Disparity in the use of Alzheimer's disease treatment in Southern Brazil.

Alzheimer's disease (AD) treatment is freely available in the Brazilian public health system. However, the prescription pattern and its associated factors have been poorly studied in our country. We reviewed all granted requests for AD treatment in the public health system in October 2021 in the Rio Grande do Sul (RS) state, Southern Brazil. We performed a spatial autocorrelation analysis with the population-adjusted patients receiving any AD medication as the outcome and correlated it with several socioeconomic variables. 2382 patients with AD were being treated during the period analyzed. The distribution of the outcome variable was not random (Moran's I 0.17562, P <.0001), with the most developed regions having a higher number of patients/100,000 receiving any AD medication. We show that although AD medications are available through the public health system, there is a clear disparity between regions of RS state. Factors related to socioeconomic development partly explain this finding.

Efficacy of a referral center for patient-centered care in multiple myeloma: a cohort study.

BACKGROUND: Within the Brazilian Unified Health System (SUS), Referral Centers (RCs) are care facilities that provide specialized services. The objective of this study was to evaluate the efficacy of care provided to patients with multiple myeloma (MM) at a specialized RC (Hospital de Clínicas de Porto Alegre Referral Center for Multiple Myeloma, CRMM-HCPA) and to compare quality of life between patients with MM treated at CRMM-HCPA and those treated at non-RC facilities. METHODS: A 6-month cohort study was conducted in patients with MM receiving thalidomide from the Rio Grande do Sul State Health Department and treated at CRMM-HCPA and patients receiving treatment at other, non-RC care facilities. Thirty-two patients were included in the study, 19 from CRMM-HCPA and 13 from other institutions. To analyze the efficacy of care provided at CRMM-HCPA, the main outcome measure was the time from diagnosis to referral for autologous hematopoietic stem cell transplantation (HSCT). This outcome measure was assessed using questionnaires specifically designed for this study. Quality of life was also assessed, using the SF-36 questionnaire. RESULTS: Time from MM diagnosis to referral for autologous HSCT in each group was measured only in patients aged ≤ 65 years (n = 25); of these, 15 were recruited from CRMM-HCPA and 10 from other institutions. In this analysis, there was a significant difference (p = 0.036) in time elapsed between diagnosis and referral for autologous HSCT, which was significantly shorter for patients treated at CRMM-HCPA (median, 9 months; IQR, 8.5-14.5) than for those treated elsewhere (median, 24 months; IQR, 16-24). On quality of life analysis, there was a significant difference in the Social Functioning domain of the SF-36 questionnaire, which relates to performance of social activities (p = 0.02). CONCLUSIONS: The Referral Center model provided seems to be a more efficient treatment strategy as compared with other health care facilities, as it enabled a reduction in time to transplantation. Patients treated at CRMM-HCPA demonstrated greater ease in performing social activities, with less interference from physical or emotional problems.

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis.

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy and safety.

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy ...

National guidelines for high-cost drugs in Brazil: achievements and constraints of an innovative national evidence-based public health policy.

INTRODUCTION: The translation of best evidence into practice has become an important purpose of policy making in health care. In Brazil, a country of continental dimensions with widespread regional and social inequalities, the dissemination and use of the best-evidence in policy making is a critical issue for the healthcare system. OBJECTIVES: The main purpose of this study is to describe an evidence-based public health policy with special emphasis on guidelines creation for high-cost medicines. We also describe how that strategy was diffused to the judiciary system and to other parts of the healthcare system. RESULTS: We present an 11-year follow-up of a national project for creating and updating guidelines for high-cost medicines in Brazil. A total of 109 national guidelines were published (new or updated versions) for 66 selected diseases, the first such effort in Brazilian history. The project influenced the Brazilian legislature, which has recently established a Federal Law requiring national guidelines for any new technology listed for payment by the Brazilian public healthcare system. CONCLUSION: We were able to involve many different stakeholders in a partnership between academia and policy makers, which made possible the widespread dissemination of the clinical practice guidelines. Problems and constraints were also encountered. This evolving public health strategy might be useful for other developing countries.

Quality of life of brazilian patients with Gaucher disease and fabry disease.

OBJECTIVE: To evaluate QoL in a sample of Brazilian patients with Gaucher (GD) and Fabry (FD) disease using the SF-36 survey. METHOD: Observational cross-sectional study. The SF-36 survey was administered to cognitively able patients 12 years or older, who were seen in the Medical Genetics Service of Hospital de Clínicas de Porto Alegre, Brazil. RESULTS: Thirty-five patients were included in the study (GD = 21, FD = 14), mean age was 29.8 ± 14.2 years and 29 (82.9%) were receiving ERT. Patients with GD receiving ERT had better scores in the general health (p = 0.046) domain of the SF-36 than patients with FD receiving ERT. Comparison of patients with GD naive to ERT and those receiving ERT revealed differences only in the bodily pain domain (p = 0.036). The Zimran score showed a moderate negative correlation with the following domains of the SF-36: physical functioning (p = 0.035), role-physical (p = 0.036), general health (p = 0.023) and role emotional (p = 0.021). DISCUSSION AND CONCLUSION: Although limited because of the small number of patients included, findings suggest that patients with GD receiving ERT have a better QoL than patients with FD or with GD not receiving ERT. Imiglucerase has a beneficial effect against pain for patients with GD. Further studies should be conducted to confirm our findings.

