Preliminary core sets of measures for disease activity and damage assessment in juvenile systemic lupus erythematosus and juvenile dermatomyositis

Objective. To identify preliminary core sets of outcome variables for disease activity and damage assessment in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). Methods. Two questionnaire surveys were mailed to 267 physicians from 46 different countries asking each member to select and rank the response variables used when assessing clinical response in patients with JSLE or JDM. Next, 40 paediatric rheumatologists from 34 countries met and, using the nominal group technique, selected the domains to be included in the disease activity and damage core sets for JSLE and JDM. Results. A total of 41 response variables for JSLE and 37 response variables for JDM were selected and ranked through the questionnaire surveys. In the consensus conference, domains selected for both JSLE and JDM activity or damage core sets included the physician and parent/patient subjective assessments and a global score tool. Domains specific for JSLE activity were the immunological tests and the kidney function parameters. Concerning JDM, functional ability and muscle strength assessments were indicated for both activity and damage core sets, whereas serum muscle enzymes were included only in the activity core set. A specific paediatric domain called 'growth and development' was introduced in the disease damage core set for both diseases and the evaluation of health-related quality of life was advised in order to capture the influence of the disease on the patient lifestyle. Conclusions. We developed preliminary core sets of measures for disease activity and damage assessment in JSLE and JDM. The prospective validation of the core sets is in progress.

Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Qualidade de vida em portadores de esclerose múltipla

Multiple sclerosis (MS) is a chronic disease which may exert significant effects on the life of patients. Traditional outcome measures in MS lack in consider the effects of the disease on health-related quality of life (HRQoL). The goal of this study is to measure HRQoL in MS patients in the city of Uberlân-dia, State of Minas Gerais, Brazil. The Brazilian version of the SF-36 was applied in 23 MS patients and in 69 subjects of general population (blood donors) in Uberlândia. MS patients scored lower in all SF-36 scales than do the general population, principally in physical function domains. Patients with EDSS scores ≤3.5 had higher mean scores in four domains than do the patients with EDSS scores ≥4.0, and lower in all domains than control group. Depressive symptoms and heat intolerance showed correlation with SF-36 domains and components. In conclusion, MS patients have a significant negative impact on all HRQoL domains measured by SF-36, compared with general population, even in the stages with lower disability.

Impulsive compulsivity in obsessive-compulsive disorder: A phenotypic marker of patients with poor clinical outcome

Although traditionally obsessive-compulsive disorder (OCD) and impulse control disorders (ICD) have represented opposing ends of a continuum, recent research has demonstrated a frequent co-occurrence of impulsive and compulsive behaviours, which may contribute to a worse clinical picture of some psychiatric disorders. We hypothesize that individuals with 'impulsive' OCD as characterized by poor insight, low resistance, and reduced control towards their compulsions will have a deteriorative course, greater severity of hoarding and/or symmetry/ordering symptoms, and comorbid ICD and/or substance use disorders (SUD). The sample consisted of 869 individuals with a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Of these, 65 had poor insight, low resistance, and reduced control towards compulsions ('poor IRC') and 444 had preserved insight, greater resistance and better control over compulsions ('good IRC'). These two groups were compared on a number of clinical and demographic variables. Individuals with poor IRC were significantly more likely to have a deteriorative course (p < 0.001), longer duration of obsessions (p = 0.017), greater severity of symmetry/ordering (p < 0.001), contamination/cleaning (p < 0.001) and hoarding (p = 0.002) symptoms, and comorbid intermittent explosive disorder (p = 0.026), trichotillomania (p = 0.014) and compulsive buying (p = 0.040). Regression analysis revealed that duration of obsessions (p = 0.037) and hoarding severity (p = 0.005) were significant predictors of poor IRC. In the absence of specific measures for impulsivity in OCD, the study highlights the utility of simple measures such as insight, resistance and control over compulsions as a phenotypic marker of a subgroup of OCD with impulsive features demonstrating poor clinical outcome. © 2012 Elsevier Ltd.

The use of severity indexes to estimate the risk of death in Intensive Care

The Simplified Acute Physiology Score II (SAPS II) and Logistic Organ Dysfunction System (LODS) are instruments used to classify Intensive Care Unit (ICU) inpatients according to the severity of their condition and risk of death, and evaluate the quality of nursing care. The objective of this study is to evaluate and compare the performance of SAPS II and LODS to predict the mortality of patients admitted to the ICU. The participants were 600 patients from four ICUs located in Sao Paulo, Brazil. Receiver Operator Characteristic (ROC) curves were used to compare the performance of the indexes. Results: The areas under the ROC curves of LODS (0.69) and SAPS II (0.71) indicated moderate discriminatory capacity to identify death or survival. No statistically significant differences were found between these areas (p=0.26). In conclusion, there was equivalence between SAPS II and LODS to estimate the risk of death of ICU patients.

