PReS-FINAL-2177: Safety and lack of autoantibody production following influenza H1N1 vaccination in patients with juvenile idiopathic arthritis (JIA)

Introduction Vaccination is an effective tool against several infectious agents including influenza. In 2010, the Advisory Committee on Immunization Practices (ACIP) recommended influenza A H1N1/2009 immunization for high risk groups, including juvenile idiopathic arthritis (JIA) patients and more recently the EULAR task force reinforced the importance of vaccination in immunosuppressed pediatric rheumatologic patients. We have recently shown that Influenza A H1N1/2009 vaccination generated protective antibody production with short-term safety profile among 93 JIA patients, but the possible impact of the vaccine in autoimmune response in JIA have not been studied. Therefore, we aimed to assess the production of some autoantibodies generated following influenza H1N1 vaccination in JIA patients. Objectives To assess the autoimmune response and H1N1 serology following influenza H1N1 vaccination in patients with JIA. Methods Cepa A/California/7/2009 (NYMC X-179A) anti-H1N1 was used to vaccinate JIA patients: 1 dose of immunization was given to all participants and those <9yrs of age received a second booster 3 weeks apart. Sera were analyzed before and 3 weeks following complete vaccination. Serology against H1N1 virus was performed by hemagglutination inhibition antibody assay, rheumatoid factor (RF) by latex fixation test, antinuclear antibodies (ANA) by IIF, IgM and IgG anticardiolipin (aCL) by ELISA.Results Among 98 JIA patients that were vaccinated, 58 sera were available for this study. Mean age of 58 JIA patients was 23.9 ± 9.5 yrs, 38 were females and 20 males with mean disease duration of 14.7 ± 10.1 yrs. JIA subtypes were: 33 (57%) poliarticular, 10 (17%) oligoarticular, 6 (10%) systemic and 9 (16%) other. Sixteen patients were off drugs while 42 (72%) were under different pharmacotherapy: 32 (55%) were on 1 DMARD/IS, 10 (17%) on 2 DMARDs/IS, 19 (33%) antimalarials, 29 (50%) MTX, 8(14%) sulfasalazine, 6 (10%) anti-TNFs, 4 (7%) abatacept; no patient was using prednisone >0.5 mg/kg/d. Seroprotection rates against H1N1 influenza increased from 23 to 83% and seroconversion rates were achieved in 78% JIA. Prior to vaccination, 31(53.4%) JIA patients were ANA+, 6(10.3%) RF+, and 4 (7%) IgM + IgG aCL+. After complete H1N1 vaccination, positivity for ANA remained the same whereas 1 patient became negative for IgG aCL, and another for RF, IgM and IgG aCL. One (1.7%) patient turned low titer IgG aCL+. Conclusion Vaccination of JIA patients against pandemic influenza A (H1N1) generated successful protective antibody production without the induction of autoantibody production, except for 1 patient that became positive for low titer IgG aCL, supporting its safety.

PReS-FINAL-2170: Work disability in adult patients with juvenile idiopathic arthritis (JIA)

