Journal articles on the topic '+519.816] (043.3)'

Abstract More than 98% of newly diagnosed childhood B-NHL expresses CD20 (Perkins/Cairo, Clin Adv Hem/Onc 2003). The prognosis for children and adolescents with recurrent CD20 positive NHL, particularly DLBCL and BL, is dismal (Cairo et al, Am J Hem, 2003, Cairo et al, Br J Hem, 2003). A radiolabeled anti-CD20 antibody, 90Y-IT, has recently received FDA approval for adults with recurrent indolent CD20+ B-NHL. The dose limiting toxicity in adults has been myelosuppression (Witzig et al, JCO, 2003). Through the COG Phase I Consortium, we evaluated the safety of 90Y-IT in Pts with refractory childhood and adolescent CD20+ lymphoma: DLBCL (n=3) 1st relapse (n=1), 2nd relapse (n=2); refractory BL (n=1); refractory PTLD (DLBCL) (n=1); M:F ratio 4:1, median age 12 yrs (5–18). Pts (n=5) had a minimum of 2 x 106 CD34/kg cryopreserved PBSC. Pts (n=5) received Rituximab 250 mg/m2 IV on Days 0 and 7 and Indium 5 mCi IV on Day 0. Gamma imaging scans and peripheral blood dosimetry studies were performed on Days 0, 1, 3, and 6. Immediately following Rituximab on Day 7 (n=4) or approximately 24 hrs post Rituximab on Day 8 (n=1), Pts received 90Y-IT if dosimetry studies demonstrated ≤2000 cGy exposure to all solid organs and ≤300 cGy to red marrow based on a dose escalation schema stratified by marrow reserve and Plt; 0.4 mCi/kg (dose level 1) (n=3), 0.1 mCi/kg (dose level 1) (post BMT) (n=2). One Pt progressed prior to DLT evaluation. No evaluable pts (n=4) experienced non-hematologic DLT defined as any Grade III or IV non-hematologic toxicity attributable to the investigational agent or hematologic DLT defined as Grade IV ANC or Grade IV thrombocytopenia of > 7 days duration, and an ANC that did not reach ≥500 mm3 and/or platelet count that did not recover to ≥20,000/mm3 by Day 35. The incidence of HAMA/HACA was 0% (n=0). Toxicities related to the 90Y-IT included Grade I muscle pain/abdominal cramping (n=2), Grade III Plts (n=1), Hgb (n=1), infection (n=1), and Grade IV ANC (n=2), Plts (n=1). One Pt experienced Grade II infusion related chills associated with Rituximab. Mean organ radiation exposure (cGy) was as follows: kidneys 341 (112–515), liver 345 (83–714), lungs 309 (155–519), red marrow 46 (20–78), spleen 565 (161–816), and total body 3.7 (2.1 – 4.8). Mean serum quantitative immunoglobulins (mg/dl) at Day 35 were as follows: IgA 65, IgG 394, and IgM 32. 5/5 Pts experienced progressive disease and went on to receive further therapy. In conclusion, 90Y-IT appears to be well tolerated in children and adolescents with recurrent/refractory CD20+ lymphoma and associated with low exposure of radiation to solid organs and marrow. Based on these findings, an investigator-initiated limited institutional Phase II study is planned to further evaluate the safety, tolerability, and response rate with dose stratification based on marrow reserve and Plt: 0.4 mCi/kg (no prior BMT and Plt ≥ 150k), 0.3 mCi/kg (no prior BMT and Plt 100-149 k), 0.2 mCi/kg (prior BMT and Plt ≥ 100k).

Computer simulation of sow culling was run in a nucleus herd. The specified constant culling rate from 15 to 21% was simulated for all parities. The resultant different age structure of a herd was studied from the aspect of piglet production and other production indicators. With increasing culling rate the percentage of mated gilts was increased in order to maintain the constant size of the sow herd. With 15% simulated culling, which required 17.09% of mated gilts, the percentage of sows at parity 1 and 2 and the percentage of sows at parities 3–5 were balanced (31.62% and 31.77%, respectively). Annual herd replacement was 37.62%. After five parities only a little more than a half (55.63%) of the total number of sows in the herd was removed. Similar results were obtained with 16% culling, which also made it possible to maintain the recommended herd structure. With higher culling rate parities 1 and 2 became dominant in the herd. With 21% culling and 19.84% of mated gilts the percentage of sows at parities 1 and 2 was 35.52% while it was only 29.90% at parities 3–5. Annual herd replacement amounted to 43.67%, and almost 70% of sows were removed after five parities in this case. With increasing culling rate the average age of sows removed from a herd decreased (1 158.1–1 021.2 days), the number of barren days in a herd per year increased (6 174–6 680 days) and the number of piglets weaned per sow per year decreased (19.54–18.92 piglets). At the same time, there was a decrease in total costs (64 789–63 519 Kč), returns (79 816–77 327 Kč) and profit (15 026–13 808 Kč) in the herd, as recalculated per sow per year, and profitability also decreased.

The space segment of all the five satellite systems capable of providing precise position services, namely BeiDou Navigation Satellite System (BDS) (including BDS-3 and BDS-2), Global Positioning System (GPS), GLObal NAvigation Satellite System (GLONASS), Galileo and Quasi-Zenith Satellite System (QZSS), has almost been fully deployed at present, and the number of available satellites is approximately 136. Currently, the precise satellite orbit and clock products from the analysis centers European Space Agency (ESA), GeoForschungsZentrum Potsdam (GFZ) and Wuhan University (WHU) can support all five satellite systems. Thus, it is necessary to investigate the positioning performance of a five-system integrated precise point positioning (PPP) (i.e., GRECJ-PPP) using the precise products from different analysis centers under the current constellation status. It should be noted that this study only focuses on the long-term performance of PPP based on daily observations. The static GRECJ-PPP can provide a convergence time of 5.9–6.9/2.6–3.1/6.3–7.1 min and a positioning accuracy of 0.2–0.3/0.2–0.3/1.0–1.1 cm in east/north/up directions, respectively, while the corresponding kinematic statistics are 6.8–8.6/3.3–4.0/7.8–8.1 min and 1.0–1.1/0.8/2.5–2.6 cm in three directions, respectively. For completeness, although the real-time precise products from the analysis center Centre National d’Etudes Spatiales (CNES) do not incorporate QZSS satellites, the performance of real-time PPP with the other four satellite systems (i.e., GREC-PPP) is also analyzed. The real-time GREC-PPP can achieve a static convergence time of 8.7/5.2/11.2 min, a static positioning accuracy of 0.6/0.8/1.3 cm, a kinematic convergence time of 11.5/6.9/13.0 min, and a kinematic positioning accuracy of 1.7/1.6/3.6 cm in the three directions, respectively. For comparison, the results of single-system and dual-system PPP are also provided. In addition, the consistency of the precise products from different analysis centers is characterized.

This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome. Sixty-six patients were enrolled according to the following French–American–British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 μg/kg·d) + epoetin alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 μg/kg·d) + placebo (3 times/wk). The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF ± epoetin alfa. Hemoglobin response (increase greater than or equal to 2 g/dL, unrelated to transfusion) occurred in 4 of 45 (9%) patients in the GM-CSF + epoetin alfa group compared with 1 of 21 (5%) patients with GM-CSF + placebo group (P = NS). Percentages of patients in the epoetin alfa and the placebo groups requiring transfusions of red blood cells were 60% and 92%, respectively, for the low-endogenous erythropoietin patients and 95% and 89% for the high-endogenous erythropoietin patients (P = NS). Similarly, the average numbers of units of red blood cells transfused during the 12-week study in the epoetin alfa and the placebo groups were 5.9 and 9.5, respectively, in the low-endogenous erythropoietin patients and 9.7 and 8.6 in the high-endogenous erythropoietin patients (P = NS). GM-CSF ± epoetin alfa had no effect on mean platelet count. Treatment was well tolerated in most patients, though 10 withdrew from the study for reasons related predominantly to GM-CSF toxicity.

To assess whether acetaminophen glucuronide accurately reflects uridyl diphosphate-glucose (UDP-glucose) derived from gluconeogenesis during fasting, three mongrel dogs received infusions of [U-14C]lactate, [1-13C]galactose, and [6-3H]glucose (after fasting overnight or for 2.5 days). After initiation of the isotopes (3 h), acetaminophen was given, and the urinary acetaminophen glucuronide was isolated. The mean plasma [14C]glucose specific activity (SA) was similar to the mean urinary acetaminophen glucuronide SA both after fasting overnight [299 +/- 19 vs. 296 +/- 14 disintegrations.min-1 (dpm).mumol-1, respectively] and after 2.5 days of fasting (511 +/- 8 vs. 562 +/- 32 dpm/mumol, respectively). Mean plasma glucose flux calculated using [6-3H]glucose decreased (P < 0.05) with two additional days of fasting (18.7 +/- 1.2 vs. 13.6 +/- 0.6 mumol.kg-1.min-1), as did intrahepatic (P < 0.05) UDP-glucose flux measured using [1-13C]galactose (8.6 +/- 0.7 vs. 5.5 +/- 0.3 mumol.kg-1.min-1). We conclude that, in fasted dogs, plasma glucose and UDP-glucose, as sampled by acetaminophen, equally reflect gluconeogenesis and appear to come from the same pool of glucose 6-phosphate. In addition, cycling of glucose moieties through UDP-glucose and glycogen decreases with an increased period of fasting.

INTRODUCTION: In-flight medical events (IMEs), although rare, are challenging due to the limited onboard resources and the time needed to reach an airport. Cabin crewmembers (CCMs) are trained to provide first aid, but their effectiveness has not been appropriately studied.METHODS: IMEs occurring in the biggest airline of Greece were prospectively recorded during a 5-yr period (20142018) and categorized according to a symptom-based taxonomy.RESULTS: During the study period 990 IMEs were recorded corresponding to 16 IMEs for each million passengers or 1.8 IMEs for every thousand flights. The most frequent events were loss of consciousness (38.4%) followed by injuries (8.6%), gastrointestinal problems (8.3%), respiratory symptoms (7.3%), anxiety (5.7%), and burns (5.9%). Diversion was decided in 3% of the cases while death on board was rare (0.3% of events). CCMs responded in 33.5% of IMEs without assistance by a volunteer health professional, achieving a 97% success rate.DISCUSSION: IMEs are rare events and the majority can be treated with simple first aid measures. CCMs acting according to a simplified algorithm were very efficient in providing first aid. A standardized symptom-based IME form will assist in creating a reliable registry for further studies.Paxinos O, Savourdos P, Alexelis V, Anastasopoulos A, Karantoni E, Grigoropoulos P, Konstantinou X. In-flight medical events and cabin crew first aid response. Aerosp Med Hum Perform. 2021; 92(1):3238.

e17083 Background: Following CARMENA and SURTIME, upfront cytoreductive nephrectomy (CN) is no longer standard of care. Intermediate and poor risk patients (pts) receive systemic therapy with the PT in place with the option to perform deferred CN in responding pts. This practice has been adopted after the recent shift to immune checkpoint inhibitor combination in frontline for mRCC. We assessed the safety and efficacy of this approach in a real-world population. Methods: A retrospective analysis of a clinical audit from 3 institutional datasets of pts treated with first-line N+I and the PT in place. Pts and tumour characteristics, International Metastatic RCC Database Consortium (IMDC) risk, overall response rate (ORR) in the PT and metastatic sites, time to response (TTR) of the PT, PT- and immune related- (ir) adverse events (AE), deferred CN rate, progression free- (PFS) and overall survival (OS) were assessed. Results: Of 41 pts treated with N+I and the PT in place, 46.3% were IMDC poor risk and 51.2% had > 3 metastatic sites. After a median follow-up of 5.9 (2-10.3) months, 29 had at least 1 CT scan from baseline. Of those, 7 (24.3% [95% confidence interval [CI] 0.10-0.43]) had a partial response (PR) of the PT with a median TTR of 5.3 (2.5-8.6) months. Mean and median PT reduction were 16.9% (+7.6 to -70.3%) and 10% from a baseline mean tumour size of 9.5 (3.8-16.1) cm. Pts with a PT reduction > median (n = 14) had a PR at metastatic sites in 86% (CI 0.57-0.98) and no progressive disease (PD). Pts with PT reduction < median (n = 14) had PR in only 21% and PD at metastatic sites in 57% (CI 0.28-0.82). None of the PT progressed. There was no complete response (CR) at metastatic sites . No CN was performed; 5 pts (12%) developed hematuria grade 1-3, requiring embolisation in 2 (4.9%). Grade 3-4 irAE were observed in 22% of pts. Median PFS and OS are 8.6 months and not reached. Conclusions: N+I with the PT in place is safe and PT reduction is associated with response at metastatic sites. Most PT responded by 6 months. No CR at metastatic sites were observed (compared to a 9% CR rate in the pivotal trial) in this real-world population with a relatively high percentage of poor-risk pts. Furthermore, no deferred CN has been performed, neither for near-CR at metastatic sites nor for PT symptoms.

Objectives: to determine the causes of ineffective observation and poor prognosis in patients undergoing ADHF, in real clinical practice and to consider the basics of the formation of specialized medical care for patients with heart failure (HF).Materials and methods: the study was conducted based on the City Center for the treatment of heart failure (center HF), N. Novgorod. The study consistently included 942 patients with heart failure (HF) at the age of 18 years and older who underwent ADHF and received inpatient treatment in center HF between March 4, 2016 and March 3, 2017. Based on the decisions of patients to continue outpatient monitoring in center HF, two groups of patients were distinguished: patients who continued to be monitored in center HF (group I, n = 510) and patients who continued to be monitored in outpatient clinics at the place of residence (group II, n = 432). The assessment of adherence to treatment, overall mortality, survival and re-admission to a depth of two years of observation was carried out. Statistical data processing was performed using Statistica 7.0 for Windows and the software package R.Results: all patients in the study groups had high comorbidity. Group 2 patients turned out to be statistically significantly older, more often had III functional class (FC) HF, lower the baseline test score of 6-minute walk, and higher the baseline clinical assessment scale. After 2 years of follow-up in group II, there was a significant deterioration in adherence to basic therapy of HF compared with group I. According to the results of multifactorial proportional risk Cox models, it was shown that observation of patients in the group 1 is an independent factor increasing the risk of overall mortality by 2.8 times by the end of the second year of observation. Survival after two years of follow-up was: in group I — 89.8 %, and in group II — 70.1 % of patients (OR = 0.3, 95 % CI 0.2 – 0.4; p1/2 < 0.001). After two years of follow-up, the proportion of re-hospitalized patients in group II was greater (78.0 % of patients) versus group 1 (50.6 % of patients, OR = 3.5, 95 % CI 2.6 – 4.6; p1/2 <0.001). The independent risk of re-hospitalization according to multinominal logit regression was 3.4 times higher in group II and 2.4 times for III – IV FC HF. Conclusions: the inclusion of patients with HF in the system of specialized medical care improves adherence to treatment, prognosis of life and reduces the risk of repeated hospitalizations. Patients of an older age and with an initially greater clinical severity refused specialized supervision in center HF.

We characterized the influence of the selective corticotropin-releasing factor 2 (CRF2) receptor agonist human urocortin 2 (Ucn 2), injected intracisternally, on gastric emptying and its mechanism of action compared with intracisternal CRF or urocortin (Ucn 1) in conscious rats. The methylcellulose phenol red solution was gavaged 20 min after peptide injection, and gastric emptying was measured 20 min later. The intracisternal injection of Ucn 2 (0.1 and 1 μg) and Ucn 1 (1 μg) decreased gastric emptying to 37.8 ± 6.9%, 23.1 ± 8.6%, and 21.6 ± 5.9%, respectively, compared with 58.4 ± 3.8% after intracisternal vehicle. At lower doses, Ucn 2 (0.03 μg) and Ucn 1 (0.1 μg) had no effect. The CRF2 antagonist astressin2-B (3 μg ic) antagonized intracisternal Ucn 2 (0.1 μg) and CRF (0.3 μg)-induced inhibition of gastric emptying. Vagotomy enhanced intracisternal Ucn 2 (0.1 or 1 μg)-induced inhibition of gastric emptying compared with sham-operated group, whereas it blocked intracisternal CRF (1 μg) inhibitory action (45.5 ± 8.4% vs. 9.7 ± 9.7%). Sympathetic blockade by bretylium prevented intracisternal and intracerebroventricular Ucn 2-induced delayed gastric emptying, whereas it did not influence intravenous Ucn 2-, intracisternal CRF-, and intracisternal Ucn 1-induced inhibition of gastric emptying. Prazosin abolished the intracisternal Ucn 2 inhibitory effect, whereas yohimbine and propranolol did not. None of the pretreatments modified basal gastric emptying. These data indicate that intracisternal Ucn 2 induced a central CRF2-mediated inhibition of gastric emptying involving sympathetic α1-adrenergic mechanisms independent from the vagus contrasting with the vagal-dependent inhibitory actions of CRF and Ucn 1.

AbstractBackgroundThe sensitivity of blood cultures increases with the volume of blood collected. However, hospitals face challenges in collecting adequate volume, and underfilled blood bottles are ubiquitous.MethodsBlood bottle fill volumes were measured using an automated monitoring system across multiples sites (10 hospitals, 3 laboratories) within a large suburban/urban health system. Baseline fill volumes were measured for 4 months. A quality improvement program was then implemented over 36 months. Strategies to improve fill volumes included education, standardized data collection, novel and unblinded information cascades, targeted communication, and bottle markings for blood collectors.ResultsA total of 516 201 blood cultures were evaluated over 40 months. In the preimplementation period (January–April 2015), no hospitals collected the recommended 8–10 mL/bottle, and the average system fill volume was 2.3 mL. In the final postimplementation period (January–April 2018), 7 of 10 hospitals achieved ≥8 mL per bottle and the system average increased to 8.6 mL (P &lt; .0001). The positivity rate increased 20%, from 7.39% to 8.85% (P &lt; .001), whereas the contamination rate did not change and remained low. Compared to the preimplementation period, the odds of positive cultures containing potential pathogens increased to 1.18 (95% confidence interval, 1.05–1.32; P = .003).ConclusionsHere we show that underfilled blood cultures are extremely common but that operational and educational strategies can result in sustained improvements across a complex network of hospitals and laboratories. This leads to increased detection of pathogens, which can have tremendous impact on the management of bloodstream infections and sepsis.