Desempenho de índices de gravidade para estimar risco de morte em Unidades de Terapia Intensiva

O Simplified Acute Physiology Score II (SAPS II) e o Logistic Organ Dysfunction System (LODS) são instrumentos utilizados para classificar pacientes internados em Unidades de Terapia Intensiva (UTI) conforme a gravidade e o risco de morte, sendo um dos parâmetros da qualidade da assistência de enfermagem. Este estudo teve por objetivo avaliar e comparar as performances do SAPS II e do LODS para predizer mortalidade de pacientes admitidos em UTI. Participaram do estudo 600 pacientes de quatro diferentes UTIs de São Paulo, Brasil. A curva Receiver Operator Characteristic (ROC) foi utilizada para comparar o desempenho discriminatório dos índices. Os resultados foram: as áreas sob a curva do LODS (0.69) e do SAPS II (0.71) apresentaram moderada capacidade discriminatória para predizer mortalidade. Não foi encontrada diferença estatisticamente significativa entre as áreas (p=0,26). Concluiu-se que houve equivalência entre SAPS II e LODS para estimar risco de morte de pacientes em UTI.

Deep gray matter atrophy in multiple sclerosis: a tensor based morphometry.

Tensor based morphometry (TBM) was applied to determine the atrophy of deep gray matter (DGM) structures in 88 relapsing multiple sclerosis (MS) patients. For group analysis of atrophy, an unbiased atlas was constructed from 20 normal brains. The MS brain images were co-registered with the unbiased atlas using a symmetric inverse consistent nonlinear registration. These studies demonstrate significant atrophy of thalamus, caudate nucleus, and putamen even at a modest clinical disability, as assessed by the expanded disability status score (EDSS). A significant correlation between atrophy and EDSS was observed for different DGM structures: (thalamus: r=-0.51, p=3.85 x 10(-7); caudate nucleus: r=-0.43, p=2.35 x 10(-5); putamen: r=-0.36, p=6.12 x 10(-6)). Atrophy of these structures also correlated with 1) T2 hyperintense lesion volumes (thalamus: r=-0.56, p=9.96 x 10(-9); caudate nucleus: r=-0.31, p=3.10 x 10(-3); putamen: r=-0.50, p=6.06 x 10(-7)), 2) T1 hypointense lesion volumes (thalamus: r=-0.61, p=2.29 x 10(-10); caudate nucleus: r=-0.35, p=9.51 x 10(-4); putamen: r=-0.43, p=3.51 x 10(-5)), and 3) normalized CSF volume (thalamus: r=-0.66, p=3.55 x 10(-12); caudate nucleus: r=-0.52, p=2.31 x 10(-7), and putamen: r=-0.66, r=2.13 x 10(-12)). More severe atrophy was observed mainly in thalamus at higher EDSS. These studies appear to suggest a link between the white matter damage and DGM atrophy in MS.

Avaliação do prognóstico com a utilização de dois escores de mortalidade em terapia intensiva pediátrica de nível de atendimento terciário

A redução da mortalidade é um objetivo fundamental das unidades de terapia intensiva pediátrica (UTIP). O estágio de gravidade da doença reflete a magnitude das comorbidades e distúrbios fisiológicos no momento da internação e pode ser avaliada pelos escores prognósticos de mortalidade. Os dois principais escores utilizados na UTIP são o Pediatric Risk of Mortality (PRISM) e o Pediatric Index of Mortality (PIM). O PRISM utiliza os piores valores de variáveis fisiológicas e laboratoriais nas primeiras 24 horas de internação enquanto o PIM2 utiliza dados da primeira hora de internação na UTIP e apenas uma gasometria arterial. Não há consenso na literatura, entre PRISM e PIM2, quanto à utilidade e padronização na admissão na terapia intensiva para as crianças e adolescentes, principalmente em uma UTI de nível de atendimento terciário. O objetivo do estudo foi estabelecer o escore de melhor performance na avaliação do prognóstico de mortalidade que seja facilmente aplicável na rotina da UTIP, para ser utilizado de forma padronizada e contínua. Foi realizado um estudo retrospectivo onde foram revisados os escores PRISM e PIM2 de 359 pacientes internados na unidade de terapia intensiva pediátrica do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP, considerada uma unidade de atendimento de nível terciário. A mortalidade foi de 15%, o principal tipo de admissão foi clinico (78%) sendo a principal causa de internação a disfunção respiratória (37,3%). Os escores dos pacientes que foram a óbito mostraram-se maiores do que o dos sobreviventes. Para o PRISM foi 15 versus 7 (p = 0,0001) e para o PIM2, 11 versus 5 (p = 0,0002), respectivamente. Para a amostra geral, o Standardized Mortality Ratio (SMR) subestimou a mortalidade tanto para o PIM2 quanto para o PRISM [1,15 (0,84 - 1,46) e 1,67 (1,23 - 2,11), respectivamente]. O teste de Hosmer-Lemeshow mostrou calibração adequada para ambos os escores [x2 = 12,96 (p = 0,11) para o PRISM e x2 = 13,7 (p = 0,09) para o PIM2]. A discriminação, realizada por meio da área sob a curva ROC, foi mais adequada para o PRISM do que para o PIM2 [0,76 (IC 95% 0,69 - 0,83) e 0,65 (IC 95% 0,57 - 0,72), respectivamente, p= 0,002]. No presente estudo, a melhor sensibilidade e especificidade para o risco de óbito do PRISM foi um escore entre 13 e 14, mostrando que, com o avanço tecnológico, o paciente precisa ter um escore mais elevado, ou seja, maior gravidade clínica do que a população original, para um maior risco de mortalidade. Os escores de gravidade podem ter seus resultados modificados em consequência: do sistema de saúde (público ou privado), da infraestrutura da UTIP (número de leitos, recursos humanos, parque tecnológico) e indicação da internação. A escolha de um escore de gravidade depende das características individuais da UTIP, como o tempo de espera na emergência, presença de doença crônica complexa (por exemplo, pacientes oncológicos) e como é realizado o transporte para a UTIP. Idealmente, estudos multicêntricos têm maior significância estatística. No entanto, estudos com populações maiores e mais homogêneas, especialmente nos países em desenvolvimento, são difíceis de serem realizados

