Sickle cell disease chronic joint pain: Clinical assessment based on maladaptive central nervous system plasticity.

Chronic joint pain (CJP) is among the significant musculoskeletal comorbidities in sickle cell disease (SCD) individuals. However, many healthcare professionals have difficulties in understanding and evaluating it. In addition, most musculoskeletal evaluation procedures do not consider central nervous system (CNS) plasticity associated with CJP, which is frequently maladaptive. This review study highlights the potential mechanisms of CNS maladaptive plasticity related to CJP in SCD and proposes reliable instruments and methods for musculoskeletal assessment adapted to those patients. A review was carried out in the PubMed and SciELO databases, searching for information that could help in the understanding of the mechanisms of CNS maladaptive plasticity related to pain in SCD and that presented assessment instruments/methods that could be used in the clinical setting by healthcare professionals who manage chronic pain in SCD individuals. Some maladaptive CNS plasticity mechanisms seem important in CJP, including the impairment of pain endogenous control systems, central sensitization, motor cortex reorganization, motor control modification, and arthrogenic muscle inhibition. Understanding the link between maladaptive CNS plasticity and CJP mechanisms and its assessment through accurate instruments and methods may help healthcare professionals to increase the quality of treatment offered to SCD patients.

Sociodemographic and clinical aspects of patients with sickle cell disease at referral centers in Salvador, Bahia / Aspectos sociodemográficos y clínicos de pacientes con enfermedad de células falciformes en centros de referencia en Salvador, Bahía / Aspectos sociodemográficos e clínicos de pacientes com doenças falciformes dos centros de referência em Salvador, Bahia

The centralization of care for patients with sickle cell diseases through the creation of reference centers through the Ministry of Health Ordinance No. 1,018/2005, enabled better monitoring of these patients. This study characterized the sociodemographic and clinical profile of patients with sickle cell diseases treated at reference centers in the city of Salvador. Women represented the largest portion of patients registered at the centers and were older and more educated than men. More than 90.0% of patients are single, demonstrating the difficulty of people with sickle cell disease to socialize due to the stigma of the disease. The most common clinical manifestations were pain crises and jaundice, and the most common complications were hospitalizations due to pain crises and blood transfusion. Associations were observed between sex and stroke, between genotype and lower limb ulcers and blood transfusion. A low percentage of patients with osteonecrosis (8.8%) was also observed, indicating possible underreporting. The low percentages of patients who use morphine and hydroxyurea point to the need to expand the offer of these drugs to reduce pain crises and improve the quality of life of patients.

La centralización de la atención a los pacientes con anemia falciforme mediante la creación de centros de referencia a través de la Ordenanza del Ministerio de Salud Nº 1.018 / 2005, permitió un mejor seguimiento de estos pacientes. Este estudio caracterizó el perfil sociodemográfico y clínico de los pacientes con drepanocitosis atendidos en centros de referencia de la ciudad de Salvador. Las mujeres representaban la mayor parte de los pacientes registrados en los centros y eran mayores y tenían más educación que los hombres. Más del 90,0% de los pacientes son solteros, lo que demuestra la dificultad de las personas con anemia falciforme para socializar debido al estigma de la enfermedad. Las manifestaciones clínicas más frecuentes fueron crisis de dolor e ictericia, y las complicaciones más frecuentes fueron hospitalizaciones por crisis de dolor y transfusión de sangre. Se observaron asociaciones entre sexo y accidente cerebrovascular, entre genotipo y úlceras de miembros inferiores y transfusión de sangre. También se observó un bajo porcentaje de pacientes con osteonecrosis (8,8%), lo que indica un posible subregistro. Los bajos porcentajes de pacientes que utilizan morfina e hidroxiurea apuntan a la necesidad de ampliar la oferta de estos fármacos para reducir las crisis de dolor y mejorar la calidad de vida de los pacientes.

