Journal articles on the topic '155.930 9596'

Number of work accidents in Kab. Padang Pariaman, West Sumatra in 2012 there were 837 cases of work accidents, in 2013 it increased to 903 cases, in 2014 there were 1050 cases, in 2015 there were a decrease in cases to 956 cases, in 2016 there was an increase in work accident cases to 1535 cases. This study aims to find and prevent potential hazards by identifying hazards, assessing and controlling risks to workers. This study used the JSA method with univariate analysis. The study population was 155 workers with a sample of 112 respondents. This study uses the Jobs Safety Analysis (JSA) sheet by means of observation and interviews and then presents the results of the analysis of the checklist and questionnaire in tabular form. There are two stages of high-risk work with a score of 20 (16-24) in the uncoiling section, two stages of high-risk work with a score of 20 (16-24) in the accumulating section, three high-risk stages with a score of 16 (16-24) in the forming section and sizing, four high-risk stages with a score of 16 (16-24) on the packing section. Risk control is carried out at high risks that produce a large enough impact. It is hoped that the company should carry out risk control in the form of engineering by assembling machines that are safe, productive and efficient.

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia.

Objective: To determined if the number and frequency of CA-125 measurements per patient reflect the 2008 NACB (National Academy of Clinical Biochemist) practice guidelines. Methods: We collected data retrospectively on CA-125 over a period of one year as apart of our ongoing practice in monitoring the tumor markers for quality assurance, The number of CA-125 results per patient as well as the time interval between the 1st and 2nd measurements was noted. To enrich this population for the likelihood that the measurement of CA-125 was used for monitoring or for detection of recurrence, we divided the population into patients from the Jurvainski Cancer Centre (JCC) and the rest of the sites. Results: The JCC patients contributed the majority of CA-125 results, representing over 75% of all results (n= 3057 results from 998 patients), whereas the remainder of the sites only yielded 959 results from 920 patients. Further analysis of the JCC patients indicated 2 main subgroups: Group A – patients with 1 or 2 results (n=624 patients); Group B - patients with 3 or more results , Overall, less than 4% of patients at the JCC had a time interval between the 1st and 2nd specimens of less than 2 weeks. Discussion: This initial analysis would indicate that physicians are ordering CA-125 in agreement with the NACB guidelines. To further improve compliance to the guidelines and to prevent subsequent measurements of CA-125 too close, we propose restricting CA-125 orders that are less than 14 days apart to only those that receive Biochemist’s approval.

9506 Background: CNS metastases are common and associated with very poor prognosis in pts with metastatic melanoma (MM). In the phase II BREAK-MB trial, D had clinical activity in BRAF V600–mut MBM. D + T has shown superiority over D alone in pts with BRAF V600–mut mm without MBM; however, efficacy of this regimen on MBM has not been characterized. Here, we report results from a phase II trial of D + T in BRAFV600–mut MBM (COMBI-MB; NCT02039947). Methods: This open-label, phase II study evaluated D 150 mg BID + T 2 mg QD in 4 MBM cohorts: (A) BRAFV600E, asymptomatic MBM, no prior local treatment (Tx); (B) BRAFV600E, asymptomatic MBM, prior local Tx; (C) BRAFV600D/K/R, asymptomatic MBM, with or without prior local Tx; and (D) BRAFV600D/E/K/R, symptomatic MBM, with or without prior local Tx. The primary objective was intracranial response rate (IRR) in cohort A (null hypothesis, IRR ≤ 35%). Secondary endpoints included IRR in cohorts B, C, and D; extracranial (ERR) and overall (ORR) response rates; intracranial (IDCR), extracranial (EDCR), and overall (ODCR) disease control rates; duration of IR, ER, and OR; PFS; OS; and safety. Results: 125 pts were enrolled (A, n = 76; B, n = 16; C, n = 16; D, n = 17). In cohort A, median age was 52, 53% were male, and 37% had LDH > ULN. At data cutoff (28 Nov 2016; median f/u, 9.0 mo), in cohort A, investigator-assessed IRR was 58% (IDCR, 78%), ERR was 55% (EDCR, 80%), and ORR was 58% (ODCR, 80%). Median duration of IR, ER, and OR was 6.5 mo (95% CI, 4.9-10.3), 10.2 mo (95% CI, 6.5-13.0), and 6.5 mo (95% CI, 4.9-10.3), respectively. Median PFS was 5.6 mo (95% CI, 5.3-7.4). Independent review supported these results. 6-mo OS was 79%; with 31 pts (41%) still in f/u, preliminary median OS was 10.8 mo (95% CI, 8.7-19.6). Efficacy in cohorts B, C, and D will be reported. AEs across cohorts (any, 98%; grade 3/4, 48%) were consistent with prior D + T studies; 10% of pts (8% in cohort A) discontinued due to AEs. Conclusions: In this first report of a phase II trial evaluating a BRAF and MEK inhibitor combination in BRAFV600–mut MBM, the primary endpoint was met. Promising IRR and IDCR were seen with D + T, but responses appear less durable than reported for mm without MBMs. No unexpected safety issues were observed. Clinical trial information: NCT02039947.

(texte complet en anglais)Eighteen one-hump black (Majaheem) young camels were used to study growth rate and carcass percentage. The animals were selected and bought of similar age (about six months) and weight (around 150 kg). They were assigned randomly into three feeding groups. Each group was fed two types of rations: (A) concentrated pellets 18% crude protein at the rate of 1.5% CWT; and (B) one of three types of roughage: (a) alfalfa hay, (b) Rhodes grass hay, or (c) wheat straw treated with ammonia gas. Roughage was weighed and fed ad libitum. The experiment was ended when anirnals were about 14 months of age. Average body weights were 315, 298.8 and 291.4 kg for the three groups, respectively. Average daily gains for the three respective groups were 932, 803 and 767 g per day. Average carcass weights/kg (and carcass percentages) of each group were 180.6 (57.3%) for alfalfa, 170.7 (57.1%) for Rhodes and 168.1 (57.7%) for treated straw. Average forequarters weights/kg (and percentages to the carcass) were 98.9 (54.8%), 95.6 (56%) and 88.1 (52.4%) for the three groups, respectively. The hindquarters average weights/kg (and percentages) for the three respective groups were: 81,7 (45.2%), 75.1 (44%) and 80 (47.6%). Eight-year records (1986-1994) on carcasses of carnels, cattle and sheep were obtained from Riyadh Modem Slaughterhouse. The total number of animals killed was 3,891,301. Comparisons were made between the number of anirnals killed and the number of carcasses destroyed for each of the three species. It was found that on average for every carnel carcass destroyed 12 carcasses of cattle and 19 carcasses of sheep were destroyed. These results show clearly that camels produce the most hygienic meat for human consumption in comparison with cattle and sheep.

Las tortugas marinas son reptiles de gran antigüedad, habitan la tierra desde más de 110 millones de años, estas especies se encuentran amenazadas por el incremento de las actividades antropogénicas. El propósito fue corroborar la importancia de playa Lagarto como sitio de anidación de tortugas marinas y determinar los principales factores antropogénicos que las afectan. La toma de datos comprendió agosto 2016 a febrero 2017, se midieron humedad, granulometría y contenido orgánico, y censos de hembras, rastros y nidos. Se obtuvo un mayor contenido orgánico (15.5 %) y humedad (9.0 %) en la zona alta donde ocurrió la mayor anidación, con predominancia de arena fina (0.125 mm) con 52.5 % y mediana (0.250 mm) con 39 % del total. Se identificó la tortuga lora (Lepidochelys olivacea) con 11 nidos y 1 013 huevos y la tortuga verde (Chelonia mydas) con cuatro nidos y 398 huevos. La tortuga lora obtuvo un promedio de 66.2 LCC, 66.9 ACC, 75.6 HE y 43.4 HI, mientas que la tortuga verde con 95.6 LCC, 88.4 ACC, 94.0 HE y 47.9 HI. Se determinó que las principales actividades antropogénicas fueron la extracción ilegal de huevos, la urbanización costera y la contaminación sólida.

Background.The emotional consequences of diabetes have been scrutinized by a number of investigative teams and there are varying reports about the association of depression with type 2 diabetes mellitus. However, there is limited data about this in Ethiopia. Therefore, the purpose of this study was to assess the prevalence of comorbid depression among type 2 diabetic outpatients.Methods and Materials.Institution based cross-sectional study design was conducted on a random sample of 276 type 2 diabetic outpatients from Black Lion General Specialized Hospital. Systematic random sampling technique was used to get these individual patients from 920 type 2 diabetic outpatients who have an appointment during the data collection period. Patients’ depression status was measured using Patient Health Questionnaire 9 (PHQ 9).Result.Totally 264 type 2 diabetic outpatients were interviewed with a response rate of 95.6%. The prevalence of depression among type 2 diabetic outpatients was 13%. Based on PHQ 9 score, 28.4% (75) fulfilled the criteria for mild depression, 12.1% (32) for moderate depression, 2.7% (7) for moderately severe depression, and 1.5% (4) for severe depression. But 45.8% (121) of patients had no clinically significant depression.Conclusion.This study demonstrated that depression is a common comorbid health problem in type 2 diabetic outpatients with a prevalence rate of 13%.

ABSTRACT For a panel of 153 Staphylococcus aureus clinical isolates (including 13 vancomycin-intermediate or heterogeneous vancomycin-intermediate and 4 vancomycin-resistant strains), MIC50s and MIC90s of three novel dihydrophthalazine antifolates, BAL0030543, BAL0030544, and BAL0030545, were 0.03 and 0.25 μg/ml, respectively, for methicillin-susceptible strains and 0.03 and ≤0.25 μg/ml, respectively, for methicillin-resistant strains. For a panel of 160 coagulase-negative staphylococci (including 5 vancomycin-intermediate and heterogeneous vancomycin-intermediate strains and 7 linezolid-nonsusceptible strains), MIC50s and MIC90s were ≤0.03 and ≤0.06 μg/ml, respectively, for methicillin-susceptible strains and 0.06 and 0.5 μg/ml, respectively, for methicillin-resistant strains. Vancomycin was active against 93.0% of 313 staphylococci examined; linezolid was active against all S. aureus strains and 95.6% of coagulase-negative staphylococcus strains, whereas elevated MICs of clindamycin, minocycline, trimethoprim, and rifampin for some strains were observed. At 4× MIC, the dihydrophthalazines were bactericidal against 11 of 12 staphylococcal strains surveyed. The prolonged serial passage of some staphylococcal strains in the presence of subinhibitory concentrations of BAL0030543, BAL0030544, and BAL0030545 produced clones for which dihydrophthalazines showed high MICs (>128 μg/ml), although rates of endogenous resistance development were much lower for the dihydrophthalazines than for trimethoprim. Single-step platings of naïve staphylococci onto media containing dihydrophthalazine antifolates indicated considerable variability among strains with respect to preexistent subpopulations nonsusceptible to dihydrophthalazine antifolates.

