Cervical headgear in Class II division 1 correction in children : Academic Dissertation

Class II division 1 malocclusion occurs in 3.5 to 13 percent of 7 12 year-old children. It is the most common reason for orthodontic treatment in Finland. Correction is most commonly performed using headgear treatment. The aim of this study was to investigate the effects of cervical headgear treatment on dentition, facial skeletal and soft tissue growth, and upper airway structure, in children. 65 schoolchildren, 36 boys and 29 girls were studied. At the onset of treatment a mean age was 9.3 (range 6.6 12.4) years. All the children were consequently referred to an orthodontist because of Class II division 1 malocclusion. The included children had protrusive maxilla and an overjet of more than 2mm (3 to 11 mm). The children were treated with a Kloehn-type cervical headgear as the only appliance until Class I first molar relationships were achieved. The essential features of the headgear were cervical strong pulling forces, a long upward bent outer bow, and an expanded inner bow. Dental casts and lateral and posteroanterior cephalograms were taken before and after the treatment. The results were compared to a historical, cross-sectional Finnish cohort or to historical, age- and sex-matched normal Class I controls. The Class I first molar relationships were achieved in all the treated children. The mean treatment time was 1.7 (range 0.3-3.1) years. Phase 2 treatments were needed in 52% of the children, most often because of excess overjet or overbite. The treatment decreased maxillary protrusion by inhibiting alveolar forward growth, while the rest of the maxilla and mandible followed normal growth. The palate rotated anteriorly downward. The expansion of the inner bow of the headgear induced widening of the maxilla, nasal cavity, and the upper and lower dental arches. Class II malocclusion was associated with narrower oro- and hypopharyngeal space than in the Class I normal controls. The treatment increased the retropalatal airway space, while the rest of the airway remained unaffected. The facial profile improved esthetically, while the facial convexity decreased. Facial soft tissues masked the facial skeletal convexity, and the soft tissue changes were smaller than skeletal changes. In conclusion, the headgear treatment with the expanded inner bow may be used as an easy and simple method for Class II correction in growing children.

Relative peripheral hyperopia does not predict development and progression of myopia in children

Purpose To test the hypothesis that relative peripheral hyperopia predicts development and progression of myopia. Methods Refraction along the horizontal visual field was measured under cycloplegia at visual field angles of 0°, ±15°, and ±30° at baseline, 1 and 2 years in over 1700 initially 7-year-old Chinese children, and at baseline and 1 year in over 1000 initially 14-year olds. One refraction classification for central refraction was “nonmyopia, myopia” (nM, M), consisting of nM greater than −0.50 diopters (D; spherical equivalent) and M less than or equal to −0.50 D. A second classification was “hyperopia, emmetropia, low myopia, and moderate/high myopia” (H, E, LM, MM) with H greater than or equal to +1.00 D, E, −0.49 to +0.99 D, LM, −2.99 to −0.50 D, and MM less than or equal to −3.00 D. Subclassifications were made on the basis of development and progression of myopia over the 2 years. Changes in central refraction over time were determined for different groups, and relative peripheral refraction over time was compared between different subgroups. Results Simple linear regression of central refraction as a function of relative peripheral refraction did not predict myopia progression as relative peripheral refraction became more hyperopic: relative peripheral hyperopia and relative peripheral myopia predicted significant myopia progression for 0% and 35% of group/visual field angle combinations, respectively. Subgroups who developed myopia did not have more initial relative peripheral hyperopia than subgroups who did not develop myopia. Conclusions Relative peripheral hyperopia does not predict development nor progression of myopia in children. This calls into question the efficacy of treatments that aim to slow progression of myopia in children by “treating” relative peripheral hyperopia.

