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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.

Lorecivivint (LOR) is a new injectable medicine being studied as a treatment for knee osteoarthritis (OA). An early (phase 2b) trial found participants with moderate-to-severe knee OA receiving LOR on average reported improved pain, function, and reduced impact of OA symptoms over 24 weeks compared with placebo. To consider how likely individuals were to respond to treatment, this study analyzed how many participants per group achieved different percentage levels of symptom improvement. Participants were given a single LOR or placebo injection into their most painful (target) knee at trial initiation. Participants reported their target knee status from day 1 (baseline) to week 24 using pain and function questionnaires. We analyzed the number of participants given 0.07 mg LOR and placebo whose symptom scores improved by 30, 50, and 70% over baseline scores at weeks 12 and 24. Results showed that 0.07 mg LOR treatment produced a higher likelihood beyond chance at week 12 of achieving a 30% improvement in some pain and function scores and a 50% improvement in other symptom scores compared with placebo. Similar 30% and 50% symptom score improvements were found at week 24. More complex scores, combining individual symptom scores into single index measures, also showed improvements beyond chance for 0.07 mg LOR from baseline compared with placebo at weeks 12 and 24. Thus, more participants with knee OA who were treated with 0.07 mg LOR demonstrated long-lasting, meaningful improvements in pain and function compared to those given placebo.

IMPORTANCE: Prolonged neonatal hypoglycemia is associated with poor long-term neurocognitive function. However, little is known about an association between early transient newborn hypoglycemia and academic achievement. OBJECTIVE: To determine if early (within the first 3 hours of life) transient hypoglycemia (a single initial low glucose concentration, followed by a second value above a cutoff) is associated with subsequent poor academic performance. DESIGN, SETTING, AND PARTICIPANTS: A retrospective population-based cohort study of all infants born between January 1, 1998, and December 31, 1998, at the University of Arkansas for Medical Sciences who had at least 1 recorded glucose concentration (a universal newborn glucose screening policy was in effect) was conducted. Medical record data from newborns with normoglycemia or transient hypoglycemia were matched with their student achievement test scores in 2008 from the Arkansas Department of Education and anonymized. Logistic regression models were developed to evaluate the association between transient hypoglycemia and school-age achievement test proficiency based on perinatal factors. Common hypoglycemia cutoffs of a glucose level less than 35 mg/dL (primary) and less than 40 and 45 mg/dL (secondary) were investigated. All 1943 normoglycemic and transiently hypoglycemic infants (23-42 weeks’ gestation) were eligible for inclusion in the study. Infants with prolonged hypoglycemia, congenital anomalies, or chromosomal abnormalities were excluded from the study. EXPOSURE: Hypoglycemia as a newborn. MAIN OUTCOMES AND MEASURES: The primary outcome was proficiency on fourth-grade literacy and mathematics achievement tests at age 10 years. We hypothesized a priori that newborns with early transient hypoglycemia would be less proficient on fourth-grade achievement tests compared with normoglycemic newborns. RESULTS: Perinatal data were matched with fourth-grade achievement test scores in 1395 newborn-student pairs (71.8%). Transient hypoglycemia (glucose level <35, <40, and <45 mg/dL) was observed in 6.4% (89 of 1395), 10.3% (143 of 1395), and 19.3% (269 of 1395) of newborns, respectively. After controlling for gestational age group, race, sex, multifetal gestation, insurance status, maternal educational level and socioeconomic status, and gravidity, transient hypoglycemia was associated with decreased probability of proficiency on literacy and mathematics fourth-grade achievement tests. For the 3 hypoglycemia cutoffs, the adjusted odds ratios (95% CIs) for literacy were 0.49 (0.28-0.83), 0.43 (0.28-0.67), and 0.62 (0.45-0.85), respectively, and the adjusted odds ratios (95% CIs) for mathematics were 0.49 (0.29-0.82), 0.51 (0.34-0.78), and 0.78 (0.57-1.08), respectively. CONCLUSIONS AND RELEVANCE: Early transient newborn hypoglycemia was associated with lower achievement test scores at age 10 years. Given that our findings are serious and contrary to expert opinion, the results need to be validated in other populations before universal newborn glucose screening should be adopted.

