Characteristics prior to and at time of diagnosis in pediatric bipolar disorder.

OBJECTIVES: Describe symptoms before and at time of register-diagnosis in children and adolescents. METHODS: A random sample was selected for chart-review from a Danish nationwide cohort of patients <18 years registered with an incident ICD-10 register-diagnosis of single hypomanic/manic episode or bipolar disorder between 1995 and 2014. Patients with symptoms which adequately documented a BD diagnosis in the chart were included for analysis. RESULTS: 521 were diagnosed in the study period. A random sample of 25% were selected, and 106 charts were possible to retrieve, with 48 chart reviews resulting in confirmation of diagnosis. Time from first reported affective symptoms to diagnosis was 2.6 ± 2.7 years for depressive symptoms, 2.5 ± 2.9 years for mixed symptoms, 1.4 ± 1.6 years for hypomanic symptoms, and 0.4 ± 0.5 years for manic symptoms. A hierarchical clustering analysis revealed three patient-profiles: primarily hypomanic/manic, primarily depressive, and more rare, primarily mixed profile. Frequently reported symptoms prior to diagnosis include anhedonia (79%), irritability (71%), hyperactivity (62.5%), decreased energy (62.5%), and psychotic symptoms (52%).Symptoms of ADHD (19%), comorbid ADHD (15%), symptoms of anxiety (52%), comorbid anxiety (4%), suicidal thoughts (50%), suicide attempts (8%), cutting (23%), substance misuse (21%), and criminal activity (10%) were reported before incident BD diagnosis. CONCLUSION: The observed patient-profiles leading to diagnosis were primarily manic or depressive, resembling presentations in adults. The presence of ADHD, anxiety, suicide attempts, cutting, and criminal activity prior to diagnosis emphasizes the need for treatment of children and adolescents with affective symptoms. The gap from appearance of the symptoms to diagnosis suggests a window for earlier treatment.

Prevalence of Various Traumatic Events Including Sexual Trauma in a Clinical Sample of Patients With an Eating Disorder.

Objective: Eating disorder (ED) and trauma have often been associated, and there is evidence that early experiences of traumatic events are associated with subsequent ED. Research results point toward an increased prevalence of sexual trauma in individuals with ED, and it has been suggested that sexual trauma precedes and contributes to the development of ED. The aim of this study was to assess the prevalence of sexual trauma as well as other types of traumatic life events in a clinical sample of children, adolescents, and adults with ED. Method: Patients (N = 329), median age 16.9 [Interquartile Range (IQR):4.5], diagnosed with various EDs in a specialized ED unit were included. Results: The majority (67%) of patients with ED reported at least one traumatic life event at time of assessment such as bullying (32%), loss (24%), or accidents (11%). Nineteen per cent of the patients reported having been the victim of a sexual trauma or another sexual traumatic event distributed as follows in terms of severity: 13% had been the victim of a negative experience associated with sex; 57% reported having experienced sexual assault other than rape; and 30% had been the victim of severe forms of sexual assault. The median time between the sexual trauma and the ED diagnosis was 3.4 years (IQR: 6.6). The median time between the sexual trauma and the onset of ED symptoms was 0 years (IQR: 5). The study results imply that the sexual trauma could be experienced either prior to or after onset of ED symptoms. Conclusions: Sixty-seven per cent of the patients with an ED reported traumatic life events at time of assessment, whereby 19% reporting negative sexual experiences or sexual abuse. However, sexual trauma does not necessarily play a causal role in the development of EDs.

Emotional dysfunction in avoidant personality disorder and borderline personality disorder: A cross-sectional comparative study.

