Initial visit symptoms in probable Behçet's syndrome is predictive of ISG criteria fulfillment in Behçet's syndrome: data from New York and Amsterdam cohorts.

OBJECTIVES: Behçet's syndrome (BS) is a systemic vasculitis with heterogeneous clinical presentation and a relapsing disease course. The International Study Group (ISG) criteria are most often used for classification. A significant proportion of patients is classified as probable BS because they do not fulfil the criteria at initial presentation. The aim of this study is to explore clinical BS symptoms present at initial patient visit predictive of ISG criteria diagnosis during follow-up. METHODS: Patients classified as probable BS at initial visit were included. Follow-up ISG status (defined as meeting criteria ISG+ vs. not meeting criteria ISG-) was abstracted from last visit. Univariable logistic regression was used to screen initial visit clinical features and symptoms with follow-up ISG status. All variables that passed screening at p<0.10 were included in the final multivariable model, which was then used to create a probability risk score. RESULTS: 189 patients were included (169 from New York and 20 from Amsterdam). 71 (37.6%) patients were classified as ISG+ during follow-up. In the final model, presence of morning stiffness, genital ulcers, skin lesions, and eye disease were associated with increased odds of ISG+, adjusting for age, symptom duration and family history. This was used to create a probability risk score. CONCLUSIONS: Over a third of patients with suspected or probable BS developed new manifestations over time that led to classification as ISG+ BS. The presence of morning stiffness, genital ulcers, skin lesions and eye disease at initial visit were independently associated with significantly higher odds for developing ISG+ Behçet's during follow-up.

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure.

BACKGROUND & AIMS: A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC; a sensitive and specific quantitative analytic assay) to detect acetaminophen protein adducts. METHODS: We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal-Wallis test or rank-sum test for continuous variables. RESULTS: AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222-1027) vs 3678 (range, 394-8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. CONCLUSIONS: The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management.

Adherence to guidelines for the treatment of Behçet's syndrome in New York and Amsterdam.

OBJECTIVES: To assess adherence to published guidelines for the treatment of Behçet's syndrome (BS) in two geographic areas. METHODS: We extracted guideline statements from the 2008 EULAR recommendations. Adherence to these statements was evaluated retrospectively in both New York (USA) and Amsterdam (The Netherlands), by reviewing records from patients fulfilling the ISG criteria. We analysed data per statement and event, and divided data according to the year in which an event occurred. We compared events prior to 2009 to those after publication of the EULAR recommendations (2009 and later). RESULTS: 474 patients were evaluated, 24 of whom were from Amsterdam. Treatment adherence varied substantially across various Behçet's manifestations, ranging from 21% vs. 31% in posterior uveitis, 50% vs. 25% in arterial disease, 29% vs. 29% in arthritis and 38% vs. 55% in erythema nodosum to 65% vs. 67% in deep venous thrombosis (DVT), before and after publication of the guidelines respectively. Topical treatment of mucocutaneous disease was only 2% vs. 8%, whereas adherence in neuro-Behçet was ≥ 94% and 100% in gastrointestinal disease. CONCLUSIONS: Adherence to treatment guidelines varies substantially by Behçet's manifestation. Lack of adherence in manifestations such as eye disease and arthritis suggests that current recommendations are not sufficient or other concurrent manifestations require more aggressive treatment. The extensive use of anti-TNF agents might indicate a shift towards more aggressive treatment. Thus, our results suggest the 2008 guidelines were not in line with treatment in clinical practice over the past years and the recent revision of the recommendations was indeed needed.

Improved Survival While Waiting and Risk Factors for Death in Pediatric Patients Listed for Cardiac Transplantation.

