Emmanuel Ecosse

Original ArticleThe French SF-36 Health Survey: Translation, Cultural Adaptation and Preliminary Psychometric Evaluation

This article reports on the main developmental stages and on the preliminary psychometric assessment of the final French version of the SF-36. A standard forward/backward translation procedure was followed. When translating survey items, the emphasis was placed on conceptual equivalence. When translating response choices, we attempted to select a set of response choices that replicate the U.S. version. The distance between the response choices was checked using visual analogue scales (N = 30). The adaptation procedure also included formal ratings of the difficulty of the translation, of the quality of the translation, and of the equivalence between the American source version and the French target version. The face validity was checked during lay panel sessions at which the translated questionnaire was administered to subjects from the general public, hospital employees, and subjects with a low level of education. Standard psychometric techniques were used to evaluate the cultural adaptation of the SF-36, using data from a general population survey. The main objective of this analysis was to determine how well the scaling assumptions (summated rating or Likert-type scaling construction) of the SF-36 were satisfied. The results support the claim that the scaling properties of the French version of the SF-36 are adequate and that health outcomes may be reliably assessed using this version of the instrument.

Long- term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study

CONTEXT Little is known about the long-term health of subjects treated with GH in childhood, and Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) is a study addressing this question. OBJECTIVE The objective of the study was to evaluate the long-term mortality of patients treated with recombinant GH in childhood in France. DESIGN This was a population-based cohort study. SETTING The setting of the study was a French population-based register. PARTICIPANTS A total of 6928 children with idiopathic isolated GH deficiency (n = 5162), neurosecretory dysfunction (n = 534), idiopathic short stature (n = 871), or born short for gestational age (n = 335) who started treatment between 1985 and 1996 participated in the study. Follow-up data on vital status were available in September 2009 for 94.7% of the patients. MAIN OUTCOME MEASURES All-cause and cause-specific mortality was measured in the study. RESULTS All-cause mortality was increased in treated subjects [standardized mortality ratio (SMR) 1.33, 95% confidence interval (CI) 1.08-1.64]. In a multivariate analysis adjusted for height, the use of GH doses greater than 50 μg/kg · d was associated with mortality rates using external and internal references (SMR 2.94, 95% CI 1.22-7.07, hazard ratio 2.79, 95% CI 1.14-6.82). All type cancer-related mortality was not increased. Bone tumor-related mortality was increased (SMR 5.00, 95% CI 1.01-14.63). An increase in mortality due to diseases of the circulatory system (SMR 3.07, 95% CI 1.40-5.83) or subarachnoid or intracerebral hemorrhage (SMR 6.66, 95% CI 1.79-17.05) was observed. CONCLUSIONS Mortality rates were increased in this population of adults treated as children with recombinant GH, particularly in those who had received the highest doses. Specific effects were detected in terms of death due to bone tumors or cerebral hemorrhage but not for all cancers. These results highlight the need for additional studies of long-term mortality and morbidity after GH treatment in childhood.

Impact of neurofibromatosis 1 on Quality of Life: a cross-sectional study of 176 American cases:

Neurofibromatosis 1 (NF1), a genetic condition most commonly characterized by the presence of dermal neurofibromas and café au lait macules, has a significant impact on Quality of Life (QoL). There is a wide range of phenotypic variability, so that affected individuals may have either medically devastating or relatively mild manifestations that do not impact their daily lives. In this study, the SF‐36 and Skindex questionnaires were used to quantitatively investigate the impact of severity and visibility on QoL in an American population. Participants were recruited primarily through advertisements distributed by The Childrens Tumor Foundation (CTF). The majority participated by completing a mailed questionnaire in which they rated themselves using Ablons visibility and Riccardis severity scales, and then completed the SF‐36 and Skindex questionnaires. Participants with NF1 reported a significant impact in all aspects of skin‐disease‐specific QoL, but the emotional aspect demonstrated the greatest effect. Participants with more visible signs of NF1 reported significantly greater overall effects on their skin‐disease‐specific QoL than those whose manifestations were more subtle. All domains of general health QoL were affected as well, especially in participants who reported having severe complications. Interestingly, greater visibility was not found to be associated with a significant decrease in general health QoL. These findings are consistent with those found in a French cohort, and demonstrate the utility of incorporating tools designed for use in both the general population and for patients with skin disease in examining the impact of NF1 on QoL.

Methodological issues in determining the dimensionality of composite health measures using principal component analysis: case illustration and suggestions for practice.

During the early steps of the construction of composite health measures, principal component analysis (PCA) is commonly used to identify ‘latent’ factors that underlie observed variables and to determine the dimensionality of the instruments. The determination of the number of components to retain is critical to PCA: it markedly influences the factorial model identified and further conditions the validity of the constructed instrument. However, many researchers developing composite health measures seem to be unaware of the importance of this determination. The purposes of the paper are to illustrate (1) the variability of the factorial models obtained by using different published rules (n=10) for determining the number of components to retain in PCA applied to two quality-of-life datasets, and (2) the value of a careful and diversified approach to the problem of the number of components to retain in PCA that we suggest, instead of the unsatisfactory ‘rule-of-thumb’ that many researchers use. This involves: (1) using robust rules (including parallel analysis and minimum average partial procedure) to generate a set of possible values for the number of components to retain, (2) repeating the analysis across samples, (3) comprehensively assessing the models obtained, and (4) considering complementary methods to PCA and especially confirmatory factor analysis.

