Integrating social vulnerability into high-resolution global flood risk mapping.

High-resolution global flood risk maps are increasingly used to inform disaster risk planning and response, particularly in lower income countries with limited data or capacity. However, current approaches do not adequately account for spatial variation in social vulnerability, which is a key determinant of variation in outcomes for exposed populations. Here we integrate annual average exceedance probability estimates from a high-resolution fluvial flood model with gridded population and poverty data to create a global vulnerability-adjusted risk index for flooding (VARI Flood) at 90-meter resolution. The index provides estimates of relative risk within or between countries and changes how we understand the geography of risk by identifying 'hotspots' characterised by high population density and high levels of social vulnerability. This approach, which emphasises risks to human well-being, could be used as a complement to traditional population or asset-centred approaches.

Test Characteristics of Cardiac Point-of-Care Ultrasound in Children With Preexisting Cardiac Conditions.

OBJECTIVE: The aim of the study is to assess diagnostic performance of cardiac point-of-care ultrasound (POCUS) performed by pediatric emergency medicine (PEM) physicians in children with preexisting cardiac disease. METHODS: We evaluated the use of cardiac POCUS performed by PEM physicians among a convenience sample of children with preexisting cardiac disease presenting to a tertiary care pediatric ED. We assessed patient characteristics and the indication for POCUS. The test characteristics of the sonologist interpretation for the assessment of both pericardial effusion as well as left ventricular systolic dysfunction were compared with expert POCUS review by PEM physicians with POCUS fellowship training. RESULTS: A total of 104 children with preexisting cardiac disease underwent cardiac POCUS examinations between July 2015 and December 2017. Among children with preexisting cardiac disease, structural defects were present in 72%, acquired conditions in 22%, and arrhythmias in 13% of patients. Cardiac POCUS was most frequently obtained because of chest pain (55%), dyspnea (18%), tachycardia (17%), and syncope (10%). Cardiac POCUS interpretation compared with expert review had a sensitivity of 100% (95% confidence interval [CI], 85.7-100) for pericardial effusion and 100% (95% CI, 71.5-100) for left ventricular systolic dysfunction; specificity was 97.5% (95% CI, 91.3.1-99.7) for pericardial effusion and 98.9% (95% CI, 93.8-99.8) for left ventricular systolic dysfunction. CONCLUSIONS: Cardiac POCUS demonstrates good sensitivity and specificity in diagnosing pericardial effusion and left ventricular systolic dysfunction in children with preexisting cardiac conditions when technically adequate studies are obtained. These findings support future studies of cardiac POCUS in children with preexisting cardiac conditions presenting to the ED.

A high-resolution daily global dataset of statistically downscaled CMIP6 models for climate impact analyses.

A large number of historical simulations and future climate projections are available from Global Climate Models, but these are typically of coarse resolution, which limits their effectiveness for assessing local scale changes in climate and attendant impacts. Here, we use a novel statistical downscaling model capable of replicating extreme events, the Bias Correction Constructed Analogues with Quantile mapping reordering (BCCAQ), to downscale daily precipitation, air-temperature, maximum and minimum temperature, wind speed, air pressure, and relative humidity from 18 GCMs from the Coupled Model Intercomparison Project Phase 6 (CMIP6). BCCAQ is calibrated using high-resolution reference datasets and showed a good performance in removing bias from GCMs and reproducing extreme events. The globally downscaled data are available at the Centre for Environmental Data Analysis ( https://doi.org/10.5285/c107618f1db34801bb88a1e927b82317 ) for the historical (1981-2014) and future (2015-2100) periods at 0.25° resolution and at daily time step across three Shared Socioeconomic Pathways (SSP2-4.5, SSP5-3.4-OS and SSP5-8.5). This new climate dataset will be useful for assessing future changes and variability in climate and for driving high-resolution impact assessment models.

Flood hazard potential reveals global floodplain settlement patterns.

Flooding is one of the most common natural hazards, causing disastrous impacts worldwide. Stress-testing the global human-Earth system to understand the sensitivity of floodplains and population exposure to a range of plausible conditions is one strategy to identify where future changes to flooding or exposure might be most critical. This study presents a global analysis of the sensitivity of inundated areas and population exposure to varying flood event magnitudes globally for 1.2 million river reaches. Here we show that topography and drainage areas correlate with flood sensitivities as well as with societal behaviour. We find clear settlement patterns in which floodplains most sensitive to frequent, low magnitude events, reveal evenly distributed exposure across hazard zones, suggesting that people have adapted to this risk. In contrast, floodplains most sensitive to extreme magnitude events have a tendency for populations to be most densely settled in these rarely flooded zones, being in significant danger from potentially increasing hazard magnitudes given climate change.

