e-Health Literacy Skills in People with Chronic Diseases and What Do the Measurements Tell Us: A Scoping Review.

Background: Use of electronic health (e-Health) technologies has increased in the past decade and inadequate e-Health literacy may lead to health-related social inequality. This is especially true for patients living with chronic diseases who are often involved in self-care. However, the measurement of e-Health literacy represents several challenges. Among available instruments, the e-Health Literacy Scale (eHEALS) is the only instrument with available psychometric properties. Aim: To identify studies measuring e-Health literacy in adults living with chronic disease and its relationship to health-related behaviors and other perceptions such as quality of life, self-efficacy, or specific disease biomarkers, and studies analyzing the impact of educational intervention on e-Health literacy. Methods: The authors searched MEDLINE, the Cochrane Library, and Web of Science databases to identify studies published in English language until April 2022. Results: Seventeen studies involving 4,877 participants were included. A majority of the studies were cross-sectional with a lack of appropriate controls. Five of the included studies were experimental, involving 758 participants. All of them reported positive effects of educational interventions on the improvements in self-reported e-Health literacy skills. However, most studies were at risk of bias. Conclusion: Despite these limitations, the findings of this review indicate the positive relationship between e-Health literacy and various health care processes in adults with chronic diseases and highlights a need for prospective controlled studies. Promoting e-Health literacy might give better opportunities for the active involvement of people with chronic diseases in self-care and for the implementation of online interventions into existing system of care.

[Care pathways for young transgender people]. / Parcours de soins des jeunes personnes transgenres.

Gender incongruence corresponds to the mismatch between gender identity and gender/sex assigned at birth gender/sex assigned at birth. It can be accompanied by psychological distress. In line with the literature, an increase in consultations for gender incongruence has been observed, especially among young people. Multidisciplinary care should be offered to this population; here we provide an example of healthcare proposed at the university hospital of Nancy.

[Using simulation for assessment: the example of OSCE in medical students]. / La simulation pour les évaluations : l'exemple des Ecos chez les étudiants en médecine.

Training of health sciences students is based on the acquisition of clinical skills. Tools assessing the application of theoretical knowledge through written examinations or the tools evaluating student's performance at patient bedsides are characterized by a low reliability. The Objective Structured Clinical Examination (OSCE) was developed to address the lack of reliability and standardization of traditional forms of the assessment of clinical performance.

E-health education interventions on HbA1c in patients with type 1 diabetes on intensive insulin therapy: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Patient-centered education improves glycemic control in subjects with type 1 diabetes (T1D). E-health technologies are widely used to support medical decision-making, patient advising or teleconsultations; however, the active participation of a patient is missing. Challenges remain whether e-health education can be effectively incorporated into clinical pathways. The purpose of the study was to examine the effects of e-health education, compared to standard care, on HbA1c. MATERIAL AND METHODS: We conducted a literature search (EMBASE, MEDLINE, The Cochrane Library and Web of Science) up to February 2018 for randomized controlled trials (RCTs) of Internet-/ mobile application-based educational interventions, with the active involvement of patients, provided in addition to, or substituting usual care in patients with T1D on intensive insulin therapy. The primary outcome was the standardized difference in means (SDM) of HbA1c change from baseline between intervention and comparator groups. RESULTS: Eight RCTs involving 757 subjects were included on 6335 screened citations. After excluding two trials with a high risk of bias from the meta-analysis, the HbA1c change from baseline did not significantly differ between intervention and comparator groups (SDM = -0.154, 95% CI: -0.335 to 0.025; P = 0.01, random-effect model). The number of studies is limited with a relatively short duration. Reporting of educational outcomes was not rigorous. CONCLUSIONS: The effect of e-health educational interventions on HbA1c in patients with T1D is comparable to the standard care. This review highlights the need for further well-designed RCTs that will investigate the opportunities of incorporating e-health education into clinical pathways.

Decrease in serum testosterone levels after short-term occupational exposure to diisononyl phthalate in male workers.

