aeruginosa em pacientes com fibrose cística. Para a elaboração desta revisão, o grupo de autores definiu as perguntas que seriam respondidas, seguindo os preceitos de PICO, acrônimo baseado em perguntas referentes aos Pacientes de interesse, Intervenção a ser estudada, Comparação da intervenção e Outcome (desfecho) de interesse. Para cada pergunta, uma revisão estruturada da literatura foi realizada nas bases de dados do Medline, buscando identificar os estudos com desenho metodológico mais adequado para responder à questão. As perguntas foram designadas para que cada um dos autores redigisse uma resposta, e um primeiro rascunho foi elaborado e discutido pelo grupo em uma reunião presencial. Após essa discussão, recomendações foram emitidas com base na força das evidências e na concordância entre os membros do grupo segundo o sistema de classificação do Oxford Centre for Evidence Based Medicine. .

Hypofractionated external-beam radiation therapy (HEBRT) versus conventional external-beam radiation (CEBRT) in patients with localized prostate cancer: a systematic review and meta-analysis.

BACKGROUND: The purpose of this work was to conduct a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy and side effect profile of hypofractionated versus conventional external-beam radiation therapy for prostate cancer. METHODS: Several databases were searched, including Medline, EmBase, LiLACS, and Central. The endpoints were freedom from biochemical failure and side effects. We performed a meta-analysis of the published data. The results are expressed as the hazard ratio (HR) or risk ratio (RR), with the corresponding 95% confidence interval (CI). RESULTS: The final analysis included nine trials comprising 2702 patients. Freedom from biochemical failure was reported in only three studies and was similar in patients who received hypofractionated or conventional radiotherapy (fixed effect, HR 1.03, 95% CI 0.88-1.20; P = 0.75), with heterogeneity [χ(2) = 15.32, df = 2 (P = 0.0005); I2 = 87%]. The incidence of acute adverse gastrointestinal events was higher in the hypofractionated group (fixed effect, RR 2.02, 95% CI 1.45-2.81; P < 0.0001). We also found moderate heterogeneity on this analysis [χ(2) = 7.47, df = 5 (P = 0.19); I2 = 33%]. Acute genitourinary toxicity was similar among the groups (fixed effect, RR 1.19, 95% CI 0.95-1.49; P = 0.13), with moderate heterogeneity [χ(2) = 5.83, df = 4 (P = 0.21); I2 = 31%]. The incidence of all late adverse events was the same in both groups (fixed effect, gastrointestinal toxicity, RR 1.17, 95% CI 0.79-1.72, P = 0.44; and acute genitourinary toxicity, RR 1.16, 95% CI 0.80-1.68, P = 0.44). CONCLUSION: Hypofractionated radiotherapy in localized prostate cancer was not superior to conventional radiotherapy and showed higher acute gastrointestinal toxicity in this meta-analysis. Because the number of published studies is still small, future assessments should be conducted to clarify better the true role of hypofractionated radiotherapy in patients with prostate cancer.

Decision tree construction and cost-effectiveness analysis of treatment of ulcerative colitis with pentasa® mesalazine 2 g sachet.

CONTEXT: Unspecified Ulcerative Rectocolitis is a chronic disease that affects between 0.5 and 24.5/105 inhabitants in the world. National and international clinical guidelines recommend the use of aminosalicylates (including mesalazine) as first-line therapy for induction of remission of unspecified ulcerative rectocolitis, and recommend the maintenance of these agents after remission is achieved. However, multiple daily doses required for the maintenance of disease remission compromise compliance with treatment, which is very low (between 45% and 65%). Use of mesalazina in granules (2 g sachet) once daily--Pentasa® sachets 2 g--can enhance treatment adherence, reflecting in an improvement in patients' outcomes. OBJECTIVE: To evaluate the evidence on the use of mesalazine for the maintenance of remission in patients with unspecified ulcerative rectocolitis and its effectiveness when taken once versus more than once a day. From an economic standpoint, to analyze the impact of the adoption of this dosage in Brazil's public health system, considering patients' adherence to treatment. METHODS: A decision tree was developed based on the Clinical Protocol and Therapeutic Guidelines for Ulcerative Colitis, published by the Ministry of Health in the lobby SAS/MS n° 861 of November 4 th, 2002 and on the algorithms published by the Associação Brasileira de Colite Ulcerativa e Doença de Crohn, aiming to get the cost-effectiveness of mesalazine once daily in granules compared with mesalazine twice daily in tablets. RESULTS: The use of mesalazine increases the chances of remission induction and maintenance when compared to placebo, and higher doses are associated with greater chance of success without increasing the risk of adverse events. CONCLUSION: The use of a single daily dose in the maintenance of remission is effective and related to higher patient compliance when compared to the multiple daily dose regimens, with lower costs.

Systematic review and meta-analysis of target terapies for the treatment of metastatic renal cancer.