ImportanceOlder patients with hypertension receiving intensive systolic blood pressure control (110-130 mm Hg) have lower incidences of cardiovascular events than those receiving standard control (130-150 mm Hg). Nevertheless, the mortality reduction is insignificant, and intensive blood pressure management results in more medical costs from treatments and subsequent adverse events.ObjectiveTo examine the incremental lifetime outcomes, costs, and cost-effectiveness of intensive vs standard blood pressure control in older patients with hypertension from the health care payer’s perspective.Design, Setting, and ParticipantsThis economic analysis was conducted with a Markov model to examine the cost-effectiveness of intensive blood pressure management among patients aged 60 to 80 years with hypertension. Treatment outcome data from the Trial of Intensive Blood-Pressure Control in Older Patients With Hypertension (STEP trial) and different cardiovascular risk assessment models for a hypothetical cohort of STEP-eligible patients were used. Costs and utilities were obtained from published sources. The incremental cost-effectiveness ratio (ICER) against the willingness-to-pay threshold was used to evaluate whether the management was cost-effective. Extensive sensitivity, subgroup, and scenario analyses were performed to address uncertainty. The US and UK population using race-specific cardiovascular risk models were conducted in the generalizability analysis. Data for the STEP trial were collected from February 10 to March 10, 2022, and were analyzed for the present study from March 10 to May 15, 2022.InterventionsHypertension treatments with a systolic blood pressure target of 110 to 130 mm Hg or 130 to 150 mm Hg.Main Outcomes and MeasuresIncremental lifetime quality-adjusted life-years (QALYs), costs, and ICER are discounted at the given rates annually.ResultsAfter simulating 10 000 STEP-eligible patients assumed to be 66 years of age (4650 men [46.5%] and 5350 women [53.5%]) in the model, the ICER values were ¥51 675 ($12 362) per QALY gained in China, $25 417 per QALY gained in the US, and £4679 ($7004) per QALY gained in the UK. Simulations projected that the intensive management in China being cost-effective were 94.3% and 100% below the willingness-to-pay thresholds of 1 time (¥89 300 [$21 364]/QALY) and 3 times (¥267 900 [$64 090]/QALY) the gross domestic product per capita, respectively. The US had 86.9% and 95.6% probabilities of cost-effectiveness at $50 000/QALY and $100 000/QALY, respectively, and the UK had 99.1% and 100% of probabilities of cost-effectiveness at £20 000 ($29 940)/QALY and £30 000 ($44 910)/QALY, respectively.Conclusions and RelevanceIn this economic evaluation, the intensive systolic blood pressure control in older patients produced fewer cardiovascular events and had acceptable costs per QALY gained, well below the typical willingness-to-pay thresholds. The cost-effective advantages of intensive blood pressure management in older patients were consistent over various clinical scenarios across different countries.

9506 Background: Although existing evidence suggests that cytokines play an intermediary role in the development of post-chemotherapy cognitive changes, specific cytokines associated with this neurotoxic sequela of chemotherapy are still unknown. This study was designed to identify pro-inflammatory biomarkers that are associated with memory and attention impairment in Asian patients receiving chemotherapy. Methods: This is a prospective, cohort study conducted at the National Cancer Centre Singapore. Early-stage Asian breast cancer patients (Stage I to III), who received anthracycline and/or taxane-based chemotherapy were recruited. Computerized neuropsychological assessments (Headminder) were administered to evaluate patients’ memory and attention performances and a panel of pro-inflammatory plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ and TNF-α) was evaluated using multiplex immunoassay at three time points: prior to chemotherapy (T1), at midpoint (T2), and end of chemotherapy (T3). Memory and attention impairment were defined as a >2.5 reduction of the Zscore from baseline, as calculated by the reliable change index for repeated cognitive measurements. Results: Thirty-six patients were included (mean age 49.7±9.0 years; 80.6% Chinese). Comparing to T1, 50.0% and 36.1% of the patients suffered memory and attention impairment at T3, respectively. Comparing patients with intact memory to those who suffered impairment from T2 to T3, they had higher levels of circulating IL-1β [median (IQR): 0.44 (0.1-0.5) vs 0.56 (0.4-0.7) pg/ml, p=0.069], IL-4 [0.41 (0.0-0.8) vs 0.85 (0.2-1.5) pg/ml, p=0.067) and TNF-α [1.78 (1.3-2.2) vs 3.01 (1.3-3.5) pg/ml, p=0.069]. At T3, reduction of attention scores were associated with higher levels of IL-1β (rs= -0.37, p=0.023) and IL-6 (rs= -0.33, p=0.045). No significant associations were identified with IL-2, IL-8, IL-10, GM-CSF and IFN-γ. Conclusions: These findings suggest that an increase in the post-chemotherapy levels of TNF-α, IL-1β, IL-4 and IL-6 may have an association with the manifestations of memory and attention impairment in Asian breast cancer patients.

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study (NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.

Background/Aims: Mortality and longevity studies of spinal cord injury (SCI) are essential for informing healthcare systems and policies. This review evaluates the current evidence among people with SCIs worldwide in relation to the WHO region and country income level; demographic and lesion characteristics; and in comparison with the general population. Methods: A systematic review of relevant databases for original studies. Pooled estimates were derived using random effects meta-analysis, restricted to traumatic SCI. Results: Seventy-four studies were included. In-hospital mortality varied, with pooled estimates of 24.1% (95% confidence interval (CI) 14.1-38.0), 7.6% (95% CI 6.3-9.0), 7.0% (95% CI 1.5-27.4), and 2.1% (95% CI 0.9-5.0) in the WHO regions of Africa, the Americas, Europe and Western Pacific. The combined estimate for low- and middle-income countries was nearly three times higher than for high-income countries. Pooled estimates of first-year survival were 86.5% (95% CI 75.3-93.1), 95.6% (95% CI 81.0-99.1), and 94.0% (95% CI 93.3-94.6) in the Americas, Europe and Western Pacific. Pooled estimates of standardized mortality ratios in tetraplegics were 2.53 (2.00-3.21) and 2.07 (1.47-2.92) in paraplegics. Conclusion: This study found substantial variation in mortality and longevity within the SCI population, compared to the general population, and between WHO regions and country income level. Improved standardization and quality of reporting is needed to improve inferences regarding the extent to which mortality outcomes following an SCI are related to healthcare systems, services and policies.

We report, for the first time to our knowledge, a diode-pumped continuous-wave microchip Er,Yb:YMgB5O10 laser. The purpose of this work was to study the growth technique, spectroscopic properties and continuous-wave laser performance of Er3+,Yb3+:YMgB5O10 novel crystal. Absorption and luminescence spectra as well as kinetics of luminescence decay were studied. Ytterbium-erbium energy transfer efficiency was determined. The output characteristics (output power, slope efficiency, laser wavelength) of Er3+,Yb3+:YMgB5O10 laser were determined.Two intensive absorption bands with peaks centered at 937 nm and 976 nm were observed in the absorption spectra at the wavelength near 1 μm. The maximum value of absorption cross-section was determined to be 1.5·10–20 cm2 at 976 nm for polarization E//Ng . A number of narrow lines were observed in the absorption spectra in the 1425–1575 nm spectral range (transition 4I15/2 → 4I13/2 of erbium ions). The lifetime of the upper laser level 4I13/2 of Er3+ ions was determined to be 390 ± 20 μs. The ytterbium-erbium energy transfer efficiency for YMgB5O10 crystal with 2 at.% of Er3+ and 11 at.% for Yb3+ was close to 84 %. The maximal continuous-wave output power of 0.2 W with slope efficiency of 8 % regarding to absorbed pump power was realized at the wavelength of 1570 nm. With the improvement of cavity parameters the output laser performance of the Er,Yb:YMgB5O10 crystal can be further enhanced.Taking into account high thermal conductivity of ≈ 6.2 W·m–1·K–1, the Er,Yb:YMgB5O10 crystal can be considered as a good gain medium for 1.5 μm lasers for applications in laser rangefinder and LIDAR systems.

Abstract Nonhuman primates are useful large animal model systems for the in vivo study of hematopoietic stem cell biology. To better understand the degree of similarity of the hematopoietic systems between humans and baboons, and to explore the relevance of such studies in nonhuman primates to humans, this study was designed to compare the global gene expression profile of bone marrow CD34+ cells isolated from these 2 species. Human complementary DNA (cDNA) filter arrays containing 25 920 human cDNAs were surveyed for this purpose. The expression pattern and relative gene abundance of the 2 RNA sources were similar, with a correlation coefficient of 0.87. A total of 15 970 of these cDNAs were expressed in human CD34+ cells, of which the majority (96%) varied less than 3-fold in their relative level of expression between human and baboon. Reverse transcriptase–polymerase chain reaction analysis of selected genes confirmed that expression was comparable between the 2 species. No species-restricted transcripts have been identified, further reinforcing the high degree of similarity between the 2 populations. A subset of 1554 cDNAs, which are expressed at levels 100-fold and greater than background, is described, which includes 959 expressed sequence tags and uncharacterized cDNAs, and 595 named genes, including many that are clearly involved in hematopoiesis. The cDNAs reported here represent a selection of some of the most highly abundant genes in hematopoietic cells and provide a starting point to develop a profile of the transcriptosome of CD34+cells.

Therapeutic use of amiodarone (AMD), a Class III antiarrhythmic drug is complicated by the development of lung fibrosis (LF) and phospholipidosis (PL). In the present study, the effectiveness of a PAF antagonist, WEB 2086, against AMD induced LF and PL has been tested in hamsters. The animals were randomly divided into four groups: (1) saline + H2O; (2) WEB + H2O; (3) saline + AMD; and (4) WEB + AMD. Saline or WEB (10 mg/kg i.p.) was given 2 days prior to intratracheal instillation of water or AMD (1.5 μmol/0.25 ml/100 g BW) and thereafter daily throughout the study. Twenty-eight days after intratracheal instillation, the animals were killed and the lungs processed for various assays. The amount of lung hydroxyproline, an index of LF, in saline + H2O, WEB + H2O, saline + AMD, and WEB + AMD groups were 959 ± 46, 1035 ± 51, 1605 ± 85 and 1374 ± 69 μg/lung, respectively. Total lung PL, an index of phospholipidosis, in the corresponding groups were 8.4 ± 0.4, 8.3 ± 0.3, 11.7 ± 0.3 and 9.9 μg/lung. Lung malondialdehyde, an index of lipid peroxidation and superoxide dismutase activity in saline + H2O WEB + H2O, saline + AMD, and WEB + AMD were 93.0 ± 4.3, 93.0 ± 2.7, 138.9 ± 6.0 and 109.0 ± 3.8 nmol/lung and 359.7 ± 13.9, 394.0 ± 22.8, 497.5 ± 19.7 and 425.5 ± 4.9 units/lung, respectively. Administration of AMD alone caused significant increases in all the above indexes of lung toxicity, and treatment with WEB 2086 minimized the AMD induced toxicity as reflected by significant decreases in these indexes. Histopathological studies revealed a marked reduction in the extent and severity of lung lesions in the WEB + AMD group compared with the saline + AMD group. Treatment with WEB 2086 also reduced the acute mortality from 35% in saline + AMD group to 22% in WEB + AMD group. It was concluded that PAF is involved in the AMD induced lung fibrosis and phospholipidosis and that the PAF receptor antagonist may, therefore, be potentially useful in reducing AMD induced lung toxicity.

ABSTRACT Carbapenemase-producing Enterobacteriaceae (CPE) are a significant threat to public health. In 2015, CDC revised the surveillance definition for CPE to include all Enterobacteriaceae resistant to any carbapenem tested. However, this definition is associated with poor specificity. We evaluated the performance of this definition, compared to carbapenemase PCR, for a collection of 125 Enterobacteriaceae . We also investigated the impact of ancillary testing for carbapenemase of isolates that met the CDC CPE surveillance definition. The two ancillary tests evaluated were the Xpert Carba-R assay, a molecular test, and the carbapenem inactivation method (CIM). Two variables were evaluated for the CIM: suspension of organisms in double-distilled water (ddH 2 O) versus tryptic soy broth (TSB) to incubate disks, and incubation of plates for 6 h versus 18 to 20 h. The sensitivity and specificity of the Carba-R assay were 100% compared to the results of in-house PCR. The sensitivities of the CIM performed with TSB were 94.6% when read at 6 h and 97.7% when read at 18 to 20 h; the sensitivities with ddH 2 O were 88.0% when read at 6 h and 93.0% when incubated for 18 to 20 h. The specificity was 100% for all variables tested. Without ancillary testing, the sensitivity of the CDC definition was 98.9% for CPE, and the specificity was 6.1%. Testing isolates that screened positive by the CDC definition with the Xpert Carba-R did not change the sensitivity, and it improved the specificity to 100%. Similarly, the use of the CIM (TSB and 18 to 20 h of incubation) to confirm screen-positive isolates resulted in a sensitivity of 95.6% and specificity of 100%.