Development and psychometric properties of the DCDDaily: a new test for clinical assessment of capacity in activities of daily living in children with developmental coordination disorder

Objective To develop the DCDDaily, an instrument for objective and standardized clinical assessment of capacity in activities of daily living (ADL) in children with developmental coordination disorder (DCD), and to investigate its usability, reliability, and validity. Subjects Five to eight-year-old children with and without DCD. Main measures The DCDDaily was developed based on thorough review of the literature and extensive expert involvement. To investigate the usability (assessment time and feasibility), reliability (internal consistency and repeatability), and validity (concurrent and discriminant validity) of the DCDDaily, children were assessed with the DCDDaily and the Movement Assessment Battery for Children-2 Test, and their parents filled in the Movement Assessment Battery for Children-2 Checklist and Developmental Coordination Disorder Questionnaire. Results 459 children were assessed (DCD group, n = 55; normative reference group, n = 404). Assessment was possible within 30 minutes and in any clinical setting. For internal consistency, Cronbach’s α = 0.83. Intraclass correlation = 0.87 for test–retest reliability and 0.89 for inter-rater reliability. Concurrent correlations with Movement Assessment Battery for Children-2 Test and questionnaires were ρ = −0.494, 0.239, and −0.284, p < 0.001. Discriminant validity measures showed significantly worse performance in the DCD group than in the control group (mean (SD) score 33 (5.6) versus 26 (4.3), p < 0.001). The area under curve characteristic = 0.872, sensitivity and specificity were 80%. Conclusions The DCDDaily is a valid and reliable instrument for clinical assessment of capacity in ADL, that is feasible for use in clinical practice.

Positive associations of serum Perfluoroalkyl substances with uric acid and hyperuricemia in children from Taiwan

To investigate the risk of hyperuricemia in relation to Perfluoroalkyl substances (PFASs) in children from Taiwan, 225 Taiwanese children aged 12-15 years were recruited from 2009 to 2010. Linear and logistic regression models were employed to examine the influence of PFASs on serum uric acid levels. Findings revealed that eight of ten PFASs analyses were detected in > 94% of the participants' serum samples. Multivariate linear regression models revealed that perfluorooctanic acid (PFOA) was positively associated with serum uric acid levels (β=0.1463, p<0.05). Of all the PFASs analyses, only PFOA showed a significant effect on elevated levels of hyperuricemia (aOR=2.16, 95%CI: 1.29-3.61). When stratified by gender, the association between serum PFOA and uric acid levels was only evident among boys (aOR=2.76, 95%CI: 1.37-5.56). In conclusion, PFOA was found to be associated with elevated serum levels of uric acid in Taiwanese children, especially boys. Further research is needed to elucidate these links.

Randomised controlled trial of three burns dressings for partial thickness burns in children

BACKGROUND This study compared the effects of three silver dressing combinations on small to medium size acute partial thickness burns in children, focusing on re-epithelialization time, pain and distress during dressing changes. METHOD Children (0-15 years) with clean, ≤ 10% total body surface area (TBSA) partial thickness burns who met the inclusion criteria were included in the study. Children received either (1) Acticoat™; (2) Acticoat™ with Mepitel™; or (3) Mepilex Ag™ dressings. Measures of burn re-epithelialization, pain, and distress were recorded at dressing changes every 3-5 days until full re-epithelialization occurred. RESULTS One hundred and three children were recruited with 96 children included for analysis. No infections were detected for the course of the study. When adjusted for burn depth, Acticoat™ significantly increased the expected days to full re-epithelialization by 40% (IRR = 1.40; 95% CI: 1.14-1.73, p < 0.01) and Acticoat™ with Mepitel™ significantly increased the expected days to full re-epithelialization by 33% (IRR = 1.33; 95% CI: 1.08-1.63, p ≤ 0.01) when compared to Mepilex Ag™. Expected FLACC scores in the Mepilex Ag™ group were 32% lower at dressing removal (p = 0.01) and 37% lower at new dressing application (p = 0.04); and scores in the Acticoat™ with Mepitel™ group were 23% lower at dressing removal (p = 0.04) and 40% lower at new dressing application (p < 0.01), in comparison to the Acticoat™ group. Expected Visual Analog Scale-Pain (VAS-P) scores were 25% lower in the Mepilex Ag™ group at dressing removal (p = 0.04) and 34% lower in the Acticoat™ with Mepitel™ group (p = 0.02) at new dressing application in comparison to the Acticoat™ group. There was no significant difference between the Mepilex Ag™ and the Acticoat™ with Mepitel™ groups at all timepoints and with any pain measure. CONCLUSION Mepilex Ag™ is an effective silver dressing, in terms of accelerated wound re-epithelialization time (compared to Acticoat™ and Acticoat™ with Mepitel™) and decreased pain during dressing changes (compared to Acticoat™), for clean, < 10% TBSA partial thickness burns in children.