Progression of left atrial volume index in a population at risk for heart failure:a substudy of the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) trial

AIMS: Limited data are available concerning the evolution of the left atrial volume index (LAVI) in pre-heart failure (HF) patients. The aim of this study was to investigate clinical characteristics and serological biomarkers in a cohort with risk factors for HF and evidence of serial atrial dilatation.

METHODS AND RESULTS: This was a prospective substudy within the framework of the STOP-HF cohort (NCT00921960) involving 518 patients with risk factors for HF electively undergoing serial clinical, echocardiographic, and natriuretic peptide assessment. Mean follow-up time between assessments was 15 ± 6 months. 'Progressors' (n = 39) were defined as those with serial LAVI change ≥3.5 mL/m(2) (and baseline LAVI between 20 and 34 mL/m(2)). This cut-off was derived from a calculated reference change value above the biological, analytical, and observer variability of serial LAVI measurement. Multivariate analysis identified significant baseline clinical associates of LAVI progression as increased age, beta-blocker usage, and left ventricular mass index (all P < 0.05). Serological biomarkers were measured in a randomly selected subcohort of 30 'Progressors' matched to 30 'Non-progressors'. For 'Progressors', relative changes in matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase 1 (TIMP1), and the TIMP1/MMP9 ratio, markers of interstitial remodelling, tracked with changes in LAVI over time (all P < 0.05).

CONCLUSION: Accelerated LAVI increase was found to occur in up to 14% of all pre-HF patients undergoing serial echocardiograms over a relatively short follow-up period. In a randomly selected subcohort of 'Progressors', changes in LAVI were closely linked with alterations in MMP9, TIMP1, and the ratio of these enzymes, a potential aid in highlighting this at-risk group.

Mucopolysaccharidosis Type Ii: Identification Of 30 Novel Mutations Among Latin American Patients.

In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature.

Correlation Between Cephalometric Data And Severity Of Sleep Apnea.

Obstructive sleep apnea syndrome has a high prevalence among adults. Cephalometric variables can be a valuable method for evaluating patients with this syndrome. To correlate cephalometric data with the apnea-hypopnea sleep index. We performed a retrospective and cross-sectional study that analyzed the cephalometric data of patients followed in the Sleep Disorders Outpatient Clinic of the Discipline of Otorhinolaryngology of a university hospital, from June 2007 to May 2012. Ninety-six patients were included, 45 men, and 51 women, with a mean age of 50.3 years. A total of 11 patients had snoring, 20 had mild apnea, 26 had moderate apnea, and 39 had severe apnea. The distance from the hyoid bone to the mandibular plane was the only variable that showed a statistically significant correlation with the apnea-hypopnea index. Cephalometric variables are useful tools for the understanding of obstructive sleep apnea syndrome. The distance from the hyoid bone to the mandibular plane showed a statistically significant correlation with the apnea-hypopnea index.

Central Auditory Processing Outcome After Stroke In Children.

To investigate central auditory processing in children with unilateral stroke and to verify whether the hemisphere affected by the lesion influenced auditory competence. 23 children (13 male) between 7 and 16 years old were evaluated through speech-in-noise tests (auditory closure); dichotic digit test and staggered spondaic word test (selective attention); pitch pattern and duration pattern sequence tests (temporal processing) and their results were compared with control children. Auditory competence was established according to the performance in auditory analysis ability. Was verified similar performance between groups in auditory closure ability and pronounced deficits in selective attention and temporal processing abilities. Most children with stroke showed an impaired auditory ability in a moderate degree. Children with stroke showed deficits in auditory processing and the degree of impairment was not related to the hemisphere affected by the lesion.