Objective: To investigate a fully automated abdominal CT-based muscle tool in a large adult screening population. Methods: A fully automated validated muscle segmentation algorithm was applied to 9310 non-contrast CT scans, including a primary screening cohort of 8037 consecutive asymptomatic adults (mean age, 57.1±7.8 years; 3555M/4482F). Sequential follow-up scans were available in a subset of 1171 individuals (mean interval, 5.1 years). Muscle tissue cross-sectional area and attenuation (Hounsfield unit, HU) at the L3 level were assessed, including change over time. Results: Mean values were significantly higher in males for both muscle area (190.6±33.6 vs 133.3±24.1 cm2, p<0.001) and density (34.3±11.1 HU vs 27.3±11.7 HU, p<0.001). Age-related losses were observed, with mean muscle area reduction of -1.5 cm2/year and attenuation reduction of -1.5 HU/year. Overall age-related muscle density (attenuation) loss was steeper than for muscle area for both sexes up to the age of 70 years. Between ages 50 and 70, relative muscle attenuation decreased significantly more in females (-30.6% vs -18.0%, p<0.001), whereas relative rates of muscle area loss were similar (-8%). Between ages 70 and 90, males lost more density (-22.4% vs -7.5%) and area (-13.4% vs -6.9%, p<0.001). Of the 1171 patients with longitudinal follow-up, 1013 (86.5%) showed a decrease in muscle attenuation, 739 (63.1%) showed a decrease in area, and 1119 (95.6%) showed a decrease in at least one of these measures. Conclusion: This fully automated CT muscle tool allows for both individualized and population-based assessment. Such data could be automatically derived at abdominal CT regardless of study indication, allowing for opportunistic sarcopenia detection. Advances in knowledge: This fully automated tool can be applied to routine abdominal CT scans for prospective or retrospective opportunistic sarcopenia assessment, regardless of the original clinical indication. Mean values were significantly higher in males for both muscle area and muscle density. Overall age-related muscle density (attenuation) loss was steeper than for muscle area for both sexes, and therefore may be a more valuable predictor of adverse outcomes.

9516 Background: KEYNOTE-022 (NCT02130466) was a phase 1/2 study of pembro + dab + tram or pembro + tram in patients (pts) with unresectable stage III/IV melanoma (parts 1-3) or solid tumors (parts 4 and 5). In previous analyses of pts with BRAFV600E/K -mutant melanoma, pembro + dab + tram was shown to have manageable safety in parts 1-3, albeit with a higher incidence of TRAEs in part 3, and substantially improved PFS, DOR, and OS vs placebo + dab + tram in part 3, although the primary end point of a statistically significant improvement in PFS was not met. Long-term follow-up of pts with BRAFV600E/K-mutant melanoma in parts 1-3 are presented. Methods: Eligible pts were ≥18 y with unresectable stage III/IV BRAFV600E/K-mutant melanoma, ≥1 measurable lesion per RECIST v1.1, ECOG PS 0/1, and no prior systemic therapy for advanced disease. In parts 1 and 2, which involved dose finding and confirmation, pts received pembro 2 mg/kg IV Q3W + dab 150 mg PO BID + tram 2 mg PO QD (MTD). In part 3, pts were randomized 1:1 to pembro + dab + tram at MTD or placebo + dab + tram. Primary end points were safety, tolerability, and MTD (parts 1 and 2); ORR per RECIST v1.1 by investigator review (part 2); and PFS per RECIST v1.1 by investigator review (part 3). Data cutoff was July 14, 2021. Results: Median (range) study follow-up was 72.9 mo (68.4-84.5) in parts 1 and 2 (n = 15) and 61.2 mo (50.7-67.5) for all pts (n = 120; 60 each arm) in part 3. Safety of pembro + dab + tram in parts 1 and 2 was consistent with prior reports; grade 3/4 TRAEs occurred in 11 pts (73%), and no additional DLTs occurred. ORR in parts 1 and 2 was 67% (95% CI, 38-88), which was similar to that reported at an earlier data cut (73% [95% CI, 45-92]); median DOR was 19.4 mo (95% CI, 2.8-NR), median OS was NR (95% CI, 10.3-NR), 48-mo OS rate was 60%, median PFS was 15.2 mo (95% CI, 4.2-NR), and 48-mo PFS rate was 28% (Ribas A et al. Nat Med. 2019;25:936-940). In part 3, median PFS was 17.0 mo (95% CI, 11.3-NR) for pembro + dab + tram vs 9.9 mo (95% CI, 6.7-15.6) for placebo + dab + tram (HR, 0.46; 95% CI, 0.29-0.74) and 24-mo PFS rate was 47% vs 16%, and median OS was 46.3 mo (95% CI, 23.9-NR) vs 26.3 mo (95% CI, 18.2-38.6); and 24-mo OS rate was 63% vs 52%, respectively. ORR was 65% (95% CI, 52-77) for pembro + dab + tram vs 72% (95% CI, 59-83) for placebo + dab + tram; median DOR was 30.2 mo (95% CI, 14.1-NR) vs 12.1 mo (95% CI, 6.0-15.7). Safety in part 3 was similar to prior reports; grade 3-5 TRAEs occurred in 42 pts (70%) in the pembro + dab + tram arm vs 27 pts (45%) in the placebo + dab + tram arm (Ferrucci PF et al. J Immunother Cancer. 2020;8:e001806). No additional grade 5 TRAEs occurred (1 grade 5 pneumonitis had occurred at prior analysis). Conclusions: At long-term follow-up, first-line pembro + dab + tram continued to show improved PFS, DOR, and OS compared with placebo + dab + tram in pts with BRAFV600E/K-mutant melanoma. TRAEs were more common with pembro + dab + tram but no new safety signals were identified. Clinical trial information: NCT02130466.

We report ion-microprobe U-Pb zircon ages from charnockites of a large Proterozoic composite batholith, Mawson Coast, Australian Antarctic Territory. The charnockites crystallized from orogenic magmas of intermediate composition (mainly 54–68% SiO2) intruded into a granulite-facies metasedimentary gneiss sequence between the second and third recognized deformations. A sample of low-Ti charnockite provides an age of 954 ± 12 Ma and a high-Ti charnockite is dated at 985 ± 29 Ma (all ages quoted at 95% confidence). The age difference is not significant at the 95% confidence level. Both these ages were obtained from zircons with igneous zoning and/or morphology and thus are thought to date igneous crystallization. Zircons from a felsic gneiss xenolith within the charnockite have cores of various ages, many from 1.7 to 2.0 Ga, but with other grains between 1.0 and 1.5 Ga and a single 2.5 Ga zircon. These zircon cores are direct evidence for an early to middle Proterozoic age for the supracrustal basement sequence in this mobile belt. Many of these zircon cores are concordant but abundant discordant grains suggest a complex history of multiple Pb-loss events. Zircon rims grew at 921 ± 19 Ma, probably during the post-charnockite deformation (D3). Previously obtained Rb-Sr dates for charnockite of 886 ± 48 Ma and 910 ± 18 Ma were probably also rest during D3. A Rb-Sr isochron date of 1061 ± 36 Ma previously reported for high-Ti charnockite from Mawson Rock is thought to be erroneous, and a new date of 959 ± 58 Ma (consistent with both the igneous and reset dates above) is interpreted from those data.

Abstract Dabigatran etexilate (Pradaxa®), an oral direct thrombin inhibitor, was recently approved in Europe for the prevention of venous thromboembolism (VTE) in patients undergoing elective total knee replacement or total hip replacement surgery. In phase III clinical trials two doses were studied: 220 mg once daily and 150 mg once daily. A post hoc pooled analysis was performed in patients with moderate renal impairment (GFR ≥30 and < 50 mL/min). The efficacy and safety of 220 mg and 150 mg dabigatran etexilate were compared with 40 mg subcutaneous enoxaparin. The analysis included data from the RE-MODEL (Eriksson BI et al. J Thromb Haemost2007; 5: 2178–2185) and the RE-NOVATE (Eriksson BI et al. Lancet2007; 370: 949–956) pivotal trials. The primary efficacy endpoint in both studies and this analysis was total VTE and all cause mortality, similarly, the key pre-specified secondary efficacy endpoint was major VTE and VTE-related mortality. Bleeding events (primary safety endpoint) were blindly adjudicated and categorized as major bleeding events (MBE) including surgical site bleeds. Of the patients treated with 220 mg dabigatran etexilate (1825), 150 mg dabigatran etexilate (1866) and 40 mg enoxaparin (1848), 337 patients had moderate renal impairment. 68% of these patients were evaluable for the primary efficacy endpoint, 242 were evaluable for the secondary efficacy endpoint, and all patients were available for safety and bleeding. The incidence of total VTE and all cause mortality was 17.7%, 23.5% and 27.8% in the 220 mg, 150 mg dabigatran etexilate and enoxaparin groups respectively. When the secondary endpoint was analyzed a similar trend, with a descriptive statistical significance for a lower event rate in the 220 mg group, was seen (see table). MBEs occurred in 6 of 113 patients in the 220 mg dabigatran treated group (5.3%), in none of the patients in the 150 mg dabigatran etexilate treated group (0.0%), and in 6 of 128 patients receiving 40 mg enoxaparin (4.7%). Notably, 3 of the 6 major bleeding events in the 220mg group started before any oral dabigatran etexilate treatment. In conclusion, in patients with moderate renal impairment undergoing hip or knee replacement surgery, oral 150 mg dabigatran etexilate showed similar efficacy compared with subcutaneous 40 mg enoxaparin, with apparently lower rates of major bleeding. Because of the potential negative impact of major bleeding especially in this population the 150 mg once daily dabigatran etexilate dose is currently recommended for this group. Table 1: Efficacy and bleeding endpoints in patients with moderate renal impairment (p-value from Fisher’s exact test compared to Enoxaparin) Event Dabigatran etexilate 220 mg qd Dabigatran etexilate 150 mg qd Enoxaparin 40 mg qd Total VTE and all cause mortality 17.7% (14/79) (CI 10.0%–27.9%) p=0.14 23.5% (16/68) (CI 14.1%–35.4%) p=0.59 27.8% (25/90) (CI 18.9%–38.2%) Major VTE and VTE related mortality 1.2% (1/83) (CI 0.0%–6.5%) p=0.04 4.3% (3/70) (CI 0.9%–12.0%) p=0.35 9.0% (8/89) (CI 4.0%–16.9%) MBE 5.3% (6/113) (CI 2.0%–11.2%) p=0.82 0.0% (0/96) (CI 0.0–3.8%) p=0.04 4.7% (6/128) (CI 1.7%–9.9%)

AbstractA selection programme was set up in 1983 in the Ivory Coast to improve the growth and live weight of the indigenous Djallonkè sheep using an open nucleus breeding system. Selection was based on male individual weights at 80, 180 and 365 days of age. Multiple sires were used in farmers' flocks. Individual animal model, using average numerator relationship was used to estimate breeding values from which genetic trends were derived. This paper reports results of the analyses of 10 417 records of 80-day weights (WT80) of lambs born between 1984 and 1992 from 29 participating farmers, and 1978 and 849 records on 180- (WT180) and 365- (WT365) day weights, respectively, of lambs from the nucleus. Phenotypic trends exhibited substantial annual fluctuation during the study period. The heaviest weights were obtained in 1986 (10·1 kg) for WT80, 1984 (23·3 kg) for WT180 and 1985 (33·7 kg) for WT365. There was an annual decline of 152 g (P<0·05) in WT80 mainly (–180 g/year) due to negative environmental trend. The phenotypic and environmental trends for WT180 were –703 and –721 g/year, respectively, while the corresponding values for WT365 were –931 and –956 g/year. Overall mean weights of the ram lambs at the three ages were 9·9, 23·3 and 33·7 kg, respectively in the base year and 9·3, 17·8 and 28·2 kg, respectively in the final year. Breeding values increased by 28, 11 and 14 g/year for WT80, WT180 and WT365, respectively. Results of this study indicate that genetic progress can be made in growth performance of Djallonkè sheep if reasonable levels of animal management as well as selection pressure are maintained.

