Healthcare use and direct medical costs in a cleft lip and palate population: an analysis of observed and protocolized care and costs.

This study was performed to describe observed healthcare utilization and medical costs for patients with a cleft, compare these costs to the expected costs based on the treatment protocol, and explore the additional costs of implementing the International Consortium for Health Outcomes Measurement (ICHOM) Standard Set for Cleft Lip and Palate (CL/P). Forty patients with unilateral CL/P between 0 and 24 years of age, treated between 2012 and 2019 at Erasmus University Medical Center, were included. Healthcare services (consultations, diagnostic and surgical procedures) were counted and costs were calculated. Expected costs based on the treatment protocol were calculated by multiplying healthcare products by the product prices. Correspondingly, the additional expected costs after implementing the ICHOM Standard Set (protocol + ICHOM) were calculated. Observed costs were compared with protocol costs, and the additional expected protocol + ICHOM costs were described. The total mean costs were highest in the first year after birth (€5596), mainly due to surgeries. The mean observed total costs (€40,859) for the complete treatment (0-24 years) were 1.6 times the expected protocol costs (€25,198) due to optional, non-protocolized procedures. Hospital admissions including surgery were the main cost drivers, accounting for 42% of observed costs and 70% of expected protocol costs. Implementing the ICHOM Standard Set increased protocol-based costs by 7%.

Instrumental variable analysis to estimate treatment effects: a simulation study showing potential benefits of conditioning on hospital.

BACKGROUND: Instrumental variable (IV) analysis holds the potential to estimate treatment effects from observational data. IV analysis potentially circumvents unmeasured confounding but makes a number of assumptions, such as that the IV shares no common cause with the outcome. When using treatment preference as an instrument, a common cause, such as a preference regarding related treatments, may exist. We aimed to explore the validity and precision of a variant of IV analysis where we additionally adjust for the provider: adjusted IV analysis. METHODS: A treatment effect on an ordinal outcome was simulated (beta - 0.5 in logistic regression) for 15.000 patients, based on a large data set (the IMPACT data, n = 8799) using different scenarios including measured and unmeasured confounders, and a common cause of IV and outcome. We compared estimated treatment effects with patient-level adjustment for confounders, IV with treatment preference as the instrument, and adjusted IV, with hospital added as a fixed effect in the regression models. RESULTS: The use of patient-level adjustment resulted in biased estimates for all the analyses that included unmeasured confounders, IV analysis was less confounded, but also less reliable. With correlation between treatment preference and hospital characteristics (a common cause) estimates were skewed for regular IV analysis, but not for adjusted IV analysis. CONCLUSION: When using IV analysis for comparing hospitals, some limitations of regular IV analysis can be overcome by adjusting for a common cause. TRIAL REGISTRATION: We do not report the results of a health care intervention.

Physical therapy in patients with systemic sclerosis: physical therapists' perspectives on current delivery and educational needs.

OBJECTIVE: To assess the perspectives of physical therapists treating patients with systemic sclerosis (SSc) on their current practice and educational needs. METHOD: In July 2019, 405 SSc patients attending a multidisciplinary SSc programme received a survey on physical therapy. Patients who indicated having received physical therapy in the past 2 years were asked to invite their treating physical therapist to complete a questionnaire including sociodemographic characteristics, referral process, content of treatment, perceived knowledge and skills, and educational needs (mostly yes/no answers). RESULTS: Forty-eight of 80 possibly eligible physical therapists treating SSc patients returned the questionnaire [median age 44 years (interquartile range 35-58); 52% female; median number of SSc patients currently treated: 1 (range 1-4)]. Eighty-one per cent (n = 39) of physical therapists had received a referral, with 69% (n = 27/39) judging its content as insufficient. The most often provided types of exercises were range of motion (96%), muscle-strengthening (85%), and aerobic (71%) exercises, followed by hand (42%) and mouth (10%) exercises. Concerning manual treatment, 65% performed either massage or passive mobilization. Regarding competences, 65% indicated feeling capable of treating SSc patients. Nevertheless, 85% expressed the need for an information website on physical therapy in SSc, and 77% for postgraduate education on SSc. CONCLUSION: Primary care physical therapists treating patients with SSc used a wide range of treatment modalities. Although most stated that they treated very few patients, the majority felt capable of treating SSc patients. Nevertheless, the large majority expressed a need for additional information and educational activities concerning SSc.

