Information and Diagnosis Networks - tools to improve diagnosis and treatment for patients with rare genetic diseases.

Brazil is a country of continental dimensions and most genetic services are concentrated in the Southeast and South, including the Medical Genetics Service of the Hospital de Clínicas de Porto Alegre (MGS/HCPA). As many areas on the country do not have adequate medical genetics support, networks were designed to extend the service of the MGS/HCPA reference center. This paper presents the information and diagnosis networks that have their headquarters at MGS/HCPA: SIAT (National Information System on Teratogenic Agents), SIEM (Information Service on Inborn Errors of Metabolism), Alô Genética (Hello Genetics - Medical Genetics Information Service for Primary Health Care Professionals); Rede MPS Brasil (MPS-Mucopolysaccharidosis Brazil Network); Rede EIM Brasil (IEM-Inborn Errors of Metabolism Brazil Network), Rede NPC Brasil (Niemann-Pick C - NPC Brazil Network), Rede DLD Brasil (LSD-Lysosomal Storage Disorders Brazil Network), Rede DXB (MSUD-Maple Syrup Urine Disease Network), RedeBRIM (Brazilian Network of Reference and Information in Microdeletion Syndromes Project), Rede Neurogenética (Neurogenetics Network), and Rede Brasileira de Câncer Hereditário (Brazilian Hereditary Cancer Network). These tools are very useful to provide access to a qualified information and/or diagnostic service for specialized and non-specialized health services, bypassing difficulties that preclude patients to access reference centers.

Training of community health agents - a strategy for earlier recognition of mucopolysaccharidoses.

Primary Health Care (PHC) is the gateway for patients in the Brazilian unified health system (Sistema Único de Saúde-SUS), playing an extremely important role in the identification of potential patients with genetic diseases, and referral to specialized and tertiary health services. The PHC is composed of a multidisciplinary team, including the Community Health Agent, who is in direct contact with the community. To implement an educational program aimed at community health agents working in several municipalities in the state of Rio Grande do Sul (RS), Brazil. The training was focused on genetic diseases in general, with a special focus on identifying patients with Mucopolysaccharidosis (MPS). Tests were applied before and after the educational intervention, in order to assess the participants' knowledge on the topic at these two moments. The study covered a total of ten training sessions carried out in eight municipalities in the RS state, training 374 community health agents. The number of correct answers in the pre-test (n = 339) was 8,4 (SD 1.2), while in the post-test (n = 361) it was 9,2 (SD 0.8). Statistical analysis showed that the educational intervention effectively provided information about genetic diseases to the participants. Considering that community health agents are of fundamental importance in the identification and prevention of diseases and in the better navigation of the patients on the SUS, these professionals play a key role in the field of rare genetic diseases, and continuous training strategies should be taken.

Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis.

In mucopolysaccharidosis VI, or Maroteaux-Lamy syndrome, deficiency of N-acetylgalactosamine 4-sulfatase leads to storage of glycosaminoglycans (GAGs) and MPS VI patients often develop spinal cord compression during the course of the disease due to GAG storage within the cervical meninges, requiring neurosurgical intervention, as intravenous (IV) enzyme replacement therapy (ERT) is not expected to cross the blood-brain barrier. We report the use of intrathecal (IT) recombinant human N-acetylgalactosamine 4-sulfatase (arylsulfatase B, or ASB) in a MPS VI child with spinal cord compression whose parents initially refused the surgical treatment. Assessments were performed at baseline, with clinical, neurological and biochemical evaluations, urodynamic studies and MRI of the CNS. Changes on these parameters were evaluated after IT infusions of ASB administered monthly via lumbar puncture (LP) in a IV ERT naive patient. To our knowledge, this was the first MPS VI patient who received IT ERT. Despite significant urodynamic improvement and some neurological amelioration, the patient developed worsening of walking capacity. After IV ERT was started, the patient presented with a generalized hypotonia and a life-saving surgical fixation of the neck was then performed. The results observed on this MPS VI patient suggest that instability of the cervical vertebrae could be unmasked by IV ERT as joint storage is reduced, and the decrease in neck stiffness and stability could confound the expected improvement of SCC manifestations following IT ERT. The study of further patients, if possible in a clinical trial setting, is needed to evaluate the potential of a non-surgical IT ERT treatment of SCC for MPS VI.

