Drug-Drug Interactions of 257 Antineoplastic and Supportive Care Agents With 7 Anticoagulants: A Comprehensive Review of Interactions and Mechanisms.

Data on drug-drug interactions (DDI) of antineoplastic drugs with anticoagulants is scarce. We aim to evaluate factors associated with DDI of antineoplastic and supportive care drugs with anticoagulants resulting in modification of pharmacokinetics of these last mentioned. A literature review on DDI databases and summaries of products characteristics (SmPC) was done. Drug-drug interactions of 257 antineoplastic and supportive care drugs with direct oral anticoagulants (DOACs), warfarin, enoxaparin, or fondaparinux were categorized as no clinically significant expected DDI, potentially weak DDI, potentially clinically significant DDI, and recommendation against coadministration. Logistic regression models were performed to analyze the association between the dependent variable potentially clinically significant interaction/recommendation against coadministration and the mechanisms of DDI. Of the 1799 associations, 84.4% were absence of DDI, 3.6% potentially weak DDI, 10.2% potentially clinically relevant DDI, and 2.0% recommendation against coadministration. Warfarin has higher DDI potential than other anticoagulants. Enoxaparin and fondaparinux have fewer DDI than others. There was no difference between DOACs. Drug-drug interactions with apixaban and rivaroxaban was independently associated with the absence of CYP3A4 competition, P-glycoprotein inhibition, CYP3A4 induction, and drug class of tyrosine kinase inhibitors. Drug-drug interactions with dabigatran and edoxaban was associated with inhibition of P-glycoprotein and tyrosine kinase inhibitors. Warfarin, induction of CYP3A4, and inhibition of CYP2C9. Enoxaparin and fondaparinux, only tyrosine kinase inhibitors. Direct oral anticoagulants did not differ regarding DDI with antineoplastic agents. Warfarin presented more DDI than other anticoagulants. P-glycoprotein inhibition and CYP3A4 induction were independently associated with DDI of antineoplastic agents with DOACs.

Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction: The SOCRATES-REDUCED Randomized Trial.

IMPORTANCE: Worsening chronic heart failure (HF) is a major public health problem. OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS: Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic. INTERVENTIONS: Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point. RESULTS: Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log-transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15). The exploratory secondary analysis suggested a dose-response relationship whereby higher vericiguat doses were associated with greater reductions in NT-proBNP level (P < .02). Rates of any adverse event were 77.2% and 71.4% among the placebo and 10-mg vericiguat groups, respectively. CONCLUSIONS AND RELEVANCE: Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01951625.

Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES).

AIMS: The clinical outcomes for patients with worsening chronic heart failure (WCHF) remain exceedingly poor despite contemporary evidence-based therapies, and effective therapies are urgently needed. Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Direct soluble guanylate cyclase (sGC) stimulators target reduced cGMP generation due to insufficient sGC stimulation and represent a promising method for cGMP enhancement. METHODS: The phase II SOluble guanylate Cyclase stimulatoR in heArT failurE Study (SOCRATES) programme consists of two randomized, parallel-group, placebo-controlled, double-blind, multicentre studies, SOCRATES-REDUCED (in patients with LVEF <45%) and SOCRATES-PRESERVED (in those with LVEF ≥ 45%), that will explore the pharmacodynamic effects, safety and tolerability, and pharmacokinetics of four dose regimens of the once-daily oral sGC stimulator vericiguat (BAY 1021189) over 12 weeks compared with placebo. These studies will enrol patients stabilized during hospitalization for HF at the time of discharge or within 4 weeks thereafter. The primary endpoint in SOCRATES-REDUCED is change in NT-proBNP at 12 weeks. The primary endpoints in SOCRATES-PRESERVED are change in NT-proBNP and left atrial volume at 12 weeks. PERSPECTIVES: SOCRATES will be the first programme to enrol specifically both inpatients and outpatients with WCHF and patients with reduced or preserved ejection fraction. Results will inform the benefits of pursuing subsequent event-driven clinical outcome trials with sGC stimulators in this patient population.

[Incidence of the burnout syndrome among Brazilian cancer physicians]. / A síndrome da estafa profissional em médicos cancerologistas brasileiros.