Objective Legal, ethical, and regulatory requirements of medical research uniformly call for informed consent. We aimed to characterize and compare consent rates for neonatal randomized controlled trials in low- and lower middle-income countries versus high-income countries, and to evaluate the influence of study characteristics on consent rates. Methods In this systematic review, we searched MEDLINE, EMBASE and Cochrane for randomized controlled trials of neonatal interventions in low- and lower middle-income countries or high-income countries published 01/01/2013 to 01/04/2018. Our primary outcome was consent rate, the proportion of eligible participants who consented amongst those approached, extracted from the article or email with the author. Using a generalised linear model for fractional dependent variables, we analysed the odds of consenting in low- and lower middle-income countries versus high-income countries across control types and interventions. Findings We screened 3523 articles, yielding 300 eligible randomized controlled trials with consent rates available for 135 low- and lower middle-income country trials and 65 high-income country trials. Median consent rates were higher for low- and lower middle-income countries (95.6%; interquartile range (IQR) 88.2–98.9) than high-income countries (82.7%; IQR 68.6–93.0; p<0.001). In adjusted regression analysis comparing low- and lower middle-income countries to high-income countries, the odds of consent for no placebo-drug/nutrition trials was 3.67 (95% Confidence Interval (CI) 1.87–7.19; p = 0.0002) and 6.40 (95%CI 3.32–12.34; p<0.0001) for placebo-drug/nutrition trials. Conclusion Neonatal randomized controlled trials in low- and lower middle-income countries report consistently higher consent rates compared to high-income country trials. Our study is limited by the overrepresentation of India among randomized controlled trials in low- and lower middle-income countries. This study raises serious concerns about the adequacy of protections for highly vulnerable populations recruited to clinical trials in low- and lower middle-income countries.

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%)

Li-ion batteries (LiBs) are one of the best solutions for energy storage due to their high capacity, high power, and cyclability1,2. The increasing need for energy storage to supply electric vehicles demands continuous innovation to optimize the LiBs, specifically the manufacturing parameters to fabricate these devices. The battery production requests improved materials, cell designs, greener manufacturing processes, and recycling3,4. For instance, developing an improved anode material could be a good approach for optimizing the LiB energy density. A blend of graphite and silicon is a promising negative electrode due to the combined stability of graphite with the high theoretical capacity of silicon5,6. Since adding silicon changes the manufacturing parameters already established for commercial graphite electrode fabrication, our goal is to understand the impact of the manufacturing process, such as the calendaring effect on the properties of the silicon/graphite blend electrodes. These electrodes were prepared with two different silicon percentages, 8%, and 15%, compared to pure graphite. We investigate the morphological changes, electrochemical aging, and tortuosity when decreasing the porosity from 55% to 30% for both electrodes to evidence the porosity threshold for obtaining adequate electrode properties. Manufacturing optimization is time and cost-consuming. Modeling approaches are an excellent choice to decrease LiB fabrication scraps. We are developing machine learning and physical models of the 3D silicon-graphite electrode fabrication process within our ARTISTIC project7, and these optimization results will help to validate them. S. Chu and A. Majumdar, Nature, 488, 294–303 (2012). J. B. Goodenough and K.-S. Park, J. Am. Chem. Soc., 135, 1167–1176 (2013). J. Li, J. Fleetwood, W. B. Hawley, and W. Kays, Chem. Rev., 122, 903–956 (2022). F. M. Zanotto et al., Batter. Supercaps, 5 (2022). M. T. McDowell, S. W. Lee, W. D. Nix, and Y. Cui, Adv. Mater., 25, 4966–4985 (2013). F. Jeschull et al., J. Electrochem. Soc., 167, 100535 (2020). C. Liu, O. Arcelus, T. Lombardo, H. Oularbi, and A. A. Franco, J. Power Sources, 512, 230486 (2021).

Abstract Background: Medical financial hardship, encompassing material, behavioral, and psychologic domains, is becoming an increasingly common consequence of illness in cancer patients. Identifying at-risk patients is the first step to develop proactive approaches to mitigate this problem. To try and address this need, Mayo Clinic Breast Disease Registry (MCBDR) is prospectively collecting data about financial concerns in addition to the usual sociodemographic and clinical information. Methods: We used data from Mayo Clinic Breast Disease Registry, a prospective cohort of consenting patients seen at Mayo Clinic Rochester within one year of initial breast cancer diagnosis. Participants completed baseline and annual follow-up surveys rating their financial concerns on a linear analogue scale from 0 (“none”) to 10 (“constant concerns”). We compared patient-reported financial concern at baseline to that on each patient’s most recent survey, with worsening concerns defined as a 1+-point increase. Logistic regression evaluated for predictors of worsening financial concerns. Results: 1,957 participants responded to financial concern questions on a baseline and at least one follow-up survey between 2015 and 2020. Mean age was 58.5 years (SD 12.5), and mean time between diagnosis and the most recent follow-up was 25.6 months (SD 16.2). 357 (18.2%) reported worsening financial concerns. Only lower baseline financial status was associated with a greater likelihood of worsening financial concerns (see Table). Conclusions: More than one in seven breast cancer survivors develop worsening financial concerns within 5-years of diagnosis, and those with less financial security at baseline appear to be most vulnerable. Funding: Breast Cancer Research Foundation (CLL) and NR015259 (KJR). Patient and tumor characteristics, compared by whether financial status worsened over time Full Cohort (n=1957) Worsening, ≥ 1-point change (n=357) Stable/Improved (n=1600) p value Full Cohort (n=1957) Worsening, ≥ 1-point change (n=357) Stable/Improved (n=1600) p value Age at diagnosis II or III 502 (25.7%) 98 (27.5%) 404 (25.3%) 0.239 ≤ 50 546 (27.9%) 105 (29.4%) 441 (27.6%) IV 67 (3.4%) 17 (4.8%) 50 (3.1%) 0.086 51-64 757 (38.7%) 136 (38.1%) 621 (38.8%) 0.562 Unknown 351 (17.9%) 65 (18.2%) 286 (17.9%) 0.536 ≥65 654 (33.4%) 116 (32.5%) 538 (33.6%) 0.506 ER and/or PR positive Race No/Unknown 482 (24.6%) 92 (25.8%) 390 (24.4%) White 1863 (95.2%) 337 (94.4%) 1526 (95.4%) Yes 1475 (75.4%) 265 (74.2%) 1210 (75.6%) 0.580 Non-white 24 (1.2%) 5 (1.4%) 19 (1.2%) 0.729 Her2 positive Other/Unknown/Choose not to respond 70 (3.6%) 15 (4.2%) 55 (3.4%) 0.478 No/Unknown 1746 (89.2%) 314 (88.0%) 1432 (89.5%) Educational status Yes 176 (9.0%) 37 (10.4%) 139 (8.7%) 0.321 Less than bachelor’s degree 880 (45.0%) 168 (47.1%) 712 (44.5%) Borderline 35 (1.8%) 6 (1.7%) 29 (1.8%) 0.898 Bachelor's degree or higher 1065 (54.4%) 187 (52.4%) 878 (54.9%) 0.384 Radiation Unknown 12 (0.6%) 2 (0.6%) 10 (0.6%) 0.832 No/Unknown 781 (39.9%) 140 (39.2%) 641 (40.1%) Financial status near time of diagnosis Yes 1176 (60.1%) 217 (60.8%) 959 (59.9%) 0.768 Pay bills, money for special things 1412 (72.2%) 244 (68.3%) 1168 (73.0%) Chemotherapy/targeted therapy Pay bills, no money for special things 367 (18.8%) 80 (22.4%) 287 (17.9%) 0.046 No/Unknown 1264 (64.6%) 221 (61.9%) 1043 (65.2%) Pay bills by making cuts 102 (5.2%) 19 (5.3%) 83 (5.2%) 0.729 Yes 693 (35.4%) 136 (38.1%) 557 (34.8%) 0.241 Unable to pay bills 56 (2.9%) 10 (2.8%) 46 (2.9%) 0.911 Hormone/endocrine therapy Unknown 20 (1.0%) 4 (1.1%) 16 (1.0%) 0.750 No/Unknown 710 (36.3%) 141 (39.5%) 569 (35.6%) Employment status at time of diagnosis Yes 1247 (63.7%) 216 (60.5%) 1031 (64.4%) 0.163 Employed full-time 462 (23.6%) 83 (23.2%) 379 (23.7%) Surgery type Employed part-time/unemployed/retired 525 (26.8%) 92 (25.8%) 433 (27.1%) 0.856 Lumpectomy 846 (43.2%) 145 (40.6%) 701 (43.8%) Not available 970 (49.6%) 182 (51.0%) 788 (49.3%) 0.716 Mastectomy 903 (46.1%) 165 (46.2%) 738 (46.1%) 0.535 Stage at time of diagnosis None/Unknown 208 (10.6%) 47 (13.2%) 161 (10.1%) 0.069 0 or I 1037 (53.0%) 177 (49.6%) 860 (53.8%) Citation Format: Michael H. Storandt, Urshila Durani, Daniela Stan, Nicole Larson, Charles Loprinzi, Fergus Couch, Janet E. Olson, Nandita Khera, Kathryn J. Ruddy. Financial hardship in breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1012.

The solution to the problems of the construction of deep wells is possible when creating downhole tools on a fundamentally new ideological basis, involving physical principles, technical solutions unconventional in the field of drilling equipment. It is important to take into account the energy resources that increase with depth. Following this concept, based on the tasks of geological exploration, a downhole layout has been developed and introduced into the production of drilling wells, with design features and technological capabilities focused on a comprehensive solution to the problems of well wiring. Structurally, the downhole layout aimed at maximizing the potential energy of the working fluid is universal, designed for drilling wells with core sampling of increased diameter (100 mm or more), and with a solid face. In addition to the outer pipe and core receiver, the downhole layout is equipped with diamond drill heads with a stepped matrix, with a separate system of flushing channels, collectively realizing the effect of hydro-mechanical destruction of rocks. By introducing into the composition of the bottom-hole layout, converting the ascending flow into a rotational-ascending one, the problem of removing sludge from under the end of the stepped matrix is effectively solved. Production tests of the downhole layout with core sampling were carried out at the polymetals deposit of Central Kazakhstan, solid face during drilling of groundwater wells in the territory of the Almaty region. According to the results of production tests, it was found that the hydro-mechanical destruction of rocks is especially effective in combination with diamond drill heads with a stepped matrix. The presence of a turbulator-expander in the bottom-hole layout made it possible to significantly increase the amount of incoming sludge of drilled rock in the well sump, especially when drilling wells with a solid face. In comparable geological and technical conditions of drilling wells, serial core sets HQ with a drilling diameter of 95.6 mm had the following indicators: energy consumption – 2.1-2.4 kW / hour, core yield with a diameter of 63 mm – 93%, specific lumpiness of the core – 5-8 pcs / per linear meter of drilling, drilling was carried out at an axial load of 2200-2500 kgf, rotation speed 500-700 rpm. Similar indicators of the downhole layout: energy consumption – 1.2-1.5 kW / hour, core yield – 98-100% with a diameter of 112 mm, specific lumpiness – 2-3 pieces, axial load – 700-900 kgf, rotation speed – 300-400 rpm.

San Martín Texmelucan en el Estado de Puebla es la principal zona productora de gladiolo (Gladiolus grandiflorus Hort.) en México. No obstante, los productores de este cultivo cuentan con poca información técnica sobre su manejo, y con frecuencia sufren pérdidas en producción y calidad. En el presente trabajo se evaluó el efecto de cuatro dosis de fertilización (DF) expresadas en kg ha-1: 65 N - 14.9 P – 171 K - 16.6 Mg - 31.2 Ca (DF1); 40.5 N – 24 P – 171 K – 23 Mg - 37.2 Ca - 0.2 B - 8.5 S (DF2); 81 N – 24 P -171 K – 23 Mg - 37.2 Ca - 0.2 B (DF3); y 81 N – 24 P – 171 K – 23 Mg - 37.2 Ca (DF4 ), en el crecimiento del cultivo, calidad de flor y sanidad de la planta de las variedades ‘Borrega roja’ (BR) y ‘Espuma’ (E). Se estimaron los grados-día de desarrollo (GDD) necesarios para las etapas fenológicas de emergencia, aparición de hojas, espigamiento, madurez comercial, y madurez fisiológica del cormo. Se midió altura de planta, índice de área foliar y porcentaje de plantas enfermas. En la cosecha se evaluó el número de botones florales y la superficie de flor. El ciclo biológico fue de 111 d para BR (1424 GDD) y de 129 d o 1662 GDD para E; ambas variedades produjeron siete hojas y 13 botones florales. BR creció más rápido a lo largo del ciclo. Las diferencias en precocidad se gestaron a partir de la aparición de la sexta hoja (931 y 956 GDD para BR y E, respectivamente). Al final del ciclo E fue superior (P < 0.05) en altura de planta (127 cm), índice de área foliar (1.5), acumulación de calor a la madurez fisiológica (1662 GDD) y superficie de flor (10.8 cm2). No hubo efecto de las dosis de fertilización en el desarrollo y crecimiento del cultivo. La dosis DF2 redujo la mortalidad de plantas a 3.3 %, sin afectar el desarrollo del cultivo ni la calidad de la flor. Los tratamientos con alto contenido de nitrógeno (DF3 y DF4) tuvieron más de 4.8 % de plantas muertas debido a enfermedades.