Ordinal outcome analysis improves the detection of between-hospital differences in outcome.

BACKGROUND: There is a growing interest in assessment of the quality of hospital care, based on outcome measures. Many quality of care comparisons rely on binary outcomes, for example mortality rates. Due to low numbers, the observed differences in outcome are partly subject to chance. We aimed to quantify the gain in efficiency by ordinal instead of binary outcome analyses for hospital comparisons. We analyzed patients with traumatic brain injury (TBI) and stroke as examples. METHODS: We sampled patients from two trials. We simulated ordinal and dichotomous outcomes based on the modified Rankin Scale (stroke) and Glasgow Outcome Scale (TBI) in scenarios with and without true differences between hospitals in outcome. The potential efficiency gain of ordinal outcomes, analyzed with ordinal logistic regression, compared to dichotomous outcomes, analyzed with binary logistic regression was expressed as the possible reduction in sample size while keeping the same statistical power to detect outliers. RESULTS: In the IMPACT study (9578 patients in 265 hospitals, mean number of patients per hospital = 36), the analysis of the ordinal scale rather than the dichotomized scale ('unfavorable outcome'), allowed for up to 32% less patients in the analysis without a loss of power. In the PRACTISE trial (1657 patients in 12 hospitals, mean number of patients per hospital = 138), ordinal analysis allowed for 13% less patients. Compared to mortality, ordinal outcome analyses allowed for up to 37 to 63% less patients. CONCLUSIONS: Ordinal analyses provide the statistical power of substantially larger studies which have been analyzed with dichotomization of endpoints. We advise to exploit ordinal outcome measures for hospital comparisons, in order to increase efficiency in quality of care measurements. TRIAL REGISTRATION: We do not report the results of a health care intervention.

Patient-Reported Outcome Measures May Add Value in Breast Cancer Surgery.

PURPOSE: Considering the comparable prognosis in early-stage breast cancer after breast-conserving therapy (BCT) and mastectomy, quality of life should be a focus in treatment decision(s). We retrospectively collected PROs and analyzed differences per type of surgery delivered. We aimed to obtain reference values helpful in shared decision-making. PATIENTS AND METHODS: pTis-T3N0-3M0 patients operated between January 2005 and September 2016 were eligible if: (1) no chemotherapy was administered < 6 months prior to enrolment, and (2) identical surgeries were performed in case of bilateral surgery. After consent, EQ-5D-5L, EORTC-QLQ-C30/BR23, and BREAST-Q were administered. PROs were evaluated per baseline characteristics using multivariable linear regression models. Outcomes were compared for different surgeries as well as for primary (PBC) and second primary or recurrent (SBC) breast cancer patients using analyses of variance (ANOVAs). RESULTS: The response rate was 68%. PROs in 612 PBC patients were comparable to those in 152 SBC patients. Multivariable analyses showed increasing age to be associated with lower "physical functioning" [ß - 0.259, p < 0.001] and "sexual functioning" [ß - 0.427, p < 0.001], and increasing time since surgery with less "fatigue" [ß - 1.083, p < 0.001]. Mastectomy [ß - 13.596, p = 0.003] and implant reconstruction [ß - 13.040, p = 0.007] were associated with lower "satisfaction with breast" scores than BCT. Radiation therapy was associated with lower satisfaction scores than absence of radiotherapy. DISCUSSION: PRO scores were associated with age, time since surgery, type of surgery, and radiation therapy in breast cancer patients. The scores serve as a reference value for different types of surgery in the study population and enable prospective use of PROs in shared decision-making.

Patient reported outcome measures in breast cancer patients.

