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1
Rousselot, Philippe, Hyacinthe Johnson-Ansah, Françoise Huguet, Laurence Legros, Martine Escoffre-Barbe, Martine Gardembas, Pascale Cony-Makhoul, et al. "Personalized Daily Doses of Imatinib By Therapeutic Drug Monitoring Increase the Rates of Molecular Responses in Patients with Chronic Myeloid Leukemia. Final Results of the Randomized OPTIM Imatinib Study." Blood 126, no. 23 (December 3, 2015): 133. http://dx.doi.org/10.1182/blood.v126.23.133.133.
Анотація:
Abstract Background Imatinib mesylate (IM) at 400 mg/d remains a standard for first line therapy in patients (pts) with newly diagnosed chronic phase CML (CP-CML). A sub analysis of the IRIS study (Larson et al. Blood, 2008) demonstrated that pts with high IM trough levels achieved higher rates of major molecular response (MMR). The level of 1000 ng/ml was established as the [C]min value threshold to predict molecular response (Picard et al. Blood, 2007). We conducted a randomized trial to evaluate the value of IM dose optimization based on the monitoring of [C]min levels in newly diagnosed CP-CML pts (OPTIM-imatinib trial, EudraCT number 2008-006854-17). Patients and Methods Pts diagnosed with CP- CML for less than 3 months, not previously treated or treated with IM for less than 3 months were eligible and treated with IM 400 mg/d. IM [C]min was determined by chromatography-tandem mass-mass spectrometry 15 days after enrollment. Pts with a [C]min < 1000 ng/ml were randomized between a dose-increase strategy aiming to reach the threshold of 1000 ng/ml (arm A1) versus standard IM management (arm A2). Pts with [C]min levels ≥1000 ng/ml were observed (arm A3). All pts were managed according to the ELN 2009 recommendations (amended with ELN 2013 recommendations). IM [C]min levels were assessed monthly in A1 and A2 and every 3 months in A3. BCR-ABLIS was assessed every 3 months. The primary end-point was MMR rates at 12 months. Results One hundred thirty nine pts were enrolled. Median follow-up was 31 months. Median age was 64y (25 to 88y), sex ratio (M/F) was 1.4 and Sokal score distribution was 21%, 41% and 38% for high, intermediate and low categories respectively, equally distributed in the 3 arms. In 6 pts the initial [C]min was not assessed (3 were intolerant and 3 declined the dosage). Thus 133 pts were studied. In 86 pts (65%), initial [C]min value was < 1000 ng/ml. These pts were randomized between A1 (43 pts) and A2 (43 pts). [C]min was ≥1000 ng/ml in the 47 remaining pts followed in A3. Table 1 shows the significant improvement of the median IM [C]min after dose adjustment in A1 (p<0.0001) as compared to standard management in A2. Correspondingly, IM daily dose increased in A1 (p<0.0001) to reach a mean value of 600 mg/d. In the experimental A1 arm, the distribution of IM doses at 12 months was 13% for 500 mg/d, 30% for 600 mg/d, 34% for 800 mg/d whereas 16% of the pts remained at 400 mg/d and 7% were dose decreased at 300 mg/d. During follow-up, a similar proportion of pts with AE was observed in A1 (58%) and A2 (51%). Eight SAE related to IM were equally distributed in A1, A2 and A3. Cumulative incidences of treatment discontinuation were comparable in the 3 arms (overall, 18.8% by 12 months and 34.1% by 24 months). Reasons for discontinuation were not similar in A1 and A2 with a trend for more treatment failures in A2 as compared to A1 (60% versus 18%, p=0.08). At 12 months, MMR was achieved in 27 out of 43 pts (63%; 95%CI 49-77) in A1 as compared to 16 out 43 pts (37%; 95%CI 23-51) in A2 (p=0,031). The rates of MMR were not statistically different between A1 and A3 (p=0.12). Conclusions Only 1/3 of pts on IM400 were correctly dosed and may not require systematic high dose IM. Two-thirds of the pts were not exposed enough to IM at standard dose and may benefit from individualized strategies. A tailored dose adjustment based on pharmacology resulted in higher MMR rate at 12 months (63% vs 37%), a magnitude in line with the results previously reported with second generation tyrosine kinase inhibitors or high dose IM front line. Our results may provide a strong rational to early personalize the use of IM and IM generic formulations in order to optimize the outcome for each patient. This study was supported by a grant from the French Department of Health (Programme Hospitalier de Recherche Clinique). Table 1. Median [C]min (ng/ml; (95% CI)) Initial Assessment M3 M6 M9 M12 A1 591; (508-654) 838; (746-922) 1001; (748-1261) 1062; (918-1221) 1013; (830-1277) A2 651; (558-797) 605; (487-786) 591; (517-722) 605; (460-720) 646; (576-894) A3 1314; (1199-1514) 1032; (899-1143) 1002; (784-1205) 935; (737-1073) 1000; (846-1098) Mean IM daily dose (mg/d; (95% CI)) Inclusion M3 M6 M9 M12 A1 400 538; (508-568) 611; (563-658) 607; (545-668) 600; (535-665) A2 400 395; (387-402) 392; (383-401) 391; (381-401) 391; (381-401) A3 400 400; (400-400) 398; (385-410) 389; (376-402) 382; (370-395) Disclosures Rousselot: BMS: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Consultancy. Johnson-Ansah:BMS: Speakers Bureau; Hybrigenics SA: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau. Huguet:PFIZER: Consultancy, Speakers Bureau; ARIAD: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding. Legros:Novartis: Research Funding, Speakers Bureau; ARIAD: Speakers Bureau; BMS: Speakers Bureau. Gardembas:Novartis: Speakers Bureau. Coiteux:ARIAD: Speakers Bureau; BMS: Speakers Bureau; Novartis: Speakers Bureau. Deau:BMS: Honoraria. Mahon:ARIAD: Consultancy; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.
2
Raghunandan, K., and Dasaratha V. Rama. "SOX Section 404 Material Weakness Disclosures and Audit Fees." AUDITING: A Journal of Practice & Theory 25, no. 1 (May 1, 2006): 99–114. http://dx.doi.org/10.2308/aud.2006.25.1.99.
Анотація:
Section 404 of the Sarbanes-Oxley Act and Auditing Standard No. 2 (PCAOB 2004) require management and the auditor to report on internal controls over financial reporting. Section 404 is arguably the most controversial element of SOX, and much of the debate around the costs of implementing section 404 has focused on auditors' fees (Ernst & Young 2005). In this paper, we examine the association between audit fees and internal control disclosures made pursuant to section 404. Our sample includes 660 manufacturing firms that have a December 31, 2004 fiscal year-end and filed the section 404 report by May 15, 2005. We find that the mean (median) audit fees for the firms in our sample for fiscal 2004 is 86 (128) percent higher than the corresponding fees for fiscal 2003. Audit fees for fiscal 2004 are 43 percent higher for clients with a material weakness disclosure compared to clients without such disclosure; however, audit fees for fiscal 2003 are not associated with an internal control material weakness disclosure (in the 10-K filed following fiscal 2004). We also find that the association between audit fees and the presence of a material weakness disclosure does not vary depending on the type of material weakness (systemic or non-systemic).
3
Dosmagambetov, S. P., B. K. Dzhenalaev, A. B. Tusupkaliev, V. V. Sarsenova, G. Z. Abdullayeva, Zh T. Baubekov, and N. S. Esenalina. "The current state of diagnostics and management of foreign bodies in the respiratory tract in children." Russian Journal of Pediatric Surgery 27, no. 2 (June 21, 2023): 137–42. http://dx.doi.org/10.55308/1560-9510-2023-27-2-137-142.
Анотація:
Introduction. Foreign body aspiration (FBA) into the respiratory tract is a severe, life-threatening condition in children which requires urgent medical and diagnostic measures. Purpose. To study outcomes after FBA diagnostics and treatment in children and to develop an algorithm for diagnosing foreign bodies in the respiratory tract in this group of patients. Material and methods. Outcomes in 86 children who were hospitalized with suspected foreign bodies in their respiratory tract to the Clinic of Pediatric Surgery in Marat Ospanov West Kazakhstan Medical University, Aktobe, Republic of Kazakhstan in 2018–2022. Results. In 73 children, out of 86, FBA was confirmed. Distribution of children with FBA by age was as follows: less than one year – 5 (6.8 %) children; 1–3 years – 46 (63.1 %); 3–5 years – 7 (9.6 %), over 5 years – 15 (20.5 %). Localization of foreign bodies in the respiratory tract was as follows: larynx –6; trachea – 10, right main bronchus –26, left main bronchus – 30, both lower lobe bronchi – 1. The revealed foreign bodied were : peanuts – 24 (32.8 %) cases, sunflower seed – 13 (17.8 %), fountain pen cap – 7 (9.6 %), plastic toy part – 5 (6.8 %), fish bone – 5 (6.8 %), stationery carnation – 4 (5.5 %), bone – 4 (5.5 %), small rock – 4 (5.5 %), carrot – 3 (4.2 %), tooth – 2 (2.7 %), bead – 1 (1.4 %), food masses –1 (1.4 %). In the diagnostics of foreign bodies, anamnesis, clinical examination, radiation and endoscopic diagnostic techniques were of great importance. On analyzing the obtained clinical material, the researchers developed their own algorithm for FBA diagnosis. Foreign bodies were removed with rigid bronchoscopy in 55 children, with fibrobronchoscopy in 9 children, direct laryngoscopy – in 6 cases, at thoracotomy and bronchotomy – in 3 children. There were no complications associated with the removal of foreign bodies. Conclusions. Foreign bodies in the respiratory tract are met most often in children , aged 1–3. In doubtful cases, MSCT was used in addition to traditional diagnostic methods. It allows to exclude or identify foreign bodies invisible at X-ray images. FBA removal should be performed at the third level medical institutions.
4
Maradiaga-Rodriguez, Walter Danilo, Adão Wagner Pêgo Evangelista, José Alves-Júnior, and Rommel Bernardes-da Costa. "Effects of vinasse and lithothanmium application on the initial growth of sugar cane (Saccharum sp. cv. RB 86-7515) irrigated and not irrigated." Acta Agronómica 67, no. 2 (April 1, 2018): 252–57. http://dx.doi.org/10.15446/acag.v67n2.66082.
Анотація:
El objetivo de este estudio es evaluar el crecimiento inicial de la caña de azúcar variedad RB 86-7515, cultivada en sistema de producción orgánica y fertilizada con dosis de lithothanmium y vinaza, se desarrolló un experimento. La investigación se llevó a cabo en la Escuela de Agronomía de la Universidade Federal de Goiás, Brasil. El delineamiento estadístico fue en un diseño completamente aleatorio con tres repeticiones, en esquema factorial (5 x 5 x 2). Las plantas fueron cultivadas en contenedores de plástico de 200 litros. Los tratamientos correspondieron a cinco dosis de vinaza (0, 165, 330, 495 e 660 m3.h-1) y cinco dosis de lithothanmium (0, 100, 200, 300 e 400 kg.ha-1) en dos ambientes: irrigado y no irrigado. El sistema de irrigación utilizado fue por goteo con emisores de 4 L.h-1. La aplicación de los tratamientos de fertilización, fueron divididas de acuerdo con la marcha de absorción de nutrientes por las plantas de caña de azúcar. Se evaluaron número de brotes (cañas), altura de plantas, índice de área foliar y diámetro del cormo a lo largo de diferentes etapas fenológicas del cultivo. Los tratamientos aplicados provocaron efectos significativos sobre los parámetros de crecimiento del cultivo, siendo las plantas irrigadas y fertilizadas con 196 kg.ha-1 de lithothanmium y 330 m3.ha-1 de vinaza, las que exhibieron los mejores resultados.
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Maradiaga, Walter Danilo, Adão Wagner Pêgo Evangelista, José Alves Júnior, Wilson Mozena Leandro, Marcus Vinicius Honorato Domingos, and Derblai Casaroli. "LITHOTHAMNIUM E VINHAÇA NA PRODUÇÃO DE CANA-DE-AÇÚCAR ORGÂNICA IRRIGADA E DE SEQUEIRO." IRRIGA 23, no. 2 (October 9, 2018): 390–401. http://dx.doi.org/10.15809/irriga.2018v23n2p390-401.