Mucopolysaccharidoses in Brazil: what happens from birth to biochemical diagnosis?

Mucopolysaccharidoses (MPS) form a group of inherited metabolic disorders characterized by intralysosomal storage of glycosaminoglycans. This study aimed to investigate the path followed by Brazilian patients from birth to diagnosis. An interview was conducted with patient's parents or guardians with subsequent review of patient's medical records. One hundred thirteen patients with MPS were included (MPS I: 18, MPS II: 43, MPS IIIA: 2, MPS IIIB: 3, MPS IIIC: 1, MPS IVA: 15, MPS IVB: 1, MPS VI: 29, MPS VII: 1) from 97 families. Median age at the onset of signs/symptoms was 18 months (MPS I: 18, MPS II: 24, MPS IVA: 8, MPS VI: 8). Skeletal abnormalities (for MPS IVA and MPS VI), joint contractures (for MPS II), and typical facial features (for MPS I) were the most frequently reported first signs/symptoms. Several health professionals were involved in patient's care as of the onset of symptoms until biochemical diagnosis was established. Median age at diagnosis was 76 months (MPS I: 75, MPS II: 95, MPS IVA: 75, MPS VI: 52). Considering the group as a whole, there was a 4.8-year delay between the onset of signs/symptoms and the establishment of the diagnosis. Considering that specific therapies are available for some of these disorders and that early treatment is likely to change more favorably the natural history of the disease, efforts should be made to minimize this delay. We believe that this situation can be improved by measures that both increase awareness of health professionals about MPS and improve access to diagnostic tests.

Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression.

In mucopolysaccharidosis I, deficiency of alpha-L-iduronidase can cause spinal cord compression (SCC) due to storage of glycosaminoglycans (GAGs) within the cervical meninges. As intravenous enzyme replacement therapy (ERT) is not likely to provide enzyme across the blood-brain barrier, standard treatment for this complication is usually surgical, which has a high morbidity and mortality risk. We report on the use of intrathecal (IT) laronidase in a MPS I patient with SCC who refused the surgical treatment. Assessments were performed at baseline, with clinical and biochemical evaluations, 4-extremity somatosensory evoked potentials, 12 min walk test and MRI studies of the CNS. Changes on these parameters were evaluated after 4 IT infusions of laronidase administered monthly via lumbar puncture. To our knowledge, this was the first MPS patient who received IT ERT. No major adverse events were observed. There were no clinically significant changes in serum chemistries. CSF GAG results revealed pretreatment values slightly above normal standards: 13.3 mg/L (NV < 12 mg/L) which after IT laronidase infusions were within normal levels (10.3 mg/L). 12MWT presented a 14% improvement, with better performance on stability and gait control. Maximum voluntary ventilation showed 55.6% improvement considering the percentage of predicted (26.7% at baseline compared to 41.9%); Maximum Inspiration Pressure improved 36.6% of predicted (26.8% at baseline to 36.7%); Pulmonary diffusion improved 17.6% of predicted %. In conclusion, although the improvement observed in this case with IT laronidase should be confirmed in further patients, this procedure seems to be a safe treatment for SCC in MPS I.

Avaliação transversal dos indicadores de saúde do programa nacional de triagem neonatal de um município do Vale do Paranhana / Cross-sectional evaluation of health indicators of the national neonatal screening program in a city of Vale do Paranhana

Objetivo: avaliar indicadores do programa nacional de triagem neonatal (PNTN) e de saúde no município de Rolante, RS, Brasil. Método: estudo transversal, por meio dos prontuários eletrônicos cadastrados entre janeiro de 2017 e julho de 2020. Foi realizado o cálculo dos indicadores do PNTN dos anos de 2017 a 2019, e análise de outras variáveis de saúde como: período e local da coleta, peso e idade de nascimento, idade materna, realização de pré-natal, realização da consulta, resultado do exame e recoleta. Resultado: a cobertura variou entre 201 de 256 (78,5%) e 229 de 272 (84,2%). Das 734 coletas 544 (74,1%) foram realizadas no período de três a cinco dias de vida, preconizado pelo Ministério da Saúde. A mediana da idade do RN na primeira consulta foi superior a 15 dias em todas as doenças triadas, exceto fenilcetonúria e deficiência de biotinidase, no período avaliado. Conclusão: a partir dos resultados foi possível observar que a cobertura do município correspondeu aos dados nacionais e estaduais no período. E, ainda que o percentual de coletas realizadas na data ideal tenha sido alto, a idade preconizada na primeira consulta não foi cumprida na maior parte das patologias