Background:Patients with juvenile idiopathic arthritis (JIA) may have lower protective levels of anti-vaccine antibodies due to high inflammatory activity, interrupted or incomplete vaccination schedule, and due to using of immune-modulating drugs, e.g. systemic corticosteroids (CS), methotrexate (MTX) and biologics.Objectives:The aim of our study was to find the predictors of low levels of anti-vaccine antibodies in patients with JIA.Methods:In the present study were included data 170 JIA (55 boys and 115 girls) aged from 2 to 17 years, who received scheduled vaccination before the age of 2 years and before JIA onset against measles, parotitis, hepatitis B, diphtheria and rubella. In all patients the Ig G anti-vaccine antibodies levels were detected with ELISA. In each patient we evaluate the type of the disease (oligoarthritis - 73, polyarthritis - 61, systemic-16 and enthesitis-related arthritis - 20), onset age, presence of uveitis, duration of JIA, treatment with corticosteroids (CS), methotrexate (MTX) and biologics. Data presented with median and 25%-75%.Results:The main demographic characteristics: age of inclusion in the study 11.4 (7.6-14.8) years, disease onset – 6.0 (3.7-9.0) years, disease duration – 3.8 (1.9-6.5) years. Treatment with CS was in 43 (25.3%), MTX in 154 (90,6%) and biologics 82 (48.2%) patients, among them 53 had TNFa-inhibitors. More than 1 biologic consequently received 16/82 (19.5%) patients. Protective levels of anti-measles antibodies was in 98 (57,6%) of all JIA population, anti-parotitis – 136 (80.0%), anti-hepatitis B – 85 (50.0%), anti-diphtheria – 88 (51,7%), anti-rubella – 167 (98.8%). Data of vaccination status and anti-vaccine antibodies levels in the table. In univariate and multivariate regression analysis the main risk factors for anti-measles antibodies levels were MTX using (p=0.045), more than 1 biologics (p=0.0004); for anti-hepatitis B – MTX (p=0.03), for anti-diphtheria antibodies: onset age (p=0.0002), JIA duration (p=0.00007), number vaccine doses (p=0.02), more than 1 biologics (p=0.01); combined treatment with biologics and other drugs (MTX or CS).ParameterNo treatment (n=14)MTT, only(n=74)Biologics±MTT±CS (n=82)P# anti-measels vaccine doses2.0 (2.0; 2.0)2.0 (1.0; 2.0)2.0 (1.0; 2.0)0.19Anti-measels IgG, Me/ml0.28 (0.1; 0.6)0.4 (0.1-0.7)0.17 (0.0; 0.29)0.0002Protective anti-measels IgG level, n (%)8 (57)50 (68)40 (49)0.06# anti-parotitis vaccine doses2.0 (2.0; 2.0)2.0 (1.0; 2.0)2.0 (1.0; 2.0)0.19Anti-parotitis IgG, Me/ml2.0 (1.2; 4.3)2.8 (1.3; 5.6)2.5 (1.0; 5.1)0.47Protective anti-parotitis IgG level, n (%)12 (86)62 (84)62 (76)0.38# anti-diphtheria vaccine doses5.0 (4.0; 5.0)4.0 (4.0; 5.0)5.0 (4.0; 5.0)0.39Anti-diphtheria IgG, Me/ml0.17 (0.0; 1.2)0.18 (0.0; 0.4)0.1 (0.0; 0.2)0.18Protective anti-diphtheria IgG level, n (%)9 (64)42 (57)37 (45)0.22# anti-hepatitis B vaccine doses3.0 (3.0; 3.0)3.0 (3.0; 3.0)3.0 (3.0; 3.0)0.91Anti-hepatitis B IgG, Me/ml0.56 (0.0; 7.5)11.4 (0.3; 44.8)10.0 (0.0; 44.1)0.08Protective anti-hepatitis B IgG level, n (%)3 (21)40 (54)42 (51)0.08# anti-rubella vaccine doses2.0 (2.0; 2.0)2.0 (1.0; 2.0)2.0 (1.0; 2.0)0.19Anti-rubella IgG, Me/ml121.8(70.0; 200.0)95.6(53.3; 198.2)56.4(37.0; 100.1)0.008Protective anti-rubella IgG level, n (%)14 (100)73 (100)80 (98)0.34Conclusion:MTX, biologics and JIA durations are factors influenced on anti-vaccine antibody level. It is necessary to regularly check the levels of anti-vaccine antibodies, especially anti-measels and anti-diphtheria for creation of the individual vaccination plan for JIA patients, treated with MTX and biologics.Disclosure of Interests:None declared

Objective: analysis of the immediate and long-term results of surgical treatment of patients with lymph node (Ln) involvement in recurrent ovarian cancer (OC), as well as the search for prognostic factors for progression-free survival (PfS) and overall survival (OS).Materials and methods. The retrospective analysis included patients under the age of 75 who underwent surgery for recurrence of OC with Ln involvement at n.n. Blokhin national medical Research Center of Oncology in the period from 2005 to 2020. All patients had previously received combined treatment due to a primary diagnosis of OC. Exclusion criteria: the presence of concomitant pathology in the decompensation phase, primary multiple malignant tumors and recurrences of non-epithelial ovarian tumors. The analysis of the main operational characteristics, the frequency of postoperative complications according to Clavien–Dindo within 30 days after surgery, PfS, OS, as well as parameters affecting the long-term results of treatment were performed.Results. The study included 123 patients: a cohort of isolated lesions of the Ln (n = 65) and a group of combined recurrence in the Ln and other anatomical locations (n = 58). The frequency of complete cytoreduction was significantly higher in the group of patients with isolated recurrence in the Ln: 86.62 % versus 53.4 % in patients with combined relapse, p <0.0001. The median duration of the operation was also significantly higher in patients with combined recurrence: 245 min versus 180 min in a cohort of patients with isolated recurrence in the Ln, p <0.0001. Postoperative complications of grade III B were more often observed in the group of combined recurrence: 6.8 % versus 1.5 % in the group of isolated recurrence in the Ln, p = 0.148. none of the patients in the group of isolated recurrence in the Ln had postoperative mortality, while in the group of combined recurrence 2 (3.4 %) patients died after surgery from developed complications. In patients with isolated recurrence in the Ln and combined recurrence of OC, the median PfS was significantly higher when complete cytoreduction was achieved: 31.0 months and 18.0 months versus 10.0 months and 9.0 months with incomplete repeated cytoreduction, p <0.0001. In patients with isolated recurrence in the Ln and combined recurrence of OC, the median OS was identically significantly higher when complete repeated cytoreduction was achieved: 97.0 months and 60.0 months versus 34.0 months and 27.0 months with incomplete cytoreduction, p <0.0001.Conclusion. Surgical treatment of recurrence of OC is justified only if it is possible to achieve complete cytoreduction and platinum-sensitive type of recurrence of OC. Low grade tumor, platinum-sensitive type of recurrence, absence of marker recurrence of OC, isolated recurrence in Ln, complete repeated cytoreduction and lymphodissection were identified as predictors of PfS in multivariate analysis. The following factors had an independent favorable effect on OS in multivariate analysis: low tumor grade, platinum-sensitive type of recurrence, satisfactory overall status on the ECOg scale (0–1 points) at the time of detection of relapse, isolated recurrence in the Ln and complete repeated cytoreduction.

BackgroundPrimary Sjögren’s syndrome (pSjS) is a chronic and complex systemic autoimmune disease, primarily characterised by inflammation and progressive destruction of the exocrine glands (ie, autoimmune epithelitis) [1].ObjectivesWe evaluated disease progression, treatment patterns, mortality, and healthcare resource utilization (HCRU) of pSjS patients in the United States (US) to understand the real-world experiences of patients with pSjS.MethodsThis retrospective cohort study utilised data from US Optum Clinformatics claims between 01 May 2000 and 31 December 2020. The study included pSjS patient cohort and general population cohort, matched (1:1) on age, sex, and index date. Baseline period of 365 days prior to the index date was used for assessment of baseline comorbidities. Descriptive statistics were used to describe baseline characteristics, HCRU, and treatment pattern while multivariable models were used to assess hazard ratios (HRs) and risk factors.ResultsOverall, 23,168 patients with pSjS (ICD-9 710.2 Sicca syndrome and ICD-10 M 35.0 Sjogren Syndrome and excluding patients with Rheumatoid arthritis [RA], Systemic sclerosis [SS] and Systemic lupus erythematosus [SLE] diagnoses codes) were included in the cohort (mean [SD] age: 61.5 [15.3] years; females: 85%). At baseline, 79.4% and 8.2% of pSjS patients had systemic complications and organ-specific autoimmune comorbidities, respectively. In a sub-set of the cohort including patients with at least 5 years of follow-up, by the end of 5 years 96.8% and 16.5% of patients developed systemic complications and organ-specific autoimmune comorbidities, respectively (Table 1). The most frequently occurring organ-specific autoimmune comorbidities over the 5-year follow-up included Graves disease (5.4%), Hashimoto disease (3.7%), and discoid/subacute cutaneous lupus erythematosus (3.5%). Mortality was reported in 7.4% of the patients during 5-year follow-up. Risk factors associated with higher mortality included systemic complications in renal (HR [95% CI]: 2.29 [2.09–2.52]), cardiovascular (HR [95% CI]: 2.42 [2.19–2.67]), lungs (HR [95% CI]: 3.73 [3.41–4.09]) and haematological domains (HR [95% CI]: 2.83 [2.56–3.13]), non-Hodgkin’s lymphoma (HR [95% CI]: 2.58 [2.12–3.14]), and primary biliary cirrhosis (HR [95% CI]: 2.17 [1.60–2.96]). Corticosteroids (28.2%), hydroxychloroquine (15.7%), and cyclosporine (10.9%) were most frequently used medications. During the year following the first pSjS diagnosis, defined as the first claim with the Sjogren Syndrome ICD code (index date), the mean all-cause healthcare costs have increased by 27% from $21,634 to $27,526 per patient per year.Table 1.Occurrence of systemic complications and organ-specific autoimmune comorbidities over follow-up of 5 yearsVariable, n (%)Baseline (N=6000)Within 5 years (N=6000)Any systemic complication4,555 (75.9%)5,806 (96.8%)Articular involvement3,176 (52.9%)5,026 (83.8%)Renal involvement352 (5.9%)1,185 (19.8%)Cardiovascular complications342 (5.7%)826 (13.8%)Muscles1,390 (23.2%)2,732 (45.5%)Pancreatic31 (0.5%)88 (1.5%)Lungs373 (6.2%)1,383 (23.1%)Peripheral nervous system766 (12.8%)2,109 (35.2%)Haematological1,016 (16.9%)2,507 (41.8%)Glandular542 (9.0%)2,274 (37.9%)Central nervous system212 (3.5%)556 (9.3%)Biological153 (2.6%)408 (6.8%)Skin517 (8.6%)1,327 (22.1%)Lymphadenopathy374 (6.2%959 (16.0%) Non-Hodgkin’s lymphoma59 (1.0%)131 (2.2%)Any organ-specific autoimmune disease464 (7.7%)992 (16.5%)ConclusionThese results provide additional evidence that pSjS is associated with substantial morbidity and clinical burden supporting the need for safe and efficacious disease modifying treatment options in this patient population.References[1]Mariette X, Criswell LA. N Engl J Med. 2018;378(10): 931-939.AcknowledgementsMedical writing and editorial assistance were provided by Sanjeev Kallapari and Chiranjit Ghosh, PhD of Sanofi. This study was funded by Sanofi.Disclosure of InterestsLAMA KALOUCHE-KHALIL Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi., Roopali Gandhi Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi., Lichen Hao Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi., Ekaterina Smolkina Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi., Fabienne Schumacher Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi.