Анотація:
LITHOTHAMNIUM E VINHAÇA NA PRODUÇÃO DE CANA-DE-AÇÚCAR ORGÂNICA IRRIGADA E DE SEQUEIRO
WALTER DANILO MARADIAGA RODRIGUEZ1; ADÃO WAGNER PÊGO EVANGELISTA1; JOSÉ ALVES JÚNIOR1; WILSON MOZENA LEANDRO1; MARCUS VINICIUS HONORATO DOMINGOS1 E DERBLAI CASAROLI1
¹Núcleo de Pesquisa em Clima e Recursos Hídricos do Cerrado – Escola de Agronomia - Universidade Federal de Goiás, Rodovia Goiânia / Nova Veneza, Km 0, Goiânia, Goiás, CEP: 74690-900, E-mail: maradiagawd@gmail.com, awpego@bol.com.br, josealvesufg@yahoo.com.br, wilsonufg@gmail.com, derblaicasaroli@yahoo.com.br, marcus-domingos@hotmail.com
1 RESUMO
Com o objetivo de avaliar a influência do lithothamnium e vinhaça na produtividade e as características tecnológicas da cana-planta variedade RB 86-7515 cultivada em sistema de produção orgânica, conduziu-se um experimento na Universidade Federal de Goiás. O delineamento estatístico utilizado foi inteiramente casualizado com 3 repetições em esquema fatorial (5x5x2). As plantas foram cultivadas no interior de tambores de 200 litros. Os tratamentos corresponderam a cinco doses de vinhaça (0, 165, 330, 495 e 660 m3 ha-1) e cinco doses de lithothamnium (0, 100, 200, 300 e 400 kg ha-1) e cultivo em regime irrigado e de sequeiro. O sistema de irrigação utilizado foi por gotejamento com emissores com vazão de 4 L h-1. Avaliaram-se: produtividade do colmo (t ha-1), teor de sólidos solúveis (Brix %), porcentagem de umidade do colmo, teor de sacarose aparente na cana (Pol %), teor de fibra (Fibra %), pureza do caldo e açúcar total recuperável (ATR) expresso em kg t ha-1. Os tratamentos aplicados produziram efeitos significativos sobre a produtividade e características tecnológicas da cultura, sendo as plantas irrigadas e adubadas com 200 kg ha-1 de lithothamnium e 330 m3 ha-1 de vinhaça as que apresentaram os melhores resultados.
Palavras-chaves: Saccharum sp., adubação, irrigação.
MARADIAGA-RODRIGUEZ, W. D.; EVANGELISTA, A. W.; ALVES JÚNIOR, J.; MOZENA, W.; DOMINGOS, M. V. H.; CASAROLI D.
LITHOTHAMNIUM AND VINASSE IN THE PRODUCTION OF ORGANIC SUGAR CANE IRRIGATED AND UNIRRIGATED
2 ABSTRACT
The objective of this study was to evaluate the productivity and technological characteristics of sugarcane, variety RB 86-7515. The experiment was carried out in the experimental area of the School of Agronomy, of the Federal University of Goiás. A completely randomized experimental design (CRD) was applied, with three replicates, in a 5x5x2 factorial scheme. The plants were grown in containers of 200 liters. The treatments were five vinasse doses (0, 165, 330, 495 and 660 m3 h-1) and five doses of lithothamnium (0, 100, 200, 300 and 400 kg ha-1) and cultivation under irrigated and unirrigated. The irrigation system used was drip emitters with flow rate of 4 L h-1. The variables evaluated were fiber % cane; Brix % juice; pol % cane; juice purity and total recoverable sugar - TRS and productivity per hectare. The treatments produced significant effects on the parameters of crop growth, and irrigated plants, fertilized with 200 kg ha-1lithothamnium and 330 m3 ha-1 of vinasse showed the best results.
Keywords: Saccharum sp., fertilization, irrigation.
6
Ghufron, Muhammad, Fitri Nur Indah Sari, Brahmanu Wisnu Saputro, and Jyh-Ming Ting. "Metal Doping in 2D Co3O4 for Enhanced ORR/OER Electrocatalytic Performance." ECS Meeting Abstracts MA2023-02, no. 4 (December 22, 2023): 527. http://dx.doi.org/10.1149/ma2023-024527mtgabs.
Анотація:
Spinel cobalt oxide or Co3O4, has been proven to be a promising material as bifunctional electrocatalyst for ORR/OER. In this study, we show further improvement of the electrocatalytic activity via metal doping. Metal-doped Co3O4 was synthesized using a simple hydrothermal method at 120° C for 24 h, followed by calcination at 400° C for 1 h. A surfactant was used to control the morphology of the sample such that either 1D or 2D structure was obtained. The 2D structure shows better electrical conductivity with Rct of 70 Ohm vs. 86 Ohm for the 1D structure. Electrochemical test show that the 2D structure gives a ∆E of 870 mV vs. 949 mV for the 1D structure, due to primarily the excellent ORR activity of the 2D structure, i.e., E-3 = 711 mV for the 2D structure vs. E-3 = 667 mV for the 1D structure. The use of the 2D structure in zinc air battery is also demonstrated.
7
Bendell, Johanna C., Bert H. O'Neil, Alexander Starodub, Derek J. Jonker, Thorvardur Ragnar Halfdanarson, William Jeffery Edenfield, Bassel F. El-Rayes, et al. "Cancer stemness inhibition and chemosensitization: Phase 1b/II study of cancer stemness inhibitor napabucasin (BBI-608) with FOLFIRI +/- bevacizumab (Bev) administered to colorectal cancer (CRC) patients (pts)." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 593. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.593.
Анотація:
593 Background: Cancer stem cells or stemness-high cancer cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin, a first-in-class cancer stemness inhibitor in clinical development, suppresses cancer stemness by targeting Stat3-driven gene transcription. Preclinical studies suggest that napabucasin sensitizes heterogeneous cancer cells to chemotherapeutics and targeted agents. Methods: This study was performed to assess signs of anti-tumor activity of napabucasin in combination with FOLFIRI +/- Bev in CRC pts. Napabucasin was administered at 240 mg BID. FOLFIRI (5-FU 400 mg/m2 bolus with 2400 mg/m2, irinotecan 180 mg/m2, and leucovorin 400 mg/m2 infusion) +/- Bev 5 mg/kg was administered biweekly until disease progression or other discontinuation criterion. pSTAT3 status of archival tumor tissue was assayed by immunohistochemistry using the H-score with pSTAT3highdefined as ≥ 5% pSTAT3+ cancer cells and tumor stroma staining at ≥ 2+ intensity. Results: 63 CRC pts with an average of >2 prior therapy lines were enrolled. No pharmacokinetic interactions or dose-limiting toxicity was observed. Most common adverse events (AEs) included grade 1/2 diarrhea, nausea, vomiting and fatigue. 25 pts had grade 3 AEs, including diarrhea (14), fatigue (4), dehydration (2), electrolyte imbalance (4), nausea (1) and weight loss (1) resolved with dose reduction and supportive care. Among 63 pts enrolled who received RECIST evaluation, disease control (CR+PR+SD) was observed in 49 pts (86%) with an overall response (CR+PR) of 28% with 1 pt achieving CR. Clinical trial information: NCT02024607. Conclusions: This phase Ib/II study suggests napabucasin may sensitize chemorefractory CRC to FOLFIRI +/- Bev. Encouraging signs of synergistic activity between napabucasin and FOLFIRI was observed in CRC pts regardless of pSTAT3 status.[Table: see text]
8
Meiners, Jan, Kristina Jansen, Natalia Gorbokon, Franziska Büscheck, Andreas M. Luebke, Martina Kluth, Claudia Hube-Magg, et al. "Angiotensin-Converting Enzyme 2 Protein Is Overexpressed in a Wide Range of Human Tumour Types: A Systematic Tissue Microarray Study on >15,000 Tumours." Biomedicines 9, no. 12 (December 3, 2021): 1831. http://dx.doi.org/10.3390/biomedicines9121831.
Анотація:
Angiotensin-converting enzyme 2 (ACE2) is a regulator in the renin-angiotensin system. ACE2 expression was analysed immunohistochemically in 15,306 samples from 119 tumour types and in 608 samples of 76 normal tissue types. In normal tissue, ACE2 was most abundant in testis and corpus luteum, kidney, small intestine and capillaries of selected organs. At least an occasional weak ACE2 positivity of tumour cells was seen in 83 of 119 (70%) tumour types. ACE2 tumour cell positivity was particularly frequent in papillary (94%) and clear cell (86%) renal cell carcinoma, colorectal adenocarcinoma (81%), mucinous ovarian cancer (61%), cholangiocarcinoma (58%), hepatocellular carcinoma (56%), and in adenocarcinomas of the stomach (47%), pancreas (42%), and the lung (35%). ACE2-positive capillaries were found in 409/12,644 (3%) of analysable tumours, most frequently in tumours with endocrine/neuroendocrine activity. Presence of ACE2-positive capillaries was linked to low stage in papillary thyroid cancer and low grade in neuroendocrine neoplasms. In conclusion, ACE2 expression can occur both in tumour cells and tumour-associated capillaries in a broad variety of different tumour types at highly variable frequencies.
9
Armstrong, I., G. Swant, and H. R. Timmermann. "Developing a woodland caribou habitat mosaic on the Ogoki-Nakina North Forests of northwestern Ontario." Rangifer 18, no. 5 (March 1, 1998): 235. http://dx.doi.org/10.7557/2.18.5.1561.
Анотація:
The Ogoki-North Nakina Forests consist of (10 638 km2) unroaded boreal forest approximately 400 km northeast of Thunder Bay, Ontario (lat 50°- 51°31'N, long 86°30'- 89°W). Woodland caribou (Rangifer tarandus caribou) inhabit discrete portions within these forests based on minimal current and past historical data. As part of the Forest Management Planning process, for the period 1997-2097, a woodland caribou habitat mosaic has been developed to coordinate present and future forest management activities with the retention and development of current and future woodland caribou habitat. Several criteria including, past fire history, forest structure, age, species composition, proximity to current road access and location of existing and potential caribou habitat, helped identify and delineate 50 mosaic harvest blocks. Each harvest block will be logged in one of five 20 year periods over a 100 year rotation (1997¬2097). The harvest blocks have been developed to simulate a pattern of past wildfire history in an area that has not been subjected to past forest management activities, while managing for woodland caribou, a locally featured species.
10
Carmosini, N., K. J. Devito, and E. E. Prepas. "Net nitrogen mineralization and nitrification in trembling aspen forest soils on the Boreal Plain." Canadian Journal of Forest Research 33, no. 11 (November 1, 2003): 2262–68. http://dx.doi.org/10.1139/x03-153.
Анотація:
In situ net N mineralization and net nitrification rates were measured in organic forest floor (LFH) and mineral horizons of mature and logged trembling aspen (Populus tremuloides Michx.) stands on the Boreal Plain in western Canada. Cumulative May to September mineralization for mature and logged plots was 1354 ± 534 and 1631 ± 1584 mg N·m2, respectively, in the LFH horizon and 810 ± 394 and 305 ± 3957 mg N·m2, respectively, in the mineral horizon. Net nitrification in mature and logged plots was 86 ± 142 and 658 ± 435 mg NO3-N·m2, respectively, in the LFH horizon and 67 ± 50 and 409 ± 325 mg NO3-N·m2, respectively, in the mineral horizon. Monthly mean NH4-N concentrations in the LFH tended to be higher in logged plots than in mature plots. Winter net N mineralization and nitrification rates in the LFH of mature plots were up to 7% and 11% of growing season net rates, respectively. In comparison, these rates in logged plots were up to 127% and 59% of the growing season net rates, respectively, indicating that winter activity may make a large contribution to annual net mineralization and nitrification after logging.
11
Rose, Susannah, Heather McKee Hurwitz, Mary Beth Mercer, Sabahat Hizlan, Kari Gali, Pei-Chun Yu, Caroline Franke, et al. "Patient Experience in Virtual Visits Hinges on Technology and the Patient-Clinician Relationship: A Large Survey Study With Open-ended Questions." Journal of Medical Internet Research 23, no. 6 (June 21, 2021): e18488. http://dx.doi.org/10.2196/18488.
Анотація:
Background Patient satisfaction with in-person medical visits includes patient-clinician engagement. However, communication, empathy, and other relationship-centered care measures in virtual visits have not been adequately investigated. Objective This study aims to comprehensively consider patient experience, including relationship-centered care measures, to assess patient satisfaction during virtual visits. Methods We conducted a large survey study with open-ended questions to comprehensively assess patients’ experiences with virtual visits in a diverse patient population. Adults with a virtual visit between June 21, 2017, and July 12, 2017, were invited to complete a survey of 21 Likert-scale items and textboxes for comments following their visit. Factor analysis of the survey items revealed three factors: experience with technology, patient-clinician engagement, and overall satisfaction. Multivariable logistic regression was used to test the associations among the three factors and patient demographics, clinician type, and prior relationship with the clinician. Using qualitative framework analysis, we identified recurrent themes in survey comments, quantitatively coded comments, and computed descriptive statistics of the coded comments. Results A total of 65.7% (426/648) of the patients completed the survey; 64.1% (273/426) of the respondents were women, and the average age was 46 (range 18-86) years. The sample was geographically diverse: 70.2% (299/426) from Ohio, 6.8% (29/426) from Florida, 4.2% (18/426) from Pennsylvania, and 18.7% (80/426) from other states. With regard to insurance coverage, 57.5% (245/426) were undetermined, 23.7% (101/426) had the hospital’s employee health insurance, and 18.7% (80/426) had other private insurance. Types of virtual visits and clinicians varied. Overall, 58.4% (249/426) of patients had an on-demand visit, whereas 41.5% (177/426) had a scheduled visit. A total of 41.8% (178/426) of patients had a virtual visit with a family physician, 20.9% (89/426) with an advanced practice provider, and the rest had a visit with a specialist. Most patients (393/423, 92.9%) agreed that their virtual visit clinician was interested in them as a person, and their virtual visit made it easy to get the care they needed (383/421, 90.9%). A total of 81.9% (344/420) of respondents agreed or strongly agreed that their virtual visit was as good as an in-person visit by a clinician. Having a prior relationship with their virtual visit clinician was associated with less comfort and ease with virtual technology among patients (odds ratio 0.58, 95% CI 0.35-0.98). In terms of technology, patients found the interface easy to use (392/423, 92.7%) and felt comfortable using it (401/423, 94.8%). Technical difficulties were associated with lower odds of overall satisfaction (odds ratio 0.46, 95% CI 0.28-0.76). Conclusions Patient-clinician engagement in virtual visits was comparable with in-person visits. This study supports the value and acceptance of virtual visits. Evaluations of virtual visits should include assessments of technology and patient-clinician engagement, as both are likely to influence patient satisfaction.
