107 research outputs found
Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency : a Swedish population-based national cohort study
CONTEXT: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms
if not treated with glucocorticoids. However, glucocorticoids may increase the
risk of cardiovascular and metabolic morbidity.
OBJECTIVE: This study aimed to
study cardiovascular and metabolic morbidity in CAH.
DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80%
with known CYP21A2 mutations) were compared with controls matched for sex, year,
and place of birth (n = 58 800). Data were obtained by linking national
population-based registers. Subgroup analyses were performed regarding sex,
clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype
(null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal
screening, age groups, and nonobesity.
MAIN OUTCOME MEASURES: To study
cardiovascular and metabolic morbidity in CAH. RESULTS: In CAH, both any
cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence
interval], 3.1-5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9-3.9) were
increased. Separate analyses of the individual diseases showed higher frequencies
in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous
thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder,
thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified
groups. On the subgroup level, females were generally more affected (especially
I172N and the nonclassic group), as were males with the null genotype.
CONCLUSIONS: CAH was associated with excess cardiovascular and metabolic
morbidity but the mechanism is not certain as the glucocorticoids were not
assessed. Hypothyroidism and obesity may be an effect of close observation.
However, more severe conditions were presumably detected equally in patients and
controls. Screening for diabetes and other metabolic disorders that increase
cardiovascular risk is important.Magn. Bergvalls FoundationKarolinska InstitutetStockholm County CouncilSwedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences, SIMSAM 340-2013-5867Manuscrip
Suboptimal psychosocial outcomes in patients with congenital adrenal hyperplasia : epidemiological studies in a nonbiased national cohort in Sweden
Context: Congenital adrenal hyperplasia (CAH), CYP21A2 deficiency, results in cortisol and aldosterone deficiency and increased production of androgens, with a good genotype phenotype correlation.
Objective: To study psychosocial outcomes in relation to clinical severity, CYP21A2 genotype, in men and women.
Design: An epidemiological study with a matched cohort control design.
Setting: All known CAH patients in Sweden.
Participants: 588 patients, >95% with known severity of CAH; 100 controls per patient matched for sex, year and place of birth.
Main outcome and measures: Proxies for quality of life were selected: level of education, employment, income, sick-leave, disability pension, marriage and children.
Results: Women with salt-wasting (SW) CAH had completed primary education less often (OR 0.3), not explained by neonatal salt-crisis or hypoglycemia since the men did not differ from controls. Men and women in the less severe I172N genotype group were more likely to have an academic education (OR 1.8) SW women were more likely to have an income in the top 20 percentile (OR 2.0 ). Both men and women had more disability pension (OR 1.5) and sick leave (OR 1.7). The men more often had long lasting employment (OR 3.1). Men were more often (OR 1.6) while women were less often married (OR 0.7). Patients had children less often (OR 0.3).
Conclusions: This study shows important outcome differences regarding education, employment, marriage and fertility depending on sex and severity of CAH. The mechanisms behind this and the increased risk for sick leave or disability pension in both men and women should be identified to improve medical and psychological care.The Swedish Research CouncilAccepte
Understanding the needs of professionals who provide psychosocial care for children and adults with disorders of sex development
Objective: Disorders in sex development (DSD) can be treated well medically, but families will encounter many psychosocial challenges. Promoting counselling to facilitate acceptance and coping is important yet equality of access is unknown. This study investigated the modalities of psychosocial care provided in centres of DSD care.
Methods: An international survey conducted among 93 providers of psychosocial care, identified through clinical networks, registries and professional forums.
Results: Forty-six respondents from 22 different countries filled out the survey (49%). Most respondents (78%) were based in hospital-based expert teams. Referrals came from paediatric endocrinologists (76%), gynaecologists (39%) and paediatric urologists (37%). Psychological counselling was most frequently given to parents (74%), followed by children (39%), adolescents (37%) and adults (11%) and was most frequently focused on coping and acceptance of DSD (54%), education (52%), the atypical body (39%) and genital (41%), decisions on genital surgery (33%), complications with sexual intercourse (29%), disclosure (28%) and acceptance of infertility (11%). Respondents most frequently observed DSD related confusion about gender (54%), acceptance of cross gender behaviour (50%), anxiety (43%) and sadness and depression (38%).