Williams syndrome (WS) is a congenital, multisystem developmental disorder affecting 1 in 8000 live births. Cardiovascular abnormalities are present in 80% of WSpatients. The present study sought to characterize fully the electrocardiographic findings in WSand correlate findings with anatomic pathology. A retrospective review was performed of the electrocardiograms (ECGs) of patients with WSevaluated at the Children's Hospital of Philadelphia from January 1, 1980 through December 31, 2007. When available, the five most recent ECGsin each patient were evaluated. Ventricular hypertrophy was diagnosed based on previously reported voltage criteria in normal populations. There were 187 patients with 499 ECGsfor evaluation. Median age at study ECGwas 8.0 years (range 0.1–58.9); median number of ECGsper patient was 2.7 (range 1–5). Heart rate, PRinterval, and QRSinterval were normal for age. Right ventricular hypertrophy (RVH) was present on 44% (219/499) of ECGs. Left ventricular hypertrophy (LVH) was present on 30% (150/499) of ECGs. Fifty‐seven percent (106/187) of subjects had ≥1 ECGdemonstrating RVH, and 39% (72/187) had ≥1 ECGdemonstrating LVH. The severity of right‐ and left‐sided obstructive lesions correlated with the ECGpresence of RVH(P< .0001, odds ratio 21.8) and LVH(P< .001, odds ratio 14.5–61), respectively. Electrocardiographic intervals in patients with WSfollow expected trends seen in normal patients. Voltage criteria for RVHand LVHare commonly met on ECGsof patients with WS. The presence of ventricular hypertrophy on ECGin WScorrelates with lesion severity.

Gout and osteoarthritis (OA) are the most prevalent arthritides, but their relationship is neither well established nor well understood.

Acquired von Willebrand factor (vWF) disease is associated with a decrease in the amount of circulating high molecular weight (HMW) vWF multimers. vWF has not been previously investigated in children on extracorporeal membrane oxygenation (ECMO) support. We hypothesized that HMW vWF multimers and vWF activity decrease over the course of ECMO support in these patients. This prospective, single center, observational, cohort pilot study was carried out between December 2010 and April 2011 and included patients 0 to 18 years old requiring ECMO support at our institution. Blood samples were tested for various aspects of vWF. Mean and standard deviation were estimated for vWF activity and multimers, whereas a generalized linear model was developed to estimate multimer changes over time.The study included six pediatric patients. The mean age of the patients was 54.9 ± 55.3 (mean ± standard deviation) months. The mean HMW vWF multimer percentage was 23.4 ± 7.3 in the pre-ECMO samples and significantly decreased over time (p<0.003). There was no significant change in low molecular weight vWF multimer percentage. An immediate decrease in vWF HMW multimers as a percentage of all multimers once ECMO is initiated was noted and persisted across the study period.

Antithrombin III (ATIII) is used during extracorporeal membrane oxygenation (ECMO) based on physiologic rationale and studies during cardiopulmonary bypass. In February 2008, our institution began using ATIII as replacement for low ATIII activity (<70) in patients supported with ECMO. We hypothesized that ATIII supplementation would reduce heparin infusion rates, increase unfractionated heparin anti-Xa levels, and prolong ECMO circuit life. Data from 40 consecutive patients (45 deployments) requiring ECMO support for >72 hours with venoarterial ECMO from January 1, 2007, through December 31, 2008, were collected. Antithrombin III concentrate was administered for ATIII activity <70 at the discretion of the attending physician. The primary outcome was whether the heparin infusion rate was reduced by 10 or more as a result of ATIII administration. No difference in heparin infusion rate (p= 0.245) as a result of ATIII administration was observed. Anti-Xa levels were lower before ATIII administration (p< 0.001) and were increased after ATIII administration (p< 0.001). There was an increased frequency of circuit failure in ATIII treatment group compared with nontreatment group (p= 0.018). Neither heparin responsiveness nor circuit life was enhanced by daily ATIII supplementation for activity <70. Future studies are warranted to evaluate the effectiveness of antithrombin replacement.

Some neonates with tetralogy of Fallot (TOF) have rapid progression of right ventricular outflow tract obstruction, requiring early repair irrespective of Doppler gradient as measured in the neonatal period. The aim of this study was to test the hypothesis that infundibular morphology in neonates with TOF is associated with the occurrence of hypercyanotic spells and need for neonatal surgery.

The use of ventricular assist devices (VADs) in children is challenging because of small patient size, frequent structural heart disease, and the need for biventricular assist devices. This report describes the role of echocardiography in the management of children supported by VADs.

Context:Pediatric residents have limited training and practice experience with palliative care. This study examined whether clinical simulation improved resident self-efficacy in pediatric palliative care. Methods:Residents were surveyed on their self-efficacy and how they perceived the importance of pediatric palliative care; they were then randomized into either a control group or an intervention group. The intervention group participated in two simulated pediatric palliative care scenarios. The residents’ responses before and after the intervention were analyzed to determine whether simulation training had influenced their responses. Results:Although there were no differences in responses on the importance of pediatric palliative care, respondents were more comfortable with suggesting that conferences are needed with families of children who have life-limiting conditions in order to explain do-not-resuscitate orders. Conclusion:Simulation improved pediatric residents’ self-efficacy with end-of-life discussions.

The objectives of the study were to analyze literacy in 194 consecutive patients at an academic rheumatology setting with the Rapid Estimate of Adult Literacy in Medicine (REALM) and an "Arthritis-Adapted" REALM (A-REALM), and to compare responses to one another and to demographic and clinical measures.