12
Kojima, Takashi, Kei Muro, Eric Francois, Chih-Hung Hsu, Toshikazu Moriwaki, Sung-Bae Kim, Se-Hoon Lee, et al. "Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase III KEYNOTE-181 study." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 2. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.2.
Анотація:
2 Background: Patients with advanced esophageal cancer after first-line chemotherapy (chemo) have a poor prognosis and limited treatment options. We present results of the phase 3 KEYNOTE-181 study of pembrolizumab vs investigator’s choice chemo as second-line therapy for patients (pts) with advanced/metastatic squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ (NCT02564263). Methods: Eligible pts were randomized 1:1 to pembrolizumab 200 mg Q3W for up to 2 years or investigator’s choice chemo of paclitaxel, docetaxel, or irinotecan. Randomization was stratified by histology (SCC vs adenocarcinoma) and region (Asia vs rest of world). Primary end points were OS in the SCC, PD-L1 combined positive score (CPS) ≥10, and ITT populations. Results: 628 pts were randomized including 401 with SCC, and 222 with CPS ≥10. As of October 15, 2018, the median follow-up was 7.1 mo (pembrolizumab) vs 6.9 mo (chemo). Pembrolizumab was superior to chemo for OS in CPS ≥10 (N=222; median 9.3 vs 6.7 mo; HR 0.69; 95% CI 0.52-0.93; P=0.0074). The 12-mo OS rate in pts with CPS ≥10 was 43% vs 20%. There was clinically meaningful improvement in OS with pembrolizumab vs chemo in pts with SCC, but this was not statistically significant per prespecified boundaries (N=401; 8.2 mo vs 7.1 mo; HR 0.78; 95% CI 0.63-0.96; P=0.0095). In the ITT population, while directionally favorable, the difference in OS was not statistically significant (N=628; 7.1 mo vs 7.1 mo; HR 0.89; 95% CI 0.75-1.05; P=0.0560). Fewer pts had any-grade (64% vs 86%) or grade 3-5 (18% vs 41%) drug-related AEs with pembrolizumab vs chemo. Conclusion: Pembrolizumab significantly improved OS compared with chemo as second-line therapy for advanced esophageal cancer with PD-L1 CPS ≥10, with a more favorable safety profile. These data support pembrolizumab as a new second-line standard of care for esophageal cancer with PD-L1 CPS ≥10. The phase 3 KEYNOTE-590 study of pembrolizumab plus chemo as first-line therapy for advanced esophageal cancer is ongoing (NCT03189719). Clinical trial information: NCT02564263.
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Budnikova, E. A., O. I. Kubar, O. V. Iozefovich, and S. M. Kharit. "The study of the formation processes and signs of the likelihood of vaccination in priority contingents in various epidemic diseases (sociological research)." Journal Infectology 15, no. 2 (July 7, 2023): 123–31. http://dx.doi.org/10.22625/2072-6732-2023-15-2-123-131.
Анотація:
The purpose of the study: to determine the development of vaccination against infections associated with contingents in an epidemic crisis.Materials and methods: the method of a sociological survey of future workers and those vaccinated in different epidemic status periods was used: 2019 – the pre-pandemic period and 2020 – the period of the COVID-19 pandemic. A sociological survey was conducted in 2019 among 212 medical workers (130 doctors and 82 nurses) and among 229 medical workers in 2020 (143 doctors and 86 nurses). Parents were also interviewed using a questionnaire. 100 and 50 respondents took part in the survey, respectively.Results: a large number of pregnant workers – 74.3-88.1% are positive about vaccination. However, 6.8% of therapists and 9.6% of nurses of adult health facilities express a wary attitude, there were no negative reactions, unlike in 2019, when the severity of 2.2% of general practitioners and 4.2% of nurses of adult health facilities was negative. The largest number of respondents of all groups among the reasons for refusing to vaccinate is called “information that vaccinations are dangerous” from 76.6% to 88.9% in 20219, from 74.1% to 93.2% in 2020. Among parents, only 34% had a positive attitude towards vaccination, 12% negatively.Conclusions: It is necessary to take prompt measures to increase adherence to vaccination of the main social groups that have a decisive influence on the attitude and effect of vaccination.
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Silvero, Melina, Francisco Crespo, Maria del Mar Serra Pesquer, Elisa Perez Bayo, Igor Fernández Peñarrubia, Alejandro Palladino, Rodolfo Fattore, and Rafael A. Palladino. "PSIX-8 Supplementing a Natural Citrus Flavonoid Extract (Bioflavex) to Finishing Cattle." Journal of Animal Science 100, Supplement_3 (September 21, 2022): 372–73. http://dx.doi.org/10.1093/jas/skac247.681.
Анотація:
Abstract Finishing cattle are exposed to diets with high amounts of starch and consequently to hindgut acidosis. Usually, antibiotics like ionophores are used to control dysbiosis at gut level. However, natural options are being evaluated as healthy alternatives. Flavonoids are well known as antibacterial agent, being an interesting alternative to antibiotics. The aim of this experiment was to evaluate the performance of finishing steers supplemented with monensin compared with citrus flavonoid extract (Bioflavex). Steers (n = 48; 214.3 kg live weight; LW) were assigned to two treatments: Monensin (MON; 30 g/tn DM) and flavonoids extract (FLAV; Bioflavex, Spain; 400 g/tn DM). Animals were allocated in 6 groups (3 pens/treatment; 8 animals/pen). Pen was considered as the experimental unit. Transition diet was offered from d 1 to 21 (CP 18% , starch 40.6%) whilst finishing diet from d 21 to 86; (CP 10.6%, starch 47.8%). The LW was registered at 0, 21 and 86 d. The DMI was estimated by difference between offered and refusals. Ruminal and feces pH were recorded (rumen liquor samples were obtained by ruminocentesis). Data were analyzed by proc mixed (treatment and time as fixed effects; pen as random). Differences were stated when P< 0.05. Only DMI was different between treatments, being FLAV greater than MON (6.68 kg/d vs 6.45 kg/d for FLAV and MON respectively; P< 0.05). No differences were found in terms of daily gain (1.355 kg/d vs 1.294 kg/d for FLAV and MON respectively; P >0.05), final weight (FLAV 331.6 kg vs MON 324.8 kg; P >0.05), neither conversion (4.95 kg/kg vs 4.98 kg/kg for FLAV and MON respectively; P >0.05). Rumen and feces pH did not differ across treatments (P >0.05). According to our results, a citrus flavonoid extract showed a similar performance comparing to monensin, being a potential alternative to antibiotics.
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Silva, Jean Jerley N., Wander R. Pavanelli, José Clayston M. Pereira, João S. Silva, and Douglas W. Franco. "Experimental Chemotherapy against Trypanosoma cruzi Infection Using Ruthenium Nitric Oxide Donors." Antimicrobial Agents and Chemotherapy 53, no. 10 (July 6, 2009): 4414–21. http://dx.doi.org/10.1128/aac.00104-09.
Анотація:
ABSTRACT The ruthenium NO donors of the group trans-[Ru(NO)(NH3)4L] n+, where the ligand (L) is N-heterocyclic H2O, SO3 2−, or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC50 try) and cytotoxicity data on mammalian V-79 cells (IC50 V79), the in vitro therapeutic indices (TIs) (IC50 V79/IC50 try) for these compounds were calculated. Compounds that exhibited an in vitro TI of ≥10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC50 try/epi of ≤100 μM were assayed in a mouse model for acute Chagas' disease, using two different routes (intraperitoneal and oral) for drug administration. A dose-effect relationship was observed, and from that, the ideal dose of 400 nmol/kg of body weight for both trans-[Ru(NO)(NH3)4isn](BF4)3 (isn, isonicotinamide) and trans-[Ru(NO)(NH3)4imN](BF4)3 (imN, imidazole) and median (50%) effective doses (ED50) of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal doses (LD50) for both compounds are higher than 125 μmol/kg, the in vivo TIs (LD50/ED50) of the compounds are 1,453 for trans-[Ru(NO)(NH3)4isn](BF4)3 and 658 for trans-[Ru(NO)(NH3)4imN](BF4)3. Although these compounds exhibit a marked trypanocidal activity and are able to react with cysteine, they exhibit very low activity in T. cruzi-glycosomal glyceraldehyde-3-phosphate dehydrogenase tests, suggesting that this enzyme is not their target. The trans-[Ru(NO)(NH3)4isn](BF4)3 and trans-[Ru(NO)(NH3)4imN](BF4)3 compounds are able to eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure the survival of all infected mice, thus opening a novel set of therapies to try against trypanosomatids.
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Carreño, Heider, Elena E. Stashenko, and Patricia Escobar. "Essential Oils Distilled from Colombian Aromatic Plants and Their Constituents as Penetration Enhancers for Transdermal Drug Delivery." Molecules 28, no. 6 (March 22, 2023): 2872. http://dx.doi.org/10.3390/molecules28062872.
Анотація:
The study aimed to determine the enhanced effects of essential oils (EOs) and plant-derived molecules (PDMs) as penetration enhancers (PEs) for transdermal drug delivery (TDD) of caffeine. A 1% w/w solution of eight EOs and seven PDMs was included in the 1% caffeine carbopol hydrogel. Franz diffusion cell experiments were performed using mice with full-thickness skin. At various times over 24 h, 300 μL of the receptor were withdrawn and replaced with fresh medium. Caffeine was analyzed spectrophotometrically at 272 nm. The skin irritation effects of the hydrogels applied once a day for 21 days were investigated in mice. The steady-state flux (JSS) of the caffeine hydrogel was 30 ± 19.6 µg cm−2 h−1. An increase in caffeine JSS was induced by Lippia origanoides > Turnera diffusa > eugenol > carvacrol > limonene, with values of 150 ± 14.1, 130 ± 47.6, 101 ± 21.7, 90 ± 18.4, and 86 ± 21.0 µg cm−2 h−1, respectively. The Kp of caffeine was 2.8 ± 0.26 cm h−1, almost 2–4 times lower than that induced by Lippia origanoides > Turnera diffusa > limonene > eugenol > carvacrol, with Kp values of 11 ± 1.7, 8.8 ± 4.2, 6.8 ± 1.7, 6.3 ± 1.2, and 5.15 ± 1.0 cm h−1, respectively. No irritating effects were observed. Lippia origanoides, Turnera diffusa, eugenol, carvacrol, and limonene improved caffeine’s skin permeation. These compounds may be as effective as the PE in TDD systems.
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Gubina, A. A., E. V. Levin, M. M. Romanovich, A. E. Degterev, N. O. Patokov, I. A. Lamkin, and S. A. Tarasov. "Optimal Spectral Radiation Composition of a LED Phytolapm for Stimulating Carrot and Tomato Seed Development." Journal of the Russian Universities. Radioelectronics 25, no. 3 (June 28, 2022): 62–72. http://dx.doi.org/10.32603/1993-8985-2022-25-3-62-72.
