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.

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.

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.

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.

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.

Improving resident self-efficacy in pediatric palliative care through clinical simulation.

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.

Comparing Patient-Reported Outcomes From Sham and Saline-Based Placebo Injections for Knee Osteoarthritis: Data From a Randomized Clinical Trial of Lorecivivint.

BACKGROUND: Durable, meaningful symptom responses to intra-articular saline placebo injections are observed in knee osteoarthritis (OA) trials, but it is unclear if these are due to physiological effects. PURPOSE: To perform a prospective comparison of patient-reported outcome responses among participants with knee OA who underwent intra-articular injection of saline-based placebo or sham (dry needle). STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: From a 24-week randomized double-blind trial, participants with moderate to severe knee OA received 2-mL intra-articular injections of saline-based placebo (PBO; 99.45% PBS) or sham (dry needle) to the target knee. Least squares mean differences of changes from baseline to week 24 were compared between the PBO and sham groups for the following: pain Numeric Rating Scale; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function; and patient global assessment. Bang Blinding Index was used to evaluate all-group blinding on day 1 and week 24. RESULTS: In total, 116 and 117 participants were randomized to the PBO and sham groups, respectively. Within the full trial population, the mean ± SD age and body mass index were 59.0 ± 8.5 years and 28.97 ± 4.01, respectively. An overall 406 (58.4%) were female, and 394 (57.3%) had Kellgren-Lawrence grade 3 target knee OA. The PBO and sham groups demonstrated clinically meaningful improvements (≥10%) from baseline in all patient-reported outcomes at all time points (ie, weeks 4-24). Mean differences (95% CI) at week 24 between the PBO and sham groups were as follows: pain Numeric Rating Scale, -0.10 (-0.79 to 0.59; P = .78); WOMAC pain, -2.89 (-9.70 to 3.92; P = .40); WOMAC stiffness, -2.37 (-9.37 to 4.63; P = .51); and WOMAC function, -1.39 (-8.06 to 5.29; P = .68). Bang Blinding Index indicated that blinding was maintained. CONCLUSION: PBO and sham groups demonstrated equivalent patient-reported outcomes at all time points through week 24, suggesting that responses attributed to saline were contextual (ie, to the procedure) and not physiological. REGISTRATION: NCT03122860 (ClinicalTrials.gov identifier).

Preemptive gastrostomy tube placement after Norwood operation.

OBJECTIVE: Because infants undergoing a Norwood operation have poor interstage weight gain, we hypothesized that preemptive gastrostomy tube (GT) placement would result in earlier discharge, improved growth, and higher survival to stage 2. STUDY DESIGN: Records of 74 neonates who underwent a Norwood operation were reviewed until stage 2 palliation. The patients were divided into conventional (n = 43) and preemptive GT groups (n = 31). Data included demographics, cardiac surgery, feeding strategy, length of hospitalization, and mortality. RESULTS: Transplant-free survival to stage 2 was significantly higher in the preemptive group, but there were no significant differences in survival to discharge after stage 1, length of hospitalization, and weight-for-age z-score at discharge and at stage 2 palliation. In the conventional group, 27 of 43 underwent GT placement, all via laparotomy, 23 with Nissen fundoplication. In the preemptive group, all underwent GT placement (21 laparoscopic, 10 laparotomy), 7 with Nissen fundoplication. A second gastric intervention was performed in 11 of 21 with laparoscopic GT (7 conversion to gastrojejunostomy tube, 4 Nissen fundoplication). CONCLUSION: Preemptive GT placement is associated with improved survival to stage 2 after a Norwood operation but not with shorter hospitalization or better growth. A thorough gastrointestinal evaluation must be performed before GT placement to avoid additional surgery.

Application of beta regression to analyze ischemic stroke volume in NINDS rt-PA clinical trials.

BACKGROUND AND PURPOSE: Ischemic stroke lesion volumes have proven difficult to analyze due to the extremely skewed shape of their underlying distribution. We introduce an extension of generalized linear models, beta regression, as a possible method of modeling extremely skewed distributions as evidenced in ischemic stroke lesion volumes. METHODS: The NINDS rt-PA clinical trials measured ischemic stroke lesion volume as a secondary trial outcome. Three-month lesion volumes from these trials were analyzed using beta regression. A multi-variable regression model associating explanatory variables with ischemic stroke lesion volumes was constructed using accepted model building strategies and compared with the previously published volumetric analysis. RESULTS: Beta regression produced a similar model when compared to the previous analysis published by the study group. All previously identified variables of importance were detected in the model building process. The age by treatment interaction described in previous studies was also found in this analysis, confirming the strong effect age has on stroke outcomes. Further, a treatment effect was elicited in terms of odds ratios, yielding a previously unknown quantification of the effect of rt-PA on lesion volumes. CONCLUSIONS: Beta regression proved adept in modeling ischemic stroke lesions and offered the interpretation of covariates in terms of odds ratios. Beta regression is seen as a legitimate alternative to analyze ischemic stroke volumes.

Individual Participant Symptom Responses to Intra-Articular Lorecivivint in Knee Osteoarthritis: Post Hoc Analysis of a Phase 2B Trial.

INTRODUCTION: Established thresholds for patient-reported outcomes (PROs) provide clinically relevant responder data from trials. Lorecivivint (LOR) is an intra-articular (IA) therapy in development for knee osteoarthritis (OA). A post hoc analysis from a phase 2b trial (NCT03122860) determined proportions of LOR responders. METHODS: A 24-week, randomized trial of 0.07 mg LOR demonstrated PRO improvements compared with PBO in moderate-to-severe knee OA participants. Participants treated with LOR and PBO achieving 30%/50%/70% improvements at weeks 12 and 24 in Pain Numeric Rating Scale (NRS), WOMAC Pain/Function subscales, Patient Global Assessment (PtGA), and OMERACT-OARSI responder criteria were determined. Odds ratios (ORs) and 95% confidence intervals [CIs] were compared with PBO. RESULTS: There were 115 and 116 participants in the LOR and PBO groups, respectively. For Pain NRS, LOR increased ORs of achieving 30% [week 12, OR = 2.47 (1.45, 4.19), P < 0.001; week 24, OR = 2.37 (1.40, 4.02), P < 0.01] and 50% [week 24, OR = 1.89 (1.11, 3.23), P < 0.05] improvements over baseline. For WOMAC Pain, LOR increased ORs of achieving 30% [week 24, OR = 1.79 (1.06, 3.01), P < 0.05] and 50% [week 12, OR = 1.79 (1.06, 3.03), P < 0.05; week 24, OR = 1.73 (1.02, 2.93), P < 0.05] improvements. For WOMAC Function, LOR increased ORs of achieving 30% [week 12, OR = 1.85 (1.10, 3.12), P < 0.05; week 24, OR = 1.93 (1.14, 3.26), P < 0.05] improvements. For PtGA, LOR increased ORs of achieving 50% [week 12, OR = 2.28 (1.25, 4.16), P < 0.01] improvements. LOR produced numerical increases at the 70% threshold. LOR increased ORs of achieving OMERACT-OARSI responses [week 12, OR = 2.21 (1.29, 3.78); P < 0.01; week 24, OR = 2.57 (1.49, 4.43), P < 0.001] and strict responses [week 12, OR = 2.13 (1.26, 3.61), P < 0.01; week 24, OR = 2.05 (1.21, 3.47), P < 0.01]. CONCLUSIONS: LOR (0.07 mg) demonstrated improved PRO threshold responses across single and composite measures of pain, function, and patient global assessment compared with PBO, with benefits sustained to 24 weeks.

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.