OBJECTIVE: The objective of the study was to examine the effects of occupational exposure to diisononyl phthalate (DINP) on serum testosterone levels in male workers. METHODS: From 2015 to 2018, 97 male workers were recruited from six French factories in the plastics industry. In a short longitudinal study, changes over 3 days in the level of total or free serum testosterone and DINP exposure were measured. DINP exposure was measured by urinary biomonitoring: mono-4-methyl-7-oxo-octyl phthalate (OXO-MINP), mono-4-methyl-7-hydroxy-octyl phthalate (OH-MINP) and mono-4-methyl-7-carboxyheptylphthalate (CX-MINP). We further analysed changes in follicle-stimulating hormone, luteinising hormone, total testosterone to oestradiol ratio and two bone turnover markers (procollagen-type-I-N propeptide, C terminal cross-linking telopeptide of type I collagen), and erectile dysfunction via standardised questionnaires (International Index of Erectile Function, Androgen Deficiency in Aging Males). Linear mixed models were used with the variables 'age' and 'abdominal diameter' included as confounder. RESULTS: Increased urinary OXO-MINP was associated with a significant decrease in total serum testosterone concentrations, but only for workers who exhibited the smallest variations and lowest exposures (p=0.002). The same pattern was observed for CX-MINP but was not significant; no association with OH-MINP was detectable. More self-reported erectile problems were found in workers exposed directly to DINP at the workstation (p=0.01). No changes were observed for the other biological parameters. CONCLUSIONS: Short-term exposure to DINP is associated with a decrease in total serum testosterone levels in male workers. Our results suggest that DINP could present weak antiandrogenic properties in humans, but these need to be confirmed by other studies.

Immunoglobulin Preparations Can Mislead Clinical Decision-Making in Follow-Up of Differentiated Thyroid Cancer.

OBJECTIVE: Intravenous and subcutaneous immunoglobulins are commonly used for immune substitution or as immune modulators in a variety of inflammatory and autoimmune disorders. Exogenous thyroid-specific thyroglobulin (Tg) antibodies present in the donor plasma may interfere with the interpretation of measurements of Tg autoantibodies (Tg-Abs) in the recipient's plasma and potentially trigger an immune response in the recipient's immune cells. Levels of antibodies causing bioassay interferences or those leading to clinically relevant changes in patient outcomes are not known. Tg is used as a biomarker in the long-term surveillance of patients with differentiated thyroid cancer (DTC) following total thyroidectomy and radioactive iodine ablation. However, the presence of Tg-Abs in the circulation interferes with Tg measurements. Assessment of levels of Tg-Abs is thus recommended as a part of standard follow-up of DTC together with Tg testing. METHODS: To understand the potential mechanisms and pathophysiologic significance of possible interferences associated with administration immunoglobulin preparations and Tg measurement, we overview the current knowledge on interactions between Tg autoimmunity and immunoglobulin preparations and illustrate diagnostic challenges and perspectives for follow-up of patients with DTC treated with exogenous immunoglobulins. RESULTS: In patients with DTC treated with immunoglobulin preparations, monitoring of thyroid cancer using Tg and Tg-Abs is challenging due to possible analytical interferences through passive transfer of exogenous antibodies from immunoglobulin preparations. CONCLUSION: Analytical interferences must be suspected when a discrepancy exists between clinical examination and diagnostic tests. Collaboration between endocrinologists, biologists, and pharmacologists is fundamental to avoid misdiagnosis and unnecessary medical or radiologic procedures. ABBREVIATIONS: CT = computed tomography; DTC = differentiated thyroid cancer; FNAB = fine-needle aspiration biopsy; HAb = heterophile antibody; IMA = immunometric assay; IVIg = intravenous immunoglobulin; RAI = radioactive iodine; RIA = radioimmunoassay; SCIg = subcutaneous immunoglobulin; Tg = thyroglobulin; Tg-Ab = thyroglobulin autoantibody; Tg-MS = thyroglobulin mass spectrometry; TPO-Ab = thyroid peroxidase autoantibody; TSHR-Ab = thyrotropin receptor autoantibody.

Fertility desires and reproductive needs of transgender people: Challenges and considerations for clinical practice.

The majority of transgender and gender nonconforming persons seeking medical care are of reproductive age. Hormonal treatment and sex reassignment surgery, which are used in the management of gender dysphoria, compromise fertility potential. Children and adolescents with gender dysphoria have specific treatment regimens starting with puberty-blocking medications. According to international guidelines, fertility preservation should be discussed before any hormonal treatment, although our knowledge on the reproductive needs of transgender and gender nonconforming persons is limited. Recently, some data have emerged on fertility management in some centres for the adult population with gender dysphoria. The goal of this review was to summarize the available evidence on the fertility desires and parental roles of transgender and gender nonconforming people. In light of newly emerging societal challenges, we aim to provide some considerations for clinical practice and suggest further areas of research.

