RESUMEN
Computed tomography (CT) is commonly used for paediatric thoracic diseases but involves radiation exposure and often requires intravenous contrast. We evaluated the performance of a magnetic resonance imaging (MRI) protocol including a 3D zero echo time (3D-ZTE) sequence for radiation-free and contrast-free imaging of the paediatric chest. In this prospective, single-centre study, children aged 6-16 years underwent chest CT and MRI within 48 h. CT and MRI exams were independently assessed by two paediatric radiologists. The primary outcome was the image quality of the 3D-ZTE sequence using a scoring system based on the acceptability of the images obtained and visibility of bronchial structures, vessels and fissures. Secondary outcomes included radiologists' ability to detect lung lesions on 3D-ZTE MRI images compared with CT images. Seventy-two children were included. Overall, the image quality achieved with the 3D-ZTE MRI sequence was inferior to that of CT for visualising pulmonary structures, with satisfactory lung image quality observed for 81.9% (59/72) and 100% (72/72) of patients, respectively. However, MRI sensitivity was excellent (above 90%) for the detection of certain lesions such as lung consolidation, proximal mucoid impactions, pulmonary cysts, ground glass opacities and honeycombing. Intermodality agreement (MRI versus CT) was consistently higher for the senior reader compared to the junior reader. CONCLUSION: Despite its overall lower image quality compared to CT, and the additional years of experience required for accurate interpretation, the 3D-ZTE MRI sequence demonstrated excellent sensitivity for several lesions, making it an appropriate imaging method in certain indications. WHAT IS KNOWN: ⢠Chest radiography and CT are the main imaging modalities for paediatric thoracic diseases but involve radiation exposure and CT often requires IV contrast. ⢠MRI is promising for radiation-free lung imaging in children but faces challenges of low signal-to-noise ratio and motion artefacts. WHAT IS NEW: ⢠An MRI protocol including a 3D zero echo time (ZTE) sequence allows satisfactory visualisation of lung parenchyma in 82% of children. ⢠Despite overall inferior image quality compared to CT, MRI demonstrated excellent sensitivity for several lesions, making it an appropriate imaging method in certain indications.
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Plasma histamine levels are increased in patients with sickle cell disease (SCD), potentially promoting endothelial P-selectin expression and vaso-occlusion via histamine type 2 (H2) receptors. We conducted a prospective, non-comparative, single-centre study to determine whether famotidine, a H2 receptor antagonist, reduces P-selectin expression in SCD children. The median plasma P-selectin level was significantly reduced after 29 days of oral famotidine (53.2 ng/mL [IQR: 46.7-63.4] vs. 69.9 ng/mL [IQR: 53.6-84.2], median difference -10.2 ng/mL [IQR: -21.8 to -2.7], p = 0.005) in 28 patients. No effect was observed on other adhesion molecules, inflammation or haemolysis markers, except decreased reticulocyte count. No adverse events deemed related to famotidine were observed. Randomized controlled trials are now needed to assess the efficacy of famotidine in preventing vaso-occlusion in SCD.