Objective: to evaluate neonatal screening national program (PNTN) and health indicators in the Rolante city, RS, Brazil.Method: cross-sectional study, using electronic medical records registered between January 2017 and July 2020. The calculation of the PNTN indicators from 2017 to 2019 was carried out. And analysis of other health variables such as: period and place of collection, weight and age at birth, maternal age, prenatal care, consultation, test results and collection. Result: coverage ranged from 201 out of 256 (78.5%) to 229 out of 272 (84.2%). Of the 734 collections, 544 (74.1%) were performed within the period of 3 to 5 days of life, recommended by the Ministry of Health. The median age of the NB at the first consultation was greater than 15 days in all screened diseases, except for phenylketonuria and biotinidase deficiency, in the period evaluated.Conclusion: from the results it was possible to observe that the coverage of the municipality corresponded to the national and state data in the period. And even though the percentage of collections carried out on the ideal date was high, the recommended age at the first consultation was not met in most pathologies

Immune tolerance induction for laronidase treatment in mucopolysaccharidosis I.

Enzyme replacement therapy (ERT) can produce anti-drug antibody (ADA) responses that reduce efficacy or lead to hypersensitivity reactions. Six patients with severe mucopolysaccharidosis type I (MPS I/Hurler syndrome) who did not receive hematopoietic stem cell transplantation underwent an immunosuppression regimen prior to initiating ERT with laronidase. The primary endpoint for immune tolerance induction was the number of patients with an ADA titer ≤ 3200 after 24 weeks of laronidase at the labeled dose. Cyclosporine levels were measured weekly and doses adjusted to maintain trough levels above 400 mg/mL. A 6-week (Cohort 1) or 12-week (Cohort 2) immune tolerance induction period with cyclosporine (initial dose: 15 or 20 mg/kg/day), azathioprine (initial dose: 2.5 or 5 mg/kg/day) and low-dose laronidase infusions (0.058-0.29 mg/kg/week) was followed by an immune-challenge period with laronidase infusions at the labeled dose (0.58 mg/kg/week) for 24 weeks. Anti-laronidase IgG titers were determined following treatment. There were 147 treatment-emergent adverse events reported, most of which were mild and not related to the study treatment. While there was no evidence of immune tolerance in 3 of 3 patients in Cohort 1, there were some indications of immune tolerance induction in 2 of 3 patients in Cohort 2. Patients with lower ADA titers showed greater reductions in urinary glycosaminoglycan excretion. Routine monitoring of plasma cyclosporine parent-compound levels by high pressure liquid chromatography proved difficult for clinical practice. The evolving clinical management of MPS I and a better understanding of the clinical impact of laronidase-related immunogenicity require reassessment of immune modulation strategies in patients with MPS I receiving laronidase treatment. CLINICAL TRIAL REGISTRATION: NCT00741338.

Prospective study of 11 Brazilian patients with mucopolysaccharidosis II.

OBJECTIVE: To assess the progression of mucopolysaccharidosis II in 11 Brazilian patients over a 12-month period. METHODS: Eleven Brazilian patients with mucopolysaccharidosis II were prospectively studied at the Division of Medical Genetics of Hospital de Clínicas de Porto Alegre. The initial assessment and the assessment at 12 months included: anamnesis, physical examination, abdominal nuclear magnetic resonance, echocardiogram, 6-minute walk test, audiometry, serum biochemical tests and urinary glycosaminoglycan concentration. RESULTS: The major findings after comparing the assessments were: 1) two patients had growth retardation; 2) two patients showed negative weight change; 3) one patient went from obese to overweight; 4) three patients revealed left ventricle hypertrophy; of these, two increased the number of cardiac valve lesions; 5) there was no statistically significant difference between the mean distances obtained on the 6-minute walk test; 6) there was splenic enlargement; 7) there was an increase in gamma-glutamyltransferase levels; 8) the urinary concentration of glycosaminoglycans remained unchanged. CONCLUSIONS: In general, echocardiographic findings were the only variable with deterioration and possible immediate clinical consequences. Although a 12-month period is too short to detect changes in most variables related to mucopolysaccharidosis II, its progressive nature should be taken into account when evaluating the efficiency of treatment protocols.