The Effect of COVID-19 Stay-At-Home Orders on the Rate of Pediatric Foreign Body Ingestions.

BACKGROUND: Foreign body ingestions are a common presentation in the emergency department (ED), particularly in young children. OBJECTIVE: We sought to determine whether the COVID-19 pandemic lockdowns had an effect on the proportion of foreign body ingestions. METHODS: We performed a retrospective review of the Pediatric Health Information System for patients younger than 19 years who were identified by International Classification of Diseases, Tenth Revision codes for foreign body ingestion. We analyzed patients in the following three groups: young children (younger than 5 years), school-aged children (5-12 years), and adolescents (13 years and older), using an interrupted time series analysis. Our primary outcome was the difference in proportion of foreign body ingestions. We compared 1 year after the declaration of the COVID-19 pandemic (March 13, 2020 to March 31, 2021) with the previous 3 years (March 1, 2017 to March 12, 2020). RESULTS: Total pediatric ED encounters decreased in the post period (p < 0.01); 4902 patients per year presented for foreign body ingestion pre-COVID-19 shutdown vs. 5235 patients per year post-COVID-19 shutdown. In all three age groups (young children, school-age children, and adolescents), there was a higher proportion of foreign body ingestions post-COVID-19 shutdown (p < 0.01, p < 0.01, and p = 0.028, respectively), driven primarily by the decrease in total ED encounters. In the youngest age group (younger than 5 years), there was also a significant increase in slope for foreign body ingestions post-COVID-19 (p = 0.010). CONCLUSIONS: The proportion of foreign body ingestions increased after the declaration of the COVID-19 pandemic, primarily driven by an overall decrease in total ED volume.

Reducing Pediatric Emergency Department Prescription Errors.

BACKGROUND: Prescription errors are a significant cause of iatrogenic harm in the health care system. Pediatric emergency department (ED) patients are particularly vulnerable to error. We sought to decrease prescription errors in an academic pediatric ED by 20% over a 24-month period by implementing identified national best practice guidelines. METHODS: From 2017 to 2019, a multidisciplinary, fellow-driven quality improvement (QI) project was conducted using the Model for Improvement. Four key drivers were identified including simplifying the electronic order entry into prescription folders, improving knowledge of dosing by indication, increasing error feedback to prescribers, and creating awareness of common prescription pitfalls. Four interventions were subsequently implemented. Outcome measures included prescription errors per 1000 prescriptions written for all medications and top 10 error-prone antibiotics. Process measures included provider awareness and use of prescription folders; the balancing measure was provider satisfaction. Differences in outcome measures were assessed by statistical process control methodology. Process and balancing measures were analyzed using 1-way analysis of variance and χ2 testing. RESULTS: Before our interventions, 8.6 errors per 1000 prescriptions written were identified, with 62% of errors from the top 10 most error-prone antibiotics. After interventions, error rate per 1000 prescriptions decreased from 8.6 to 4.5 overall and from 20.1 to 8.8 for top 10 error-prone antibiotics. Provider awareness of prescription folders was significantly increased. CONCLUSION: QI efforts to implement previously defined best practices, including simplifying and standardizing computerized provider order entry (CPOE), significantly reduced prescription errors. Synergistic effect of educational and technological efforts likely contributed to the measured improvement.

Refining sonographic criteria for paediatric appendicitis: combined effects of age-based appendiceal size and secondary findings.

OBJECTIVE: Appendiceal diameter is a primary sonographic determinant of paediatric appendicitis. We sought to determine if the diagnostic performance of outer appendiceal diameter differs based on age or with the addition of secondary sonographic findings. METHODS: We retrospectively reviewed patients aged less than 19 years who presented to the Boston Children's Hospital ED and had an ultrasound (US) for the evaluation of appendicitis between November 2015 and October 2018. Our primary outcome was the presence of appendicitis. We analysed the cases to evaluate the optimal outer appendiceal diameter as a predictor for appendicitis stratified by age (<6, 6 to <11, 11 to <19 years), and with the addition of one or more secondary sonographic findings. RESULTS: Overall, 945 patients met criteria for inclusion, of which 43.9% had appendicitis. Overall, appendiceal diameter as a continuous measure demonstrated excellent test performance across all age groups (area under the curve (AUC) >0.95) but was most predictive of appendicitis in the youngest age group (AUC=0.99 (0.98-1.00)). Although there was no significant difference in optimal diameter threshold between age groups, both 7- and 8-mm thresholds were more predictive than 6 mm across all groups (p<0.001). The addition of individual (particularly appendicolith or echogenic fat) or combinations of secondary sonographic findings increased the diagnostic value for appendicitis above diameter alone. CONCLUSIONS: Appendiceal diameter as a continuous measure was more predictive of appendicitis in the youngest group. Across all age groups, the optimal diameter threshold was 7 mm for the diagnosis of paediatric appendicitis. The addition of individual or combination secondary sonographic findings increases diagnostic performance.

Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis.

OBJECTIVE: To evaluate the efficacy and safety of an oral selective tyrosine kinase 2 (TYK2) inhibitor, deucravacitinib, in patients with active psoriatic arthritis (PsA). METHODS: In this double-blind, phase II trial, 203 patients with PsA were randomised 1:1:1 to placebo, deucravacitinib 6 mg once a day or 12 mg once a day. The primary endpoint was American College of Rheumatology-20 (ACR-20) response at week 16. RESULTS: ACR-20 response was significantly higher with deucravacitinib 6 mg once a day (52.9%, p=0.0134) and 12 mg once a day (62.7%, p=0.0004) versus placebo (31.8%) at week 16. Both deucravacitinib doses resulted in significant improvements versus placebo (p≤0.05) in the multiplicity-controlled secondary endpoints of change from baseline in Health Assessment Questionnaire-Disability Index and Short Form-36 Physical Component Summary score and in Psoriasis Area and Severity Index-75 response. Improvements were also seen in multiple exploratory endpoints with deucravacitinib treatment. The most common adverse events (AEs) (≥5%) in deucravacitinib-treated patients were nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, rash, headache and diarrhoea. There were no serious AEs and no occurrence of herpes zoster, opportunistic infections and major adverse cardiovascular events, or differences versus placebo in mean changes in laboratory parameters with deucravacitinib treatment. CONCLUSIONS: Treatment with the selective TYK2 inhibitor deucravacitinib was well tolerated and resulted in greater improvements than placebo in ACR-20, multiplicity-controlled secondary endpoints and other exploratory efficacy measures in patients with PsA. Larger trials over longer periods of time with deucravacitinib are warranted to confirm its safety profile and benefits in PsA. TRIAL REGISTRATION NUMBER: NCT03881059.

Development of a Consensus-Based Definition of Focused Assessment With Sonography for Trauma in Children.

Importance: The wide variation in the accuracy and reliability of the Focused Assessment With Sonography for Trauma (FAST) and the extended FAST (E-FAST) for children after blunt abdominal trauma reflects user expertise. FAST and E-FAST that are performed by experts tend to be more complete, better quality, and more often clinically valuable. Objective: To develop definitions of a complete, high-quality, and accurate interpretation for the FAST and E-FAST in children with injury using an expert, consensus-based modified Delphi technique. Design, Setting, and Participants: This consensus-based qualitative study was conducted between May 1 to June 30, 2021. It used a scoping review and iterative Delphi technique and involved 2 rounds of online surveys and a live webinar to achieve consensus among a 26-member panel. This panel consisted of international experts in pediatric emergency point-of-care ultrasonography. Main Outcomes and Measures: Definitions of complete, high-quality, and accurate FAST and E-FAST studies for children after injury. Results: Of the 29 invited pediatric FAST experts, 26 (15 men [58%]) agreed to participate in the panel. All 26 panelists completed the 2 rounds of surveys, and 24 (92%) participated in the live and asynchronous online discussions. Consensus was reached on FAST and E-FAST study definitions, and the panelists rated these 5 anatomic views as important and appropriate for a complete FAST: right upper-quadrant abdominal view, left upper-quadrant abdominal view, suprapubic views (transverse and sagittal), and subxiphoid cardiac view. For E-FAST, the same FAST anatomic views with the addition of the lung or pneumothorax view were deemed appropriate and important. In addition, the panelists rated a total of 32 landmarks as important for assessing completeness. Similarly, the panelists rated 14 statements on quality and 20 statements on accurate interpretation as appropriate. Conclusions and Relevance: This qualitative study generated definitions for complete FAST and E-FAST studies with high image quality and accurate interpretation in children with injury. These definitions are similar to those in adults with injury and may be used for future education, quality assurance, and research. Future research may focus on interpretation of trace volumes of abdominal free fluid and the use of serial FAST.