A centralização do atendimento dos pacientes com doenças falciformes através da criação de centros de referência possibilitou um melhor acompanhamento desses pacientes. Este estudo caracterizou o perfil sociodemográfico e clínico dos pacientes com doenças falciformes atendidos nos centros de referência no município de Salvador. Os resultados deste estudo corroboram com a literatura e podem ajudar a melhorar os serviços oferecidos nos centros de referência pesquisados. As mulheres representaram a maior parcela dos pacientes registrados nos centros e com maior faixa etária e escolaridade do que os homens. Mais de 90,0% dos pacientes são solteiros, demonstrando a dificuldade das pessoas com doenças falciformes se socializarem devido ao estigma da doença. As manifestações clínicas mais comuns foram as crises álgicas e a icterícia e as intercorrências mais comuns foram internações devido as crises álgicas e hemotransfusão. Foram observadas associações entre sexo e acidente vascular cerebral, entre o genótipo e úlceras de membros inferiores e hemotransfusão. Também foi observado um percentual baixo de pacientes com osteonecrose indicando possível subnotificação. Os percentuais baixos de pacientes que fazem uso da morfina e hidroxiureia apontam para a necessidade de ampliar a oferta desses medicamentos para diminuir as crises álgicas e melhorar a qualidade de vida dos pacientes.

Epidemiological profile of breast cancer in a reference hospital in the north region / Perfil epidemiológico do câncer de mama em hospital de referência da Região Norte

Introduction: Breast cancer is a public health issue, not only in underdeveloped countries, as is the case of Brazil, but also in developed ones, such as the United States and some Western European countries. The frequency of distribution of different types of cancer varies according to the characteristics of each region, which emphasizes the need to study geographical variations, risk factors, and disease patterns that pervade regional particularities. Objective: The present study describes the epidemiological profile of patients treated at a reference cancer hospital in the North Region of the country and determines the variables of clinical and epidemiological interest related to risk factors for breast cancer. Methods: This is a cross-sectional descriptive study conducted through interviews and analysis of medical records of 114 patients treated at Hospital Ophir Loyola between 2016 and 2017 in the city of Belém, Pará. Data were presented as absolute and relative frequencies. Results: Most women who participated in the study were multiracial, overweight, with a mean age of 51 years, and had low schooling. A little over half of them were born in the inland of the state; the majority lived in the metropolitan area of Belém, 42% in the inland, and only 11% in the countryside. The mean interval between clinical suspicion and diagnostic confirmation was almost 13 months. The most frequent histopathological classification was invasive ductal carcinoma, and the immunohistochemical profile with the higher incidence was luminal B, followed by luminal A. Conclusions: Overweight, considered a risk factor for breast cancer, is modifiable, which underlines the importance of awareness actions for early diagnosis, knowledge of the disease, and encouragement to physical activity and healthy eating habits, in order to reduce morbidity and mortality, and improve the prognosis of women affected by this pathology

Introdução: O câncer de mama é um problema de saúde pública não só em países subdesenvolvidos, como é o caso do Brasil, mas também nos desenvolvidos, como Estados Unidos e alguns países da Europa Ocidental. A frequência de distribuição dos diferentes tipos de câncer é variável em função das características de cada região, o que enfatiza a necessidade do estudo das variações geográficas, dos fatores de risco e dos padrões dessa doença que perpassam pelas particularidades regionais. Objetivo: O presente estudo descreve o perfil epidemiológico das pacientes atendidas no hospital de referência em oncologia da região Norte do país e determina as variáveis de interesse clínico e epidemiológico que se relacionam aos fatores de risco na ocorrência do câncer de mama. Métodos: O e studo é t ransversal e descritivo, realizado p or meio de entrevista e análise de prontuários clínicos de 114 p acientes atendidas no Hospital Ophir Loyola entre os anos de 2016 e 2017, no município de Belém, no estado do Pará. Os dados foram apresentados em forma de frequências absoluta e relativa. Resultados: A maioria das mulheres pesquisadas era parda, com média de idade de 51 anos, encontrava-se acima do peso e apresentava baixa escolaridade. Um pouco mais da metade era natural do interior do estado, e a maioria era procedente da região metropolitana de Belém, 42% delas vinham do interior e apenas 11% residiam em zona rural. A média de tempo entre a suspeita clínica e a confirmação diagnóstica foi de quase 13 meses. A classificação histopatológica de maior frequência foi carcinoma ductal invasivo e o perfil imunohistoquímico de maior ocorrência foi o luminal B, seguido de luminal A. Conclusões: O sobrepeso, considerado fator de risco para o câncer de mama, é passível de modificação, o que evidencia a importância de ações de esclarecimento sobre detecção precoce, conhecimento da doença e incentivo à prática de exercício físico e alimentação saudável, a fim de reduzir a morbidade e mortalidade, melhorando o prognóstico das mulheres acometidas por essa patologia

