The thesis of judicialization of health care by the elites : medication for mucopolysaccharidosis

O artigo avalia a hipótese de se a judicialização de medicamentos para o tratamento das mucopolissacaridoses no Brasil seria uma ação das elites econômicas. Debatem-se estudos prévios que defendem a tese da judicialização pelas elites em outros medicamentos. Discute-se, a metodologia desses estudos e as inferências dela derivadas e o respaldo empírico dessa tese no caso de um dos medicamentos judicializados de mais alto custo para o SUS. Foram analisados os 196 processos julgados entre fevereiro de 2006 e dezembro de 2010 que determinam a provisão gratuita dos medicamentos para mucopolissacaridoses pelo Ministério da Saúde. Há evidências de que os custos advocatícios sejam financiados por entidades interessadas nos resultados da judicialização, como as empresas distribuidoras ou indústrias farmacêuticas, de que pode haver migração dos pacientes para diagnóstico e tratamentos em centros universitários de referência para a inovação médica no país, e de que a opção por serviços públicos se dá por sua capacidade técnica e científica superior à de outras instituições. Logo, a advocacia privada, indicadores de exclusão social do local de residência dos pacientes e uso de serviços públicos não são informações de classe que corroborem ou refutem a tese da judicialização pelas elites. _________________________________________________________________________________ ABSTRACTThis paper evaluates the hypothesis that the judicialization of medicine for mucopolysaccharidosis in Brazil is an action promoted by economic elites. Previous studies upholding the thesis of judicialization by elites in the case of other types of medication that are more costly for the Unified Health Service are discussed. An analysis of all 196 processes containing information about judicial processes brought to court between February 2006 and December 2010 that ended by determining that the State should provide such medication free of charge to patients was conducted. There is evidence that attorneys’ fees were covered by entities interested in the results of judicialization, such as the distributors or pharmaceutical industries. Patients may also be migrating for diagnosis and treatment to university centers that are a benchmark for medical innovation in the country, as the option for public health services is related to their higher technical and scientific capacity. Therefore, the resort to private lawyers, indicators of social exclusion based on the address of patients and the use of public health services, are not adequate class information to corroborate or refute the thesis of judicialization by the elites

Development of an inventory to assess perceived barriers related to PKU treatment

Background: According to studies of phenylketonuria (PKU), the Brazilian population’s metabolic control shows unsatisfactory indexes from childhood. Research on patients’ perceived difficulties or barriers to adherence to treatment can help us to comprehend how these outcomes are associated. The present study aimed to: (1) describe the development of an inventory for identifying the most frequent and relevant perceived barriers to PKU treatment from the perspective of patients, caregivers, and healthcare professionals; (2) evaluate certain psychometric characteristics of the new measure; and, (3) explore potential predictors (sociodemographic and medical characteristics) that may contribute to increasing the number of perceived barriers and examine whether the number of barriers is associated with the degree of adherence shown by the patient. Results: Participants in the study were 23 patients with PKU (M age = 18.0 years; SD = 7.3; range 6 to 34 years; 69% early-treated) in classical (n = 11) and mild (n = 12) form, and 11 caregivers. The inventory, developed to ascertain perceived barriers to treatment, was completed by patients (≥ 13 years) and caregivers of patients aged 6 to 17 years. Analyses were conducted to investigate whether barrier inventory scores were associated with adherence to treatment as measured by phenylalanine levels in patients’ medical records. Scores on the inventory differed across the patient age groups: adolescents had lower scores (i.e. reported fewer barriers) compared with those of adults (U = 8.000, p = 0.008); patients with better recent metabolic control also reported fewer perceived barriers than did patients with poor adherence (U = 20.000, p = 0.009); and the number of perceived barriers was positively associated with recent blood phenylalanine concentration (Kendall’s taub = 0.41; p = 0.001). Conclusions: These results suggest that the inventory has merit in assessing perceived barriers and support the need for further research on barriers perceived by PKU patients

Prevalence of thrombophilia and thrombotic events in patients with fabry disease in a Reference Center for Lysosomal Disorders in Southern Brazil