Randomized clinical trial of a phytotherapic compound containing Pimpinella anisum, Foeniculum vulgare, Sambucus nigra, and Cassia augustifolia for chronic constipation.

BACKGROUND: A phytotherapic compound containing Pimpinella anisum L., Foeniculum vulgare Miller, Sambucus nigra L., and Cassia augustifolia is largely used in Brazil for the treatment of constipation. However, the laxative efficacy of the compound has never been tested in a randomized clinical trial. The aim of this study was to evaluate the efficacy and safety of the product. METHODS: This randomized, crossover, placebo-controlled, single-blinded trial included 20 patients presenting with chronic constipation according to the criteria of the American Association of Gastroenterology. The order of treatments was counterbalanced across subjects: half of the subjects received the phytotherapic compound for a 5-day period, whereas the other half received placebo for the same period. Both treatment periods were separated by a 9-day washout period followed by the reverse treatment for another 5-day period. The primary endpoint was colonic transit time (CTT), measured radiologically. Secondary endpoints included number of evacuations per day, perception of bowel function, adverse effects, and quality of life. RESULTS: Mean CTT assessed by X ray was 15.7 hours (95%CI 11.1-20.2) in the active treatment period and 42.3 hours (95%CI 33.5-51.1) during the placebo treatment (p < 0.001). Number of evacuations per day increased during the use of active tea; significant differences were observed as of the second day of treatment (p < 0.001). Patient perception of bowel function was improved (p < 0.01), but quality of life did not show significant differences among the study periods. Except for a small reduction in serum potassium levels during the active treatment, no significant differences were observed in terms of adverse effects throughout the study period. CONCLUSIONS: The findings of this randomized controlled trial allow to conclude that the phytotherapic compound assessed has laxative efficacy and is a safe alternative option for the treatment of constipation. TRIAL REGISTRATION: ClinicalTrial.gov NCT00872430.

Treatment of hepatitis C with peginterferon and ribavirin in a public health program.

BACKGROUND/AIMS: In hepatitis C treatment, literature is limited with regard to independent studies developed outside the context of clinical assays. To evaluate the sustained virological response to the treatment of patients with chronic hepatitis C genotype 1 in a public program in the south of Brazil. METHODOLOGY: It is a mixed cohort, the data of all patients with chronic hepatitis C treated with peginterferon associated with ribavirin for 48 weeks were collected. If there was no early virological response on week 12 the treatment was discontinued. The significance level adopted in the statistical analysis was micro = 0.05. RESULTS: The cohort was comprised of 323 individuals. The treatment was completed in 215 (66.6%) patients. With the intention to treat analysis, the sustained virological response was obtained in 114 (35.3%) patients. The factors predictive of the response were lower age (below 40 years) and minor fibrosis (< F3 according METAVIR score), as well as viral load less than 600,000 IU/ml and the absence of hepatitis C virus viremia on 12th week of treatment. CONCLUSION: The sustained virological response in patients with chronic hepatitis C genotype 1 treated with peginterferon and ribavirin in a public health system did not reproduce the results obtained in the major clinical trials.

Comparison of the Mini Mental State Examination and depressive symptoms between high cardiovascular risk and healthy community elderly groups.

The aging of the population is a universal phenomenon with direct consequences upon the public health system. One of the main repercussions of the growth in this sector of the population is the increased prevalence of disorders such as dementia and depression which are very frequent among the elderly. The relationship between cardiovascular risk factors, dementia and depression have been addressed in many recent investigations. OBJECTIVES: To evaluate the relationship of cognitive performance and depressive symptoms with cardiovascular risk in the elderly. METHODS: 94 high cardiovascular risk elderly patients and 160 healthy community elderly were evaluated cross-sectionally. The Mini Mental State Examination (MMSE) and the Geriatric Depression Scale (GDS-15) were used as the main measures. The cutoff for presence of depression was 6 on the GDS. RESULTS: The high cardiovascular risk elderly group showed significantly lower scores on the MMSE (p<0.001) and was significantly associated to depression (p<0.001), independently of education. The logistic regression analysis for depression as the dependent variable, age and group (healthy community or high cardiovascular risk elderly) were kept in the final equation. Higher age (Odds Ratio=0.92; 95% CI 0.86-0.98) and high cardiovascular risk elderly (OR=2.99; 95% CI 1.36-6.59) were associated to depression. CONCLUSIONS: The present findings corroborate the different cognitive performance of elderly with high cardiovascular risk factors and the association of depressive symptoms with this group.