Does Transcranial Direct Current Stimulation Combined with Peripheral Electrical Stimulation Have an Additive Effect in the Control of Hip Joint Osteonecrosis Pain Associated with Sickle Cell Disease? A Protocol for a One-Session Double Blind, Block-Randomized Clinical Trial.

Chronic pain in Sickle Cell Disease (SCD) is probably related to maladaptive plasticity of brain areas involved in nociceptive processing. Transcranial Direct Current Stimulation (tDCS) and Peripheral Electrical Stimulation (PES) can modulate cortical excitability and help to control chronic pain. Studies have shown that combined use of tDCS and PES has additive effects. However, to date, no study investigated additive effects of these neuromodulatory techniques on chronic pain in patients with SCD. This protocol describes a study aiming to assess whether combined use of tDCS and PES more effectively alleviate pain in patients with SCD compared to single use of each technique. The study consists of a one-session double blind, block-randomized clinical trial (NCT02813629) in which 128 participants with SCD and femoral osteonecrosis will be enrolled. Stepwise procedures will occur on two independent days. On day 1, participants will be screened for eligibility criteria. On day 2, data collection will occur in four stages: sample characterization, baseline assessment, intervention, and post-intervention assessment. These procedures will last ~5 h. Participants will be divided into two groups according to homozygous for S allele (HbSS) (n = 64) and heterozygous for S and C alleles (HbSC) (n = 64) genotypes. Participants in each group will be randomly assigned, equally, to one of the following interventions: (1) active tDCS + active PES; (2) active tDCS + sham PES; (3) sham tDCS + active PES; and (4) sham tDCS + sham PES. Active tDCS intervention will consist of 20 min 2 mA anodic stimulation over the primary motor cortex contralateral to the most painful hip. Active PES intervention will consist of 30 min sensory electrical stimulation at 100 Hz over the most painful hip. The main study outcome will be pain intensity, measured by a Visual Analogue Scale. In addition, electroencephalographic power density, cortical maps of the gluteus maximus muscle elicited by Transcranial Magnetic Stimulation (TMS), serum levels of Brain-derived Neurotrophic Factor (BDNF), and Tumor Necrosis Factor (TNF) will be assessed as secondary outcomes. Data will be analyzed using ANOVA of repeated measures, controlling for confounding variables.

Características de los menores de 12 años con examen médico forense por sospecha de abuso sexual en Salvador, Brasil / Characteristics of children under 12 years subjected to forensic examination on suspicion of child sexual abuse in Salvador Brazil