Анотація:
Introduction. Light-emitting diode (LED) irradiation is widely used in various spheres of human activity, including agriculture. Due to the growing urban population and aggravating environmental situation, the problem of high-quality food provision is increasingly attracting research attention. In this context, it is important to develop energy-efficient optical systems for ensuring optimal irradiation conditions for accelerating the growth of various types of plants and improving the quality of products in autonomous agro-industrial complexes.Aim. Determination of an optimal spectral radiation composition of a phytolamp consisting of LEDs based on AlGalnP (660 and 730 nm) and InGaN (440 nm), as well as phyto-LEDs (400. _ .800 nm), to stimulate the growth and development of tomato and carrot sprouts at the germination stage. Calculation of the LED optical power and photosynthetic photon flux density (PPFD).Materials and methods. Experiments were carried out to study the influence of visible radiation of different quality and quantity on the development parameters of carrot and tomato seeds, including germination energy, the appearance of cotyledon and primary leaves, seed germination, average hypocotyl and root length. Optimal spectral composition and radiation power parameters ensuring effective growth of plants were determined.Results. Additional 660-nm irradiation of tomato sprouts at the germination stage was shown to exhibit a positive effect on germination, average sprout length and root development. The best results of carrot germination and development were achieved when irradiated with short-wavelength light (PPFD 243 µmol∙s–1∙m–2). Irradiation of ~ 170 µmol∙s–1∙m–2 blue and 86 µmol∙s–1∙m–2 red light was found to be effective for enhancing carrot cultivation.Conclusion. The developed irradiation schemes can be used to vary the spectral radiation composition and PPFD at different stages of crop growth and development, thereby increasing yields and reducing energy costs. In the future, this technology can be used in space research, where high energy efficiency is fundamental.
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Shen, Lin, Ken Kato, Sung-Bae Kim, Jaffer A. Ajani, Kuaile Zhao, Zhiyong He, Xinmin Yu, et al. "RATIONALE 302: Randomized, phase 3 study of tislelizumab versus chemotherapy as second-line treatment for advanced unresectable/metastatic esophageal squamous cell carcinoma." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 4012. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.4012.
Анотація:
4012 Background: Tislelizumab (tisle) monotherapy or plus chemotherapy demonstrated antitumor activity in patients (pts) with solid tumors, including esophageal squamous cell carcinoma (ESCC) (NCT03469557 and CTR20160872). Methods: In this global phase 3 study (NCT03430843), adults with histologically confirmed advanced/unresectable or metastatic ESCC whose disease progressed following prior systemic therapy with ≥1 evaluable lesion per RECIST v1.1 and an Eastern Cooperative Oncology Group performance score (ECOG PS) of ≤1 were included. Pts were randomized (1:1) to receive tisle 200 mg intravenously every 3 weeks or investigator-chosen standard chemotherapy ([ICC]; paclitaxel, docetaxel, or irinotecan) and treated until disease progression, unacceptable toxicity, or withdrawal. Stratification factors included ICC option, region, and ECOG PS. The primary endpoint was overall survival (OS) in the intent-to-treat (ITT) population. The key secondary endpoint was OS in the programmed death-ligand 1 (PD-L1)+ population (visually-estimated combined positive score [vCPS] ≥10%, by VENTANA PD-L1 SP263 assay). Other secondary endpoints included (by RECIST v1.1) progression-free survival, overall response rate (ORR), duration of response (DoR), and safety. Results: Overall, 512 pts (median age: 62 years; range 35-86 years) from 132 sites in 10 countries in Asia (404 pts [79%]), Europe, and North America (108 pts [21%]) were randomized to tisle (n=256) or ICC (n=256) (ITT population). Of these, 157 pts (tisle [n=89], ICC [n=68]) had vCPS ≥10% (PD-L1+ population). On 1 Dec 2020 (data cut-off), median follow-up was 8.5 months (m) with tisle and 5.8 m with ICC. The study met its primary endpoint: tisle clinically and significantly improved OS vs ICC in the ITT population (median OS: 8.6 vs 6.3 m; HR 0.70, 95% CI 0.57-0.85, p=0.0001). Tisle also demonstrated significant improvement in OS vs ICC in the PD-L1+ population (median OS: 10.3 vs 6.8 m; HR 0.54, 95% CI: 0.36-0.79, p=0.0006). Survival benefit was consistently observed across pre-defined subgroups, including baseline PD-L1 status and region. Treatment with tisle was also associated with a higher ORR (20.3% vs 9.8%) and more durable response (median DoR: 7.1 vs 4.0 m; HR 0.42, 95% CI 0.23-0.75) than ICC in the ITT population. Fewer pts had ≥Grade 3 (46% vs 68%) treatment-emergent adverse events with tisle vs ICC. Of these, fewer ≥Grade 3 AEs were treatment-related (TR) with tisle vs ICC (19% vs 56%). Fewer pts discontinued tisle vs ICC (7% vs 14%) due to a TRAE. Conclusion: Tisle demonstrated statistically significant and clinically meaningful improvement in OS vs ICC in pts with advanced or metastatic ESCC who had disease progression during or after first-line systemic therapy. Tisle showed a higher and longer response vs ICC. The safety profile of tisle was more favorable than ICC. Clinical trial information: NCT03430843.
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Barclay, Johanna L., Carolyn J. Petersons, Sahar Keshvari, Jane Sorbello, Brenda L. Mangelsdorf, Campbell H. Thompson, Johannes B. Prins, Morton G. Burt, Jonathan P. Whitehead, and Warrick J. Inder. "Thrombospondin-1 is a glucocorticoid responsive protein in humans." European Journal of Endocrinology 174, no. 2 (February 2016): 193–201. http://dx.doi.org/10.1530/eje-15-0964.
Анотація:
ObjectiveThrombospondin-1 (TSP1) is a matricellular protein whose gene expression has previously been shown to increase acutely after exposure to dexamethasone in vitro. The aim of this study was to determine if TSP1 is altered by acute and chronic states of glucocorticoid excess in human subjects.Design and methodsThree studies have been undertaken to assess the difference or change in TSP1 in response to altered glucocorticoid activity: i) an acute interventional study assessed the effects of a single 4 mg dose of dexamethasone in 20 healthy volunteers; ii) a cross-sectional study compared plasma TSP1 in 20 healthy volunteers and eight patients with Cushing's syndrome; iii) an interventional study assessed the effect on plasma TSP1 of an increase in hydrocortisone dose from ≤20 mg/day to 30 mg/day for 7 days in 16 patients with secondary adrenal insufficiency.ResultsIn healthy volunteers, 4 mg dexamethasone significantly increased peripheral blood mononuclear cell (PBMC) TSP1 mRNA levels (P<0.0001) and plasma TSP1 concentrations (P<0.0001), peaking at 12 h. Median (interquartile range) plasma TSP1 was higher in Cushing's, 638 (535–756) ng/ml, than in healthy volunteers, 272 (237–336) ng/ml (P<0.0001). Plasma TSP1 >400 ng/ml diagnosed Cushing's syndrome with sensitivity of 100% and specificity of 85%. The higher hydrocortisone dose increased plasma TSP1 from 139 (86–199) to 256 (133–516) ng/ml, (P<0.01) in patients with secondary adrenal insufficiency.ConclusionsTSP1 is a glucocorticoid responsive protein in humans. Further research is required to determine if plasma TSP1 has a role as a glucocorticoid biomarker.
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Lykas, Christos, Constantinos Kittas, Nikolaos Katsoulas, and Maria Papafotiou. "Gardenia jasminoides Height Control Using a Photoselective Polyethylene Film." HortScience 43, no. 7 (December 2008): 2027–33. http://dx.doi.org/10.21273/hortsci.43.7.2027.
Анотація:
The use of chemical growth retardants is a standard practice for compact gardenia plant production. The aim of this study was to investigate the possibility of using a photoselective polyethylene greenhouse covering film as an alternative to chemical treatment for production of compact potted gardenia (Gardenia jasminoides Ellis) plants. Two types of experiments were carried out: 1) on gardenia cuttings rooted in rooting benches; and 2) on young potted plants grown under low tunnels. In both experiments, two types of cover materials were used: 1) a photoselective polyethylene (P-PE), filtering light within the wavelength range 600 to 750 nm; and 2) a common polyethylene film (C-PE) routinely used in greenhouse practice. Values of photosynthetically active radiation (in a wavelength of 400 to 700 nm), cover materials' spectral properties (in a wavelength range of 400 to 1100 nm), air temperature, and relative humidity were recorded inside the rooting benches and under the low tunnels. Plant growth parameters (main shoot length and leaf area and lateral shoot number, leaf area, and fresh and dry weight) were determined along the growth cycle. Cuttings rooted under the P-PE film received light with high ζn values (ratio of Rn: 655 to 665 nm to far red FRn: 725 to 735 nm) and high blue (B: 400 to 500 nm) to red (R: 600 to 700 nm) ratio (B:R) and were 68.7% shorter and had 21% lower leaf area compared with cuttings rooted under the C-PE film. Similarly, plants that were rooted and then grown under the low tunnels covered with the P-PE film, compared with plants rooted and grown under C-PE film, were 59% shorter, had 85% lower leaf area, 89% lower fresh weight, and 86% lower dry weight, whereas they did not produce lateral shoots. However, plants rooted under the C-PE film and then grown under the P-PE-covered low tunnels were 26% shorter and developed fewer laterals than plants rooted and grown under tunnels covered with C-PE film. Finally, plants rooted under the P-PE film and then grown under tunnels covered with C-PE film developed into compact, well-shaped plants, because they had a drastic reduction of height (56%) without an effect on leaf area, shoot and leaf fresh and dry weight, and the number of lateral shoots.
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Ding, Dale, Chun-Po Yen, Zhiyuan Xu, Robert M. Starke, and Jason P. Sheehan. "Radiosurgery for patients with unruptured intracranial arteriovenous malformations." Journal of Neurosurgery 118, no. 5 (May 2013): 958–66. http://dx.doi.org/10.3171/2013.2.jns121239.
Анотація:
Object The appropriate management of unruptured intracranial arteriovenous malformations (AVMs) remains controversial. In the present study, the authors evaluate the radiographic and clinical outcomes of radiosurgery for a large cohort of patients with unruptured AVMs. Methods From a prospective database of 1204 cases of AVMs involving patients treated with radiosurgery at their institution, the authors identified 444 patients without evidence of rupture prior to radiosurgery. The patients' mean age was 36.9 years, and 50% were male. The mean AVM nidus volume was 4.2 cm3, 13.5% of the AVMs were in a deep location, and 44.4% were at least Spetzler-Martin Grade III. The median radiosurgical prescription dose was 20 Gy. Univariate and multivariate Cox regression analyses were used to determine risk factors associated with obliteration, postradiosurgery hemorrhage, radiation-induced changes, and postradiosurgery cyst formation. The mean duration of radiological and clinical follow-up was 76 months and 86 months, respectively. Results The cumulative AVM obliteration rate was 62%, and the postradiosurgery annual hemorrhage rate was 1.6%. Radiation-induced changes were symptomatic in 13.7% and permanent in 2.0% of patients. The statistically significant independent positive predictors of obliteration were no preradiosurgery embolization (p < 0.001), increased prescription dose (p < 0.001), single draining vein (p < 0.001), radiological presence of radiation-induced changes (p = 0.004), and lower Spetzler-Martin grade (p = 0.016). Increased volume and higher Pittsburgh radiosurgery-based AVM score were predictors of postradiosurgery hemorrhage in the univariate analysis only. Clinical deterioration occurred in 30 patients (6.8%), more commonly in patients with postradiosurgery hemorrhage (p = 0.018). Conclusions Radiosurgery afforded a reasonable chance of obliteration of unruptured AVMs with relatively low rates of clinical and radiological complications.
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Lezhenina, S., N. Shuvalova, and E. Guryanova. "AB1569-PARE WHAT DO PATIENTS KNOW ABOUT RHEUMATOID ARTHRITIS?" Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1884.2–1884. http://dx.doi.org/10.1136/annrheumdis-2022-eular.628.
Анотація:
BackgroundPatient awareness of rheumatoid arthritis (RA) contributes to more effective prevention of this disease. It is necessary to study the initial level of knowledge of patients about rheumatoid arthritis and analyze which sections of the educational program need to be studied carefully.ObjectivesTo analyze what patients know about rheumatoid arthritis, and do patients with this nosology want to be trained in various educational programs?MethodsA survey of 86 patients with RA of varying severity was conducted. The diagnosis of RA was established according to the (EULAR)/ACR criteria. Patients were divided into 2 groups by age: group 1 - 18-44 years old (young patients, N= 43), group 2 - 45-65 years old (middle-aged patients, N= 43. The study was conducted in the Central District Hospital of the city of Kanash. Questioning was conducted from January to December 2021. The questionnaire consisted of 2 parts: the first part (part A) included 20 questions (2 points were awarded for each correct answer). Questions related to the relationship between the onset of the disease and hypothermia, infection, stress, injuries of the musculoskeletal the presence of rheumatoid arthritis in close relatives. The knowledge of one’s own role in the process of treatment and prevention of RA was assessed. The second part of the questionnaire (part B) consisted of 6 questions. The need for obtaining information about RA and the desire of patients to be trained in various educational programs was studied. It was studied in what format they would like to study (remote or full-time) Survey data was processed in Statistical Analysis Software 15.0. Statistical significance was handled using Analysis of Variation analysis of variance.Results43.7% of group 1 and 56.8% of group 2 correctly classified rheumatoid arthritis as a disease that occurs predominantly in women. 14.6% of young respondents knew about the role of infection in the occurrence of RA, 32.8% - middle-aged. 52.2% of middle-aged patients, 22.8% of young patients knew about the influence of heredity in the occurrence of the disease. 28.0% of young respondents knew about the negative impact of stress on the onset and course of RA, middle-aged respondents - 58.2%. 21.6% of young respondents were aware of the impact of injuries of the musculoskeletal system on the occurrence of RA compared to 55.3% of middle-aged respondents. The awareness of patients about their own role in the treatment process in group 1 was 4.2%, in group 2 - 5.4%. 10.6% of young respondents and 14.8% of middle-aged respondents consider it possible to prevent RA relapses.92.1% of group 1 and 89.1% of group 2 expressed the need for additional information about RA. Distance learning was preferred by 80.1% of young patients and 65.7% of middle-aged respondents. 56.9% were not aware of the negative impact of stress on the course of RA. 62.5% did not know about the influence of hereditary factors. 95.2% of respondents underestimate their own role in the treatment of rheumatoid arthritis and 87.3% consider it impossible to prevent RA exacerbations. A positive factor was that 90.6% of the respondents report a need to obtain additional information about the disease.ConclusionIt is necessary to actively implement various educational programs, in which more attention should be paid to the prevention of RA and the participation of the patient himself in the treatment process. Training for patients is preferable to be carried out in a distance learning format.Disclosure of InterestsNone declared
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Koniukhovskaia, J., E. Pervichko, O. Stepanova, and E. Dorokhov. "Psychopathological symptoms among the russian population during the COVID-19 pandemic in the spring of 2020." European Psychiatry 64, S1 (April 2021): S305. http://dx.doi.org/10.1192/j.eurpsy.2021.821.
