The nature of co-morbid psychopathology in adolescents with gender dysphoria.

Gender-referred adolescents (GR) have been reported to present with considerable psychiatric symptomatology compared to their age-peers. There is, however, little research on how they compare to adolescents referred due to mental health problems (MHR). We set out to compare psychopathology in adolescents referred to our specialized gender identity unit (n = 84) and adolescents referred to a general adolescent psychiatric clinic (n = 293) in a university hospital setting in Finland. Of the GR adolescents, 40.9% had not received any psychiatric diagnosis during adolescence. Eating disorders were less common in the GR than in the MHR group, but otherwise the prevalences of disorders did not differ statistically significantly. At the symptom level, the GR adolescents displayed significantly more suicidal ideation and talk and less alcohol abuse and eating disorder symptoms than did the MHR adolescents, but otherwise their symptom profiles were comparable. Additionally, the GR adolescents had significantly fewer total externalizing symptoms than did the MHR adolescents. Adolescents seeking gender affirming treatments present with psychiatric symptoms and disorders comparable to those seen among adolescent psychiatric patients. Medical gender affirming care may not be a sufficient intervention for treating psychiatric comorbidities of adolescents with gender dysphoria.

Dreaming and awareness during dexmedetomidine- and propofol-induced unresponsiveness.

BACKGROUND: Experiences during anaesthetic-induced unresponsiveness have previously been investigated by interviews after recovery. To explore whether experiences occur during drug administration, we interviewed participants during target-controlled infusion (TCI) of dexmedetomidine or propofol and after recovery. METHODS: Healthy participants received dexmedetomidine (n=23) or propofol (n=24) in stepwise increments until loss of responsiveness (LOR1). During TCI we attempted to arouse them for interview (return of responsiveness, ROR1). After the interview, if unresponsiveness ensued with the same dose (LOR2), the procedure was repeated (ROR2). Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness (LOC), infusion terminated, and the participants interviewed upon recovery (ROR3). An emotional sound stimulus was presented during LORs and LOC, and memory for stimuli was assessed with recognition task after recovery. Interview transcripts were content analysed. RESULTS: Of participants receiving dexmedetomidine, 18/23 were arousable from LOR1 and LOR2. Of participants receiving propofol, 10/24 were arousable from LOR1 and two of four were arousable from LOR2. Of 93 interviews performed, 84% included experiences from periods of unresponsiveness (dexmedetomidine 90%, propofol 74%). Internally generated experiences (dreaming) were present in 86% of reports from unresponsive periods, while externally generated experiences (awareness) were rare and linked to brief arousals. No within drug differences in the prevalence or content of experiences during infusion vs after recovery were observed, but participants receiving dexmedetomidine reported dreaming and awareness more often. Participants receiving dexmedetomidine recognised the emotional sounds better than participants receiving propofol (42% vs 15%), but none reported references to sounds spontaneously. CONCLUSION: Anaesthetic-induced unresponsiveness does not induce unconsciousness or necessarily even disconnectedness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Freedom Constrained Liner for the Treatment and Prevention of Dislocation in Total Hip Arthroplasty.

BACKGROUND AND PURPOSE: Dislocation is one of the most common complications following total hip arthroplasty. The aim of our study was to assess failure rate of the Biomet Freedom constrained liner (Biomet, Warsaw, IN, USA) either in revision surgery for recurrent dislocation, or as a preventive method in high dislocation risk patients. PATIENTS AND METHODS: We assessed retrospectively 105 consecutive surgical procedures in 103 patients where a Freedom constrained liner or cup was used in Turku University Hospital over a 7-year period from 2007 to 2014. The mechanical failure rate of the device was assessed based on medical records. The average age of the patients was 73.4 years. The number of male patients was 53 (51%). Mean follow-up time was 2.5 years. The association between failure of the device and potential risk factors-age, gender, indication, and approach-was analyzed with logistic regression. Results were expressed by odd ratios and 95% confidence intervals. RESULTS: The mechanical failure rate of the Freedom device was 6 out of 105 (5.7%). None of the 11 preventive primary THAs against dislocation failed, 4 out of 52 (7.7%) preventive revision THAs against dislocation failed, and 2 out of 42 (4.8%) of the treated dislocation cases failed. Four out of six failures were dislocations due to impingement and failure of the locking mechanism. Two liners failed because of loosening. The risk factors assessed were not associated with failure of the device. INTERPRETATION: We found out that the mechanical failure rate of a Freedom constrained device was low. These results encourage us to continue using the device.