The present study was conducted to investigate effects of stocking density on growth performances of gold fish (Carassius auratus) in hapas. Experiment was conducted for a month with three treatments where three stocking densities were T1 (10 fry/hapa), T2 (15 fry/hapa) andT3 (20 fry/hapa) each having three replications which were selected randomly. In the present experiment hapa (3ft × 2ft × 2ft) with 1 mm mesh net was used. Gold fish fry having a mean body weight of 0.007 g were used in all treatments. Fishes were fed at the rate of 10% of their body weight containing 34.11% protein. Water quality parameters were monitored at 10 days interval and the ranges were –temperature 24.75 to 27.75 oC, dissolved oxygen 3.68 to 4.09 mg/L, pH 7.3 to 8.16, ammonia 0.3 to 1 mg/L, nitrite 0.01 to 0.03 mg/L, phosphate 0.6 to 1 mg/L and alkalinity 119 to 187 mg/L. At the growth performances were evaluated by comparing mean final body weight, specific growth rate and food conversion ratio. The present study showed that the gold fish fry in T1 resulted the best mean final weight gain (1.188 g) followed by T2 (0.834 g) and T3 (0.686 g). The SGR ranged between 6.64 and 7.43% per day and FCR ranged between 3.56 and 4.12 with T1 showing the lowest FCR. The survival rate (%) ranged between 76.67% to 85.67%. From the present experiment it was found that individual fish growth rate was decreased with the increase of stocking density.Asian J. Med. Biol. Res. December 2017, 3(4): 504-515

Objective: Evaluation of the efficacy and safety of atezolizumab/bevacizumab in a real-world HCC cohort, including patients with impaired liver function and prior systemic therapy. Methods: Retrospective analysis of 147 HCC patients treated with atezolizumab/bevacizumab at six sites in Germany and Austria. Results: The overall response rate and disease control rate were 20.4% and 51.7%, respectively. Seventy-three patients (49.7%) met at least one major exclusion criterion of the IMbrave150 trial (IMbrave-OUT), whereas 74 patients (50.3%) were eligible (IMbrave-IN). Median overall survival (mOS) as well as median progression-free survival (mPFS) was significantly longer in IMbrave-IN versus IMbrave-OUT patients [mOS: 15.0 months (95% confidence interval (CI): 10.7–19.3] versus 6.0 months (95% CI: 3.2–8.9; p < 0.001) and mPFS: 8.7 months (95% CI: 5.9–11.5) versus 3.7 months (95% CI: 2.7–4.7; p < 0.001)]. Prior systemic treatment did not significantly affect mOS [hazard ratio (HR): 1.32 (95% CI: 0.78–2.23; p = 0.305)]. mOS according to ALBI grades 1/2/3 were 15.0 months (95% CI: not estimable), 8.6 months (95% CI: 5.4–11.7), and 3.2 months (95% CI: 0.3–6.1), respectively. ALBI grade and ECOG score were identified as independent prognostic factors [ALBI grade 2 versus 1; HR: 2.40 (95% CI: 1.34 – 4.30; p = 0.003), ALBI grade 3 versus 1; HR: 7.28 (95% CI: 3.30–16.08; p < 0.001), and ECOG ⩾2 versus 0; HR: 2.09 (95% CI: 1.03 – 4.23; p = 0.042)], respectively. Sixty-seven patients (45.6%) experienced an adverse event classified as CTCAE grade ⩾3. Patients in the IMbrave-OUT group were at increased risk of hepatic decompensation with encephalopathy (13.7% versus 1.4%, p = 0.004) and/or ascites (39.7% versus 9.5%; p < 0.001). Conclusion: In this real-world cohort, efficacy was comparable to the results of the IMbrave150 study and not affected by prior systemic treatment. ALBI grade and ECOG score were independently associated with survival. IMbrave-OUT patients were more likely to experience hepatic decompensation.

Context Instrument-assisted soft tissue mobilization (IASTM) is a popular myofascial intervention used by health care professionals. Objective To document IASTM clinical practice patterns among health care professionals in the United States. Design Cross-sectional study. Setting Online survey. Patients or Other Participants A total of 853 members of the National Athletic Trainers' Association (n = 249) and the American Physical Therapy Association (n = 604). Main Outcome Measure(s) Responses to a 55-item electronic survey that assessed 4 areas, namely, IASTM training and experience, IASTM application, perception of IASTM in practice, and demographic information. Results Most (n = 705, 83%) of the 853 respondents used IASTM in their practice, and they had an average of 15 years of work experience. Approximately 86% (n = 731) reported completing some type of formal training, and 61% (n = 518) had completed some type of informal training. Respondents used &gt;34 different IASTM tools. Seventy-one percent (n = 606) indicated either not knowing how to quantify the amount of force applied by the tool during treatment or not trying to quantify. Fifteen percent (n = 128) estimated a force ranging from 100 to 500g. The treatment time for a specific lesion and location ranged from 1 to ≤5 minutes, with an average total treatment time of 14.46 ± 14.70 minutes. Respondents used 31 different interventions before or after IASTM. Approximately 66% (n = 564) reported following treatment recommendations, and 19% (n = 162) described rarely or never following recommendations learned during training. A total of 94% (n = 801) recounted using some type of clinical outcome measure to assess their treatment. Cluster analysis identified 3 distinct cluster groupings among professionals, with most (89%, n = 729/818) indicating that IASTM was an effective treatment. Conclusions This survey documented the IASTM practice patterns of health care professionals. Cluster profiles characterized group differences in IASTM training and clinical application. The gaps among research, clinical practice, and training need to be bridged to establish IASTM best practices.

Background:Juvenile idiopathic arthritis (JIA) can cause considerable pain and disability in childhood and adulthood. Studies exploring the efficacy of medications in adult JIA patients are limited, although tumor necrosis factor inhibitors (TNFi) have been increasingly used in this patient group.Objectives:To explore the efficacy of TNFi ± comedication on disease activity in adult JIA patients, compared to a weighted rheumatoid arthritis (RA) cohort.Methods:Data from NOR-DMARD, a longitudinal observational study including patients > 18 years starting or switching DMARD treatment, was used [1]. Patients with a clinical JIA diagnosis, or patients with other inflammatory joint diseases diagnosed before 16 years were identified from the study population. RA patients were included for comparative purposes.Disease activity measurements and remission rates among patients starting treatment with TNFi ± comedication were collected at baseline, 3 and 6 months. Changes in disease activity and absolute remission rates after 3 and 6 months were calculated. Remission rates and change in disease activity from baseline were compared between JIA patients and a weighted RA cohort with weights based on age and gender, using linear and logistic regression for continuous and categorical variables, respectively.Results:281 JIA patients (68.9% female, mean (SD) age 32.1 (11.1) years, mean (SD) diagnosis duration 23.5 (12.2) years) and 1374 RA patients (71.6% female, mean (SD) age 52.7 (14.5) years, mean (SD) diagnosis duration 9.5 (10.0) years) were included in the analyses. Age, gender distribution and disease duration differed significantly between cohorts.Both groups had a significant improvement across all disease activity measures after 3 months (Table 1), which was maintained after 6 months across all measures except MHAQ. The RA group had a significantly greater 3- and 6-month improvement in SJC28. Both groups had an overall 6-month increase in absolute remission rates. The JIA group had a significantly higher 3-month DAS28 remission rate (Figure 1). This difference was not significant after 6 months, as remission rates from 3 to 6 months in the JIA group declined across all measures.Table 1.BaselineChange to 3 monthsChange to 6 monthsJIA*RA*Diff.§JIA*RA*Diff.§JIA*RA*Diff.§ESR, mm/h18.7 (18.9)25.5 (22.0)1.3 (-2.3 to 4.9)-7.4 (15.8)-7.6 (16.6)-0.3 (-4.4 to 3.8)-7.4 (16.8)-8.5 (18.2)0.0 (-5.7 to 5.7)SJC282.5 (3.6)5.5 (5.4)1.6 (1.3 to 2.0)-1.4 (3.4)-3.1 (4.7)-1.0 (-1.7 to -0.3)-1.6 (3.2)-3.5 (5.1)-1.0 (-1.9 to -0.1)TJC 284.0 (5.6)6.6 (6.4)1.3 (0.4 to 2.3)-1.8 (3.9)-3.1 (5.9)-0.6 (-1.4 to 0.2)-1.8 (3.9)-3.9 (6.2)-1.0 (-2.0 to 0.1)DAS283.6 (1.4)4.5 (1.6)0.3 (0.1 to 0.6)-1.2 (1.3)-1.2 (1.4)-0.0 (-0.3 to 0.3)-1.2 (1.3)-1.5 (1.4)-0.2 (-0.6 to 0.2)SDAI16.8 (10.6)23.1 (14.3)2.4 (0.3 to 4.5)-7.7 (9.9)-10.9 (12.7)-2.0 (-4.2 to 0.2)-7.9 (8.6)-13.2 (13.6)-2.8 (-5.8 to 0.2)PGA51.4 (26.3)49.9 (25.5)-4.0 (-8.5 to 0.5)-20.6 (26.7)-17.0 (26.7)2.7 (-2.2 to 7.6)-21.6 (25.3)-19.1 (28.7)3.4 (-3.0 to 9.8)MHAQ0.6 (0.5)0.7 (0.5)0.0 (-0.1 to 0.1)-0.24 (0.42)-0.22 (0.42)0.0(-0.1 to 0.1)-0.23 (0.40)-0.25 (0.45)0.0 (-0.1 to 0.1)*Mean (SD)§ Weighted group difference, RA coefficient (95 % confidence interval)Figure 1.Mean 3- and 6-month remission rates with error bars (SE)Conclusion:TNFi was equally effective in reducing disease activity in the JIA and RA cohort after 3 and 6 months, and in inducing remission after 6 months. Absolute remission rates in the JIA group declined from 3 to 6 months across all measures, and studies with longer duration are needed to explore the long-term efficacy of TNFi in the patient groups.References:[1]Kvien, T.K., et al., A Norwegian DMARD register: prescriptions of DMARDs and biological agents to patients with inflammatory rheumatic diseases. Clin Exp Rheumatol, 2005. 23(5 Suppl 39): p. S188-94.Disclosure of Interests:Imane Bardan: None declared, Karen Minde Fagerli: None declared, Joe Sexton: None declared, Gunnstein Bakland Speakers bureau: Abbvie, Consultant of: UCB, Pfizer, Novartis, Pawel Mielnik: None declared, Liz Marina Paucar Loli: None declared, Tore K. Kvien Speakers bureau: Fees for speaking: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi, Consultant of: Fees for consulting: AbbVie, Amgen, Biogen, Celltrion, Eli Lilly, Gliead, Mylan, Novartis, Pfizer, Sandoz, Sanofi, Grant/research support from: Received research funding to Diakonhjemmet Hospital from Abbvie, Amgen, BMS, MSD, Pfizer and UCB, Eirik kristianslund: None declared, Anna-Birgitte Aga Grant/research support from: Dr. Aga reports personal fees from Abbvie, Eli Lilly, Novartis and Pfizer, outside the submitted work

Twenty-four first parity and 48 multiparity crossbred sows (Yorkshire × Landrace) were used in a 2 × 2 factorial design involving high (H) or low (L) lactation feed intakes and the intramuscular injection, or not, of 50 μg of gonadotrophin-releasing hormone (GnRH) at the onset of the first postweaning estrus. All sows were weighed at farrowing and weaning. The H feed intake entailed feeding sows at levels of 10, 13, and 14% of each sow's immediate postfarrowing metabolic weight during weeks 1, 2, and 3–4 of lactation, respectively. Low-fed sows received 50% of the H feed level. The diet contained 12.5 MJ DE kg−1 and 16% crude protein. Between weaning and mating, and following mating, all sows were fed 2.25 kg daily of the lactation diet. After weaning, sows were exposed to a boar twice daily to facilitate estrus detection. GnRH was administered at the onset of standing heat. All sows were slaughtered 25 d after mating at which time the reproductive tracts were removed and examined to determine the number of ovulations and the number of viable embryos. Low-level feeding resulted in an extension of the remating interval (5.9 ± 0.3 vs. 4.5 ± 0.2 d; P < 0.05), an increased incidence of anestrus (16.7 vs. 3.6%; P > 0.1) and a reduction in pregnancy rates (69.7 vs. 81.6%; P > 0.1). Interactions were noted between lactation feeding level and GnRH injection (P < 0.05) and between parity and GnRH injection (P < 0.05) for number of viable embryos. The data obtained suggest that both low level of feeding during lactation and a young age are associated with decreased embryo numbers, but this situation is alleviated by the administration of GnRH. Key words: Sows, feed intake, estrus, GnRH

ObjectivesTo determine whether a team illness prevention strategy (TIPS) would reduce the incidence of acute illness during the Super Rugby tournament.MethodsWe studied 1340 male professional rugby union player seasons from six South African teams that participated in the Super Rugby tournament (2010–2016). Medical staff recorded all illnesses daily (126 850 player days) in a 3-year control (C: 2010–2012; 47 553 player days) and a 4-year intervention (I: 2013–2016; 79 297 player days) period. A five-element TIPS was implemented in the I period, following agreement by consensus. Incidence rate (IR: per 1000 player days; 95% CI) of all acute illnesses, illness by main organ system, infectious illness and illness burden (days lost due to illness per 1000 player days) were compared between C and I period.ResultsThe IR of acute illness was significantly lower in the I (5.5: 4.7 to 6.4) versus the C period (13.2: 9.7 to 18.0) (p<0.001). The IR of respiratory (C=8.6: 6.3 to 11.7; I=3.8: 3.3 to 4.3) (p<0.0001), digestive (C=2.5: 1.8 to 3.6; I=1.1: 0.8 to 1.4) (p<0.001), skin and subcutaneous tissue illness (C=0.7: 0.4 to 1.4; I=0.3: 0.2 to 0.5) (p=0.0238), all infections (C=8.4: 5.9 to 11.9; I=4.3: 3.7 to 4.9) (p<0.001) and illness burden (C=9.2: 6.8 to 12.5; I=5.7: 4.1 to 7.8) (p=0.0314) were significantly lower in the I versus the C period.ConclusionA TIPS during the Super Rugby tournament was associated with a lower incidence of all acute illnesses (59%), infectious illness (49%) and illness burden (39%). Our findings may have important clinical implications for other travelling team sport settings.

Background:The anti–interleukin-6 (IL-6) receptor-α antibody tocilizumab (TCZ) demonstrated skin score improvement and forced vital capacity (FVC) preservation in patients with systemic sclerosis (SSc) in a phase 2 randomized controlled trial.1,2Data from the 48-week, double-blind (DB), placebo (PBO)-controlled period of the focuSSced phase 3 trial were previously presented,3and open-label (OL) data up to week 96 are presented herein.Objectives:To assess the long-term safety and efficacy of TCZ in SSc patients.Methods:Adult patients with active SSc (≤60-month duration, modified Rodnan skin score [mRSS] 10-35, and elevated acute-phase reactants) treated with PBO or TCZ in the DB period received OL TCZ 162 mg SC weekly from weeks 48 to 96 in the OL period (PBO→OL TCZ and TCZ→OL TCZ, respectively). Exploratory analysis of data up to week 96 included no formal statistical analyses. Changes in mRSS and percent predicted FVC (ppFVC) were assessed.Results:Overall, 92/105 TCZ (88%) and 89/107 PBO (83%) patients entered the OL TCZ treatment period at week 48, and 85/105 TCZ→OL TCZ (81%) and 82/107 PBO→OL TCZ (77%) patients completed treatment up to week 96. Continued decline in mRSS was observed in the OL period for PBO→OL TCZ and TCZ→OL TCZ patients (Table). Change in ppFVC for patients who switched from PBO to TCZ (PBO→OL TCZ) was comparable between weeks 48 and 96 (OL period) to the change in patients who received TCZ from BL to week 48 in the DB period (Table). Rates (95% CI) of serious adverse events from weeks 48 to 96 were 15.8 (8.6, 26.5) per 100 PY for TCZ→OL TCZ patients, 14.8 (7.9, 25.3) per 100 PY for PBO→OL TCZ patients, and 15.4 (11.0, 20.9) for all TCZ exposure over 96 weeks (n = 193). Rates (95% CI) of serious infections were 2.3 (0.3, 8.1) per 100 PY for TCZ→OL TCZ patients, 3.4 (0.7, 10.0) per 100 PY for PBO→OL TCZ patients, and 3.0 (1.3, 5.9) for all TCZ exposure over 96 weeks. One death occurred during the OL period in each arm.Conclusion:Although OL data have to be interpreted with caution, results from OL TCZ treatment show numeric improvements in mRSS and FVC preservation similar to those of the DB period, with a beneficial effect on trajectory of FVC decline in patients who switched from PBO to TCZ. Long-term safety results were consistent with the known safety profile of TCZ, and no new or unexpected events were observed.References:[1]Khanna D et al.Lancet2016;387:2630-40.[2]Khanna D et al.Ann Rheum Dis.2018;77:212-20.[3]Khanna D et al.Arthritis Rheumatol2018;70(suppl 10):abst 898.Table.Change in Efficacy From BaselineBaseline to Week 48Baseline to Week 96Week 48 to Week 96PBOTCZPBO→OL TCZTCZ→OL TCZPBO→OL TCZTCZ→OL TCZmRSS, mean (95% CI)a–5.3 (–6.9, –3.7)n = 92–6.7 (–8.0, –5.4)n = 97–8.4 (–10.0, –6.8)n = 83–9.6 (–10.9, –8.4)n = 85–2.5(–3.3, –1.6)n = 82–2.3(–3.2, –1.5)n = 85ppFVC, mean (95% CI) [median]–4.1 (–5.8, –2.4) [–3.9]n = 92–0.2 (–1.6, 1.2) [–0.7]n = 94–3.3 (–5.1, –1.5) [–3.1]n = 79–0.5 (–2.4, 1.3) [–1.4]n = 840.6 (–0.7, 1.9) [0.3]n = 78–0.3 (–1.7, 1.1) [0.0]n = 82Decline in ppFVC ≥10%, n/N (%)a15/91(16.5)5/93(5.4)14/79 (17.7)11/84 (13.1)NANAImprovement in ppFVC, n/N (%)a26/91(28.6)43/93(46.2)22/79(27.8)35/84(41.7)NANAaObserved data. NA, not assessed.Disclosure of Interests:Dinesh Khanna Shareholder of: Eicos, Grant/research support from: NIH NIAID, NIH NIAMS, Consultant of: Acceleron, Actelion, Bayer, BMS, Boehringer-Ingelheim, Corbus, Galapagos, Genentech/Roche, GSK, Mitsubishi Tanabi, Sanofi-Aventis/Genzyme, UCB Pharma, Celia J. F. Lin Employee of: Genentech, Helen Spotswood Shareholder of: Roche Products Ltd, Employee of: Roche Products Ltd, Jeff Siegel Employee of: Genentech, Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer

Background:Anemia is widespread in rheumatic patients and is an important extra-articular manifestation that correlates with physical disability and increased mortality. The pathogenesis of such anemia is complex and multifactorial, including due to the influence of pro-inflammatory cytokines.Objectives:Our aim was to study the characteristics of the secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) with anemia of chronic diseases (ACD), iron deficiency anemia (IDA) and a combination of ACD / IDA, as well as to study the effect of these cytokines on the development of anemia.Methods:There were examined 69 (54 (7 men /47 women, 50.6 ± 4.1 years) with anemia, 15 (6 men/9 women, 53.5 ± 2.74 years) without anemia) of RA patients. According to the criteria of Van Santen and Worwood, by determining the transferrin saturation index (TSI), ferritin, C-reactive protein (CRP), patients were divided into 4 groups: group 1 - ACD, 22 (5/17) patients (hemoglobin 79 [IQR, 95.6-111], red blood cells 3.5 [IQR, 3.6-4], TSI 25 [IQR, 14.7-26.2], ferritin 326.2 [IQR, 197.8-451.7], CRP 63.7 [IQR, 10.2-104.8]), group 2 - ACD / IDA, 18 (0/18) patients (hemoglobin 101 [IQR, 94-114], red blood cells 3.9 [IQR, 4-4.4], TSI 12.5 [IQR, 7.7-15], ferritin 50.1 [IQR, 11.9-74.9], CRP 45.8 [IQR, 17.6-54.9]), group 3 - IDA, 14 (2/12) patients (hemoglobin 108 [IQR, 100-115], red blood cells 4.5 [IQR, 4.1-4.9], TSI 9.7 [IQR 3-14], ferritin 21.8 [IQR, 7.2-28.9], CRP 8.6 [IQR, 2.7-8.6]), group 4 (control) - 15 patients without anemia (hemoglobin 141.4 [IQR, 133-147], red blood cells 4.6 [IQR, 4.3-4.9], TSI 23.1 [IQR, 16.6-27.8], ferritin 78.5 [IQR, 36-90.7], CRP 4.6 [IQR, 1.2-5.8]). The diagnosis of rheumatoid arthritis was made based on the 2010 ACR/EULAR classification criteria. The number of red blood cells and hemoglobin levels were determined on a Sysmex XS-500i analyzer (Japan). Concentrations of ferritin, CRP, TSI were determined on an Olympus Au 480 analyzer (Beckman Coulter, USA). Concentrations of IL-6, IL-10, and TNF-α were determined using a Stat Fax 2100 analyzer (Awareness Technology Inc., USA). The significance of differences between several unrelated groups was determined using the Kruskal-Wallis test at a significance level (p) of less than 0.05. To assess the relationship between the variables, the Spearman correlation coefficient (r) was calculatedResults:In the ACD group, there were the highest concentrations of CRP, ferritin in comparison with the other groups (p <0.05). TSI in the ACD group was higher compared with the IDA and ACD / IDA groups (p <0.05) and did not differ from the control group (p> 0.05). The maximum concentration of IL-6 was found in the ACD group (36.2 [IQR, 6.7-41]) compared with the ACD / IDA group (21.7 [IQR, 7.2-20.4]) (p <0, 05) and the IDA group (5.9 [IQR, 1.5-3.7]) (p <0.05) and without anemia (2.7 [IQR, 1.5-3) (p <0.05). Regarding IL-10 and TNF-α, no intergroup differences were found. A moderate correlation was found between the number of red blood cells and the concentration of IL-6 (r = -0.3), IL-10 (r = -0.4), TNF-α (r = -0.3). The relationship between the concentration of hemoglobin and IL-6 (r = -0.6), IL-10 (r = -0.4), TNF-α (r = -0.3) was revealed.Conclusion:In RA patients, IDA, ACD, as well as their combination, may occur. It is very important to clarify the genesis of anemia. ACD should be isolated separately because it has a complex pathogenesis, one of the important components of which are cytokines and their effect on erythropoiesis. The increased concentration of IL-6 in the group of patients with ACD, as well as the presence of a correlation between IL-6, red blood cells and hemoglobin, indicate the importance of this cytokine in the development of anemia. An increase in the concentration of ferritin and CRP also reflects the inflammatory genesis of anemia in patients with this anemia. The presence of a correlation between IL-10, TNF-α and hemogram indices suggests their influence on the development of anemia.Disclosure of Interests:None declared