According to the literature, avoidant personality disorder (APD) is often overlooked in research on personality disorders. In the present study, patients with APD were compared to patients with borderline personality disorder (BPD) with respect to emotional dysfunction. Emotional dysfunction was operationalized through the Affect Integration Inventory. Sixty-one patients receiving treatment at specialized outpatient hospital facilities for either BPD (n = 25) or APD (n = 36) (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) were included in a cross-sectional study. Supporting our expectations of no difference in the global capacity for affect integration between groups, the estimated difference was 0.00 (95% confidence interval [CI] [-0.53, 0.53]). On the other hand, the expected increased dysfunction in APD regarding Expression could not be confirmed. Furthermore, problems with specific affects distinguished the groups; integration of Interest was worse in APD (p = 0.01), whereas integration of Jealousy was worse in BPD (p = 0.04). In terms of prototypical modes of experiencing affects, APD was characterized by decreased access to the motivational properties of Interest (p < 0.01), while BPD was more driven by Interest (p < 0.01), Anger (p < 0.01), and Jealousy (p = 0.01). In conclusion, even though the two disorders are characterized by similar overall levels of emotional dysfunction, they differ systematically and predictably regarding specific affects and modes of experiencing. These findings carry implications for the understanding of emotional dysfunction in APD and BPD, suggesting specific areas of emotional dysfunction that could be targeted in tailored psychotherapeutic interventions.

The Relationship between Affect Integration and Psychopathology in Patients with Personality Disorder: A Cross-Sectional Study.

Background and Objectives: Emotional dysfunction is considered a key component in personality disorders; however, only few studies have examined the relationship between the two. In this study, emotional dysfunction was operationalized through the Affect Integration Inventory, and the aim was to examine the relationships between the level of affect integration and the levels of symptom distress, interpersonal problems, and personality functioning in patients diagnosed with personality disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Materials and Methods: Within a hospital-based psychiatric outpatient setting, 87 patients with personality disorder referred for treatment were identified for assessment with the Affect Integration Inventory and other measures (e.g., the Symptom Checklist-90, Revised, the Inventory of Interpersonal Problems 64 circumplex version, and the Severity Indices of Personality Problems). Results: The analyses revealed that problems with affect integration were strongly and statistically significantly correlated with high levels of symptom distress, interpersonal problems, and maladaptive personality functioning. Additionally, low scores on the Affect Integration Inventory regarding discrete affects were associated with distinct and differentiated patterns of interpersonal problems. Conclusion: Taken together, emotional dysfunction, as measured by the Affect Integration Inventory, appeared to be a central component of the pathological self-organization associated with personality disorder. These findings have several implications for the understanding and psychotherapeutic treatment of personality pathology. Furthermore, they highlight the importance of considering the integration of discrete affects and their specific contributions in the conceptualization and treatment of emotional dysfunction in patients with personality disorders.

Psychiatric Disorders in Children and Adolescents With Psychogenic Nonepileptic Seizures.

OBJECTIVE: Knowledge regarding psychiatric disorders in children and adolescents with psychogenic nonepileptic seizures (PNES) is limited. This study outlines the spectrum and risk of psychiatric disorders in childhood-onset PNES. METHODS: We performed a nationwide matched cohort study of children and adolescents with PNES 5 to 17 years of age at the time of diagnosis between January 1, 1996, and December 31, 2014. Two matched comparison groups were included: children and adolescents with epilepsy (ES) and children and adolescents without PNES or epilepsy, called healthy controls (HC). Outcomes were prevalent psychiatric disorders before index (i.e., date of diagnosis or corresponding date for HC) and incident psychiatric disorders 2 years after index. Relative risks (RRs) were calculated and adjusted for potential confounders. RESULTS: We included 384 children and adolescents with validated PNES, 1,152 with ES, and 1,920 HC. Among the cases of PNES, 153 (39.8%) had prevalent psychiatric disorders and 150 (39.1%) had incident psychiatric disorders. Compared to the ES and HC groups, children and adolescents with PNES had elevated risks of both prevalent psychiatric disorders (adjusted RRPNES/ES 1.87, 95% confidence interval [CI] 1.59-2.21, adjusted RRPNES/HC 5.54, 95% CI 4.50-6.81) and incident psychiatric disorders (adjusted RRPNES/ES 2.33, 95% CI 1.92-2.83, adjusted RRPNES/HC 8.37, 95% CI 6.31-11.11). A wide spectrum of specific psychiatric disorders displayed elevated RRs. CONCLUSIONS: Children and adolescents with PNES are at higher risk of a wide range of psychiatric disorders compared to children and adolescents with ES and HC. A careful psychiatric evaluation is warranted to optimize and individualize treatment.