Immune response to insulin and changes in the gut immune system in children with or at risk for type 1 diabetes

Type 1 diabetes (T1D) is considered to be an autoimmune disease. The cause of T1D is the destruction of insulin-producing β-cells in the pancreatic islets. The autoimmune nature of T1D is characterized by the presence of autoreactive T-cells and autoantibodies against β-cell molecules. Insulin is the only β-cell-specific autoantigen associated with T1D but the insulin autoantibodies (IAAs) are difficult to measure with proper sensitivity. T-cell assays for detection of autoreactive T-cells, such as insulin-specific T-cells, have also proven to be difficult to perform. The genetic risk of T1D is associated with the HLA gene region but the environmental factors also play an important role. The most studied environmental risk factors of T1D are enteroviruses and cow's milk which both affect the immune system through the gut. One hypothesis is that the insulin-specific immune response develops against bovine insulin in cow's milk during early infancy and later spreads to include human insulin. The aims of this study were to determine whether the separation of immunoglobulin (Ig)G from plasma would improve the sensitivity of the IAA assay and how insulin treatment affects the cellular immune response to insulin in newly diagnosed patients. Furthermore, the effect of insulin concentration in mother's breast milk on the development of antibodies to dietary insulin in the child was examined. Small intestinal biopsies were also obtained from children with T1D to characterize any immunological changes associated with T1D in the gut. The isolation of the IgG fraction from the plasma of T1D patients negative for plasma IAA led to detectable IAA levels that exceeded those in the control children. Thus the isolation of IgG may improve the sensitivity of the IAA assay. The effect of insulin treatment on insulin-specific T-cells was studied by culturing peripheral blood mononuclear cells with insulin. The insulin stimulation induced increased expression of regulatory T-cell markers, such as Foxp3, in those patients treated with insulin than in patients examined before initiating insulin treatment. This finding suggests that insulin treatment in patients with T1D stimulates regulatory T-cells in vivo and this may partly explain the difficulties in measuring autoantigen-specific T-cell responses in recently diagnosed patients. The stimulation of regulatory T-cells by insulin treatment may also explain the remission period often seen after initiating insulin treatment. In the third study we showed that insulin concentration in mother's breast milk correlates inversely with the levels of bovine insulin-specific antibodies in those infants who were exposed to cow's milk proteins in their diet, suggesting that human insulin in breast milk induces tolerance to dietary bovine insulin. However, in infants who later developed T1D-associated autoantibodies, the insulin concentration in their mother's breast milk was increased. This finding may indicate that in those children prone to β-cell autoimmunity, breast milk insulin does not promote tolerance to insulin. In the small intestinal biopsies the presence of several immunological markers were quantified with the RT-PCR. From these markers the expression of the interleukin (IL)-18 cytokine was significantly increased in the gut in patients with T1D compared with children with celiac disease or control children. The increased IL-18 expression lends further support for the hypothesis that the gut immune system is involved in the pathogenesis of T1D.

Study of sleep and evaluation of sumatriptan and rizatriptan in the acute treatment of migraine in children and adolescents