Анотація:
IntroductionThe COVID-19 pandemic has affected the lifestyle and psychological well-being of millions of people.ObjectivesThe aim of the study was to assess the prevalence of psychopathological symptoms in the Russian population in the COVID- 19 pandemic context.MethodsWe used a socio-demographic questionnaire (20 questions) and a Short Scale for Psychopathological Symptom Checklist (SCL -32) (Derogatis 1977; Mitina, Gorbunova, 2011). 582 Russian residents (496 women and 86 men) aged 18-64 years participated in the online survey in May 2020.ResultsWomen were significantly more likely than men to have somatic dysfunctions (5.6±2.54vs4.8±1.9;p=0.001), interpersonal problems (6.97±2.9vs6.0±2.8; p=0.005), depression signs (6.9±3.2vs5.7±2.9;p=0.001) and anxiety disorders (6.8±2.8vs5.2 ±2.1;p=0.000), as well as sleep disorders (6.4±2.8vs5.9±2.1;p=0.049) and suicidal thoughts (4.2±1.8vs3.7±1.8;p=0.032). In addition, women are more hostile than men are (6.3±2.7 vs 5.1±2.3; p=0.000). Respondents under the age of 30 are more likely than older people to have interpersonal problems (p=0.286, p=0.000), as well as signs of depression (p=0.216, p=0.000), hostility (p=0.226, p=0.000) and psychoticism (p=0.203, p=0.000). Respondents’ low income is statistically associated with interpersonal problems (p=0.139,p=0.001), anxiety (p=0.131, p=0.002), hostility (p=0.156, p=0.000), psychoticism (p=0.137, p=0.001), and suicidal intentions (p=0.152,p=0.000). Among respondents whose relatives had COVID-19, signs of anxiety disorders (7.2±3vs3.5±2.9;p=0.027) and obsessive disorders (8.1±3.2 vs 7.3±2.6; p=0.029) were significantly more common than in the whole sample.ConclusionsThe study highlights socio-demographic factors of vulnerability to psychopathological symptoms in the COVID-19 pandemic context, which should be taken into account when organizing medical and psychological assistance to the population.
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Lee, Yun Jeong, Seung Chan Lee, Seo Young Wy, Hoo Young Lee, Hyang Lim Lee, Woo Hyung Lee, Byung-Mo Oh, and Jin Wook Jeoung. "Ocular Manifestations, Visual Field Pattern, and Visual Field Test Performance in Traumatic Brain Injury and Stroke." Journal of Ophthalmology 2022 (January 7, 2022): 1–6. http://dx.doi.org/10.1155/2022/1703806.
Анотація:
Purpose. To analyze ocular manifestations, visual field (VF) pattern, and VF test performance in traumatic brain injury (TBI) and stroke patients. Methods. This retrospective, cross-sectional study included 118 patients (236 eyes) with TBI and stroke who had undergone VF testing by standard automated perimetry with the central 24-2 threshold test. Clinical features including best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular manifestations, and VF test results including VF defect pattern, reliability, and global indices were analyzed and compared between the TBI and stroke patients. Results. In TBI patients, ocular manifestations included strabismus (11.1%), cataract (4.2%), and glaucoma suspect (2.8%), whereas in stroke patients, cataract (15.2%), strabismus (8.5%), diabetic retinopathy (4.9%), extraocular movement (EOM) limitation (3.0%), glaucoma suspect (3.0%), nystagmus (2.4%), drusen (1.2%), and vitreous hemorrhage (1.2%) were found. The VF test results showed that 47 eyes (85.5%) in TBI and 86 (65.2%) in stroke had VF defect; in TBI, the scattered pattern was the most common (56.4%), followed by homonymous hemianopsia (14.5%), homonymous quadrantanopia (10.9%), and total defect (3.6%), whereas in stroke, homonymous hemianopsia was the most common (31.8%), followed by scattered pattern (16.7%), homonymous quadrantanopia (12.1%), and total defect (4.5%). Only 15 eyes (27.3%) in TBI and 32 (24.2%) in stroke showed reliable VF indices. The mean deviation (MD) was −10.5 ± 7.1 dB in TBI and −9.5 ± 6.8 dB in stroke, and the pattern standard deviation (PSD) was 4.9 ± 3.3 dB in TBI and 6.1 ± 3.9 dB in stroke, without statistically significant differences between the two groups. Conclusion. Various ocular manifestations were found, and a considerable proportion of patients were experiencing VF defects and showed unreliable VF test performance. Our findings suggest that accurate evaluation and rehabilitation of visual function should be a matter of greater concern and emphasis in the management of TBI and stroke patients, besides systemic diseases.
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Chen, Ying, Yifan Chu, Wen Yao, Luyao Wang, Wanjiang Zeng, and Jing Yue. "Comparison of Cumulative Live Birth Rates between Flexible and Conventional Progestin-Primed Ovarian Stimulation Protocol in Poor Ovarian Response Patients According to POSEIDON Criteria: A Cohort Study." Journal of Clinical Medicine 12, no. 18 (September 5, 2023): 5775. http://dx.doi.org/10.3390/jcm12185775.
Анотація:
Research Question: To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. Design: Poor ovarian response women, according to POSEIDON criteria, who underwent the first PPOS protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between January 2018 and December 2020 were included. The fPPOS group involved 113 participants, and the cPPOS group included 1119 participants. In the cPPOS group, medroxyprogesterone acetate (MPA) (10 mg/d) was administrated on the gonadotropin injection the same day as gonadotropin injections in the cPPOS group, while MPA was started either on the day when the leading follicle with mean diameter > 12mm was present and/or serum E2 was >300 pg/mL in the fPPOS protocol group. The primary outcome was CLBR. Results: The fPPOS protocol had higher CLBR per oocyte retrieval cycle compared to the cPPOS group, even without a statistically significant difference (29.6% vs. 24.9%, p = 0.365). The fPPOS group had fewer numbers of retrieved oocytes (2.87 ± 2.03 vs. 3.76 ± 2.32, p < 0.001) but a higher MII oocyte rate (89.8% vs. 84.7%, p = 0.016). In addition, the number of available embryos in the two groups was comparable (1.37 ± 1.24 vs. 1.63 ± 1.38, p = 0.095). There were five women in the fPPOS group, and 86 women in the cPPOS group had a premature LH surge (4.2% vs. 6.8%, p = 0.261). In the fPPOS group, there was one instance of premature ovulation, while in the cPPOS group, there were six occurrences of premature ovulation (0.8 vs. 0.5%, p = 1.000). Conclusion(s): The novel fPPOS protocol appears to achieve higher CLBR even without significant differences and with MPA consumption compared with cPPOS protocol in low-prognosis patients.
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Kim, Dong-Wook, Camille Granvil, Eren Demirhan, John Reynolds, Yu Jin, Yanfeng Wang, Michele Baccarani, et al. "Comparison of Steady-State Imatinib (IM) Trough Levels, Clinical Response, and Safety Between Caucasian and Asian Patients with Chronic Lyeloid Leukemia in Chronic Phase (CML-CP) Treated with 400mg and 800mg Daily Doses of IM in the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) Study." Blood 114, no. 22 (November 20, 2009): 1127. http://dx.doi.org/10.1182/blood.v114.22.1127.1127.
Анотація:
Abstract Abstract 1127 Poster Board I-149 Background In the TOPS study, IM trough levels (Cmin) were collected from different race groups, mainly Caucasian and Asian, but also Black and others. Inter-ethnic differences in the PK of a drug are known to be important factors accounting for inter-individual variation in drug responsiveness. This analysis reports the comparison between Caucasian and Asian CML patients (pts) treated at doses of 400 mg QD and 400 mg bid (800 mg daily) of IM Cmin on Day 29 of initial treatment, clinical response, safety and tolerability. Methods Steady state IM Cmin on Day 29 and clinical response and safety data obtained during the first 12 months (mos) of treatment were obtained from pts randomized 2:1 to 800 mg or 400 mg daily IM. The steady-state Cmin was defined as predose concentration collected approximately within ±3 hours of the scheduled dosing time on Day 29. The associations of race with the rates of major molecular response (MMR) and complete cytogenetic response (CCyR) were evaluated. Correlation of IM exposure with clinical response (MMR and CCyR) was assessed by grouping pts into quartiles based on their measured IM Cmin levels at Day 29. The safety endpoint for each pt was the presence or absence of an adverse event (AE) of grade 3 or higher in the first 12 mos from the first dose. Results IM Cmin levels were available from 229 pts in TOPS including 54 Caucasians, 18 Asians, and 14 Black and others at 400 mg (total 86) and 103 Caucasians, 29 Asians, and 11 Black and others at 800 mg (total 143). For the first 12 mos, the means of the average dose intensities for Asian (mean [range], 362 [267-400] in 400 mg and 666 [226-800] in 800 mg) were not significantly different from Caucasian (386 [204-597] in 400 mg and 666 [289-800] in 800 mg) (P=0.070 and P=0.995 for the 400 mg and 800 mg arms, respectively). Mean (± SD) of IM Cmin levels (ng/mL) with respect to race are shown in Table 1. IM Cmin was slightly over-proportional to dose and showed large interpatient variability (CV=42-60%) for both dose groups regardless of the race group. In the lower quartile Cmin group (Cmin<1290 ng/mL), the differences in CCyR and MMR rates between Asian and Caucasian pts were significant (P=0.031 and P=0.022 respectively), which was probably due to a higher rate of dose interruptions in the 1st 12 mos in Asian pts. A definitive conclusion cannot be drawn due to the small number of Asian pts. Occurrences of at least one grade 3 or 4 adverse event were found to be significantly higher in Asian pts (69% and 75% in the 1st 6 and 12 mos respectively) compared to Caucasian pts (53% and 57% in the 1st 6 and 12 mos respectively) (P=0.028 and P=0.008 respectively). Conclusion The results of this analysis from TOPS show that IM Cmin levels were similar between Caucasian and Asian CML pts in each treatment arm. There were no major differences in efficacy, as measured by MMR and CCyR rates by 12 mos, between Asian and Caucasian pts. There were no unexpected differences in patterns of AEs between Caucasian and Asian pts; however, occurrences of one or more grade 3 AEs were higher in Asian. Further analysis on a larger group of CML pts will be needed to evaluate the impact of AE rate differences between Caucasian and Asian pts. Disclosures Kim: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Wyeth: Research Funding. Granvil:Novartis: Employment. Demirhan:Novartis: Employment. Reynolds:Novartis: Employment. Jin:Novartis: Employment. Wang:Novartis: Employment, Equity Ownership. Baccarani:Novartis Pharma: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Mayer Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cortes-Franco:Novartis: Honoraria, Research Funding, Speakers Bureau; Wyeth: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau. Druker:OHSU patent #843 - Mutate ABL Kinase Domains: Patents & Royalties; MolecularMD: Equity Ownership; Roche: Consultancy; Cylene Pharmaceuticals: Consultancy; Calistoga Pharmaceuticals: Consultancy; Avalon Pharmaceuticals: Consultancy; Ambit Biosciences: Consultancy; Millipore via Dana-Farber Cancer Institute: Patents & Royalties; Novartis, ARIAD, Bristol-Myers Squibb: Research Funding. Hughes:Bristol-Myers Squibb: Advisor, Honoraria, Research Funding; Novartis: Advisor, Honoraria, Research Funding. Guilhot:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria.