Our aim is to determine (a) the effect of changes in pre-transplant management and era of listing on survival of children listed for HTx and (b) risk factors for death while waiting. This retrospective study included all children listed between 1/1993 and 12/2009 at our center. Survival was determined using survival analysis and competing outcomes modeling. There were 254 listed patients of whom 144 (57%) had congenital heart disease, 208 (82%) were status 1, 52 used ECMO (20%), and 28 used ventricular assist device support (VAD) (11%) beginning in 2005. Overall mortality while waiting was 17% at 6 months, and 69% underwent transplant. Seven of 95 patients (7%) died waiting after 2004 compared to 36 of 159 (23%) before. ECMO and earlier year of listing were significant risk factors (p < 0.001) for wait-list mortality, whereas mortality was significantly lower (p = 0.002) after availability of VADs. Race, gender, blood type, and congenital diagnosis were not significant risk factors for death. Survival in pediatric patients listed for HTx has improved significantly in the current era at our institution. The availability of pediatric VADs has had a significant impact on survival while waiting in children listed for transplantation.

Use of Biologic Therapy in Racial Minorities With Rheumatoid Arthritis From 2 US Health Care Systems.

BACKGROUND: In the United States, there is racial/ethnic disparity in the care of rheumatoid arthritis (RA), yet there are limited data regarding the impact of varied health care systems on treatment outcomes. OBJECTIVE: The aim fo this study was to compare the frequencies of use of disease-modifying antirheumatic drugs and biologic agents in racial minorities with RA in a single-payer and variable-access health systems. METHODS: Rheumatoid arthritis disease status was examined in the Ethnic Minority Rheumatoid Arthritis Consortium (EMRAC) and Veterans Affairs Rheumatoid Arthritis Registry (VARA); frequencies of prednisone and disease-modifying antirheumatic drugs and biologic agent use at enrollment were documented. Comparisons in frequencies of RA therapies between RA cohorts and white and nonwhite racial subsets were evaluated. RESULTS: The combined cohorts provided 2899 subjects for analysis (EMRAC = 943, VARA = 1956). Routine Assessment of Patient Index Data 3 and Disease Activity Score in 28 Joints scores were equivalent (cohort, racial subsets), as was biologic agent use (26% vs. 28%) between whites and nonwhites. Disease-modifying antirheumatic drug use was greater in EMRAC nonwhites compared with their white counterparts, but similar to all VARA patients (33% vs. 22% [P < 0.001], 36%, 39%, respectively). However, biologic agent use was significantly greater in EMRAC versus VARA patients (37% vs. 22%, P < 0.001). In VARA patients, there was no difference in biologic agent use among racial subsets (22% vs. 21%). In EMRAC patients, biologic agent use was greater in whites than in nonwhites (EMRAC white 45% vs. EMRAC nonwhite 33%, P < 0.001; odds ratio, 1.66) and compared with all VARA subjects (EMRAC white 45% vs. all VARA 22%, P < 0.001; odds ratio, 2.91). Younger age, advanced education, longstanding disease, and severe disease were associated with biologic agent use. CONCLUSIONS: When compared with more variable-access systems, a VA system of care that includes a single-payer insurance may afford equality in use of biologic agents among different racial subsets.

Video intervention changes parent perception of all-terrain vehicle (ATV) safety for children.

BACKGROUND: Children aged <16 years account for 25% of deaths on all-terrain vehicles (ATVs), despite public health and industry warning against paediatric use. Parents often underestimate instability and other risks associated with ATVs. OBJECTIVE: To determine if a brief intervention consisting of validated computer simulations of ATV performance with a child driver changes attitudes, beliefs and planned safety behaviours of parents of children who ride ATVs. DESIGN/METHODS: Participants were parents of children presenting to a children's hospital emergency department. All participants had children who had ridden an ATV in the past year. Subjects viewed a video simulation of ATVs in scenarios featuring 6-year-old and 10-year-old biofidelic anthropomorphic test devices. Parents completed a survey both before and after viewing the video to report attitudes/beliefs on ATV safety for children, use of safety equipment and family ATV use, as well as risk and safety perception. RESULTS: Surveys were collected from 99 parents, mostly mothers (79%), Caucasian (61%) and had high school education or less (64%). The intervention shifted parents' belief in overall ATV safety (48% unsafe pre-intervention, 73% unsafe post-intervention, p<0.001). After viewing the video simulation, parents were almost six times more likely to perceive ATVs as unsafe (OR 5.96, 95% CI 2.32 to 15.31, p<0.001) and many parents (71%) planned to change family ATV safety rules. CONCLUSION: Video simulations of ATV performance with child riders changed short-term risk perception and planned safety behaviours of parents whose children ride ATVs. Similar educational interventions hold promise for larger-scale studies in at-risk populations.