Medical Costs Related to Enzyme Replacement Therapy for Mucopolysaccharidosis Types I, II, and VI in Brazil: A Multicenter Study.

BACKGROUND: Mucopolysaccharidosis (MPS) type I (MPS I), MPS type II (MPS II), and MPS type VI (MPS VI) are lysosomal storage disorders for which enzyme replacement therapy (ERT) is available. OBJECTIVE: The objective of this study was to evaluate the frequency of medical interventions in a cohort of patients with MPS I, II, and VI on ERT to estimate the impact of direct medical costs associated with the treatment of MPS and compare its frequency with that observed among patients not on ERT. METHODS: This was a multicenter study using a retrospective design including a convenience sampling of Brazilian patients with MPS I, II, and VI. Data on the number and type of medical appointments, hospital admissions, medications used, and surgical procedures performed per patient were obtained through a review of medical records, as were data on ERT. These variables were then compared between patients undergoing ERT and those not on ERT. RESULTS: Thirty-four patients (27 on ERT) were included in the study. Overall, between-group differences were found in median absolute frequencies of hospital admissions and surgical procedures per year, both of which were higher in the non-ERT group. Furthermore, we observed a high rate of failure to record medication dosage regimens. CONCLUSIONS: Our findings suggest that Brazilian patients with MPS I, II, and VI who are on ERT undergo fewer medical interventions, which can lead to a reduction in direct medical costs to the publicly funded health care system. The cost of ERT, however, is extremely high and probably outweighs this reduction.

Indicadores de Qualidade na condução de estudos clínicos / Quality indicators in the conduct of clinical studies

Introdução: A geração, análise e difusão de indicadores pertinentes é uma das estratégias fundamentais do processo de gestão de qualidade. Indicadores são mensurações que avaliam direta ou indiretamente os processos e desfechos da assistência ao participante de pesquisa. Padrões rigorosos de qualidade garantirão a validade dos dados obtidos nos estudos clínicos. Métodos: Estudo transversal descritivo e analítico, com dados coletados no Centro de Pesquisa Clínica de um Hospital Universitário, durante Novembro/2016 a Fevereiro/2019 quanto ao tempo de inclusão de dados no electronic case report form (IID), tempo de comunicação de desvios de protocolo ao Comitê de Ética em Pesquisa (ICD), tempo de resposta aos feasibilities recebidos (IRF) e tempo de resposta às pendências de monitoria (IRP). Resultados: Variações substanciais foram encontradas entre os escores de qualidade ao longo de 27 meses. O desempenho geral da equipe do Escritório de Projetos em Pesquisa alcançou a classificação excelente ou satisfatória em 61,40% das observações: 50,87% e 10,52% respectivamente. Entre 38,59% de observações críticas, 17,54% foram expressas pelo IRP, seguido de 12,28% por ICD e 7% atribuído ao IID que não atingiram a meta proposta. Conclusão: O Escritório de Projetos em Pesquisa elencou dois indicadores de qualidade, IID e IRP, que podem melhorar o tempo e a eficácia das entregas propostas da equipe. (AU)

Introduction: The generation, analysis and dissemination of relevant indicators is a fundamental strategy in the quality management process. Indicators are measurements that directly or indirectly evaluate the processes and outcomes of the care provided to research participants. Rigorous quality standards will guarantee the validity of the data obtained in clinical studies. Methods: This descriptive, analytical cross-sectional study collected data at the Clinical Research Center of a University Hospital, covering the period from November 2016 to February 2019, regarding the time of data inclusion in the electronic case report form (IID), communication of protocol deviations to the Research Ethics Committee (ICD), response time to received feasibilities (IRF) and response time to monitoring pending issues (IRP). Results: Substantial variations were found between quality scores in a period of 27 months. The overall performance of the Research Project Office team was excellent or satisfactory in 61.40% of the observations (50.87% and 10.52% respectively). Among critical observations (38.59%), 17.54% were expressed by IRP, 12.28% by ICD and 7% by IID, indicating those that did not reach the proposed target. Conclusions: The Research Project Office has listed two quality indicators, IID and IRP, which can improve the time and effectiveness of team deliveries.(AU)

Assistência de enfermagem ao paciente com delirium na unidade de terapia intensiva: uma revisão integrativa / Nursing care for delirium patient in the intensive care unit: an integrative review / Atención de enfermería para pacientes de delirium en la unidad de atención intensiva: una revisión integrativa