Seasonal variation of diagnosis of Type 1 diabetes mellitus in children worldwide.

AIMS: To determine if there is a worldwide seasonal pattern in the clinical onset of Type 1 diabetes. METHODS: Analysis of the seasonality in diagnosis of Type 1 diabetes was based on the incidence data in 0- to 14-year-old children collected by the World Health Organization Diabetes Mondiale (WHO DiaMond) Project over the period 1990-1999. One hundred and five centres from 53 countries worldwide provided enough data for the seasonality analysis. The incidence seasonality patterns were also determined for age- and sex-specific groups. RESULTS: Forty-two out of 105 centres exhibited significant seasonality in the incidence of Type 1 diabetes (P < 0.05). The existence of significant seasonal patterns correlated with higher level of incidence and of the average yearly counts. The correlation disappeared after adjustment for latitude. Twenty-eight of those centres had peaks in October to January and 33 had troughs in June to August. Two out of the four centres with significant seasonality in the southern hemisphere demonstrated a different pattern with a peak in July to September and a trough in January to March. CONCLUSIONS: The seasonality of the incidence of Type 1 diabetes mellitus in children under 15 years of age is a real phenomenon, as was reported previously and as is now demonstrated by this large standardized study. The seasonality pattern appears to be dependent on the geographical position, at least as far as the northern/southern hemisphere dichotomy is concerned. However, more data are needed on the populations living below the 30th parallel north in order to complete the picture.

Childhood BMI trajectories and the risk of developing young adult-onset diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the effects of childhood BMI growth dynamics on the risk of developing young adult-onset type 1 and type 2 diabetes. METHODS: Finnish national healthcare registers were used to identify individuals with diabetes diagnosed between 1992 and 1996 at 15-39 years of age. Non-diabetic control participants were chosen from the National Population Registry. Anthropometric measurements were obtained from the original child welfare clinic records. Only the case-control pairs with sufficient growth data recorded were included in the analyses (218/1,388 for type 1 diabetes [16%] and 64/1,121 for type 2 diabetes [6%]). Two developmental stages in BMI growth (the points of infancy maximum BMI and the BMI rebound) were examined, and conditional logistic regression was applied to the variables of interest. RESULTS: The risk for type 1 diabetes increased 1.19-fold per 1 kg/m(2) rise in the infancy maximum BMI (p = 0.02). In addition, there was a 1.77-fold increase in the risk for type 2 diabetes per 1 kg/m(2) rise in the level of BMI at the BMI rebound (p = 0.04). Higher values of BMI at these points corresponded to a larger BMI gain from birth to that developmental stage. Age at the infancy maximum BMI or age at the BMI rebound did not affect the risk for either type of diabetes. CONCLUSIONS/INTERPRETATION: The BMI gain in infancy among individuals who subsequently developed young adult-onset type 1 diabetes was faster than that of those who remained healthy. The excess BMI gain in individuals who developed young adult-onset type 2 diabetes could already be seen during early childhood.

The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults.

AIMS/HYPOTHESIS: The aim of this study was to examine the effects of birth order and parental age on the risk of type 1 and type 2 diabetes among Finnish individuals aged 15-39 years. METHODS: Data on all cases of type 1 diabetes (n = 1,345) and type 2 diabetes (n = 1,072), diagnosed between 1992 and 1996, were collected from four sources: standardised national reports from diabetes nurses, the National Hospital Discharge Register, the Drug Prescription Register and the Drug Reimbursement Register. Information on matched controls and the family members of all study subjects were obtained from the National Population Registry. The odds ratios (ORs) for both types of diabetes were estimated using a conditional logistic regression model. RESULTS: There was a U-shaped relationship between maternal age and the risk of type 2 diabetes in the offspring: the risk was higher in children born to young and old mothers compared with children born to mothers aged around 30 years. The children born second (OR 0.76, 95% CI 0.62-0.94), third (OR 0.73, 95% CI 0.55-0.95), or fourth (OR 0.66, 95% CI 0.47-0.94) had a lower risk of type 2 diabetes than the first-born children. Maternal age, paternal age, and birth order did not have an effect on the risk of type 1 diabetes in the individuals aged 15-39 years at the time of diagnosis. CONCLUSIONS/INTERPRETATION: Maternal age and birth order are both associated with the risk of early-onset type 2 diabetes. However, part of these associations may be due to low birthweight. In this study neither parental age nor birth order showed a significant association with the risk of type 1 diabetes diagnosed after 15 years of age.