Occurrence and accuracy of a register-based diagnosis of pediatric bipolar disorder: A nationwide cohort study.

OBJECTIVE: To investigate the accuracy of a diagnosis of pediatric bipolar disorder in the Danish National Register compared to the patient charts. Second, we reported on the occurrence of a diagnosis of pediatric bipolar disorder during the study period. METHODS: All persons appearing in the Danish nationwide registers between 1995 and 2014 with an incident ICD-10 diagnosis of single hypomanic/manic episode or a diagnosis of bipolar disorder (summarized as bipolar disorder [BD]) before turning 18 years were identified (n = 521) and a random sample (n = 131) hereof was selected for chart review. Each chart was reviewed by two independent Schedules for Clinical Assessment in Neuropsychiatry (SCAN) certified raters to assess whether symptoms documented in the chart were consistent with a formal diagnosis of BD according to the ICD-10 criteria or not. RESULTS: The formal diagnostic criteria for BD according to the ICD-10 were fulfilled in 48 charts (45.3%, 95% CI: [36.1%, 54.8%]) out of 106 reviewable charts, age at index = 16.4 ± 1.6 (range = 9.1-18.3) years. Cohen's Kappa ranged from 94.4% to 100%. The estimate of a lifetime prevalence up till the current age for bipolar disorder for those of aged 5-18 years, was 0.019% in 2014. CONCLUSION: Less than half of the register-based pediatric BD diagnoses were confirmed by chart review, which was lower than expected. The occurrence of a register diagnosis of pediatric BD was relatively low.

Effect of blue LED phototherapy centered at 478 nm versus 459 nm in hyperbilirubinemic neonates: a randomized study.

BACKGROUND: Treatment of choice for hyperbilirubinemic neonates is blue light matching the absorption spectrum of bilirubin-albumin in vitro with maximum absorption at 459 nm. Blue LED light centered at 478 nm was hypothesized as being more efficient than that centered at 459 nm. This study compares the bilirubin-reducing effect of the two light qualities with equal irradiance in a randomized nonblinded clinical trial. METHODS: Inclusion criteria were healthy hyperbilirubinemic neonates with gestational age ≥33 weeks. Forty-nine neonates included in each group received phototherapy from above for 24 h. Mean irradiances were 9.2 × 1015 and 9.0 × 1015 photons/cm2/s for the 478 and 459 nm groups, respectively. RESULTS: Mean [95% CI] decreases in total serum bilirubin were 150 [141, 158] and 120 [111, 130] µmol/L for the 478 and 459 nm groups, respectively; mean difference was 29 [17, 42] µmol/L. Mean [95% CI] percentage decreases in bilirubin were 54.8% [52.5, 57.0] and 41.8% [39.3, 44.3]; mean difference was 12.9 [9.6, 16.3] percentage points. After adjustment this difference was 13.4 [10.2, 16.7] percentage points. All differences were highly statistically significant (P < 0.001). CONCLUSION: Blue LED light centered at 478 nm had a greater bilirubin-reducing effect than that centered at 459 nm with equal irradiance quantified as photon fluence rate. IMPACT: Blue LED light centered at 478 nm had a greater in vivo bilirubin-reducing effect than blue LED light centered at 459 nm with equal irradiance quantified as photon fluence rate in the treatment of hyperbilirubinemic late preterm or term neonates. LED light centered at 478 nm might reduce the duration of phototherapy compared to LED light centered at 459 nm as the same effect can be obtained while exposing the infants to fewer photons. Blue light matching the absorption spectrum of the bilirubin-albumin complex in vitro with peak absorption at 459 nm is used worldwide as it is considered to be the most effective light for phototherapy of jaundiced neonates. This study showed that blue LED light centered at 478 nm had a greater bilirubin-reducing effect than blue LED light centered at 459 nm. Therefore, blue LED light centered at 478 nm should be used instead of blue light centered at 459 nm. By this, the risk of potential side effects might be minimized, and the duration of phototherapy potentially reduced.

