Development of interactive empowerment services in support of personalised medicine

In an epoch where shared decision making is gaining importance, a patient\u2019s commitment to and knowledge about his/her health condition is becoming more and more relevant. Health literacy is one of the most important factors in enhancing the involvement of patients in their care. Nevertheless, other factors can impair patient processing and understanding of health information: psychological aspects and cognitive style may affect the way patients approach, select, and retain information. This paper describes the development and validation of a short and easy to fill-out questionnaire that measures and collects psycho-cognitive information about patients, named ALGA-C. ALGA-C is a multilingual, multidevice instrument, and its validation was carried out in healthy people and breast cancer patients. In addition to the aforementioned questionnaire, a patient profiling mechanism has also been developed. The ALGA-C Profiler enables physicians to rapidly inspect each patient\u2019s individual cognitive profile and see at a glance the areas of concern. With this tool, doctors can modulate the language, vocabulary, and content of subsequent discussions with the patient, thus enabling easier understanding by the patient. This, in turn, helps the patient formulate questions and participate on an equal footing in the decision-making processes. Finally, a preview is given on the techniques under consideration for exploiting the constructed patient profile by a personal health record (PHR). Predefined rules will use a patient\u2019s profile to personalise the contents of the information presented and to customise ways in which users complete their tasks in a PHR system. This optimises information delivery to patients and makes it easier for the patient to decide what is of interest to him/her at the moment

The Effect of a Comprehensive Life-Style Intervention Program of Diet and Exercise on Four Bone-Derived Proteins, FGF-23, Osteopontin, NGAL and Sclerostin, in Overweight or Obese Children and Adolescents

The adipose and bone tissues demonstrate considerable interconnected endocrine function. In the present study, we determined the concentrations of fibroblast growth factor-23 (FGF-23), osteopontin, neutrophil gelatinase-associated lipocalin (NGAL) and sclerostin in 345 children and adolescents who were overweight or obese (mean age ± SD mean: 10.36 ± 0.16 years; 172 males, 173 females; 181 prepubertal; and 164 pubertal) before and after their participation in a comprehensive life-style intervention program of diet and exercise for one year. Following the one-year life-style interventions, there was a significant decrease in BMI (p < 0.01), FGF-23 (p < 0.05), osteopontin (p < 0.01) and NGAL (p < 0.01), and an increase in sclerostin (p < 0.01) concentrations. BMI z-score (b = 0.242, p < 0.05) and fat mass (b = 0.431, p < 0.05) were the best positive predictors and waist-to-height ratio (WHtR) (b = −0.344, p < 0.05) was the best negative predictor of the change of osteopontin. NGAL concentrations correlated positively with HbA1C (b = 0.326, p < 0.05), WHtR (b = 0.439, p < 0.05) and HOMA-IR (b = 0.401, p < 0.05), while BMI (b = 0.264, p < 0.05), fat mass (b = 1.207, p < 0.05), HDL (b = 0.359, p < 0.05) and waist circumference (b = 0.263, p < 0.05) were the best positive predictors of NGAL. These results indicate that FGF-23, osteopontin, NGAL and sclerostin are associated with being overweight or obese and are altered in relation to alterations in BMI. They also indicate a crosstalk between adipose tissue and bone tissue and may play a role as potential biomarkers of glucose metabolism. Further studies are required to delineate the physiological mechanisms underlying this association in children and adolescents

Rheumatoid arthritis patients on persistent moderate disease activity on biologics have adverse 5-year outcome compared to persistent low-remission status and represent a heterogeneous group

Background: The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods: We included longitudinally monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥ 50% of a 5-year period) moderate (pMDA, 3.2 < DAS28 ≤ 5.1) or remission/low (pRLDA, DAS28 ≤ 3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28 < 4.2) and higher-moderate (phMDA, DAS28 ≥ 4.2) subgroups. Five-year trajectories of functionality (HAQ) were the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups. Results: We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n = 133, 45%) and phMDA (n = 162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+ 0.27 HAQ units, CI 95% + 0.22 to + 0.33; p < 0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+ 0.26 HAQ units, CI 95% 0.18 to 0.36; p < 0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2 ± 0.48 vs pMDA: 0.5 ± 0.96, p = 0.006; plMDA: 0.32 ± 0.6 vs phMDA: 0.64 ± 1.16, p = 0.038]. Male gender (p = 0.017), lower baseline DAS28 (p < 0.001), HAQ improvement > 0.22 (p = 0.029), and lower average DAS28 during the first trimester since treatment initiation (p = 0.001) independently predicted grouping into pRLDA. Conclusions: In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments. © 2020 The Author(s)

A national e-health program for the prevention and management of overweight and obesity in childhood and adolescence in Greece