Growth hormone treatment for childhood short stature and risk of stroke in early adulthood

Objectives: We investigated the incidence of stroke and stroke subtypes in a population-based cohort of patients in France treated with growth hormone (GH) for short stature in childhood. Methods: Adult morbidity data were obtained in 2008–2010 for 6,874 children with idiopathic isolated GH deficiency or short stature who started GH treatment between 1985 and 1996. Cerebrovascular events were validated using medical reports and imaging data and classified according to standard definitions of subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke. Case ascertainment completeness was estimated with capture-recapture methods. The incidence of stroke and of stroke subtypes was calculated and compared with population values extracted from registries in Dijon and Oxford, between 2000 and 2012. Results: Using both Dijon and Oxford population-based registries as references, there was a significantly higher risk of stroke among patients treated with GH in childhood. The excess risk of stroke was mainly attributable to a very substantially and significantly higher risk of hemorrhagic stroke (standardized incidence ratio from 3.5 to 7.0 according to the registry rates considered, and accounting or not accounting for missed cases), and particularly subarachnoid hemorrhage (standardized incidence ratio from 5.7 to 9.3). Conclusions: We report a strong relationship between hemorrhagic stroke and GH treatment in childhood for isolated growth hormone deficiency or childhood short stature. Patients treated with GH worldwide should be advised about this association and further studies should evaluate the potentially causal role of GH treatment in these findings.

Determinants of medical care for young women with Turner syndrome.

CONTEXT Turner syndrome is associated with reduced life expectancy. Lifelong follow-up is strongly recommended, but follow-up during the transition between pediatric and adult care has been little evaluated. OBJECTIVE Our objective was to evaluate the medical follow-up of a population-based cohort of young adult patients. DESIGN, SETTING, AND PATIENTS A questionnaire study was conducted with a national cohort of 568 women, aged 22.6 +/- 2.6 yr (range, 18.3-31.2), a mean of 6 yr after stopping GH treatment (StaTur cohort). MAIN OUTCOME MEASURES We assessed the proportion of patients with adequate follow-up at seven medical assessments over 4 yr and its determinants. RESULTS Most participants were followed by gynecologists or general practitioners. Medical assessments were performed in 16% (audiometry) to 68% (lipid level determinations) of participants, with little consistency in individual patients. Only 20 of 568 patients (3.5%) underwent all assessments in the 4-yr period. Multivariate analysis identified the type of physician as the only factor consistently associated with follow-up, which was more adequate with endocrinologists than with other physicians. Other variables associated with at least one adequate follow-up assessment were paternal socioeconomic class, education level, number of Turner syndrome disease components, size of the medical center following the patient in childhood, and physical health dimensions of Short Form 36 questionnaire. CONCLUSIONS By contrast with the intensive medical follow-up in childhood, follow-up was grossly inadequate during the transition phase. During this phase, patients should be sent to physicians specializing in Turner syndrome and particular attention should be paid to patients with lower levels of education and from families of low socioeconomic status.

Efficiency of Neonatal Screening for Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency in Children Born in Mainland France Between 1996 and 2003

OBJECTIVE To assess the efficiency of the French national screening program for 21-hydroxylase deficiency (21-OHD). Neonatal screening for congenital adrenal hyperplasia due to 21-OHD is mainly intended to prevent death due to salt wasting but remains controversial because of the number of false-positive results and the ease with which most female cases can be identified by virilized genitalia at birth. DESIGN Population-based study. SETTING National neonatal screening program, pediatric endocrinologists nationwide, and reference center for genotyping. PARTICIPANTS All neonates screened for 21-OHD in mainland France between January 1, 1996, and December 31, 2003. OUTCOME MEASURES Screening efficiency indicators, disease severity, contribution of screening to early diagnosis, and disease-specific mortality before and during the study period. RESULTS A total of 6,012,798 neonates were screened; results in 15,407 were considered positive for 21-OHD. Three hundred eighty-three cases were identified, giving a prevalence of 1 for every 15,699 births. The positive predictive value of screening was 2.3% (95% CI, 2.1%-2.6%), with a sensitivity of 93.5% (90.9%-95.9%) and a specificity of 99.7% (99.7%-99.7%). The false-positive rate was particularly high in preterm infants, for which the positive predictive value was 0.4% (95% CI, 0.2%-0.5%). Screening allowed clinical diagnosis in 162 of 383 cases (42.3%), with the others being detected clinically or through family history. There was a trend toward declining neonatal mortality due to 21-OHD. CONCLUSIONS In this large population-based study, the efficiency of routine 21-OHD screening was moderate in neonates born at term and very low in preterm neonates. We recommend the discontinuation of screening, as currently performed in France, in preterm neonates.