Migraine is a common disease in children and adolescents, affecting roughly 10% of school-aged children. Recent studies have revealed an increasing incidence of childhood migraine, but migraine remains an underrecognized and undertreated condition in the pediatric population. Migraine attacks are painful and disabling and can affect a child´s life in many ways. Effective drug treatment is usually needed. The new migraine drugs, triptans, were introduced at the beginning of the 1990s and have since been shown to be very effective in the treatment of migraine attacks in adults. Although they are widely used in adults, the acute treatment of migraine in children and adolescents is still based on paracetamol and nonsteroidal anti-inflammatory drugs. Some children can control their attacks satisfactorily with simple analgesics, but at least one-third need more powerful treatments. When this thesis work commenced, hardly any information existed on the efficacy and safety of triptans in children. The study aim of the thesis was to identify more efficient treatments of migraine for children and adolescents by investigating the efficacy of sumatriptan nasal spray and oral rizatriptan compared with placebo in them. Sleep has an impact on migraine in many aspects. Despite the clinical relevance and common manifestation of sleep in the context of migraine in children, very little research data on the true frequency of sleep exist. As sleeping is so often related to childhood migraine, it can be a confounding factor in clinical drug trials of migraine treatments in children and adolescents. How the results of a sleeping child should be analyzed is under continual debate. The aim of the thesis was also to clarify this as well as to evaluate the frequency of sleeping during migraine attacks in children and factors affecting frequency. Both nasal sumatriptan and oral rizatriptan were effective (superior to placebo), and well tolerated in treatment of migraine attacks in children and adolescents aged 8-17 and 6-17 years, respectively. No serous adverse effects were observed. The results of this work suggest that nasal sumatriptan 20 mg and rizatriptan 10 mg can be effectively and safely used to treat migraine attacks in adolescents aged over 12 years if more effective drugs than NSAIDs are needed. No difference was observed in efficacy or safety of nasal sumatriptan and rizatriptan between children aged younger than 12 years and older children, but because the treated number of patients under 12 years is still small, more studies are needed before sumatriptan or rizatriptan can be recommended for use in this population. Sleeping during migraine attacks was very common, and most children at least occasionally slept during an attack. Falling asleep was especially common in children under eight years of age and during the first hour after the onset of attack. Children who were able to sleep soon after attack onset were more likely pain-free at two hours. Sleeping probably both improves recovery from a migraine attack and is a sign of headache relief. Falling asleep should be classified as a sign of headache relief in clinical drug trials when studying migraine treatments in children and adolescents.

Associations of serum perfluoroalkyl acid levels with T-helper cell-specific cytokines in children: By gender and asthma status

Perfluoroalkyl acids (PFAAs) are a group of common chemicals that ubiquitously exist in wildlife and humans. Experimental data suggest that they may alter T-lymphocyte functioning in situ by preferentially enhancing the development of T-helper 2 (TH2)- and inhibiting TH1-lymphocyte development and might increase allergic inflammation, but few human studies have been conducted. To evaluate the association between serum PFAAs concentrations and T-lymphocyte-related immunological markers of asthma in children, and further to assess whether gender modified this association, 231 asthmatic children and 225 non-asthmatic control children from Northern Taiwan were recruited into the Genetic and Biomarker study for Childhood Asthma. Serum concentrations of ten PFAAs and levels of TH1 [interferon (IFN)-γ, interleukin (IL)-2] and TH2 (IL-4 and IL-5) cytokines were measured. The results showed that asthmatics had significantly higher serum PFAAs concentrations compared with the healthy controls. When stratified by gender, a greater number of significant associations between PFAAs and asthma outcomeswere found in males than in females. Among males, adjusted odds ratios for asthma among those with the highest versus lowest quartile of PFAAs exposure ranged from 2.59 (95% CI: 1.14, 5.87) for the perfluorobutanesulfonate (PFBS) to 4.38 (95% CI: 2.02, 9.50) for perfluorooctanesulfonate (PFOS); and serum PFAAs were associated positively with TH2 cytokines and inversely with TH1 cytokines among male asthmatics. Among females, no significant associations between PFAAs and TH2 cytokines could be detected. In conclusion, increased serum PFAAs levels may promote TH cell dysregulation and alter the availability of key TH1 and TH2 cytokines, ultimately contributing to the development of asthma that may differentially impact males to a greater degree than females. These results have potential relevance in asthma prevention.