Asunto(s)
Anemia de Células Falciformes , Famotidina , Niño , Humanos , Famotidina/uso terapéutico , Selectina-P/metabolismo , Histamina , Estudios ProspectivosRESUMEN
Background: Robotic-assisted laparoscopic pyeloplasty (RALP) has been gaining acceptance among paediatric urologists. Objective: To compare surgical variables and clinical outcomes, including complications and success rate, with RALP using the transperitoneal (T-RALP) and retroperitoneal (R-RALP) approaches. Design setting and participants: We performed a multicentre, prospective, cohort study (NCT03274050) between November 2016 and October 2021 in three paediatric urology teaching centres (transperitoneal approach, n = 2; retroperitoneal approach, n = 1). The diagnosis of ureteropelvic junction obstruction (UPJO) was confirmed by renal ultrasound and mercaptoacetyltriglycine-3 renal scan or uro-magnetic resonance imaging with functional evaluation. The exclusion criteria were children <2 yr old, persistent UPJO after failed pyeloplasty, and horseshoe and ectopic kidney. Intervention: We performed dismembered pyeloplasty using running monofilament 6-0 absorbable suture. Outcome measurements and statistical analysis: We assessed intra- and postoperative morbidity (primary outcome) and success (secondary outcome). Data were expressed as medians and interquartile range (25th and 75th percentiles) for quantitative variables, and analysed comparatively. Results and limitations: We operated on 106 children (T-RALP, n = 53; R-RALP, n = 53). Preoperative data were comparable between groups (median age 9.1 [6.2-11.2] yr; median weight 26.8 [21-40] kg). Set-up time (10 vs 31 min), anastomotic time (49 vs 73 min), and console time (97 vs 153 min) were significantly shorter with T-RALP than with R-RALP (p < 0.001). No intraoperative complications occurred. No conversion to open surgery was necessary. The median hospital stay was longer after T-RALP (2 d) than after R-RALP (1 d; p < 0.001). Overall, postoperative complication rates were similar. No failure had occurred at the mean follow-up of 25.4 (15.1-34.7) mo. Conclusions: In selected children, RALP is safe and effective using either the transperitoneal or the retroperitoneal approach, with a shorter hospital stay after R-RALP. Patient summary: In our multicentre, prospective study, we compared the results and complications of robotic-assisted laparoscopic pyeloplasty (RALP) using the transperitoneal and retroperitoneal approaches. We found that RALP is safe and effective using either approach, with a shorter hospital stay after R-RALP.
RESUMEN
BACKGROUND: Childhood cancer survival currently exceeds 80 % five years after diagnosis in high-income countries. In this study, we aimed to describe long-term trends and to investigate socioeconomic and spatial disparities in childhood cancer survival. METHODS: The study included 28,073 cases recorded in the French National Registry of Childhood Cancers from 2000 to 2015. Contextual census data (deprivation indices, population density, spatial accessibility to general practitioners) were allocated to each case based on the residence at diagnosis. Overall survival (OS) and conditional 10-year OS for 5-year survivors were estimated for all cancers combined and by diagnostic group and subgroup. Comparisons were conducted by sex, age at diagnosis, period of diagnosis, and contextual indicators. Hazard ratios for death were estimated using Cox models. RESULTS: All cancers combined, the OS reached 82.8 % [95 % CI: 82.4-83.3] at 5 years and 80.8 % [95 % CI: 80.3-81.3] at 10 years. Conditional 10-year OS of 5-year survivors reached 97.5 % [95 % CI: 97.3-97.7] and was higher than 95 % for all subgroups except osteosarcomas and most subgroups of the central nervous system. In addition to disparities by sex, age at diagnosis, and period of diagnosis, we observed a slight decrease in survival for cases living in the most deprived areas at diagnosis, not consistent across diagnostic groups. CONCLUSION: Our results confirm the high 5-year survival for childhood cancer and show an excellent 10-year conditional survival of 5-year survivors. Additional individual data are needed to clarify the factors underlying the slight decrease in childhood cancer survival observed in the most deprived areas.
Asunto(s)
Supervivientes de Cáncer , Neoplasias , Supervivientes de Cáncer/estadística & datos numéricos , Niño , Estudios de Cohortes , Femenino , Francia/epidemiología , Humanos , Masculino , Neoplasias/mortalidad , Sistema de Registros , Factores Socioeconómicos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Although studies have consistently found an association between childhood leukaemia risk and magnetic fields, the associations between childhood leukaemia and distance to overhead power lines have been inconsistent. We pooled data from multiple studies to assess the association with distance and evaluate whether it is due to magnetic fields or other factors associated with distance from lines. METHODS: We present a pooled analysis combining individual-level data (29,049 cases and 68,231 controls) from 11 record-based studies. RESULTS: There was no material association between childhood leukaemia and distance to nearest overhead power line of any voltage. Among children living < 50 m from 200 + kV power lines, the adjusted odds ratio for childhood leukaemia was 1.33 (95% CI: 0.92-1.93). The odds ratio was higher among children diagnosed before age 5 years. There was no association with calculated magnetic fields. Odds ratios remained unchanged with adjustment for potential confounders. CONCLUSIONS: In this first comprehensive pooled analysis of childhood leukaemia and distance to power lines, we found a small and imprecise risk for residences < 50 m of 200 + kV lines that was not explained by high magnetic fields. Reasons for the increased risk, found in this and many other studies, remains to be elucidated.