Incidence rates and characteristics of pediatric onset psychogenic nonepileptic seizures.

BACKGROUND: Pediatric onset psychogenic nonepileptic seizures (PNES) is a highly disabling disorder and potentially misdiagnosed as epilepsy. Still, knowledge regarding PNES in children and adolescents is limited and data on both incidence and characteristics are scarce. This study investigated the incidence rate (IR) and clinical characteristics of pediatric onset PNES, including possible differences when having comorbid epilepsy. METHODS: A population-based study of children and adolescents aged 5-17 years with an incident diagnosis of PNES in the Danish healthcare registries between 1996 and 2014. In total, 386 children and adolescents were included after assessment of diagnostic validity using medical record data. RESULTS: The IR increased during the study period with the maximum IR observed in 2014 (7.4 per 100,000 person-years). A history of both neurologic and psychiatric problems as well as negative life events was identified. Comorbid epilepsy was confirmed for 55 cases (14.2%) and was associated with intellectual disabilities, school support and prolonged delay in PNES diagnosis. CONCLUSIONS: PNES are increasingly diagnosed in children and adolescents, and the clinical profile of both neurologic and psychiatric health problems underscores the need for collaborative pediatric and mental healthcare. These findings provide important information for future healthcare planning in this area. IMPACT: This nationwide study is the first to report population-based incidence rates of pediatric onset PNES documenting markedly increasing incidence rates between 1996 and 2014. A history of both neurologic and psychiatric problems as well as negative life events was identified for pediatric onset PNES. Comorbid epileptic seizures were associated with intellectual disabilities, school support and prolonged delay in PNES diagnosis. The clinical profile of both neurologic and psychiatric health problems underscores the need for collaborative pediatric and mental healthcare. The increasing number of children and adolescents diagnosed with PNES is important information for future healthcare planning in this area.

Diagnostic stability in children and adolescents with bipolar disorder, a nationwide register-based study.

BACKGROUND: Diagnostic stability of bipolar disorder (BD) in children and adolescents, beyond the first contact has been investigated sparsely. The aim of this study was to investigate the diagnostic stability of BD in children and adolescents using over two decades of nationwide register-based data, and to examine factors associated with change from BD to schizophrenia (ICD-10: F20.x), schizoaffective disorder (ICD-10: F25.x) or other primary psychotic disorders (ICD-10 F23.x-24.x and F28.x-29.x). METHODS: Danish register-based data for all incident BD patients diagnosed prior to age 18 years, between January 1st 1995 and December 31st 2014 (N = 519). We graphically illustrated diagnostic change at different follow-up times and studied variables associated with diagnostic change after 3-year follow-up using Poisson regression with robust standard error estimates. RESULTS: The diagnosis of incident BD was relatively stable. The diagnosis did not change for 93% of those followed for at least 6 months, and remained unchanged for 86% and 73% of those followed at least 3 years and 10 years, respectively. In patients followed for at least 3 years after index BD (N = 478), the risk of diagnostic change was 61% higher in males versus females. The risk of diagnostic change for patients diagnosed during hospitalization was 74% higher compared to patients diagnosed at outpatient clinics/emergency rooms. The risk of diagnostic change for patients abusing substances other than alcohol and cannabis was 173% higher compared to patients not abusing such substances. The risk of diagnostic change for patients previously diagnosed with schizophrenia or related diagnosis was 257% higher compared to patients not having been diagnosed with such diagnosis previously, while the risk of diagnostic change in offspring of parents with schizophrenia or related diagnosis was 126% higher compared to patients who did not have parents diagnosed with such disorders. CONCLUSION: Overall, the stability of the BD diagnosis in the Danish nationwide healthcare registers was high. Factors associated with risk of diagnostic change within 3 years of the initial diagnosis were being male, diagnosis given during hospitalization, substance abuse other than alcohol and cannabis, and a prior diagnosis of schizophrenia or related diagnosis in the patient or in their parents.