Obesity in childhood and adolescence represents one of the most challenging public health problems of the 21st century owing to its epidemic proportions worldwide and the associated significant morbidity, mortality and public health costs. In Greece, the prevalence of overweight and obesity in childhood and adolescence exceeds 30–35%. To address the increasing prevalence of overweight and obesity in children and adolescents in our country, we developed the ‘National e-Health Program for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence’, which provides specific and detailed guidance to all primary health care physicians about the personalized management of children and adolescents with overweight or obesity. In the present study we evaluated 2400 children and adolescents [mean age ± SD: 10.10 ± 0.09 years.; Males: 1088, Females: 1312; Obesity (n = 1370, 57.1%), Overweight (n = 674, 28.1%), normal BMI (n = 356, 14.8%)], who followed the personalized multi-disciplinary management plan specified by the ‘National e-Health Program for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence’, and were studied prospectively for 1 year. We demonstrated that at the end of the first year, the prevalence of obesity decreased by 32.1%, the prevalence of overweight decreased by 26.7%, and the cardiometabolic risk factors improved significantly. These findings indicate that our National e-Health Program is effective at reducing the prevalence of overweight and obesity in childhood and adolescence after one year of intervention in the largest sample size reported to date. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

The Effect of a Life-Style Intervention Program of Diet and Exercise on Irisin and FGF-21 Concentrations in Children and Adolescents with Overweight and Obesity

Overweight and obesity in childhood and adolescence represent major public health problems of our century, and account for increased morbidity and mortality in adult life. Irisin and Fibroblast Growth Factor 21 (FGF-21) have been proposed as prognostic and/or diagnostic biomarkers in subjects with obesity and metabolic syndrome, because they increase earlier than other traditional biomarkers. We determined the concentrations of Irisin and FGF-21 in children and adolescents with overweight and obesity before and after one year of a life-style intervention program of diet and physical exercise and explored the impact of body mass index (BMI) reduction on the concentrations of Irisin, FGF-21 and other cardiometabolic risk factors. Three hundred and ten (n = 310) children and adolescents (mean age ± SD: 10.5 ± 2.9 years) were studied prospectively. Following one year of the life-style intervention program, there was a significant decrease in BMI (p = 0.001), waist-to-hip ratio (p = 0.024), waist-to-height ratio (p = 0.024), and Irisin concentrations (p = 0.001), and an improvement in cardiometabolic risk factors. There was no alteration in FGF-21 concentrations. These findings indicate that Irisin concentrations decreased significantly as a result of BMI reduction in children and adolescents with overweight and obesity. Further studies are required to investigate the potential role of Irisin as a biomarker for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors

Hair Cortisol Concentrations in Overweight and Obese Children and Adolescents

Introduction: Obesity in childhood and adolescence is associated with complications that resemble those seen in hypercortisolism. Hair cortisol concentration (HCC) in children is a reliable marker of long-term endogenous cortisol concentrations. We determined HCC in overweight and obese children and adolescents, and examined the relation between HCC and other cardiometabolic parameters. Methods: Three hundred children and adolescents aged 4-18 years (mean age ± standard error of the mean [SEM]: 10.49 ± 0.15 years; 140 [46.7%] obese, 94 [31.3%] overweight, 66 [22%] of normal BMI; 76 males, 224 females) were studied prospectively. Blood samples for determination of hematological, biochemical, and endocrinologic parameters were obtained. Systolic (SBP) and diastolic blood pressure (DBP) was determined. Scalp hair samples were collected from the posterior vertex, and HCC was measured using an electrochemiluminescence immunoassay. Results: Obese subjects had significantly higher SBP, DBP, waist and hip circumferences, waist-to-hip ratio, waist-to-height ratio, ALT, γ-GT, triglycerides, apolipoprotein-B, insulin, and HbA1C concentrations than overweight and normal-BMI subjects. HCC did not differ significantly among the three groups of subjects (mean ± SEM: 8.74 ± 0.43 vs. 8.88 ± 0.52 vs. 9.33 ± 0.72, all p > 0.05). No significant association was noted between HCC and cardiometabolic or body composition parameters. HCC was significantly higher in prepubertal girls than prepubertal boys (9.45 ± 0.38 vs. 7.35 ± 0.39, p = 0.007). Conclusion: In our study, overweight and obesity was not associated with elevated HCC. Furthermore, no association was found between HCC with cardiometabolic parameters and fat mass. Further studies are required to delineate the association between overweight/obesity and HCC. © 2019 S. Karger AG, Basel. Copyright: All rights reserved

A Comprehensive, Multidisciplinary, Personalized, Lifestyle Intervention Program Is Associated with Increased Leukocyte Telomere Length in Children and Adolescents with Overweight and Obesity