INTRODUCTION: In the International Consortium for Health Outcome Measures (ICHOM) breast cancer outcome set Patient Reported Outcome Measurements (PROMs) form an important but rather innovative part. Few data exist on scores per type of breast surgery and how to use scores in surgical practice. We evaluated PROM scores as well as satisfaction with and expectations of the use of PROMs in breast cancer patients using the national and local patient advocate society. METHODS: Through an online survey patients were asked to report age, type of breast cancer surgery (whether Breast Conserving Therapy (BCT), mastectomy, autologous or implant breast reconstruction) and time since surgery. PROMs (EORTC-QLQ-C30/BR23 and BREAST-Q postoperative modules) were compared for the different surgeries. Additional comparison was made with literature normative and reference scores. Three questions evaluated satisfaction with PROMs and expectations. RESULTS: 496 patients completed all PROMs and 487 the satisfaction/expectation-questions. Significantly reduced physical functioning was reported following BCT as compared to other surgeries and literature reference values. Satisfaction scores were higher following autologous reconstruction and lower following implant reconstruction as compared to BCT. PRO scores were comparable to normative and references scores except for the 'physical functioning' (BREAST-Q) scores that reported lower in the present study. Ninety-four percent of the participants was (highly) satisfied with future PROM use. CONCLUSIONS: Statistical significant differences were found for PROMs following different types of breast surgery. The significance of these results should become clearer trough collection of future data. The great majority of participants considered PROMs as (highly) acceptable and reacted positively on their proposed future use.

Validated age-specific reference values for CSF total protein levels in children.

OBJECTIVE: To define age-specific reference values for cerebrospinal fluid (CSF) total protein levels for children and validate these values in children with Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). METHODS: Reference values for CSF total protein levels were determined in an extensive cohort of diagnostic samples from children (<18 year) evaluated at Erasmus Medical Center/Sophia Children's Hospital. These reference values were confirmed in children diagnosed with disorders unrelated to raised CSF total protein level and validated in children with GBS, ADEM and MS. RESULTS: The test results of 6145 diagnostic CSF samples from 3623 children were used to define reference values. The reference values based on the upper limit of the 95% CI (i.e. upper limit of normal) were for 6 months-2 years 0.25 g/L, 2-6 years 0.25 g/L, 6-12 years 0.28 g/L, 12-18 years 0.34 g/L. These reference values were confirmed in a subgroup of 378 children diagnosed with disorders that are not typically associated with increased CSF total protein. In addition, the CSF total protein levels in these children in the first 6 months after birth were highly variable (median 0.47 g/L, IQR 0.26-0.65). According to these new reference values, CSF total protein level was elevated in 85% of children with GBS, 66% with ADEM and 23% with MS. CONCLUSION: More accurate age-specific reference values for CSF total protein levels in children were determined. These new reference values are more sensitive than currently used values for diagnosing GBS and ADEM in children.

Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.

Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2-K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D.

Crying Without Tears: Dimensions of Crying and Relations With Ocular Dryness and Mental Well-Being in Patients With Sjögren's Syndrome.

This study examined dimensions of crying and its relations with ocular dryness and mental well-being in patients with Sjögren's syndrome, a systemic autoimmune disease with dryness as primary symptom. Three-hundred patients with Sjögren's syndrome completed questionnaires on crying, dryness, and well-being. The crying questionnaire revealed four dimensions: "Cryability" (comprising both crying sensibility and ability to cry), Somatic consequences, Frustration, and Suppression. Compared to 100 demographically-matched control participants from the general population, patients scored low on Cryability and high on Somatic consequences and Frustration. The crying dimensions generally showed significant but weak associations with ocular dryness and mental well-being in patients. This is the first quantitative study indicating that crying problems are more common in patients with Sjögren's syndrome than in the general population. Perhaps, patients who experience problems with crying could be helped to rely on other ways of expressing emotions than crying in tear-inducing situations.

[Acculturation orientations and psychosocial adaptation among adolescents with immigrant background]. / Orientations d'acculturation et adaptation psychosociale des adolescents issus de l'immigration.

OBJECTIVE: The aim of the study was to explore the typology of adolescents with immigrant background based on the orientations of acculturation and to estimate the psychosocial adaptation of the various subtypes. METHOD: A sample of 228 French high school students with an immigrant background completed a questionnaire assessing acculturation orientations (Immigrant Acculturation Scale; Barrette et al., 2004), antisocial behaviors, depressive symptoms and self-esteem. Cluster analysis based on acculturation orientations was performed using the k-means method. RESULTS: Cluster analysis produced four distinct acculturation profiles: bicultural (31%), separated (28%), marginalized (21%), and assimilated-individualistic (20%). Adolescents in the separated and marginalized clusters, both characterized by rejection of the host culture, reported higher levels of antisocial behavior. Depressive symptoms and self-esteem did not differ between clusters. DISCUSSION: Several hypotheses may explain the association between separation and delinquency. First, separation and rejection of the host culture may lead to rebellious behavior such as delinquency. Conversely, delinquent behavior may provoke rejection or discrimination by peers or school, or legal sanctions that induce a reciprocal process of rejection of the host culture and separation. The relationship between separation and antisocial behavior may be bidirectional, each one reinforcing the other, resulting in a negative spiral. This study confirms the interest of the study of the orientations of acculturation in the understanding of the antisocial behavior of adolescents with immigrant background.