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Barbosa, Patricia R., Sally P. Stabler, Mario H. Hirata, Rosario D. C. Hirata, Robert H. Allen, Luiz F. Sampaio-Neto, and Elvira M. Guerra-Shinohara. "Effects of Methionine Synthase (MS) A2756G and Methionine Synthase Reductase (MSR) A66G Polymorphisms on Methionine Metabolism in Brazilian Pregnant Women and Their Neonates." Blood 104, no. 11 (November 16, 2004): 3686. http://dx.doi.org/10.1182/blood.v104.11.3686.3686.
Анотація:
Abstract Methionine synthase (MS) is a cobalamin dependent enzyme that catalyses the remethylation of homocysteine to methionine. The methionine synthase reductase (MSR) maintains adequate levels of methylcob(III)alamin, the activated cofactor for MS. The aim of this study was to investigate the effect of MS A2756G and MSR A66G polymorphisms on total homocysteine (tHcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) levels in 390 pregnant women and their 292 newborns, from Sorocaba city, Brazil. Genotypes of two polymorphisms were determined by PCR-RFLP. Pregnant women with MS 2756AA genotype have higher tHcy and lower Cbl levels than those with 2756G alleles. The MMA values were increased in neonates with MS 2756AA genotypes (Table 1). There are no difference between the maternal values of Cbl, serum folate, tHcy, MMA and SAM according to MSR A66G genotypes.The values of SAM were lower in neonates with MSR 66G alleles than those with AA genotypes (Table 2). We conclude that MS 2756AA genotypes are associated with higher tHcy levels in pregnant women and higher MMA levels in neonates. The MSR 66GG genotypes is associated with lower SAM levels in neonates. Table 1- Distribution of geometric means and confidence intervals 95% (CI 95%) and numbers of subjects for maternal and neonatal values of cobalamin (Cbl), serum folate, total homocysteine (tHcy), methymalonic acid (MMA) and S- adenosylmethionine (SAM) according to genotypes for the polymorphism MS A2756G. Variables Genotypes for MS A2756G Student t Test AA AG + GG Pregnant Women Cbl (pmol/L) 139 (133 – 144) 235 156 (146 – 166) 129 P= 0.001 SF (nmol/L) 14.3 (13.6 – 15.0) 234 14.5 (13.6 – 15.5) 129 P= 0.667 tHcy( μmol/L) 6.8 (6.5 – 7.1) 235 6.2 (5.9 – 6.6) 128 P= 0.036 MMA(nmol/L) 234 (219 – 245) 194 241 (219 – 265) 106 P= 0.610 SAM(nmol/L) 81.8 (77.9 – 86,0) 229 83.1 (79.1 – 87.4) 124 P= 0.663 Neonates Cbl (pmol/L) 227 (212 – 244) 188 234 (213 – 257) 101 P= 0.646 SF (nmol/L) 32.0 (31.0 – 33.0) 186 32.0 (30.8 – 33.2) 99 P= 0.967 tHcy μmol/L) 5.8 (5.5 – 6.1) 185 5.5 (5.1 – 5.9) 100 P= 0.229 MMA(nmol/L) 383 (364 – 402) 183 342 (317 – 369) 100 P= 0.011 SAM(nmol/L) 188 (181 – 196) 178 182 (168 – 197) 98 P= 0.491 Table 2 - Distribution of geometric means and confidence intervals 95% (CI (%%) and number of subjects for neonatal values of cobalamin (Cbl), serum folate, total homocysteine (tHcy), methylmalonic acid (MMA) and S- adenosylmethionine (SAM) according to genotypes for the polymorphism MSR A66G. Variables Genotypes MSR A66G Student t Test AA AG GG Groups not sharing a common superscript letter are significantly different at P<0.05 based on Tukey’s test Neonates Cbl (pmol/L) 225 (202 – 249) 86 229 (214 – 246) 166 247 (205 – 298) 35 P= 0.602 SF (nmol/L) 33.0 (31.6 – 34.4) 84 31.7 (30.7 – 32.7) 166 31.8 (29.7 – 34.2) 33 P= 0.352 tHcy μmol/L) ( 5.7 (5.3 – 6.2) 84 5.6 (5.3 – 5.9) 165 5.9 (5.3 – 6.6) 34 P= 0.618 MMA (nmol/L) 360 (334 – 389) 84 378 (357 – 400) 163 339 (299 – 384) 34 P= 0.230 SAM (nmol/L) 200 (186 – 215)a 82 184 (176 – 192)a 159 170 (149 – 195)b 33 P= 0.032
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Walker, Irwin R., Donald M. Arnold, and Jim A. Julian. "Survival of HIV Infected Individuals with Hemophilia after 20 Years: From the Canadian Hemophilia Registry." Blood 104, no. 11 (November 16, 2004): 3085. http://dx.doi.org/10.1182/blood.v104.11.3085.3085.
Анотація:
Abstract Background : Patients with hemophilia A and B have been tracked by the Canadian Hemophilia Registry since 1980. The total number on the Registry is 3307 (A=2721, B=586) of which 662 were/are HIV-positive. New HIV and HCV infections ceased after 1985 and 1988 respectively with the introduction of safer blood products; HIV-infected individuals with hemophilia therefore resemble a cohort with HIV infection that was acquired in a relatively narrow time period about 20 years ago. Current status of HIV-positive patients is Active 250 (37.8%), Deceased 406 (61.3%), Lost to Follow Up 9 (0.9%). Follow up data is available for 3135/3307 (95% of all patients), and for 656/662 (99% of HIV-positive patients). We previously reported (Haemophilia1998;4:714) a peak in the death rate of HIV-positive individuals during the years 1991 to 1993 with a subsequent decline. Objective : To update the rate and causes of death among HIV positive hemophilia patients in Canada with current information. HIV-Related Mortality : The annual number of deaths in the HIV-positive group has been [year-#(deaths per 100 person-years)], 1980-0(0), 81-0(0),82-0(0),83-3(0.45),84-1(0.15),85-2(0.30),86-12(1.8),87-12(1.9),88-21(3.3),89-25(4.1),90-24(4.1),91-45(8.0),92-38(7.4),93-Currently, 256/662 (38.7%) are alive. Causes of Death (HIV+) : The commonest primary causes of death in HIV-positive individuals have been: [cause #(%)] AIDS 284(70), liver failure 45(11), bleeding 18(4.4) and infections 15(3.7). Twenty-eight patients had liver disease listed as a secondary or contributing cause of death; thus liver disease was the primary or contributory cause of death in 45+28=73 individuals (18% of HIV-positive deaths). HCV-Related Deaths : HCV status is positive in 1151 of the total population of 3307 (35%) individuals in the registry, negative in 1260 (38%) and unknown in 896 (27%). Of HIV-positive individuals, 448 (68%) are co-infected with HCV, 53 of whom have died with liver failure (12% overall, 18% of deaths). HIV/HCV co-infected individuals have higher overall mortality than those not co-infected (46% vs. 12%, p<0.0001). In addition, HCV singly-infected individuals have lower overall mortality (7%). 703 HIV-negative individuals are infected with HCV, of whom 7 have died with liver failure (1% overall, 13% of deaths). Conclusions : The death rate of HIV-positive individuals peaked in the years 1991-3 and decreased thereafter with 38% of individuals still living at 20 years follow up. However deaths still occur at an annual rate of 3–5%. HIV/HCV co-infected individuals have the highest mortality and HCV single-infected individuals have the lowest mortality of those with transfusion-transmitted infection. Liver failure is a common mode of death in both HIV- and HCV-infected individuals.
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Shamanna, Paramesh, Mala Dharmalingam, Arun Vadavi, Jahangir Mohammed, Terrence Poon, Mohamed Thajudeen, Ashok Keshavamurthy, and Suchitra Bhonsley. "Response to Twin Enabled Precision Treatment for Reversing Diabetes: An Initial Analysis at 4 Weeks of the Ongoing Randomised Controlled Trial." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A474—A475. http://dx.doi.org/10.1210/jendso/bvab048.970.
Анотація:
Abstract Introduction: Technology enabled precision nutrition, a combination of macro, micro and biota nutrients, along with Continuous Glucose Monitoring (CGM) have been demonstrated to be a key for reversal of diabetes. Methods: We conducted an initial analysis (n=23) of the ongoing randomized controlled trial of Twin Precision Treatment (TPT): a novel whole-body digital twin enabled precision treatment for reversing diabetes. The clinical and the biochemical parameters were evaluated as the longitudinal follow up at the first follow up visit at 4 weeks. The target sample size is 300 with an estimated duration of 5 years. Descriptive statistics were used Results: 8/23 (35%) patients achieved the intended outcome of reversal of HbA1c and off any anti-diabetic medications. There was a statistically significant improvement in HbA1c % (8.5 ± 1.6 to 6.8 ± 0.66; p<0.0001), Fasting Blood Glucose mg/dL (FBS) (151 ± 44 to 98 ± 18; p<0.0001), HOMA2-IR (1.7 ± 0.64 to 1 ± 0.45; p=0.0001), HOMA2-Beta (53 ± 28 to 86 ± 38; p=0.0013), Systolic BP (129 ± 11 to 120 ± 11; p=0.008) and serum albumin g/dL (4.5 ± 0.21 to 4.2 ± 0.31; p=0.0042). The baseline values for the other parameters including body weight, waist circumference, Diastolic BP, Alanine transaminase (ALT), Gamma-glutamyl transferase (GGT), eGFR, WBC, Platelet, Globulin, ESR, demonstrated a clinically relevant, superior change Discussion: The initial analysis for the prospectively designed trial reveals a remarkable improvement in the clinical and the biochemical parameters that would determine the complete and the prolonged remission of diabetes. The initial results are an early indicator for the translation of the scientific rationale for the technological intervention, through digital twin technology, powered by Internet of Things (IoT) and Artificial Intelligence (AI), as a modality to enable reversal of diabetes into an achievable outcome that would be durable. The impactful glycemic control appears to have positive meaningful metabolic health consequences Trial Registration: The trial has been prospectively registered in Clinical Trial Registry – India: Reference no. CTRI/2020/08/027072 on August 10, 2020
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D’Onofrio, Rosario, Anas Radi Alashram, Giuseppe Annino, Matteo Masucci, Cristian Romagnoli, Elvira Padua, and Vincenzo Manzi. "Prevention of Secondary Injury after Anterior Cruciate Ligament Reconstruction: Relationship between Pelvic-Drop and Dynamic Knee Valgus." International Journal of Environmental Research and Public Health 20, no. 4 (February 9, 2023): 3063. http://dx.doi.org/10.3390/ijerph20043063.
Анотація:
(1) Background: Optimal neuromuscular, Lumbo-Pelvic-Hip Complex, and lower extremity control are associated with decreased risk factors for secondary anterior cruciate ligament (ACL) injury. This study aimed to analyze any asymmetries and malalignments in the Lumbo-Pelvic-Hip Complex and the lower limbs at 6 months after ACL reconstruction (ACLR). (2) Methods: We conducted an exploratory retrospective observational single-center study in patients during the outpatient postoperative rehabilitation program at ICOT (Latina, Italy). From January 2014 to June 2020, 181 patients were recruited, but only 100 patients (86 male 28 ± 0.6 years, 178 ± 0.5 height; 14 female 24 ± 2.0 years, 178 ± 3.0 height) were eligible for the inclusion criteria and studied 6 months after ACL reconstruction surgery. (3) Statistical analysis: Student’s t-tests and Pearson’s product-moment correlation coefficient were used to determine significant differences between affected and non-affected limbs and variables’ association. (4) Results: The study shows a decrease in neuromuscular control of the Lumbo-Pelvic-Hip Complex and dynamic adaptive valgus of the knee at 6 months after ACLR (mean difference between pathological and healthy limb of dynamic adaptive valgus was −10.11 ± 8.19° 95% CI −14.84 to −9.34; mean value was 16.3 ± 6.8° 95% CI 14.04 to 18.55 for healthy limb and 4.2 ± 3.1° 95% CI 3.15 to 5.21 for pathological limb, p < 0.0001). The results also showed a relationship between dynamic adaptive valgus and contralateral pelvic drop (r = 0.78, 95% CI 0.62 to 0.88, magnitude of correlation very large). (5) Conclusions: The analysis showed an associative correlation between decreased postural control of the pelvic girdle and dynamic adaptive valgus of the knee in 38% of patients; this study highlights the usefulness of the Single-Leg Squat Test (SLST) as a clinical/functional assessment to evaluate the rehabilitation process and as a preventive tool to reduce the risk of second ACL injuries during the return to sport.
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Main, Stephanie, Rina Triasih, Jane Greig, Arif Hidayat, Immanuel Billy Brilliandi, Syarifah Khodijah, Geoff Chan, et al. "The prevalence and risk factors for tuberculosis among healthcare workers in Yogyakarta, Indonesia." PLOS ONE 18, no. 5 (May 18, 2023): e0279215. http://dx.doi.org/10.1371/journal.pone.0279215.