Background: Hip arthroscopy for femoroacetabular impingement syndrome (FAIS) is a rapidly expanding field, and preoperative factors predictive of persistent postoperative pain are currently unknown. Purpose: To identify predictors for persistent postoperative pain at the site of surgery after hip arthroscopy for FAIS. Study Design: Case-control study; Level of evidence, 3. Methods: Patients who underwent hip arthroscopy for FAIS and had a minimum 2-year follow-up with patient-reported outcomes (PROs) were included in this study. Patients with previous open hip surgery and diagnoses other than FAIS were excluded. Patients were grouped by visual analog scale scores for pain as limited (<30) and persistent (≥30). Patient factors and outcomes were analyzed with univariate and correlation analyses to build a logistic regression model to identify predictors of persistent postoperative pain. Results: The limited pain (n = 514) and persistent pain (n = 174) groups totaled 688 patients (449 females). There was a statistically significant difference in age between groups, with the persistent pain group being older than the low pain group (35.9 ± 12.2 vs 32.4 ± 12.6, respectively; P = .002). Patients with persistent postoperative pain demonstrated significantly lower preoperative PRO scores in the Hip Outcome Score–Activities of Daily Living (57.6 ± 21.2 vs 67.7 ± 16.8), Hip Outcome Score–Sport Specific (35.9 ± 23.9 vs 44.1 ± 22.7), modified Harris Hip Score (51.6 ± 16.2 vs 59.6 ± 12.9), and International Hip Outcome Tool (32.0 ± 16.8 vs 40.0 ± 17.82) but no significant differences in preoperative visual analog scale scores for pain (7.3 ± 1.8 vs 7.2 ± 1.7). Mean postoperative PRO differences between pain groups were all statistically significant. Bivariate logistic regression analysis demonstrated that history of anxiety or depression (odds ratio, 1.8; 95% CI, 1.02-3.32; P = .042), revision hip arthroscopy (odds ratio, 8.6; 95% CI, 1.79-40.88; P = .007), and a low preoperative modified Harris Hip Score (odds ratio, 0.97; 95% CI, 0.95-0.99; P = .30) were predictors of persistent postoperative pain. Conclusion: Independent predictors for persistent postoperative pain include revision hip arthroscopy and mental health history positive for anxiety and depression. Our analysis demonstrated significant improvements in pain and functional PROs in the limited pain and persistent pain groups; however, those with persistent pain demonstrated significantly lower PRO scores.

AbstractIncompressible flow in toroidal pipes of circular cross-section was investigated by three-dimensional, time-dependent numerical simulations using a finite volume method. The computational domain included a whole torus and was discretized by up to ${\ensuremath{\sim} }11. 4\ensuremath{\times} 1{0}^{6} $ nodes. Two curvatures $\delta $ (radius of the cross-section/radius of the torus), namely 0.3 and 0.1, were examined; a streamwise forcing term was imposed, and its magnitude was made to vary so that the bulk Reynolds number ranged between ${\ensuremath{\sim} }3500$ and ${\ensuremath{\sim} }14\hspace{0.167em} 700$. The results were processed by different techniques in order to confirm the spatio-temporal structure of the flow. Consecutive transitions between different flow regimes were found, from stationary to periodic, quasi-periodic and chaotic flow. At low Reynolds number, stationary flow was predicted, exhibiting a symmetric couple of Dean vortex rings and a strong shift of the streamwise velocity maximum towards the outer wall. For $\delta = 0. 3$, between $\mathit{Re}= 4556$ and $\mathit{Re}= 4605$ a first transition occurred from stationary to periodic flow, associated with a supercritical Hopf bifurcation and giving rise to a travelling wave which took the form of a varicose streamwise modulation of the Dean vortex ring intensity. A further transition, associated with a secondary Hopf bifurcation, occurred between $\mathit{Re}= 5042$ and $\mathit{Re}= 5270$ and led to a quasi-periodic flow characterized by two independent fundamental frequencies associated with distinct travelling waves, the first affecting mainly the Dean vortex rings and similar to that observed in purely periodic flow, the second localized mainly in the secondary flow boundary layers and manifesting itself as an array of oblique vortices produced at the edge of the Dean vortex regions. Both the periodic and the quasi-periodic regimes were characterized by an instantaneous anti-symmetry of the oscillatory components with respect to the equatorial midplane of the torus. For $\delta = 0. 1$, between $\mathit{Re}= 5139$ and $\mathit{Re}= 5208$ a direct (‘hard’) transition from steady to quasi-periodic flow occurred. Hysteresis was also observed: starting from a quasi-periodic solution and letting the Reynolds number decrease, both quasi-periodic and periodic stable solutions were obtained at Reynolds numbers below the critical value. A further decrease in $\mathit{Re}$ led to steady-state solutions. This behaviour suggests the existence of a subcritical Hopf bifurcation followed by a secondary Hopf bifurcation. The resulting periodic and quasi-periodic flows were similar to those observed for the higher curvature, but the travelling modes were now instantaneously symmetric with respect to the equatorial midplane of the torus. Also, the further transition from quasi-periodic to chaotic flow occurred with different modalities for the two curvatures. For $\delta = 0. 3$, a centrifugal instability of the main flow in the outer region occurred abruptly between $\mathit{Re}= 7850$ and $\mathit{Re}= 8160$, while a further increase of $\mathit{Re}$ up to 13 180 did not cause any relevant change in the distribution and intensity of the fluctuations. For $\delta = 0. 1$ the transition to chaotic flow was gradual in the range $\mathit{Re}= 6280$ to 8160 and affected mainly the inner region; only a further increase of $\mathit{Re}$ to 14 700 caused fluctuations to appear also in the outer region.

Background: Timely evaluation of acute chest pain is necessary, although most evaluations will not find significant coronary disease. With employers increasingly adopting high-deductible health plans (HDHP), how HDHPs impact subsequent care after an emergency department (ED) diagnosis of nonspecific chest pain is unclear. Methods: Using a commercial and Medicare Advantage claims database, we identified members 19 to 63 years old whose employers exclusively offered low-deductible (≤$500) plans in 1 year, then, at an index date, mandated enrollment in HDHPs (≥$1000) for a subsequent year. We matched them with contemporaneous members whose employers only offered low-deductible plans. Primary outcomes included population rates of index ED visits with a principal diagnosis of nonspecific chest pain, admission during index ED visits, and index ED visits followed by noninvasive cardiac testing within 3 and 30 days, coronary revascularization, and acute myocardial infarction hospitalization within 30 days. We performed a cumulative interrupted time-series analysis, comparing changes in annual outcomes between the HDHP and control groups before and after the index date using aggregate-level segmented regression. Members from higher-poverty neighborhoods were a subgroup of interest. Results: After matching, we included 557 501 members in the HDHP group and 5 861 990 in the control group, with mean ages of 42.0 years, 48% to 49% female, and 67% to 68% non-Hispanic White individuals. Employer-mandated HDHP switches were associated with a relative decrease of 4.3% (95% CI, –5.9 to –2.7; absolute change, –4.5 [95% CI, –6.3 to –2.8] per 10 000 person-years) in nonspecific chest pain ED visits and 11.3% (95% CI, –14.0 to –8.6) decrease (absolute change, –1.7 per 10 000 person-years [95% CI, –2.1 to –1.2]) in visits leading to hospitalization. There was no significant decrease in subsequent noninvasive testing or revascularization procedures. An increase in 30-day acute myocardial infarction admissions was not statistically significant (15.9% [95% CI, –1.0 to 32.7]; absolute change, 0.3 per 10 000 person-years [95% CI, –0.01 to 0.5]) but was significant among members from higher-poverty neighborhoods. Conclusions: Employer-mandated HDHP switches were associated with decreased nonspecific chest pain ED visits and hospitalization from these ED visits, but no significant change in post-ED cardiac testing. However, HDHP enrollment was associated with increased 30-day acute myocardial infarction admission after ED diagnosis of nonspecific chest pain among members from higher-poverty neighborhoods.

Abstract Background. The prognostic significance of bone marrow (BM) fibrosis grade in pts with primary myelofibrosis (PMF) is debated. A fibrosis grade greater than 1 was associated with a 2-fold higher risk of death compared with pts with early/prefibrotic MF (grade 0) [Thiele J, Ann Hematol 2006]. Recent data suggest that more accurate prediction of survival is achieved when fibrosis grade is added to IPSS [Verner C, Blood 2008; Giannelli U, Mod Pathol 2012]. Aim. To analyze the prognostic impact of fibrosis in diagnostic BM samples of 540 WHO-2008 diagnosed PMF pts with extensive clinical and molecular information collected in 6 Italian centers belonging to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative). Methods. The clinical variables assessed were those previously identified as prognostically relevant in the IPSS score. Published methods were used to screen mutations of JAK2, MPL, CALR, EZH2, ASXL1, IDH1/2 and SRSF2. European consensus scoring system was used to grade fibrosis (on a scale of MF-0 to MF-3). The prognostic value of fibrosis with regard to overall survival (OS) was estimated by Kaplan-Meier method and Cox regression. Results. Pts' median age was 61y; median follow-up 3.7y; median OS 10.5y; 184 pts (34.1%) died. IPSS risk category: low 33.7%, Int-1 27.7%, Int-2 19.1%, High-risk 19.5%. Mutational rate: JAK2 V617F 62.6%, CALR 20.7% (type-1/1-like 77.7%, type2/2-like-2 21.4%), MPL W515 5.9%; 62 (11.5%) were triple negative (TN). 171 pts (31.7%) were High-Molecular Risk (HMR) category (Vannucchi AM, Leukemia 2013); mutation rate: EZH2 7.2%, ASXL1 22.2%, IDH1-2 2.4%, SRSF2 8.3%. According to fibrosis grading, 50 pts were MF-0 (9.3%), 180 MF-1 (33.3%), 196 MF-2 (36.3%), 114 MF-3 (21.1%). Compared with both MF-0 and MF-1, MF-2 and MF-3 pts presented more frequently constitutional symptoms (P<.0001), larger splenomegaly (P<.0001), greater risk of developing anemia (P<.0001) or thrombocytopenia (P=.003). We found a significant association (P<.0001) between IPSS higher/Int-2 risk categories and MF-2 and -3 (20.5% and 37.8%, respectively, vs 14.8% and 6.0% for MF-0 and -1). There was no correlation between fibrosis grade and phenotypic driver mutations; in particular, TN pts were equally distributed among MF fibrosis grades (10%, 10.6%, 14.3% and 8.8% from MF-0 to -3, respectively). Conversely, the frequency of HMR pts increased progressively according to fibrosis grade: 8 pts MF-0 (16%), 46 MF-1 (25.6%), 66 MF-2 (33.7%) and 51 MF-3 (44.7%) (P<.0001). In particular, we found a significant association between fibrosis grade and ASXL1 (12%, 15%, 23.5% and 36% from MF-0 to -3; P<.0001) and EZH2 (2%, 3.9%, 8.2%, 13.2%; P=.01) mutations. Also, pts with 2 or more HMR mutated genes were preferentially MF-2 or -3 ( 0%, 4.4% 10.2% and 10.5% from MF-0 to -3; P=.001). Median OS was significantly shorter in pts with MF-2 (OS 6.7y, HR 7.3, IC95% 2.7-20.0; P<.0001) and MF-3 (OS 7.2y, HR 8.7, IC95% 3.1-24.2; P<.0001) compared with MF-1 (14.7y; HR 3.9, IC95% 1.4-10.9, P=.008) and MF-0 (P<.0001) used as reference group (OS not reached) (Figure). Excluding MF-0, MF-2 and -3 maintained negative prognostic impact with HR 1.9 (1.3-2.6; P=.001) and 2.2 (1.5-3.3; P<.0001) respectively vs MF-1. The impact of fibrosis on OS was maintained when analysis was restricted to younger (≤65y) pts. In multivariate analysis using the individual IPSS variables, grade MF-2 and -3 were independently predictive of survival (HR 3.9 (1.4-10.8), and HR 4.2 (1.5-12.0), respectively, P=.008 for both). The negative impact on survival of MF-2/-3 was maintained regardless of IPSS category, HMR status, number of HMR mutated genes and driver mutations, included as covariates (Table). In low, Int-1 and Int-2, but not high-risk IPSS categories, MF-2/-3 associated with reduced survival (P<.03). Conclusions. Overall, these results indicate that higher grades (MF-2 and MF-3) of fibrosis correlate with defined clinical and molecular variables and independently negatively impact on OS in PMF, suggesting the opportunity to explore its value in the setting of clinical and molecular prognostic scores for PMF. Table. Multivariate Analysis Variables HR 95% CI P value HMR status 2.4 1.5-3.7 <.0001 HMR≥2mutations 4.3 2.8-6.4 .009 IPSS scoring Int1 2.9 1.6-5.1 <.0001 Int2 10.0 5.6-17.7 <.0001 High 9.7 5.5-17.2 <.0001 Driver mutations CALR type2 3.4 1.3-8.6 .010 JAK2/MPL 2.4 1.4-4.3 .003 TN 4.5 2.3-8.8 <.0001 Fibrosis MF-2/MF-3 3.8 1.4-10.6 .010 Figure 1. Figure 1. Disclosures Passamonti: Novartis: Consultancy, Honoraria, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Vannucchi:Shire: Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Background:Hip osteoarthritis (HOA) is a severe outcome of juvenile idiopathic arthritis (JIA) itself and also can be result of corticosteroid (CS) treatment, if it was used. Total hip arthroplasty (THA) is the last step in JIA treatment and indicates ineffectiveness of conservative treatment.Objectives:We aimed to evaluate risk factors which lead to THA in JIA patients with HOA.Methods:753 patients aged 2-17 years were included in our retrospective study during the last 10 years. Diagnosis was made according to ILAR criteria. Clinical, laboratory and radial examinations were evaluated. Diagnosis of HOA was made on MRI, CT and planar radiograms and confirmed by morphological examination of removed femoral heads.Results:Total 153/753 (20.3%) patients with JIA had hip involvement. HOA developed in 48/153 (31.4%) of JIA patients and 16/48 (33.3%) of them had THA was undergone. Prevalence of HOA and THA (%) in JIA subtypes: in polyarticular (5/32 (15.6%) and 8/16 (50%), systemic (6/32 (18.7%) and 5/16 (31.2%)), enthesitis-related (19/32 (59.4%) and 3/16 (18.8%)) and psoriatic (2/32 (6.7%) and 0/16) subtypes respectively, р=0,0000001. Patients who underwent THA initially had higher level of inflammation: elevated ESR (33 vs 5 mm/h, p=0.002) and CRP (14.7 vs 1.9 mg/l, p=0.03), more active joint, and especially involvement of joints of upper limbs: elbows (p=0.004) and proximal interphalangeal joints (p=0.001), arthritis of subtalar joint (p=0.02). Delayed biologic treatment (7.5 vs 3.4 years, p=0.043) and delayed achievement of remission (9.2 vs 5.6 years, p=0.047) were main predictors of THA. Patients with HOA without biologics had increased cumulative probability of THA: HR=1.99 (1.01; 3.98), p=0.049 (Figure 1). Patients with THA received corticosteroids (93.7 vs 50%, p=0.003) more often including high dose pulse-therapy regimes, but differences in the cumulative doses were not observed (5000 vs 4500 mg, p=0.54) between groups, CS administration was independent risk factor of HOA and THA.Figure 1.Cumulative probability of THA in JIA patients with hip osteoarthritis.Conclusion:the main risk factors of THA are systemic and polyarticular course because of their activity, systemic CS and delayed biologic treatment. Corticosteroids should be avoided in those group of patients because of risk of avascular pathway HOA formation.This work supported by the Russian Foundation for Basic Research (grant № 18-515-57001).Table 1.The features of JIA patients with hip osteoarthritis depending onJIA featuresTHA, (n=16)HOA without THA, (n=32)pTime to THA, years5.2 (3.6; 10.2)4.6 (2.2; 8.7)0.4Onset age, years7.95 (3.5; 11.1)8.3 (4.3; 13.1)0.5JIA duration, years8.5 (6.5; 13.2)5.43 (2.8; 11.1)0.07Polyarticular JIA, n (%)8 (50.0)5 (15.6)0.037Systemic JIA, n (%)5 (31.3)6 (7.0)0.037ANA, n (%)3/8 (37.5)5/16 (31.3)0.760HLA B27, n (%)3/6 (50)9/19 (47.4)0.911RF, n (%)0/9 (0)1/15 (6.7)0.429Uveitis, n (%)1/16 (6.3)3/24 (12.5)0.519ESR, mm/h33 (13; 54)5 (3; 27)0.002CRP, mg/l14.7 (2.9; 72.3)1.9 (0.3; 12.7)0.03Active joints, n21.5 (8.5; 52.5)9 (5; 16)0.02Elbows, n (%)11 (68.7)8 (25.0)0.004Proximal interphalangeal joints, n (%)10 (62.5)5 (15.6)0.001Subtalar, n(%)4 (25.0)1 (3.1)0.02Pulse-therapy GCS, n(%)11 (68.7)10 (31.3)0.014Cumulative GCS dose, mg5000 (3000; 14000)4500 (500; 20000)0.54Time to biologic, years7.6 (4.3; 11.4)3.4 (1.9; 8.6)0.04Achievement of remission, years9.2 (6.6; 15.4)5.6 (3.3; 11.4)0.047Disclosure of Interests:None declared

OBJECTIVEPediatric firearm injury is a leading cause of death and disability in the youth of the United States. The epidemiology of and outcomes following gunshot wounds to the head (GSWHs) are in need of systematic characterization. Here, the authors analyzed pediatric GSWHs from a population-based sample to identify predictors of prolonged hospitalization, morbidity, and death.METHODSAll patients younger than 18 years of age and diagnosed with a GSWH in the National Sample Program (NSP) of the National Trauma Data Bank (NTDB) in 2003–2012 were eligible for inclusion in this study. Variables of interest included injury intent, firearm type, site of incident, age, sex, race, health insurance, geographic region, trauma center level, isolated traumatic brain injury (TBI), hypotension in the emergency department, Glasgow Coma Scale (GCS) score, and Injury Severity Score (ISS). Risk predictors for a prolonged hospital stay, morbidity, and mortality were identified. Odds ratios, mean increases or decreases (B), and 95% confidence intervals were reported. Statistical significance was assessed at α < 0.001 accounting for multiple comparisons.RESULTSIn a weighted sample of 2847 pediatric patients with GSWHs, the mean age was 14.8 ± 3.3 years, 79.2% were male, and 59.0% had severe TBI (GCS score 3–8). The mechanism of assault (63.0%), the handgun as firearm (45.6%), and an injury incurred in a residential area (40.6%) were most common. The mean hospital length of stay was 11.6 ± 14.4 days for the survivors, for whom suicide injuries involved longer hospitalizations (B = 5.9-day increase, 95% CI 3.3–8.6, p < 0.001) relative to those for accidental injuries. Mortality was 45.1% overall but was greater with injury due to suicidal intent (mortality 71.5%, p < 0.001) or caused by a shotgun (mortality 56.5%, p < 0.001). Lower GCS scores, higher ISSs, and emergency room hypotension predicted poorer outcomes. Patients with private insurance had lower mortality odds than those with Medicare/Medicaid (OR 2.4, 95% CI 1.7–3.4, p < 0.001) or government insurance (OR 3.6, 95% CI 2.2–5.8, p < 0.001). Management at level II centers, compared to level I, was associated with lower odds of returning home (OR 0.3, 95% CI 0.2–0.5, p < 0.001).CONCLUSIONSFrom 2003 to 2012, with regard to pediatric TBI hospitalizations due to GSWHs, their proportion remained stable, those caused by accidental injuries decreased, and those attributable to suicide increased. Overall mortality was 45%. Hypotension, cranial and overall injury severity, and suicidal intent were associated with poor prognoses. Patients treated at level II trauma centers had lower odds of being discharged home. Given the spectrum of risk factors that predispose children to GSWHs, emphasis on screening, parental education, and standardization of critical care management is needed to improve outcomes.