Association of Antegrade Pulmonary Artery Diastolic Velocity with Spontaneous Closure of the Patent Ductus Arteriosus in Extremely Low-Birth-Weight Infants.

OBJECTIVE: This study aims to determine echocardiographic parameters associated with spontaneous patent ductus arteriosus (PDA) closure in extremely low-birth-weight (ELBW) infants. STUDY DESIGN: Retrospective demographic review and analysis of echocardiograms from 189 ELBW infants with suspected and confirmed hemodynamically significant PDA identified on an initial echocardiogram was performed. Comparison of echocardiographic parameters was made between infants with spontaneous closure versus those who received treatment. RESULTS: The mean birth weight (787 ± 142 vs. 724 ± 141 g, p = 0.04) and gestational age (27.4 ± 2.8 vs. 26.2 ± 1.6 weeks, p = 0.03) were higher in the spontaneous closure versus the treatment group. Antegrade pulmonary artery (PA) diastolic velocity was lower in infants with spontaneous PDA closure versus those who received treatment (0.15 ± 0.06 vs. 0.22 ± 0.12 m/s, p = 0.009). CONCLUSION: Heavier and more mature ELBW infants with a lower antegrade PA diastolic velocity were likely to have spontaneous closure of the PDA.

Surgeon-performed bedside ultrasound to assess volume status: a feasibility study.

PURPOSE: Rapid assessment of volume status in children is often difficult. The purpose of this study was to evaluate the feasibility of surgeon-performed ultrasound to assess volume status in patients with hypertrophic pyloric stenosis. METHODS: Ultrasounds were performed on admission and before operation. The diameters of the inferior vena cava (IVC) and aorta (Ao) were measured and IVC/Ao ratios were calculated. Electrolytes were measured on admission and repeated if warranted. Logistic regression was used to associate the clinical outcome, defined as CO2 ≤30 mEq/L, with IVC/Ao ratios. Predictive capacity was estimated from the logistic regression for IVC/Ao ratios. Linear regression was used to estimate associations between CO2 values and IVC/Ao ratios. RESULTS: Thirty-one patients were enrolled. The IVC/Ao ratio is highly associated with actual CO2 values (P < 0.001) and the clinical outcome (P = 0.004). For every 0.05 unit increase in IVC/Ao ratio, predicted CO2 decreased 1.1 units. For every 0.05 unit increase in the IVC/Ao ratio, the odds of having a CO2 ≤30 mEq/L increased 48% [OR = 1.48, 95% CI (1.13,1.94)]. Predictive capacity is maximized at an IVC/Ao ratio of 0.75 as 83.9 % of subjects were correctly classified and specificity and PPV = 100%. CONCLUSIONS: Surgeon-performed ultrasound to determine IVC/Ao ratio is feasible. An IVC/Ao ratio of 0.75 predicted adequate resuscitation.

Presence of gout is associated with increased prevalence and severity of knee osteoarthritis among older men: results of a pilot study.