Анотація:
Healthcare workers (HCWs) are at risk of contracting TB, particularly when in high tuberculosis (TB) burden settings. Routine surveillance data and evidence are limited on the burden of TB amongst HCWs in Indonesia. We aimed to measure the prevalence of TB infection (TBI) and disease among HCWs in four healthcare facilities in Yogyakarta province in Indonesia, and explore risk factors for TBI. A cross-sectional TB screening study targeted all HCWs from four pre-selected facilities (1 hospital, 3 primary care) in Yogyakarta, Indonesia. Voluntary screening included symptom assessment, Chest X-ray (CXR), Xpert MTB/RIF (if indicated) and tuberculin skin test (TST). Analyses were descriptive and included multivariable logistic regression. Of 792 HCWs, 681 consented (86%) to the screening; 59% (n = 401) were female, 62% were medical staff (n = 421), 77% worked in the one participating hospital (n = 524), and the median time working in the health sector was 13 years (IQR: 6–25 years). Nearly half had provided services for people with TB (46%, n = 316) and 9% reported ever having TB (n = 60). Among participants with presumptive TB (15%, n = 99/662), none were diagnosed microbiologically or clinically with active TB disease. TBI was detected in 25% (95% CI: 22–30; n = 112/441) of eligible HCWs with a TST result. A significant association was found between TB infection and being male (adjusted Odds Ratio (aOR) 2.02 (95%CI: 1.29–3.17)), currently working in the participating hospital compared to primary care (aOR 3.15 (95%CI: 1.75–5.66)), and older age (1.05 OR increase per year of life between 19–73 years (95%CI: 1.02–1.06)). This study supports prioritisation of HCWs as a high-risk group for TB infection and disease, and the need for comprehensive prevention and control programs in Indonesia. Further, it identifies characteristics of HCWs in Yogyakarta at higher risk of TBI, who could be prioritised in screening programs if universal coverage of prevention and control measures cannot be achieved.
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Kroviakov, S. O., and V. O. Kryzhanovskyi. "INFLUENCE OF FIBER REINFORCEMENT ON CONCRETE SHRINKAGE FOR RIGID ROAD AND AIRFIELD PAVEMENT REPAIR." Bulletin of Odessa State Academy of Civil Engineering and Architecture, no. 84 (September 30, 2021): 78–86. http://dx.doi.org/10.31650/2415-377x-2021-84-78-86.
Анотація:
Abstract. The influence of fiber reinforcement with steel anchor fiber on the shrinkage of modified concrete for rigid airfield pavements repair has been determined. A 2-factor experiment was carried out, in which the following composition factors were varied: the amount of hardening accelerator Sika Rapid 3 from 0 to 2.4% of the cement content (0-9.6 kg/m3); the amount of steel anchor fiber with 1 mm diameter and 50 mm length, from 0 to 100 kg/m3. For the concrete batching were used: Portland cement CEM II / AS 42.5 in the amount of 400 kg/m3, granite crushed stone 5-20 mm, quartz sand, plasticizer admixture BASF MasterGlenium SKY 608 in the amount of 1.2% by cement content. The workability of the mixtures was S2 (6-8 cm); W/C ratio depended on the concrete composition. Due to the use of superplasticizers, the W/C of all investigated mixtures was in the range of 0.309-0.343. The shrinkage of the prism specimens was recorded after 3 hours, 6 hours, 1, 2, 3 and 7 days of being in air-dry conditions. The shrinkage process does not end after 7 days of concrete hardening, however, the general nature of the influence of variable factors on its value remains. It has been established that fiber-reinforced concretes, with a fiber amount of 50 kg/m3 and with a fiber amount of 100 kg/m3, have 10-15% less shrinkage compared to unreinforced concretes. Compositions with a fiber amount of 50 kg/m3 and 100 kg/m3 have practically the same shrinkage, which is explained by an increase in W/C ratio with an increase in the amount of fiber reinforcement. The amount of hardening accelerator has a less noticeable effect on the amount of concrete shrinkage. By adding Sika Rapid 3, concrete shrinkage at the age of 7 days is reduced by 2-9%. This effect can be explained by the fact that internal stresses arising in the process of structure formation and moisture loss in concrete are contained in a more durable cement-sand matrix. The concrete shrinkage without fiber and accelerator was also measured up to the age of 98 days. It was found that the limiting shrinkage for such concrete is 2.5×10-4. The analysis of the drawn experimental-statistical model showed that with the amount of metal fiber from 60 to 90 kg/m3 and the amount of the hardening accelerator from 0.9 to 2.4%, the shrinkage of the investigated concretes is minimal (7 = 1.3×10-4). Thus, the use of fiber reinforcement with anchor steel fiber and a hardening accelerator can significantly reduce the concrete shrinkage for the rigid airfield pavements repair is important for this material.
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Kutluk, M. Tezer, and Akif Yeşilipek. "Pediatric Cancer Registry in Turkey 2009-2021 (TPOG & TPHD)." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e22020-e22020. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e22020.
Анотація:
e22020 Background: The pediatric cancers is in the global agenda to improve the survival rates which is still low in LMICs although it is more than 80% in HICs. More than 300.000 pediatric cancer cases annually are expected in children and adolescents aged 0-14 globally. Registry is the first step of an efficient cancer control. Here, we present the most updated results of the pediatric cancer registry fromTurkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association has established the pediatric cancer registry in 2002. The childhood cancer cases registered between 2009-2021 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 13 years from 2009 to 2021, 24080 cases were registered. For all cases, median age was 6.7 year (0-19; M/F 13461/10609, 4 hermaphrodite, 6 unknown). Age distribution was 0-4 yrs, 40.8%; 5-9 yrs, 23.8%; 10-14 yrs, 23.3%; 15-19 yrs, 12.1%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (5819, 24.2%, 5.5, 3366/2453); Lymphoma & other RES tumors (4446, 18.5%, 9.8, 2956/1487, 1 hermaphrodite & 2 unknown); CNS [brain & spinal] (3730, 15.5%, 6.8, 2061/1668, 1 unkown); Symphatetic system (1965, 8.2%, 2.3, 1010/955); Retinoblastoma (675, 2.8%, 1.4, 375/300); Renal (1160, 4.8%, 3.1, 557/601, 1 hermaphrodite & 1 unknown); Liver (409, 1.7%, 2.2, 234/175); Malignant bone (1584, 6.6%, 12.6, 864/720); Soft tissue sarcomas (1726, 7.2%, 7.7, 983/743); Germ cell (1593, 6.6%, 9.6, 588/1001, 2 hermaphrodite, 2 unknown); Carcinoma & other malignant epithelial (804, 3.3%, 13.5, 381/423); Other/non-specific malignant (169, 0.7%, 7.9, 86/83). Five year survival rate was found as 72.3%. Conclusions: The registry shows that the survival rates for children and adolescents have been improved to 72% which reflects the status of the pediatric cancer care in Turkey. The data from this work became a valuable source for all stakeholders in national and international level working on improvement the pediatric cancer control.
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Arellano-Rodrigo, Eduardo, Alberto Alvarez-Larran, Francisco Cervantes, Juan-Carlos Reverter, Neus Villamor, and Emili Montserrat. "Increased Platelet Turnover and Platelet P-Selectin in Patients with Essential Thrombocythemia and Thrombosis." Blood 104, no. 11 (November 16, 2004): 4744. http://dx.doi.org/10.1182/blood.v104.11.4744.4744.
Анотація:
Abstract Essential thrombocythemia (ET) is a myeloproliferative disorder associated with an increased tendency to thrombosis, the pathogenesis of which is not well known. The aim of the present study was to analyze the relationship between platelet turnover and activation and a history of thrombosis in patients with ET. The expression of platelet P-selectin (measured both in unstimulated platelets and after agonist-stimulation with ADP, thrombin, arachidonic acid (AA), collagen or epinephrine) and the percentage of reticulated platelets (RP) were measured in 53 ET patients with (n=26) or without (n=27) previous thrombosis and in 26 healthy controls. Both variable were assessed using quantitative whole blood cytometry and the results were expressed as percentages and in MESF (molecules of equivalent soluble fluorochrome) units. The results were as follows: 1) patients with thrombosis showed a significantly higher basal platelet P-selectin expression (6.1%, 95% CI: 4.6–6.8) than those without thrombosis (4.6%, 95% CI: 3.7–5.5)) and the healthy controls (3%, 95% CI: 2–4.2) (p= 0.0001 for all comparisons); 2) following thrombin activation, ET patients had a higher mean percentage of platelet P-selectin expression than the controls (61% versus 46%, p = 0.01), but no difference was seen between the two groups of patients; 3) after AA activation, patients with ET and thrombosis also showed higher platelet P-selectin values (78%, 95% CI: 69–86) than those without thrombosis (63%, 95% CI: 55–76) and the controls (46%, 95% CI: 33–58) (p=0.001 for all comparisons); 4) ET patients with thrombosis had a significantly higher mean percentage of RP (18%, 95% CI: 13–20) than patients without thrombosis (13%, 95% CI: 11–18) and the controls (8%, 95% CI: 5–10) (p = 0.0001 for all comparisons). No differences were observed when the patients were separated on the basis of the treatment that they received at the time of study. The above results point at a possible role of AA-induced platelet acitvation in the development of thrombosis in ET and give conceptual support to the prohylactic use of aspirin in such patients.
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Brenner, Andrew Jacob, Yael Cohen, James J. Vredenburgh, Katherine B. Peters, Eyal Breitbart, Livnat Bangio, Naamit Sher, Dror Harats, and Patrick Y. Wen. "Phase I/II dose-escalation study of VB-111, an antiangiogenic gene therapy, in patients with recurrent glioblastoma multiforme." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): TPS2102. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.tps2102.
Анотація:
TPS2102 Background: VB-111 is an anti-angiogenic agent consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a fas-chimera transgene in angiogenic endothelial cells. In a phase I/II dose-escalation study, safety and efficacy of VB-111 in patients with recurrent Glioblastoma Multiforme (GBM) were evaluated. Methods: VB-111 was administered as a single intravenous infusion at escalating doses from 1x1012 to 3x1012 viral particles (VPs), followed by repeat doses of 3x1012 or 1x1013every 2 months. Assessments included safety, pharmacokinetics, tumor response (RANO criteria) and overall survival (OS). Results: Twenty eight patients aged 26 – 74 years at 3 medical centers in the US received up to 8 repeat doses of VB-111. The median OS was 360 [range: 70-574] and 266 days [range: 28-664] for patients receiving at least one dose of 1x1013VPs (high dose) vs. subjects who received lower doses, respectively (p NS). Progression free survival was 87 vs 55 days for patients who received high dose and for lower doses, respectively (p = 0.01). Median follow-up was 232 days. Three patients had a partial response (PR) at 82, 86 and 408 days post initial VB-111 dosing. Twenty one of the patients who progressed on VB-111 treatment received bevacizumab off study; 7 of the 15 evaluable patients (47%) had a PR compared to 30% expected according to literature. VB-111 was safe and well tolerated, 53 adverse events were reported, 14 were classified as possibly related to VB-111. All events were of CTCAE grade 1-2 except one grade 3 pulmonary embolism. There were no study related deaths. One patient developed peri-tumoral edema, which resolved with corticosteroid therapy. Events occurring in > 10% of the patients included headache and fatigue. Conclusions: VB-111 was safe and well tolerated in patients with recurrent GBM with repeat doses of up to 1x1013 VPs. Tumor responses were seen. Overall survival was about 3 months longer than historical data in recurrent GBM, including standard of care anti-angiogenic agents. Data suggests that VB-111 potentiates the response to bevacizumab given at further progression. Clinical trial information: NCT01260506.
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Ghanem, Hady A., Dan Jones, Hagop M. Kantarjian, Stefan Faderl, Elihu H. Estey, Sherry Pierce, Susan O’Brien, Jorge Cortes, and Farhad Ravandi. "Effect of FMS-Like Tyrosine Kinase-3 Mutations on Prognosis in Acute Myeloid Leukemia: A Single Institution Experience between 2000 and 2007." Blood 110, no. 11 (November 16, 2007): 3489. http://dx.doi.org/10.1182/blood.v110.11.3489.3489.