Abstract Background: Ninety percent of hypercalcemia cases are related to either primary hyperparathyroidism or malignancy (1). This case presents one of the atypical etiologies of hypercalcemia. Clinical Case: A 53-year-old man with past medical history of nephrectomy was admitted for acute respiratory distress syndrome secondary to SARS-CoV-2. Hospital stay was complicated by septic shock and acute kidney injury requiring hemodialysis. Three months post hospital admission, the patient developed non-parathyroid (PTH) mediated hypercalcemia. Lab work results showed elevated serum calcium of 12.7 mg/dl (8.6–10.6), ionized calcium 6.8 mg/dl (4.2–5.4), albumin 2.6 g/dl (3.4–5.4), serum creatinine of 3.5 mg/dl (0.5–1.5), eGFR of 18.4 ml/min, and a PTH of 4 pg/ml (12–88). Liver profile - total bilirubin of 10.5 mg/dl (0–1.2), direct bilirubin of 5.9 mg/dl (0–0.2), GGTP 2055 U/L (6–60), alkaline phosphatase of 936 u/L (40–125), bone fractionated alkaline phosphatase 216 u/L (0–55), 25-OH Vitamin D of 11 ng/nl (20–80), 1,25 OH vitamin D of &lt;5 pg/ml (19–79), TSH of 3.56 mciu/mL (0.35–4.0), CPK of 20 u/L (21–232) and a normal SPEP and immune-electrophoresisTreatment for hypercalcemia was initiated with calcitonin and oral steroids (prednisone 40mg/day for 4 days, 20mg/day for 1 day, and 10mg/day for 2 days), resulting in normalization of serum calcium. Patient received tube feedings that contained 2192 mcg retinol activity equivalents of vitamin A daily, which is associated with vitamin A intoxication in the presence of renal insufficiency. Vitamin A returned 0.78 mg/L (0.3–1.2). Serum Parathyroid hormone-related peptide (PTHrP) was elevated at 12.4 pmol/L (0.0–2.0). There was no obvious malignancy on various imaging studies. A magnetic resonance cholangiopancreatography (MRCP) showed biliary stricturing suggestive of primary sclerosing cholangitis (PSC), however, liver biopsy was not consistent with PSC. Serum IgG4 level was found to be elevated to 142 mg/dl (range: 1–123) which raised suspicion for autoimmune cholangiopathy. Discussion: Patient presented with non-PTH mediated hypercalcemia with low serum 1,25 OHD levels and elevated serum PTHrP level. Although most cases of elevated PTHrP associated with hypercalcemia are due to solid tumors, increased PTHrP levels have been seen in hypercalcemic patients with hematological malignancies and rare benign causes such as pneumonia (5). Association of elevated hypercalcemia with elevated IgG4 levels and PTHrP levels has not been previously reported. MRCP findings and abnormal morphology detailed in liver biopsy are suggestive of IgG4-related disease (IgG4RD) (3). The responsiveness in hypercalcemia to prednisone also supports this diagnosis. IgG4RD is associated with multi-organ autoimmune involvement. This case report highlights another complication of IgG4RD (i.e. hypercalcemia) associated with elevated PTHrP levels.

Background:Gastrointestinal (GI) involvement is common in patients with SSc and may lead to weight loss and malnutrition. In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks, with mainly GI adverse events. The Malnutrition Universal Screening Tool (MUST) was developed to identify adults who are at risk of malnutrition and has been used in studies of patients with SSc.Objectives:To evaluate nutritional status over 52 weeks in the SENSCIS trial based on a modified MUST score.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients who had taken a stable dose of mycophenolate for ≥6 months were eligible to participate. Patients were randomised to receive nintedanib 150 mg bid or placebo. Dose reductions to 100 mg bid and treatment interruptions were allowed to manage adverse events and specific recommendations were provided for the management of diarrhoea. We calculated a modified MUST score at baseline and weeks 12, 24, 36 and 52 based on (A) BMI, (B) weight loss (week 12 vs baseline; week 24 vs week 12; week 36 vs week 24; week 52 vs week 36), and (C) a surrogate for acute disease effect (if the patient had any serious adverse event that led to hospitalisation between weight assessments and received ≥1 medication from the WHO classification code for “solutions for parenteral nutrition” for ≥5 days). MUST score at baseline was based solely on BMI. With scores ranging from 0 to 6, the risk of malnutrition is defined as low (score = 0), medium (score = 1) or high (score ≥2).Results:Among 576 patients who received nintedanib (n=288) or placebo (n=288), mean (SD) age at baseline was 54.0 (12.2) years, weight was 69.7 (15.9) kg and BMI was 25.9 (5.0) kg/m2; median time since onset of first non-Raynaud symptom was 3.4 years; and 75.2% of patients were female. In the nintedanib and placebo groups, respectively, MUST scores suggested that 74.0% and 78.1% of patients were at low risk of malnutrition at baseline and remained at low risk at their last measurement (Table 1). At weeks 12 and 52, respectively, mean (SD) MUST scores were 0.3 (0.6) and 0.4 (0.7) in the nintedanib group and 0.2 (0.5) and 0.2 (0.6) in the placebo group. At weeks 12, 24, 36 and 52, respectively, the proportions of patients at low risk of malnutrition were 81.8%, 80.9%, 72.9% and 76.5% in the nintedanib group and 86.6%, 86.4%, 88.3% and 80.8% in the placebo group; the proportions at medium risk were 12.1%, 13.1%, 18.0% and 13.5% in the nintedanib group and 8.5%, 8.6%, 5.8% and 13.1% in the placebo group; and the proportions of patients at high risk were 6.1%, 5.6%, 8.3% and 9.6% in the nintedanib group and 4.9%, 4.3%, 4.7% and 5.4% in the placebo group.Table 1.Risk of malnutrition at baseline and at last assessment over 52 weeks in the SENSCIS trial.Last assessment of riskNintedanib (n=288)Placebo (n=288)Baseline riskBaseline riskLowMediumHighTotalLowMediumHighTotalLow213 (74.0)1 (0.3)0214 (74.3)225 (78.1)7 (2.4)0232 (80.6)Medium31 (10.8)8 (2.8)039 (13.5)20 (6.9)14 (4.9)4 (1.4)38 (13.2)High13 (4.5)8 (2.8)7 (2.4)28 (9.7)3 (1.0)2 (0.7)10 (3.5)15 (5.2)Missing7 (2.4)007 (2.4)3 (1.0)003 (1.0)Total264 (91.7)17 (5.9)7 (2.4)288 (100)251 (87.2)23 (8.0)14 (4.9)288 (100)MUST score ranges from 0 to 6. Score of 0 = low risk: score of 1 = medium risk; score of ≥2 = high risk. Baseline MUST score was based solely on BMI.Conclusion:In the SENSCIS trial, scores based on a modified MUST indicated that most patients treated with nintedanib were at low risk of malnutrition at baseline and remained at low risk over 52 weeks. The proportions of patients at high risk of malnutrition were low but were numerically greater in patients who received nintedanib than placebo. Management of disease manifestations and gastrointestinal adverse events that may be associated with weight loss is important to reduce the risk of malnutrition in patients with SSc-ILD treated with nintedanib.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Zsuzsanna McMahan: None declared, Sindhu Johnson Consultant of: Boehringer Ingelheim, CSL Behring and Ikaria, Grant/research support from: Bayer, Boehringer Ingelheim, Corbus, GlaxoSmithKline, Merck and Roche, Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Research Foundation - Flanders (FWO) and Janssen, Stéphane Jouneau Speakers bureau: Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GlaxoSmithKline, LVL Mediphar, Mundipharma, Novartis, Pfizer, Roche and Sanofi, Consultant of: AIRB, Boehringer Ingelheim, Novartis and Roche, Grant/research support from: AIRB, Boehringer Ingelheim, LVL Mediphar, Novartis and Roche, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Ariane Herrick Speakers bureau: Janssen, Consultant of: Boehringer Ingelheim, Camurus, CSL Behring and Gesynta Pharma, Grant/research support from: Actelion and Gesynta Pharma

Background:Osteoporosis is one of the major comorbidities in patients with rheumatoid arthritis (RA). There are a lot of evidence that denosumab increase bone mineral density (BMD) in patients with osteoporosis. However, there are few reports investigated the influence of denosumab in patients with RA.Objectives:We evaluated the BMD change in patients with RA treated denosumab and assessed the effect of various factors, such as disease activity, biological disease-modifying anti-rheumatic drugs (bDMARDs) use, concomitant medications of osteoporosis and pretreatment of osteoporosis.Methods:This study included 140 consecutive RA patients (135 female, mean age was 70.6 ± 8.6 years) who fullfilled the criteria of osteoporosis and treated with denosumab. BMD at the lumbar spine, proximal femoral and femoral neck were evaluated by dual energy X-ray absorptiometry at baseline and one year after treatment. We evaluated the influence of disease activity, bDMARDs use, the concomitant type of vitamin D and pretreatment of osteoporosis for BMD change.Results:BMD change at the lumbar spine, proximal femoral and femoral neck were 5.9% (p<0.01), 4.0% (p<0.01), and 1.2% (p=0.36) durling one year. There were no differences in improvement ratio of BMD between each parameters (fig 1). Disease activity: 75 patients in remission or low disease activity and 65 patients in moderate or high disease activity were 6.4 vs 5.3% (p=0.91), 3.0 vs 5.1% (p=0.73), 2.0 vs 0.3% (p=0.1). bDMARDs: 45 patients with bDMARDs (anti-tumor necrosis factor inhibitors (TNF): 23, tocilizmab (TCZ): 13, abatacept (ABT): 7, Tofacitinib: 2) and 93 patients without bDMARDs were 6.0 vs 5.8% (p=0.31), 4.3 vs 4.1% (p=0.57), -0.2 vs 1.8% (p=0.18). Type of vitamin D: 47 patients taking active form vitamin D and 60 patients taking native form vitamin D were 5.5 vs 6.8% (p=0.82), 3.1 vs 3.8% (p=0.93), 0.4 vs 1.9% (p=0.14). Pretreatment of osteoporosis: 74 patients with pretreatment of osteoporosis (bisphosphonate:58, teriparatide:16) and 66 patients without pretreatment of osteoporosis were 6.9 vs 5.4% (p=0.41), 0.9 vs 4.0% (p=0.22), 2.0 vs 1.2% (p=0.68). Moreover, BMD change were not different in bDMARDs type, 5.0, 6.4, 0.5% in TNF group, 4.8, 0.7, -1.9% in TCZ group, 9.7, 4.9, 0.2% in ABT group (TNF vs TCZ: p=0.83, 0.98, 0.81, TNF vs ABT: p=0.83, 0.41, 0.97, TCZ vs ABT: p=0.98, 0.43, 0.9). There were no difference between bisphosphonate and teriparatide (6.2 vs 6.9%: p=0.49, 4.8 vs 0.9%: p=0.35, 0.9 vs 2.0%: p=0.49).Conclusion:Denosumab improved BMD in patients with RA independently regardless of disease activity, bDMARDs, the concomitant type of vitamin D and pretreatment of osteoporosis.References:[1]Y Nakamura et al, Arch Osteoporos: 2017; 12:80.[2]K Kaneko et al, Journal of Experimental Orthopaedics: 2019; 6:41.[3]T Suzuki et al, Therapeutics and Clinical Risk Management: 2018; 14:453–459.Acknowledgments:We wish to thank Atsuko Kamiyama, Tomoko Nakatsuka, Masato Uematsu and all participants in this study.Disclosure of Interests:Shohei Anno: None declared, Tadashi Okano Grant/research support from: AbbVie, Eisai, Mitsubishi Tanabe Pharma Corporation and Nipponkayaku, Speakers bureau: AbbVie, Asahikasei, Astellas Pharma Inc, Ayumi Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiich Sankyo, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Ono Pharmaceutical, Pfizer, Sanofi, Takeda Pharmaceutical, Teijin Pharma and UCB, Kentaro Inui Grant/research support from: Janssen Pharmaceutical K.K., Astellas Pharma Inc., Sanofi K.K., Abbvie GK, Takeda Pharmaceutical Co. Ltd., QOL RD Co. Ltd., Mitsubishi Tanabe Pharma, Ono Pharmaceutical Co. Ltd., Eisai Co.,Ltd.,, Speakers bureau: Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Takeda Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Abbvie GK, Pfizer Inc., Eisai Co.,Ltd., Chugai Pharmaceutical Co., Ltd., Tatsuya Koike Grant/research support from: AbbVie, Astellas Pharma Inc, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical, Pfizer, Roche, Takeda Pharmaceutical, Teijin Pharma, and UCB, Speakers bureau: AbbVie, Astellas Pharma Inc, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical, Pfizer, Roche, Takeda Pharmaceutical, Teijin Pharma, and UCB, Hiroaki Nakamura Grant/research support from: Astellas Pharma Inc. and Asahi Kasei Pharma Co.

Background: Concussion injuries are synonymous with vestibular impairments and symptoms include dizziness, impaired balance, and problems with gaze stability (Covassin et al., 2014). Common ocular motor impairments after a concussion include convergence/accommodative insufficiencies and saccadic dysfunction (Mucha et al., 2014). Vestibular and ocular motor impairments have been linked to worse outcomes following concussion (Pearce et al., 2015), including prolonged recovery (Corwin et al., 2015). The purpose of the current study was to determine which VOMS impairments were linked with longer recovery. Methods: Pediatric patients diagnosed with concussion (n = 131) presenting to an outpatient concussion clinic within 7 days from their initial date of injury were administered a standardized version of the VOMS. Patients were administered the VOMS by certified athletic trainers educated and trained on administration. The VOMS consists of nine measures and was validated by the University of Pittsburgh (Mucha et al., 2014) as a symptom provocation measure with a symptom rating of 0-10 with convergence measured in centimeters, and scores of 6 cm or greater being indicative of abnormal. Demographic, acute injury, and baseline values were summarized using descriptive statistics. Point estimates and 95% confidence intervals were calculated for all end points. Results: 131 patients with a mean age of 13.5 + 2.4 completed the VOMS within 7 days (mean = 3.2 + 1.7) of a diagnosed concussion. The sample was evenly divided by gender (52.7% male, 47.3% female). Patients were grouped by recovery time: <14 days (n = 19, 14.5%) 15-28 days (n = 64, 48.9%), and 29-120 days (n = 48, 36.6%). In the <14 day recovery group, 5.2% (n = 2) reported a history of concussion, 15.8% (n = 3) reported a history of migraine, and 5.2% (n = 2) reported a history of psychiatric diagnosis. In the 15-28 day recovery group, 21.9% (n = 14) reported a history of concussion, 9.4% (n = 6) reported a history of migraine, and 6.5% (n = 4) reported a history of psychiatric diagnosis. In the 29-120 day recovery group, 25% (n = 12) reported a history of concussion, 25% (n = 12) reported a history of migraine, and 6.25% (n = 3) reported a history of psychiatric diagnosis. Descriptive statistics for baseline VOMS symptoms were recorded for the <14 day recovery group; headache (mean = 1 + 1.49, CI = 0.7 -1.3), dizziness (mean = 0.2 + 0.5, CI = 0.1-0.3), nausea (mean = 0 + 0, CI = 0-0), and fogginess (mean = 0.9 + 1.5, CI = 0.5 -1.3), for the 15-28 day recovery group; headache (mean = 3.3 + 2.4, CI = 3-3.6), dizziness (mean = 1.5 + 1.9, CI = 1.3 -1.7), nausea (mean = 0.8 + 1.7, CI = 0.6 -1), and fogginess (mean = 1.7 + 2.2, CI = 1.4-2), for the 29-120 day recovery group; headache (mean = 4.4 + 2.2, CI = 4.1-4.7), dizziness (mean = 1.9 + 2.2, CI = 1.6-2.2), nausea (mean = 1.4 + 2.2, CI = 1.1 -1.7), and fogginess (mean = 2.4 + 2.9, CI = 2-2.8). VOMS convergence in centimeters across trials for the <14 day recovery group; T1 (mean = 2.6 + 2.4, CI = 2.1-3.1), T2 (mean = 3.4 + 2.4, CI = 2.9-3.9), and T3 (mean = 3.8 + 2.5, CI = 3.2-4.4), for the 15-29 day recovery group; T1 (mean = 3.9 + 3.9, CI = 3.4-4.4), T2 (mean = 4.8 + 4.2, CI = 4.3-5.3), and T3 (mean = 5.3 + 5.1, CI = 4.7-5.9), for the 29-120 day recovery group; T1 (mean = 6.9 + 5.2, CI = 6.1-7.7), T2 (mean = 8.3 + 1.8, CI = 7.4-9.2), and T3 (mean = 9.6 + 2.1, CI = 8.6-10.6). VOMS symptom provocation increase of +2 and +3 from baseline were totaled for each recovery group. Abnormal convergence greater than 6 cm on any trial was totaled for each group. Percentages for all 3 recovery groups with symptom provocation of +2, +3, and abnormal convergence were calculated. In the <14 day recovery group, 21% had a +2 symptom provocation on at least one symptom, 16% had a +3 symptom increase on at least one symptom, and 16% had abnormal convergence greater than 6 cm on at least one convergence trial. 11% of the <14 day recovery group had a +2, +3, increase and abnormal convergence greater than 6 cm. In the 15-29 day recovery group, 69% had a +2 symptom provocation on at least one symptom, 34% had a +3 symptom increase on at least one symptom, and 38% had abnormal convergence greater than 6 cm on at least one convergence trial. 13% of the 15-29 day recovery group had a +2, +3, increase and abnormal convergence greater than 6 cm. In the 29-120 day recovery group, 85% had a +2 symptom provocation on at least one symptom, 60% had a +3 symptom increase on at least one symptom, and 58% had abnormal convergence greater than 6 cm on at least one convergence trial. 38% of the 29-120 day recovery group had a +2, +3, increase and abnormal convergence greater than 6 cm. Conclusion: The current study identified symptom provocation of +2 and +3 as well as abnormal convergence greater than 6 cm were the most synonymous with recovery across the three recovery groups. Clinicians should consider these findings in providing recommendations and discussing anticipated recovery with patients. Further research is needed to determine more definitive parameters when predicting recovery following concussion.