BACKGROUND: Gout and osteoarthritis (OA) are the most prevalent arthritides, but their relationship is neither well established nor well understood. OBJECTIVES: We assessed whether a diagnosis of gout or asymptomatic hyperuricemia (AH) is associated with increased prevalence/severity of knee OA. METHODS: One hundred nineteen male patients aged 55 to 85 years were sequentially enrolled from the primary care clinics of an urban Veterans Affairs hospital, assessed and categorized into 3 groups: gout (American College of Rheumatology Classification Criteria), AH (serum urate ≥6.8 mg/dL, no gout), and control (serum urate <6.8 mg/dL, no gout). Twenty-five patients from each group subsequently underwent formal assessment of knee OA presence and severity (American College of Rheumatology Clinical/Radiographic Criteria, Kellgren-Lawrence grade). Musculoskeletal ultrasound was used to detect monosodium urate deposition at the knees and first metatarsophalangeal joints. RESULTS: The study showed 68.0% of gout, 52.0% of AH, and 28.0% of age-matched control subjects had knee OA (gout vs control, P = 0.017). Odds ratio for knee OA in gout versus control subjects was 5.46 prior to and 3.80 after adjusting for body mass index. Gout subjects also had higher Kellgren-Lawrence grades than did the control subjects (P = 0.001). Subjects with sonographically detected monosodium urate crystal deposition on cartilage were more likely to have OA than those without (60.0 vs 27.5%, P = 0.037), with crystal deposition at the first metatarsophalangeal joints correlating most closely with OA knee involvement. CONCLUSIONS: Knee OA was more prevalent in gout patients versus control subjects and intermediate in AH. Knee OA was more severe in gout patients versus control subjects.

Unfractionated heparin activity measured by anti-factor Xa levels is associated with the need for extracorporeal membrane oxygenation circuit/membrane oxygenator change: a retrospective pediatric study.

OBJECTIVE: Investigate whether anti-Factor Xa levels are associated with the need for change of circuit/membrane oxygenator secondary to thrombus formation in pediatric patients. DESIGN AND SETTINGS: Retrospective single institution study. PATIENTS: Retrospective record review of 62 pediatric patients supported with extracorporeal membrane oxygenation from 2009 to 2011. INTERVENTIONS: Data on standard demographic characteristics, indications for extracorporeal membrane oxygenation, duration of extracorporeal membrane oxygenation, activated clotting time measurements, anti-Factor Xa measurements, and heparin infusion rate were collected. Generalized linear models were used to associate anti-Factor Xa concentrations and need for change of either entire circuit/membrane oxygenator secondary to thrombus formation. MEASUREMENTS AND MAIN RESULTS: Sixty-two patients met study inclusion criteria. No-circuit change was required in 45 of 62 patients. Of 62 patients, 17 required change of circuit/membrane oxygenator due to thrombus formation. Multivariate analysis of daily anti-Factor Xa measurements throughout duration of extracorporeal membrane oxygenation support estimated a mean anti-Factor Xa concentration of 0.20 IU/mL (95% CI, 0.16, 0.24) in no-complete-circuit group that was significantly higher than the estimated concentration of 0.13 IU/mL (95% CI, 0.12, 0.14) in complete-circuit group (p = 0.001). A 0.01 IU/mL decrease in anti-Factor Xa increased odds of need for circuit/membrane oxygenator change by 5% (odds ratio = 1.105; 95% CI, 1.00, 1.10; p = 0.044). Based on the observed anti-Factor Xa concentrations, complete-circuit group had 41% increased odds for requiring circuit/membrane oxygenator change compared with no-complete-circuit group (odds ratio = 1.41; 95% CI, 1.01, 1.96; p = 0.044). Mean daily activated clotting time measurement (p = 0.192) was not different between groups, but mean daily heparin infusion rate (p < 0.001) was significantly different between the two groups. CONCLUSIONS: Higher anti-Factor Xa concentrations were associated with freedom from circuit/membrane oxygenator change due to thrombus formation in pediatric patients during extracorporeal membrane oxygenation support. Activated clotting time measurements did not differ significantly between groups with or without circuit/membrane oxygenator change. This is the first study to link anti-Factor Xa concentrations with a clinically relevant measure of thrombosis in pediatric patients during extracorporeal membrane oxygenation support. Further prospective study is warranted.

Academic proficiency in children after early congenital heart disease surgery.