Asunto(s)
Suministros de Energía Eléctrica/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Leucemia/epidemiología , Campos Magnéticos/efectos adversos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Leucemia/etiología , Leucemia/patología , Masculino , Características de la Residencia , Factores de RiesgoRESUMEN
BACKGROUND: Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. METHODS: AL cases diagnosed over 1990-2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002-2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. RESULTS: AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. CONCLUSIONS: Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland.
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Radiación de Fondo , Leucemia Inducida por Radiación/epidemiología , Exposición a la Radiación/estadística & datos numéricos , Niño , Femenino , Francia/epidemiología , Rayos gamma , Vivienda/estadística & datos numéricos , Humanos , Masculino , Radiación Ionizante , Radón , Medición de RiesgoRESUMEN
BACKGROUND: Socio-economic status is related to many life style and environmental factors, some of which have been suggested to influence the risk of childhood cancer. Studies requiring subject participation are usually hampered by selection of more educated parents. To prevent such bias, we used unselected nationwide Geographical Information System (GIS)-based registry data, to investigate the influence of socio-economic disparities on the risk of childhood cancer. METHODS: The Geocap study included all French residents diagnosed with cancer aged up to 15 years over the period 2002-2010 (15 111 cases) and 45 000 contemporaneous controls representative of the childhood population. Area socio-economic characteristics used to calculate the European Deprivation Index (EDI) were based on census data collected on the fine scale of the Merged Islet for Statistical Information (IRIS). RESULTS: Overall, the risk of acute lymphoblastic leukaemia (ALL) was lower in the most deprived quintile than in the other quintiles of EDI (ORQ5vsAsunto(s)
Neoplasias/epidemiología
, Adolescente
, Distribución por Edad
, Estudios de Casos y Controles
, Niño
, Preescolar
, Francia/epidemiología
, Humanos
, Lactante
, Recién Nacido
, Estilo de Vida
, Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología
, Sistema de Registros
, Características de la Residencia/estadística & datos numéricos
, Factores de Riesgo
, Salud Rural/estadística & datos numéricos
, Factores Socioeconómicos
, Salud Urbana/estadística & datos numéricos
RESUMEN
Childhood leukemia may be associated with traffic-related environmental exposure to benzene, and additional data are needed. The Géolocalisation des Cancers Pédiatriques (GEOCAP) Study, a nationwide French case-control study, was designed to avoid selection bias due to differential participation and misclassification. The study compared the 2,760 childhood leukemia cases diagnosed in France between 2002 and 2007 (including 2,275 cases of acute lymphoblastic leukemia (ALL) and 418 cases of acute myeloblastic leukemia (AML)) with 30,000 contemporaneous child population controls. The residence addresses were precisely geocoded, and 3 indicators of residential proximity to traffic were considered. Estimates of benzene concentrations were also available for the Île-de-France region (including Paris). A 300-m increase in major road length within 150 m of the geocoded address was significantly associated with AML (odds ratio = 1.2, 95% confidence interval: 1.0, 1.4) but not with ALL (odds ratio = 1.0, 95% confidence interval: 0.9, 1.1), and the association was reinforced in the Île-de-France region when this indicator was combined with benzene estimates. These results, which were free from any participation bias and based on objectively determined indices of exposure, showed an increased incidence of AML associated with heavy-traffic road density near a child's home. The results support a role for traffic-related benzene exposure in the etiology of childhood AML.