Aims/Objectives/BackgroundGlobally, injuries cause more than 5 million deaths annually. Children and young people are a particularly vulnerable group and injuries are the leading cause of death in people aged 5–24 years globally and a leading cause of disability.In most low and middle-income countries where the majority of global child injury burden occurs, systems for routinely collecting injury data are limited. There is a continuing need for better data on childhood injuries and for injury surveillance.The aim of our study was to introduce a hospital-based injury surveillance tool – the first of its kind in Nepal and explore its feasibility. We undertook prospective collection of data on all injuries/trauma presenting to 2 hospital emergency departments to describe the epidemiology of paediatric hospital injury presentations and associated risk factors.Methods/DesignA new injury surveillance system for use in emergency departments in Nepal was designed and used to collect data on patients presenting with injuries. Data were collected prospectively in two hospitals 24 h a day over 12 months (April 2019 - March 2020) by trained data collectors using tablet computers.Abstract 432 Table 1Socio-demographic profile and characteristics of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020 (N=2696)CharacteristicsFrequencyGender Male 1778 Female 918 Age groups 0–4 years 653 5–9 years 866 10–14 years 680 15–17 years 497 Median year (IRQ) 8 (5 – 13) Ethnicity/caste Janajati 1384 Brahmin/Chhetri 892 Dalit 148 Madhesi 146 Muslim 74 Others 50 Unknown 2 Place where injury occurred Home/Compound 1576 Highway/road/street 636 School 233 Recreational area 138 Workplace 76 Other 37 Activities at the time injury occurred Leisure/Play 1889 Travelling (other than to/from school/work) 296 Work 202 Travelling (to/from school/work) 184 Education 42 Organised sports 11 Other 52 Unknown 20 Intent of injury Unintentional 2560 Intentional (self-harm) 61 Intentional (assault) 75 Unintentional (n=2560) Fall 912 Animal or insect related 728 Road traffic injury 356 Injured by a blunt force 201 Stabbed, cut or pierced 176 Fire, burn or scald 65 Poisoning 52 Suffocation/choking 36 Electrocution 12 Drowning and submersion 7 Other 13 Unknown 2 Self-harm (n=61) Poisoning 38 Hanging, strangulation, suffocation 12 Stabbed, cut or pierced 6 Injured by blunt object 4 Other 1 Assault (n=75) Bodily force (physical violence) 43 Injured by blunt object 18 Stabbed, cut or pierced 8 Pushing from a high place 2 Poisoning 2 Sexual assault 1 Other 1 Nature of injury (one most severe) Cuts, bites or open wound 1378 Bruise or superficial injury 383 Fracture 299 Sprain, strain or dislocation 243 Internal injury 124 Head Injury/Concussion 83 Burns 67 Other 115 Unknown 2 Not recorded 2 Severity of injury No apparent injury 125 Minor 1645 Moderate 813 Severe 111 Not recorded 2 Disposition Discharged 2317 Admitted to hospital 164 Transferred to another hospital 179 Died 21 Leave Against Medical Advice (LAMA) 11 Unknown 2 Not recorded 2 Note:Not recorded = missing cases95% CI calculated using one proportion test and normal approximation method in Minitab.Abstract 432 Table 2Distribution of injuries by age-group, sex and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups & Sex0 - 4 years5 - 9 years10–14 years15–17 yearsMaleFemaleTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 239 (26.2) 328 (36.0) 249 (27.3) 96 (10.5) 636 (69.7) 276 (30.3) 912 (100) Animal or insect related 175 (24.0) 260 (35.7) 190 (26.1) 103 (14.1) 470 (64.6) 258 (35.4) 728 (100) Road traffic injury 49 (13.8) 108 (30.3) 86 (24.2) 113 (31.7) 223 (62.6) 133 (37.4) 356 (100) Injured by a blunt force 54 (26.9) 74 (36.8) 49 (24.4) 24 (11.9) 150 (74.6) 51 (25.4) 201 (100) Stabbed, cut or pierced 20 (11.4) 56 (31.8) 49 (27.8) 51 (29.0) 127 (72.2) 49 (27.8) 176 (100) Fire, burn or scald 42 (64.6) 10 (15.4) 9 (13.8) 4 (6.2) 27 (41.5) 38 (58.5) 65 (100) Poisoning 33 (63.5) 6 (11.5) 5 (9.6) 8 (15.4) 26 (50.0) 26 (50.0) 52 (100) Suffocation/choking 24 (66.7) 5 (13.9) 2 (5.6) 5 (13.9) 20 (55.6) 16 (44.4) 36 (100) Electrocution 2 (15.7) 0 (0.0) 3 (25.0) 7 (58.3) 10 (83.3) 2 (16.7) 12 (100) Drowning and submersion 1 (14.3) 1 (14.3) 3 (42.9) 2 (28.6) 3 (42.9) 4 (57.1) 7 (100) Other 6 (46.2) 4 (30.8) 3 (23.1) 0 (0.0) 10 (76.9) 3 (23.1) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) 2 (100) Total 647 (25.3) 852 (33.3) 648 (25.3) 413 (16.1) 1702 (66.5) 858 (33.5) 2560 (100) Self-harm Poisoning 0 (0.0) 0 (0.0) 6 (15.8) 32 (84.2) 7 (18.4) 31 (81.6) 38 (100) Hanging 0 (0.0) 0 (0.0) 3 (25.0) 9 (75.0) 4 (33.3) 8 (66.7) 12 (100) Stabbed, cut or pierced 0 (0.0) 0 (0.0) 2 (33.3) 4 (66.7) 1 (16.7) 5 (83.3) 6 (100) Injured by blunt object 0 (0.0) 2 (50.0) 2 (50.0) 0 (0.0) 4 (100) 0 (0.0) 4 (100) Other 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) 0 (0.0) 1 (100) Total 0 (0.0) 2 (3.3) 13 (21.3) 46 (75.4) 17 (27.9) 44 (72.1) 61 (100) Assault Bodily force (physical violence) 3 (7.0) 1 (2.3) 11 (25.6) 28 (65.1) 37 (86.0) 6 (14.0) 43 (100) Injured by blunt object 2 (11.1) 8 (44.4) 4 (22.2) 4 (22.2) 13 (72.2) 5 (27.8) 18 (100) Stabbed, cut or pierced 1 (12.5) 0 (0.0) 2 (25.0) 5 (62.5) 7 (87.5) 1 (12.5) 8 (100) Pushing from a high place 0 (0.0) 1 (50.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 2 (100) Poisoning 0 (0.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 1 (50.0) 2 (100) Sexual assault 0 (0.0) 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Other 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Total 6 (8.0) 12 (16.0) 19 (25.3) 38 (50.7) 59 (78.7) 16 (21.3) 75 (100) Abstract 432 Table 3Association of injury location, nature and severity with age among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups0 – 4 years5 – 9 years10–14 years15–17 yearsTotalChi-SquareInjury characteristicsn (%)n (%)n (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 537 (34.1) 504 (32.0) 319 (20.2) 216 (13.7) 1576 (100) <0.001 Highway/road/street 85 (13.4) 196 (30.8) 190 (29.9) 165 (25.9) 636 (100) School 15 (6.4) 107 (45.9) 85 (36.5) 26 (11.2) 233 (100) Recreational area 9 (6.5) 44 (31.9) 55 (39.9) 30 (21.7) 138 (100) Workplace 1 (1.3) 4 (5.3) 19 (25.0) 52 (68.4) 76 (100) Other 6 (16.2) 11 (29.7) 12 (32.4) 8 (21.6) 37 (100) Total 653 (24.2) 866 (32.1) 680 (25.2) 497 (18.4) 2696 (100) Nature of injury Cuts, bites or open wound 328 (23.8) 506 (36.7) 314 (22.8) 230 (16.7) 1378 (100) <0.001 Bruise or superficial injury 81 (21.1) 99 (25.8) 118 (30.8) 85 (22.2) 383 (100) Fracture 48 (16.1) 101 (33.8) 112 (37.5) 38 (12.7) 299 (100) Sprain, strain or dislocation 48 (19.8) 78 (32.1) 72 (29.6) 45 (18.5) 243 (100) Internal injury 44 (35.5) 8 (6.5) 18 (14.5) 54 (43.5) 124 (100) Head Injury/Concussion 18 (21.7) 26 (31.3) 18 (21.7) 21 (25.3) 83 (100) Burns 42 (62.7) 9 (13.4) 10 (14.9) 6 (9.0) 67 (100) Other 41 (35.7) 38 (33.0) 18 (15.7) 18 (15.7) 115 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Severity of injury No apparent injury 39 (31.2) 45 (36.0) 26 (20.8) 15 (12.0) 125 (100) <0.001 Minor 419 (25.5) 535 (32.5) 406 (24.7) 285 (17.3) 1645 (100) Moderate 171 (21.0) 262 (32.2) 225 (27.7) 155 (19.1) 813 (100) Severe 23 (20.7) 23 (20.7) 23 (20.7) 42 (37.8) 111 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Abstract 432 Table 4Association of injury location, nature and severity with sex among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020SexMaleFemaleTotalChi-SquareInjury characteristicsn (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 979 (62.1) 597 (37.9) 1576 (100) <0.001 Highway/road/street 421 (66.2) 215 (33.8) 636 (100) School 176 (75.5) 57 (24.5) 233 (100) Recreational area 111 (80.4) 27 (19.6) 138 (100) Workplace 62 (81.6) 14 (18.4) 76 (100) Other 29 (78.4) 8 (21.6) 37 (100) Total 1778 (65.9) 918 (34.1) 2696 (100) Nature of injury Cuts, bites or open wound 959 (69.6) 419 (30.4) 1378 (100) <0.001 Bruise or superficial injury 246 (64.2) 137 (35.8) 383 (100) Fracture 200 (66.9) 99 (33.1) 299 (100) Sprain, strain or dislocation 154 (63.4) 89 (36.6) 243 (100) Internal injury 50 (40.3) 74 (59.7) 124 (100) Head Injury/Concussion 59 (71.1) 24 (28.9) 83 (100) Burns 27 (40.3) 40 (59.7) 67 (100) Other 79 (68.7) 36 (31.3) 115 (100) Unknown 2 (100) 0 (0.0) 2 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Severity of injury No apparent injury 81 (64.8) 44 (35.2) 125 (100) 0.048 Minor 1102 (67.0) 543 (33.0) 1645 (100) Moderate 533 (65.6) 280 (34.4) 813 (100) Severe 60 (54.1) 51 (45.9) 111 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Abstract 432 Table 5Distribution of injuries by outcome and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Outcome of injuryDischargedAdmittedTransferredDiedLAMAUnknownTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 787 (86.5) 65 (7.1) 53 (5.8) 0 (0.0) 4 (0.4) 1 (0.1) 910 (100) Animal/insect bite/sting 704 (96.7) 3 (0.4) 19 (2.6) 0 (0.0) 1 (0.1) 1 (0.1) 728 (100) Road traffic injury 260 (73.0) 47 (13.2) 44 (12.4) 5 (1.4) 0 (0.0) 0 (0.0) 356 (100) Injured by a blunt force 190 (94.5) 4 (2.0) 6 (3.0) 0 (0.0) 1 (0.5) 0 (0.0) 201 (100) Stabbed, cut or pierced 165 (93.8) 8 (4.5) 3 (1.7) 0 (0.0) 0 (0.0) 0 (0.0) 176 (100) Fire, burn or scald 52 (80.0) 12 (18.5) 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) 65 (100) Poisoning 30 (57.7) 4 (7.7) 16 (30.8) 1 (1.9) 1 (1.9) 0 (0.0) 52 (100) Suffocation/choking/asphyxia 24 (66.7) 4 (11.1) 6 (16.7) 1 (2.8) 1 (2.8) 0 (0.0) 36 (100) Electrocution 7 (58.3) 2 (16.7) 2 (16.7) 1 (8.3) 0 (0.0) 0 (0.0) 12 (100) Drowning and submersion 4 (57.1) 0 (0.0) 0 (0.0) 3 (42.9) 0 (0.0) 0 (0.0) 7 (100) Other 12 (92.3) 1 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 2237 (87.5) 150 (5.9) 150 (5.9) 11 (0.4) 8 (0.3) 2 (0.1) 2558 (100) Self-harm Poisoning 5 (13.2) 8 (21.1) 23 (60.5) 0 (0.0) 2 (5.3) 0 (0.0) 38 (100) Hanging 1 (8.3) 0 (0.0) 1 (8.3) 10 (83.3) 0 (0.0) 0 (0.0) 12 (100) Stabbed, cut or pierced 6 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 6 (100) Injured by blunt object 4 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 17 (27.9) 8 (13.1) 24 (39.3) 10 (16.4) 2 (3.3) 0 (0.0) 61 (100) Assault Bodily force (physical violence) 34 (79.1) 5 (11.6) 3 (7.0) 0 (0.0) 1 (2.3) 0 (0.0) 43 (100) Injured by blunt object 18 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 18 (100) Stabbed, cut or pierced 6 (75.0) 1 (12.5) 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 8 (100) Pushing from a high place 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Poisoning 1 (50) 0 (0.0) 1 (50.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Sexual assault 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 63 (84.0) 6 (8.0) 5 (6.7) 0 (0.0) 1 (1.3) 0 (0.0) 75 (100) Abstract 432 Figure 1Seasonal variation of injuries identified by the injury surveillance system over a year among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Results/ConclusionsThe total number of ED patients with injury in the study was 10,154.2,696 were patients aged <18 years. Most injuries in children were unintentional and over half of children presenting with injuries were <10 years of age. Falls, animal bites/stings and road traffic injuries accounted for nearly 75% of all injuries with some (drowning, poisonings and burns) under-represented. Over half of injuries were cuts, bites and open wounds. The next most common injury types were superficial injuries (14.2%); fractures (11.1%); sprains/dislocations (9.0%). Child mortality was 1%.This is the biggest prospective injury surveillance study in a low or middle country in recent years and supports the use of injury surveillance in Nepal for reducing child morbidity and mortality through improved data.CHILD PAPER: RESULTS SECTIONTotal number of ED patients: 33046Total number of ED patient with injury: 10154 (adult=7458 & children=2696)8.2% (n=2696) patients with injury were children aged <18 yearsHetauda hospital: 2274 (84.3%)Chure hill hospital: 422 (15.7%)

Abstract Abstract 3785 Bosutinib (BOS) is an orally active, dual Src/Abl tyrosine kinase inhibitor (TKI). This open-label, phase 1/2 study evaluated BOS in patients (pts) with chronic phase chronic myeloid leukemia (CP CML) following TKI failure. A total of 119 pts aged ≥18 y with prior imatinib (IM) failure plus dasatinib (DAS) resistance (n = 38), DAS intolerance (n = 50), nilotinib (NIL) resistance (n = 27), NIL intolerance (n = 1), or failure of DAS and NIL (n = 3) received BOS starting at 500 mg/d. Median age was 56 y (range, 20–79 y); 45% of pts were male; median time from CML diagnosis was 6.5 y (range, 0.6–18.3 y). Median BOS duration was 8.6 mo (range, 0.2–60.8 mo); 24% of pts are still on treatment. Dose escalation to BOS 600 mg/d occurred in 19% of pts. Time from last pt's first dose to data cutoff was 25 mo (median follow-up duration of 31.4 mo [range, 0.3–66.0 mo]). A confirmed complete hematologic response (CHR) was attained/maintained by 73% of evaluable pts (Table). The Kaplan-Meier (KM) probability of maintaining a CHR at 2 y was 67%. A major cytogenetic response (MCyR) was attained/maintained by 41%, including 32% with a complete cytogenetic response (CCyR). Among evaluable pts without a baseline CCyR, 36% (n = 37/102) achieved a MCyR, including 28 (28%) with a CCyR. The KM probability of maintaining a MCyR at 2 y was 71%. Of 86 pts with baseline mutation status, 40 (47%) pts had 19 unique Bcr-Abl kinase domain mutations, including 7 (8%) pts with T315I. Responses were seen across mutations (75% CHR, 43% MCyR excluding T315I), including those conferring resistance to other TKIs; responses in pts with T315I were low (29% CHR; 14% MCyR). Nine of 37 pts evaluated at baseline and treatment discontinuation had ≥1 new mutation (V299L, n = 4; L248V, n = 2; T315I, n = 2; F359C, n = 1; G250E, n = 1); 8 of 9 pts had discontinued BOS due to disease progression or lack of efficacy. On-treatment transformation to accelerated phase CML occurred in 5 (4%) pts after 16 to 428 d on study; no pt transformed to blast phase CML. KM-estimated on-treatment progression-free survival (PFS) at 2 y was 75%; KM-estimated overall survival (OS) at 2 y was 84% (Table). There were 23 (19%) deaths on study, with 6 deaths occurring ≤30 d after the last BOS dose. Most deaths were due to disease progression (n = 10 [8%]) or an adverse event (AE; n = 10 [8%]; including 1 treatment-related death due to gastrointestinal bleeding). Three deaths were due to unknown cause ≥509 d after the last BOS dose. Non-hematologic treatment-emergent AEs (TEAEs) seen in ≥20% of pts (all grades; grade 3/4) included diarrhea (82%; 8%), nausea (49%; 1%), vomiting (40%; 1%), rash (27%; 3%), headache (26%; 3%), fatigue (24%; 1%), and abdominal pain (20%; 1%). The incidence of individual TEAEs was generally similar across groups regardless of prior TKI exposure. Diarrhea TEAEs were predominantly grade 1/2, first reported early during treatment (median time to first event of 1.5 d [range, 1–210 d]), and transient (median event duration of 2 d [range, 1–524 d]). The incidence of pleural effusion was highest among DAS-intolerant pts (n = 11 [22%], including 3 pts with grade 3 events); for 9 of 11 pts pleural effusion had been indicated as a reason for intolerance to prior DAS. Grade 3/4 laboratory abnormalities reported in ≥10% of pts included thrombocytopenia (25%), neutropenia (19%), lymphopenia (17%), and hypermagnesemia (12%). Dose reductions and interruptions were used to manage AEs in 50% and 66% of pts. A total of 32 (27%) pts discontinued treatment due to an AE, most commonly hematologic events. In conclusion, BOS therapy continues to demonstrate durable efficacy and manageable toxicity after follow-up of ≥24 mo in CP CML following resistance or intolerance to multiple TKIs, with a majority of pts maintaining response at 2 y and few new transformations, deaths, TEAEs, or discontinuations due to AEs since the prior report ∼1 y earlier (Blood 2012;119:4303–12). n (%) IM + DAS-R IM + DAS-I IM + NIL-R IM + DAS ± NILa Total Evaluableb 37 49 25 4 115 CHR 23 (62) 39 (80) 19 (76) 3 (75) 84 (73) Evaluableb 36 44 26 4 110 MCyR 12 (33) 21 (48) 10 (39) 2 (50) 45 (41) CCyR 7 (19) 19 (43) 7 (27) 2 (50) 35 (32) Treated 38 50 27 4 119 PFS at 2 yc 70% 81% 79% 38% 75% OS at 2 yc 77% 85% 92% 75% 84% R, resistant; I, intolerant. a Includes 3 pts with prior exposure to all 3 TKIs and 1 NIL-I pt. KM rates may be unreliable due to the small number of pts in this cohort. b Received ≥1 dose of BOS and had a valid baseline response assessment. c Based on KM estimates Disclosures: Gambacorti-Passerini: Pfizer Inc: Consultancy, Research Funding; Novartis, Bristol Myer Squibb: Consultancy. Kantarjian:Pfizer: Research Funding. Kim:BMS, Novartis, Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Marin:Novartis: Research Funding; BMS: Research Funding. Dorlhiac-Llacer:Novartis, Bristol Myer Squibb, Pfizer: Research Funding. Bullorsky:Novartis, BMS: Consultancy, Speakers Bureau. Leip:Pfizer Inc: Employment. Kelly:Pfizer Inc: Employment, Equity Ownership. Turnbull:Pfizer Inc, l3/Inventiv Clinical Solutions: Employment. Besson:Pfizer Inc: Employment. Cortes:Novartis, Bristol Myers Squibb, Pfizer, Ariad, Chemgenex: Consultancy, Research Funding.