Background. Artisanal and small-scale gold mining is a human health concern, especially in low-income countries like Uganda due to the use of mercury (Hg) in the mining process. Objective. The aim of the present study was to assess Hg exposure among artisanal and small-scale gold miners in Uganda through biologic monitoring parameters and Hg-related clinical manifestations. Methods. A cross-sectional study was conducted from June to July 2018 among 183 miners from Ibanda (Western region), Mubende (Central region), Amudat (Karamoja region) and Busia (Eastern region) in Uganda. An interviewer-administered questionnaire and health assessment were used to collect socio-demographic, exposure and self-reported Hg poisoning symptoms. In addition, 41 urine, 41 blood and 26 environment samples were assessed. Descriptive statistics, Kruskal-Wallis test and Wilcoxon signed-rank test for comparison of Hg levels in urine and blood among miners were performed while logistic regression was used to assess associations between exposure and Hg poisoning-related symptoms. Results: The miners ranged from 15 to 65 years old and were primarily male (72.6%). The majority (73.3%) had worked directly with Hg for an average duration of 5.3 years. Symptoms associated with working directly with Hg included chest pain (odds ratio (OR)=9.0, confidence interval (CI)=3.3 to 24.6), numbness (OR=8.5, CI=2.1 to 34.4), back pain (OR=6.2, CI= 2.2 to 17.5), fatigue and stress (OR=5.4, 2.0 to CI=14.9), headache (OR=4.7, CI=1.9 to 11.3), dizziness (OR=3.8, CI=1.5 to 9.7) joint pain (OR=3.2, CI=1.3 to 8.3) and respiratory problems (3.2, 1.0 to 10.1). Statistically significant differences in Hg levels with p-values less than 0.05 were observed across district, gender and type of work. Mubende had the highest blood and urine levels (136 μg/l and 105.5 μg/l) in comparison with Busia (60 μg/l and 70.6 μg/l) and Ibanda (43 μg/l and 58 μg/l). Females (84.7 μg/l), panners (109 μg/l) and those with knowledge of occupational health and safety measures (95.6 μg/l) reported higher levels of Hg in urine. The average levels of Hg in water and soil samples were 23.79 μg/l and 0.21 μg/l, respectively. Conclusions. Variation in Hg levels were attributed to varied duration of exposure across geographical sites. There was considerable exposure to Hg as indicated by both clinical manifestations and biologic parameters among miners in Uganda with Hg in urine exceeding the recommended thresholds. Participant Consent. Obtained Ethics Approval. Ethical approval was obtained from the Makerere University School of Health Science Institutional Review Board (reference number SHSREC REF 2018–2019) and Uganda National Council for Science and Technology (reference number SS 4577) Competing Interests. The authors declare no competing financial interests.

Abstract An experiment with four volumes of irrigation and five controlled-release fertilizers (CRFs) was conducted to evaluate effects on plant growth and mineral nutrient content. Rooted cuttings of Cotoneaster dammeri ‘Skogholm’ and seedlings of Rudbeckia fulgida ‘Goldsturm’ were grown in 3.8 liter (4 qt) containers in a pine bark:sand substrate (8:1, by vol) incorporated with 3.5 g (0.12 oz) N per container with one of the following five CRFs: Meister 21N–3.5P–11.1K (21–7–14), Osmocote 24N–2.0P–5.6K (24–4–7), Scotts 23N–2.0P–6.4K (23–4–8), Sustane 5N–0.9P–3.3K (5–2–4) or Woodace 21N–3.0P–9.5K (21–6–12). Irrigation volumes of 200 ml (0.3 in), 400 ml (0.6 in), 800 ml (1.1 in), or 1200 ml (1.7 in) were applied once daily (single) or in two equal applications with a two hr interval between irrigation allotments (cyclic). All measured variables were unaffected by irrigation application (cyclic or single). Top dry weight of cotoneaster increased quadratically with increasing irrigation volume for all CRFs. Maximum top dry weight was obtained with 612 ml (0.8 in), 921 ml (1.3 in), 928 ml (1.3 in), 300 ml (0.6 in), or 909 ml (1.3 in) for plants fertilized with Meister, Osmocote, Scotts, Sustane, and Woodace, respectively. Osmocote, Scotts, and Woodace produced 90% of maximum top weight over a wide range of irrigation volumes [≈ 550 ml (0.8 in) to 1200 ml (1.5 in)]. Stomatal conductance of cotoneaster fertilized with Osmocote 24–4–7 increased linearly with increasing volume of irrigation, whereas net photosynthetic rate increased quadratically and was highest at 800 ml (1.1 in). All CRFs, excluding Sustane, had similar dry weights when irrigated with 200 ml (0.3 in). At 800 ml (1.1 in) and 1200 ml (1.7 in), cotoneaster fertilized with Osmocote 24–4–7 and Scotts 23–4–8 produced greater top dry weight compared to Meister, Sustane, and Woodace. Top dry weight of rudbeckia increased quadratically with increasing irrigation volume regardless of CRFs. Maximum dry weight was produced with 1160 ml, 931 ml, 959 ml, 1091 ml, or 1009 ml for plants grown with Meister, Osmocote, Scotts, Sustane, or Woodace, respectively. Ninety percent of the maximum top dry weight of both species within each CRF could be obtained with a 40% reduction in irrigation volume. Nitrogen content of cotoneaster and rudbeckia were unaffected by irrigation volume, whereas P and K content, depending upon CRF and plant, was reduced at low irrigation volumes.

A study on the adsorption characteristic of Iron onto Poly[eugenol-co-(divinyl benzene)] (EDVB) from aqueous solution has been conducted. EDVB was produced and characterized by using FTIR spectroscopy. The adsorption was studied by a batch method by considering the factors affecting the adsorption such as initial metal ion concentration, adsorption selectivity, and mechanism of adsorption using a sequential desorption method. The adsorption of Iron onto EDVB followed a pseudo-2 order kinetics model with the rate constant of 0,144 L2 mmol-1 min-1. The adsorption isotherm was studied with Tempkin, Langmuir and Freundlich models. The adsorption capacity (Qmax) obtained by Langmuir isotherms was 250mg.L-1 while the equilibrium value was 0.8 Lmg-1. A competitive adsorption study showed that EDVB is adsorbed selectively towards Iron rather than Chromium, Coppers and Cadmium ions. 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Abstract Introduction Recent results from the HELIOS phase 3 study in relapsed/refractory CLL/SLL demonstrated that the addition of ibrutinib to chemoimmunotherapy with bendamustine/rituximab (BR) leads to an 80% reduction in risk of progression or death compared with placebo + BR (Chanan-Khan et al. ASCO 2015). In addition to prolongation of progression-free survival (PFS; median not reached vs 13.3 months; hazard ratio: 0.203, 95% confidence interval: 0.150-0.276, p<0.0001), overall response rate (ORR) and rates of complete response (CR) or CR with incomplete marrow recovery (CRi) were significantly improved with ibrutinib + BR (ORR: 82.7% vs 67.8%; CR/CRi: 10.4% vs 2.8%). Here we report additional analyses on the quality of response with ibrutinib combined with BR. Methods In total, 578 patients (pts) with relapsed/refractory CLL/SLL requiring treatment were randomized 1:1 (289 per arm) to receive BR (≤ 6 cycles) with either ibrutinib (420 mg daily) or placebo. Purine analog refractoriness (yes vs no) and number of prior therapies (1 vs > 1) were stratification factors. Pts with deletion 17p (del17p; > 20% of cells) were excluded. All pts were required to have ≥ 1 abnormal lymph node (LN; defined as a measurable lesion > 1.5 cm). The primary end point was independent review committee (IRC)-assessed PFS. In this analysis, individual parameters of response (LN, spleen, overall radiology, absolute lymphocyte count [ALC], complete blood count [CBC], and bone marrow [BM]) were evaluated. Minimal residual disease (MRD) was assessed by flow cytometry using an 8-color panel (Rawstron AC, et al. Leukemia. 2007;21:956-964); MRD samples were collected at confirmation of suspected CR (bone marrow) and every 3 months thereafter (peripheral blood). Rate of MRD-negative response was defined as the proportion of pts who reached negative disease status (< 0.01%, ie, < 1 CLL cell/10,000 leukocytes) in any sample. Reported MRD rates are based on the intent-to-treat (ITT) population. Results The ORR assessed by the IRC was 82.7% with ibrutinib + BR vs 67.8% with placebo + BR (p < 0.0001), and was consistent with ORR reported by the treating physician (investigator assessed) (ORR: 86.2% vs 68.9%, p < 0.0001). However, rates of CR/CRi were higher by investigator assessment (21.4%, ibrutinib + BR vs 5.9%, placebo + BR) than IRC (10.4% vs 2.8%). The IRC employed an independent evaluation of radiological scans including stringent evaluation of LN and volumetric assessment of spleen size-the main reasons for the difference in CR/CRi rates between investigator and IRC assessment. At baseline, similar proportions of pts in each arm had bulky disease defined as LN > 5 cm (54%-58%) or abnormal spleen (~40%) as assessed by IRC. Complete resolution of previous CLL/SLL manifestations as assessed by the IRC was achieved more often in the ibrutinib + BR arm in comparison with placebo + BR for LN (34.6% vs 15.2%), spleen (56.7% vs 37.0%), overall radiology (21.1% vs 9.0%), and BM (19.7% vs 5.9%). Rates of normalization of ALC (> 90%) and CBC (> 70%) were high and similar in the 2 arms. MRD was assessed in 120 pts treated with ibrutinib + BR and 57 pts treated with placebo + BR and was negative in 37 pts and 14 pts, respectively, which corresponds with an MRD-negative response rate of 12.8% vs 4.8% for ibrutinib + BR vs placebo + BR (p = 0.0011). Investigator-determined responses by different levels of MRD are shown in Table 1. The percentage of pts with an MRD level < 1% was higher with ibrutinib + BR vs placebo + BR (32.2% vs 11.8%). Moreover, the percentage of pts with an MRD level < 0.1% was higher for ibrutinib + BR vs placebo + BR (24.6% vs 7.6%) suggesting that the depth of response with ibrutinib + BR was superior. Kaplan-Meier plots by MRD level (Figure 1) show that a lower MRD level was associated with a longer PFS. However, pts in the ibrutinib + BR arm had a more sustained response at every MRD level compared with pts in the placebo + BR arm. Conclusions Pts treated with ibrutinib + BR showed not only a higher ORR, but also a greater depth of response, with more CRs and a higher rate of resolution of LN, spleen, and BM involvement. Furthermore, the rate and depth of MRD negativity was improved, and appeared to last longer in pts treated with ibrutinib + BR compared with pts receiving placebo + BR. With a median follow up of 17 months in the ibrutinib + BR arm, no MRD-negative pts and few MRD-positive pts had progressed, thus evaluating a trend in PFS with MRD negativity is currently limited in this arm. Disclosures Cramer: Gilead: Other: Travel grant, Research Funding; Glaxo Smith Klein/Novartis: Research Funding; Astellas: Other: Travel grant; Mundipharma: Other: Travel grant; Janssen: Other: Travel grant, Research Funding, Speakers Bureau; Hoffman LaRoche: Other: Travel grant, Research Funding, Speakers Bureau. Off Label Use: Combination of bendamustine, obinutuzumab and ibrutinib for treatment of CLL. Fraser:Hoffman LaRoche: Consultancy, Honoraria; Janssen: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Demirkan:Amgen: Consultancy; Celgene: Other: Travel reimbursement. Santucci Silva:Merck: Research Funding; Celgene: Research Funding; GSK: Research Funding; Janssen: Other: Travel reimbursement, Research Funding; Hoffman LaRoche: Other: Travel reimbursement, Research Funding; Novartis: Other: Travel reimbursement. Janssens:Mundipharma: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy. Goy:Allos, Biogen Idec, Celgene, Genentech, and Millennium. Gilead: Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Mayer:Janssen: Research Funding. Dilhuydy:Roche: Honoraria, Other: Travel reimbursement; Janssen: Honoraria, Other: Travel reimbursement; Mundipharma: Honoraria. Bartlett:Millenium: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; ImaginAB: Research Funding; Astra Zeneca: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Gilead: Consultancy; Seattle Genetics: Consultancy, Research Funding; Celgene: Research Funding. Rule:Roche: Consultancy, Other: Travel reimbursement; J&J: Consultancy, Other: Travel reimbursement, Research Funding; Celgene: Consultancy, Other: Travel reimbursement; Gilead: Research Funding. Sun:Janssen/J&J: Employment, Equity Ownership. Phelps:Janssen/J&J: Employment, Equity Ownership. Mahler:Janssen: Employment, Other: Travel reimbursement. Salman:Janssen/J&J: Employment, Equity Ownership. Schaffer:Janssen: Employment. Balasubramanian:Pharmacyclics LLC, an AbbVie Company: Equity Ownership; Janssen: Employment, Equity Ownership. Howes:Janssen/J&J: Employment, Equity Ownership. Hallek:AbbVie: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Celgene: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Pharmacyclics: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Gilead: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Boehringher Ingelheim: Honoraria, Other: Speakers Bureau and/or Advisory Boards; Roche: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Mundipharma: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Janssen: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding.