Introduction: Venous thromboembolism (VTE) is a multifactorial genetic disorder that occurs in approximately one in a thousand adults per year. Because there is no laboratory test or clinical marker useful for predicting which patients with Fabry disease may develop thrombotic events, this study aimed to determine whether there is a hereditary predisposition to hypercoagulation in these patients. Methods: The prevalence of p.R506Q mutation in the factor V gene and of c.G20210A mutation in Factor II (prothrombin) gene was evaluated in 39 patients with Fabry disease from Southern Brazil and correlated with clinical findings. The DNA analysis was performed by real-time polymerase chain reaction on genomic DNA using TaqMan probes. Results: In this group of patients, the frequency of mutation in the prothrombin gene was 1.28%, whereas no patient showed mutation in the factor V gene; additionally, there was no correlation between these mutations and the incidence of thrombotic events. Conclusion: Hereditary thrombophilia due to mutations in factor V and prothrombin genes does not seem to be related to thrombotic events in Fabry patients in our cohort, although studies in larger cohorts and the inclusion of additional factors may be required to determine if a correlation exists

Clinical genetics and public policies : how should rare diseases be managed?

The implementation of a specific policy for rare diseases in the Brazilian Unified Health System presents challenges in terms of its rationale. Recognizing the importance of rarity in the context of public health means understanding genetics as one of the dimensions of disease and accepting that Brazil is undergoing a period of transition in health indicators. Although most rare diseases lack pharmacological treatment and genetic counseling constitutes the best strategy for their prevention, the cost of “orphan drugs” and their consequent lack of cost-effectiveness are still claimed as hurdles to the implementation of public policies in this field. Epidemiological aspects should not be used as isolated criteria for prioritization in public policies

Impact of the COVID-19 pandemic on the standard of care for patients with lysosomal storage diseases : a survey of healthcare professionals in the Fabry, Gaucher, and Hunter Outcome Survey registries

the needs of their healthcare providers were explored using a 12-question survey. Overall, 80/91 respondents (88%) indicated that the pandemic had negatively affected standards of care. With increased reliance on tele-medicine, the respondents highlighted the need for a personalized approach to care, direct and frequent communication with patients, and greater involvement of patients and caregivers

Influence of CYP19A1 polymorphisms on the treatment of breast cancer with aromatase inhibitors : a systematic review and meta-analysis

Background: Many clinical trials have shown the efficacy of aromatase inhibitors (AIs) in the management of breast cancer (BC). There is growing evidence that CYP19A1 single-nucleotide polymorphisms (SNPs) are associated with clinical response (CR) and adverse effects (AEs) among BC patients treated with AIs. The aim of this study was to analyze the association between CYP19A1 polymorphisms and AI treatment in BC patients. Methods: A systematic review was performed in MEDLINE, EMBASE, and LILACS. A meta-analysis was conducted to compare the association between CYP19A1 variants and treatment response among BC patients. Results: A total of 12 studies were included in the final analysis. There was significant variation among the populations studied and the SNPs and outcomes investigated. A meta-analysis was only possible for the evaluation of SNP rs4646 vs. the wild-type variant with respect to time to progression (TTP) among metastatic BC patients treated with AI. TTP was significantly increased in patients with the rs4646 variant compared with the wild-type gene (hazard ratio (HR) = 0.51 [95 % confidence interval (CI), 0.33–0.78], P = 0.002). Seven studies analyzed the association between AEs with different polymorphisms of CYP19A1. Although there was a statistically significant association with musculoskeletal adverse events (rs934635, rs60271534, rs700518rs, and haplotype M_3_5) and with vasomotor symptoms (rs934635, rs1694189, rs7176005, and haplotype M_5_3) in individual studies, similar associations were not observed in further studies. No statistically significant association between musculoskeletal AEs and SNPs rs4646, rs10046, rs727479, and rs1062033 was found. Conclusions: These findings suggest that the presence of the rs4646 variant may be a predictive factor of the benefit of AI treatment for BC. The effects of CYP19A1 polymorphisms on clinical outcomes were most often detected in individual studies, suggesting that longer-term studies will better clarify these associations. Additional studies are needed to clarify the predictive value of other SNPs and whether CYP19A1 genotyping should be used to guide AI treatment

Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease : functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome

Objectives: To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease. Methods: This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling. Results: The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys. Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients). Patients’ primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the Alpk1 T237M mutation exhibited subclinical inflammation. Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow. Conclusion: ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in ALPK1 and some features of disease are amenable to immunomodulatory therapy