Extracellular vesicles as immune mediators in response to kidney injury.

Important progress has been made on cytokine signaling in response to kidney injury in the past decade, especially cytokine signaling mediated by extracellular vesicles (EVs). For example, EVs released by injured renal tubular epithelial cells (TECs) can regulate intercellular communications and influence tissue recovery via both regulating the expression and transferring cytokines, growth factors, as well as other bioactive molecules at the site of injury. The effects of EVs on kidney tissue seem to vary depending on the sources of EVs; however, the literature data are often inconsistent. For example, in rodents EVs derived from mesenchymal stem cells (MSC-EVs) and endothelial progenitor cells (EPC-EVs) can have both beneficial and harmful effects on injured renal tissue. Caution is thus needed in the interpretation of these data as contradictory findings on EVs may not only be related to the origin of EVs, they can also be caused by the different methods used for EV isolation and the physiological and pathological states of the tissues/cells under which they were obtained. Here, we review and discuss our current understanding related to the immunomodulatory function of EVs in renal tubular repair in the hope of encouraging further investigations on mechanisms related to their antiinflammatory and reparative role to better define the therapeutic potential of EVs in renal diseases.

Role of post-transcriptional regulation of mRNA stability in renal pathophysiology: focus on chronic kidney disease.

Chronic kidney disease (CKD) represents an important public health problem. Its progression to end-stage renal disease is associated with increased morbidity and mortality. The determinants of renal function decline are not fully understood. Recent progress in the understanding of post-transcriptional regulation of mRNA stability has helped the identification of both the trans- and cis-acting elements of mRNA as potential markers and therapeutic targets for difficult-to-diagnose and -treat diseases, including CKDs such as diabetic nephropathy. Human antigen R (HuR), a trans-acting element of mRNA, is an RNA binding factor (RBF) best known for its ability to stabilize AU-rich-element-containing mRNAs. Deregulated HuR subcellular localization or expression occurs in a wide range of renal diseases, such as metabolic acidosis, ischemia, and fibrosis. Besides RBFs, recent evidence revealed that noncoding RNA, such as microRNA and long noncoding RNA, participates in regulating mRNA stability and that aberrant noncoding RNA expression accounts for many pathologic renal conditions. The goal of this review is to provide an overview of our current understanding of the post-transcriptional regulation of mRNA stability in renal pathophysiology and to offer perspectives for this class of diseases. We use examples of diverse renal diseases to illustrate different mRNA stability pathways in specific cellular compartments and discuss the roles and impacts of both the cis- and trans-activating factors on the regulation of mRNA stability in these diseases.-Feigerlová, E., Battaglia-Hsu, S.-F. Role of post-transcriptional regulation of mRNA stability in renal pathophysiology: focus on chronic kidney disease.

Plasma levels of hsa-miR-152-3p are associated with diabetic nephropathy in patients with type 2 diabetes.

Background: MicroRNAs (miRNAs) are small non-coding RNAs participating in post-transcriptional regulation of genes. Their key role in modulating the susceptibility to human diseases is now widely recognized, in particular in the context of cardiometabolic disorders. The aim of the present study was to identify miRNAs associated with diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Methods: A next-generation sequencing-based miRNA profiling was performed in a case-control study for DN in plasma samples of 23 T2D patients with DN (cases) and 23 T2D without (controls). The main associations were confirmed using quantitative reverse transcription-polymerase chain reaction and tested for replication in an independent case-control collection of 100 T2D patients, 50 with DN and 50 without. Results: From the 381 known mature miRNAs that were found highly expressed in the discovery samples, we observed and replicated an association between increased plasma levels of hsa-miR-152-3p and DN (P = 4.03 × 10-4 in the combined samples). Hsa-miR-152-3p plasma levels were further found to be positively correlated (P = 0.003) to plasma osmolarity, a surrogate marker for solute carrier net activity, whose regulation is controlled by several genes including SLC5A3, one of the predicted targets of hsa-miR-152-3p. Conclusions: We observed strong evidence for the association of hsa-miR-152-3p plasma levels and DN in patients with T2D, confirming an association previously observed in patients with type 1 diabetes.

