The effects of oral clefts on hospital use throughout the lifespan

<p>Abstract</p> <p>Background</p> <p>Oral clefts are one of the most common birth defects worldwide. They require multiple healthcare interventions and add significant burden on the health and quality of life of affected individuals. However, not much is known about the long term effects of oral clefts on health and healthcare use of affected individuals. In this study, we evaluate the effects of oral clefts on hospital use throughout the lifespan.</p> <p>Methods</p> <p>We estimate two-part regression models for hospital admission and length of stay for several age groups up to 68 years of age. The study employs unique secondary population-based data from several administrative inpatient, civil registration, demographic and labor market databases for 7,670 individuals born with oral clefts between 1936 and 2002 in Denmark, and 220,113 individuals without oral clefts from a 5% random sample of the total birth population from 1936 to 2002.</p> <p>Results</p> <p>Oral clefts significantly increase hospital use for most ages below 60 years by up to 233% for children ages 0-10 years and 16% for middle age adults. The more severe cleft forms (cleft lip with palate) have significantly larger effects on hospitalizations than less severe forms.</p> <p>Conclusions</p> <p>The results suggest that individuals with oral clefts have higher hospitalization risks than the general population throughout most of the lifespan.</p

Psychiatric Diagnoses in Individuals with Non-Syndromic Oral Clefts:A Danish Population-Based Cohort Study

The aim of this study was to investigate the risk of psychiatric diagnoses in individuals with non-syndromic oral clefts (OC) compared with individuals without OC, including ages from 1 to 76 years.Linking four Danish nationwide registers, we investigated the risk of psychiatric diagnoses at Danish psychiatric hospitals during the period 1969-2012 for individuals born with non-syndromic OC in Denmark 1936-2009 compared with a cohort of 10 individuals without OC per individual with OC, matched by sex and birth year. The sample included 8,568 individuals with OC, observed for 247,821 person-years, and 85,653 individuals without OC followed for 2,501,129 person-years.A total of 953 (11.1%) of the individuals with OC (9.6% for cleft lip (CL), 10.8% for cleft lip and palate (CLP) and 13.1% for cleft palate (CP)) and 8,117 (9.5%) in the comparison group had at least one psychiatric diagnosis. Cox proportional hazard regression model revealed that individuals with OC had significantly higher risk of a psychiatric diagnosis (hazard ratio (HR) = 1.19, 95% CI: 1.12-1.28). When examining cleft type, no difference was found for CL (HR = 1.03, 95% CI: 0.90-1.17), but CLP was associated with a small increased risk (HR = 1.13, 95% CI: 1.01-1.26), whereas individuals with CP had the largest increased risk (HR = 1.45, 95% CI: 1.30-1.62). The largest differences were found in schizophrenia-like disorders, mental retardation and pervasive developmental disorders, but we found no increased risk of mood disorders and anxiety-related disorders.Individuals with non-syndromic OC had significantly higher risk of psychiatric diagnoses compared with individuals without OC. However, the elevated risk was observed for individuals with CLP and CP but not for individuals with CL and the absolute risk increase was modest

Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins

IntroductionPregnancy-associated plasma protein-A (PAPP-A) is an IGF-activating enzyme suggested to influence aging-related diseases. However, knowledge on serum PAPP-A concentration and regulation in elderly subjects is limited. Therefore, we measured serum PAPP-A in elderly same-sex monozygotic (MZ) and dizygotic (DZ) twins, as this allowed us to describe the age-relationship of PAPP-A, and to test the hypothesis that serum PAPP-A concentrations are genetically determined. As PAPP-A is functionally related to stanniocalcin-2 (STC2), an endogenous PAPP-A inhibitor, we included measurements on STC2 as well as IGF-I and IGF-II.MethodsThe twin cohort contained 596 subjects (250 MZ twins, 346 DZ twins), whereof 33% were males. The age ranged from 73.2 to 94.3 (mean 78.8) years. Serum was analyzed for PAPP-A, STC2, IGF-I, and IGF-II by commercial immunoassays.ResultsIn the twin cohort, PAPP-A increased with age (r=0.19; P&lt;0.05), whereas IGF-I decreased (r=-0.12; P&lt;0.05). Neither STC2 nor IGF-II showed any age relationship. When analyzed according to sex, PAPP-A correlated positively with age in males (r=0.18; P&lt;0.05) and females (r=0.25; P&lt;0.01), whereas IGF-I correlated inversely in females only (r=-0.15; P&lt;0.01). Males had higher levels of PAPP-A (29%), STC2 (18%) and IGF-I (19%), whereas serum IGF-II was 28% higher in females (all P&lt;0.001). For all four proteins, within-pair correlations were significantly higher for MZ twins than for DZ twins, and they demonstrated substantial and significant heritability, which after adjustment for age and sex averaged 59% for PAPP-A, 66% for STC2, 58% for IGF-I, and 52% for IGF-II.DiscussionThis twin study confirms our hypothesis that the heritability of PAPP-A serum concentrations is substantial, and the same is true for STC2. As regards the age relationship, PAPP-A increases with age, whereas STC2 remains unchanged, thereby supporting the idea that the ability of STC2 to inhibit PAPP-A enzymatic activity decreases with increasing age

Studies of Metabolic Phenotypic Correlates of 15 Obesity Associated Gene Variants

Genome-wide association studies have identified novel BMI/obesity associated susceptibility loci. The purpose of this study is to determine associations with overweight, obesity, morbid obesity and/or general adiposity in a Danish population. Moreover, we want to investigate if these loci associate with type 2 diabetes and to elucidate potential underlying metabolic mechanisms.15 gene variants in 14 loci including TMEM18 (rs7561317), SH2B1 (rs7498665), KCTD15 (rs29941), NEGR1 (rs2568958), ETV5 (rs7647305), BDNF (rs4923461, rs925946), SEC16B (rs10913469), FAIM2 (rs7138803), GNPDA2 (rs10938397), MTCH2 (rs10838738), BAT2 (rs2260000), NPC1 (rs1805081), MAF (rs1424233), and PTER (rs10508503) were genotyped in 18,014 middle-aged Danes.Five of the 15 gene variants associated with overweight, obesity and/or morbid obesity. Per allele ORs ranged from 1.15-1.20 for overweight, 1.10-1.25 for obesity, and 1.41-1.46 for morbid obesity. Five of the 15 variants moreover associated with increased measures of adiposity. BDNF rs4923461 displayed a borderline BMI-dependent protective effect on type 2 diabetes (0.87 (0.78-0.96, p = 0.008)), whereas SH2B1 rs7498665 associated with nominally BMI-independent increased risk of type 2 diabetes (1.16 (1.07-1.27, p = 7.8×10(-4))).Associations with overweight and/or obesity and measures of obesity were confirmed for seven out of the 15 gene variants. The obesity risk allele of BDNF rs4923461 protected against type 2 diabetes, which could suggest neuronal and peripheral distinctive ways of actions for the protein. SH2B1 rs7498665 associated with type 2 diabetes independently of BMI

Hazard Ratios of Contact to a Psychiatric Hospital for Specific Psychiatric Diagnoses among Individuals with Non-Syndromic Oral Cleft Compared With the Matched Comparison Cohort.

<p>Hazard Ratios of Contact to a Psychiatric Hospital for Specific Psychiatric Diagnoses among Individuals with Non-Syndromic Oral Cleft Compared With the Matched Comparison Cohort.</p

Characteristics of Individuals with Non-Syndromic Oral Cleft and the Matched Comparison Cohort.

<p>Characteristics of Individuals with Non-Syndromic Oral Cleft and the Matched Comparison Cohort.</p

Inclusion Criteria for Individuals with Non-Syndromic Oral Cleft and Matched Comparison Cohort.

<p>Inclusion Criteria for Individuals with Non-Syndromic Oral Cleft and Matched Comparison Cohort.</p