Juvenile rheumatoid knee : Management of knee growth disturbances in children with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is associated with growth disturbances, especially leg length discrepancy (LLD) and knee valgus deformity (KVD). Studies have demonstrated growth plate stimulation with chronic arthritis. In the context of surgical treatment of LLD or KVD of a growing knee, the less invasive procedures, which allow immediate mobilisation, are preferred. Establishment of the skeletal age and the correction potential in the knees of rheumatic children is difficult due to rheumatic changes. In this present work, an analysis of the efficacy, safety and long-term results of temporary epiphyseal arrests performed in Rheumatism Foundation Hospital (Heinola, Finland). The distribution of diagnoses among children (n=71) with JIA and LLD (68 knees) was consistent with the normal oligoarthritis-predominated population of children with JIA. A higher male:female ratio (1:1.7 vs. 1:2.4 in population-based studies (PBS)) and earlier mean onset age (4 vs. 7 years in PBSs) were, however, distinct features in the study population. In most cases the correction was reliable and temporary arrest produced a mean correction of 1mm per month. The time of arrest required, however, varied significantly, probably due to the effect of underlying diseases and medication, and the age of the child. All complications encountered (10%) were minor. The correction achieved persisted in long-term follow-up. KVD (n=112, 177 knees) was associated with a high proportion of polyarthritic disease subtype (45% vs. 12-31% in PBSs), and the male:female distribution was grossly female-dominated (1:4.9 vs. 1:2.4 in PBSs). The early mean onset age (3 vs. 7 years in PBSs) was also notable in this cohort. Successful correction was achieved in 2/3 cases and the mean angular correction was 0.7 degrees per month. The required time of arrest, however, varied considerably. In 13% of knees the paucity of follow-up visits resulted in over-correction to varus. The complication rate (3%) in the knees operated for KVD was considerably lower compared to ten per cent in the management of LLD. Most of the complications related to epiphyseal stapling were reversible. However, the risk of premature closure of growth plates does exist. The number of over-corrections was notably high, with 13% knees turning to varus. The correction achieved persisted in long-term follow-up.

Protocol for assessing maternal, environmental and epigenetic risk factors for dental caries in children

Background Expenditure on dental and oral health services in Australia is $3.4 billion AUD annually. This is the sixth highest health cost and accounts for 7 % of total national health expenditure. Approximately 49 % of Australian children aged 6 years have caries experience in their deciduous teeth and this is rising. The aetiology of dental caries involves a complex interplay of individual, behavioural, social, economic, political and environmental conditions, and there is increasing interest in genetic predisposition and epigenetic modification. Methods The Oral Health Sub-study; a cross sectional study of a birth cohort began in November 2012 by examining mothers and their children who were six years old by the time of initiation of the study, which is ongoing. Data from detailed questionnaires of families from birth onwards and data on mothers’ knowledge, attitudes and practices towards oral health collected at the time of clinical examination are used. Subjects’ height, weight and mid-waist circumference are taken and Body Mass Index (BMI) computed, using an electronic Bio-Impedance balance. Dental caries experience is scored using the International Caries Detection and Assessment System (ICDAS). Saliva is collected for physiological measures. Salivary Deoxyribose Nucleic Acid (DNA) is extracted for genetic studies including epigenetics using the SeqCap Epi Enrichment Kit. Targets of interest are being confirmed by pyrosequencing to identify potential epigenetic markers of caries risk. Discussion This study will examine a wide range of potential determinants for childhood dental caries and evaluate inter-relationships amongst them. The findings will provide an evidence base to plan and implement improved preventive strategies.

Bone Health in Children and Adolescents with Juvenile Idiopathic Arthritis and Solid Organ Transplant

Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes to increased fracture risk. Childhood and adolescence are critical periods for bone mass gain. Peak bone mass is mostly acquired by the age of 18 years and is an important determinant of adult bone health and lifetime risk for fractures. Medications, especially glucocorticoids (GCs), chronic inflammation, decreased physical activity, hormonal deficiencies, delayed puberty, and poor nutrition may predispose children and adolescents with a chronic disease to impaired bone health. In this work, we studied overall bone health, the incidence and prevalence of fractures in children and adolescents who were treated for juvenile idiopathic arthritis (JIA) or had undergone solid organ transplantation. The first study cohort included 62 patients diagnosed with JIA and treated with GCs. The epidemiology of fractures after transplantation was investigated in 196 patients and a more detailed analysis of bone health determinants was performed on 40 liver (LTx) and 106 renal (RTx) transplantation patients. Bone mineral density (BMD) and vertebral morphology were assessed by dual-energy x-ray absorptiometry. Standard radiographs were obtained to detect vertebral fractures and to determine bone age; BMD values were adjusted for skeletal maturity. Our study showed that median BMD values were subnormal in all patient cohorts. The values were highest in patients with JIA and lowest in patients with LTx. Age at transplantation influenced BMD values in LTx but not RTx patients; BMD values were higher in patients who had LTx before the age of two years. BMD was lowest during the immediate posttransplantation years and increased subnormally during puberty. Delayed skeletal maturation was common in all patient groups. The prevalence of vertebral fractures ranged from 10% to 19% in the cohorts. Most of the fractures were asymptomatic and diagnosed only at screening. Vertebral fractures were most common in LTx patients. Vitamin D deficiency was common in all patient groups, and only 3% of patients with JIA and 25% of transplantation patients were considered to have adequate serum vitamin D levels. The total cumulative weight-adjusted dose of GC was not associated with BMD values in JIA or LTx patients. The combination of female gender and age over 15 years, parathyroid hormone concentration over 100 ng/L, and cumulative weight-adjusted methylprednisolone dose over 150 mg/kg during the three preceding years were found to be important predictors for low lumbar spine BMD in RTx patients. Based on the high prevalence of osteoporosis in the study cohorts more efforts should be put to prevention and early diagnosis of osteoporosis in these pediatric patients.

Assessment of Risk for Type 1 Diabetes in Children of Affected Families and in the General Population : Role of Immunological and Metabolic Markers

Background and aims. Type 1 diabetes (T1D), an autoimmune disease in which the insulin producing beta cells are gradually destroyed, is preceded by a prodromal phase characterized by appearance of diabetes-associated autoantibodies in circulation. Both the timing of the appearance of autoantibodies and their quality have been used in the prediction of T1D among first-degree relatives of diabetic patients (FDRs). So far, no general strategies for identifying individuals at increased disease risk in the general population have been established, although the majority of new cases originate in this population. The current work aimed at assessing the predictive role of diabetes-associated immunologic and metabolic risk factors in the general population, and comparing these factors with data obtained from studies on FDRs. Subjects and methods. Study subjects in the current work were subcohorts of participants of the Childhood Diabetes in Finland Study (DiMe; n=755), the Cardiovascular Risk in Young Finns Study (LASERI; n=3475), and the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP) Study subjects (n=7410). These children were observed for signs of beta-cell autoimmunity and progression to T1D, and the results obtained were compared between the FDRs and the general population cohorts. --- Results and conclusions. By combining HLA and autoantibody screening, T1D risks similar to those reported for autoantibody-positive FDRs are observed in the pediatric general population. Progression rate to T1D is high in genetically susceptible children with persistent multipositivity. Measurement of IAA affinity failed in stratifying the risk assessment in young IAA-positive children with HLA-conferred disease susceptibility, among whom affinity of IAA did not increase during the prediabetic period. Young age at seroconversion, increased weight-for-height, decreased early insulin response, and increased IAA and IA-2A levels predict T1D in young children with genetic disease susceptibility and signs of advanced beta-cell autoimmunity. Since the incidence of T1D continues to increase, efforts aimed at preventing T1D are important, and reliable disease prediction is needed both for intervention trials and for effective and safe preventive therapies in the future. Our observations confirmed that combined HLA-based screening and regular autoantibody measurements reveal similar disease risks in pediatric general population as those seen in prediabetic FDRs, and that risk assessment can be stratified further by studying glucose metabolism of prediabetic subjects. As these screening efforts are feasible in practice, the knowledge now obtained can be exploited while designing intervention trials aimed at secondary prevention of T1D.