Significance of Sonographic Subcentimeter, Subpleural Consolidations in Pediatric Patients Evaluated for Pneumonia.

OBJECTIVES: To investigate the rates of radiographic pneumonia and clinical outcomes of children with suspected pneumonia and subcentimeter, subpleural consolidations on point-of-care lung ultrasound. STUDY DESIGN: We enrolled a prospective convenience sample of children aged 6 months to 18 years undergoing chest radiography (CXR) for pneumonia evaluation in a single tertiary-care pediatric emergency department. Point-of-care lung ultrasound was performed by an emergency medicine physician with subsequent expert review. We determined rates of radiographic pneumonia and clinical outcomes in the children with subcentimeter, subpleural consolidations, stratified by the presence of larger (>1 cm) sonographic consolidations. The children were followed prospectively for 2 weeks to identify a delayed diagnosis of pneumonia. RESULTS: A total of 188 patients, with a median age of 5.8 years (IQR, 3.5-11.0 years), were evaluated. Of these patients, 62 (33%) had subcentimeter, subpleural consolidations on lung ultrasound, and 23 (37%) also had larger (>1 cm) consolidations. Patients with subcentimeter, subpleural consolidations and larger consolidations had the highest rates of definite radiographic pneumonia (61%), compared with 21% among children with isolated subcentimeter, subpleural consolidations. Overall, 23 children with isolated subcentimeter, subpleural consolidations (59%) had no evidence of pneumonia on CXR. Among 16 children with isolated subcentimeter, subpleural consolidations and not treated with antibiotics, none had a subsequent pneumonia diagnosis within the 2-week follow-up period. CONCLUSIONS: Children with subcentimeter, subpleural consolidations often had radiographic pneumonia; however, this occurred most frequently when subcentimeter, subpleural consolidations were identified in combination with larger consolidations. Isolated subcentimeter, subpleural consolidations in the absence of larger consolidations should not be viewed as synonymous with pneumonia; CXR may provide adjunctive information in these cases.

Use of Cardiac Point-of-Care Ultrasound in the Pediatric Emergency Department.

OBJECTIVES: We sought to describe the test characteristics of cardiac point-of-care ultrasound (POCUS) performed by pediatric emergency medicine (PEM) physicians after structured cardiac POCUS training. METHODS: We evaluated the use of clinically indicated cardiac POCUS by PEM physicians in a single tertiary care pediatric emergency department after implementation of a focused cardiac POCUS training curriculum. The test characteristics of the sonologist interpretation were compared with expert POCUS review, by PEM physicians who have completed PEM POCUS fellowship training, for the assessment of both pericardial effusion and left ventricular systolic dysfunction. RESULTS: A total of 1241 cardiac POCUS examinations were performed between July 2015 and December 2017, of which 456 were clinically indicated and underwent expert POCUS review and comprised the study sample. These examinations were performed by 33 different PEM attending sonologists. Chest pain (52%), dyspnea (20%), and tachycardia (18%) were the most common indications for cardiac POCUS. Prevalence of pericardial effusion and global systolic dysfunction based on expert POCUS review were 11% (48/443) and 4% (16/435), respectively. Real-time cardiac POCUS interpretation had a sensitivity and specificity of 100% and 99.5%, respectively, for both pericardial effusion and left ventricular systolic dysfunction when compared with expert POCUS review. CONCLUSIONS: Cardiac POCUS is both sensitive and specific for identifying pericardial effusion and left ventricular systolic dysfunction when performed by PEM attendings with focused training.

Yield of Plain Radiography in Addition to Ultrasound Among Children with Hip Pain.