Abstract Abstract 811 Background: High-dose therapy and autologous hematopoietic stem cell transplantation (ASCT) is the standard of care for many patients (pts) with high-risk or relapsed B-cell non-Hodgkin lymphoma (B-NHL). Despite the use of transplant, relapse is likely for most with indolent or mantle cell lymphoma (MCL) as well as for aggressive B-NHL recurring after rituximab (R)-based chemotherapy. Total body irradiation (TBI) has been incorporated into ASCT regimens to overcome chemotherapy resistance and improve outcomes, but studies to date indicate that escalation of TBI is not feasible due to toxicity in non-target organs. We hypothesized that radioimmunotherapy (RIT) could supplant TBI and identified the maximally tolerated dose (MTD) of high-dose RIT using I-131-tositumomab that could be safely combined with high-dose etoposide (VP-16) and cyclophosphamide (CY) prior to ASCT (Press, Blood 2000). We now present the mature data of a large prospective phase II trial at the MTD of high-dose I-131-tositumomab, VP-16, and CY. Methods: Pts were eligible if they were <60 years of age, had MCL in first remission or any relapsed/refractory B-NHL, an ECOG PS of 0–1, acceptable organ function, >2×106 autologous CD34+ peripheral blood stem cells/kg collected, <20 Gy prior radiation to critical organs, and no human-anti-mouse-antibodies. All pts underwent outpatient biodistribution studies using tositumomab (1.7 mg/kg, n= 64 or 485mg flat dose, n= 43) labeled with ∼10mCi I-131 followed by serial quantitative gamma camera imaging to calculate individualized organ-specific absorbed dose estimates. Pts then received therapeutic infusions of I-131-tositumomab to deliver 25Gy to the critical normal organ receiving the highest radiation absorbed dose. When residual radiation was <7mR/hr at 1m (median 10 days) pts received 60mg/kg VP-16 followed 48 hours later by 100mg/kg CY. ASCT occurred when residual radiation was <2mR/hr at 1m. Toxicity was scored on the Bearman transplant scale and CTCAE 2.0. Response followed standard criteria. Results: Between June 1999 and April 2011 107 pts were transplanted on this protocol. Baseline characteristics included: median age 52 yrs (range 32–60), stage III/IV = 104 (97%), median number of prior regimens = 3 (range 1–11), prior R = 98 (92%), R refractory = 35 (33%), chemoresistant disease (defined as < a partial response [PR] to the most recent regimen) = 41 (40%), >1 extranodal site = 36 (33%), elevated LDH = 46 (42%). Histological strata: Indolent 43% (45 follicular lymphoma [FL], 1 lymphoplasmacytic lymphoma), MCL = 31%, Aggressive 27% (27 diffuse large B-cell including 12 with transformed disease, 2 Burkitt's). Dose limiting critical normal organs receiving up to 25Gy included lung (71), liver (29), kidney (6), and heart (1) from a median administered I-131 activity of 557 mCi (range 231–1353) resulting in a median whole body dose of 4.4Gy. ASCT occurred an average of 14 days after the I-131-tositumomab infusion with a median of 5.9×106 CD34/kg (range 2–20×106 CD34/kg). An unsupported ANC>500/μL and platelets >20K/μL occurred at a median of day 12 and day 13, respectively. Bearman toxicity of grade III/IV was observed in 6 pts (5.6%) with 3 (3%) non-relapse deaths (all cardiopulmonary toxicity) by day 100. Pulmonary toxicity of ≥ grade 4 CTCAE occurred in 10 (9%) pts. Responses to therapy included: CR/CRu = 87 (81%), PR = 8 (7%), SD = 11 (10%), and PD = 1 (1%). Currently, 76 (71%) pts are alive with 59 (55%) progression-free. The estimated 5-year overall survival (OS), progression-free survival (PFS) and relapse were 72%, 56%, and 36%, respectively (figure, median follow up of 5.2 years). Five-year OS/PFS estimates for the 3 histological groups included indolent (81%/61%), aggressive (69%/51%), and MCL (57%/52%). MCL pts with relapsed/refractory disease had a 5-year OS/PFS of 55%/42%. Multivariable analysis only identified chemoresistant disease as associated with death (HR 3.07 (1.46–6.44, p=.003) and relapse or death (HR 2.12 (1.17–3.86, p=.01). Secondary AML/MDS occurred in 1 patient to-date. Conclusions: This largest prospective trial of myeloablative RIT demonstrates that I-131-tositumomab delivering 225Gy to critical organs along with high-dose VP-16 and CY prior to ASCT is feasible and effective with toxicities comparable to TBI-based regimens. These data provide the foundation for future approaches incorporating RIT into transplant conditioning regimens for lymphoma. Disclosures: Gopal: GSK: Research Funding; Spectrum: Research Funding. Off Label Use: high-dose use of I-131-tositumomab. Rajendran:GSK: Research Funding. Pagel:GSK: Research Funding. Maloney:GSK: Research Funding. Press:GSK: Research Funding.

В работе предложена модель формирования морфологии тетраподов ZnO,основанная на описании процесса полиморфного перехода от октаэдрических кластеровс кристаллической структурой сфалерита B3 к четырем стрежневым кристаллам со струк-турой вюрцита B4 как разрыва топологического пространства роста на наномасштабе. Примоделировании предкристаллизационного этапа формирования тетраподов в условияхдинамического хаоса частиц методом системы итерированных функций используютсяпараметры отображений, задающих ориентацию топологических пространств роста крис-таллических элементов иерархической структуры тетрапода ЛИТЕРАТУРА1. Tsuneta T., Tanda S. Formation and growth of NbSe3 topological crystals // Journal of Crystal Growth,2004, v. 264(1−3), pp. 223-231. DOI: https://doi.org/10.1016/j.jcrysgro.2003.12.0202. Liu Y., Chen Z., Kang Z., Bello I., Fan X., Ismathullakhan Shafi q, Zhang W., Lee S.-T. 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Abstract Introduction: Aberrant DNA methylation occurs frequently in hematologic malignancies and is associated with altered gene expression. Consequently, DNA hypomethylating agents (HMAs), e.g. 5-aza-2'-deoxycytidine (DAC), have been tested for in vivo demethylation and have become accepted as first-line treatment of older MDS and AML patients (pts). While HMAs are already routinely used for the treatment of MDS and AML, only very few outcome predictors have been established thus far. Expression of the β-like globin gene locus is tightly regulated by methylation, is HMA-sensitive in vitro, and fetal hemoglobin (HbF) expression is under study as a potential biomarker for response of MDS pts to 5-azacytidine. Here, we present the first study of serial HbF measurements in MDS and AML pts receiving DAC in order to investigate a potential clinical application of HbF as a predictor of outcome to this treatment. Methods: 16 MDS and 36 AML pts enrolled on two clinical trials, the 06011 EORTC-GMDSSG phase III trial of higher-risk MDS, and the 00331 phase II trial of older, non-fit AML pts (Lübbert M et al., Haematologica 2012), were treated with DAC. MDS pts received nine 4-hour infusions of 15 mg/m2 given over 72 hours, repeated every 6 weeks for a minimum of four courses. AML pts were treated with nine 3-hour infusions of 15 mg/m2 given over 72 hours, repeated every 6 weeks for four courses followed by maintenance treatment with DAC at 20 mg/m2 when responding (defined by CR, PR or an antileukemic effect). HbF levels were measured in peripheral blood by HPLC before treatment and sequentially, i. e. after the end of each treatment course (every 6 weeks). HbF levels >1% of total hemoglobin were considered elevated. Results: Baseline HbF was elevated (>1.0%) in 7/16 MDS and 12/36 AML pts. Clinical baseline characteristics were uniformly distributed between pts with normal and elevated HbF levels. HbF induction was observed in 81% of MDS pts after a median of 2 (range 2-6) courses of DAC and in 54% of AML pts after a median of 3 (2-11) courses. Four AML pts receiving standard cytarabine-based induction chemotherapy and four pts with pancreatic cancer receiving gemcitabine-based treatment did not show HbF induction to >1%. When analyzing clinical survival endpoints, elevated baseline HbF was associated with longer median overall survival (OS) for MDS: 26.6 vs. 8.6 months (HR 8.56, 95% CI 1.74-42.49, p=0.008). Similarly, median PFS and AMLFS was prolonged in "HbF high" MDS pts with 15.4 compared to 5.9 months (p=0.016) and 26.3 compared to 8.8 months (p=0.03), respectively. A statistically non-significant trend towards higher HbF baseline values (median 1.5%, range 0.3% to 3.9%) in MDS pts achieving a CR, PR or hematological improvement compared to non-responders (median baseline 0.4%, range 0.1% - 1.9%) was noted. Likewise, OS for AML pts with elevated pre-treatment HbF was prolonged with 10.0 vs. 2.9 months OS (HR 3.01, 95% CI 1.26-7.22, p=0.014). HbF baseline values were comparable in the group that did achieve any response (CR, PR, antileukemic effect) vs. the non-responding group. In a multivariate analysis including LDH and age, the predictive value of HbF was retained. Time-dependent Cox models revealed that the predictive value of treatment-induced HbF induction was markedly inferior to that of baseline HbF. Conclusion: We provide first evidence for in vivo induction of HbF by DAC in MDS and AML pts. Notably, HbF values elevated already prior to treatment harbor highly significant predictive value for survival benefit upon DAC whereas HbF induction is inferior to a stronger effect of pre-treatment HbF. Our findings warrant incorporation of HbF as potential predictive biomarker in larger prospective studies. Disclosures Claus: Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria, Other: Travel Funding. Becker:BMS: Honoraria; Novartis: Honoraria. Lübbert:Ratiopharm: Other: Study drug valproic acid; Janssen-Cilag: Other: Travel Funding, Research Funding; Celgene: Other: Travel Funding.

Background:The importance of presarcopenia (low lean mass) in clinical practice is accompanied by a high risk of adverse effects such as early disability, reduced quality of life, and increased mortality.Objectives:The aim of the study was to assess the link between bone mineral density (BMD) and the state of the muscular system in adult patients with juvenile idiopathic arthritis (JIA).Methods:The study was performed in Oleksandrivska Clinical Hospital of Kyiv, Ukraine, where adult patients were transferred from pediatric rheumatologists. Inclusion criteria: patients aged 18-44 years at the time of signing the informed consent; diagnosis of JIA in childhood, verified according to ILAR criteria, duration of JIA >3 years. According to the European Working Group on Sarcopenia in the Elderly (EWGSOP) 2019, patients with a decrease in muscle mass alone were diagnosed with presarcopenia. The BMD and muscle tissue were determined in standard localizations using dual X-ray absorptiometry (DXA).Results:The study included 26 adult patients with JIA, including 10 male patients and 16 female patients. The mean age at the time of examination was 22.3 ± 8.15 years; the mean age at the onset of the disease was 9.04 ± 4.9 years. According to the ILAR classification, patients had the following variants of JIA: 3 patients with RF-negative polyarticular variant, 8 patients with persistent oligoarthritis, 4 patients with extended oligoarthritis, 6 patients with RF-positive polyarthritis variant, and 5 patients with systemic JIA. According to the EWGSOP, 2019 reduced muscle mass was calculated by skeletal muscle index (SMI); the cut-off points were considered by SMI <7 kg/m2 for male, <6 kg/m2 for female. Patients were divided into two groups depending on the presence or absence of presarcopenia. The first group (1-st group) included 16 patients with reduced muscle mass (SMI – 5,22± 0,72 kg/m2), and the second group (2-nd group) included 10 patients without reduced muscle mass (SMI – 8,05± 0,94 kg/m2). It was found that the height and weight of patients in the group of presarcopenia was lower than in the group without a low lean mass (height 1,6±0,07 m vs 1,7±0,09 m, t=-2,53; p=0,01; weight 55,06±8,3 kg, 70,0±10,8 kg, t=-3,9; p=0,0007, respectively). The age of patients (25,3±10,1 and 21,3±5,9 years for 1-st and 2-nd groups respectively) and the duration of the disease (17,1±9,5 and 10,3±6,1 for 1-st and 2-nd groups respectively) did not differ statistically between the groups. The age of the onset of JIA in both groups also did not differ (7,8±4,5 and 11,5±4,1 for the 1-st and 2-nd group respectively). The following data were obtained by DXA. The patients of 1-st group had statistically reduced BMD in the region of femoral neck - 0,927±0,15 g/cm2 vs 1,179±0,13 g/cm2, t=-3,18; p=0,006; total hip - 0,977±0,16 g/cm2 vs 1,184±0,05 g/cm2, t=-3,05, p=0,0080; total body - 1,080±0,1 g/cm2 vs 1,193±0,15 g/cm2, t=-2,19; p=0,03; and ultra-distal radius - 0,286±0,06 g/cm2 vs 0,482±0,11 g/cm2, t=-3,60; p=0,007. The BMD in the region of lumbar spine did not differ in two groups - 1,152±0,16 g/cm2 vs 1,137±0,17 g/cm2, t=0,21; p=0,8. In the group of presarcopenia there was a visible decrease in the level of the metabolite of vitamin 25(OH)D3, but not statistically significant: 15,5±7,3 nmol/l vs 19,7±8,6 nmol/l, t =1,0; p=0,3. The study has strengths such as first described presarcopenia in young adults with JIA and potential limitations such as mono-center study and a small number of patients.Conclusion:The BMD in the region of total hip, femoral neck, ultra-distal radius, and total body in patients with decreased muscle mass was significantly lower than in patients without low lean mass.References:[1]Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis [published correction appears in Age Ageing. 2019 Jul 1;48(4):601]. Age Ageing. 2019;48(1):16-31Disclosure of Interests:None declared

Abstract Background: Multiple myeloma (MM) and plasma cell dyscrasias (PCD) are associated with increased risk of venous thromboembolism (VTE) which is further enhanced by treatments with immunomodulatory agents, melphalan or steroids. The optimization of VTE prevention in patients with MM is an unmet need. According to Virchow's triad, blood hypercoagulabilty is one of the three conditions required for thrombosis. Elaboration of a risk assessment model, which includes biomarkers of hypercoagulability, could lead to better identification of MM patients eligible for pharmacological thromboprophylaxis. Aims: We conducted a longitudinal observational study, to explore the relationship of MM with cellular and plasma hypercoagulability aiming to identify the most relevant biomarkers which could be used in the RAM for VTE. Materials and Methods: Newly diagnosed patients (n=72) with PCD were recruited from July 2014 to May 2015. The control group (CG) was consisted of 30 healthy age and sex-matched individuals. A systematic compression ultrasound was performed at baseline and 6 months post-therapy. Blood samples were obtained at time of diagnosis and at 3-6 months post therapy. Samples of platelet poor plasma were assessed for thrombin generation (TG) with the PPP-Reagent® (5pMTF and 4μM phospholipids), P-selectin, D-dimers (D-Di), activated FVII (FVIIa), Tissue Factor (TFa), fibrin monomers (FM), and procoagulant phospholipid dependent clotting time (PPL-ct). The upper and lower normal limits (UNL and LNL) were calculated by the mean±2sd. We present herein the data obtained at the inclusion of the patients. Results: Forty-three patients had MM, 16 had asymptomatic MM (AMM), 13 had MGUS. The median age was 68 years (40-84 years); 44% of patients were males. The median time to follow up was 6 months (range: 2-12 months). Patients with PCD as compared to the CG had significantly shorter PPL-ct, which it has been shown that it is inversely correlated with the concentration of platelet derived procoagulant microparticles. PCD patients had also lower Endogenous thrombin potential (ETP), shorter time to thrombin Peak (ttPeak) and lower mean rate index (MRI) of the propagation phase of TG as compared to the controls. The levels of P-selectin were not significantly different between the two groups. Patients with MM as compared to MGUS and AMM patients had significantly higher levels of TFa, FVIIa, FM, D-Di, Peak and MRI (Table 1). Among MM patients 72% had PPL-ct below the LNL, 62% and 28% had TFa and FM above the UNL respectively, 4% had MRI above the UNL and 29% had MRI below the LNL. Among patients who received therapy, 46% also received thromboprophylaxis with either aspirin (76%, n=22) or LMWH (24%, n=5); all were MM patients who received IMiD-based therapies. During the follow-up period the rate of VTE events in MM patients was 7% (all MM patients under treatment). Conclusion: In patients with PCD increased procoagulant microparticles of cellular origin is a generalized phenomenon. In addition, patients with MM present significant TF pathway activation and increased in vivo TG. A significant part, but not all of the patients present strong signs of plasma hypercoagulability. The finding of high inter-individual variability of TG underlines the heterogeneity of blood coagulation alterations in MM patients. The data of the prospective part of this study will allow to validate the clinical significance of this finding. Table 1. Biomarkers of plasma and cellular hypercoagulablity in newly diagnosed patients with PCD. ETP: endogenous thrombin potential; MRI: mean rate index of the propagation phase of thrombin generation. FM: fibrin monomers Parameters Controls (n=30) MGUS (n=13) AMM (n=16) MM (n=43) PPL (sec) 62.8±8.6 38.1±8.2* 41.3±6.8* 39.9±13.7* P-Selectin (pg/ml) 62660±10390 35127±12462 29697.7±9090.45 36223±13638 FTa (ng/ml) 0.3±0.1 2.1±1.4* 1.9±1.3* 7.5±23.3*$ FVIIa (U/ml) 50.9±10.6 60.2±27.5 64.4±48.6 102.1±203.5*$ FM (μg/ml) 3.5±0.8 8.1±8.4* 5.7±1.7* 17.7±38.3*$ D-Di (μg/ml) 0.3±0.1 1.1±1.1 0.6±0.5 1.8±2.8*$ Thrombin generation Lagtime (min) 2.5±0.4 3.4±1.2 3.43±0.71 4.2±2.3*$ ETP (nM/min) 1496±191 1029±205 1045.87±288.9 1202±516$ Peak (nM) 289±36 168±60 174±64 216±74$ ttPeak (min) 5.3±0.7 7.3±1.8 7.17±1.23 7.1±2.7 MRI 110±24 48±24 52±28 82±44$ *p<0.05 versus Controls $p<0.05 versus MGUS and SMM Disclosures Van Dreden: Diagnostica Stago: Employment. Dimopoulos:Janssen-Cilag: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Genesis: Honoraria; Onyx: Honoraria.

Abstract Abstract 4159 Waldenstrom's macroglobulinemia (WM) is a B-cell malignancy characterized as an IgM secreting lymphoplasmacytic lymphoma. Familial predisposition is common in WM. Studies to date by us and others have revealed three identifiable clinical subtypes for WM predisposition: * Sporadic; proband has WM, but there is an absence of WM or other B-cell disorders in other family members; * Familial, Mixed B-cell Disorders Subtype; proband has WM, and various B-cell disorders are manifested by other family members. * Familial, WM Only Subtype; proband has WM, and only WM is present in other family members; While these studies suggest a separate genetic predisposition for WM, the correlation of additional cancer risk among all patients with WM and their kin, and well as those sub typed by familial WM predisposition may herald important information for common genetic risks to cancer. We therefore examined the incidence of additional malignancies in 923 consecutive WM patients seen at our Institution, and characterized the frequencies of additional malignancies based on familial subtype and against SEER data. In addition, we also characterized the incidence of solid cancers in kin of WM patients, and sub typed these cancers based on familial WM presentation. Of the 923 patients, 221 (23.9%) patients had at least one additional malignancy to WM. Among these patients, 32 had 2, and 4 (0.43%) had 3 additional malignancies. For 167/221 (75.5%), the associated cancers were diagnosed before WM. The associated malignancies for all patients were as follows: Prostate (n=53; 9.2% of all males); Breast (n=27; 7.7% of all females); Skin (Basal and Squamous; n=61; 6.6%); Skin (Melanoma; n=16; 1.7%); Lung (n=12; 1.3%); Thyroid (n=10; 1.1%); Colorectal (n=7; 0.8%); Bladder (n=8; 0.9%) Other B-cell Malignancies (n=18; 2.0%); Renal (n=6; 0.7%); MDS (n=6; 0.65%); Other (n=11; 1.2%). The incidence of Lung (p=0.002) and Prostate (p=0.07) were higher among WM patients with Familial, Mixed B-cell Disorders Subtype. To avoid potential treatment related impact on additional cancer development, we next adjusted the observed versus expected frequencies based on SEER-17 data. The age adjusted incidence for development of any malignancy among WM patients was 7.6 fold higher when the development of another cancer antedated the diagnosis of WM. Among all WM patients, the incidence of solid cancers among first degree kin were as follows: Prostate (n=98; 10.6%); Breast (n=133; 14.4%); Skin (Basal and Squamous; n=21; 2.3%); Skin (Melanoma; n=21; 2.3%); Lung (n=116; 12.5%); Thyroid (n=9; 1.0%), Colorectal (n=79; 8.6%); Renal (n=8; 0.9%); and Gastric (n=20; 2.2%). The incidence of Breast (p=0.0098), and Skin (Melanoma) (p=0.037) cancers were higher among first degree kin of patients with the Sporadic versus Familial, Mixed B-cell Disorders Subtype. In summary, the above data suggest an increased risk for additional cancers among all WM patients, as well as specific risks for lung and prostate cancer among patients with Familial, Mixed B-cell Disorders Subtype. Moreover, these data also show the association of specific types of solid cancers in first degree kin of WM patients, particularly for WM patients with the Sporadic Subtype. n= Age (Yrs) Gender % Treated Additional Cancers Sporadic 666 60 (29–91) 64% M; 36% F 515 (77%) 163 (24.4%) Familial, Mixed B–cell Disorders 212 58 (36–85) 57% M; 43% F 156 (73%) 50 (23.5%) Familial, WM Only 45 61 (35–89) 56% M; 44% F 35 (77%) 8 (17.7%) Total 923 59 (29–91) 62% M; 38% F 706 (76.4%) 221 (23.9%) Disclosures: No relevant conflicts of interest to declare.