The pandemic of COVID-19 has afflicted every individual and has initiated a cascade of directly or indirectly involved events in precipitating mental health issues. The human species is a wanderer and hunter-gatherer by nature, and physical social distancing and nationwide lockdown have confined an individual to physical isolation. The present review article was conceived to address psychosocial and other issues and their aetiology related to the current pandemic of COVID-19. The elderly age group has most suffered the wrath of SARS-CoV-2, and social isolation as a preventive measure may further induce mental health issues. Animal model studies have demonstrated an inappropriate interacting endogenous neurotransmitter milieu of dopamine, serotonin, glutamate, and opioids, induced by social isolation that could probably lead to observable phenomena of deviant psychosocial behavior. Conflicting and manipulated information related to COVID-19 on social media has also been recognized as a global threat. Psychological stress during the current pandemic in frontline health care workers, migrant workers, children, and adolescents is also a serious concern. Mental health issues in the current situation could also be induced by being quarantined, uncertainty in business, jobs, economy, hampered academic activities, increased screen time on social media, and domestic violence incidences. The gravity of mental health issues associated with the pandemic of COVID-19 should be identified at the earliest. Mental health organization dedicated to current and future pandemics should be established along with Government policies addressing psychological issues to prevent and treat mental health issues need to be developed. References World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard. 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Abstract Introduction Lichen sclerosus (LS) is an autoimmune inflammatory skin condition primarily affecting the vulva and perianal areas and leading to scarring that can affect sexual function. Most research on symptomatology of LS to date includes predominantly postmenopausal populations and focuses on pruritis, not sexual pain symptoms. Objective This study aims to characterize sexual pain symptoms associated vulvar LS among premenopausal women. Methods A cross-sectional web-based study was conducted in premenopausal women with clinical and/or biopsy-confirmed vulvar LS between the ages of 18-50 years. Participants completed a 28-question survey evaluating demographics, characteristics of symptoms, timing and accuracy of diagnosis, and concomitant autoimmune conditions. Numerical data were expressed as mean +/- standard deviation. Bivariate Pearson correlation was used to determine the relationship between age of symptom onset and time interval to diagnosis. Results Of the 956 responses received, 910 met inclusion criteria. Self-reported ethnicity of the study population was 87% White, 4% Latina or Hispanic, 3% Asian, and 1% Black. The mean age of the population was 36.5 years, ranging from 18-50 years. There was a 4.3-year mean delay in diagnosis, with average age of symptom onset of 27.7 years and average age of diagnosis of 33.2 years. There was an inverse correlation between the age at which symptoms began and the time interval to diagnosis with a Pearson correlation coefficient of -0.509 (t(805)=16.752, p&lt;0.0001). Most prevalent symptoms were vulvar fissures (68%), dyspareunia (68%), tearing with intercourse or vaginal insertion (63%), and labial resorption (61%), with vulvar fissures (49%) and dyspareunia (46%). These symptoms were more common than introital stenosis (34%). Vulvar fissures (41%) and dyspareunia (35%) most often prompted medical attention. Thirty-six percent reported clitoral phimosis and 34% reported decreased clitoral sensation. Only 4% of respondents reported that decreased clitoral sensation prompted medical attention. Over 75% of respondents initially received an alternative diagnosis, most commonly vulvovaginal yeast infection (54%) or bacterial vaginosis (22%). Most common concomitant autoimmune condition reported was hypothyroidism (10%); which was significantly greater than the general population prevalence (2%) (p&lt;0.0001). Post-hoc analysis indicated no statistical difference between biopsy-confirmed and clinically-diagnosed LS across all demographics and responses. Conclusions Vulvar LS affects sexual function in premenopausal women. LS symptoms in premenopausal women include vulvar fissures, dyspareunia, tearing with intercourse or vaginal insertion, and decreased clitoral sensation. Dyspareunia is present is over two-thirds of premenopausal women with vulvar LS, with vulvar fissures and tearing much more common and bothersome than introital stenosis. Patients are less likely to be affected by or seek medical attention for clitoral phimosis, even though it is present in over one-third of those with LS. Vulvar LS should be considered and evaluated in women of all ages presenting with vulvar symptoms. Sexual health and function should be a core outcome measure in LS research and addressed in the evaluation and treatment of this condition. Disclosure No

Abstract Background Disconnected pancreatic duct syndrome (DPDS) is a complication of acute necrotizing pancreatitis in the neck and body of the pancreas often manifesting as persistent pancreatic fluid collection (PFC) or external pancreatic fistula (EPF). This systematic review and pairwise meta-analysis aimed to review the definitions, clinical presentation, intervention, and outcomes for DPDS. Methods The PubMed, EMBASE, MEDLINE, and SCOPUS databases were systematically searched until February 2020 using the PRISMA framework. A meta-analysis was performed to assess the success rates of endoscopic and surgical interventions for the treatment of DPDS. Success of DPDS treatment was defined as long-term resolution of symptoms without recurrence of PFC, EPF, or pancreatic ascites. Results Thirty studies were included in the quantitative analysis comprising 1355 patients. Acute pancreatitis was the most common etiology (95.3%, 936/982), followed by chronic pancreatitis (3.1%, 30/982). DPDS commonly presented with PFC (83.2%, 948/1140) and EPF (13.4%, 153/1140). There was significant heterogeneity in the definition of DPDS in the literature. Weighted success rate of endoscopic transmural drainage (90.6%, 95%-CI 81.0–95.6%) was significantly higher than transpapillary drainage (58.5%, 95%-CI 36.7–77.4). Pairwise meta-analysis showed comparable success rates between endoscopic and surgical intervention, which were 82% (weighted 95%-CI 68.6–90.5) and 87.4% (95%-CI 81.2–91.8), respectively (P = 0.389). Conclusions Endoscopic transmural drainage was superior to transpapillary drainage for the management of DPDS. Endoscopic and surgical interventions had comparable success rates. The significant variability in the definitions and treatment strategies for DPDS warrant standardisation for further research.

AbstractThis study was aimed to evaluate the success rate of high-flow nasal cannula (HFNC) oxygen therapy and factors causing therapy failure. This prospective observational study included 131 children who received HFNC oxygen and followed-up in the pediatric emergency department, pediatric clinics, and pediatric intensive care unit between March 2018 and December 2019. The median age was 23.0 months (interquartile range [IQR]: 9.0–92.0) and 65 patients were male (49.6%). The most common reason for requiring HFNC oxygen therapy was pneumonia (n = 75, 57.3%). A complex chronic condition was present in 112 (85.5%) patients. Therapy success was achieved in 116 patients (88.5%). The reason for requiring treatment and the patients' complex chronic condition did not affect the success of the therapy (p = 0.294 and 0.091, respectively). In the first 24 hours of treatment, a significant improvement in pulse rate, respiratory rate, pH, and lactate level were observed in successful HFNC oxygen patients (p < 0.05). In addition, these patients showed a significant improvement in SpO2 and SpO2/FiO2 ratio, and a significant decrease in FiO2 and flow rate (p < 0.05). HFNC oxygen success rate was 95.6% in patients with SpO2/FiO2 ≥ 150 at the 24th hour; it was 58.0% in those with SpO2/FiO2 < 150 (p < 0.001). Caution should be exercised in terms of HFNC oxygen failure in patients with no significant improvement in vital signs and with SpO2/FiO2 < 150 during treatment.

BACKGROUND: Pregnancy hypertension continues to cause maternal and perinatal morbidity. Two linked UK randomized trials showed adding self-monitoring of blood pressure (SMBP) with automated telemonitoring to usual antenatal care did not result in earlier detection or better control of pregnancy hypertension. This article reports the trials’ integrated cost analyses. METHODS: Two cost analyses. SMBP with usual care was compared with usual care alone in pregnant individuals at risk of hypertension (BUMP 1 trial [Blood Pressure Monitoring in High Risk Pregnancy to Improve the Detection and Monitoring of Hypertension], n=2441) and with hypertension (BUMP 2 trial, n=850). Clinical notes review identified participant-level antenatal, intrapartum, and postnatal care and these were costed. Comparisons between trial arms used means and 95% CIs. Within BUMP 2, chronic and gestational hypertension cohorts were analyzed separately. Telemonitoring system costs were reported separately. RESULTS: In BUMP 1, mean (SE) total costs with SMBP and with usual care were £7200 (£323) and £7063 (£245), respectively, mean difference (95% CI), £151 (−£633 to £936). For the BUMP 2 chronic hypertension cohort, corresponding figures were £13 384 (£1230), £12 614 (£1081), mean difference £323 (−£2904 to £3549) and for the gestational hypertension cohort were £11 456 (£901), £11 145 (£959), mean difference £41 (−£2486 to £2567). The per-person cost of telemonitoring was £6 in BUMP 1 and £29 in BUMP 2. CONCLUSIONS: SMBP was not associated with changes in the cost of health care contacts for individuals at risk of, or with, pregnancy hypertension. This is reassuring as SMBP in pregnancy is widely prevalent, particularly because the COVID-19 pandemic. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03334149.

Abstract Aim The aim of this article was to evaluate uterocervical angle (UCA) and cervical length (CL) measured at 16 to 24 weeks of gestation using transvaginal sonography (TVS) as predictors of spontaneous preterm birth. Methods In this prospective study, TVS was performed in 159 primigravidas with a singleton, uncomplicated pregnancy at 16 to 24 weeks of gestation to measure the anterior UCA and CL. All the cases were followed until labor to document gestational age at delivery. Results The risk of spontaneous preterm birth was higher in women with obtuse UCA (>95 degrees) with sensitivity of 86.7%, specificity of 93.0%, positive predictive value of 83.0%, negative predictive value of 94.6%, and p-value of <0.001. The difference between the means was statistically significant (p-value < 0.001). UCAs ≥105degrees and 95 to 105 degrees were found to be significantly associated with spontaneous preterm births at <34 weeks and 34 to 37 weeks, respectively. CL <2.5 cm was found to predict spontaneous preterm births at <37 weeks with sensitivity of 31.1%, specificity of 95.6%, and p-value of <0.001. UCA was found to be a better predictor of spontaneous preterm birth with a higher coefficient of variation (56.4%) when compared with CL (16.9%). Conclusions UCA proved to be a novel ultrasound parameter that can serve as a better predictor of spontaneous preterm births in comparison to CL. A strong correlation exists between obtuse UCA and a risk of spontaneous preterm birth.