Methyl donor deficiency impairs bone development via peroxisome proliferator-activated receptor-γ coactivator-1α-dependent vitamin D receptor pathway.

Deficiency in methyl donor (folate and vitamin B12) and in vitamin D is independently associated with altered bone development. Previously, methyl donor deficiency (MDD) was shown to weaken the activity of nuclear receptor coactivator, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), for nuclear signaling in rat pups, including estrogen receptor-α and estrogen-related receptor-α; its effect on vitamin D receptor (VDR) signaling, however, is unknown. We studied bone development under MDD in rat pups and used human MG-63 preosteoblast cells to better understand the associated molecular mechanism. In young rats, MDD decreased total body bone mineral density, reduced tibia length, and impaired growth plate maturation, and in preosteoblasts, MDD slowed cellular proliferation. Mechanistic studies revealed decreased expression of VDR, estrogen receptor-α, PGC1α, arginine methyltransferase 1, and sirtuin 1 in both rat proximal diaphysis of femur and in MG-63, as well as decreased nuclear VDR-PGC1α interaction in MG-63 cells. The weaker VDR-PGC1α interaction could be attributed to the reduced protein expression, imbalanced PGC1α methylation/acetylation, and nuclear VDR sequestration by heat shock protein 90 (HSP90). These together compromised bone development, which is reflected by lowered bone alkaline phosphatase and increased proadipogenic peroxisome proliferator-activated receptor-γ, adiponectin, and estrogen-related receptor-α expression. Of interest, under MDD, the bone development effects of 1,25-dihydroxyvitamin D3 were ineffectual and these could be rescued by the addition of S-adenosylmethionine, which restored expression of arginine methyltransferase 1, PGC1α, adiponectin, and HSP90. In conclusion, MDD inactivates vitamin D signaling via both disruption of VDR-PGC1α interaction and sequestration of nuclear VDR attributable to HSP90 overexpression. These data suggest that vitamin D treatment may be ineffective under MDD.-Feigerlova, E., Demarquet, L., Melhem, H., Ghemrawi, R., Battaglia-Hsu, S.-F., Ewu, E., Alberto, J.-M., Helle, D., Weryha, G., Guéant, J.-L. Methyl donor deficiency impairs bone development via peroxisome proliferator-activated receptor-γ coactivator-1α-dependent vitamin D receptor pathway.

Cytokines in Endocrine Dysfunction of Plasma Cell Disorders.

Monoclonal gammopathies (MG) are classically associated with lytic bone lesions, hypercalcemia, anemia, and renal insufficiency. However, in some cases, symptoms of endocrine dysfunction are more prominent than these classical signs and misdiagnosis can thus be possible. This concerns especially the situation where the presence of M-protein is limited and the serum protein electrophoresis (sPEP) appears normal. To understand the origin of the endocrine symptoms associated with MG, we overview here the current knowledge on the complexity of interactions between cytokines and the endocrine system in MG and discuss the perspectives for both the diagnosis and treatments for this class of diseases. We also illustrate the role of major cytokines and growth factors such as IL-6, IL-1ß, TNF-α, and VEGF in the endocrine system, as these tumor-relevant signaling molecules not only help the clonal expansion and invasion of the tumor cells but also influence cellular metabolism through autocrine, paracrine, and endocrine mechanisms. We further discuss the broader impact of these tumor environment-derived molecules and proinflammatory state on systemic hormone signaling. The diagnostic challenges and clinical work-up are illustrated from the point of view of an endocrinologist.

Death, end-stage renal disease and renal function decline in patients with diabetic nephropathy in French cohorts of type 1 and type 2 diabetes.