BACKGROUND: The Burnout syndrome can be characterized by abnormalities in three domains: emotional exhaustion (EE), depersonalization (DP) and lack of personal realization (PR). In the medical profession, oncologists are especially prone to this syndrome. This study evaluates its prevalence among cancer physicians in Brazil correlating it to their demographic, work related variables and seeks possible solutions to prevent burnout. METHODS: We mailed three questionnaires (Maslach burnout inventory, general and opinion questionnaires) to all 645 members of the Brazilian Cancer Society and received 136 responses after 10 weeks. RESULTS: The response rate was of 21%. The burnout syndrome was present at moderate or severe levels in all three domains analyzed in 15.7% of the physicians. For each of these the frequency of moderate or severe dysfunction was analyzed and found to be present in 55.8% for EE, 96.1% for DP and 23.4% for RP. Practicing physical activity or having a hobby correlated significantly with lower levels of EE (p = 0.008) while working only for the private sector correlated with higher DP scores (p = 0.021). Cancer physicians pointed out that less paper work (73.5%) and a lower patient load (72.7%) were the most important factors for prevention of this syndrome. CONCLUSION: Burnout syndrome is frequent among Brazilian cancer physicians and further studies should be conducted to evaluate its prevalence and prevention among other sub specialists.

[Acceptance of chemotherapy by Brazilian women with breast cancer]. / Aceitação de quimioterapia por brasileiras com câncer de mama.

INTRODUCTION: Breast cancer has the second highest incidence and is the first cause of death by cancer among Brazilian women. Under the physician's perspective chemotherapy should be indicated according to the risk benefit ratio in each case. However, from the Brazilian breast cancer patient's perspective this risk benefit ratio requires further classification. OBJECTIVE: In patients with breast cancer who have already received chemotherapy evaluate the minimum benefit considered necessary for a renewed administration and learn which factors may influence this decision. METHODS: we surveyed 53 patients comprising general, clinical and cancer related variables, as well as issues related to the minimal expected benefit which would induce the patient to agree to undergo chemotherapy. RESULTS: 75% would accept to receive chemotherapy again even if it would not change their probability of relapse, 50% would accept chemotherapy again, even though it would not increase survival rates. Similarly, 81.54% would submit once more to chemotherapy even though it would not increase their probability of cure. Acceptance of a new chemotherapy treatment yielding minimal benefits correlated significantly with more age, with a lower educational level and with no previous administration of Adriamycin. CONCLUSION: Even with a minimal benefit, the majority of formerly treated breast cancer patients are willing to submit to another chemotherapy treatment.

A síndrome da estafa profissional em médicos cancerologistas brasileiros / Incidence of the burnout syndrome among Brazilian cancer physicians

OBJETIVOS: A síndrome da estafa profissional (burnout) é um quadro caracterizado por três dimensões: exaustão emocional (EE), despersonalização (DP) e baixa realização pessoal (RP). Na área médica, os cancerologistas estão particularmente predispostos a esta síndrome. O objetivo deste estudo é avaliar sua prevalência entre cancerologistas brasileiros, correlacionando-a com dados demográficos e características de trabalho destes profissionais, avaliando também quais as suas sugestões para prevenção do quadro. MÉTODOS: Três questionários foram enviados aos 645 membros da Sociedade Brasileira de Cancerologia, por correio, e, após dez semanas, foram recebidas 136 respostas. Os questionários utilizados foram um de opinião, um geral e o inventário de Maslach de exaustão profissional, que avalia as supramencionadas dimensões separadamente, caracterizando-as em níveis leve, moderado ou grave. DISCUSSÃO: A taxa de resposta obtida foi 21 por cento. A síndrome foi observada em níveis moderados ou graves nas três dimensões em 15,7 por cento dos médicos. Para EE, 55,8 por cento apresentaram os níveis moderado ou grave. Para DP, esse número foi de 96,1 por cento e, para RP, 23,4 por cento. Correlacionando o questionário Maslach com os dados demográficos, encontramos significância estatística entre prática de atividade física ou hobby e menores níveis de EE (p=0,008) e trabalhar apenas em instituições privadas com maiores níveis de DP (p=0,021). Os cancerologistas apontaram como alternativas mais relevantes na prevenção da síndrome menos burocracia (73,5 por cento) e limitação do número de pacientes atendidos (72,7 por cento). CONCLUSÃO: A síndrome da estafa profissional é freqüente entre médicos cancerologistas brasileiros, e outros estudos devem ser desenvolvidos para averiguar sua prevalência e prevenção em outras especialidades médicas.