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Contaminación del Aire/efectos adversos , Benceno/toxicidad , Carcinógenos/toxicidad , Leucemia Mieloide Aguda/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Características de la Residencia/estadística & datos numéricos , Emisiones de Vehículos/toxicidad , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Francia/epidemiología , Vivienda/estadística & datos numéricos , Humanos , Incidencia , Lactante , Leucemia Mieloide Aguda/inducido químicamente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/inducido químicamente , Medición de Riesgo , Factores de Riesgo , Población Urbana/estadística & datos numéricosRESUMEN
PURPOSE: Few studies have investigated the relationship between solar ultraviolet radiation (UV) and childhood hematological malignancies (CHM). This study addresses the associations between residential UV exposure at diagnosis and the incidence of types and subtypes of CHM, by age and gender, in France, over a long period, on the fine scale of the 36,326 Communes that constitute mainland France. METHODS: The 9,082 cases of acute leukemia and 3,563 cases of lymphoma diagnosed before the age of 15 years from 1990 to 2009 were provided by the French National Registry of Childhood Hematological Malignancies. The incidence of CHM was calculated by Commune, year, age and gender and expressed as the standardized incidence ratio (SIR). UV data from 1988 to 2007 were extracted from the EUROSUN database. RESULTS: The annual daily average UV exposure of the children ranged from 85.5 to 137.8 J/cm(2). For each additional 25 J/cm(2), there was a significant increase in precursor B-cell acute lymphoblastic leukemia (PBC-ALL) in children aged less than 5 years (SIR 1.18; 95% CI 1.10-1.27). Further analysis of PBC-ALL in the young children suggested a better fit of models with a threshold, with the risk increasing above 100 J/cm(2), for which the SIR was 1.24 (95% CI 1.14-1.36) for a 25 J/cm(2) increase. The results remained stable in analyses stratifying by deprivation index or degree of urbanization of the Communes. CONCLUSION: The study suggests that higher residential UV exposure may be positively associated with a higher incidence of PBC-ALL in early childhood.
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Leucemia/epidemiología , Linfoma/epidemiología , Rayos Ultravioleta/efectos adversos , Adolescente , Niño , Preescolar , Femenino , Francia/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Leucemia/etiología , Linfoma/etiología , Masculino , Sistema de RegistrosRESUMEN
OBJECTIVE: To assess the diagnostic accuracy of portable polygraphy (PG) for the detection of sleep apnea (SA) in multiple system atrophy (MSA). METHODS: Thirty consecutive patients with probable MSA underwent PG (overnight recording of nasal flow, thoracic/abdominal movements and pulse oximetry), followed 4 weeks later by full polysomnography (PSG) (reference standard). The accuracy of PG was first assessed using the same threshold as for PSG (apnea-hypopnea index [AHI]≥5), then for all possible AHI thresholds using the area under the receiver operating characteristics (AUROC) curve. Inter-rater reliability of PG was assessed using the kappa coefficient. RESULTS: Among 30 patients enrolled, seven were excluded for technical problems on PG or PSG and 23 were included in the main analysis. Eight out of 23 had an AHI≥5 on PSG. With the same threshold, sensitivity, specificity, positive and negative predictive values of PG for the diagnosis of SA were 87.5% (95% confidence interval: 47-99), 80% (52-96), 70% (35-93) and 92.3% (64-99), respectively. The kappa between PG raters was 0.75 (0.49-1.00) indicating good agreement. The AUROC was 0.93 (0.82-1.00). No association was found between sleep and excessive daytime sleepiness questionnaires and SA. CONCLUSION: Portable PG seems to be valuable for ruling out SA in MSA.
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Monitoreo Ambulatorio/instrumentación , Atrofia de Múltiples Sistemas/diagnóstico , Polisomnografía/instrumentación , Apnea Obstructiva del Sueño/diagnóstico , Anciano , Trastornos de Somnolencia Excesiva/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
BACKGROUND: Mycoplasma pneumoniae has been implicated in asthma exacerbations and chronic asthma. A 2-year longitudinal study has been conducted to investigate the role of M. pneumoniae infections in 168 and 20 hospitalized children and adults, respectively, with asthma exacerbation compared with outpatients (88 children and 48 adults) with chronic asthma (without an exacerbation). The prevalence of Chlamydia pneumoniae and respiratory viruses was also assessed in these 2 populations. METHODS: Lung function testing, blood sampling and microbiological testing (polymerase chain reaction, culture and serology) were performed for 256 children and 68 adults followed by a 7-week, follow-up visit with repeated blood sampling for serological testing and phone interviews at 6 and 12 months later. RESULTS: M. pneumoniae infection was more prevalent in children with chronic asthma (13.6%) compared with children with exacerbation (7.1%), while the reverse was true in adults (6.3 vs. 10.0%, respectively). However, these differences were not statistically significant. Acute C. pneumoniae infection was identified in 3.9% of children and 7.4% adults. Children seen for chronic asthma were significantly more likely to be infected with C. pneumoniae than children hospitalized for an asthma exacerbation. Viruses were the most prevalent microorganisms detected in children with an asthma exacerbation. No differences in the outcome parameters were identified between M. pneumoniae-infected and noninfected patients. CONCLUSIONS: The present study suggests that M. pneumoniae does not play a direct role in the pathogenicity of acute or chronic asthma in most children.
