Long-term add-on therapy (compassionate use) with oral artesunate in patients with metastatic breast cancer after participating in a phase I study (ARTIC M33/2).

BACKGROUND: The antimalarial artesunate (ART), a semisynthetic derivative of artemisinin from the Chinese herb artemisia annua has remarkable anticancer properties in vitro and in vivo. Its excellent safety profile known from short-term therapy in malaria was confirmed in an open phase I trial (ARTIC M33/2) for dose-finding as add-on therapy for four weeks. PURPOSE: Patients with metastatic breast cancer, who had not experienced any clinically relevant adverse events (AE) during participation in ARTIC M33/2, were offered to continue ART as compassionate use (CU). Regular monitoring was continued in order to ensure adequate individual safety and tolerability and to collect information about long-term treatment with ART. Clinically relevant AEs or second progression of disease during ART were reasons for discontinuation of the add-on therapy. STUDY DESIGN: Compassionate use was offered open-label to participants of ARTIC M33/2. METHODS: Patients continued to take 100, 150 or 200 mg oral ART daily as add-on therapy to their guideline-based oncological therapy. Clinical and laboratory monitoring included audiological and neurological examination, ECG, NTproBNP and reticulocyte determination. Cumulative treatment days and cumulative ART doses encompass both the phase I study as well as the continued add-on treatment period (CU). RESULTS: Following the 4 ±â€¯1 weeks of the phase I trial, thirteen patients continued the add-on therapy as CU, resulting in a total of 3825 treatment days. In individual patients up to 1115 cumulative treatment days (37 months) and cumulative ART doses up to 167.3 g were reached. A total of 25 AEs grade ≥ 2 at least possibly related to ART long-term add-on therapy were documented, two, six and 17 in dose groups 100, 150 and 200 mg/d ART respectively. Six of these AEs were classified as grade 3, two in patients taking 150 and four in patients on 200 mg/d, none of them being probably or certainly related to ART. CONCLUSIONS: In thirteen patients with metastatic breast cancer up to 200 mg/d long-term oral ART (2.3-4.1 mg/kg BW/d) in up to 1115 cumulative treatment days (37 months) did not result in any major safety concerns.

Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2).

PURPOSE: The antimalarial drug artesunate (ART) is a promising candidate for cancer treatment as it displays anticancer effects in various models. While in short-term treatment of malaria, an excellent safety profile has been found for ART, the potential long-term treatment of cancer patients demands a phase I dose-finding clinical trial determining the daily ART dose which would be well tolerated as add-on therapy. METHODS: Patients with metastatic breast cancer were to receive either 100 or 150 or 200 mg oral ART daily as add-on to their guideline-based oncological therapy for a study period of four weeks with frequent clinical and laboratory monitoring until 4-8 weeks thereafter. According to the statistical design, recruitment was scheduled in groups of three patients in order not to miss a more than 33% frequency of dose-limiting adverse events (DL-AE) prior to dose escalation. RESULTS: Twenty-three patients were recruited, and all planned dose levels were applied. During the actual trial period of 4 ± 1 weeks, three patients experienced six DL-AEs altogether (leucopenia, neutropenia, asthenia, anemia) possibly related to ART (not exceeding 33% in any dose level). CONCLUSIONS: Up to 200 mg/d (2.2-3.9 mg/kg/d) oral ART were safe and well tolerated; therefore, 200 mg/d are recommended for phase II/III trials. Safety monitoring should include reticulocytes, NTproBNP, as well as audiological and neurological exploration.

Education to a Healthy Lifestyle Improves Symptoms and Cardiovascular Risk Factors – AsuRiesgo Study / Educação para um Estilo de Vida Saudável Melhora Sintomas e Fatores de Risco Cardiovasculares – Estudo AsuRiesgo

Background: Cardiovascular diseases are the current leading causes of death and disability globally. Objective: To assess the effects of a basic educational program for cardiovascular prevention in an unselected outpatient population. Methods: All participants received an educational program to change to a healthy lifestyle. Assessments were conducted at study enrollment and during follow-up. Symptoms, habits, ATP III parameters for metabolic syndrome, and American Heart Association’s 2020 parameters of cardiovascular health were assessed. Results: A total of 15,073 participants aged ≥ 18 years entered the study. Data analysis was conducted in 3,009 patients who completed a second assessment. An improvement in weight (from 76.6 ± 15.3 to 76.4 ± 15.3 kg, p = 0.002), dyspnea on exertion NYHA grade II (from 23.4% to 21.0%) and grade III (from 15.8% to 14.0%) and a decrease in the proportion of current active smokers (from 3.6% to 2.9%, p = 0.002) could be documented. The proportion of patients with levels of triglycerides > 150 mg/dL (from 46.3% to 42.4%, p < 0.001) and LDL cholesterol > 100 mg/dL (from 69.3% to 65.5%, p < 0.001) improved. A ≥ 20% improvement of AHA 2020 metrics at the level graded as poor was found for smoking (-21.1%), diet (-29.8%), and cholesterol level (-23.6%). A large dropout as a surrogate indicator for low patient adherence was documented throughout the first 5 visits, 80% between the first and second assessments, 55.6% between the second and third assessments, 43.6% between the third and fourth assessments, and 38% between the fourth and fifth assessments. Conclusion: A simple, basic educational program may improve symptoms and modifiable cardiovascular risk factors, but shows low patient adherence. .