Children with early surgery for congenital heart disease (CHD) are known to have impaired neurodevelopment; their performance on school-age achievement tests and their need for special education remains largely unexplored. The study aimed to determine predictors of academic achievement at school age and placement in special education services among early CHD surgery survivors. Children with CHD surgery at <1 year of age from January 1, 1998 to December 31, 2003, at the Arkansas Children's Hospital were identified. Out-of-state births and infants with known genetic and/or neurologic conditions were excluded. Infants were matched to an Arkansas Department of Education database containing standardized assessments at early school age and special-education codes. Predictors for achieving proficiency in literacy and mathematics and the receipt of special education were determined. Two hundred fifty-six children who attended Arkansas public schools and who had surgery as infants were included; 77.7 % had either school-age achievement-test scores or special-education codes of mental retardation or multiple disabilities. Scores on achievement tests for these children were 7-13 % lower than those of Arkansas students (p < 0.01). They had an eightfold increase in receipt of special education due to multiple disabilities [odds ratio (OR) 10.66, 95 % confidence interval (CI) 4.23-22.35] or mental retardation (OR 4.96, 95 % CI 2.6-8.64). Surgery after the neonatal period was associated with decreased literacy proficiency, and cardiopulmonary bypass during the first surgery was associated with decreased mathematics proficiency. Children who had early CHD surgery were less proficient on standardized school assessments, and many received special education. This is concerning because achievement-test scores at school age are "real-world" predictors of long-term outcomes.

Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally.

Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL+/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28mg/kg/day) postnatally from birth until 6weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice.

Characteristics and hemodynamic effects of extubation failure in children undergoing complete repair for tetralogy of Fallot.

This study aimed to identify the prevalence, etiology, and outcomes of extubation failure in children after complete repair for tetralogy of Fallot at a single tertiary-care, academic children's hospital. The secondary aim of this study was to determine the cardiorespiratory effects of the transition from positive-pressure ventilation to spontaneous breathing in children with extubation success and extubation failure. For this study, extubation was defined as the need for reintubation within 96 h after extubation. Demographics as well as pre-, intra-, post-, and periextubation data were collected in a retrospective observational format for patients who underwent complete repair for tetralogy of Fallot during the period January 2001-June 2011. Patients with multiple aortopulmonary collateral arteries or associated complete atrioventricular septal defects were excluded from the study. The cardiorespiratory variables collected before and immediately after extubation included heart rate, respiratory rate, mean arterial blood pressure, central venous pressures, near-infrared spectroscopy, oxygen saturations, and lactate levels. The clinical outcomes evaluated included the success or failure of extubation and the hospital length of stay. Descriptive and univariate statistics were used to compare the group with extubation failure and the group with extubation success. Extubation failure occurred for 7 % (12/164) of the 164 eligible patients during the study period. The median age of the patients at surgery was 200 days (range 98-356 days), and their median weight was 6.8 kg (range 5.2-8.5 kg). For 6 % (10/164) of the patients, intubation was performed before surgery. The median duration of mechanical ventilation was 33 h (range 19.5-73 h), and the median hospital stay was 10 days (range 7-15 days). Of the 12 patients with extubation failure, 2 had extubation failure in first 2 h after extubation, 6 had failure in 2-24 h, 3 had failure in 24-48 h, and 1 had failure in 48-96 h. The patients in the extubation success and extubation failure groups were similar in age, sex, and body weight at the time of surgery. All preexisting conditions also were similar in the two groups. The intraoperative variables and postoperative complications did not differ between the two groups. The hospital stay was longer for the children with extubation failure (p < 0.001). The partial pressure of oxygen in arterial blood (PaO2), tachycardia, mean arterial blood pressure, and inotrope score improved significantly at conversion from positive-pressure ventilation to spontaneous ventilation in the patients with extubation success. This study demonstrated that extubation failure in patients after complete repair for tetralogy of Fallot is low and that the etiology is diverse. The majority of extubation failures in these patients occurred in the first 24 h. Extubation success in the children after repair for tetralogy of Fallot was associated with improvement in PaO2, tachycardia, and mean arterial pressure, with a decrease in inotrope score. Extubation failure is associated with a longer hospital stay.

Multi-tiered analysis of brain injury in neonates with congenital heart disease.