A cohort study of the effects of multidisciplinary in-patient primary care in older adults.

PURPOSE: To evaluate short and long-term effects of a multifactorial and multidisciplinary in-patient municipality intervention including training of activities of daily living, cardiovascular exercise, resistance training and social activities on quality-of-life, need-of-care, and physical function in older adults at risk of further functional decline. METHOD: A cohort study including data collected rigorously during 3.5 years at an in-patient municipality rehabilitation center in Aalborg, Denmark. Patients received a multifactorial and multidisciplinary intervention. Outcomes were quality-of-life (EQ5D), weekly need-of-care hours, and test of physical functioning (sit-to-stand, 6-min walking test, tandem balance). RESULTS: Data was collected from 532 patients (63.3% women). The median [5; 95 percentiles] age was 79 [55; 92] years with a length-of-stay of 21 [8; 55] days. The mean (95% CI) EQ5D index score showed a clinically relevant improvement from admission 0.46 (0.44; 0.48) to discharge 0.69 (0.67; 0.71) and there was no decline 6-month postdischarge 0.67 (0.64; 0.70). The weekly need-of-care decreased significantly by 7.2 (6.6, 7.9) h from a mean of 9.8 h before admission to 2.6 h 6-month postdischarge. Sit-to-stand improved from 6.3 (6.0; 6.7) to 9.3 (8.9; 9.6) repetitions, 6-min walking test from 147 (138; 156) to 217 (207; 227) m, and tandem balance from 20.7 (19.8; 21.6) to 25.2 (24.8; 26.2) s. CONCLUSION: Our results were remarkable and highlight that a well-structured multifactorial and interdisciplinary intervention with a clear aim and inclusion criteria related to functional decline may lead to long-term clinically relevant improvements in functionally declining older adults. Future studies should, however, explore similar interventions in comparable populations preferably in randomized controlled designs.

Extreme neonatal hyperbilirubinemia and kernicterus spectrum disorder in Denmark during the years 2000-2015.

OBJECTIVE: To determine the incidence and etiology of extreme neonatal hyperbilirubinemia, defined as total serum bilirubin (TSB) ≥450 µmol/L, and kernicterus spectrum disorder (KSD) in Denmark between 2000 and 2015. STUDY DESIGN: We identified all infants born between 01.01.2000 and 31.12.2015 with TSB ≥450 µmol/L, ratio of conjugated to TSB <0.30, gestational age ≥35 weeks, and postnatal age ≤4 weeks, using Danish hospitals' laboratory databases. RESULT: We included 408 infants. The incidence of extreme neonatal hyperbilirubinemia among infants with gestational age ≥35 weeks was 42/100,000 during the study period with a seemingly decreasing incidence between 2005 and 2015. Twelve of the 408 infants developed KSD, (incidence 1.2/100,000) Blood type ABO isohemolytic disease was the most common explanatory etiology. CONCLUSIONS: Our study stresses the importance of a systematic approach to neonatal jaundice and ongoing surveillance of extreme neonatal hyperbilirubinemia and KSD.

Breastfeeding and skin-to-skin contact as non-pharmacological prevention of neonatal hypoglycemia in infants born to women with gestational diabetes; a Danish quasi-experimental study.