Introduction Approximately 20% JIA patients enters adulthood with clinically active disease and disabled, therefore work condition may be affected. Objectives To assess the prevalence of work disability among adult patients with JIA regularly attending a tertiary heumatology center and to determine possible associated risk factors. Methods This was a cross-sectional study that enrolled 43 JIA patients according to 2004 revised ILAR criteria. A questionnaire was developed in order to evaluate working status and labor activity: occupation, current/previous work, employment status and withdrawal rate were actively searched. Demographic data, JIA characteristics, clinical activity (DAS28>2.6), therapeutic intervention, comorbidities, physical activity, sedentarism (WHO definitions), functional class (1991 ACR criteria), HAQ and SF-36 were recorded. The prevalence of work disability was calculated using 95% confidence interval, and compared to all parameters; qualitative variables were analyzed using tests of association (chi-square test) and quantitative variables by Mann-Whitney or student test. Results Patients' mean age was 29+7.4 yrs (range 19-41) with mean JIA duration = 17.2+12.3 yrs (range 3-33); 63% were males and 37% females. JIA subtypes were 64% polyarticular, 11% oligoarticular, 9% systemic, 9% ERA, 2% extended oligoarticular, 2% psoriatic arthritis; 7% had uveitis. Serum RF was positive in 21% and ANA in 21%. The majority (72%, n = 31) of JIA patients were employed, whereas 28% (n = 12) were currently not working. In the latter group, 83% (10/12) were retired due to JIA related disability. Further analysis comparing those currently working vs. Those not working revealed similar age (25,3 yrs vs.29,5 yrs, p = 0,09). Although not significantly, most patients currently working had Poly onset JIA (22 vs. 6 p = 0,37), higher frequencies of good education level >12 yrs of school (31 vs.9, p = 0,38), functional class I (p = 0,96), practiced regular physical activity (9 vs. 0, p = 0,89), were singles (26 vs. 8, p = 0,15). Both groups had comparable HAQ and DAS 28 scores (0,62 vs. 0.59, p = 0,47 and 2,51 vs.2,07, p = 0,64) and similar arthroplasty rate (8 vs. 4, p = 0,427). Frequencies of hypertension (3 vs.1, p = 0,999), dyslipidemia (1 vs. 1, p = 0,125), diabetes (1 vs. 0 p = 0,999), depression (1 vs. 0, p = 0,999) and smokers (3 vs. 1, p = 0,99) were alike in both groups. Remarkably, employed patients had higher SF 36 mental health component (84.0 vs. 70.42, P = 0.01). Conclusion High prevalence of almost 1/3 work disability and of retirement due to disease related incapacity remain major problems for adult JIA individuals. We also identified worse mental health in employed patients indicating that further research is needed, in addition to intense affirmative disability actions in order to remove possible disabling barriers and to adapt restrictive environments for these patients. Moreover, enhanced strategies and policy for inclusion of JIA patients in the job market is urged.

PReS-FINAL-2357: Effects of anti-melanocyte stimulating hormone in murine pristine-induced lupus

Introduction Alfa-melanocyte stimulating hormone (α-MSH) has a variety of biological functions such as downregulation of pro-inflammatory pathways, reduction of skin delayed-type hypersensitivity and blockage of leukocyte migration. Inhibition of experimental disease models development including inflammatory bowel disease and rheumatoid arthritis has been shown, however the immunomodulatory and anti-inflammatory effects of α-MSH on murine lupus remain undetermined. Objectives To evaluate the effect of α-MSH analogue (NDP α-MSH) on pristane-induced murine lupus. Methods Thirty-five BALB/c mice were injected with 0.5 ml intraperitoneal (IP) pristane for lupus-like model induction and 5 age/gender matched control mice were given saline. Pristane-induced lupus animals received daily IP saline (n = 5) or treatments with 3.1 mg/kg/d chloroquine (n = 10), 1.25 mg/kg/d NDP α-MSH (n = 10) or 2.5 mg/kg/d NDP α-MSH (n = 10). Prior and 180 days after induction, clinical and laboratorial lupus-like parameters were examined. Sera ANA was tested by IF using Hep2 cells. Statistical analysis was performed by Mann-Whitney and Fisher test and P < 0,05 considered significant. Results Arthritis in both hind legs and large amounts of lipogranulomas in peritoneal cavity were observed in all lupus-like animals in contrast to all controls. By visual observation, all lupus animals treated with both doses of α-MSH had significant less amount and lower size lipogranulomas. Mean arthritis score in 5 untreated mice, 9 animals treated with chloroquine and 8 with α-MSH 2.5 mg/kg/d was 5.2, 3.33 and 3.1 respectively. Remarkably, mean arthritis score of animals treated with α-MSH 1.25 mg/kg/d was 1.6, significantly lower than untreated mice (1.6 vs 5.2, p = 0.0291). ANAs were negative in sera from all 40 animals before pristane lupus injection; 180 days after induction, ANAs remained negative in normal mice but became positive in all 5 (100%) untreated lupus animals, 7 (77%), 4 (50%) and 3 (35%) lupus models treated with chloroquine, α-MSH 2.5 mg/kg/d and α-MSH 1.25 mg/kg/d (100% vs 35%, p = 0,0256), respectively. Before the end of the experiment, by day 150, 3 animals died: 1 treated with chloroquine and 2 with higher doses of α-MSH. Conclusion NDP α-MSH promoted improvement of clinical and serological parameters in pristane-induced murine lupus suggesting a potential role for this drug in human SLE.

The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis.

Objective To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables. Methods Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the “gold standard measure,” chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions. Results The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process. Conclusion We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM.