Aceitação de quimioterapia por brasileiras com câncer de mama / Acceptance of chemotherapy by Brazilian women with breast cancer

INTRODUÇAO: O câncer de mama é o segundo tipo de câncer mais incidente e a primeira causa de morte por câncer entre as mulheres brasileiras. Na perspectiva do médico, a indicação da quimioterapia adjuvante como parte de seu tratamento deve se pautar pelos seus riscos e benefícios. Do ponto de vista da paciente, entretanto, em nosso meio, há poucos dados acerca de suas opiniões quanto à magnitude dos benefícios e riscos associados a este tratamento. OBJETIVOS: Avaliar o benefício mínimo necessário para que pacientes com câncer de mama que já tenham realizado quimioterapia aceitem-na novamente, caso hipoteticamente isso se fizesse necessário e conhecer fatores que, eventualmente, poderiam influenciar nessa decisão. MÉTODOS: Foram aplicados questionários a 52 pacientes sobre dados gerais e clínicos de cada paciente, além de perguntas a respeito do benefício mínimo necessário para a aceitação de uma eventual nova quimioterapia. RESULTADOS: 75 por cento fariam uma nova quimioterapia mesmo se ela não alterasse a chance de recidiva da doença em cinco anos; metade das pacientes a fariam mesmo que esta não aumentasse a sua sobrevida e 61,54 por cento se submeteriam novamente a um tratamento quimioterápico mesmo que este não aumentasse a sua chance de cura. A aceitação de uma nova quimioterapia que produzisse mínimos benefícios foi significativamente maior dentre pacientes mais idosas, com menor escolaridade e entre aquelas que não receberam quimioterapia prévia com adriamicina. CONCLUSAO: Mesmo por um benefício muito pequeno, a grande maioria das pacientes estudadas aceitaria ser submetida a uma nova quimioterapia, se indicada por seus médicos.

Continuous infusion of amphotericin B: preliminary experience at Faculdade de Medicina da Fundação ABC.

CONTEXT AND OBJECTIVE: Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy. DESIGN AND SETTING: Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André. METHODS: From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D. RESULTS: The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles. CONCLUSIONS: Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug.

Continuous infusion of amphotericin B: preliminary experience at Faculdade de Medicina da Fundação ABC

CONTEXTO E OBJETIVO: Pacientes neutropênicos com febre persistente podem apresentar infecções fúngicas com freqüência. A administração de anfotericina B deoxicolato tem sido padrão para estes pacientes, no entanto sua infusão endovenosa, usualmente administrada em quatro horas, pode levar a nefrotoxicidade, hepatotoxicidade e efeitos adversos relacionados à infusão, como tremores e calafrios. A literatura evidencia que o uso de anfotericina B deoxicolato em infusão contínua de 24 horas pode ser menos tóxica em relação à administração usual. O objetivo do estudo foi avaliar a eficácia, segurança e toxicidade da anfotericina B infusional contínua em pacientes onco-hematológicos após quimioterapia com neutropenia febril persistente. TIPO DE ESTUDO E LOCAL: Estudo observacional e retrospectivo de nossa experiência com anfotericina B deoxicolato em infusão contínua de 24 horas, na Faculdade de Medicina da Fundação ABC e Hospital Estadual Mário Covas, em Santo André. MÉTODOS: No período entre outubro de 2003 e maio de 2004, 12 pacientes com neoplasias hematológicas e neutropenia febril induzida por quimioterapia receberam 13 ciclos de anfotericina B deoxicolato infusional. RESULTADOS: A dose média da infusão foi de 0,84 mg/kg/dia. O uso concomitante de outras drogas nefrotóxicas ocorreu em 92% dos ciclos. Foram observados nefrotoxicidade em 30,76%, hipocalemia em 16,67%, hepatotoxicidade em 30% e efeitos adversos relacionados à infusão em 23% dos ciclos. Todos os pacientes sobreviveram aos sete primeiros dias após o início do tratamento e a resolução clínica ocorreu em 76% dos ciclos. CONCLUSÃO: A infusão contínua de anfotericina B é exeqüível para uso em nossa instituição como alternativa à infusão em quatro horas (mais tóxica) e possivelmente às caras formulações lípidicas desta droga.

[Evaluation of non-oncologist physician's knowledge and attitude towards cancer screening and preventive actions]. / Estudo da atitude e do conhecimento dos médicos não oncologistas em relação às medidas de prevenção e rastreamento do câncer.