Fundamentos: As doenças cardiovasculares são, atualmente, as maiores causas de óbito e incapacitação em todo o mundo. Objetivos: Avaliar os efeitos de um programa educativo básico para prevenção cardiovascular em uma população de pacientes ambulatoriais não selecionados. Métodos: Todos os participantes frequentaram um programa educativo de mudança para um estilo de vida saudável. Foram realizadas avaliações à admissão no estudo e durante o acompanhamento. Foram avaliados sintomas, hábitos, parâmetros do ATP III para síndrome metabólica e parâmetros da American Heart Association 2020 para saúde cardiovascular. Resultados: Foram incluídos no estudo 15.073 participantes com idade ≥ 18 anos. Foi feita a análise de dados dos 3.009 pacientes que completaram a segunda avaliação. Foram documentados perda de peso (de 76,6 ± 15,3 para 76,4 ± 15,3 kg, p = 0,002), melhora da dispneia aos esforços graus II-NYHA (de 23,4% para 21,0%) e III (de 15,8% para 14,0%), e redução na proporção de fumantes ativos atuais (de 3,6% para 2,9%, p = 0,002). Houve melhora na proporção de pacientes com níveis de triglicérides > 150 mg/dL (de 46,3% para 42,4%, p < 0,001) e de colesterol LDL > 100 mg/dL (de 69,3% para 65,5%, p < 0,001). Houve melhora ≥ 20% na métrica AHA 2020 no nível classificado como ruim para tabagismo (-21,1%), alimentação (-29,8%), e nível de colesterol (23,6%). Foi documentada grande evasão como indicador substituto para baixa adesão de paciente nas primeiras 5 consultas, sendo 80% entre a primeira e a segunda avaliação, 55,6% entre a segunda e a terceira, 43,6% entre a terceira e a quarta, e 38% entre a quarta e a quinta. Conclusão: Um programa educativo básico e simples pode melhorar os sintomas e fatores de risco cardiovasculares modificáveis, mas conta com pouca adesão por parte dos pacientes. .

Education to a Healthy Lifestyle Improves Symptoms and Cardiovascular Risk Factors - AsuRiesgo Study.

BACKGROUND: Cardiovascular diseases are the current leading causes of death and disability globally. OBJECTIVE: To assess the effects of a basic educational program for cardiovascular prevention in an unselected outpatient population. METHODS: All participants received an educational program to change to a healthy lifestyle. Assessments were conducted at study enrollment and during follow-up. Symptoms, habits, ATP III parameters for metabolic syndrome, and American Heart Association's 2020 parameters of cardiovascular health were assessed. RESULTS: A total of 15,073 participants aged ≥ 18 years entered the study. Data analysis was conducted in 3,009 patients who completed a second assessment. An improvement in weight (from 76.6 ± 15.3 to 76.4 ± 15.3 kg, p = 0.002), dyspnea on exertion NYHA grade II (from 23.4% to 21.0%) and grade III (from 15.8% to 14.0%) and a decrease in the proportion of current active smokers (from 3.6% to 2.9%, p = 0.002) could be documented. The proportion of patients with levels of triglycerides > 150 mg/dL (from 46.3% to 42.4%, p < 0.001) and LDL cholesterol > 100 mg/dL (from 69.3% to 65.5%, p < 0.001) improved. A ≥ 20% improvement of AHA 2020 metrics at the level graded as poor was found for smoking (-21.1%), diet (-29.8%), and cholesterol level (-23.6%). A large dropout as a surrogate indicator for low patient adherence was documented throughout the first 5 visits, 80% between the first and second assessments, 55.6% between the second and third assessments, 43.6% between the third and fourth assessments, and 38% between the fourth and fifth assessments. CONCLUSION: A simple, basic educational program may improve symptoms and modifiable cardiovascular risk factors, but shows low patient adherence.

Prevalence of rotator cuff tear in paraplegic patients compared with controls.

BACKGROUND: Musculoskeletal injuries of the shoulder in paraplegic patients with long-term survival can result from overuse and/or inappropriate use of wheelchairs. The purpose of the present study was to evaluate the prevalence and risk of pathological changes in the weight-bearing shoulder girdle of paraplegic patients who have been wheelchair-dependent for more than thirty years in comparison with able-bodied volunteers. METHODS: One hundred paraplegic patients were matched for sex and age with a group of 100 able-bodied volunteers. Two hundred shoulders from each group were evaluated with use of magnetic resonance imaging. Collected outcome measures included a standardized clinical examination protocol, the Constant score, and a visual analog score for pain intensity. RESULTS: Shoulder function according to the Constant score was significantly worse in the paraplegic patients than in the able-bodied volunteers. Similarly, the visual analog scale pain scores were significantly worse for the paraplegic patients. Magnetic resonance imaging showed that the prevalence of rotator cuff tears in either shoulder was significantly higher in the paraplegic patients than in the able-bodied volunteers (63% compared with 15%), resulting in a tenfold higher risk of rotator cuff rupture among paraplegic patients. CONCLUSIONS: The present study demonstrates that the structural and functional changes of the shoulder joint are more severe and the risk of development of shoulder girdle damage is significantly higher in individuals with long-term paraplegia than in age-matched controls.