[Cannabis use and antisocial behaviors in high-school students]. / Consommation de cannabis et comportements antisociaux dans un échantillon d'adolescents scolarisés.

OBJECTIVE: The aim of the study was to evaluate the contribution of cannabis to the prediction of delinquent behaviors. METHOD: Participants were 312 high-school students who completed self-report questionnaires measuring antisocial behaviors, the frequency of cannabis and alcohol use, psychopathic traits using the Youth Psychopathic traits Inventory, borderline traits, depressive symptoms, socio-economic status, life events, attachment to parents, and low academic achievement. Hierarchical multiple regression analyses were conducted to investigate the contribution of cannabis use and potential confounding variables to antisocial behaviors. RESULTS: Boys reported a greater number of delinquent behaviors than girls (10.2±9.2 vs. 5.4±5.3, t=9.2, P<0.001). Thirty-seven percent of boys and 24 % of girls reported having used cannabis at least once during the last six months (P<0.001). Among cannabis users, boys reported a greater frequency of use than girls: average use for boys was 2-3 times per month whereas average use for girls was once a month (3.4±2.3 vs. 2.6±2, t=2.9, P=0.004). Cannabis users reported a greater number of antisocial behaviors than non-users (13.2±9.9 vs. 6.1±6.3, t=13.6, P<0.001). Multiple regression analyses showed that cannabis use was a significant independent predictor of antisocial behaviors in both gender (ß=.35, P<.001 in boys, ß=.29, P<.001 in girls) after adjustment for alcohol use, psychopathological and sociofamilial variables. DISCUSSION: The unique and independent association between frequency of cannabis use and antisocial behaviors does not indicate the causal direction of the relationship. It may be that cannabis use induces antisocial behaviors by enhancing impulsivity or irritability or by the need for money to buy cannabis. Conversely, antisocial behaviors may lead to cannabis use either through becoming used to transgressions or through the influence of delinquent peers using cannabis. This link is probably bidirectional, cannabis use and antisocial behaviors influencing mutually in a negative interactive spiral. This association suggests that these two problems are to be jointly approached when treating adolescents using cannabis or having antisocial behaviors.

Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and type 2 diabetes susceptibility.

AIMS: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic ß-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to type 2 diabetes in humans. METHODS: Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for type 2 diabetes susceptibility in up to 25 000 people (8148 with type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. RESULTS: rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*104) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*104) but again not in men (P = 0.34). CONCLUSION: The present data identify DRD2/ANKK1 as a potential sex-specific type 2 diabetes susceptibility gene.

Low mitochondrial DNA content associates with familial longevity: the Leiden Longevity Study.

Long-lived individuals delay aging and age-related diseases like diabetes, hypertension, and cardiovascular disease. The exact underlying mechanisms are largely unknown, but enhanced mitochondrial biogenesis and preservation of mitochondrial function have been suggested to explain healthy ageing. We investigated whether individuals belonging to long-lived families have altered mitochondrial DNA (mtDNA) content, as a biomarker of mitochondrial biogenesis and measured expression of genes regulating mitochondrial biogenesis. mtDNA and nuclear DNA (nDNA) levels were measured in blood samples from 2,734 participants from the Leiden Longevity Study: 704 nonagenarian siblings, 1,388 of their middle-aged offspring and 642 controls. We confirmed a negative correlation of mtDNA content in blood with age and a higher content in females. The middle-aged offspring had, on average, lower levels of mtDNA than controls and the nonagenarian siblings had an even lower mtDNA content (mtDNA/nDNA ratio = 0.744 ± 0.065, 0.767 ± 0.058 and 0.698 ± 0.074, respectively; p controls-offspring = 3.4 × 10(-12), p controls-nonagenarians = 6.5 × 10(-6)), which was independent of the confounding effects of age and gender. Subsequently, we examined in a subset of the study the expression in blood of two genes regulating mitochondrial biogenesis, YY1 and PGC-1α. We found a positive association of YY1 expression and mtDNA content in controls. The observed absence of such an association in the offspring suggests an altered regulation of mitochondrial biogenesis in the members of long-lived families. In conclusion, in this study, we show that mtDNA content decreases with age and that low mtDNA content is associated with familial longevity. Our data suggest that preservation of mitochondrial function rather than enhancing mitochondrial biogenesis is a characteristic of long-lived families.