OBJECTIVE: To investigate the effect on infant blood glucose levels of an intervention consisting of early, frequent breastfeeding and two hours of immediate uninterrupted skin-to-skin contact following birth of term infants born to mothers with diet-treated gestational diabetes (GDM). STUDY DESIGN: Quasi-experimental study design with a historical control group (n = 132) and an intervention group (n = 401) testing a procedure to prevent neonatal hypoglycemia. MAIN OUTCOME MEASURES: Data collection on blood glucose levels, hypoglycemia incidence with a cut-off of <2.5 mmol/l, breastfeeding within the first two hours after birth, breastfeeding frequency within the first six hours, and amount of formula given to hypoglycemic infants. RESULTS: Mean blood glucose levels in the intervention group at two and four hours were within safe limits: 3.37 mmol/l (95% CI: [3.30, 3.44]) and 3.40 mmol/l (95% CI: [3.34, 3.46]), respectively. Infants suffering a hypoglycemic event within four hours after birth decreased from 22.7% (n = 30/132) in the control group to 10.2% (n = 41/401) in the intervention group. The mean number of breastfeeds in the intervention group (six hours) was 2.41 compared to 1.34 in the control group (seven hours), an increase of 80%. Only 41 of 401 infants in the intervention group were interrupted in immediate interaction with their mother because of hypoglycemia. We failed to obtain sufficient data on skin-to-skin contact. CONCLUSION: Maintaining skin-to-skin contact for infants of mothers with diet-treated GDM, monitoring blood glucose levels until obtaining two values >2.4 mmol/l and encouraging early frequent breastfeeding is a safe strategy to prevent hypoglycemia.

DEMMI Scores, Length of Stay, and 30-Day Readmission of Acute Geriatric Patients in Denmark: A Cross-Sectional Observational Study with Longitudinal Follow-Up.

The aims of this study are to describe the mobility of acute geriatric patients, the length of stay, and to characterise patients who were readmitted within 30 days based on the De Morton Mobility Index (DEMMI). A cross-sectional observational study with longitudinal follow-up was conducted in the period from 1 March 2016 to 31 August 2016. Inclusion criteria were acute geriatric patients hospitalised for a minimum of 24 h. Of the 418 patients hospitalised during the study period, 246 (59%) participated in this study (44% male, median age 83 years [70; 94]). For patients in an acute geriatric department, the median DEMMI score was 41 and the mean score was 39.95. Patients with a DEMMI score ≤40 show a significantly lower Barthel 100 index, lower 30 s. sit-to-stand scores and were significantly more likely to be bedridden or, amongst those not bedridden, to use a mobility aid. Lower DEMMI scores were associated with longer admissions. DEMMI seems to have the ability to predict discharge within one week. There was no significant association between a lower DEMMI score and higher risk for 30-day readmission. Further research is needed to determine whether the DEMMI is suitable for identifying the patient's need for further rehabilitation following the discharge.

The Prevalence of Oropharyngeal Dysphagia in Acute Geriatric Patients.

Oropharyngeal dysphagia (OD) is underdiagnosed and undertreated in many geriatric centers. The aim of this study is to explore the prevalence of OD in acute geriatric patients. The outcome was mortality during hospitalization, mortality, and rehospitalization within 0⁻30 and 31⁻180 days of discharge. A total of 313 consecutive acute geriatric patients (44.1% male, mean age 83.1 years (SD 7.8)) hospitalized from 1 March to 31 August 2016 in the North Denmark Regional Hospital were included in this study. The volume-viscosity swallow test and the Minimal Eating Observation Form-II were conducted for each patient in order to screen for OD. A total of 50% patients presented with OD. In the group of patients with OD, significantly more lived in nursing homes; had a lower weight, DEMMI score, and handgrip strength; and smaller circumference of arms and legs compared with non-dysphagia patients. Patients with OD presented an increased length of stay in hospital of one day (p = 0.70). Intra-hospital mortality was 5.8% vs. 0.7%, (p < 0.001) compared with patients with no symptoms of OD. OD is prevalent in acute geriatric patients, and the mortality is 34% within six months of hospitalization. Screening for OD should be given more attention and included in geriatric guidelines.

