The paradoxical relationship between severity of cerebral palsy and renal function in middle-aged adults: better renal function or inappropriate clinical assessment?

PURPOSE: To determine the association between severity of cerebral palsy with serum creatinine (sCr) and sCr-based equations to estimate glomerular filtration rate (eGFR), a marker of renal function. METHODS: A clinic-based sample of 30-64 year-olds with cerebral palsy was examined and stratified by motor impairment: gross motor function classification system (GMFCS) I/II (n = 79), GMFCS III (n = 78), and GMFCS IV/V (n = 137). sCr, which is influenced by muscle mass, was obtained and sCr-based eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. RESULTS: sCr was lower with increasing GMFCS. The opposite pattern was observed for eGFR: GMFCS IV/V had significantly higher eGFR derived from MDRD compared to other GMFCS groups; GMFCS III had significantly higher eGFR compared to GMFCS I/II. The pattern was similar for CKD-EPI derived eGFR. CONCLUSIONS: According to widely used clinical assessment methods for renal function, higher severity of cerebral palsy among adults is associated with better renal function, which is incongruent with their other biological systems. This paradoxical relationship is likely driven by lower muscle rather than true renal function, and thus, sCr-based eGFR may overestimate renal function, especially for GMFCS IV/V. Further prospective studies are needed.Implications for rehabilitationCommon methods of clinical assessment may over-estimate renal function for adults with cerebral palsy (CP), potentially giving a false positive for normal renal health due to their reliance on muscle mass.This study of a clinic-based sample of middle-aged adults with CP highlights the paradoxical relationship between severity of CP and renal function, which is likely driven by methodological limitations in the presence of low muscle mass rather than actual better renal function.It is recommended that clinicians have a high suspicion of abnormal renal function and the need for a nephrology consultation, especially with changes in creatinine levels, even within the normal range.Rehabilitation for adults with CP must have a strong focus on muscle and kidney health, especially for patients with more severe forms of CP.

Cost-effectiveness of five prenatal screening strategies for trisomies and other unbalanced chromosomal abnormalities: model-based analysis.

OBJECTIVE: To evaluate the cost-effectiveness of five prenatal screening strategies for trisomies (13/18/21) and other unbalanced chromosomal abnormalities (UBCA), following the introduction of cell-free DNA (cfDNA) analysis. METHODS: A model-based cost-effectiveness analysis was performed to estimate prevalence, safety, screening-program costs and healthcare costs of five different prenatal screening strategies, using a virtual cohort of 652 653 pregnant women in France. Data were derived from the French Biomedicine Agency and published articles. Uncertainty was addressed using one-way sensitivity analysis. The five strategies compared were: (i) cfDNA testing for women with a risk following first-trimester screening of ≥ 1/250; (ii) cfDNA testing for women with a risk of ≥ 1/1000 (currently recommended); (iii) cfDNA testing in the general population (regardless of risk); (iv) invasive testing for women with a risk of ≥ 1/250 (historical strategy); and (v) invasive testing for women with a risk of ≥ 1/1000. RESULTS: In our virtual population, at similar risk thresholds, cfDNA testing compared with invasive testing was cheaper but less effective. Compared with the historical strategy, cfDNA testing at the ≥ 1/1000 risk threshold was a more expensive strategy that detected 158 additional trisomies, but also 175 fewer other UBCA. Implementation of cfDNA testing in the general population would give an incremental cost-effectiveness ratio of €9 166 689 per additional anomaly detected compared with the historical strategy. CONCLUSION: Extending cfDNA to lower risk thresholds or even to all pregnancies would detect more trisomies, but at greater expense and with lower detection rate of other UBCA, compared with the historical strategy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Relación costo-eficacia de cinco estrategias de cribado prenatal para trisomías y otras anomalías cromosómicas no equilibradas: un análisis basado en modelos OBJETIVO: Evaluar la eficacia en función de los costos de cinco estrategias de cribado prenatal para trisomías (13/18/21) y otras anomalías cromosómicas no equilibradas (UBCA, por sus siglas en inglés), tras la introducción del análisis de ADN fetal (cfDNA, por sus siglas en inglés). MÉTODOS: Se realizó un análisis de la relación costo-eficacia basado en modelos para estimar la prevalencia, la seguridad, los costos de los programas de cribado y los costos sanitarios de cinco estrategias diferentes de cribado prenatal, para lo cual se usó una cohorte virtual de 652 653 mujeres embarazadas en Francia. Los datos se obtuvieron de la Agencia Francesa de Biomedicina y de artículos publicados. La incertidumbre se abordó mediante un análisis de sensibilidad unidireccional. Las cinco estrategias comparadas fueron: (i) pruebas de cfDNA para mujeres con un riesgo ≥1/250 después del examen del primer trimestre; (ii) pruebas de cfDNA para mujeres con un riesgo ≥1/1000 (las recomendadas actualmente); (iii) pruebas de cfDNA en la población general (independientemente del riesgo); (iv) pruebas invasivas para mujeres con un riesgo ≥1/250 (estrategia histórica); y (v) pruebas invasivas para mujeres con un riesgo ≥1/1000. RESULTADOS: En esta población virtual, con umbrales de riesgo similares, la prueba de cfDNA fue más barata pero menos efectiva en comparación con la prueba invasiva. En comparación con la estrategia histórica, la prueba de cfDNA para el umbral de riesgo de ≥1/1000 fue una estrategia más costosa que detectó 158 trisomías adicionales, pero también 175 menos de otras UBCA. La aplicación de las pruebas de cfDNA en la población general daría una relación costo-eficacia incremental de 9 166 689 EUR por cada anomalía adicional detectada en comparación con la estrategia histórica. CONCLUSIÓN: Extender las pruebas de cfDNA a umbrales de riesgo más bajos o incluso a todos los embarazos detectaría más trisomías, pero a un costo mayor y con una tasa de detección más baja de otras UBCA, en comparación con la estrategia histórica.