Effects of pediatric obesity on joint kinematics and kinetics during 2 walking cadences

Objective: To determine whether differences existed in lower-extremity joint biomechanics during self-selected walking cadence (SW) and fast walking cadence (FW) in overweight- and normal-weight children.---------- Design: Survey.---------- Setting: Institutional gait study center.---------- Participants: Participants (N=20; mean age ± SD, 10.4±1.6y) from referred and volunteer samples were classified based on body mass index percentiles and stratified by age and sex. Exclusion criteria were a history of diabetes, neuromuscular disorder, or recent lower-extremity injury.---------- Main Outcome Measures: Sagittal, frontal, and transverse plane angular displacements (degrees) and peak moments (newton meters) at the hip, knee, and ankle joints.---------- Results: The level of significance was set at P less than .008. Compared with normal-weight children, overweight children had greater absolute peak joint moments at the hip (flexor, extensor, abductor, external rotator), the knee (flexor, extensor, abductor, adductor, internal rotator), and the ankle (plantarflexor, inverter, external/internal rotators). After including body weight as a covariate, overweight children had greater peak ankle dorsiflexor moments than normal-weight children. No kinematic differences existed between groups. Greater peak hip extensor moments and less peak ankle inverter moments occurred during FW than SW. There was greater angular displacement during hip flexion as well as less angular displacement at the hip (extension, abduction), knee (flexion, extension), and ankle (plantarflexion, inversion) during FW than SW.---------- Conclusions: Overweight children experienced increased joint moments, which can have long-term orthopedic implications and suggest a need for more nonweight-bearing activities within exercise prescription. The percent of increase in joint moments from SW to FW was not different for overweight and normal-weight children. These findings can be used in developing an exercise prescription that must involve weight-bearing activity.

The association between cold spells and pediatric outpatient visits for asthma in Shanghai, China

Background Asthma is a serious global health problem. However, few studies have investigated the relationship between cold spells and pediatric outpatient visits for asthma. Objective To examine the association between cold spells and pediatric outpatient visits for asthma in Shanghai, China. Methods We collected daily data on pediatric outpatient visits for asthma, mean temperature, relative humidity, and ozone from Shanghai between 1 January 2007 and 31 December 2009. We defined cold spells as four or more consecutive days with temperature below the 5th percentile of temperature during 2007–2009. We used a Poisson regression model to examine the impact of temperature on pediatric outpatient visits for asthma in cold seasons during 2007 and 2009. We examined the effect of cold spells on asthma compared with non-cold spell days. Results There was a significant relationship between cold temperatures and pediatric outpatient visits for asthma. The cold effects on children's asthma were observed at different lags. The lower the temperatures, the higher the risk for asthma attacks among children. Conclusion Cold temperatures, particularly cold spells, significantly increase the risk of pediatric outpatient visits for asthma. The findings suggest that asthma children need to be better protected from cold effects in winter.

Identification of radiological alveolar pneumonia in children with high rates of hospitalized respiratory infections : Comparison of WHO-defined and pediatric pulmonologist diagnosis in the clinical context

Background A reliable standardized diagnosis of pneumonia in children has long been difficult to achieve. Clinical and radiological criteria have been developed by the World Health Organization (WHO), however, their generalizability to different populations is uncertain. We evaluated WHO defined chest radiograph (CXRs) confirmed alveolar pneumonia in the clinical context in Central Australian Aboriginal children, a high risk population, hospitalized with acute lower respiratory illness (ALRI). Methods CXRs in children (aged 1-60 months) hospitalized and treated with intravenous antibiotics for ALRI and enrolled in a randomized controlled trial (RCT) of Vitamin A/Zinc supplementation were matched with data collected during a population-based study of WHO-defined primary endpoint pneumonia (WHO-EPC). These CXRs were reread by a pediatric pulmonologist (PP) and classified as pneumonia-PP when alveolar changes were present. Sensitivities, specificities, positive and negative predictive values (PPV, NPV) for clinical presentations were compared between WHO-EPC and pneumonia-PP. Results Of the 147 episodes of hospitalized ALRI, WHO-EPC was significantly less commonly diagnosed in 40 (27.2%) compared to pneumonia-PP (difference 20.4%, 95% CI 9.6-31.2, P < 0.001). Clinical signs on admission were poor predictors for both pneumonia-PP and WHO-EPC; the sensitivities of clinical signs ranged from a high of 45% for tachypnea to 5% for fever + tachypnea + chest-indrawing. The PPV range was 40-20%, respectively. Higher PPVs were observed against the pediatric pulmonologist's diagnosis compared to WHO-EPC. Conclusions WHO-EPC underestimates alveolar consolidation in a clinical context. Its use in clinical practice or in research designed to inform clinical management in this population should be avoided. Pediatr Pulmonol. 2012; 47:386-392. (C) 2011 Wiley Periodicals, Inc.