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Asma , Neumonía por Mycoplasma/complicaciones , Neumonía por Mycoplasma/epidemiología , Adulto , Asma/complicaciones , Asma/epidemiología , Asma/microbiología , Niño , Infecciones por Chlamydophila/complicaciones , Infecciones por Chlamydophila/epidemiología , Enfermedad Crónica , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mycoplasma pneumoniae , Neumonía por Mycoplasma/terapia , Prevalencia , Virosis/complicaciones , Virosis/epidemiologíaRESUMEN
BACKGROUND: There is limited data regarding factors influencing the respiratory outcome at school age of ex-preterms born since the introduction of antenatal steroids, surfactant replacement together with less aggressive ventilation. OBJECTIVES: To establish the main antenatal, neonatal and early childhood respiratory correlates of respiratory status in school-aged children born at ≤ 32 weeks of gestation. METHODS: Ex-preterm children born at ≤ 32 weeks of gestation between 1997 and 2001 at Bordeaux University Hospital were evaluated at school age, using a respiratory questionnaire and lung function tests (spirometry, plethysmography, exercise challenge test and CO lung diffusing capacity DLCO measurements). Factors associated with lung function were investigated using polynomial regression analyses. RESULTS: Of the 151 included children [mean age: 8.6 ± 0.8 years; mean gestational age, 30.1 ± 1.7 weeks; mean birth weight = 1310 ± 380 g; 68.2% ventilated at birth; 46.4% treated with surfactant; 36.4% with prior bronchopulmonary dysplasia (BPD)], 47% presented obstructive lung abnormalities, 11% restrictive or mixed lung abnormalities, 41% exercise-induced bronchoconstriction, and 15.5% reduced DLCO. Surfactant therapy was independently associated with a lower risk of lung abnormalities (p < 0.05). The association between BPD and lung abnormalities at school age was not significant, but prior BPD increased the risk of restrictive or mixed abnormalities (odds ratio: 6.11, confidence interval [1.1; 33.99]). Early childhood respiratory events were not associated with the occurrence of lung abnormalities. CONCLUSION: Children born at ≤ 32 weeks of gestation remain at risk for impaired lung function at school age in particular when they did not receive surfactant. Restrictive or mixed lung defects are mainly associated with prior BPD.
Asunto(s)
Recien Nacido Prematuro/fisiología , Trastornos Respiratorios/fisiopatología , Asma Inducida por Ejercicio/fisiopatología , Displasia Broncopulmonar/fisiopatología , Niño , Femenino , Edad Gestacional , Humanos , Recién Nacido , Enfermedades Pulmonares Obstructivas/fisiopatología , Masculino , Surfactantes Pulmonares/uso terapéutico , Pruebas de Función Respiratoria , Ruidos Respiratorios/fisiología , Estudios Retrospectivos , Esteroides/uso terapéuticoRESUMEN
OBJECTIVES: Large unselected studies on representative samples of HIV-infected patients with a whole battery of neuropsychological tests and cerebral MRI scan are required to assess the frequency of neurocognitive impairment (NCI), the determinants of mild neurocognitive disorders (MNDs), or HIV-associated dementia (HAD) and the relationship between NCI and MRI scan findings. METHODS: Investigation of 400 consecutively enrolled HIV-1-infected adults from the ANRS CO3 Aquitaine Cohort, using standardized neurocognitive tests chosen to achieve consistency with Frascati's criteria. Half of the patients had a cerebral MRI scan allowing gray and white matter volume measurement. Factors associated with NCI were studied by logistic regression models. RESULTS: Median age of participants was 47 years, 79% were male and 89% received combination antiretroviral treatment (cART), of whom 93% had plasma HIV RNA below 500 copies/ml. Median CD4 cell count was 515 cells/µl. Prevalence of NCI was 59%, including 21% of asymptomatic NCI, 31% of MND, and 7% of HAD. A low level of education, prior neurologic AIDS-defining disorders event, anxiety, depressive symptoms, and prior history of brain damage were independently associated with MND or HAD, but neither HIV nor cART-related variables. The presence of NCI was significantly associated with lower gray matter fraction. INTERPRETATION: In this large unselected cohort, a high prevalence of symptomatic neurocognitive disorders was mainly related to its traditional determinants and associated with gray matter atrophy at early stages of the disease.