Early brain injury occurs in newborns with congenital heart disease (CHD) placing them at risk for impaired neurodevelopmental outcomes. Predictors for preoperative brain injury have not been well described in CHD newborns. This study aimed to analyze, retrospectively, brain magnetic resonance imaging (MRI) in a heterogeneous group of newborns who had CHD surgery during the first month of life using a detailed qualitative CHD MRI Injury Score, quantitative imaging assessments (regional apparent diffusion coefficient [ADC] values and brain volumes), and clinical characteristics. Seventy-three newborns who had CHD surgery at 8 ± 5 (mean ± SD) days of life and preoperative brain MRI were included; 38 also had postoperative MRI. Thirty-four (34 of 73, 47 %) had at least one type of preoperative brain injury, and 28 of 38 (74 %) had postoperative brain injury. The 5-min APGAR score was negatively associated with preoperative injury, but there was no difference between CHD types. Infants with intraparenchymal hemorrhage, deep gray matter injury, and/or watershed infarcts had the highest CHD MRI Injury Scores. ADC values and brain volumes were not different in infants with different CHD types or in those with and without brain injury. In a mixed group of CHD newborns, brain injury was found preoperatively on MRI in almost 50 %, and there were no significant baseline characteristic differences to predict this early brain injury except 5-min APGAR score. We conclude that all infants, regardless of CHD type, who require early surgery should be evaluated with MRI because they are all at high risk for brain injury.

Differences in clinical manifestations, treatment, and concordance rates with two major sets of criteria for Behçet's syndrome for patients in the US and Japan: data from a large, three-center cohort study.

OBJECTIVE: To compare Behçet's syndrome (BS) cohorts from the US and Japan in terms of rates of concordance with the International Study Group (ISG) criteria and Japanese criteria, disease manifestations, and treatment. METHODS: All BS patients seen at the NYU Hospital for Joint Diseases in the US and the Kameda Medical Center and St. Luke's International Hospital in Japan between 2003 and 2010 were included. Diagnosis of BS was made on the basis of clinical manifestations and the clinical decisions of experienced specialists familiar with BS. We classified the patients into complete and incomplete types based on their symptoms; both complete or incomplete types were assumed to fulfil the Japanese criteria. RESULTS: A total of 769 patients (US n = 634, Japan n = 135) were reviewed. 61.5 % in the US and 63.7 % in Japan fulfilled the ISG criteria. Similarly, there was no difference in the proportions of US and Japanese patients who fulfilled the Japanese criteria. Japanese patients were less likely to be female and to have genital ulcers, but were more likely to have epididymitis and pulmonary disease. Significantly more patients were treated with colchicine, sulfasalazine/mesalazine, and NSAIDs in Japan, while significantly more patients in the US received first-line immunosuppressants. CONCLUSIONS: The concordance rates for ISG and Japanese criteria fulfillment in the US and Japan were not significantly different. These findings could help to clarify regional differences in the diagnostic and clinical features of BS.

Safety, Tolerability, and Pharmacokinetics of Same-Knee Intra-Articular Injection of Corticosteroid and Lorecivivint Within 7 Days: An Open-Label, Randomized, Parallel-Arm Study.