O envelhecimento da população é um fenômeno mundial com conseqüências diretas no sistema de saúde pública. Uma das principais conseqüências do crescimento desta parcela da população é o aumento da prevalência de doenças como demência e depressão que são muito freqüentes entre os idosos. Recentemente, a relação entre fatores de risco cardiovasculares, depressão e demência foi abordada em várias investigações. OBJETIVOS: Avaliar a relação de desempenho cognitivo e sintomas depressivos com risco cardiovascular em idosos. MÉTODOS: 94 idosos de alto risco cardiovascular e 160 idosos saudáveis da comunidade foram avaliados num corte transversal. O Mini-Exame do Estado Mental (MEEM) e a escala de depressão geriátrica (GDS-15) foram usados para as medidas principais. O ponto de corte para presença de sintomas depressivos foi 6 na GDS. RESULTADOS: O grupo de alto risco cardiovascular mostrou escores significativamente mais baixos no MEEM (p<0001) independente da educação, e foi significativamente associado a depressão (p<0,001). A análise de regressão logística para depressão como variável dependente, idade e grupo (idosos saudáveis da comunidade ou idosos de alto risco cardiovascular) foram mantidos na equação final. Maior idade (Razão de Chance=0,92, IC 95% 0,86­0,98) e idosos de alto risco cardiovascular (RC=2,99; IC 95% 1,36­6,59) estavam associados à presença de depressão. CONCLUSÕES: Os achados do presente estudo corroboram o desempenho cognitivo diferencial dos idosos de alto risco cardiovascular e a associação de sintomas depressivos a este grupo.

Oral L-arginine administration does not inhibit thrombosis on an experimental model of arterial thrombosis: the effect on the apyrasic activity of the arterial wall.

Despite the extensive research on the pharmacology of L-arginine, there are only few data on its antithrombotic properties. We studied the effect of oral L-arginine administration in a model of arterial thrombosis in rabbits divided into three groups: group 1, group without intervention; group 2, control group, treated with normal diet and submitted to the thrombosis-triggering protocol; group 3, treated for 2 weeks with L-arginine (2.25%) prior the protocol. L-Arginine did not alter platelet aggregation nor coagulation parameters but reduced vascular activities of both ADPase (49.1 +/- 8.5 versus 28.9 +/- 8.3 versus 18.8 +/- 10.3 nmoles inorganic phosphate/min per mg protein; mean +/- SD; group 1 versus group 2 versus group 3, respectively; ANOVA F = 19.21; P < 0.0001) and ATPase (97.8 +/- 15.8 versus 52.1 +/- 11.6 versus 31.9 +/- 16.3 nmoles inorganic phosphate/min per mg protein; mean +/- SD; group 1 versus group 2 versus group 3, respectively; ANOVA, F = 34.65; P < 0.0001). L-Arginine did not reduce the thrombi area (17.1 mm, 9.02 and 48.07, versus 27.04 mm, 25.4 and 70.39, median, percentile 25 and 75 respectively, P = 0.079; group 2 versus group 3, respectively). In conclusion, oral L-arginine administration did not inhibit thrombosis, and, conversely, it significantly reduced the arterial wall ADPase and ATPase activities. This effect may limit its antithrombotic properties.

Intravenous apyrase administration reduces arterial thrombosis in a rabbit model of endothelial denudation in vivo.

The role of adenine nucleotides on vascular and platelet functions has long been established. Apyrase (CD39) takes part of a family of ecto-enzymes that hydrolyze adenosine diphosphate and adenosine triphosphate. The participation of apyrase in the thromboregulatory system is under study. An in vivo experimental model of acute arterial thrombosis was used to test the hypothesis that administering a soluble form of potato apyrase could prevent thrombus formation. Twenty-five white New Zealand male rabbits suffered balloon aortic endothelium denudation and, after 15 days, they were submitted to a thrombosis-triggering protocol with a procoagulant (Russel's viper venom) and epinephrine. After the thrombosis-triggering protocol, 12 animals received two soluble apyrase administrations intravenously (with 90 min intervals), while 13 control animals received no apyrase. Three hours after the triggering protocol, the animals were killed and the rate and area of arterial thrombosis were analyzed. The rate of thrombosis in the apyrase group was significantly lower than that of the control group (16.7 versus 69%, respectively; P = 0.015), as was the area of thrombosis (1.7 +/- 4.3 versus 21.7 +/- 37.4 mm2, respectively; P = 0.008). Our results confirm that apyrase participates in homeostasis through a potent anti-thrombotic effect.