OBJETIVO: Avaliar o nível de conhecimento do enfermeiro na identificação do Delirium na UTI. METODOLOGIA: Trata-se de uma revisão integrativa, na base de dados SciELO, LILACS e BDENF em março/abril de 2018. Foi dividido em categorias acerca do Delirium, tais como: Reconhecimento do Delirium, Papel da Enfermagem na Utilização da Escala CAM-ICU e Aplicação nas UTIs e Medidas preventivas pelo enfermeiro. RESULTADOS: Para coleta de dados, utilizou-se um instrumento sobre à identificação do artigo, autor (es), periódico publicado, ano da publicação, metodologia do artigo e país de publicação na totalidade de 10 produções. CONCLUSÃO: A dificuldade na identificação da patologia existe, uma vez, que a mesma é subvalorizada e de difícil reconhecimento. Percebemos como uma prática complexa e minuciosa com alguns pontos de fragilidade no que se refere a percepção do Delirium pela equipe multidisciplinar com a finalidade de evitar agravos ao quadro clínico do paciente.(AU)

OBJECTIVE: Assess the level of knowledge of nurses in the identification of Delirium in the ICU. METHODOLOGY: this is an integrative review in SciELO, LILACS and BDENF in March/April 2018. Was divided into categories about the of the Delirium, such as: Recognition of Delirium, and the Role of Nursing in the use of the Scale CAM-ICU and the ICUs and preventive Measures by the nurse. RESULTS: For data collection we used an instrument on the identification of the article, the author (s) journal published, year of publication, methodology of the article and country of publication in all 10 productions. CONCLUSION: The difficulty in identifying the pathology once exists is that it is undervalued and difficult to recognize. We perceive as a complex and meticulous practice with some fragility points regarding the perception of Delirium by the multidisciplinary team with the purpose of avoiding damages to the clinical picture of the patient.(AU)

OBJETIVO: Evaluar el nivel de conocimiento del enfermero en la identificación del Delirium en la UTI. METODOLOGÍA: Se trata de una revisión integrativa, en la base de datos SciELO, LILACS y BDENF en marzo/abril de 2018. Se dividieron en categorías acerca del Delirium, tales como: Reconocimiento del Delirium, Papel de la Enfermería en la Utilización de la Escala CAM-ICU y Aplicación en las UTIs y Medidas preventivas por El enfermero. RESULTADOS: Para la recolección de datos se utilizó un instrumento sobre la identificación del artículo, autor (es), periódico publicado, año de la publicación, metodología del artículo y país de publicación en la totalidad de 10 producciones. CONCLUSIÓN: La dificultad en la identificación de la patología existe, una vez, que la misma es subvalorizada y de difícil reconocimiento. Percibimos como una práctica compleja y minuciosa con algunos puntos de fragilidad en lo que se refiere a la percepción del Delirium por el equipo multidisciplinario con la finalidad de evitar agravios al cuadro clínico del paciente.(AU)

Practical and reliable enzyme test for the detection of mucopolysaccharidosis IVA (Morquio Syndrome type A) in dried blood samples.

BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA), or Morquio Syndrome type A, is an autosomal recessive disease caused by deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS), resulting in excessive lysosomal storage of keratan sulfate in many tissues and organs. This accumulation causes a severe skeletal dysplasia with short stature, and affects the eye, heart and other organs, with many signs and symptoms. Morquio A syndrome is estimated to occur in 1 in 200,000 to 300,000 live births. Clinical trials with enzyme replacement therapy for this disease are in progress, and it is probable that the treatment, when available, would be more effective if started early. We describe an innovative fluorometric method for the assay of GALNS in dried blood spots (DBS). METHODS: We used dried blood spots (DBS) as the enzyme source and compared it with leukocytes samples, having studied 25 MPS IVA patients and 54 healthy controls. We optimized the assay conditions, including incubation time and stability of DBS samples. To eppendorf type tubes containing a 3-mm diameter blood spot we added elution liquid and substrate solution. After 2 different incubations at 37°C, the amount of hydrolyzed product was compared with a calibrator to allow the quantification of the enzyme activity. Results in DBS were compared to the ones obtained in leukocytes using the standard technique. RESULTS: The fluorescent methodology was validated in our laboratory and the assay was found sensitive and specific, allowing reliable detection of MPS IVA patients. The use of DBS simplifies the collection and transport steps, and is especially useful for testing patients from more remote areas of large countries, and when samples need to cross country borders. CONCLUSION: This assay could be easily incorporated into the protocol of reference laboratories and play a role in the screening for MPS IVA, contributing to earlier detection of affected patients.