Impact of the Leu7Pro polymorphism of preproNPY on diurnal NPY and hormone secretion in type 2 diabetes.

Neuropeptide Y (NPY) is a sympathetic neurotransmitter that plays a role in e.g. circulation, hormone release and angiogenesis. Earlier studies have shown that the Leucine 7 to Proline 7 (Leu7Pro) polymorphism of preproNPY is associated with increased risk for vascular complications in type 2 diabetes. The mechanism for this maybe altered transmitter and hormone levels or altered cardiovascular functions, which have been observed in healthy subjects having the Leu7Pro polymorphism. The current study was undertaken to explore if the Leu7Pro polymorphism has an impact on these functions in subjects with type 2 diabetes. Diurnal measurements were performed for Finnish Caucasian type 2 diabetes patients of two preproNPY genotypes (matched by sex, age, BMI, duration of diabetes and HbA1c) in resting position to prevent sympathetic stimulation. Standard meals were offered during the 24-hour study period. Nine subjects with the Leu7Pro polymorphism and ten subjects without this polymorphism were studied. Plasma concentrations of NPY, glucose, insulin, cortisol, prolactin and leptin were measured by taking blood samples at 20 time points (from 8 a.m. to 8 a.m.). Heart rate and blood pressure were measured at the same time points. The results show that NPY concentrations were similar in both preproNPY genotypes. Glucose, insulin, cortisol and leptin concentrations as well as heart rate and blood pressure were also similar. However, a significant difference between genotypes was found in the association of NPY concentrations with cortisol concentrations (p for difference=0.002). Also a statistically significant negative association of plasma NPY levels with plasma glucose levels was found in both genotypes. Since no impact of preproNPY genotype on mean NPY or hormone levels were detected in subjects with type 2 diabetes, the mechanisms for the increased risk for diabetic complications in the subjects with the Leu7Pro polymorphism need to be further explored.

A high incidence of type 1 diabetes and an alarming increase in the incidence of type 2 diabetes among young adults in Finland between 1992 and 1996.

AIMS/HYPOTHESIS: The aim of this study was to examine the incidence and trends of type 1 and type 2 diabetes in the 15-39 year-old population between 1992 and 1996 in Finland. SUBJECTS AND METHODS: Data on the nationwide incidence of diabetes were obtained from four data sources: standardised reports from diabetes nurses, the Finnish National Hospital Discharge Register, the Drug Reimbursement Register and the Drug Prescription Register. The inclusion criterion was consistency in the diagnosis of diabetes across at least two data sources. The sex- and age-specific incidence was calculated for 5-year age groups, both for type 1 and type 2 diabetes. The effects of age, sex and year of diagnosis were assessed by fitting the linear regression model to the incidence data. RESULTS: Between 1992 and 1996 the age-adjusted incidence of type 1 diabetes among 15-39 year olds was 15.9 per 100,000/year. The incidence was highest among the 15-19 year olds and decreased with age. Conversely, the incidence of type 2 diabetes was very low among 15-19 year olds and increased with age. The total age-adjusted incidence of type 2 diabetes among 15-39 year olds was 11.8 per 100,000/year. The average annual increase in the incidence of type 2 diabetes was 7.9% (95% CI 3.7-12.2%). CONCLUSIONS/INTERPRETATION: The age at which the Finnish population is at risk of type 1 diabetes extends into young adulthood. The rapid increase in the incidence of type 2 diabetes in the young adult population is a current public health problem.

A hierarchical Bayesian birth cohort analysis from incomplete registry data: evaluating the trends in the age of onset of insulin-dependent diabetes mellitus (T1DM).

Childhood diabetes is one of the major non-communicable diseases in children under 15 years of age. It requires a life-long insulin treatment and may lead to serious complications. Along with the worldwide increase in the incidence several countries have recently reported a decreasing trend in the age of onset of the disease. The aim of this study is to analyse long-term data on the incidence of the childhood diabetes in Finland from the birth cohorts perspective. The annual incidence data were available for the period 1965--1996 which translates into 1951--1996 birth cohorts. Hence the data consist of completely and partially observed cohorts. Bayesian modelling was employed in the analysis. Several different priors and cohort combinations were tried in order to determine the sensitivity of the results. The cumulative birth cohort incidence of diabetes was determined to have an increasing average annual trend of 2.5 per cent. Although the average birth cohort-specific age of onset was estimated to have decreased slightly over the years of observation, the trend could be a result of random variation.