BACKGROUND: Children with limp or hip pain often undergo radiographs and ultrasound as part of their initial evaluation. Previous research suggests that hip radiography may have limited utility, and early use of ultrasound may safely reduce the use of radiographs. OBJECTIVES: We sought to assess the utility of radiography in addition to ultrasound by evaluating the rate of bony abnormalities present on hip radiographs among children with and without effusion on ultrasound. We also assessed the agreement of point-of-care and Radiology-performed ultrasounds for the detection of effusion. METHODS: This is a retrospective cohort study of children presenting to a pediatric emergency department with acute atraumatic limp or hip pain. Data from patients who received both hip ultrasound and hip radiography as part of their evaluation were analyzed. We included both point-of-care and Radiology-performed hip ultrasounds. RESULTS: We identified 134 patients who received both hip ultrasound and hip radiographs. Sixty-eight patients (51%) had a hip effusion present on ultrasound and none of these had bony abnormalities on radiography (0%, 95% confidence interval 0-5.3%). Of the 66 patients (49%) who had no effusion on hip ultrasound, 2 patients were found to have a bony abnormality (3%, 95% confidence interval 0.4-10.5%). For patients who received both point-of-care and Radiology-performed ultrasound, the overall agreement for diagnosis of effusion was 92.6% (kappa = 0.82). CONCLUSIONS: We observed that no children with an effusion on ultrasound had bony pathology on plain radiography, suggesting that the routine performance of hip radiography may not be indicated in all children. Future studies are needed to evaluate the negative predictive value of effusion in larger numbers of patients with known bony abnormalities.

Does age affect the test performance of secondary sonographic findings for pediatric appendicitis?

BACKGROUND: Secondary sonographic findings of appendicitis can aid image analysis and support diagnosis with and without visualization of an appendix. OBJECTIVE: We sought to determine if age affected the test performance of secondary findings for pediatric appendicitis. MATERIALS AND METHODS: We performed a medical record review of emergency department patients younger than 19 years of age who had a sonogram for suspected appendicitis. Our primary patient outcome was appendicitis, as determined by pathology or by image-confirmed perforation/abscess. Our primary analysis was test performance of secondary sonographic findings as recorded by sonographers on the final diagnosis of appendicitis stratified by age (<6 years, 6 to <11 years, 11 to <19 years). RESULTS: A total of 1,219 patients with suspected appendicitis were evaluated by ultrasound, and 1,147 patients met the criteria for analysis. Of the 1,147 patients, 431 (37.6%) had a final diagnosis of appendicitis. Across all age groups, echogenic fat was the most accurate secondary finding (92.5% [95% confidence interval (CI): 91.0, 94.0]) and free fluid was the least accurate secondary finding (54.7% [95% CI: 51.8, 57.5]). There was no significant difference in the age-stratified test performance of secondary sonographic findings except that (1) appendicolith was a more accurate predictor in patients <6 years old than in the middle group (P<0.001) or the oldest group (P<0.001), and (2) free fluid was a more accurate predictor in the middle group than in the oldest group (P=0.02). CONCLUSION: There are no significant differences in the age-stratified test performance of secondary sonographic findings in the prediction of pediatric appendicitis except that appendicolith is more predictive in younger patients.

A Young Boy with Fever and Grunting.

CASE PRESENTATION: A 16-month-old boy presented with a temperature of 99°Fahrenheit (F) (down from 102°F at home after antipyretics), grunting, and tachypnea. On examination, he was tachycardic, tachypneic, and ill-appearing with abdominal distention and diffuse tenderness. A plain film abdominal radiograph showed moderate free air, and emergent laparoscopy revealed perforated Meckel's diverticulitis with peritonitis. DISCUSSION: Although tachypnea and grunting in preverbal or nonverbal patients are often considered to be signs of respiratory illness, these findings may reflect intra-abdominal emergencies. Perforated Meckel's diverticulitis is an important differential consideration in patients with pneumoperitoneum.

The Variability of Preferred Infant Lumbar Puncture Insertion Site Between Novice and Experienced Physicians.

BACKGROUND: We sought to determine if vertebral interspace selection for performance of infant lumbar puncture (LP) varies between less experienced trainees and more experienced pediatric emergency medicine (PEM) attending physicians. METHODS: We performed an observational prospective study using a convenience sample of infants aged 0 to 12 months presenting to a single emergency department. Trainees with limited LP experience (defined as less than 10 infant LPs performed) marked their preferred LP insertion site with an invisible ultraviolet pen. PEM attending physicians subsequently marked their preferred LP insertion site with a visible pen. A trained sonographer then performed a bedside ultrasound to confirm interspace concordance or discordance. Our primary outcome was the proportion of concordant marked insertion sites. RESULTS: Of the 110 patients enrolled, 102 (92.8%) completed study procedures. Trainee and PEM attending LP interspace markings were concordant in 27% of cases. Trainees marked a preferred interspace below the level of the attending in 55% of patients: 29 (28.4%) marked one spot inferior, 20 (19.6%) marked two spots inferior, and seven (6.9%) marked three spots inferior in relation to the attending. CONCLUSIONS: There is variability of preferred LP insertion site based on provider experience. Trainees with limited LP experience tended to mark insertion spaces more caudal than those marked by the attending physicians in an area where the subarachnoid space is slightly smaller.