AIMS/HYPOTHESIS: Microvascular complications are a common feature of diabetes but additional research is needed regarding diabetic nephropathy endpoints in type 1 and type 2 diabetes. METHODS: We compared 277 type 1 diabetes patients with 942 type 2 diabetes patients, with clinical proteinuria and no endstage renal disease (ESRD) at baseline, prospectively followed for death, ESRD and decline in estimated glomerular filtration rate (eGFR, all available measures). RESULTS: The incidence rate of death was 67.0 (95% CI 59.2, 74.8) vs. 24.6 (95% CI, 19.0, 30.2) per 1,000 patient-years, in type 2 diabetes and type 1 diabetes, respectively. Unadjusted risk for death was greater for type 2 diabetes patients (HR 3.423; 95% CI, 2.501, 4.683; p<0.0001), but the difference did not persist after adjustment for age (HRage-adj 0.859; 95% CI 0.581, 1.269; p=0.445). The incidence rate of ESRD was 18.4 (95% CI 14.2, 22.5) vs. 47.1 (95%CI 38.4, 55.9) per 1,000 patient-years, in type 2 diabetes and type 1 diabetes, respectively. Unadjusted risk for ESRD was lower in type 2 diabetes (HR 0.399; 95% CI 0.287, 0.554; p<0.0001), but the difference did not persist after adjustment for sex, age and baseline serum creatinine (HRadj 0.989; 95% CI 0.597, 1.639; p=0.965). In a mixed linear model, eGFR decline was not significantly different in type 2 vs. type 1 diabetes (difference in slope −0.19 [0.28] ml min(−1) 1.73 m(−2) year(−1); p=0.512). CONCLUSIONS/INTERPRETATION: In diabetic nephropathy, once baseline risk factors were taken into account the risk for death, ESRD and renal function decline did not significantly differ between type 1 diabetes and type 2 diabetes.

Nutritional models of foetal programming and nutrigenomic and epigenomic dysregulations of fatty acid metabolism in the liver and heart.

Barker's concept of 'foetal programming' proposes that intrauterine growth restriction (IUGR) predicts complex metabolic diseases through relationships that may be further modified by the postnatal environment. Dietary restriction and deficit in methyl donors, folate, vitamin B12, and choline are used as experimental conditions of foetal programming as they lead to IUGR and decreased birth weight. Overfeeding and deficit in methyl donors increase central fat mass and lead to a dramatic increase of plasma free fatty acids (FFA) in offspring. Conversely, supplementing the mothers under protein restriction with folic acid reverses metabolic and epigenomic phenotypes of offspring. High-fat diet or methyl donor deficiency (MDD) during pregnancy and lactation produce liver steatosis and myocardium hypertrophy that result from increased import of FFA and impaired fatty acid ß-oxidation, respectively. The underlying molecular mechanisms show dysregulations related with similar decreased expression and activity of sirtuin 1 (SIRT1) and hyperacetylation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). High-fat diet and overfeeding impair AMPK-dependent phosphorylation of PGC-1α, while MDD decreases PGC-1α methylation through decreased expression of PRMT1 and cellular level of S-adenosyl methionine. The visceral manifestations of metabolic syndrome are under the influence of endoplasmic reticulum (ER) stress in overnourished animal models. These mechanisms should also deserve attention in the foetal programming effects of MDD since vitamin B12 influences ER stress through impaired SIRT1 deacetylation of HSF1. Taken together, similarities and synergies of high-fat diet and MDD suggest, therefore, considering their consecutive or contemporary influence in the mechanisms of complex metabolic diseases.

Training framework for high-stakes OSCE: Experience from volunteer standardized patients' bank.

BACKGROUND: Training of standardized patients (SPs) for national high-stakes OSCE helps to ensure a reliable assessment of student performance in various clinical scenarios. However, workflow protocols to train SPs vary. Medical schools adopt specific measures to ensure standardization. APPROACH: We present a development workflow of the SPs' training framework for high-stakes OSCE using a volunteer SPs' bank. Our approach was guided by the social learning theory. Three educators and 17/20 (85%) members of our volunteer SPs' bank worked in a collaborative partnership on the construction of pedagogical content of the training framework comprising three 2-hour sessions. Since SPs have to demonstrate acquired behaviors, intended learning outcomes used the words "apply", "perform" and "participate." EVALUATION: A principal part of the evaluation was the achievement of intended learning outcomes by the SPs during 3 formative OSCEs. Seventeen SPs, 356 fourth year medical students and 60 examiners participated. Quantitative and qualitative data were collected by post-session questionnaires and analyzed using descriptive statistics and thematic analysis. Twelve examiners evaluated a mean of 29.7+/-0.14 SD patient-student encounters. In total, 15/16 SPs (93.8%) considered the contact with students as easy and 4 SPs (31%) reported the experience as stressful. Two themes emerged from the free-text comments: "Gaining experience as SP" and "Concerns for evaluated students." IMPLICATION: The proposed SPs' training framework for high-stakes OSCE may be useful for other medical disciplines and health professions initiating SP-based assessment programs. The strategy of development and evaluation are outlined to guide a successful application of the curriculum standards.