Zinc and nitrate in the ground water and the incidence of Type 1 diabetes in Finland.

AIMS: In Finland, the risk of childhood Type 1 diabetes varies geographically. Therefore we investigated the association between spatial variation of Type 1 diabetes and its putative environmental risk factors, zinc and nitrates. METHODS: The association was evaluated using Bayesian modelling and the geo-referenced data on diabetes cases and population. RESULTS: Neither zinc nor nitrate nor the urban/rural status of the area had a significant effect on the variation in incidence of childhood Type 1 diabetes. CONCLUSIONS: The results showed that although there was no significant difference in incidence between rural and urban areas, there was a tendency to increasing risk of Type 1 diabetes with the increasing concentration of NO3 in drinking water. The fact that no significant effect was found may stem from the aggregated data being too crude to detect it.

Geochemistry of ground water and the incidence of acute myocardial infarction in Finland.

STUDY OBJECTIVE: To examine the association of spatial variation in acute myocardial infarction (AMI) incidence and its putative environmental determinants in ground water such as total water hardness, the concentration of calcium, magnesium, fluoride, iron, copper, zinc, nitrate, and aluminium. DESIGN: Small area study using Bayesian modelling and the geo-referenced data aggregated into 10 km x 10 km cells. SETTING: The population data were obtained from Statistics Finland, AMI case data from the National Death Register and the Hospital Discharge Register, and the geochemical data from hydrogeochemical database of Geological Survey of Finland. PARTICIPANTS: A total of 18 946 men aged 35-74 years with the first AMI attack in the years 1983, 1988, and 1993. MAIN RESULTS: One unit (in German degree degrees dH) increment in water hardness decreased the risk of AMI by 1%. Geochemical elements in ground water included in this study did not show a statistically significant effect on the incidence and spatial variation of AMI, even though suggestive findings were detected for fluoride (protective), iron and copper (increasing). CONCLUSIONS: The results of this study with more specific Bayesian statistical analysis confirm findings from earlier observations of the inverse relation between water hardness and coronary heart disease. The role of environmental geochemistry in the geographical variation of the AMI incidence should be studied further in more detail incorporating the individual intake of both food borne and water borne nutrients. Geochemical-spatial analysis provides a basis for the selection of areas suitable for such research.

Electrocardiographic assessment of left ventricular hypertrophy with time-voltage QRS and QRST-wave areas.

The sum of time-voltage QRS areas in the 12-lead electrocardiogram (ECG) has outperformed other 12-lead ECG indices for detection of left ventricular hypertrophy (LVH). We assessed indices of time-voltage QRS and T-wave (QRST) areas from body surface potential mapping (BSPM) for detection of and quantitation of the degree of LVH. We studied 42 patients with echocardiographic LVH (LVH group) and 11 healthy controls (controls). QRST area sums were calculated from 123-lead BSPM and from the 12-lead ECG for comparison. Leadwise discriminant indices and correlation coefficients were used to identify optimal recording locations for QRST area-based LVH assessment. BSPM QRS area sum was greater in the LVH group than in controls (3752 +/- 1259 vs 2278 +/- 627 microV s, respectively; P<0.001) and at 91% specificity showed 74% sensitivity for LVH detection. The 12-lead QRS area sum performed similarly. Taking T-wave areas into account did not improve the results. QRS area sum from two most informative leads (located in the upper and lower right precordium) also separated the LVH group from controls (61.1 +/- 23.5 vs 27.8 +/- 6.5 microV s, respectively; P<0.00001). This 2-lead QRS area sum showed 90% sensitivity with 100% specificity for LVH detection and maintained high correlation to indexed left ventricular mass (r=0.732; P<0.001). In conclusion, the BSPM QRS area sum compared to 12-lead QRS area sum does not substantially improve LVH assessment. The 2-lead QRS area sum may improve ECG QRS area-based LVH assessment.

The incidence of type 1 diabetes among children in Finland--rural-urban difference.