ObjectiveTo compare the Routine Assessment of Patient Index Data 3 RAPID3 on a Multidimensional Health Assessment Questionnaire MDHAQ with the Disease Activity Score DAS28, Clinical Disease Activity Index CDAI, and individual core data set measures for correlations, agreement of activity levels, and time to score.MethodsFour rheumatologists each assessed 50 patients with rheumatoid arthritis in “realtime” clinical care. Patients completed an MDHAQ. The rheumatologist then calculated RAPID3 physical function, pain, patient global estimate, performed a 28joint count, assigned a physician global estimate, and scored a CDAI, each timed by an observer. Erythrocyte sedimentation rate ESR was tested on the same date, and the DAS28ESR was computed later, again timed by an observer. Spearmans rankorder correlations and comparisons of patients classified as high activity, moderate activity, low activity, and remission according to the DAS28, CDAI, and RAPID3 were computed and compared with kappa statistics. A second study of 25 “paper patients” was also performed to compare time to score the DAS28, CDAI, and RAPID3 on a 0–10 versus 0–30 scale. Mean and median times to score each index were computed.ResultsThe 3 indices were correlated significantly, including agreement for >80 of patients for highmoderate activity. The mean time to perform a 28joint count was 94 seconds, and the mean times to score the DAS28, CDAI, RAPID3 on a 0–10 scale, and RAPID3 on a 0–30 scale were 114, 106, 9.6, and 4.6 seconds, respectively.ConclusionRAPID3 scores provide similar quantitative information to DAS28 and CDAI, while calculated on a 0–30 scale in about 5 of the time.

This study aims to examine resource utilization and outcomes of trauma patients with extremely high blood alcohol concentrations. We hypothesized that higher blood alcohol concentration (BAC) predicts greater resource utilization and poorer outcomes. A retrospective analysis was performed on trauma patients admitted to an urban Level I trauma center over a 5-year period. Admission BAC categories were constructed using standard laboratory norms and legal definitions. Demographic data, premorbid conditions, injury severity scores (ISS), resource utilization (intensive care unit (ICU) admission rates/length of stay, total hospital days, use of consultants), and mortality were analyzed. Positive BAC on admission was associated with increased ISS (P< 0.001), length of stay (P< 0.003), and total ICU days (P< 0.001). Increased BAC admission level of patients was associated with a decreased ISS score (P= 0.0073), a higher probability of ICU admission (P= 0.0013), and an increased percentage of ICU days (P= 0.001). A positive BAC at admission was a significant predictor of both ICU admission and mortality (odds ratios 1.72 and 1.27, respectively). This study demonstrates that a positive BAC is associated with increased ISS, increased resource utilization, and worsened outcomes. Extreme levels of BAC are associated with increased resource utilization despite lower injury severity scores.

OBJECTIVE To assess the predictive value of baseline measures of impairment, disability, and quality of life for the timing of initiation of symptomatic treatment in early Parkinson disease (PD). DESIGN Inception cohort analysis. SETTING Ambulatory population from multiple sites in the United States and Canada. PARTICIPANTS Four hundred thirteen patients with early, untreated PD who participated in 2 double-blind trials that assessed the potential of experimental drugs to serve as disease-modifying agents in PD. INTERVENTION Participants were randomized into treatment groups: creatine (n = 67), minocycline (n = 66), coenzyme Q10 (n = 71), GPI-1485 (n = 71), and placebo (n = 138). MAIN OUTCOME MEASURE Time between baseline assessment and need for the initiation of symptomatic treatment for PD. The following baseline variables were assessed for their relation to the main outcome measure, while adjusting for possible treatment effect: sex; age; level of education; race/ethnicity; disease duration; occupational status; and Unified Parkinson Disease Rating Scale (UPDRS), Medical Outcomes Study Short Form Survey, Modified Rankin Scale, Schwab and England Activities of Daily Living Scale, Total Functional Capacity Scale, 39-item Parkinson Disease Questionnaire, and Geriatric Depression Scale scores. Variables reaching statistical threshold in univariate analyses (α = .15) were entered into a multivariable Cox proportional hazards regression model using time to symptomatic treatment as the dependent variable. RESULTS Approximately half (48.5%) of the participants reached end point within 12 months. Higher baseline impairment and disability, as determined by UPDRS III (motor section), UPDRS II (activities of daily living section, participant rating), and Modified Rankin Scale scores and level of education were independently associated with an earlier need for symptomatic treatment. CONCLUSIONS In early PD, greater impairment and disability and higher level of education are independently associated with an earlier need for symptomatic treatment.Published online July 13, 2009 (doi:10.1001/archneurol.2009.159).Arch Neurol. 2009;66(9):1099-1104--