BACKGROUND: New cancer cases are most often diagnosed by non-oncologist physicians. It is therefore essential for all physicians to be aware of cancer preventive practices and use them appropriately with their patients. METHODS: Questionnaires were administered to 120 non-oncologist physicians of various specialties attending the "Faculdade de Medicina do ABC" who deal directly with adult patients. Replies were collected and classified as appropriate or not according to one of these three cancer prevention guidelines: INCA, American Cancer Society and Canadian Task Force. RESULTS: The percentage of replied questionnaires was 58.3% (70 questionnaires). Mean age of physicians was 33.9 years; 57.1% were women and 10% smokers. Most of the current preventive practices adopted by the participating physicians (45.72% to 100%) regarding the most common and preventable tumors (breast, cervix, prostate, colon and rectum and non-melanoma skin cancer) did not agree with any of the guidelines mentioned above. When questioned about possible impediments for the appropriate practice of cancer prevention, 82.86% reported absence of health education agents working with the population, 77.14% scarceness of knowledge or training concerning prevention, and 70.15% lack of financial support for ordering tests. Frequently, whenever there was disagreement between the guidelines and the physician's current practices, preventive tests were ordered in excess of those recommended by the guidelines. CONCLUSIONS: Physicians had a tendency to order excessive laboratory tests, an action which can be related to lack of knowledge and to divergence among guidelines. A more intensive educational effort regarding cancer prevention, directed towards teaching physicians in training, seems to be warranted.

Estudo da atitude e do conhecimento dos médicos não oncologistas em relação às medidas de prevenção e rastreamento do câncer / Evaluation of non-oncologist physician's knowledge and attitude towards cancer screening and preventive actions

OBJETIVO: Avaliar o nível de informação e as atitudes preventivas em uso corrente pelos médicos ligados à FMABC. MÉTODOS: Foram entregues questionários para 120 médicos não oncologistas que lidam diretamente com pacientes adultos. RESULTADOS: A taxa de resposta foi de 58,3 por cento. A idade média dos médicos foi de 33,9 anos, sendo 57,1 por cento mulheres e 10 por cento tabagistas. As práticas preventivas para os cânceres mais comuns (mama, colo de útero, próstata, colorretal e pele não-melanoma) foram analisadas e comparadas com as recomendadas pelos consensos adotados (INCA, Sociedade Americana de Cancerologia e Força-Tarefa Canadense). Observou-se que a maioria das práticas (45,72 por cento a 100 por cento) não se adequou a nenhum deles. Sobre possíveis barreiras para o adequado exercício da prevenção do câncer, 82,86 por cento considerou falta de agentes educadores em saúde para a população, 77,14 por cento poucos conhecimento ou treinamento e 70,15 por cento falta de verba para custear exames. Houve uma tendência ao excesso de pedidos de exames de rastreamento. CONCLUSÕES: As práticas preventivas utilizadas pelos médicos entrevistados são heterogêneas e, em sua maioria, não preconizadas pelos consensos de condutas preventivas consultados, o que pode ser relacionado tanto à sua falta de conhecimento em relação a estes consensos como às divergências entre eles. Dessa forma, faz-se necessário um esforço educativo enfatizando a importância da prevenção do câncer no aprendizado e na prática médica.

Involvement of C4 allotypes in the pathogenesis of human diseases.

The complement system is an important humoral defense mechanism that plays a relevant role against microbial agents, inflammatory response control, and immunocomplex clearance. Classical complement pathway activation is antibody-dependent. The C4 component participates in the initial step of activation, and C4 expression is determined by 2 pairs of allotypes: C4A and C4B. Deficiencies in C4 allotypes have been associated with several diseases. The aim of the present review is evaluate the reported data in the literature regarding specific C4A and C4B deficiencies and characterize their clinical relevance. We searched the MEDLINE and LILACS databases. Papers referring to total C4 deficiency without allotype evaluation and case reports of primary C4 deficiency were not included. Deficiencies in C4 allotypes have been associated with Mycobacterium leprae infection, erythema nodosum, systemic sclerosis with anti-topoisomerase I antibodies, intermediate congenital adrenal hyperplasia with DR5 genotype, diabetes mellitus type 1 with DR3,4 genotype, and diabetes mellitus with antibodies against islet cells. C4 allotype deficiency is also related to C4B deficiency and autoimmune-associated diseases, such as systemic lupus erythematosus, or diseases with an autoimmune component, such as autism. Some reports associate C4A with thyroiditis after delivery as well as limited and systemic sclerosis without anti-topoisomerase I antibodies. However, the studies with C4A and C4B have been concentrated in isolated populations, and some of the studies could not be reproduced by other authors.

Praying correlates with higher quality of life: results from a survey on complementary/alternative medicine use among a group of Brazilian cancer patients.