The impact of hemoglobin on the efficacy of phototherapy in hyperbilirubinemic infants.

BackgroundPhototherapy is the routine treatment for neonatal hyperbilirubinemia. Absorption of light in the skin transforms the native Z,Z-bilirubin to photobilirubins. This study investigates whether the hemoglobin concentration has an impact on efficacy of phototherapy, expressed by the decline of total serum bilirubin concentration (TsB).MethodsA trial was conducted on 93 infants, gestational age ≥33 weeks, with uncomplicated hyperbilirubinemia. The infants were treated with conventional phototherapy using LED light for 24 h. The median light irradiance was 66.8 µW/cm2/nm.ResultsThe median decrease in TsB after 24 h was 121 (57-199) µmol/l; the median hemoglobin was 12.0 (7.0-14.7) mmol/l. There was a significant effect of hemoglobin concentration on the decrease in TsB of -3.61 µmol/mmol hemoglobin (P=0.022), after adjusting for initial TsB and postnatal age. That is, assuming the same initial TsB and postnatal age, for each mmol/l increase in hemoglobin, the decrease in TsB was 3.61 µmol/l smaller. In our hemoglobin range, the decrease in TsB is reduced by 28 µmol/l (23%).ConclusionIncreasing hemoglobin levels led to a decrease in the efficacy of phototherapy. Our data provide additional support for the conclusion that the transformation of bilirubin to photobilirubins takes place mainly in the superficial capillaries of the skin.

Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival.

The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single-nucleotide polymorphisms (SNPs) involved in the immune response and a subsequent statistical analysis that focusses on the association of SNPs, certain haplotypes or SNP-SNP interactions with MM risk and prognosis. We genotyped 348 Danish patients and 355 controls for 13 SNPs located in the TNFA, IL-4, IL-6, IL-10 and CHI3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors were studied for expression in normal B-cell subsets and myeloma plasma cells. We observed a significantly reduced risk when harboring the TNFA-238A allele (OR = 0.51 (0.29-0.86)) and interactions between the TNFA-1031T/C * and IL-10 -3575T/A (p = .007) as well as the TNFA-308G/A * and IL-10-1082G/A (p = .008) allels. By statistical approaches, we observed association between prognosis and the TNFA-857CC genotype (HR = 2.80 (1.29-6.10)) and IL-10-1082GG + GA genotypes (HR = 1.93 (1.07-3.49)) and interactions between IL-6-174G/C and IL-10-3575T/A (p = .001) and between TNFA-308G/A and IL-4-1098T/G (p= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential expressed in malignant plasma cells when comparing poor and good prognosis groups based on to the TC classification. In summary, these findings suggest that TNFA, IL-4, IL-6, IL-10 and CHI3L1 might be important players in MM pathogenesis during disease initiation and drug resistance in multiple myeloma.

Surgically assisted rapid maxillary expansion (SARME) with or without intraoperative releasing of the nasal septum.

OBJECTIVE: To assess nasal septum deviation after surgically assisted rapid maxillary expansion (SARME) with or without intraoperative releasing of the nasal septum. STUDY DESIGN: A total of 20 consecutive adult patients with transverse maxillary deficiency underwent SARME with intraoperative releasing (n = 10) or nonreleasing (n = 10) of the nasal septum. Cone beam computed tomography scans were obtained immediately after surgery (T1), after the end of distraction (T2), and 6 months after SARME (T3). Deviation of the nasal septum was evaluated by angular measurements on superimposed cone beam computed tomography images from T1 to T3. Moreover, visible nasal septum deviation was assessed by using superimposed clinical photos obtained preoperatively (CP1) and before second-stage surgery (CP2). RESULTS: No significant differences were found between releasing and nonreleasing of the nasal septum in angular radiographic measurements from T1 to T3 (0 degrees; 95% confidence interval -0.62 to 0.62; P = .5) or visible nasal deviation from CP1 to CP2 (-0.14 degrees; 95% confidence interval -0.64 to 0.36; P = .28). CONCLUSIONS: The results of the present study indicate that there is no need for intraoperative releasing of the nasal septum during SARME. However, further randomized studies based on large patient groups are needed before final conclusions on this topic can be reached.