Expression of the disease on female carriers of X-linked lysosomal disorders: a brief review.

Most lysosomal diseases (LD) are inherited as autosomal recessive traits, but two important conditions have X-linked inheritance: Fabry disease and Mucopolysaccharidosis II (MPS II). These two diseases show a very different pattern regarding expression on heterozygotes, which does not seem to be explained by the X-inactivation mechanism only. While MPS II heterozygotes are asymptomatic in most instances, in Fabry disease most of female carriers show some disease manifestation, which is sometimes severe. It is known that there is a major difference among X-linked diseases depending on the cell autonomy of the gene product involved and, therefore, on the occurrence of cross-correction. Since lysosomal enzymes are usually secreted and uptaken by neighbor cells, the different findings between MPS II and Fabry disease heterozygotes can also be due to different efficiency of cross-correction (higher in MPS II and lower in Fabry disease). In this paper, we review these two X-linked LD in order to discuss the mechanisms that could explain the different rates of penetrance and expressivity observed in the heterozygotes; this could be helpful to better understand the expression of X-linked traits.

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment.

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.

[Enzyme replacement therapy for mucopolysaccharidoses I, II and VI: recommendations from a group of Brazilian F experts]. / Terapia de reposição enzimática para as mucopolissacaridoses I, II e VI: recomendações de um grupo de especialistas brasileiros.

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by deficiency of specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG). Accumulation of GAG in various organs and tissues in MPS patients results in a series of signs and symptoms, producing a multisystemic condition affecting bones and joints, the respiratory and cardiovascular systems and many other organs and tissues, including in some cases, cognitive performance. So far, eleven enzyme defects that cause seven different types of MPS have been identified. Before introduction of therapies to restore deficient enzyme activity, treatment of MPS focused primarily on prevention and care of complications, still a very important aspect in the management of these patients. In the 80's treatment of MPS with bone marrow transplantation/hematopoietic stem cells transplantation (BMT/HSCT) was proposed and in the 90's, enzyme replacement therapy (ERT),began to be developed and was approved for clinical use in MPS I, II and VI in the first decade of the 21st century. The authors of this paper are convinced that a better future for patients affected by mucopolysaccharidoses depends upon identifying, understanding and appropriately managing the multisystemic manifestations of these diseases. This includes the provision of support measures (which should be part of regular multidisciplinary care of these patients) and of specific therapies. Although inhibition of synthesis of GAG and the recovery of enzyme activity with small molecules also may play a role in the management of MPS, the breakthrough is the currently available intravenous ERT. ERT radically changed the setting for treatment of mucopolysaccharidosis I, II and VI in the last decade., Benefits can even be extended soon to MPS IV A (ERT for this condition is already in clinical development), with prediction for treatment of MPS III A and the cognitive deficit in MPS II by administration of the enzyme directly into the central nervous system (CNS). A large number of Brazilian services, from all regions of the country, already have experience with ERT for MPS I, II and VI. This experience was gained not only by treating patients but also with the participation of some groups in clinical trials involving ERT for these conditions. Summing up the three types of MPS, more than 250 patients have already been treated with ERT in Brazil. The experience of professionals coupled to the data available in international literature, allowed us to elaborate this document, produced with the goal of bringing together and harmonize the information available for the treatment of these severe and progressive diseases, which, fortunately, are now treatable, a situation which bring new perspectives for Brazilian patients, affected by these conditions.