The role of pharmacogenetics in drug disposition and response of oral glucose-lowering drugs.

The primary goal of type 2 diabetes mellitus (T2DM) disease management is improvement of quality of life and prevention of complications. One way to achieve these goals is improving glycemic control by using different types of oral glucose-lowering medications. Currently seven different pharmacological oral glucose-lowering drug classes are available, each with its own mechanism of action and characteristics regarding absorption, distribution, metabolism, and elimination. Unfortunately, the response to the different types of glucose-lowering medication is highly variable between individuals resulting in unnecessary treatment failure. Genetic factors are thought to contribute to the variability in response and may present an opportunity to improve treatment outcome. In recent years, many efforts were taken to identify genetic variants that influence the pharmacokinetics, pharmacodynamics, and ultimately the therapeutic response of the different oral glucose-lowering drugs. Indeed several genetic variants are associated with the response to oral glucose-lowering drugs. This review comprises current knowledge on genetic variants affecting both pharmacokinetics and pharmacodynamics of oral glucose-lowering drugs. Included variants are located in genes coding for drug transporters, i.e., the organic anion-transporting family and the organic cation transporter family; genes involved in metabolism, i.e., cytochrome P450 superfamily; genes coding for drug receptors; T2DM-associated genes; and genes identified by genome-wide association studies (GWASs). Furthermore, this review provides insight into current status and future directions for personalized medicine in T2DM.

[Psychometric properties of the French version of the How I Think Questionnaire]. / Étude des qualités psychométriques de la version française du How I Think Questionnaire dans un échantillon d'adolescents français.

UNLABELLED: Certain research has pointed out the relative importance of cognitive distortions in the development of antisocial behavior. Distortions of social cognitions that facilitate aggression and other types of antisocial behavior have been described as self-serving cognitive distortions (Barriga et al., 2001 [2]). Considering the importance of the assessment of delinquent cognitive distortions, an instrument has been validated to measure self-serving cognitive distortions: the How I Think Questionnaire (HIT-Q, Barriga et al., 2001 [2]). Thus, the aim of the present study was to evaluate the convergent, discriminant and concurrent validity of a French version of the HIT-Q and its four dimensions (self-centered, blaming other, minimizing/mislabeling and assuming the worst). METHOD: A sample of 972 French high-school students completed the Youth Psychopathic traits Inventory (YPI ; Andershed et al., 2002 ; Andershed et al., 2007 [26,27]) used to evaluate the convergent validity of the HIT-Q. To investigate discriminant validity, participants also completed the Sociomoral Reflection Measure-Short Form (SMR-SF ; Gibbs et al., 1992 [28]) and the Interpersonal Reactivity Index (IRI ; Davis, 1983 [29]) used to assess cognitive and affective empathy. To measure antisocial behavior, the French versions of the Self-Reported Delinquency Questionnaire (SRDQ ; Le Blanc and Frechette, 1989 [22]), the Antisocial Behavior Scale (ABS ; Schawb-Stone et al., 1996 [23]), the Self-Reported Delinquency Behavior (SRDB ; Elliott and Menard, 1996 [24]) and three items of the Sexual Experiences Survey (SES ; Koss et al., 2007 [25]) were used. Two samples were composed based on the same socio-demographic (age and gender) and socio-economic characteristics and ethnic background. French males scoring in the upper quartile on the antisocial behavior total score were classified in the antisocial group (n=135) and the rest of the sample in the non-antisocial group (n=306). Convergent and discriminant validity was determined using Pearson coefficients of correlation. One-way analyses of variance were used for mean scores comparisons. Regression analysis was used to evaluate the relative contribution of self-serving cognitive distortions to the prediction of antisocial behavior. RESULTS: The French version of the HIT-Q showed acceptable reliability and validity and also a satisfying convergent and discriminant validity. The HIT-Q and its dimensions were positively and highly correlated to psychopathic traits (r=0.50 to r=0.61, p<0.05) ; these findings suggested a good convergent validity. The correlation between self-serving cognitive distortions and social moral reasoning (r=-0.23 to r=-0.28, p<0.05) and empathy (r=-0.13 to r=-0.20, p<0.05) appeared to be negative and low ; this relationship was conclusive and showed a satisfying discriminant validity. Mean comparison showed that participants in the antisocial group reported higher scores of self-serving cognitive distortions and its dimensions than the non-antisocial group. Self-serving cognitive distortions significantly predicted antisocial behavior (ß=0.58, SE=0.02, p<0.001) and explained 34% of the variance. DISCUSSION: The study of the convergent validity of the HIT-Q with the YPI as external criteria showed they were closely linked, which suggests self-serving cognitive distortion may be the cognitive expression of psychopathic traits. The discriminant validity of the HIT-Q with moral reasoning and empathy was satisfying and similar to previous results (Lardén et al., 2006 [20]). In concordance with previous studies, delinquent cognitive distortions appeared to be a significant predictor of antisocial behavior and moreover, participants in the antisocial group reported higher scores of self-serving cognitive distortions (Capuano, 2007 ; Barriga and Gibbs, 1996 ; Nas et al., 2008 [10-12]). CONCLUSION: The present study showed that the French version of the HIT-Q presents good psychometric properties.