Conclusions: Most psychosocial care is provided to parents. It is assumed that parental support is important as acceptance is conditional to become affectionate caretakers. Although it may be more difficult for youngsters to communicate about their condition and treatment, providing opportunity to bring up issues that are important for them, is imperative. Clinicians and parents should be aware that parental and patients’ interests may not correspond completely. Psychosocial management should also include transition and adult care
Hypospadias and increased risk for neurodevelopmental disorders
BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the
penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether
this common malformation is associated with increased psychiatric morbidity later
in life. Studies of individuals with hypospadias also provide an opportunity to
examine whether difference in androgen signaling is related to neurodevelopmental
disorders. To elucidate the mechanisms behind a possible association, we also
studied psychiatric outcomes among brothers of the hypospadias patients. METHODS:
Registry study within a national cohort of all 9,262 males with hypospadias and
their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with
hypospadias and their brothers were matched with controls by year of birth and
county. The following outcomes were evaluated (1) any psychiatric (2) psychotic,
(3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance
misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum
disorders (ASD), (10) intellectual disability, and (11) other
behavioral/emotional disorders with onset in childhood. RESULTS: Patients with
hypospadias were more likely to be diagnosed with intellectual disability (OR
3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and
behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls.
Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1)
and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5)
in comparison to siblings of healthy individuals. A slightly higher, although not
statistically significant, risk was found for intellectual disability (1.3;
1.0-1.9). No relation between other psychiatric diagnosis and hypospadias was
found. CONCLUSIONS: This is the first study to identify an increased risk for
neurodevelopmental disorders in patients with hypospadias, as well as an
increased risk for ASD in their brothers, suggesting a common familial (genetic
and/or environmental) liability.The Swedish Research CouncilThe Polish Ministry of Science and Higher EducationAccepte
The CAG repeat polymorphism in the Androgen receptor gene modifies the risk for hypospadias in Caucasians
Risk of venous thromboembolism in children after general surgery
Background/purpose: The purpose of the study was to determine absolute and relative rates of venous thromboembolism (VTE) following general surgical procedures in children compared to the general population.
Methods: We analyzed data from all patients under the age of 18 years in the Clinical Practice Research Datalink, linked to Hospital Episode Statistics from England (2001–2011) undergoing a general surgical procedure and population controls. Crude rates of VTE and adjusted hazard ratios were calculated using Cox regression. Results We identified 15,637 children who had a surgical procedure with 161,594 controls. Six children undergoing surgery had a VTE diagnosed in the year after compared to five children in the population cohort. The overall rate of VTE following surgery was 0.4 per 1000 person years (pyrs) (95% confidence interval [CI] 0.15–0.88) compared to 0.04 per 1000 pyrs (95% CI 0.02–0.09) in the population cohort. This represented a 9 fold increase in risk compared to the population cohort (adjusted hazard ratio [HR] 8.80; 95% CI 2.59–29.94).
Conclusions Children are at increased risk for VTE following general surgical procedures compared to the general population however the absolute risk is small and given this the benefits of thromboprophylaxis need to be balanced against the risk of complications following its use
Involving individuals with disorders of sex development and their parents in exploring new models of shared learning: Proceedings from a DSDnet COST Action workshop
The level of connection between health care professionals and people who experience a condition that affects sex development is variable. These people and associated support groups need to be included in discussions about research and healthcare delivery. The aim of this study was to understand the experiences of individuals with disorders of sexual development (DSD), their parents, health care providers, and support groups. Workshop planning, preparation, delivery, and evaluation involved members of working groups from the COST Action DSDnet. A coordinator, in collaboration with a support group representative, led the workshop design and delivery. Our successful, facilitated workshop involved 33 attendees from 8 EU countries. The workshop provided individuals with DSD, parents, advisory groups, and professionals with an opportunity for shared learning. Outputs focused on 7 key areas, including diagnosis, childhood, and transition to adult care as well as fostering discussion around registries, future research topics, consent processes, and information needs across the life course. The importance of trustworthy and knowledgeable providers, time to understand such rare conditions, and the place support groups have in a life course approach were valuable learning points for all attendees. In conclusion, workshops can be designed and delivered in meaningful ways for all those involved in care of individuals with rare conditions
A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility
- …