INTRODUCTION: Knee osteoarthritis (OA) is a common painful disorder. Intra-articular (IA) corticosteroid injections are frequently prescribed to treat knee pain. Lorecivivint (LOR), a novel IA cdc2-Like Kinase (CLK)/Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase (DYRK) inhibitor thought to modulate Wnt and inflammatory pathways, has appeared safe and demonstrated improved patient-reported outcomes compared with placebo. While LOR is proposed for stand-alone use, in clinical practice, providers might administer LOR in close time proximity to IA corticosteroid. This open-label, parallel-arm, healthy volunteer study assessed potential short-term safety, tolerability and pharmacokinetic (PK) interactions between IA LOR and triamcinolone acetonide (TCA) administered 7 days apart. METHODS: Healthy volunteers were randomized to Treatment Sequence 1 (IA 40 mg TCA followed by IA 0.07 mg LOR) or Treatment Sequence 2 (IA 0.07 mg LOR followed by IA 40 mg TCA). Treatment-emergent adverse events (TEAEs) were categorized by "epoch", with epoch 1 spanning from first until second injection, and epoch 2 spanning from second injection until end of study. Plasma PK was assessed pre injection and out to 22 days after to assess PK treatment interaction. RESULTS: A total of 18 TEAEs were reported by 11 (27.5%) of 40 enrolled participants, and there were no serious adverse events. Thirteen TEAEs were reported in Treatment Sequence 1 and five in Treatment Sequence 2, similarly distributed between epochs 1 and 2. In all participants and at all time points, plasma LOR concentrations were below the limit of quantification (0.100 ng/mL). Geometric mean concentrations and PK parameters for TCA were similar between treatment sequences. CONCLUSION: No safety signals were observed. There were no quantifiable plasma concentrations of LOR in either Treatment Sequence. The PK of TCA was unaffected by previous LOR injection. These results suggest that IA administration of LOR and TCA in close time proximity is unlikely to pose a safety concern. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04598542.

Knee osteoarthritis (OA) is a common disorder characterized by pain and loss of function. This clinical trial tested if two different treatments for OA injected into the same knee 1 week apart would impact the safety or exposure of either treatment. The treatments evaluated were an injection of a corticosteroid, triamcinolone acetonide, and a potential OA treatment in development, lorecivivint, a novel small molecule thought to inhibit inflammation and a biological pathway called the Wnt pathway. The amount of either treatment found in circulation was not different when injected before or after the other treatment. The order of injection did not change the safety profile for either agent, suggesting injection of the two agents 1 week apart is unlikely to pose a safety concern.

Associations of Cost Sharing With Rheumatoid Arthritis Disease Burden.

OBJECTIVE: To evaluate the regional variation of cost sharing and associations with rheumatoid arthritis (RA) disease burden in the US. METHODS: Patients with RA from rheumatology practices in Northeast, South, and West US regions were evaluated. Sociodemographics, RA disease status, and comorbidities were collected, and Rheumatic Disease Comorbidity Index (RDCI) score was calculated. Primary insurance types and copay for office visits (OVs) and medications were documented. Univariable pairwise differences between regions were conducted, and multivariable regression models were estimated to evaluate associations of RDCI with insurance, geographical region, and race. RESULTS: In a cohort of 402 predominantly female, White patients with RA, most received government versus private sponsored primary insurance (40% vs. 27.9%). Disease activity and RDCI were highest for patients in the South region, where copays for OVs were more frequently more than $25. Copays for OVs and medications were less than $10 in 45% and 31.8% of observations, respectively, and more prevalent in the Northeast and West patient subsets than in the South subset. Overall, RDCI score was significantly higher for OV copays less than $10 as well as for medication copays less than $25, both independent of region or race. Additionally, RDCI was significantly lower for privately insured than Medicare individuals (RDCI -0.78, 95% CI [-0.41 to -1.15], P < 0.001) and Medicaid (RDCI -0.83, 95% CI [-0.13 to -1.54], P = 0.020), independent of region and race. CONCLUSION: Cost sharing may not facilitate optimum care for patients with RA, especially in the Southern regions. More support may be required of government insurance plans to accommodate patients with RA with a high disease burden.

Alternative approaches to expanding pediatric urology services and productivity.

PURPOSE: We critically assessed the outcomes of a new model of pediatric urology delivery using alternative approaches to expand care without increasing the number of pediatric urologists. The approaches included the use of advanced practice nurse practitioners, pediatric physician specialists, part-time contract pediatric urologists from neighboring institutions and part-time contract adult urologists from our university. MATERIALS AND METHODS: Data were collected from the Division of Pediatric Urology at Arkansas Children's Hospital during 2009 and 2010. The only pediatric urologist at our institution retired in December 2009 with an immediate transition to a new pediatric urologist in January 2010. Comparisons were made in the numbers of clinic visits, inpatient admissions/consultations, surgical volume and patient satisfaction scores. RESULTS: Average clinic monthly visits in 2009 and 2010 were 153 and 271, respectively (p <0.0001). Inpatient admissions increased from 43 in 2009 to 162 in 2010. Inpatient initial consultations and followup consultations increased by 115 and 112, respectively, from 2009 to 2010. Surgical volume increased 26.7% in 2010 (p = 0.0832) and Press Ganey® scores were comparable or improved from 2009 to 2010. CONCLUSIONS: The use of advance practice nurse practitioners, part-time contract adult and pediatric urologists, and pediatric physician specialists can effectively increase the number of patients treated without adding full-time pediatric urology staff. The assignment of patient and disease populations to each team member has been an ongoing process of critically defining and updating responsibilities in an attempt to expand care, increase productivity and maximize the quality of delivery of these services.