Leucocyte telomere length (LTL) is a robust marker of biological aging and is associated with obesity and cardiometabolic risk factors in childhood and adolescence. We investigated the effect of a structured, comprehensive, multidisciplinary, personalized, lifestyle intervention program of healthy diet and physical exercise on LTL in 508 children and adolescents (239 males, 269 females; 282 prepubertal, 226 pubertal), aged 10.14 ± 0.13 years. Participants were classified as obese (n = 267, 52.6%), overweight (n = 174, 34.2%), or of normal BMI (n = 67, 13.2%) according to the International Obesity Task Force (IOTF) cutoff points and were studied prospectively for one year. We demonstrated that LTL increased significantly after 1 year of the lifestyle interventions, irrespective of gender, pubertal status, or body mass index (BMI). Waist circumference was the best negative predictor of LTL at initial assessment. The implementation of the lifestyle interventions also resulted in a significant improvement in clinical (BMI, BMI z-score and waist to height ratio) and body composition indices of obesity, inflammatory markers, hepatic enzymes, glycated hemoglobin (HbA1C), quantitative insulin sensitivity check index (QUICKI), and lipid profile in all participants. These findings indicate that the increased LTL may be associated with a more favorable metabolic profile and decreased morbidity later in life

In an early SLE cohort the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria classify non-overlapping groups of patients: use of all three criteria ensures optimal capture for clinical studies while their modification earlier classification and treatment

OBJECTIVES: Classification criteria are biased towards classifying long-standing disease. We compared the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)-2019, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and ACR-1997 criteria in an early (median 48 months) systemic lupus erythematosus (SLE) cohort. METHODS: Patients diagnosed with SLE (n=690) or control diseases (n=401). Sensitivity, specificity of the criteria and time-to-classification were calculated. Modified classification algorithms were derived from a random 80% and validated in the remaining 20% of the dataset running multiple iterations. RESULTS: At last assessment, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 85.7%, 91.3% and 88.6%, with specificities 93.0%, 93.8% and 97.3%, respectively. Both SLICC and EULAR/ACR enabled earlier classification. Only 76.7% of patients with SLE met all three criteria suggesting non-overlapping groups. Notably, unclassified patients had high prevalence of British Isles Lupus Assessment Group moderate/severe manifestations (43.3%-60%) and SLICC/ACR organ damage (30%-50%). At diagnosis, criteria missed 25.6%-30.5% of patients. Modification of EULAR/ACR and SLICC algorithms to include hypocomplementaemia and/or positive anti-phospholipid antibodies as alternative entry criterion, and/or allow classification with fewer clinical criteria from multiple organs, increased their sensitivity at diagnosis (median 82.0% and 86.2%) and overall (93.7% and 97.1%) with modest decreases in specificity. Importantly, patients who were still missed by the modified criteria had lower incidence of major organ involvement, use of immunosuppressive/biological therapies and organ damage. CONCLUSIONS: The SLICC and EULAR/ACR are more sensitive than the ACR and the EULAR/ACR criteria have superior specificity in early SLE, although patients with significant disease can be missed. Combination and/or modification of the classification algorithms may enhance their sensitivity, allowing earlier classification and treatment of more patients with high disease burden. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ

Lupus or not? SLE Risk Probability Index (SLERPI): A simple, clinician-friendly machine learning-based model to assist the diagnosis of systemic lupus erythematosus

Objectives: Diagnostic reasoning in systemic lupus erythematosus (SLE) is a complex process reflecting the probability of disease at a given timepoint against competing diagnoses. We applied machine learning in well-characterised patient data sets to develop an algorithm that can aid SLE diagnosis. Methods: From a discovery cohort of randomly selected 802 adults with SLE or control rheumatologic diseases, clinically selected panels of deconvoluted classification criteria and non-criteria features were analysed. Feature selection and model construction were done with Random Forests and Least Absolute Shrinkage and Selection Operator-logistic regression (LASSO-LR). The best model in 10-fold cross-validation was tested in a validation cohort (512 SLE, 143 disease controls). Results: A novel LASSO-LR model had the best performance and included 14 variably weighed features with thrombocytopenia/haemolytic anaemia, malar/maculopapular rash, proteinuria, low C3 and C4, antinuclear antibodies (ANA) and immunologic disorder being the strongest SLE predictors. Our model produced SLE risk probabilities (depending on the combination of features) correlating positively with disease severity and organ damage, and allowing the unbiased classification of a validation cohort into diagnostic certainty levels (unlikely, possible, likely, definitive SLE) based on the likelihood of SLE against other diagnoses. Operating the model as binary (lupus/not-lupus), we noted excellent accuracy (94.8%) for identifying SLE, and high sensitivity for early disease (93.8%), nephritis (97.9%), neuropsychiatric (91.8%) and severe lupus requiring immunosuppressives/biologics (96.4%). This was converted into a scoring system, whereby a score >7 has 94.2% accuracy. Conclusions: We have developed and validated an accurate, clinician-friendly algorithm based on classical disease features for early SLE diagnosis and treatment to improve patient outcomes