Background FDG-PET is used in staging and response assessments in patients (pts) with DLBCL. An analysis of 158 pts with DLBCL receiving R-CHOP or DA-EPOCH-R on CALGB/Alliance 50303 failed to show an association between the interim PET (iPET, after cycle 2 of therapy) visual 5-point scale score (5-PS) by central review and progression-free survival (PFS) or overall survival (OS), but did show a significant association between percent change in FDG uptake from baseline to after cycle 2 (∆SUV) and PFS/OS (Schoder et al. 2020). As central review of FDG-PET is not feasible in routine practice, we retrospectively compared local vs central readings, and determined associations from local imaging data with PFS/OS. Methods 126 pts at baseline and 109 at iPET had local imaging data submitted across 21 institutions. Visual scores 1-3 defined PET- and scores 4-5 defined PET+ disease. ∆SUV was defined as the percent change in the maximum SUV at any site (maxSUV) from baseline to iPET. Continuous ∆SUV and categorized ∆SUV (&lt;66% vs &gt;66%) were analyzed. Differences in quantitative measures were calculated as the local minus central result. The Kappa statistic estimated agreement in PET and ∆SUV groups between local and central review. PFS and OS distributions for local PET and ∆SUV groups were landmarked at iPET, estimated with the Kaplan-Meier method, and compared using the log-rank test. Results At baseline, maxSUV was reported locally and centrally in 118 pts. Median maxSUV was 24.3 (range: 5.9-77.3) by local review and 24.3 (range: 5.9-77.0) by central review. The median difference in maxSUV was 0 (range: -12.9 to 21.9), with 50% of differences between -1.1 and 0.1, and 90% of differences between -7.8 and 4.1. In 106 pts with visual iPET 5-PS results, 52 (49.1%) were PET+ by local review and 37 (34.9%) by central review. Agreement in local and central review was moderate (kappa=0.53), occurring in 81 pts (76.4%; 32 PET+ and 49 PET-). Disagreement occurred in 25 patients, 20 with local PET+ but central PET- and 5 with local PET- but central PET+. iPET maxSUV was reported locally and centrally in 90 pts. Median maxSUV was 3.4 (range: 0-18.3) by local review and 3.3 (range: 1.2-18.2) by central review. The median difference in maxSUV was 0 (range: -8.6 to 2.4), with 50% of differences between -0.3 and 0.4, and 90% of differences between -4.4 and 1.8. ∆SUV was calculated in 87 pts. Median ∆SUV was 84.6% (range: -3.0% to 95.9%) by local review and 85.1% (range: -34.9% to 95.8%) by central review. The median difference in ∆SUV was -0.3 (range: -19.6 to 31.9), with 50% of differences between -2.1 and 1.1, and 90% of differences between -7.1 and 12.3. ∆SUV was &lt;66% in 12 (13.8%) pts by local review and 12 pts by central review. Agreement in local and central review was high (kappa=0.81), occurring in 83 pts (95.4%; 10 with ∆SUV &lt;66%, 73 with ∆SUV &gt;66%). Disagreement occurred in 4 pts, 2 in each direction. Using local data, PFS and OS estimates were numerically lower in pts with iPET+ vs iPET- disease, but did not reach statistical significance (p=0.12 and p=0.15). Two-year estimates for PFS were 79% (95% CI 68-91%) and 89% (95% CI 81-98%), and 2-year estimates for OS were 84% (95% CI 75-95%) and 96% (95% CI 91-100%) in pts with iPET+ and iPET-, respectively. In contrast, ∆SUV groups were significantly associated with PFS and OS (p=0.03 and p=0.002). Two-year estimates for PFS were 56% (95% CI 34-94%) and 87% (95% CI 79-95%) and 2-year estimates for OS were 56% (95% CI 34-94%) and 93% (95% CI 88-99%) in pts with ∆SUV &lt;66% and ∆SUV &gt;66%, respectively. Conclusion Agreement in visual 5-PS at iPET was moderate; most discrepancies arose from a local PET+ result when central review called PET-. Differences in maxSUV and ∆SUV tended to be small. Grouping ∆SUV resulted in only 4 discrepancies (4.6%). Similar to the previous analysis using central data, the separation in PFS and OS curves using local data for ∆SUV was greater than by visual 5-PS. Encouragingly, the agreement in ∆SUV of &lt;66% vs ≥66% was high between local and central review. Overall agreement however may be unduly influenced by the large proportion of pts with ∆SUV ≥66%, with less certainty in agreement for pts with ∆SUV &lt;66%. Larger prospective studies comparing local and central imaging data are warranted to best determine the utility of local imaging in clinical trials. Support: P30 CA008748, U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. ClinicalTrials.gov Identifier: NCT00118209 (CALGB 50303) Disclosures Kahl: Acerta: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy. Friedberg:Astellas: Consultancy; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Portola Pharmaceuticals: Consultancy; Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Kite Pharmaceuticals: Research Funding; Bayer: Consultancy. Leonard:MEI Pharma: Consultancy; Sutro: Consultancy; Bayer: Consultancy; BMS/Celgene: Consultancy; GenMab: Consultancy; Roche/Genentech: Consultancy; Gilead/Kite: Consultancy; ADC Therapeutics: Consultancy; Regeneron: Consultancy; Epizyme: Consultancy; Miltenyi: Consultancy; AstraZeneca: Consultancy; Karyopharm: Consultancy. Bartlett:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Millennium: Research Funding; Merck: Research Funding; Kite, a Gilead Company: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Forty Seven: Research Funding; BMS/Celgene: Research Funding; BTG: Consultancy; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche/Genentech: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Acerta: Consultancy; Affimed Therapeutics: Research Funding; ADC Therapeutics: Consultancy; Autolus: Research Funding.

Premature discontinuation of asparaginase reduces cure rate in contemporary acute lymphoblastic leukemia (ALL) treatment. One of the commonest causes of asparaginase truncation is asparaginase-associated pancreatitis (AAP). We prospectively registered AAP during treatment of 2,448 consecutive Nordic/Baltic ALL patients aged 1.0-45.9 years treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol (7/2008-10/2018). The Day 280 cumulative incidence of first-time AAP (including 99% (167/168) of AAP events at this time point) was 8.3% (95% confidence interval (CI) 7.0-9.9) with a median time of 104 days (interquartile range (IQR) 70-145) from ALL diagnosis to AAP, with a median of 10 days (IQR 6-13) from last asparaginase exposure, and after a median number of five asparaginase doses (IQR 3-7, max 14 doses). All patients received polyethylene glycol conjugated Escherichia coli-derived asparaginase as standard treatment. Eighty-five percent (140/164, unknown in N=4) of AAP events were severe (AAP-associated symptoms and/or pancreatic enzymes >3x upper normal limit lasting >72 hours or with hemorrhagic pancreatitis, pancreatic abscess, or pseudocyst). Four age groups were defined: 1.0-4.9, 5.0-8.9, 9.0-16.9, and 17.0-45.9 years-each containing approximately 25% of the AAP events. Compared with patients aged 1.0-4.9 years, adjusted (sex, immunophenotype, and white blood cell count) hazard ratios (HR) of AAP were associated with higher age (5.0-8.9 years: HR 2.3, 95% CI 1.5-3.6, P<.0001; 9.0-16.9 years: HR 2.5, 95% CI 1.6-3.8, P<.0001; and 17.0-45.9 years: HR 2.5, 95% CI 1.6-3.8, P<.0001). When analyzing the odds of developing any AAP-related complication among patients with ≥100 days of follow-up after the AAP diagnosis, older children (≥5.0 years) and adolescents had increased odds of developing any complication compared with younger children aged 1.0-4.9 years, notably a more than six-fold increase among adolescents (5.0-8.9 years: odds ratio (OR) 2.67, 95% CI 1.07-6.68, P=.04 and 9.0-16.9 years: OR 6.52, 95% CI 2.35-18.1, P=.0003)-including acute and permanent insulin need; intensive care unit admission; pancreatic pseudocyst development; recurrent abdominal pain; elevated pancreatic enzymes at last-follow-up; imaging compatible with pancreatitis (pancreatic inflammation/edema/pseudocysts/hemorrhage) at last follow-up; and AAP-related death. Adult age was not associated with development of any AAP-related complication (17.0-45.9 years: OR 2.3, 95% CI 0.9-5.9, P=.07). Three patients aged 8.6, 17.3, and 18.6 years died of first-time AAP within 0-29 days from AAP diagnosis. Of 168 AAP patients, 34 (20%) were re-challenged with asparaginase. Fifty percent (17/34) developed a second episode of AAP-41% being severe (7/17). The median time to a second AAP event from asparaginase re-exposure was 29 days (IQR 16-94) and occurred after a median of two asparaginase doses (range 0-7). Neither age group nor severity of the first AAP was associated with increased hazard of a second AAP event. None of the patients with a second AAP were further re-exposed to asparaginase, and none died of the second AAP. Among a total of 196 ALL relapses, 21 patients have had AAP including 17 patients with asparaginase truncation. However, the hazard of relapse (age- and sex-adjusted) was not increased among AAP patients with asparaginase truncation versus AAP patients with asparaginase re-exposure (5.0-year cumulative incidence of relapse: 13.2% versus 14.2%) (HR 1.0, 95% CI 0.3-3.1, P=1.0). When analyzing time to relapse among AAP patients versus non-AAP patients, no difference in hazard of relapse was found (HR 2.0, 95% CI 0.8-4.9, P=.2). In conclusion, adolescents and young adults tolerated asparaginase treatment as well as children; however, the risk of AAP was higher for patients older than 5.0 years of age with no difference with increasing age. Despite a low AAP-related mortality, the morbidity was considerable and most profound for patients aged 9.0-16.9 years. Since asparaginase re-exposure was associated with a high risk of a second AAP event and neither AAP development nor AAP-related asparaginase truncation was associated with increased relapse risk, asparaginase re-exposure should be attempted only in patients with a high risk of leukemic relapse. Finally, there is an unmet need for preventive strategies toward AAP. Disclosures Wolthers: Novo Nordisk: Employment.

Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting the musculoskeletal system as well as skin and nails. The prevalence of depression in psoriasis and PsA is high and ranges from 7-40% [1]. Persistent depressive mood may influence disease activity outcome in PsA, especially patient-reported outcomes.Objectives:To assess the correlation of depressive symptoms with PsA-specific outcome parameters.Methods:RABBIT-SpA is a prospective longitudinal cohort study including PsA patients enrolled at start of a new conventional treatment or b/tsDMARD treatment. In regularly provided follow-up questionnaires, physician- and patient-reported information on the disease course including the depression screening tool WHO-5 to assess mental health is collected. For the current analysis, the WHO-5 score was categorised into 4 groups using validated cut-offs: severe depressive symptoms <13, moderate depressive symptoms 13-28, mild depressive symptoms 29-50, well-being >50. Spearman correlation coefficient was calculated to analyse the relationship between the WHO-5 score and various PsA related outcome parameters.Results:936 PsA patients were included. Baseline characteristics are shown in Table 1. In 411 patients (43.9%) the WHO-5 score indicated well-being, 249 (26.6%) had mild depressive, 203 (21.7%) moderate depressive and 73 patients (7.8%) severe depressive symptoms. WHO-5 results correlated with patient reported skin involvement (DLQI: -0.25, patient assessment skin: -0.17), and the composite scores DAPSA (-0.33) and DAS28 (-0.28) as well as with patient reported pain (-0.43) and patient global disease assessment (-0.42). The highest correlation was found for physician assessed global health status (-0.51) and PSAID (-0.62). No significant correlation was found with CRP, swollen joint count and physician assessed skin involvement including body surface area (BSA).Table 1.Baseline characteristics of patients included in the analysis stratified by WHO-5 categories.ParameterWHO-5 (<13) severeN=73WHO-5 (13-28) moderateN=203WHO-5 (29-50) mildN=249WHO-5 (>50) well-beingN=411TotalN=936Age, mean (SD)52.6 (11.4)51 (11.3)51.4 (12.5)52.8 (12.7)52 (12.2)Female, n (%)52 (71.2)127 (62.6)157 (63.1)227 (55.2)563 (60.1)Disease duration, years, mean (SD)8.3 (8.7)6 (7.9)6.2 (6.7)6.4 (7.5)6.4 (7.5)Dactylitis, n (%)14 (19.7)31 (15.5)46 (18.5)77 (18.8)168 (18.1)Axial involvement, n (%)14 (19.7)54 (26.9)49 (19.7)71 (17.3)188 (20.2)Nail involvement, n (%)34 (47.2)85 (42.3)106 (42.6)158 (38.6)383 (41.1)BMI>=30, n (%)37 (51.4)75 (37.1)98 (39.5)125 (30.9)335 (36.2)CRP of >=5 mg/L, n (%)33 (51.6)84 (45.4)99 (46.5)138 (39.1)354 (43.4)BSA (0-100), mean (SD)10.1 (18.3)9.5 (16.8)8.5 (14.9)8.1 (14.6)8.7 (15.5)Physician assessed global health (NRS 0-10), mean (SD)6.3 (1.5)5.6 (1.8)5.2 (1.7)4.9 (1.9)5.2 (1.9)TJC68, mean (SD)9.9 (7.1)8.6 (7.6)8.2 (7.6)7.3 (8.2)8 (7.8)SJC66, mean (SD)6 (5.2)4.8 (4.9)4.7 (4.4)4.3 (3.8)4.6 (4.4)DAPSA, mean (SD)29.3 (11.1)25.1 (12.9)23.4 (12.1)18.9 (12.4)22.3 (12.8)DAS28-CRP, mean (SD)4.1 (1)3.8 (1.2)3.7 (1.1)3.2 (1.1)3.6 (1.2)Patient assessed global health (NRS 0-10), mean (SD)7.9 (2.1)6.6 (2.1)5.9 (2)4.8 (2.3)5.7 (2.4)Patient assessed pain (NRS 0-10), mean (SD)7.8 (1.8)6.4 (2.1)5.8 (2)4.6 (2.4)5.5 (2.4)DLQI (0-30), mean (SD)8.5 (8.2)7.8 (7.2)5.4 (5.7)4.1 (4.9)5.6 (6.2)PSAID (0-10), mean (SD)6.9 (1.8)5.5 (1.8)4.4 (1.7)3 (1.7)4.2 (2.2)Conclusion:The impact of depressive symptoms on outcome parameters used in rheumatology is increasingly being recognised. Interestingly, direct measures of inflammatory disease activity of joint and skin disease such as BSA, CRP, and swollen joint count were not correlated with depressive symptoms. The highest correlation was found for broader assessments like global health status and PSAID.References:[1]Haugeberg et al. Arthritis research & Therapy, 2020, 22:198Acknowledgements:RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.We thank all participating rheumatologists and patients.Disclosure of Interests:Anne Regierer Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Anja Weiß Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Martin Bohl-Buehler: None declared, Xenofon Baraliakos: None declared, Frank Behrens: None declared, Georg Schett: None declared, Anja Strangfeld Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.

Climate change induced sea-level rise (SLR) is on its increase globally. Regionally the lowlands of China, Vietnam, Bangladesh, and islands of the Malaysian, Indonesian and Philippine archipelagos are among the world’s most threatened regions. Sea-level rise has major impacts on the ecosystems and society. It threatens coastal populations, economic activities, and fragile ecosystems as mangroves, coastal salt-marches and wetlands. This paper provides a summary of the current state of knowledge of sea level-rise and its effects on both human and natural ecosystems. The focus is on coastal urban areas and low lying deltas in South-East Asia and Vietnam, as one of the most threatened areas in the world. About 3 mm per year reflects the growing consensus on the average SLR worldwide. The trend speeds up during recent decades. The figures are subject to local, temporal and methodological variation. In Vietnam the average values of 3.3 mm per year during the 1993-2014 period are above the worldwide average. Although a basic conceptual understanding exists that the increasing global frequency of the strongest tropical cyclones is related with the increasing temperature and SLR, this relationship is insufficiently understood. Moreover the precise, complex environmental, economic, social, and health impacts are currently unclear. SLR, storms and changing precipitation patterns increase flood risks, in particular in urban areas. Part of the current scientific debate is on how urban agglomeration can be made more resilient to flood risks. Where originally mainly technical interventions dominated this discussion, it becomes increasingly clear that proactive special planning, flood defense, flood risk mitigation, flood preparation, and flood recovery are important, but costly instruments. Next to the main focus on SLR and its effects on resilience, the paper reviews main SLR associated impacts: Floods and inundation, salinization, shoreline change, and effects on mangroves and wetlands. The hazards of SLR related floods increase fastest in urban areas. This is related with both the increasing surface major cities are expected to occupy during the decades to come and the increasing coastal population. In particular Asia and its megacities in the southern part of the continent are increasingly at risk. The discussion points to complexity, inter-disciplinarity, and the related uncertainty, as core characteristics. An integrated combination of mitigation, adaptation and resilience measures is currently considered as the most indicated way to resist SLR today and in the near future.References Aerts J.C.J.H., Hassan A., Savenije H.H.G., Khan M.F., 2000. Using GIS tools and rapid assessment techniques for determining salt intrusion: Stream a river basin management instrument. 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Abstract The American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) Classification of Cancer 8th edition (AJCC8) was officially introduced in January 2018 as a replacement for the previous version (AJCC7). Validation studies using data obtained from large cancer registries in North America demonstrated the superiority of AJCC8 over AJCC7 for prediction of survival. Subsequent studies from Europe and East Asia have mostly shown similar findings. However, these data may not be generalizable to other parts of the world. In this first study from the Middle East (Saudi Arabia), we compared these two versions of AJCC staging for their concordance and prediction of outcome in a large unselected sample of patients (pts) with DTC managed at a major referral medical center. We also compared the AJCC staging systems with the American Thyroid Association (ATA) Risk Classification. Of 814 consecutive pts seen during this period, 94 were excluded either due to their diagnosis being medullary or anaplastic thyroid cancer (37) or because of deficient data. The remaining 720 pts (149 males (20.7%), 571 females (79.3%) were included. The median age at the diagnosis was 37 yrs (range, 6-83). Total thyroidectomy was performed in 693 pts (96.3%) and central and/or lateral lymph node dissections in 487 pts (67.6%). I-131 was administered to 626 pts (87%). The tumors were classic PTC in 519 pts (72%), follicular variant PTC in 100 (13.9%), Tall cell PTC in 22 (3.1%), diffuse sclerosing PTC in 10 (1.4%), follicular thyroid cancer in 21 (2.9%) and other rare subtypes in 48 pts (6.8%). The number (%) of pts within each stage group by AJCC7 and AJCC8 respectively are as follows: Stage 1: 514 (71.4%) vs. 597 (82.9%), Stage 2: 46 (6.4%) vs. 75 (10.4%), Stage 3: 63 (8.8%) vs. 11 (1.5%), Stage 4: 97 (13.5%) vs. 37 (5.1%). Comparing AJCC8 with the ATA risk stratification system in 709 pts in which data were available, we found a high correlation with 96.8% of ATA low risk group being stage 1 in AJCC8, 2.9% stage 2 and 0.3% stage 3 and none in stage 4. The ATA intermediate risk group was 87.4% AJCC8 stage 1, 12.3% stage 2, 0.4% stage 3 and none in stage 4. The ATA high risk group was 19.1% in AJCC8 stage 1, 33% in stage 2, 9.6% in stage 3 and 38.3% in stage 4. In addition, AJCC8 was more predictive of the outcome with 80% of pts with evidence of disease (biochemically and structurally incomplete) being in AJCC8 stage 3 or 4 compared with 60% in AJCC7. For ATA staging, 8.6%, 22.4% and 67.7% of low, intermediate and high risk groups had evidence of disease at the last follow up, respectively. Conclusion: In this Middle Eastern population, AJCC8 downstaged a significant percentage of pts with DTC from higher stages in AJCC7. It also correlated better with the outcome and with the ATA risk classification system.