Air pollution, temperature and pediatric influenza in Brisbane, Australia

Previous studies have demonstrated the importance of weather variables in influencing the incidence of influenza. However, the role of air pollution is often ignored in identifying the environmental drivers of influenza. This research aims to examine the impacts of air pollutants and temperature on the incidence of pediatric influenza in Brisbane, Australia. Lab-confirmed daily data on influenza counts among children aged 0-14years in Brisbane from 2001 January 1st to 2008 December 31st were retrieved from Queensland Health. Daily data on maximum and minimum temperatures for the same period were supplied by the Australian Bureau of Meteorology. Winter was chosen as the main study season due to it having the highest pediatric influenza incidence. Four Poisson log-linear regression models, with daily pediatric seasonal influenza counts as the outcome, were used to examine the impacts of air pollutants (i.e., ozone (O3), particulate matter≤10μm (PM10) and nitrogen dioxide (NO2)) and temperature (using a moving average of ten days for these variables) on pediatric influenza. The results show that mean temperature (Relative risk (RR): 0.86; 95% Confidence Interval (CI): 0.82-0.89) was negatively associated with pediatric seasonal influenza in Brisbane, and high concentrations of O3 (RR: 1.28; 95% CI: 1.25-1.31) and PM10 (RR: 1.11; 95% CI: 1.10-1.13) were associated with more pediatric influenza cases. There was a significant interaction effect (RR: 0.94; 95% CI: 0.93-0.95) between PM10 and mean temperature on pediatric influenza. Adding the interaction term between mean temperature and PM10 substantially improved the model fit. This study provides evidence that PM10 needs to be taken into account when evaluating the temperature-influenza relationship. O3 was also an important predictor, independent of temperature.

Predictors of re-epithelialization in pediatric burn

INTRODUCTION An important treatment goal for burn wounds is to promote early wound closure. This study identifies factors associated with delayed re-epithelialization following pediatric burn. METHODS Data were collected from August 2011 to August 2012, at a pediatric tertiary burn center. A total of 106 burn wounds were analyzed from 77 participants aged 4-12 years. Percentage of wound re-epithelialization at each dressing change was calculated using Visitrak. Mixed effect regression analysis was performed to identify the demographic factors, wound and clinical characteristics associated with delayed re-epithelialization. RESULTS Burn depth determined by laser Doppler imaging, ethnicity, pain scores, total body surface area (TBSA), mechanism of injury and days taken to present to the burn center were significant predictors of delayed re-epithelialization, accounting for 69% of variance. Flame burns delayed re-epithelialization by 39% compared to all other mechanisms (p=0.003). When initial presentation to the burn center was on day 5, burns took an average of 42% longer to re-epithelialize, compared to those who presented on day 2 post burn (p<0.000). Re-epithelialization was delayed by 14% when pain scores were reported as 10 (on the FPS-R), compared to 4 on the first dressing change (p=0.015) for children who did not receive specialized preparation/distraction intervention. A larger TBSA was also a predictor of delayed re-epithelialization (p=0.030). Darker skin complexion re-epithelialized 25% faster than lighter skin complexion (p=0.001). CONCLUSIONS Burn depth, mechanism of injury and TBSA are always considered when developing the treatment and surgical management plan for patients with burns. This study identifies other factors influencing re-epithelialization, which can be controlled by the treating team, such as effective pain management and rapid referral to a specialized burn center, to achieve optimal outcomes.