[Relationships between emotional intelligence, alexithymia and interpersonal delinquent behaviour in a sample of high-school students]. / Relations entre intelligence émotionnelle, alexithymie et comportements délinquants de type interpersonnel dans un échantillon d'adolescents scolarisés.

INTRODUCTION: A positive link between alexithymia and delinquency, as well as a negative link between alexithymia and emotional intelligence, has already been demonstrated. Previous studies have highlighted that emotional intelligence is associated with antisocial behaviour. Even though the frequency of alexithymia has been explored in non-clinical samples of adolescents, the relationship between alexithymia and delinquency has not been studied in community samples of adolescents. Furthermore, the link between alexithymia, emotional intelligence and interpersonal delinquency has never been explored in such a sample. The aim of the current study was to explore the relationship between alexithymia, emotional intelligence and interpersonal delinquency in a sample of high-school students. METHOD: A sample of 176 high school students (98 girls and 78 boys; mean age=16.6±0.77) completed self-report questionnaires. Interpersonal delinquency was measured using self-report delinquency questionnaires. The answers are rated on a 5-point scale (from 0 times to 5 or more times) depending on the frequency of the involvement during the past year. Alexithymia was assessed using the Toronto Alexithymia Scale (TAS-20; Bagby et al., 1994 [14]). Three specific dimensions of alexithymia can be assessed: the difficulty to identify feelings, the difficulty to describe feelings, and the externally-oriented cognitive style (α=.71; α=.60, α=.43, respectively). Emotional intelligence was assessed using the French version of the Trait Emotional Intelligence Questionnaire-Adolescent Short Form (TEIQue-ASF). RESULTS: Among participants with a moderate to high level of interpersonal delinquent behaviour, boys presented significantly higher scores on the total TAS score than boys with a lower level of delinquent behaviour. This difference was almost significant among girls. Among boys and girls, only the score on the "difficulty to identify feelings" subscale was significantly higher in the group with a moderate to high level of delinquent behaviour. There was no significant difference in TEIque-ASF total score depending on the gender. As boys reported a higher level of interpersonal delinquency than girls, regression analysis was conducted for males and females separately. Alexithymia and emotional intelligence were entered in both analyses. These variables explained 12% of the variance in interpersonal delinquency among boys (F (7, 110)<6.08, P<.05), and 6% among girls, (F (7, 110)<4.02, P<.05). Alexithymia was the only significant predictor of interpersonal delinquency for both genders. A second multiple regression analysis was conducted using the three subscales of the TAS-20 (Difficulty to identify feelings; Difficulty to describe feelings; Externally-oriented cognitive style). These variables explained 7% of the variance in interpersonal delinquency among boys (F (7, 110)<2.87, P<.05), and 8% among girls, (F (7, 110)<3.79, P<.05). The difficulty to identify feelings was the only significant predictor of interpersonal delinquency. DISCUSSION: In line with previous studies, emotional intelligence was linked to delinquent behaviour. The results of the current study show that only alexithymia, especially the difficulty to identify feelings, and to distinguish them from bodily sensations, was significantly linked to interpersonal delinquency among both girls and boys. Difficulty to identify feelings, especially when cognitive treatment is required, could be the root cause of dysfunctional behaviours. As a consequence, individuals are led "to outsource their internal tensions" by dysfunctional behaviours such as delinquency. CONCLUSION: Our findings suggest the importance of taking into account the emotional dimensions in the care of teenagers presenting antisocial behaviours. It appears of prime importance to lead young people presenting antisocial behaviours to identify their feelings.