CONTEXT: The use of complementary/alternative medicine has been little studied in Brazil. OBJECTIVE: The purpose of this study was to determine the prevalence of complementary/alternative medicine use among a group of Brazilian cancer patients and correlate these findings with the patients' quality of life. TYPE OF STUDY: Descriptive. SETTING: Oncology Institute of the Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil. PARTICIPANTS: 100 cancer patients. PROCEDURES: The EORTC QLQ C-30 quality of life questionnaire was applied together with another questionnaire on the use of complementary/alternative medicine. MAIN MEASUREMENTS: Use of complementary/alternative medicine and quality of life. RESULTS: 89% of the patients had already used complementary/alternative medicine, 63% were currently using it and most of them (77.7%) believed in the efficacy of complementary/alternative medicine for their treatment. The type most used was individual prayer (77.5%). We found a significant association between believing in the efficacy of complementary/alternative medicine and praying (individually or in groups), in comparison with better scores on the functional (p = 0.001) and overall health (p = 0.001) quality of life scales. Multivariate analysis confirmed these findings regarding praying and also showed that believing in complementary/alternative medicine correlated significantly with functional and symptom quality of life scores. CONCLUSION: The prevalence of complementary/alternative medicine use in this group of cancer patients was high. Praying and belief in the efficacy of complementary/alternative medicine correlated significantly with an overall better quality of life, and therefore these practices should not be discouraged by physicians. New prospective studies should be conducted in order to better characterize the efficacy of such alternative therapeutic approaches.

Efficacy of a triple therapy for Helicobacter pylori eradication in a well-developed urban area in Brazil.

CONTEXT: Helicobacter pylori eradication has become the standard treatment for peptic ulcer disease. Triple therapy with omeprazole plus two antibiotics has been used. Due to the lack of ideal treatment and the high rates of primary resistance to nitroimidazoles, the use of clarithromycin has been adopted. OBJECTIVE: To determine the Helicobacter pylori eradication rates using lansoprazole, amoxicillin and clarithromycin for seven days, in patients with peptic ulcer disease in a well developed urban area in Brazil. METHODS: This was a retrospective, open-label study carried out at the School of Medicine of the Fundação ABC. It included 130 patients with peptic ulcer disease (upper endoscopy) who had been tested positive for Helicobacter pylori infection (urease test, histology or breath test), without previous treatment. Patients were treated with lansoprazole 30 mg, amoxicillin 1,000 mg and clarithromycin 500 mg b.i.d., for seven days. Eradication was verified after 90 days. RESULTS: Follow-up data were available for 94 patients. Their mean age was 52.23 years; 51.54% were woman, 84.31% white, 37.69% smokers, 20.77% using nonsteroidal anti-inflammatory drugs and 8.46% alcoholics. Upper endoscopy revealed that 78.46% had duodenal ulcers and 21.53% had gastric ulcers (a 4:1 DU:GU ratio). The eradication rates were 85.11% per protocol and 61.54% by intention to treat; 97% had no adverse effects. CONCLUSION: Triple therapy using lansoprazole, amoxicillin and clarithromycin is well tolerated with high eradication rates and forms a good alternative for developing countries.

Involvement of C4 allotypes in the pathogenesis of human diseases

O sistema complemento constitui um importante sistema de defesa humoral, exercendo papel relevante na resposta contra agentes microbianos, no controle da resposta inflamatória e na depuração de imunocomplexos. A ativação da via clássica é dependente da formação do complexo antígeno-anticorpo. O componente C4 do complemento participa da etapa inicial de ativação desta via e a sua expressão é determinada por dois alótipos : C4A e C4B. A deficiência dos alótipos de C4 tem sido relacionada a várias doenças. O objetivo do presente estudo foi avaliar os dados de literatura que descrevem as deficiências específicas de C4A e C4B com a finalidade de caracterizar seu significado clínico. Foi realizada uma ampla revisão bibliográfica através do MEDLINE e LILACS, avaliando-se os dados de literatura. Excluiu-se estudos com a avaliação de C4 total sem a análise dos alótipos e relatos de caso isolados de deficiência total de C4. Verificou-se que a deficiência dos alótipos de C4 está relacionada com algumas doenças: hanseníase, esclerose sistêmica com anticorpos anti-topoisomerase I, hiperplasia adrenal congênita intermediária com genótipo DR5, diabetes mellitus tipo 1 com genótipo DR3,4 e diabetes mellitus tipo 1 com anticorpos anti-células das ilhotas. Também foram observadas algumas associações entre C4B e doenças auto-imunes como lupus eritematoso sistêmico, ou que se supõe terem um componente autoûimune como o autismo. Estudos demonstraram associações do C4A com tireoidite pós-parto, esclerose limitada e esclerose sistêmica sem anticorpos anti-topoisomerase I. Porém, os estudos dos alótipos de C4 se concentraram em populações isoladas e alguns destes não conseguiram ser reproduzidos por outros autores.