Objetivo. Describir las características demográficas y clínicas de la población de menores de 12 años sometidos a pericia de sexología forense y la proporción de los casos confirmados de abuso sexual por prueba material. Material y métodos. El diseño fue un estudio descriptivo retrospectivo. Se revisaron todos los informes de examen de sexología forense por sospecha de abuso sexual en menores de 12 años, que fueron realizados por el instituto médico-forense de Salvador, Brasil, en el periodo de 2005-2010. Resultados. En el periodo estudiado, 2.802 menores de 12 años fueron sometidos a examen de sexología forense por sospecha de abuso sexual. La edad media fue de 6,6 años (DT 3,09). Del total de menores examinados, 78,4% eran niñas. En cuanto al motivo de la pericia, en el 84,9% de los casos hubo en la historia clínica un relato de abuso sexual. En el 67,0% de los menores examinados no fue detectada ninguna alteración en el examen físico. La proporción de casos confirmados de abuso sexual por prueba material fue de 8,9% (248 casos). Conclusiones. Ante el consenso en la literatura de la pequeña proporción de falsos relatos de abuso sexual efectuados por menores, los datos encontrados en este estudio resaltan la baja sensibilidad del examen del cuerpo del delito para la confirmación de abuso sexual por prueba material y la necesidad de que esto sea comprendido por todos aquellos a quienes se destinan los informes de dichos exámenes (AU)

Objective. To describe the demographic and clinical characteristics of a population of children under 12 years submitted to forensic sexual examination and the proportion of confirmed cases of sex abuse by material evidence. Material and Methods. A retrospective descriptive study was conducted by reviewing all examination reports of forensic sexology for suspicion of child sexual abuse carried out at the forensic institute of Salvador, Brazil, between 2005 and 2010. Results. During the study period, 2802 children under 12 years with suspicion of sexual abuse were submitted for forensic examination. The mean age was 6.6 years (SD 3.09), and 78.4% were female. In 84.9% of the cases, examination was required based on previous allegations of sexual abuse. The physical examination showed no alteration in 67.0% of the children investigated. The proportion of confirmed cases of sexual abuse by material evidence was 8.9% (248 cases). Conclusion. In view of the consensus of the low proportion of false allegation of sexual abuse made by children found in the specialised literature, the data obtained in this study emphasize the low sensitivity of the forensic examination for the confirmation of sexual abuse by material evidence, as well as the need for the comprehension of this fact by all those to whom these examinations are intended (AU)

Resting blood lactate in individuals with sickle cell disease

BACKGROUND: The most common hereditary hemoglobin disorder, affecting 20 million individuals worldwide, is sickle cell disease. The vascular obstruction resulting from the sickling of cells in this disease can produce local hypoxemia, pain crises and infarction in several tissues, including the bones, spleen, kidneys and lungs. METHODS: The present study is characterized as a case control study, with the aim of identifying the baseline blood lactate concentration in individuals with hemoglobin SS and SC diseases. One-way ANOVA with the Tukey post-test was used to analyze the results and a p-value < 0.05 was considered significant. Calculations were made using the INSTAT statistical program. The graphs were generated using the ORING program. The study sample was composed of 31 men and women residing in the city of Santo Antônio de Jesus, Bahia, Brazil. The individuals were divided into two groups: Group GC of 16 subjects who did not present with any type of structural hemoglobinopathy; and Group GE composed of 15 individuals with ages between 2 and 35 years old, who had the SS and SC genotypes. Sample analyses were performed with 3 mL of blood during fasting. RESULTS: The baseline blood lactate concentration of the SS and SC individuals was higher than that of the control group (p<0.001) with means of 4.86 ± 0.95; 3.30 ± 0.33; 1.31 ± 0.08 IU/L for SS, SC and controls, respectively. This corroborates the initial research hypothesis. CONCLUSION: The baseline blood lactate of SS and SC individuals is 3 to 4 times higher than that of healthy subjects, probably due to the fact that these patients have a metabolic deviation to the anaerobic pathway.

Resting blood lactate in individuals with sickle cell disease.