Glucocorticoid receptor gene polymorphisms are associated with reduced first-phase glucose-stimulated insulin secretion and disposition index in women, but not in men.

AIM: Glucocorticoids are efficacious anti-inflammatory agents, but, in susceptible individuals, these drugs may induce glucose intolerance and diabetes by affecting ß-cell function and insulin sensitivity. We assessed whether polymorphisms in the glucocorticoid receptor gene NR3C1 associate with measures of ß-cell function and insulin sensitivity derived from hyperglycaemic clamps in subjects with normal or impaired glucose tolerance. METHODS: A cross-sectional cohort study was conducted in four academic medical centres in the Netherlands and Germany. Four hundred and forty-nine volunteers (188 men; 261 women) were recruited with normal glucose tolerance (n=261) and impaired glucose tolerance (n=188). From 2-h hyperglycaemic clamps, first- and second-phase glucose-stimulated insulin secretion, as well as insulin sensitivity index and disposition index, were calculated. All participants were genotyped for the functional NR3C1 polymorphisms N363S (rs6195), BclI (rs41423247), ER22/23EK (rs6189/6190), 9ß A/G (rs6198) and ThtIIII (rs10052957). Associations between these polymorphisms and ß-cell function parameters were assessed. RESULTS: In women, but not in men, the N363S polymorphism was associated with reduced disposition index (P=1.06 10(-4) ). Also only in women, the ER22/23EK polymorphism was associated with reduced first-phase glucose-stimulated insulin secretion (P=0.011) and disposition index (P=0.003). The other single-nucleotide polymorphisms were not associated with ß-cell function. Finally, none of the polymorphisms was related to insulin sensitivity. CONCLUSION: The N363S and ER22/23EK polymorphisms of the NR3C1 gene are negatively associated with parameters of ß-cell function in women, but not in men.

A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts.

AIMS/HYPOTHESIS: In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations. METHODS: Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n = 929) and the Rotterdam Study (n = 182) from the Netherlands, and the CARDS Trial (n = 254) from the UK were genotyped for rs11212617 and tested for an association with both HbA(1c) reduction and treatment success, defined as the ability to reach the treatment target of an HbA(1c) ≤ 7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed. RESULTS: In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p = 0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p = 0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metformin treatment success (OR 1.24, 95% CI 1.04, 1.49, p = 0.016 and OR 1.25, 95% CI 1.33, 1.38, p = 7.8 × 10(-6), respectively). CONCLUSIONS/INTERPRETATION: A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetic patients from the Netherlands and the UK. This is the first robustly replicated common susceptibility locus found to be associated with metformin treatment response.

A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females.

Mineralocorticoid (MR) and glucocorticoid receptors (GR) are abundantly expressed in the limbic brain and mediate cortisol effects on the stress-response and behavioral adaptation. Dysregulation of the stress response impairs adaptation and is a risk factor for depression, which is twice as abundant in women than in men. Because of the importance of MR for appraisal processes underlying the initial phase of the stress response we investigated whether specific MR haplotypes were associated with personality traits that predict the risk of depression. We discovered a common gene variant (haplotype 2, frequency ∼0.38) resulting in enhanced MR activity. Haplotype 2 was associated with heightened dispositional optimism in study 1 and with less hopelessness and rumination in study 2. Using data from a large genome-wide association study we then established that haplotype 2 was associated with a lower risk of depression. Interestingly, all effects were restricted to women. We propose that common functional MR haplotypes are important determinants of inter-individual variability in resilience to depression in women by differentially mediating cortisol effects on the stress system.