Abstract Background No randomized trial has compared efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF). Previous real-world comparisons could be biased by patient characteristics of importance for treatment selection, but instrumental variables could potentially account for measured and unmeasured confounders. Purpose To compare efficacy and safety of rivaroxaban and apixaban using facility preference for type of NOAC as instrumental variable. Methods AF patients started on apixaban or rivaroxaban were identified using nationwide registries. We categorized patients according to facility preference for type of NOAC, measured as percentage of the prior 20 AF patients started on rivaroxaban in the same facility. Occurrence of stroke/thromboembolism (TE), major bleeding, myocardial infarction and all-cause mortality during two years of follow-up were investigated using adjusted Cox regressions. To further examine general frailty according to facility preferences we also investigated occurrence of cancer, urogenital tract infection, dehydration and fracture. Results We analyzed 6264 AF patients initiated on rivaroxaban or apixaban. Compared with patients treated in facilities that used rivaroxaban in 0–20% of cases, the adjusted hazard ratio for bleeding was 1.05 when treated in a facility with 25–40% use; 1.40 with 45–60% use; 1.50 with 65–80% use; and 1.81 for 85–100% use (Ptrend=0.002). Higher facility level use of rivaroxaban was not associated with increased risk of stroke/TE (Ptrend=0.06), myocardial infarction (Ptrend=0.87) or all-cause mortality (Ptrend=0.91), and there was no association between facility preference for rivaroxaban and risk of cancer (Ptrend=0.83), urogenital tract infection (Ptrend=0.49), dehydration (Ptrend=0.91) or fracture (Ptrend=0.47). Characteristics by facility preference Percent of previous AF patients from facility started on rivaroxaban P for trend 0–20% 25–40% 45–60% 65–80% 85–100% No. of patients 1406 1421 1551 930 956 Received rivaroxaban, (%) 279, (19.8) 499, (35.1) 711, (45.8) 632, (68.0) 774, (81.0) <0.001 Standard dose, (%) 1216, (86.5) 1232, (86.7%) 1366, (88.1%) 793, (85.3%) 824, (86.2%) 0.62 Median age, (interquartile range) 70, (63.3–74) 69, (63–74) 70, (64–74) 70, (64–75) 70, (63–75) 0.11 Below median income, (%) 740, (52.6) 699, (49.2) 764, (49.3) 458, (49.3) 471, (49.3) 0.31 Prior stroke, (%) 99, (7.0) 115, (8.1) 134, (8.6) 69, (7.4) 74, (7.7) 0.56 Prior bleeding, (%) 136, (9.7) 141, (9.9) 163, (10.5) 91, (9.8) 97, (10.1) 0.51 Antiplatelet therapy, (%) 445, (31.7) 465, (32.7) 491, (31.7) 303, (32.6) 317, (33.2) 0.49 Rate of events according to instrument Conclusion High facility preference for rivaroxaban increases risk of major bleeding compared to facility preference for apixaban. Acknowledgement/Funding This study was funded by an unrestricted grant from the Capital Region of Denmark, Foundation for Health Research.

Introduction: The present work aims to increase the saturation solubility and the bioavailability of Olmesartan medoxomil (OM) via an acid-base neutralization-based nanosuspension technique. Method: The initial screening studies revealed that changes in the concentration of HPMC E15 (100-200 mg), mechanical stirring speed (SS) (900-1200 rpm) and stirring time (ST) (60-120 min) affected the responses. Effects produced by the factors (HPMC E15, SS, and ST) on responses (particle size, PDI, and cumulative % drug release (%CDR)) were investigated using a 2!!! !!!fractional factorial design with replicates and four midpoints. For the development of Olmesartan medoxomil nanosuspension, an acid-base neutralization technique was employed. Result: Pareto chart, perturbation plots and ANOVA were used to identify significant factors. The p-value <0.05 indicated the factors to be considered significant. The Particle size and PDI of all formulations ranged from 286.7 nm - 718.1 nm and 0.146 – 0.415, respectively. Drug release from all formulations ranged from74.0-103.7%. Pure drug solubility and optimized formula solubility were reported to be 108.6 g/ml and 1650.72 g/ml, respectively. Contour and 3D surface plots led to the identification of design space in which HPMC E15, SS and ST can be oriented at 148.8-151 mg, 959-1000 rpm and 106-120 min, respectively, to get particle size <500 nm, PDI <0.5 and % CDR >95%.SEM results indicated that the particles were nearly spherical. Conclusion: In vivo pharmacokinetic studies conducted in Wistar rats exhibited ∼4.7 folds enhancement in optimized OM nanosuspension oral bioavailability compared to pure drug. It can be concluded that the selected method and application of the design of the experimentation technique enhanced the saturation solubility and bioavailability of OM.

ObjectivesAntimicrobial resistance in Mycoplasma genitalium (MG) is a poorly surveyed and controlled global health concern. We evaluated the first commercial dual resistance assay, AmpliSens M. genitalium-ML/FQ-Resist-FL assay, for detection of potential macrolide and quinolone resistance-associated mutations (MRAMs and QRAMs, respectively) and estimated the prevalence of these mutations in MG in St. Petersburg, Russia.MethodsUrogenital samples positive (n=145 from 2007 to 2020) and negative (n=56 from 2021) for MG in routine diagnostics were retrospectively analysed using the AmpliSens M. genitalium-ML/FQ-Resist-FL assay (Central Research Institute of Epidemiology, Moscow, Russia) and Sanger sequencing for validation.ResultsThe AmpliSens M. genitalium-ML/FQ-Resist-FL assay detected potential MRAMs and QRAMs with sensitivities of 100% (CI95% 83.9 to 100) and 92.3% (CI95% 66.7 to 99.6) and specificities of 99.2% (CI95% 95.6 to 100) and 100% (CI95% 97.2 to 100), respectively, in clinical specimens with ≥1000 MG geq/mL. In total, MRAMs were detected in 13.8% (CI95% 9.1 to 20.3) of samples, with 23S rRNA A2058G being the most prevalent mutation (45.0% (CI95% 25.8 to 65.8)). QRAMs were found in 9.0% (CI95% 5.3 to 14.7) of samples, with S83I the most frequent mutation (53.8% (CI95% 29.1 to 76.8)). Dual resistance was observed in 5.5% (CI95% 2.8 to 10.5) of samples. Potential MRAM and dual resistance rates significantly increased over time: from 0% in 2007–2008 to 25% (ptrend=0.0009) and 10% (ptrend=0.0447), respectively, in 2018–2020. QRAM rate appeared to increase (from 0% to 13%), but significance was not reached (ptrend=0.0605).ConclusionsThe rapid increase in MG antimicrobial resistance in St. Petersburg, especially prominent for MRAMs, necessitates implementation of macrolide resistance-guided therapy in Russia. The first commercial dual resistance assay, AmpliSens M. genitalium-ML/FQ-Resist-FL assay, was sensitive and specific for detection of potential MRAMs and QRAMs and could be valuable in macrolide resistance-guided therapies and possibly for surveillance of QRAMs. International surveillance of antimicrobial resistance-associated mutations in MG, further research into clinical relevance of several parC mutations and novel treatments are essential.

ImportanceEvidence of the efficacy and safety of messenger RNA (mRNA) COVID-19 vaccines in children aged 5 to 11 years has been emerging. Collecting these data will inform clinicians, families, and policy makers.ObjectiveTo evaluate the efficacy and safety of mRNA COVID-19 vaccines in children aged 5 to 11 years in a systematic review and meta-analysis.Data SourcesPubMed and Embase databases were searched on September 29, 2022, without language restrictions.Study SelectionRandomized clinical trials and observational studies comparing vaccinated vs unvaccinated children aged 5 to 11 years and reporting efficacy or safety outcomes were included. Studies reporting safety outcomes in vaccinated children only (ie, no control group) were also included.Data Extraction and SynthesisTwo investigators independently extracted relevant data from each study. Odds ratios (ORs) for efficacy and safety outcomes and incidences of adverse events (AEs) following vaccination were synthesized using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines.Main Outcomes and MeasuresThe primary outcome was SARS-CoV-2 infections with or without symptoms. The secondary outcomes included symptomatic SARS-CoV-2 infections, hospitalizations, and multisystem inflammatory syndrome in children. The incidences of each AE following vaccination were also evaluated.ResultsTwo randomized clinical trials and 15 observational studies involving 10 935 541 vaccinated children (median or mean age range, 8.0-9.5 years) and 2 635 251 unvaccinated children (median or mean age range, 7.0-9.5 years) were included. Two-dose mRNA COVID-19 vaccination compared with no vaccination was associated with lower risks of SARS-CoV-2 infections with or without symptoms (OR, 0.47; 95% CI, 0.35-0.64), symptomatic SARS-CoV-2 infections (OR, 0.53; 95% CI, 0.41-0.70), hospitalizations (OR, 0.32; 95% CI, 0.15-0.68), and multisystem inflammatory syndrome in children (OR, 0.05; 95% CI, 0.02-0.10). Two randomized clinical trials and 5 observational studies investigated AEs among vaccinated children. Most vaccinated children experienced at least 1 local AE following the first injection (32 494 of 55 959 [86.3%]) and second injection (28 135 of 46 447 [86.3%]). Vaccination was associated with a higher risk of any AEs compared with placebo (OR, 1.92; 95% CI, 1.26-2.91). The incidence of AEs that prevented normal daily activities was 8.8% (95% CI, 5.4%-14.2%) and that of myocarditis was estimated to be 1.8 per million (95% CI, 0.000%-0.001%) following the second injection.Conclusions and RelevanceIn this systematic review and meta-analysis, COVID-19 mRNA vaccines among children aged 5 to 11 years were associated with measures of efficacy in preventing SARS-CoV-2 infection and severe COVID-19–related illnesses. While most children developed local AEs, severe AEs were rare, and most of AEs resolved within several days. These data provide evidence for future recommendations.

Abstract Funding Acknowledgements Type of funding sources: None. Background Male and female athletes present difference spectrum of cardiac remodelling related to their sport activity. However data in elite female athletes are scarce and mainly limited to echocardiography evaluation. Purpose The aim of the study was to assess gender difference in extreme cardiac remodelling in Olympic athletes engaged in endurance sport assessed by non-contrast Cardiovascular Magnetic Resonance including Mapping. Methods Olympic athletes engaged in endurance sport (rowing, canoeing, mid/long distance swimming) were examined with history, physical examination, 12-lead and exercise electrocardiogram, and echocardiography as part of their evaluation prior the Olympic games (Tokyo 2020). Athletes with unremarkable evaluation were undergone to non-contrast CMR including Mapping. The following parameters were calculated: indexed left ventricle (LV) and right ventricle (RV) end-diastolic (EDVi) and end-systolic volumes (ESVi), stroke volume (SVi), ejection fraction (EF), left and right atria area (LAAi and RAAi), LV Mass (Massi) and maximum wall thickness (MWT), RV/LV EDV ratio, spericity index [SI=(long axis diameter/2)3 * 4,187], myocardial native T1 (nT1) and T2 Mapping. Results 51 caucasian elite athletes (without difference in term of age, years of training and hours of training/week) were enrolled and 59% were male. Male showed greater LV EDVi (123 ± 28 ml vs 103 ± 10, p = 0.003), ESVi (55 ± 14 ml vs 44 ± 7, p = 0.001), SVi (68 ± 15 ml vs 59 ± 7, p = 0.023), Massi (76 ± 19 vs 57 ± 10, p &lt; 0.001), MWT (10 ± 1 mm vs 8 ± 1, p &lt; 0.001) and RV EDVi (129 ± 48 ml vs 104 ± 13, p = 0.026), ESVi (57 ± 10 ml vs 45 ± 9, p &lt; 0.001), SVi (68 ± 15 ml vs 59 ± 7, p = 0.018) compared to female, as expected. LVEF (p = 0.05) and RVEF (p = 0.17) did not show significant difference. Despite greater volumes, SI (43 ± 12% vs 44 ± 8, p = 0.8) and RV/LV EDV ratio (0.99 ± 0.05 vs 1 ± 0.05, p = 0.405) did not differ between male and female athletes, as well as LAAi (13 ± 3 cm2 vs 13 ± 1.5, p = 0.86) and RAAi (13 ± 1.9 vs 13 ± 18, p = 0.56). Native T1 mapping was lower in male compared with female (934 ± 21 ms vs 956 ± 33, p = 0.028) while T2 Map values were slightly higher (53 ± 3.9 ms vs 50 ± 3.8, p = 0.027) . Conclusions Male endurance Olympic athletes presented higher volumes and LV mass compared to their female counterparts, while atria dimension, systolic function and sphericity index did not differ. Ventricles showed balanced dilatation in both gender. Lower T1 value observed in male suggested cellular hypertrophy. Figure 1 showed CMR images in a male (top row) and a female (bottom row) Olympic athletes: 4 chamber end-diastolic and end-systolic frame and end-diastolic basal short axis (SAX) showed balanced dilatation. Graphs showed higher EDVi and Massi in male compared o female, no difference in sphericity index and lower native T1 mapping. Abstract Figure 1