The aim of the study was to investigate the incidence of type 1 diabetes among children aged 14 years or under according to the level of urbanization of the place of residence of children at the time of diagnosis in Finland during 1987 to 1996. The analysis was carried out using a Bayesian approach and GIS. The incidence was the highest in the rural heartland areas while the increase in incidence was sharpest in urban areas. The level of urbanization seems to explain only a part of the spatial variation in the incidence in Finland. It is possible that some environmental risk factors for type 1 diabetes have been more prevalent in rural heartland areas than in the rest of the country. These factors might have increased in urban environments in Finland particularly during the first half of 1990s.

Further evidence for the rising incidence of childhood Type 1 diabetes in Kuwait.

AIMS: To provide age-gender standardized incidence rate, temporal trend and seasonal variation of Type 1 diabetes in Kuwaiti children aged < or = 14 years. METHODS: Data were prospectively collected over a period of 6 years (1992-1997) according to the DiaMond Project protocol using the capture-recapture method of ascertainment. RESULTS: Data ascertainment varied between 90% and 96%. The incidence rate of Type 1 diabetes was 20.1 per 100,000 children 0-14 years (95% confidence interval (CI) 18.0-22.1); age-standardized incidence rate 20.9 (95% CI 18.8-23.0). The incidence rate among boys, 21.1 per 100,000 (95% CI 18.1-24.1) was slightly higher than that among girls, 19.0 per 100,000 (95% CI 16.1-21.8). The age-standardized incidence rate was 21.9 (95% CI 18.9-24.8) in boys, and 19.9 (95 CI 17.1-22.8) in girls. Incidence rates increased with age in both sexes (boys chi(2) for linear trend = 13.5, P < 0.001; and for girls chi(2) = 27.8, P < 0.0001). There was a significant trend towards increase in overall incidence during the 6-year period (chi(2) = 6.210, P = 0.013), and in age group 5-9 (chi(2) = 10.8, P = 0.001). Seasonality was demonstrated overall, in boys and girls (P < 0.001). CONCLUSION: The incidence of Type 1 diabetes in Kuwait is high compared with the neighbouring Arab countries, and it appears to be increasing as in many European populations.

A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference.

METHODS: We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg/m(2)) and waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finnish, French Canadian and Nigerian were studied. We tested effects of individual alleles, joint effects of alleles at multiple loci, epistatic effects among alleles at different loci, effect modification by age, sex, diabetes and ethnicity, and pleiotropic genotype effects on BMI and WC. RESULTS: We found that none of the effects were significant at the 0.05 level. Heterogeneity tests showed that the variations of the non-significant effects are within the range of sampling variation. CONCLUSIONS: We conclude that, although certain genotypic effects could be population-specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or WC in the overall population.

The impact of the leucine 7 to proline 7 polymorphism of the neuropeptide Y gene on postprandial lipemia and on the response of serum total and lipoprotein lipids to a reduced fat diet.

OBJECTIVE: The aim of the study was to examine the impact of the leucine7 to proline7 (Leu7Pro) polymorphism of the NPY gene on postprandial (PP) lipemia, post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and the response of serum lipids to a reduced fat diet. DESIGN AND SUBJECTS: Seven middle-aged obese subjects with Leu7Pro genotype were matched with seven subjects with Leu7Leu genotype for gender, age, apolipoprotein E phenotype and BMI. These 14 subjects participated in the oral 8 h fat tolerance test. Sixty-eight slightly obese middle-aged subjects (10 with the Leu7Pro genotype) had participated in intervention studies and consumed a reduced fat diet for 8 weeks. RESULTS: There were no statistically significant differences in PP areas under the curve of plasma total triglycerides (TG), chylomicron TG, VLDL-TG or insulin between the genotype groups. The TG-to-cholesterol (C) ratio in VLDL was significantly lower in the subjects with Leu7Pro genotype compared to those with the Leu7Leu genotype at time points 30 min and 1 h in the fat tolerance test. Heparin-induced activities of LPL or HL or the response of serum total or LDL-C to the reduced fat diet did not differ between the groups. CONCLUSIONS: The NPY genotype neither affects the magnitude of postprandial lipemia induced by a fat tolerance test nor the response of serum total lipids or lipids in different lipoprotein classes to the reduced fat diet. However, this preliminary study suggests that there might be compositional differences in the lipoprotein particles between the genotype groups that affect postprandial lipid metabolism. SPONSORSHIP: The Council for Health Sciences of the Academy of Finland, Kuopio University Hospital and the National Technology Agency, Finland.

Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.

Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general population.