Comparative clinical efficacy and safety of the proposed biosimilar ABP 710 with infliximab reference product in patients with rheumatoid arthritis.

BACKGROUND: ABP 710 is being developed as a biosimilar to infliximab reference product (RP). Analytical similarity and pharmacokinetic equivalence between the two have been previously demonstrated. Here we report results from a comparative clinical study that evaluated the efficacy and safety of ABP 710 relative to the RP in patients with rheumatoid arthritis (RA). METHODS: In this multicenter, randomized, double-blind, 50-week equivalence study, patients with moderate to severe active RA despite methotrexate received 3-mg/kg infusions of ABP 710 or RP at predetermined intervals based on initial randomization and then with re-randomization at week 22. The primary endpoint was response difference (RD) of ACR20 at week 22, with clinical equivalence evaluated based on 90% CI of - 15%, 15%. Secondary endpoints included Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), ACR20, ACR50, and ACR70 across time, as well as safety and immunogenicity assessments. RESULTS: A total of 558 patients were randomized for the initial treatment (ABP 710 n = 279; RP n = 279). The estimated RD of ACR20 at week 22 was 9.37% with 90% CI (2.67%, 15.96%). The lower bound was within the pre-specified criteria, thus confirming non-inferiority; the upper bound exceeded the pre-specified criteria by 0.96% such that superiority could not be ruled out statistically. In a post hoc analysis with adjustment for random imbalance in baseline factors, the CI of RD was narrowed (0.75%, 13.62%). Changes from baseline in DAS28-CRP as well as ACR20, ACR50, and ACR70 response rates across time and hybrid ACR evaluations were similar for the initial and initial/re-randomized treatment groups. Adverse events and incidence of anti-drug antibodies were similar between treatment groups. CONCLUSIONS: These efficacy and safety results support similarity with no clinically meaningful differences between ABP 710 and infliximab RP. Although we were unable to statistically confirm non-superiority, post hoc analysis was supportive of non-superiority. DAS28-CRP, ACR20, ACR50, ACR70, and hybrid ACR evaluations over the entire study were consistently comparable as were safety and immunogenicity. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT02937701. Registered August 30, 2016.

Secukinumab in Active Rheumatoid Arthritis: A Phase III Randomized, Double-Blind, Active Comparator- and Placebo-Controlled Study.

OBJECTIVE: To evaluate the efficacy and safety of secukinumab in patients with active rheumatoid arthritis (RA) who had an inadequate response to or intolerance of tumor necrosis factor (TNF) inhibitors. METHODS: In this phase III study, 551 patients were randomized (1:1:1:1) to receive intravenous secukinumab at a dose of 10 mg/kg (at baseline and weeks 2 and 4) followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks or, alternatively, abatacept or placebo on the same dosing schedule. The primary end point was the proportion of patients achieving 20% improvement in disease activity according to the American College of Rheumatology response criteria (ACR20) at week 24 in the secukinumab 150 mg or 75 mg treatment groups as compared with placebo. Key secondary end points included change from baseline to week 24 in the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) and the Health Assessment Questionnaire disability index (HAQ DI), as well as the ACR 50% improvement (ACR50) response rate at week 24. RESULTS: The primary efficacy end point was met in patients receiving 150 mg secukinumab, in whom the ACR20 response rate at week 24 was significantly higher than that in the placebo group. The ACR20 response rates at week 24 were 30.7% in patients receiving 150 mg secukinumab (P = 0.0305), 28.3% in those receiving 75 mg secukinumab (P = 0.0916), and 42.8% in those receiving abatacept, compared with 18.1% in the placebo group. A significant reduction in the DAS28-CRP was seen in patients treated with 150 mg secukinumab (P = 0.0495), but not in patients treated with 75 mg secukinumab. Improvements in the HAQ DI and ACR50 response rates were not significant in the 2 secukinumab dose groups compared with the placebo group. The overall safety profile was similar across all treatment groups. CONCLUSION: Secukinumab at a dose of 150 mg resulted in improvement in signs and symptoms and reduced disease activity in patients with active RA who had an inadequate response to TNF inhibitors. Improvements observed with abatacept were numerically higher than with secukinumab. There were no new or unexpected safety signals with secukinumab in this study.