NTproBNP as a marker of rejection in pediatric heart transplant recipients.

Acute rejection is a major morbidity in heart transplant recipients; diagnosis is difficult, and rejection must often be treated reactively. Various serum biomarkers have been investigated for non-invasive monitoring of the cardiac allograft. NTproBNP is produced by the ventricular myocardium and may increase with evolving rejection allowing earlier diagnosis. Retrospective review of serum NTproBNP levels in pediatric heart transplant recipients has been carried out to evaluate the association with episodes of acute rejection. Repeated measures logistic regression was used to model associations for variables with first rejection and within an individual for change in NTproBNP and first rejection. Odds ratios for rejection risk given an increase in serum NTproBNP were calculated. Correlation of NTproBNP levels with renal function as estimated by modified Schwartz equation was performed to look for confounding. Higher serum NTproBNP level was associated with increased risk of rejection, but intersubject variability was wide. However, increase in an individual subject's serum level showed increased risk of rejection, greater with greater rise. Serum NTproBNP levels appear not greatly affected by renal function. NTproBNP shows promise in surveillance for pediatric heart transplant recipients. The greatest use appears to be in following trends for an individual instead of using an absolute value.

Ketamine as a neuroprotective and anti-inflammatory agent in children undergoing surgery on cardiopulmonary bypass: a pilot randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Infants are potentially more susceptible to cell death mediated via glutamate excitotoxicity attributed to cardiopulmonary bypass. We hypothesized that ketamine, via N-methyl D-aspartate receptor blockade and anti-inflammatory effects, would reduce central nervous system injury during cardiopulmonary bypass. METHODS: We randomized 24 infants, without chromosomal abnormalities, to receive ketamine (2 mg/kg, n = 13) or placebo (saline, n = 11) before cardiopulmonary bypass for repair of ventricular septal defects. Plasma markers of inflammation and central nervous system injury were compared at the end of surgery, and 6, 24, and 48 hrs after surgery. Magnetic resonance imaging and spectroscopy before cardiopulmonary bypass and at the time of hospital discharge were performed in a subset of cases and controls (n = 5 in each group). Cerebral hemodynamics were monitored postoperatively using near-infrared spectroscopy, and neurodevelopmental outcomes were assessed using Bayley Scales of Infant Development-II before and 2-3 wks after surgery. RESULTS: Statistically significant differences were noted in preoperative inspired oxygen levels, intraoperative cooling and postoperative temperature, respiratory rate, platelet count, and bicarbonate levels. The peak concentration of C-reactive protein was lower in cases compared to controls at 24 hrs (p = .048) and 48 hrs (p = .001). No significant differences were noted in the expression of various cytokines, chemokines, S100, and neuron-specific enolase between the cases and controls. Magnetic resonance imaging with spectroscopy studies showed that ketamine administration led to a significant decrease in choline and glutamate plus glutamine/creatine in frontal white matter. No statistically significant differences occurred between pre- and postoperative Bayley Scales of Infant Development-II scores. CONCLUSIONS: We did not find any evidence for neuroprotection or neurotoxicity in our pilot study. A large, adequately powered randomized control trial is needed to discern the central nervous system effect of ketamine on the developing brain. brain. TRIAL REGISTRATION: The trial is registered at www.ClinicalTrials.gov, NCT00556361.