BACKGROUND: The most common hereditary hemoglobin disorder, affecting 20 million individuals worldwide, is sickle cell disease. The vascular obstruction resulting from the sickling of cells in this disease can produce local hypoxemia, pain crises and infarction in several tissues, including the bones, spleen, kidneys and lungs. OBJECTIVE: To determine red blood group genes in a Brazilian populations. METHODS: The present study is characterized as a case control study, with the aim of identifying the baseline blood lactate concentration in individuals with hemoglobin SS and SC diseases. One-way ANOVA with the Tukey post-test was used to analyze the results and a p-value < 0.05 was considered significant. Calculations were made using the INSTAT statistical program. The graphs were generated using the ORING program. The study sample was composed of 31 men and women residing in the city of Santo Antônio de Jesus, Bahia, Brazil. The individuals were divided into two groups: Group GC of 16 subjects who did not present with any type of structural hemoglobinopathy; and Group GE composed of 15 individuals with ages between 2 and 35 years old, who had the SS and SC genotypes. Sample analyses were performed with 3 mL of blood during fasting. RESULTS: The baseline blood lactate concentration of the SS and SC individuals was higher than that of the control group (p<0.001) with means of 4.86 ± 0.95; 3.30 ± 0.33; 1.31 ± 0.08 IU/L for SS, SC and controls, respectively. This corroborates the initial research hypothesis. CONCLUSION: The baseline blood lactate of SS and SC individuals is 3 to 4 times higher than that of healthy subjects, probably due to the fact that these patients have a metabolic deviation to the anaerobic pathway.

Beta-globin haplotypes in normal and hemoglobinopathic individuals from Reconcavo Baiano, State of Bahia, Brazil

Five restriction site polymorphisms in the Beta-globin gene cluster (HincII-5'épsilon, HindIII-Ggama, HindIII-Agama, HincII-PsiBeta1 and HincII-3'PsiBeta1) were analyzed in three populations (n = 114) from Reconcavo Baiano, State of Bahia, Brazil. The groups included two urban populations from the towns of Cachoeira and Maragojipe and one rural Afro-descendant population, known as the "quilombo community", from Cachoeira municipality. The number of haplotypes found in the populations ranged from 10 to 13, which indicated higher diversity than in the parental populations. The haplotypes 2 (+----), 3 (----+), 4 (-+--+) and 6 (-++-+) on the BetaA chromosomes were the most common, and two haplotypes, 9 (-++++) and 14 (++--+), were found exclusively in the Maragojipe population. The other haplotypes (1, 5, 9, 11, 12, 13, 14 and 16) had lower frequencies. Restriction site analysis and the derived haplotypes indicated homogeneity among the populations. Thirty-two individuals with hemoglobinopathies (17 sickle cell disease, 12 HbSC disease and 3 HbCC disease) were also analyzed. The haplotype frequencies of these patients differed significantly from those of the general population. In the sickle cell disease subgroup, the predominant haplotypes were BEN (Benin) and CAR (Central African Republic), with frequencies of 52.9 percent and 32.4 percent, respectively. The high frequency of the BEN haplotype agreed with the historical origin of the afro-descendant population in the state of Bahia. However, this frequency differed from that of Salvador, the state capital, where the CAR and BEN haplotypes have similar frequencies, probably as a consequence of domestic slave trade and subsequent internal migrations to other regions of Brazil.

Avaliação da cobertura do programa de triagem neonatal de hemoglobinopatias em populações do Recôncavo Baiano, Brasil / Evaluation of coverage by a neonatal screening program for hemoglobinopathies in the Recôncavo region of Bahia, Brazil

Em 2001, a Portaria n. 822/2001 do Ministério da Saúde tornou obrigatória a triagem neonatal para as hemoglobinopatias, especialmente a anemia falciforme, a doença genética mais comum no Brasil. A Bahia, em decorrência de sua história de povoamento, é o Estado com maior prevalência dessa doença no país. No presente trabalho, apresentamos a cobertura da triagem neonatal (número de recém-nascidos/número de triagens realizadas) no período de 2001 a 2003 nos municípios de Cachoeira, São Félix e Maragogipe, localizados na região do Recôncavo Baiano, e a freqüência das hemoglobinas variantes HbS e HbC na população dos mesmos municípios, com exceção de São Félix. A freqüência total estimada de portadores para as duas hemoglobinas nessas populações foi de 13,0 por cento e nos recém-nascidos de 8,5 por cento em 2001, 6,5 por cento em 2002 e 11,6 por cento em 2003. A cobertura da triagem neonatal, quando se considera o período de 2001 a 2003, caiu de 82,6 por cento para 46,4 por cento no Município de Cachoeira, aumentou de 23,7 por cento para 56,2 por cento em Maragogipe e em São Félix atingiu 100 por cento. Os dados aqui apresentados apontam para a necessidade de um melhor preparo dos serviços de saúde pública na maioria dos municípios analisados do Recôncavo Baiano para a cobertura da triagem neonatal.