Factors Associated With Hearing Impairment in Patients With Congenital Hypothyroidism Treated Since the Neonatal Period: A National Population-Based Study

CONTEXT Untreated hypothyroidism is known to impair hearing, but little is known about the long-term hearing of patients treated for congenital hypothyroidism (CH) since the neonatal period. OBJECTIVE The purpose of this study was to assess hearing and its determinants in a population-based registry of young adult patients with CH. DESIGN, SETTING, AND PARTICIPANTS Self-declared hearing loss was evaluated in 1202 of the 1748 eligible patients with CH who completed a questionnaire on health status at a median age of 23.4 years. Audiograms were obtained for one third of the patients declaring hearing loss (37 of 107). MAIN OUTCOME MEASURES Self-declared hearing loss and audiogram characteristics for patients reporting hearing impairment were measured. RESULTS These patients had a risk of self-declared hearing loss more than 3 times higher than that for the reference population (relative risk [RR] = 3.7; 95% confidence interval [CI], 2.9-4.7). Hearing impairment was diagnosed at a median age of 7.0 (25th-75th percentiles, 3.4-19.0) years, and 17% of affected patients required hearing support in early adulthood. Hearing loss was associated with the type of CH (patients with athyreosis and gland in situ were more frequently affected than those with an ectopic gland [RR = 2.61; 95% CI, 1.77-3.88]), with disease severity, as assessed by bone maturation delay at the time of diagnosis, with at least one knee epiphyseal ossification center absent in the most severe form (RR = 2.29; 95% CI, 1.39-3.79), and with other associated chronic diseases (RR = 3.64; 95% CI, 2.35-5.62). A trend for association with serum free T4 concentration at diagnosis was also observed (RR = 1.47; 95% CI, 0.96-2.23). Hearing loss was mostly bilateral (90%), mild to moderate (96%), of the sensorineural type (76%), and concerned high or very high frequencies. CONCLUSION Despite major improvements in prognosis, hearing loss remains a significant problem, particularly in patients with severe CH. Parents and primary care providers should be aware of this risk, because early diagnosis and intervention could improve the long-term prognosis in these patients.

Measurement properties of the osteoarthritis of knee and hip quality of life OAKHQOL questionnaire: an item response theory analysis

OBJECTIVE To further document the measurement properties of each domain of the OA of knee and hip quality of life (OAKHQOL) questionnaire by a Rasch analysis. METHODS The OAKHQOL self-administered questionnaire has been developed to assess health-related quality of life in lower limb OA. Patients with various degrees of severity of knee or hip OA answered the questionnaire. For each domain, their responses to the items were analysed with a Rasch family model, the partial credit model. We examined the fit of data to model expectations, as well as assumptions of unidimensionality and local independence. Invariance was assessed by analysis of differential item functioning (DIF) by sex, age and joint. Analyses used the RUMM2020 software (Rumm Laboratory, Perth, Western Australia). RESULTS Responses for 544 patients were analysed: 297 had medically managed OA and 247 were waiting for arthroplasty surgery. For the 40 items of the OAKHQOL, data analysis showed 5 with disordered thresholds and 9 with DIF (5 for joint, 3 for sex and 1 for age). Ten pairs of items showed local dependence and four domains showed unidimensionality. Full-item domains and domains without the misfitted items did not differ in patient-estimates data; therefore any bias at the item level is negligible when considering the domain scores. CONCLUSION The five domains of the OAKHQOL questionnaire show good measurement properties by Rasch analysis and provide valid scales.

Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty

CONTEXT AND OBJECTIVE Idiopathic central precocious puberty (iCPP) is defined as early activation of the hypothalamic-pituitary-gonadal axis in the absence of identifiable central lesions. Mutations of the makorin RING finger 3 (MKRN3) gene are associated with iCPP. We aimed to assess the frequency of MKRN3 mutations in iCPP and to compare the phenotypes of patients with and without MKRN3 mutations. DESIGN An observational study was carried out on patients recruited at pediatric hospitals in France and Italy. Forty-six index CPP cases were screened for mutations in the MKRN3 coding sequence: 28 index cases of familial cases and 18 cases did not report any familial history of CPP. The endocrine phenotype was compared between MKRN3 mutated and non-mutated patients. RESULTS MKRN3 mutations were identified in one sporadic and 13 familial cases. We identified five new heterozygous missense mutations predicted to be deleterious for protein function and two frameshift mutations, one new and the other recurrent, predicted to result in truncated proteins. Age at puberty onset varied very little among patients with MKRN3 mutations and puberty occurred earlier in these patients than in those without MKRN3 mutations (6.0 years (5.4-6.0) vs 7.0 years (6.0-7.0), P=0.01). CONCLUSIONS MKRN3 mutations are common in familial iCPP. MKRN3 is one of the gatekeepers of the postnatal activation of the gonadotropic axis.