Assessment of the Central Effects of Natural Uranium via Behavioural Performances and the Cerebrospinal Fluid Metabolome.

Natural uranium (NU), a component of the earth's crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.5, 10, or 40 mg·L(-1) for male rats and 40 mg·L(-1) for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg·L(-1) NU. In male rats, spatial working memory and anxiety- and depressive-like behaviour were only altered by exposure to 40 mg·L(-1) NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function.

[Cancer patient's satisfaction assessment using the EORTC QLQ-SAT32: comparison between self-assessment and interview response]. / Satisfaction par rapport aux soins en oncologie évaluée par le QLQ-SAT32 de l'EORTC: comparaison entre auto-passation et entretien téléphonique.

BACKGROUND: For pertinent investigation of patient satisfaction it is important to know what type of data collection procedure yields optimal results. In this study, we compared a self- versus interview administration of the European Organisation for Research and Treatment of Cancer (EORTC) patient satisfaction questionnaire (QLQ-SAT32), noting response and item omission rates. We also assessed the correlation and agreement between responses according to these modalities of questionnaire administration. METHODS: 123 patients recruited in two anti-cancer Centers in France were asked to complete the QLQ-SAT32 at home within 2 weeks of hospital discharge and were randomly allocated to participate in a telephone interview-administration of the QLQ-SAT32, either before or after self-completing the QLQ-SAT32. RESULTS: 104 patients completed both modalities of questionnaire administration. Agreement proved excellent for the doctors' and nurses' subscales and satisfactory for the services' subscale and the general satisfaction single item. However, a significant difference in response rate showed up between Centers (different interviewers) and the interview modality revealed an item omission rate higher than for the self-administration modality. CONCLUSION: Self- and interview-administration of the QLQ-SAT32 provided similar responses however different response rate between interviewers and higher item omission rate in interviews suggests a biasing effect of that modality of data collection.

Validation of the EORTC QLQ-SAT32 cancer inpatient satisfaction questionnaire by self- versus interview-assessment comparison.

Doubts are expressed on the validity of patient satisfaction questionnaires. High satisfaction levels are consistently reported. Within the European Organisation for Research and Treatment of Cancer (EORTC) quality of life group, we developed a cancer inpatient satisfaction questionnaire (QLQ-SAT32), adopting several precautions to overcome the ceiling effect commonly reported in satisfaction ratings. Since patients are often more critical when expressing themselves in an interview, in order to study the validity of the QLQ-SAT32, we assessed the agreement between self- and interview-administered QLQ-SAT32 responses. One hundred and twenty three patients were asked to complete the QLQ-SAT32 at home within 2 weeks of hospital discharge and were randomly allocated to participate in a telephone interview-administration of the QLQ-SAT32, either before or after self-completing the QLQ-SAT32. One hundred and four of them completed both modalities of questionnaire administration. Correlation and agreement between self- and interview-administered QLQ-SAT32 ratings were examined, for each subscale and the general satisfaction item of the QLQ-SAT32, using Spearman correlation, intra-class correlation coefficients (ICC) or weighted kappa coefficients. Agreement showed excellent for the doctors' and nurses' subscales and satisfactory for the services' subscale and the general satisfaction single item. The telephone interview-administration modality did not prove an adequate procedure to assess the validity of a patient satisfaction questionnaire.