In 2001, government ruling n. MS 822/01 by the Brazilian Ministry of Health made neonatal screening mandatory for hemoglobinopathies, with special focus on sickle cell disease, the most common hemoglobinopathy in Brazil. Bahia is the State of Brazil with the highest prevalence of this disease. The current paper reports on the prevalence of hemoglobin variants HbS and HbC, which cause sickle cell disease, in the cities of Cachoeira, Maragogipe, and São Félix, Bahia State. The overall proportion of carriers for the two forms of hemoglobin was 13 percent. From 2001 to 2003, the neonatal screening rate decreased from 82.6 percent to 46.4 percent in Cachoeira and increased from 37.0 percent to 56.2 percent in Maragogipe. Thus, only about one-half of children are being tested in these cities. The findings show that the public health care system in these cities is poorly prepared to screen for sickle cell disease in newborns and that there was a lack of health care personnel to follow up on newly diagnosed sickle cell patients or carriers of the sickle cell trait.

[Evaluation of coverage by a neonatal screening program for hemoglobinopathies in the Recôncavo region of Bahia, Brazil]. / Avaliação da cobertura do programa de triagem neonatal de hemoglobinopatias em populações do Recôncavo Baiano, Brasil.

In 2001, government ruling n. MS 822/01 by the Brazilian Ministry of Health made neonatal screening mandatory for hemoglobinopathies, with special focus on sickle cell disease, the most common hemoglobinopathy in Brazil. Bahia is the State of Brazil with the highest prevalence of this disease. The current paper reports on the prevalence of hemoglobin variants HbS and HbC, which cause sickle cell disease, in the cities of Cachoeira, Maragogipe, and São Félix, Bahia State. The overall proportion of carriers for the two forms of hemoglobin was 13%. From 2001 to 2003, the neonatal screening rate decreased from 82.6% to 46.4% in Cachoeira and increased from 37.0% to 56.2% in Maragogipe. Thus, only about one-half of children are being tested in these cities. The findings show that the public health care system in these cities is poorly prepared to screen for sickle cell disease in newborns and that there was a lack of health care personnel to follow up on newly diagnosed sickle cell patients or carriers of the sickle cell trait.

Estudo da origem do cromossomo 21 extra em portadores de síndrome de Down / Study of the origin of extra chromosome 21 in patients with Down syndrome

A trissomia do cromossomo 21, mais conhecida como síndrome de Down, geralmente resulta da falta de disjunção cromossômica durante a meiose. A origem da não disjunção vem sendo estudada através do uso de heteromorfismos citogenéticos e pelo estudo dos polimorfismos de DNA. Pequenas seqüências repetitivas foram descritas como uma classe abundante de polimorfismos de DNA no genoma humano as quais podem ser tipadas através da técnica de reação de polimerase em cadeia (PCR). A análise destes polimorfismos provê um conhecimento maior sobre a origem e o estágio meiótico da não disjunção. Neste trabalho foram utilizados os marcadores D21S13E, D21S16 e D21S120, localizados na região pericentromérica do cromossomo 21, além do HMG14-GT2, localizado na região 21q22.3, para estudar a origem e o estágio meiótico da não disjunção do cromossomo 21 extra em 32 famílias com um filho portador de síndrome de Down. Entre estas, 7 famílias (22%) foram informativas, mostrando que a não disjunção ocorreu na meiose I, e 3 casos foram de origem materna, comprovados através do estudo do sistema HMG14-GT2. Para os outros sistemas moleculares estudados no presente trabalho, nenhuma família se mostrou informativa.