Systemic Inflammatory Indices and Liver Dysfunction in Turner Syndrome Patients: A Retrospective Case-control Study.

Context: Liver function abnormalities have been reported in patients with Turner syndrome (TS); however, the pathophysiological mechanisms have not been well elucidated. Low-grade inflammation has been associated with metabolic dysfunction-associated steatotic liver disease. Objective: We studied systemic inflammatory indices [aspartate transaminase to lymphocyte ratio index (ALRI), aspartate transaminase to platelet ratio index (APRI), gamma-glutamyl transferase to platelet ratio (GPR), neutrophil-lymphocyte-ratio (NLR), and platelet lymphocyte ratio and examined their associations with the hepatic abnormalities observed in these subjects. Methods: We performed a retrospective analysis of the medical records of 79 patients with TS (mean age 32.5 ± 9.2 SD years) who were treated at the University Hospital of Nancy. Using matched-pair analyses based on age and body mass index (BMI), we compared 66 patients with TS (25.6 ± 7.3 years; BMI 25.9 ± 6.3 kg/m2) to 66 healthy control participants (24.7 ± 6.8 years; BMI 26 ± 6.7 kg/m2). Results: Liver function abnormalities were present in 57% of the patients with TS. The ALRI, APRI, GPR, and NLR were significantly greater in patients with TS who presented with liver dysfunction than in patients with TS who had normal liver function. According to the matched-pair analyses, the ALRI, APRI, and GPR were greater in patients with TS than in healthy control participants. Logistic regression revealed that a diagnosis of TS was significantly associated with ALRI, APRI, and GPR and liver dysfunction. Conclusion: Noninvasive inflammatory indices (ALRI, APRI, and GPR) might be a promising indicators of liver dysfunction in patients with TS. Future prospective studies are needed to confirm our findings and to explore the clinical significance and prognostic value of systemic inflammatory indices in Turner syndrome.

Assessing the quality of life of health-referred children and adolescents with short stature: development and psychometric testing of the QoLISSY instrument.

BACKGROUND: When evaluating the outcomes of treatment in paediatric endocrinology, the health-related quality of life (HrQoL) of the child is to be taken into consideration. Since few self-reported HrQoL instruments exist for children with diagnosed short stature (dSS), the objective of this study was to develop and psychometrically test a targeted HrQoL instrument for use in multinational clinical research. METHODS: The target population were short stature (height<-2 SDS) children and adolescents (age 8-12 and 13-18 years) with a diagnosis of growth hormone deficiency (GHD) or idiopathic short stature (ISS), differing in growth hormone treatment status. Focus group discussions for concept and item generation, piloting of the questionnaire with cognitive debriefing, and instrument field testing with a retest were conducted simultaneously in five countries. After qualitative and preliminary quantitative analyses, psychometric testing of field test data in terms of reliability and validity including confirmatory factor analyses (CFA) was performed. RESULTS: Following item generation from focus group discussions, 124 items were included in a pilot test with a cognitive debriefing exercise providing preliminary feedback on item and domain operating characteristics. A field test with 268 participants showed high internal consistency reliabilities (alpha 0.82-0.95), good correlations with generic measures (up to r=.58), significant known group differences (e.g. in height: F=32, df 244, p<0.001) and an acceptable CFA model fit suggesting construct validity of the three-domain core structure with 22 items, supplemented by three mediator domains with 28 items. CONCLUSIONS: The QoLISSY questionnaire is a promising step forward in assessing the impact of dSS on HrQoL. It is based on items generated from the subjective experience of short stature children referred for endocrine investigation, is validated for use in five languages and it is easy to administer in clinical and research settings.

Parental perception of health-related quality of life in children and adolescents with short stature: literature review and introduction of the parent-reported QoLISSY instrument.