Skeletal Stability after Large Mandibular Advancement (> 10 mm) with Bilateral Sagittal Split Osteotomy and Skeletal Elastic Intermaxillary Fixation.

OBJECTIVES: The aim of the present study was to assess the skeletal stability after large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation and to correlate the skeletal stability with the vertical facial type. MATERIAL AND METHODS: A total of 33 consecutive patients underwent bimaxillary surgery to correct skeletal Class II malocclusion with a mandibular advancement (> 10 mm) measured at B-point and postoperative skeletal elastic intermaxillary fixation for 16 weeks. Skeletal stability was evaluated using lateral cephalometric radiographs obtained preoperative (T1), 8 weeks postoperatively (T2), and 18 month postoperatively (T3). B-point and pogonion (Pog) was used to measure the skeletal relapse and the mandibular plane angle (MP-angle) was used to determine the vertical facial type. RESULTS: The mean advancement from T1 to T2 were 11.6 mm and 13.5 mm at B-point and Pog, respectively. The mean skeletal relapse from T2 to T3 was -1.3 mm at B-point and -1.6 mm at Pog. The nineteen patients characterized as long facial types, showed the highest amount of skeletal relapse (-1.5 mm at B-point and -1.9 mm at Pog). CONCLUSIONS: The present study showed a limited amount of skeletal relapse in large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation. Bilateral sagittal split osteotomy in combination with skeletal intermaxillary fixation can therefore be an alternative to distraction osteogenesis in large mandibular advancements.

Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival.

BACKGROUND: Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment. METHODS: We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin's lymphoma (B-NHL) samples encompassing 216 diffuse large B cell lymphoma (DLBCL) and 139 follicular lymphoma (FL) and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included. RESULTS: We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS) in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010) * IL10 (rs1800890) (HR = 0.11 (0.02-0.50)). Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center. CONCLUSIONS: The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis.

Attitudes toward Catheter Ablation for Atrial Fibrillation: A Nationwide Survey among Danish Cardiologists.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is an important but expensive procedure that is the subject of some debate. Physicians' attitudes toward catheter ablation may influence promotion and patient acceptance. This is the first study to examine the attitudes of Danish cardiologists toward catheter ablation for AF, using a nationwide survey. METHODS AND RESULTS: We developed a purpose-designed questionnaire to evaluate attitudes toward catheter ablation for AF that was sent to all Danish cardiologists (n = 401; response n = 272 (67.8%)). There was no association between attitudes toward ablation and the experience or age of the cardiologist with respect to patients with recurrent AF episodes with a duration of <48 hours or >7 days and/or need for cardioversion. The majority (69%) expected a recurrence of AF after catheter ablation in more than 30% of the cases. For patients with persistent longstanding AF with a duration of >1 year, the attitude toward ablation for longstanding AF was more likely to be positive with increasing age (P < 0.01) and years of experience of the cardiologist (P = 0.002). CONCLUSIONS: Danish cardiologists generally have a positive attitude toward catheter ablation for AF, maintain up-to-date knowledge of the procedure, and are aware what information on ablation treatment should be given to patients with AF. The cardiologists had a positive attitude toward ablation for AF in patients with AF episodes <48 hours and patients with episodes >7 days, or those who needed medical/electrical conversion, but a more negative attitude toward treating longstanding AF patients.