Abstract Background Feelings of fat are common for people with eating disorders, but ways of measuring its intensity are needed. Therefore, our goal was to develop a self-report feelings of fat scale that asked participants to indicate how intensely they currently felt statements such as “I feel fat”. With such a scale we can determine how strongly feelings of fat relate to evidence of disordered eating. Methods We conducted three studies of eating disorders with undergraduate women taking introductory psychology classes. The combined sample was 472 participants. A previous eating disorder diagnosis was self-reported by 33 participants and a current diagnosis by 11. All participants completed the EDE-Q and the seven (Study 1) or nine item (Studies 2 and 3) “State Feelings of Fat” (SFF) scales we developed. Each item asked them to rate the intensity with which they felt statements such “I feel fat” on a seven-point scale from “not at all” to “the most I have ever felt”. Results Both the seven and nine item SFF scales were highly coherent (Cronbach’s α were .94, .95 and .94), but factor analysis supported the seven-item version. We found high correlations between SFF and EDE-Q scores (Study 1: .816; Study 2: .808; Study 3: .841). SFF scores distinguished participants self-reporting no eating disorder diagnosis from those with a former diagnosis, t (361) = 2.33, p = .021, who in turn were distinguished from those with a current diagnosis, t (42) = 2.09, p = .043. Due to the high coherence of the scale, the single item “I feel fat” captured most of the variance in EDE-Q scores (r [472] = .793). Conclusions We have constructed an eating disorders relevant feelings of fat scale. Given that the EDE-Q is considered a valid questionnaire for measuring severity of eating disorders, our findings suggests that feelings of fat are core to the psychopathology of eating disorders. To the extent that EDE-Q scores are stable it also suggests that feelings of fat are surprisingly stable. Furthermore, the single item “I feel fat” alone may capture most of what the EDE-Q measures.

Por su potencial como fuente alimenticia, se analizó la composición química de huevo de Lepidochelys olivacea en La Escobilla, Oaxaca, México. El Instituto de Ciencias del Mar y Limnología de la Universidad Nacional Autónoma de México proporcionó 250 muestras de huevo liofilizado de 25 tortugas, que se analizaron siguiendo métodos oficiales para humedad, cenizas, proteína, grasa, lípidos totales(LT) y análisis microbiológicos; además de ácidos grasos(AG) por cromatografía de gases, aminoácidos(AA), vitaminas y colesterol(col) por HPLC. Los resultados fueron los siguientes: (g/100g) humedad(4.7), cenizas(3.8), proteína(53.7) y grasa(47.4). AA esenciales (g aa/100g Proteína): Ile (4.4), Lys(6.6), Leu(7.4), Met+Cys (8.8), Phe+Tyr (10.8); retinol (340µg/100g), colecalciferol (5.9 µg/100g), tocoferol (8.6), tiamina (0.3) y riboflavina (1.1) (mg/100g). Y los de (LT), (AG) y (Col) se concentraron en tres grupos por peso de tortuga: (LT) (44.3-48.7-49.1g/100g), (Col) (518.4-522.5-728.7 mg/100g). Entonces se identificaron 17 AGSaturados, 8 AGMonoinsaturados y 11 AGPoliinsaturados. Los AGS más abundantes (mg/100g): C16:0 (485-1263), AGM: C16:1 (456-716), C18:1n-9c (904- 1754) y AGP: C20:4n-6 (105-217), EPA (48-103) y DHA (97-189). También, existió diferencia significativa (Fisher, p<0.05) para (Col), AG totales, AGS, AGM, AGP y AG n-3 (EPA+DHA). No se detectó presencia de agentes microbiológicos. El huevo liofilizado de L. olivacea es una opción para el desarrollo de productos alimenticios por su proteína de alto valor biológico y ácidos grasos n-3.

Abstract Background Lifestyle interventions are widely recommended for weight management, particularly in patients with diabetes and cardiovascular disease. The intensity and duration of interventions needed to achieve sustained weight reduction are uncertain. Objectives To investigate the importance of the frequency and duration of lifestyle interventions for achieving weight loss over ≥ one year, and to evaluate associations between weight loss and all-cause mortality. Method Meta-analysis of randomised trials published in English-language journals from 1980 to June 2018 that assessed lifestyle compared to control interventions on weight loss in ≥100 subjects, and which reported weight change and mortality for ≥ one year. Results 31 randomised trials with a total of 20 816 overweight or obese participants, 70% of whom had cardiometabolic risk factors, were included. The weighted mean difference in body weight between diet and lifestyle intervention and control arms at 1 year was −3.65, 95% confidence interval (CI) −4.66, −2.65 kg, and at 3 years was −2.45, 95% CI: −3.73, −1.17kg. Weight loss at one year was greater in studies with more compared to fewer interventions (>vs ≤28/year (−4.53 [IQR −5.93, −3.12] kg vs −2.38 [−3.98, −0.78] kg, p=0.001). There were 593 deaths (rate ∼0.3%/year), and the odds ratio for mortality for weight loss interventions compared to the controls was 0.86 (95% CI 0.74, 1.01), p=0.09. Table 1. Association with intervention intensity with weight loss achieved and mortality Number of interventions in first year N studies# Number of patients Mean difference p Total deaths Odds ratio p Random effect model (kg) (95% CI) Fixed effect model (95% CI) ≤6 3 510 −0.84 [−1.40, −0.28] <0.0001 5 1.45 [0.22, 9.40] 0.7 7–12 6 2022 −2.04 [−3.24, −0.84] <0.0001 10 1.34 [0.35, 5.16] 0.67 13–24 6* 3490 −2.46 [−5.59, 0.67] <0.0001 23 1.20 [0.49, 2.96] 0.69 ≥25 18 13717 −3.53 [−4.13, −2.92] <0.0001 555 0.84 [0.71, 1.00] 0.05 Total 31 100 −2.98 Total 31 *2 studies reported mortality but not weight loss. Conclusion Lifestyle programs with frequent patient interactions sustained over a year or more achieve modest weight loss. The level of intervention needed for clinically meaningful weight reduction may be unrealistic for most medical practices. There is a modest non-significant reduction in mortality with lifestyle programs, but limited data on whether lifestyle interventions for obesity decrease mortality in persons at higher risk because of cancer, heart failure or ischaemic heart disease. Acknowledgement/Funding None

The occurrence of endoparasites in Swedish adult dogs (n = 303) was investigated between January and October 2014. Included dogs had to be clinically healthy, older than 1 year and untreated with anthelmintics or endectocides for at least 3 months prior to sampling. They were grouped according to age, category of dog and time since last antiparasitic treatment. Samples were analyzed by flotation to detect parasitic eggs and cysts/oocysts. Among these, 129 (43%) dogs were also analyzed with the Baermann-technique to detect cardiopulmonary larval stages. Parasite dispersal stages were found in 24 (7.9%, CI 95% 4.9–10.1) of the dogs at flotation, while no dog shed cardiopulmonary larval stages. Giardia sp. cysts were observed in 2.6% (n = 8) of dogs examined, cysts of Sarcocystis spp. were observed in 0.6% (n = 2), oocysts of Cystosisopora ohioensis were found in one dog (0.3%). Eggs of Toxocara canis (2.3%, n = 7), Uncinaria stenocephala (1.3%, n = 4) and Trichuris vulpis (0.3%, one dog) were found. None of the dogs were diagnosed with more than one species. Although the occurrence of endoparasites was above the average in dogs ≤ 2 years of age (11.5%), nematodes were more common in older dogs ≥4 years (77.0%). Although the occurrence was lower in working/exhibition dogs (5.9%) than in companion dogs (8.4%) and hunting-dogs (8.6%), these differences were not significant. However, dogs exposed to prey according to the owner had a statistically significant higher prevalence than other dogs (20.5 vs. 5.7%). The Odds Ratio (OR) was 4.0 (CI 95%, 1.58–10.11) for dogs having access to prey, 2.4 (CI 95%, 0.37–8.06) for dogs staying at day-care, and 2 (CI 95%, 0.96–5.96) for bitches. Furthermore, a significant association was observed between infection with nematodes and exposures to prey (p = 0.006). As a reference, data on the endoparasites in canine fecal samples submitted to the National Veterinary Institute (SVA, Uppsala) during 2014 are presented. Overall, this study shows a low occurrence of endoparasites among dogs in Sweden. Any risk-assessment on zoonotic parasites as well as deworming recommendations will take advantage from these updated figures.

Abstract INTRODUCTION Firearm injury is a leading cause of death and disability in the American youth. Epidemiology and outcomes following gunshot wound to the head (GSWH) are in need of systematic characterization. Here, we analyzed pediatric GSWH to identify predictors of prolonged hospitalization, morbidity and mortality. METHODS All patients < 18 yr with GSWH in the National Sample Program (NSP) of the National Trauma Data Bank (NTDB) from 2003 to 2012 were identified. Variables included injury intent, firearm choice, injury site, age, sex, race, health insurance, geographic region, trauma center level, isolated TBI, emergency department (ED) hypotension, Glasgow Coma Scale (GCS), and Injury Severity Score (ISS). Outcomes were hospital length of stay (HLOS), morbidity and mortality. Odds ratios (OR), mean increase/decrease (B), and 95% confidence intervals (CI) were reported. Statistical significance was assessed at a < 0.001 accounting for multiple comparisons. RESULTS In a weighted sample of 2847 pediatric GSWHs, age was 14.8 ± 3.3 yr, 79.2% were male, and 59.0% had severe traumatic brain injury (TBI; Glasgow Coma Scale [GCS] score 3-8). Assault (63.0%), handgun as firearm (45.6%), and injury in residential areas (40.6%) were most common. HLOS was 11.6 ± 14.4 d for the survivors, for which suicide injuries had longer hospitalization (B = 5.9 day increase, 95% CI [3.3-8.6], P < .001) relative to accidents. The overall mortality was 45.1%, and was greater with suicide intent (mortality = 71.5%, P < .001) and shotgun as firearm (mortality = 56.5%, P < .001). Lower GCS, higher ISS, and hypotension predicted poorer outcomes. Management at level II centers was associated with lower odds of returning home (OR = 0.3, [0.2-0.5], P < .001). CONCLUSION From 2003 to 2012, the proportion of accidental injuries decreased while suicides increased. The overall mortality was 45%, with hypotension, cranial and overall injury severity, and suicide intent being associated with poor prognosis. Patients treated at level II trauma centers had lower odds of being discharged home. Improved risk screening, parental education and standardization of critical care management are needed.

Abstract Background A reliable expected date of delivery (EDD) is important for pregnant women in planning for a safe delivery and critical for management of obstetric emergencies. We compared the accuracy of LMP recall, an early ultrasound (EUS) and a Smartphone App in predicting the EDD in South African pregnant women. We further evaluated the rates of preterm and post-term births based on using the different measures. Methods This is a retrospective sub-study of pregnant women enrolled in a randomized controlled trial between October 2017-December 2019. EDD and gestational age (GA) at delivery were calculated from EUS, LMP and Smartphone App. Data were analysed using SPSS version 25. A Bland–Altman plot was constructed to determine the limits of agreement between LMP and EUS. Results Three hundred twenty-five pregnant women who delivered at term (≥ 37 weeks by EUS) and without pregnancy complications were included in this analysis. Women had an EUS at a mean GA of 16 weeks and 3 days). The mean difference between LMP dating and EUS is 0.8 days with the limits of agreement 31.4–30.3 days (Concordance Correlation Co-efficient 0.835; 95%CI 0.802, 0.867). The mean(SD) of the marginal time distribution of the two methods differ significantly (p = 0.00187). EDDs were < 14 days of the actual date of delivery (ADD) for 287 (88.3%;95%CI 84.4–91.4), 279 (85.9%;95%CI 81.6–89.2) and 215 (66.2%;95%CI 60.9–71.1) women for EUS, Smartphone App and LMP respectively but overall agreement between EUS and LMP was only 46.5% using a five category scale for EDD-ADD with a kappa of .22. EUS 14–24 weeks and EUS < 14 weeks predicted EDDs < 14 days of ADD in 88.1% and 79.3% of women respectively. The proportion of births classified as preterm (< 37 weeks) was 9.9% (95%CI 7.1–13.6) by LMP and 0.3% (95%CI 0.1–1.7) by Smartphone App. The proportion of post-term (> 42 weeks gestation) births was 11.4% (95%CI 8.4–15.3), 1.9% (95%CI 0.9–3.9) and 3.4% (95%CI 1.9–5.9) by LMP, EUS and Smartphone respectively. Conclusions EUS and Smartphone App were the most accurate to estimate the EDD in pregnant women. LMP-based dating resulted in misclassification of a significantly greater number of preterm and post-term deliveries compared to EUS and the Smartphone App.

Abstract BACKGROUND AND AIMS Conventional haemodialysis (HD) with low-flux membranes does not provide adequate middle molecular weight (MMW) clearance of uremic toxins [1]. The potential for better removal of parathyroid hormone (PTH) and β2-microglobulin (β2M) was investigated using a combination of low-flux HD and haemoperfusion (HP) (HD + HP). METHOD A total of 16 stable HD male patients, free of infections, malignancies or haematological disorders, under usual medications for anaemia and hyperparathyroidism, treated with low-flux polysulfone membranes, were randomized into two groups: group A (GA) included eight patients under HD + HP and group B (GΒ) included eight patients under HD only. In GA patients, a type HA130 HP cartridge was connected in parallel to the dialyzer, once a week for the first month, once every 2 weeks for the second month and once a month for the next 4 months. A third group C (GC) was also studied, consisting of eight males undergoing online haemodiafiltration (OL-HDF). In all three groups, serum β2M and iPTH levels were determined at months 0 and 6, before (preD) and after (postD) the mid-week session. RESULTS Serum preD-β2M levels were similar in groups A and B at month 0 (44.1 ± 8.6 versus 34.6 ± 16.2 mg/L; P = NS) and at month 6 (46.1 ± 7.6 versus 41.1 ± 18.9 mg/L; P = NS). In GC, preD–β2M values were lower compared with GA at month 0 (31.1 ± 4.2 mg/L; P = .008) and at month 6 (33.8 ± 6.82 mg/L; P = .02), and postD–β2M values decreased significantly at month 0 (7.4 ± 1.9 mg/L; P &lt; .001) and at month 6 (9.9 ± 3.8 mg/L; P &lt; 0.001). The reduction was maintained, with no difference between month 0 and month 6. An improvement/decrease in β2M values was observed between month 0 and month 6 only in GA (–5.8 ± 7. 2 versus 1.8 ± 5 mg/L; P = .03) but not in GB. PreD–iPTH values did not differ between groups A, B and C at month 0 (623 ± 432 versus 434 ± 350 versus 710 ± 286 pg/mL, respectively; P = NS) and at month 6 (758 ± 550 versus 383 ± 186 versus 559 ± 296 pg/mL, respectively; P = NS). PostD–iPTH values showed a decrease at month 6 in GA (from 758 ± 550 to 514 ± 474 pg/mL; P = .04) but not in GB and a mild decrease in GC (from 559 ± 296 to 363 ± 295 pg/mL; P = .05), with a marginal reduction improvement between month 0 and month 6 in GC (41 ± 55 versus 196 ± 87 pg/mL; P = .046). CONCLUSION OL-HDF is obviously the most effective method for the elimination of MMW uremic toxins [2]. Interestingly, the combination HD + HP seems to be more effective than low-flux HD alone [3], and it could be useful for specific patient cases in daily clinical practice.

Internet banking (IB) is believed to bring a lot of banefits to customers and is provided by most of the banks in Vietnam, but the number of users is still limited. The purpose of this study is to investigate the reasons and consumption-decision structure why not many people in Vietnam is willing to use the service. The study is based on Mean Means-End Chain theory (MEC) and uses laddering interview to collect data. Data from a sample of 71 respondents are analysed by employing Association Pattern Technique (APT) and then are demonstrated on Hierarchical Value Map (HVM). The research findings show that there are 06 attributes, leading to 05 consequences, driving to Unsafety and Inconvenience as 02 crucial values which prevent customers from using IB. Some recommendations are proposed accordingly to improve IS usage. Keywords Internet banking, Means-end chain theory, soft/hard laddering interview References [1] Phương, M. (2017, December 01). 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Abstract Background and Aims The urea & electrolyte panel (U&E) is a basic test commonly performed in clinical medicine. A quick evaluation can often reveal the presence of acid-base disturbances which in turn flags up potentially serious physiologic disturbances and critical conditions. While there are a few ways to screen for acid-base disorders, evaluation of the anion gap remains popular today. The AG is the difference between measured cations and anions and calculated from the main components of the U&E. For mixed acid-base disorders, the delta gap (ΔGap) provides further information (Table 1). However, every test has a range within tolerance limits. The tolerance limit in turn depends on the precision of the laboratory methodology. Figure 1 illustrates how tolerance intervals are determined in a normal distribution. To date, most clinical texts quote a tolerance interval of ±6 mEq/L for ΔGap, referencing the 1990 article by Dr Kieth Wrenn (Ann Emerg Med. 1990 Nov;19(11):1310). The range of ±6 mEq/L was calculated using the standard deviation (SD) of the tests for Na, Cl and bicarbonate in the 1980s, and an ΔGap &gt; +6 or &lt; –6 mEq/L suggests a mixed disorder. Derivation of tolerance interval of ΔGap: ΔGap = ΔAG – ΔHCO3- ΔGap = (AG –12) – (24 – HCO3-) ΔGap = (Na+ – Cl- – HCO3- –12) – (24 – HCO3-) Variance (SD2) of ΔGap = Sum of variances of component electrolytes Variance (SD2) of ΔGap = SD2Na + SD2Cl + SD2HCO+ SD2HCO Standard deviation (SD) of ΔGap = √( SD2ΔGap) Tolerance interval of ΔGap = ±1.96 x SDΔGap However, laboratory techniques have improved in precision since the 1980s. A ΔGap of ±6 mEq/L may be too wide, inadvertently missing mixed metabolic disorders. The aim of this study was to update the reference range of the ΔGap based on current laboratory precision. Interpretation of the acid-base disorder will be applied using the updated ΔGap range in a validation cohort. Method The current SD for Na, Cl and bicarbonate was obtained from the laboratory system data sheet and the tolerance interval of ΔGap was calculated . A validation cohort was generated retrospectively from electronic medical records according to a pre-determined criteria from 1 Jan – 31 Dec 2018. We identified a group of patients with a strong possibility of mixed HAGMA and MALK in the presence of: 1. High AG 2. Significant organic acidosis (lactic acidosis, ketosis or elevated salicylates) AND 3. A serum bicarbonate ≥19.0 mmol/L despite the presence of organic acids. The ΔGap was computed and interpreted based on the original vs new tolerance range. The Chi Square test was used to compare the interpretations based on the 2 tolerance ranges. Results The current SD of Na, Cl, bicarbonate was 0.9, 0.7, 0.3 respectively and the new tolerance interval of AG was ±2.3 mEq/L (rounded to ±2 mEq/L) The validation cohort comprised of 1,565 patients with HAGMA and MALK, aged 58.0±30.9 years with 873 (55.8%) males. Using the original range of ±6 mEq/L, 165 (10.5%) cases were classified correctly. With the new range of ±2 mEq/L, the 813 (51.9%) cases were classified correctly (P&lt;0.001). Conclusion In summary, based on the precision of current laboratory techiques, the tolerance interval of AG is proposed as ±2 mEq/L. This was validated to significantly increase correct classification of mixed acid-base disorders.