OBJECTIVES: At present there are several drugs for the treatment of advanced renal cell carcinoma (ARCC). The main objective of this work was to perform a systematic review (SR) and meta-analysis (MA) of clinical randomized studies that compared target cell therapies (TCT). MATERIALS AND METHODS: SR identified clinical randomized trials that compared TCT versus interferon-alpha in the treatment of patients with ARCC. In order to analyze efficiency, it was evaluated free-survival progression (FSP), total survival (TS) and response rate (RR). RESULTS: In relation to first line treatment, seven studies of TCT were identified using sunitinib, sorafenib, bevacizumab and temsirolimus; and two studies with sorafenib and everolimus for second line treatment. Relative risk (RRi) of MA for FSP of first line therapies was: 0.83, CI = 0.78-0.87, I2 = 94% and p < 0.00001. Best results of RR of specific FSP among studies were: 0.38, sunitinib, CI = 0.25-0.58, bevacizumab, 0.62, CI = 0.47-0.83; and temsirolimus, 0.78, CI = 0.70-0.87. MA didn't show any benefit regarding TS of first line treatment of all analyzed drugs. As for RR significant results were: sunitinib, 3.83 CI = 2.86-5.12; bevacizumab, 2.52 CI = 1.78-3.57 and bevacizumab, 1.97 CI = 1.43-2.71. CONCLUSIONS: For first line treatment, sunitinib was the most effective TCT in relation to FPS; there was no alteration of TS and RR was small but significant for sunitinib and bevacizumab. Available studies could not conclude any results for second line treatments.

Implante por cateter de bioprótese valvular aórtica para tratamento de estenose valvar aórtica grave em pacientes inoperáveis sob perspectiva da saúde suplementar: análise de custo-efetividade / Transcatheter aortic valve implantation for the treatment of severe aortic valve stenosis in inoperable patients under the perspective of the brazilian supplemental health system: cost-effectiveness analysis

INTRODUÇÃO: O implante por cateter de bioprótese valvular aórtica (TAVI, do inglês transcatheter aortic valve implantation) constitui nova modalidade de tratamento destinada, sobretudo, aos pacientes com elevado risco cirúrgico. Para esses pacientes, o TAVI resultou em aumento da sobrevivência e melhora da qualidade de vida, comparativamente ao tratamento padrão (medicamentoso, com ou sem valvuloplastia aórtica percutânea). Nosso objetivo foi realizar análise de custo-efetividade da implementação do TAVI no Sistema de Saúde Suplementar brasileiro. MÉTODOS: Foram desenvolvidos um modelo preditivo, para avaliar custo-efetividade real do procedimento em longo prazo, e uma regressão de Weibull com tempo horizonte de 5 e 10 anos, para estimar dados de sobrevida por mais de 24 meses. Adicionalmente, foi desenvolvido modelo de Markov sequencial e determinístico. Resultados foram expressos como razão de custo-efetividade incremental (RCEI) por anos de vida ganhos e anos de vida livres de progressão. RESULTADOS: Para o cenário padrão, no qual o custo da TAVI foi estipulado em R$ 65 mil, o valor da RCEI (custo/ano de vida salvo) em 5 anos foi de R$ 72.520,65. Alterando-se o tempo horizonte para 10 anos, esse valor diminuiu para R$ 41.653,01. CONCLUSÕES: O modelo apontou que o TAVI apresenta efetividade superior e maior custo incremental. Além disso, a incorporação do TAVI no Rol de Procedimentos e Eventos em Saúde da Agência Nacional de Saúde Suplementar acarretaria impacto orçamentário incremental nos próximos 5 anos, variando de R$ 70 milhões a R$ 121 milhões, compatível com o de outras tecnologias já incorporadas no âmbito da Saúde Suplementar.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a new modality of treatment especially dedicated to patients with high surgical risk. In these patients, TAVI increased survival and improved quality of life when compared to standard treatment (drug therapy with or without percutaneous aortic balloon valvuloplasty). Our objective was to perform a cost-efficacy analysis of the implementation of TAVI in the Brazilian Supplemental Health System. METHODS: We developed a predictive model to assess the cost-effectiveness of the procedure in the long-term, and a Weibull regression analysis with a time horizon of 5 and 10 years, to estimate survival data for over 24 months. In addition, a deterministic sequential Markov model was developed. Results were expressed as incremental cost-effectiveness ratio (ICER) per years of life saved and progression-free years of life. RESULTS: In a standard scenario, where the cost of TAVI was estimated as R$ 65 millions, the ICER value (cost/year of life saved) in 5 years was R$ 72,520.65. When the time horizon was adjusted for 10 years, this amount decreased to R$ 41,653.01. CONCLUSIONS: The model indicated that TAVI has superior effectiveness and higher incremental cost. Furthermore, the incorporation of TAVI in the List of Health Procedures and Events of the Brazilian Supplemental Health System would have an incremental budgetary impact over the next 5 years, ranging from R$ 70 millions to R$ 121 millions, consistent with other technologies which have already been incorporated by the system.