Whole Cortical And Default Mode Network Mean Functional Connectivity As Potential Biomarkers For Mild Alzheimer's Disease.

The search for an Alzheimer's disease (AD) biomarker is one of the most relevant contemporary research topics due to the high prevalence and social costs of the disease. Functional connectivity (FC) of the default mode network (DMN) is a plausible candidate for such a biomarker. We evaluated 22 patients with mild AD and 26 age- and gender-matched healthy controls. All subjects underwent resting functional magnetic resonance imaging (fMRI) in a 3.0 T scanner. To identify the DMN, seed-based FC of the posterior cingulate was calculated. We also measured the sensitivity/specificity of the method, and verified a correlation with cognitive performance. We found a significant difference between patients with mild AD and controls in average z-scores: DMN, whole cortical positive (WCP) and absolute values. DMN individual values showed a sensitivity of 77.3% and specificity of 70%. DMN and WCP values were correlated to global cognition and episodic memory performance. We showed that individual measures of DMN connectivity could be considered a promising method to differentiate AD, even at an early phase, from normal aging. Further studies with larger numbers of participants, as well as validation of normal values, are needed for more definitive conclusions.

Volumetric Capnography For The Evaluation Of Chronic Airways Diseases.

Obstructive lung diseases of different etiologies present with progressive peripheral airway involvement. The peripheral airways, known as the silent lung zone, are not adequately evaluated with conventional function tests. The principle of gas washout has been used to detect pulmonary ventilation inhomogeneity and to estimate the location of the underlying disease process. Volumetric capnography (VC) analyzes the pattern of CO2 elimination as a function of expired volume. To measure normalized phase 3 slopes with VC in patients with non-cystic fibrosis bronchiectasis (NCB) and in bronchitic patients with chronic obstructive pulmonary disease (COPD) in order to compare the slopes obtained for the groups. NCB and severe COPD were enrolled sequentially from an outpatient clinic (Hospital of the State University of Campinas). A control group was established for the NCB group, paired by sex and age. All subjects performed spirometry, VC, and the 6-Minute Walk Test (6MWT). Two comparisons were made: NCB group versus its control group, and NCB group versus COPD group. The project was approved by the ethical committee of the institution. Statistical tests used were Wilcoxon or Student's t-test; P<0.05 was considered to be a statistically significant difference. Concerning the NCB group (N=20) versus the control group (N=20), significant differences were found in body mass index and in several functional variables (spirometric, VC, 6MWT) with worse results observed in the NCB group. In the comparison between the COPD group (N=20) versus the NCB group, although patients with COPD had worse spirometric and 6MWT values, the capnographic variables mean phase 2 slope (Slp2), mean phase 3 slope normalized by the mean expiratory volume, or mean phase 3 slope normalized by the end-tidal CO2 concentration were similar. These findings may indicate that the gas elimination curves are not sensitive enough to monitor the severity of structural abnormalities. The role of normalized phase 3 slope may be worth exploring as a more sensitive index of small airway disease, even though it may not be equally sensitive in discriminating the severity of the alterations.

Musculoskeletal Evaluation In Severe Haemophilia A Patients From Latin America.

There is a paucity of literature on haemophilia treatment in Latin American countries, a region characterized by rapidly improving systems of care, but with substantial disparities in treatment between countries. The aim of this study was to evaluate the musculoskeletal status of haemophilia patients from Latin America and to examine the relationship between musculoskeletal status and treatment practices across countries. The Committee of Latin America on the Therapeutics of Inhibitor Groups conducted a survey of its member country representatives on key aspects of haemophilia treatment in 10 countries. Musculoskeletal status of patients was obtained during routine comprehensive evaluations between March 2009 and March 2011. Eligible patients had severe haemophilia A (factor VIII <1%) without inhibitors (<0.6 BU mL(-1) ) and were ≥5 years of age. Musculoskeletal status was compared between three groups of countries, based primarily on differences in the availability of long-term prophylaxis. Overall, 143 patients (5-66 years of age) were enrolled from nine countries. In countries where long-term prophylaxis had been available for at least 10 years (Group A), patients aged 5-10 years had significantly better mean World Federation of Hemophilia clinical scores, fewer target joints and fewer affected joints than patients from countries where long-term prophylaxis has been available for about 5 years (Group B) or was not available (Group C). In Latin America, the musculoskeletal status of patients with severe haemophilia without inhibitors has improved significantly in association with the provision of long-term prophylaxis. As more countries in Latin America institute this practice, further improvements are anticipated.