BACKGROUND: Health-related quality of life (HrQoL) of the child diagnosed with short stature is an important outcome to be assessed both from the patient as well as from the parental perspective. The objective of this study was to review the literature on parent-reported HrQoL and to subsequently develop and psychometrically test the parent-reported version of the Quality of Life in Short Stature Youth (QoLISSY) instrument for use in clinical and epidemiologic research. METHODS: A review of the literature on parental assessment of child HrQoL via PUBMED was followed by a psychometric analysis of data collected within the European QoLISSY study, in which 686 eligible parents of short statured children/adolescents (aged 4-18 years) meeting inclusion criteria participated. Patient inclusion criteria were a height below -2 SD, a diagnosis of growth hormone deficiency (GHD) or idiopathic short stature (ISS), and treatment status in terms of receiving or not receiving recombinant human growth hormone therapy. Focus groups eliciting parental HrQoL statements, pilot testing with cognitive debriefing, and a field test in 317 parents with a retest in 148 parents were conducted simultaneously in France, Germany, Spain, Sweden and the UK. The psychometric performance of the parent-reported instrument, developed in parallel to the child/ adolescent self-report version, was assessed using standard tests of reliability and validity. RESULTS: Literature search failed to identify a cross-culturally developed height specific instrument available for both patient self-report and parental observer report. Analysis of the QoLISSY focus group phase conducted separately in children, adolescents and parents yielded 169 items generated from parent focus groups. A cognitive debriefing exercise followed by a pilot test of preliminary psychometric characteristics resulted in deleting poorly performing items. Field testing of the parent-reported version suggested a three-domain core HrQoL structure with 22 items, additional 44 items assessing three mediator domains and two parent specific domains. The parent report version demonstrated good criterion and construct validity as well as internal consistency and test retest reliability. CONCLUSIONS: The QoLISSY parent report questionnaire closes a gap in the simultaneous assessment of parent and child perception of HrQoL in an international context. It is based on items generated from the experience of short statured children, adolescents and their parents and is validated for use in five European languages. It is feasible, relevant for this population, psychometrically sound and is easy to administer in research and clinical settings.

MAST1-related mega-corpus-callosum syndrome with central hypogonadism.

OBJECTIVE: Heterozygous variations in microtubule-associated serine/threonine kinase 1 gene (MAST1) were recently described in the mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM, MIM 618273), revealing the importance of the MAST genes family in global brain development. To date, patients with MAST1 gene mutations were mostly young children with central nervous system involvement, impaired motor function, speech delay, and brain magnetic resonance imaging (MRI) abnormalities. Here, we report the clinical presentation of an adult patient with a rare and de novo MAST1 mutation with central hypogonadism that could extend this phenotype. METHODS: A panel of 333 genes involved in epilepsy or cortical development was sequenced in the described patient. Routine biochemical analyses were performed, and hormonal status was investigated. RESULT: We report a 22-year-old man with a de novo, heterozygous missense variant in MAST1 (Chr19(GRCh37):g.12975903G > A, NP_055790.1:p.Gly517Ser). He presented with an epileptic encephalopathy associated with cerebral malformations, short stature, hypogonadotropic hypogonadism, and secondary osteopenia. CONCLUSION: This is the first patient with MAST1 gene mutation described with central hypogonadism, which may be associated with the phenotype of MCCCHCM syndrome.

User-centered approach in the development of an eHealth tool for self-management skills in functional insulin therapy to prevent complications of diabetes.

One of the biggest tasks for health professionals is to address the needs of persons with chronic illnesses like type 1 diabetes (T1D) and to support the acquisition of all necessary self-management behaviors. Functional insulin therapy (FIT) enables patients to adapt insulin doses according to everyday situations and reduces the risk of complications of diabetes. The aim was to describe the co-development, with patient as partners, of an eHealth tool for the acquisition of skills in FIT, to evaluate the user's acceptability and learning effectiveness on a sample of T1D patients followed in the University Hospital of Nancy. Subjects were invited to participate between July and August 2020. A total of 35 participants from different professional categories, median age of 41 years (IQR 27; 60) were included. In 22 subjects having access to all learning activities, there were positive relationships between the success score and the task (Spearman's rank correlation coefficient rs = 0.5), between the intent to use and following parameters: perceived utility (rs = 0.694), educational adequacy (rs = 0.786), tasks rs = (0.664), technology (rs = 0.520) and ease of use (rs = 0.659). This pilot study describes a user-centered approach to development of an eHealth tool for the acquisition of self-management skills in FIT. The online tool was well accepted and showed a positive impact on learning. The concept presented here will be useful to prompt future eHealth interventions in T1D or other chronic conditions aiming to increase patients' autonomy to prevent disease-related complications.