Praying correlates with higher quality of life: results from a survey on complementary/alternative medicine use among a group of Brazilian cancer patients

CONTEXTO: O uso da medicina alternativa/complementar no Brasil é pouco estudado. OBJETIVO: Verificar a prevalência do uso de medicina alternativa/complementar por pacientes oncológicos e correlacionar os achados com a qualidade de vida. TIPO DE ESTUDO: Descritivo. LOCAL: Instituto de Oncologia da Faculdade de Medicina da Fundação do ABC. PARTICIPANTES: 100 pacientes com câncer. PROCEDIMENTOS: Aplicamos questionário de qualidade de vida da EORTC QLQ C-30 quality of life e um questionário sobre o uso de medicina alternativa/complementar. VARIAVEIS ESTUDADAS: Uso de medicina alternativa/complementar e qualidade de vida. RESULTADOS: 89% dos pacientes já usaram medicina alternativa/complementar alguma vez, 63% estavam usando no momento do estudo e a maioria dos pacientes (77,7%) acredita na eficácia da medicina alternativa/complementar para o seu tratamento. O tipo de medicina alternativa/complementar mais utilizado foi a oração individual (77,5%). Encontramos associação significativa entre acreditar em medicina alternativa/complementar e a prática de orações (individual ou em grupo) com uma melhor qualidade de vida em relação à escala funcional (p = 0,001) e saúde global (p = 0,001). A análise multivariada confirmou estes achados, mostrando que rezar e acreditar na medicina alternativa/complementar se correlacionam significativamente com uma melhor qualidade de vida nas escalas funcionais e de sintomas. CONCLUSAO: A utilização de medicina alternativa/complementar em nosso meio é freqüente em pacientes com câncer e a crença na sua eficácia e a prática de orações se correlacionaram significativamente com uma melhor qualidade de vida, de forma que tais práticas não devem ser desestimuladas pelos profissionais da área médica. Novos trabalhos prospectivos devem ser conduzidos para melhor caracterizar a eficácia destas práticas terapêuticas alternativas.

Efficacy of a triple therapy for Helicobacter pylori eradication in a well-developed urban area in Brazil

CONTEXTO: A erradicação do Helicobacter pylori tem sido o principal tratamento para a doença ulcerosa péptica. Consiste em uma terapia tripla com omeprazol juntamente com dois antibióticos. Devido à inexistência de uma medicação ideal, assim como a um alto índice de resistência primária aos nitroimidazólicos em nosso meio, tem-se adotado o uso da claritromicina. OBJETIVOS: Determinar o índice de erradicação do Helicobacter pylori em pacientes com doença ulcerosa péptica mediante a terapia com lanzoprazol, amoxicilina e claritromicina, por sete dias. MÉTODOS: Num estudo retrospectivo, aberto e realizado na Faculdade de Medicina do ABC, foram incluídos 130 pacientes portadores de doença ulcerosa péptica (endoscopia digestiva alta) e com infecção por Helicobacter pylori diagnosticada pelos testes da urease, respiratório e histológico; todos sem tratamento prévio. Os pacientes foram tratados com lanzoprazol (30 mg), amoxicilina (1.000 mg) e claritromicina (500 mg) duas vezes ao dia por sete dias. Os índices de erradicação foram avaliados noventa dias após o tratamento. RESULTADOS: 94 pacientes completaram o estudo, sendo a média de idade 52,23 anos, 51,54% mulheres, 84,31% brancos, 37,69% tabagistas, 20,77% usuários de antiinflamatórios não-hormonais e 8,46% de etilistas. A endoscopia digestiva alta revelou: 78,46% de úlcera duodenal (UD) e 21,53% de úlcera gástrica (UG) (4UD:1UG). O índice de erradicação por protocolo foi de 85,11% e por intenção de tratamento foi de 97%. Foram observados poucos efeitos colaterais. CONCLUSAO: A terapia tríplice com lanzoprazol, amoxicilina e claritromicina mostrou-se bem tolerável, com altos índices de erradicação, sendo uma boa alternativa para países em desenvolvimento.