Asunto(s)
Complejo SIDA Demencia/patología , Encéfalo/patología , Trastornos del Conocimiento/patología , Infecciones por VIH/patología , Complejo SIDA Demencia/epidemiología , Terapia Antirretroviral Altamente Activa , Atrofia , Índice de Masa Corporal , Encéfalo/virología , Recuento de Linfocito CD4 , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/virología , Femenino , Estudios de Seguimiento , Francia/epidemiología , Infecciones por VIH/epidemiología , Humanos , Modelos Logísticos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Prevalencia , ARN Viral/sangre , ARN Viral/aislamiento & purificación , Encuestas y CuestionariosRESUMEN
BACKGROUND: Multiple system atrophy (MSA) has considerable effect on health-related quality of life (Hr-QoL). The aim of this study was to prospectively evaluate Hr-QoL by using the MSA health-related Quality of Life (MSA-QoL) scale. METHODS: Evaluation of 100 patients at baseline and after a mean follow-up of 11.5 months was performed. Assessment was made of potential associations with established markers of disease progression. Calculation was performed of sample-size estimates for various effect sizes. RESULTS: MSA-QoL scale scores were less responsive to change than Unified MSA Rating Scale (UMSARS) scores. Responsiveness was largely improved and reasonable sample-size estimates were obtained when limiting the analysis to items with significant change over time. CONCLUSIONS: The UMSARS remains the "gold standard" for disease-modifying/neuroprotection trials. An MSA-QoL Change Scale, based on the most responsive items, may become a valuable tool.
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Atrofia de Múltiples Sistemas/diagnóstico , Atrofia de Múltiples Sistemas/psicología , Calidad de Vida , Anciano , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
CONTEXT: The link between C-reactive protein (CRP) and adiposity deserves to be further explored, considering the controversial diabetogenic role of CRP. OBJECTIVE: We explored the potential causal role of CRP on measures of adiposity. DESIGN: We used a Mendelian randomization approach with the CRP and LEPR genes as instrumental variables in a cross-sectional Caucasian population-based study comprising 2526 men and 2836 women. Adiposity was measured using body mass index (BMI), fat and lean mass estimated by bioelectrical impedance, and waist circumference. RESULTS: Log-transformed CRP explained by the rs7553007 single-nucleotide polymorphism tagging the CRP gene was significantly associated with BMI [regression coefficient: 1.22 (0.18; 2.25), P = 0.02] and fat mass [2.67 (0.65; 4.68), P = 0.01] but not with lean mass in women, whereas no association was found in men. Log-transformed CRP explained by the rs1805096 LEPR single-nucleotide polymorphism was also positively associated, although not significantly, with BMI or fat mass. The combined CRP-LEPR instrument explained 2.24 and 0.77% of CRP variance in women and men, respectively. Log-transformed CRP explained by this combined instrument was significantly associated with BMI [0.98 (0.32; 1.63), P = 0.004], fat mass [2.07 (0.79; 3.34), P = 0.001], and waist [2.09 (0.39; 3.78), P = 0.01] in women but not men. CONCLUSION: Our data suggest that CRP is causally and positively related to BMI in women and that this is mainly due to fat mass. Results on the combined CRP-LEPR instrument suggest that leptin may play a role in the causal association between CRP and adiposity in women. Results in men were not significant.