A terapia de reposição enzimática pode mudar a frequência de intervenções médicas na mucopolissacaridose tipo I? Um estudo retrospectivo e exploratório / Can enzyme replacement therapy change the frequency of medical interventions in mucopolysaccharidosis type I? An exploratory retrospective study

Introdução: A mucopolissacaridose tipo I (MPS I) é uma doença lisossômica (DL) para a qual está disponível a terapia de reposição enzimática (TRE) com laronidase. Objetivo: caracterizar o efeito da TRE em pacientes com MPS I avaliados por um único centro de referências para DL a partir da análise da frequência de intervenções médicas. Métodos: Estudo retrospectivo e exploratório com comparações pré e pós-intervenção. O número/ano/paciente de consultas, medicamentos usados, internações, cirurgias e exames realizados, foi obtido por meio de revisão de prontuário médico. Essas variáveis foram, então, comparadas entre dois períodos: pré-TRE e pós-TRE. Resultados: Nove pacientes (graves=3, atenuados=6) foram incluídos no estudo. A mediana de idade de início da TRE foi 9 anos e a mediana de duração da TRE foi 4 anos. Em média, os pacientes realizaram 90% das infusões previstas para o período. Somente o número de cirurgias/ano/paciente foi dependente do tempo de doença (p=0,0004) e da gravidade do fenótipo (p=0,014). Com relação às comparações pré e pós-TRE, as variáveis que apresentaram diferença significativa (média do número/ano/paciente) foram: exames (pré-TRE=10,2±2,7; pós-TRE=22,5±2,1; p=0,005) e internações (pré-TRE=0,05±0,04; pós-TRE=0,30±0,11; p=0,013). Conclusão: Nossos dados sugerem que a TRE não alterou a história natural da MPS I em relação aos desfechos analisados. Este achado pode ser devido à idade relativamente avançada de início do tratamento no nosso centro.

Background: Mucopolysaccharidosis type I (MPSI) is a lysosomal disorder (LSD) which can be treated with enzyme replacement therapy (ERT) with laronidase. Aim: To describe the effect of ERT on MPSI patients evaluated at a single referral center for LSD by assessing the frequency of medical interventions. Methods: An exploratory, retrospective study with pre- and post-intervention assessments. We reviewed medical records to collect data on the number of medical appointments/year/patient, medications used, hospital admissions, surgeries, and exams performed. These variables were then compared between the pre- and the post-ERT periods.Results: Nine patients (severe=3; attenuated=6) were included in the study.The median age for the start of ERT was 9 years, and the median time on ERT was 4 years. On average, patients received 90% of the infusions predicted for the study period. Only the number of surgeries/year/patient was found to be dependent on length of disease (p=0.0004) and on severity of phenotype (p=0.014). Regarding pre- and post-ERT comparisons, there was a significant difference (mean number/year/patient in exams (pre-ERT, 10.2±2.7; post-ERT, 22.5±2.1; p=0.005) and hospital admissions (pre-ERT, 0.05±0.04; post-ERT, 0.30±0.11; p=0.013). Conclusion: Our data suggest ERT didn’t alter the natural history of MPSI the outcomes assessed in this study. This may be due to the relatively advanced age of patients when they started treatment at our Center.

O viver e o morar: relações interpessoais de moradores dos serviços residenciais terapêuticos / Living and residing: interpersonal relations of residents at therapeutic residential services / El vivir y el morar: relaciones interpersonales de habitantes de los servicios terapéuticos residenciales

Este estudo objetivou analisar as relações que os moradores de serviços residenciais terapêuticos de Teresina-PI estabelecem interna e externamente ao convívio social. Trata-se de uma pesquisa qualitativa com nove moradores. Os dados foram produzidos por meio de roteiro de entrevista semiestruturado, no período de dezembro de 2010 a janeiro de 2011 e submetidos à análise de conteúdo. Desse processo resultou a construção de duas categorias: Divisão de tarefas, liberdade emelhoria da qualidade de vida; e Relações externas insatisfatórias e estigmatizantes com os vizinhos. A partir desta análise percebe-se uma visível melhoria na qualidade de vida, uma vez que as relações estabelecidas internamente denotam o início de um processo de readaptação e reinserção dessas pessoas na sociedade. Entretanto, as relações externas ainda encontram-se permeadas por estigmas e preconceitos advindos do coletivo social.

This study analyzes internal and external social relations established by residents at therapeutic residential services at Teresina-Pi, Brazil. It is a qualitative study with nine residents. Data were produced by means of a semi-structuredinterview script, from December, 2010 to January, 2011 and were then submitted to content analysis. Results accounted for the construction of two categories: division of labor, freedom, and improved quality of life; and poor and stigmatizing external relations with neighbors. This analysis shows a visible improvement in quality of life, since the relations established internally point to a beginning process of rehabilitation and reintegration of those people in society. However, external relations are still permeated by stigma and prejudice arising from the social collective sphere.