Play and heal : randomized controlled trial of Ditto intervention efficacy on improving re-epithelialization in pediatric burns

BACKGROUND: The relationships between pain, stress and anxiety, and their effect on burn wound re-epithelialization have not been well explored to-date. The aim of this study was to investigate the effect of the Ditto (a hand-held electronic medical device providing procedural preparation and distraction) intervention on re-epithelialization rates in acute pediatric burns. METHODS/DESIGN: From August 2011 to August 2012, children (4-12 years) with an acute burn presenting to the Royal Children's Hospital, Brisbane, Australia fulfilled the study requirements and were randomized to [1] Ditto intervention or [2] standard practice. Burn re-epithelialization, pain intensity, anxiety and stress measures were obtained at every dressing change until complete wound re-epithelialization. RESULTS: One hundred and seventeen children were randomized and 75 children were analyzed (n=40 standard group; n=35 Ditto group). Inability to predict wound management resulted in 42 participants no longer meeting the eligibility criteria. Wounds in the Ditto intervention group re-epithelialized faster than the standard practice group (-2.14 days (CI: -4.38 to 0.10), p-value=0.061), and significantly faster when analyses were adjusted for mean burn depth (-2.26 days (CI: -4.48 to -0.04), p-value=0.046). Following procedural preparation at the first change of dressing, the Ditto group reported lower pain intensity scores (-0.64 (CI: -1.28, 0.01) p=0.052) and lower anxiety ratings (-1.79 (CI: -3.59, 0.01) p=0.051). At the second and third dressing removals average pain (FPS-R and FLACC) and anxiety scores (VAS-A) were at least one point lower when Ditto intervention was received. CONCLUSIONS: The Ditto procedural preparation and distraction device is a useful tool alongside pharmacological intervention to improve the rate of burn re-epithelialization and manage pain and anxiety during burn wound care procedures.

Biological markers of stress in pediatric acute burn injury

BACKGROUND Burns and their associated wound care procedures evoke significant stress and anxiety, particularly for children. Little is known about the body's physiological stress reactions throughout the stages of re-epithelialization following an acute burn injury. Previously, serum and urinary cortisol have been used to measure stress in burn patients, however these measures are not suitable for a pediatric burn outpatient setting. AIM To assess the sensitivity of salivary cortisol and sAA in detecting stress during acute burn wound care procedures and to investigate the body's physiological stress reactions throughout burn re-epithelialization. METHODS Seventy-seven participants aged four to thirteen years who presented with an acute burn injury to the burn center at the Royal Children's Hospital, Brisbane, Australia, were recruited between August 2011 and August 2012. RESULTS Both biomarkers were responsive to the stress of burn wound care procedures. sAA levels were on average 50.2U/ml higher (p<0.001) at 10min post-dressing removal compared to baseline levels. Salivary cortisol levels showed a blunted effect with average levels at ten minutes post dressing removal decreasing by 0.54nmol/L (p<0.001) compared to baseline levels. sAA levels were associated with pain (p=0.021), no medication (p=0.047) and Child Trauma Screening Questionnaire scores at three months post re-epithelialization (p=0.008). Similarly, salivary cortisol was associated with no medication (p<0.001), pain scores (p=0.045) and total body surface area of the burn (p=0.010). CONCLUSION Factors which support the use of sAA over salivary cortisol to assess stress during morning acute burn wound care procedures include; sensitivity, morning clinic times relative to cortisol's diurnal peaks, and relative cost.

An audit of first-aid treatment of pediatric burns patients and their clinical outcome

This study describes the first aid used and clinical outcomes of all patients who presented to the Royal Children's Hospital, Brisbane, Australia in 2005 with an acute burn injury. A retrospective audit was performed with the charts of 459 patients and information concerning burn injury, first-aid treatment, and clinical outcomes was collected. First aid was used on 86.1% of patients, with 8.7% receiving no first aid and unknown treatment in 5.2% of cases. A majority of patients had cold water as first aid (80.2%), however, only 12.1% applied the cold water for the recommended 20 minutes or longer. Recommended first aid (cold water for >or=20 minutes) was associated with significantly reduced reepithelialization time for children with contact injuries (P=.011). Superficial depth burns were significantly more likely to be associated with the use of recommended first aid (P=.03). Suboptimal treatment was more common for children younger than 3.5 years (P<.001) and for children with friction burns. This report is one of the few publications to relate first-aid treatment to clinical outcomes. Some positive clinical outcomes were associated with recommended first-aid use; however, wound outcomes were more strongly associated with burn depth and mechanism of injury. There is also a need for more public awareness of recommended first-aid treatment.