Este estudio tuvo como objetivo analizar las relaciones que los habitantes de los Servicios Terapéuticos Residenciales de Teresina-PI-Brasil establecen interna y externamente al convivir social. Se trata de un estudio cualitativo con nueve residentes. Los datos fueron producidos por un guión de entrevista semiestructurada, de diciembre 2010 a enero 2011 y sometidos al análisis de contenido. Este proceso dio lugar a la construcción de dos categorías: división de tareas, libertad y mejoría de la calidad de vida; y relaciones externas insatisfactorias y estigmatizadoras con los vecinos. De este análisis se percibe una mejora visible en la calidad de vida, ya que las relaciones establecidas internamente denotan el comienzo de un proceso de rehabilitación y reinserción de estas personas en la sociedad. Sin embargo, las relaciones exteriores siguen siendo permeada por el estigma y los prejuicios derivados de la colectividad social.

Recomendações para o processo de obtenção do consentimento na pesquisa com seres humanos realizada no Hospital de Clínicas de Porto Alegre: [revisão] / Hospital de Clínicas de Porto Alegre directives for the informed consent process in human experimentation: [review]

São apresentadas recomendações institucionais para o processo de consentimento em pesquisas envolvendo seres humanos, especialmente para a elaboração e aplicação do Termo de Consentimento Livre e Esclarecido. Estas recomendações visam esclarecer os pesquisadores, com ênfase nos critérios utilizados pelo Comitê de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre na avaliação de projetos, sobre aspectos fundamentais que devem ser levados em consideração quando da elaboração e obtenção do consentimento de potenciais participantes de um projeto de pesquisa.

Institutionals directives are proposed for the informed consent process in research involving human beings, especially for the development and implementation of the Informed Consent Form. These recommendations aim to clarify the researchers, using the Research Ethics Committee of Hospital de Clinicas de Porto Alegre in project review, on key aspects that must be taken into account when preparing and obtaining the consent of the prospects participants in a research project.

A humanização no cuidar da criança portadora de câncer: fatores limitantes e facilitadores / Humanization in the care given to children with cancer: limiting and facilitating factors

Objetivo - Identificar os meios utilizados pela enfermagem para prestar cuidados humanizados às crianças com câncer, bem como os fatores limitantes e facilitadores deste cuidar. Métodos - Estudo exploratório, descritivo e qualitativo. Foram entrevistados nove profissionais de enfermagem do setor oncológico pediátrico de um hospital filantrópico de Teresina-PI. Os dados foram coletados por meio de entrevista gravada em aparelho digital e, posteriormente, transcritos e classificados em categorias analíticas. Resultados - O estabelecimento e valorização do vinculo de confiança e amizade entre profissional, criança e família foram os meios utilizados pela enfermagem no cuidado humano à criança. Foram achados fatores que dificultam a busca da assistência humanizada como a não cooperação de alguns pais frente aos cuidados prestados e o ambiente pouco acolhedor oferecido à criança e família. Entretanto, há fatores que facilitam a assistência como a empatia do profissional de enfermagem com o setor de oncologia e a visão da criança de que este exerce um cuidado muito importante durante a hospitalização. Conclusão - Foi possível identificar os meios utilizados pela enfermagem para se prestar cuidados humanizados, bem como os fatores limitantes e facilitadores deste cuidar. É fundamental a utilização desses meios, pois contribuem para a melhoria da assistência prestada a esses sujeitos.

Objective - To identify the means used by nurses to provide humane care for children with cancer as well as the limiting and facilitating factors of such care. Methods - It is an exploratory, descriptive and qualitative study. Nine nurses in the pediatric oncology ward of a philanthropic hospital in Teresina-PI were interviewed. Data were collected through interviews recorded on digital device and later transcribed and categorized into analytical categories. Results - The establishment and enhancement of the bond of trust and friendship between professional, child and family were the means used by nurses in giving children humane care. Factors that hinder the search for humanized care were found such as the non-cooperation by some parents before the care given and unwelcoming environment offered to children and family. However, there are factors that facilitate the assistance like the nurse's empathy towards the cancer ward and the child's view that this professional gives him or her very important care during hospitalization. Conclusion - It was possible to identify the means used by nurses to provide humane care, as well as the limiting and facilitating factors of such care. It is essential to use such means, in that they contribute to improving the care given to these people.