Анотація:
Abstract Mutations of the FMS-like tyrosine kinase-3 gene (FLT3), including internal tandem duplication (ITD) of the juxtamembrane domain or activating point mutations of the second tyrosine kinase domain involving codon 835 or 836 are among the most common molecular abnormalities in acute myeloid leukemia (AML). A clear negative impact of FLT3 mutation on survival has been demonstrated in AML patients younger than 60 years; however, this negative effect on prognosis or survival has not been confirmed in older patients. We evaluated 661 patients with AML treated at MD Anderson Cancer center between 2000 and 2007 for FLT3 mutations including 281 patients ≤ 60 years and 380 patients > 60 years. Median age for the entire group was 65 years (range, 17 to 86). A FLT3 mutation was present in 124 patients (18.7%). Patients with FLT3 mutations had a significantly higher WBC (median, 16.5 vs. 4.2, p<0.001) and a higher percentage of bone marrow blasts (median, 62% V/S 40%, p<0.001) at initial presentation. These differences were equally seen in both sexes. Patients with FLT3 mutations were younger than those without mutations (median age 58 vs. 64, p=0.005). Patients with FLT3 mutations were less likely to have an antecedent hematological disease compared to those without mutations (p<0.001). FLT3 mutations were less frequent in patients with core binding factor leukemia [t(8;21), inv(16)]. FLT3 mutations were more common in patients with acute promyelocytic leukemia (APL) than other FAB subgroups (p<0.001). Induction death and complete remission rates were not affected by FLT3 status. When favorable prognosis subgroups [APL, t(8;21), inv(16)] were excluded, patients with FLT3 mutations had a significantly shorter overall survival; this difference was seen in patients younger than 60 (p=0.019), as well as in patients over 60 (p=0.015). We have further confirmed a clear negative impact of FLT3 mutations on survival in patients ≤ 60 years and have demonstrated a negative impact on survival even in patients older than 60 years. FLT3 inhibitors should be considered as a component of therapy in older patients with non-favorable AML and FLT3 mutation.
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Iurlo, Alessandra, Roberto Latagliata, Cristina Bucelli, Dario Ferrero, Fausto Castagnetti, Massimo Breccia, Elisabetta Abruzzese, et al. "Very Elderly Patients with Chronic Phase-Chronic Myeloid Leukemia on Imatinib: No Impact of Concomitant Drugs on Complete Cytogenetic Response." Blood 126, no. 23 (December 3, 2015): 1582. http://dx.doi.org/10.1182/blood.v126.23.1582.1582.
Анотація:
Abstract Tyrosine-kinase inhibitors (TKIs)have completely changed the expected survival of chronic myeloid leukemia (CML) patients which is now approaching that of the general population: a relevant proportion of CML patients are currently elderly or very elderly. Very elderly patients represent generally a small proportion in published experiences. Older CML patients imatinib treated, as it happens in the general population, receive other drug treatments for associated chronic illnesses. Our aim is to assess if and which classes of concomitant drugs have an impact on cytogenetic response in chronic phase (CP)-CML very elderly (age >75 years) patients. Two hundred and twelve very elderly CP-CML patients, imatinib treated at 33 italian hematological institutions have been retrospectively evaluated. Median age at diagnosis was 78.5 years (range 75.0-93.0); 111 (52.4%) were male. Sixty-two (29.2%) were Sokal high risk. Sixty-seven (31.8%) were treated with reduced dose imatinib (<400 mg/day), and the remaining patients with imatinib >400 mg/day. Concomitant drugs were 1-2 in 73 (34.4%) patients, 3-4 in 59 (27.8%), and >5 in 64 (30.2%); 16 (7.6%) did not assume any concomitant drug. Drugs more frequently used were antiplatelets, assumed by 104 (49.1%) patients, followed by diuretics in 91 (42.9%) patients, proton pump inhibitors (PPIs) in 86 (40.6%), ACE inhibitors in 55 (25.9%), beta blockers in 44 (20.7%), angiotensin II receptors blockers (ARB) in 41 (19.3%), calcium channel blockers in 34 (16%), statins in 25 (11.8%), and alpha blockers in 11 (5.2%). Univariate logistic regression models were computed to assess the association between cytogenetic response after 6 or 12 months of imatinib treatment and number of concomitant drugs or selected drug classes. Statistical analyses were done using JMP 11.1 (SAS Institute Inc., Cary, NC, USA). Complete cytogenetic response (CCyR) was obtained in 124 (58.8%) patients, of whom 70 (33%) within 6 months. Consequently, we focused our study on the impact of number and types of drugs on CCyR rate, which represents the primary therapeutic endpoint in the elderly. Cytogenetic response distribution according to concomitant drugs is reported in table 1. We did not find any significant correlation between number of concomitant drugs, single classes of antihypertensive drugs, antiplatelets, PPIs or statins and CCyR rate at 6 or 12 months. Even though few pharmacokinetic interactions are reported between imatinib and some of medications we considered, this does not seem to have an impact on cytogenetic response rate in our cohort. Indeed, our results confirm the well-known safety and efficacy of imatinib also in very elderly CML patients. Table 1. Cytogenetic response according to concomitant drugs Drug classes Cytogenetic response CCyR <6 months CCyR 7-12 months CCyR >12 months No CCyR Antiplatelets (n=104) 38 (36.5%) 31 (29.8%) 11 (10.6%) 24 (23.1%) Diuretics (n=91) 32 (35.2%) 21 (23.1%) 13 (14.3%) 25 (27.4%) Proton pump inhibitors (n=86) 30 (34.9%) 22 (25.6%) 13 (15.1%) 21 (24.4%) ACE inhibitors (n=55) 19 (34.6%) 11 (20%) 12 (21.8%) 13 (23.6%) Beta blockers (n=44) 18 (40.9%) 11 (25%) 3 (6.8%) 12 (27.3%) Angiotensin II receptor blockers (n=41) 19 (46.3%) 11 (26.8%) 5 (12.3%) 6 (14.6%) Calcium channel blockers (n=34) 10 (29.4%) 7 (20.6%) 6 (17.7%) 11 (32.3%) Statins (n=25) 9 (36%) 7 (28%) 2 (8%) 7 (28%) Alpha blockers (n=11) 4 (36.4%) / 1 (9.1%) 6 (54.5%) Disclosures Castagnetti: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. Abruzzese:BMS, Novartis, Pfizer, Ariad: Consultancy. Tiribelli:Bristol Myers Squibb: Consultancy, Speakers Bureau; Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Novartis Farma: Consultancy, Speakers Bureau. Rosti:Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau.
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Neu, E., M. Michailov, U. Welscher, M. Schratz, and G. Weber. "On psychiatry and psychology." European Psychiatry 64, S1 (April 2021): S487. http://dx.doi.org/10.1192/j.eurpsy.2021.1302.
Анотація:
IntroductionPsychiatry is fundamental interdisciplinary medical science with essential importance for enormous health-problems of humanity. Creation of integrative-psychiary in context of multidimensional&holistic medicine, founded by HIPPOCRATES-GALENUS-HUA T’UA-AVICENA-PARACELSUS is necessary to counteract disastrous human health-situation. Psychiatry needs new integrative therapy-models considering application of psychopharmacotherapy as well as practices of psycho-somatic (Th.v.UEXKÜLL) and somato-psychic theories (Y.IKEMI). Emperor AKIHITO during Opening-Ceremony of ICPM-2005-Kobe appointed to consider “total symptoms of mind-body, seeking ways of holistic care”.ObjectivesREFERENCES. PSYCHIATRY: EPA-2020-virtual/Madrid, Eur.Psychiatry 63S, EPP0834/5+EPV0581/1470; EPA-2019-Warsaw, Eur. Psychiatry 56S,S689; EPA-2018-Nice, Eur.Psychiatry 48/S1, S623&567&662. WPA-2019-Lisbon, E-Poster WCP19-2137, -1822, -1839; 2018-Mexico-City, Abs.-Book WCP18-0584/-0625/-0643/-0654. 2011-Buenos-Aires,AB:PO1.200. PSYCHOLOGY: EFPA-2019-Moscow, Abs.-Book 1529,1530,1549. IUPsyS-2012-Cape-Town, IntJPsychol 47:407; -2008-Berlin, 43/3-4:154, 248,615,799; -2004-Beijing, AB:49,587. PSYCHOSOMATICS: ICPM-2017-Beijing, AB:ID: 648493,648895,648749,648878; -2005-Kobe, J.Psychosom.Res. 58:85-86.MethodsEvaluation of psychic-“polar-attitude-list”/physiological-parameters: heart-rate, blood-pressure,etc. from patients/probands after training by occidental/oriental practices (Music-/Yogatherapy/others) (ref.).ResultsObservations demonstrate strong positive influence after music[1], respiratory[2], hatha-yoga[3] therapies. Items of psycho-physiological (relaxed), emotional (tranquil/happy), cognitive (few/ordered thoughts), voluntary (active/spontaneous), social (open/assertive), consciousness (clear/sleepy) categories are significantly positive changed 25-50%. The 3-therapies have specific psychic-effects,e.g. items “relaxed/tranquil” after respiratory- (+45/50%) and music- (+20/5%), also item “open” after music-therapy (+25%) are positive, but negative after respiratory-therapy (-20%). Psychic-effects are correlated with positive physiological-ones,e.g. heart/respiratory-frequency decreased 25-30%, voluntary-apnoea prolonged 55%. Mountain-altitude (>2000-3000m), hypothermia (<20 to 0°C) influenced positively psychic/physiological-parameters,e.g. heart-rate/blood-pressure decrease (n=125,P<0.05-0.01).ConclusionsDifferent methods of integrative psychiatric therapy are with preference,e.g. for depression is suitable respiratory/physical-training, also hypothermia&high-mountain therapy (activation-euphoria), for mania:music-therapy (inhibitory-effect). Systematically research about single/combined therapies is necessary,e.g. for epilepsy: Respiratory-therapy/hypothermia,etc. could help patients (hypo-/hypercapnia: inhibitory/excitatory effects on CNS-structures).
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Cheaib, Joseph G., Sunil H. Patel, Ridwan Alam, Meredith Metcalf, Bruce Trock, Yuezhuo Jing, Yasser Ged, Mohamad Allaf, Phil Pierorazio, and Nirmish Singla. "Racial differences in the natural history of small renal masses: A prospective registry study." Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022): 295. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.295.
Анотація:
295 Background: Patients with small renal masses (SRM) can be managed conservatively by active surveillance (AS) or active treatment. A subset of patients who elect for AS undergo delayed intervention, either due to progression or other factors. Using a large, prospective registry of patients with SRMs we characterize differences in SRM growth trajectories on AS and pathologic differences among resected SRMs between African Americans (AA) and Caucasians. Methods: We stratified patients enrolled in the prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry by race. DISSRM includes AS, primary intervention (PI), and delayed intervention (DI). The growth rate for patients who elected for AS was compared between AA and Caucasian patients. Pathologic features among patients who underwent PI or DI were compared by race. Results: We enrolled 745 patients in DISSRM who were either AA (n = 117, 15.7%) or Caucasian (n = 628 (84.3%)), with median follow-up of 3.3 years [IQR 1.5-6.6]. 410 patients elected for AS (84% Caucasian, 16% AA) and 401 opted for PI (n = 335) or DI (n = 66) (86% Caucasian, 14% AA). Within the AS cohort, no differences were seen in age, comorbidities, or tumor size, though Caucasians were more male-predominant (60.9% vs. 38.5%, p = 0.001), and body mass index was higher among AA (p = 0.03). Median overall growth rate for AA vs Caucasian was 0.04 cm/year [-0.03-0.3] vs 0.1 cm/year [0-0.33], p = 0.2 (Figure).In the DI arm, median time to intervention was 12.5 months, with HR (AA vs Caucasian) being 0.32 (0.13-0.82), p = 0.02. There were no differences in baseline clinical characteristics or tumor size in the DI or PI arm, however AA were more likely to undergo radical nephrectomy (24.6% vs. 10.4%, p = 0.01). pT stage and grade were similar between groups, and papillary histology was more common among AA (34.1% vs 19.9%, p = 0.007). There were 31 deaths among patients undergoing intervention, which was significantly worse for AA after multivariable adjustment (HR 2.51, p = 0.025). Conclusions: Using the largest prospective registry of SRM, we found the natural history of SRM on AS to be similar between AA and Caucasians. However, histology, surgical approach, and survival differed between groups, with worse OS among AA. Further socioeconomic and molecular analyses will help elucidate biological differences and identify strategies to improve outcomes among patients with SRM.
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Mlinar, B., B. A. Biagi, and J. J. Enyeart. "Voltage-gated transient currents in bovine adrenal fasciculata cells. I. T-type Ca2+ current." Journal of General Physiology 102, no. 2 (August 1, 1993): 217–37. http://dx.doi.org/10.1085/jgp.102.2.217.
Анотація:
The whole cell version of the patch clamp technique was used to identify and characterize voltage-gated Ca2+ channels in enzymatically dissociated bovine adrenal zona fasciculata (AZF) cells. The great majority of cells (84 of 86) expressed only low voltage-activated, rapidly inactivating Ca2+ current with properties of T-type Ca2+ current described in other cells. Voltage-dependent activation of this current was fit by a Boltzmann function raised to an integer power of 4 with a midpoint at -17 mV. Independent estimates of the single channel gating charge obtained from the activation curve and using the "limiting logarithmic potential sensitivity" were 8.1 and 6.8 elementary charges, respectively. Inactivation was a steep function of voltage with a v1/2 of -49.9 mV and a slope factor K of 3.73 mV. The expression of a single Ca2+ channel subtype by AZF cells allowed the voltage-dependent gating and kinetic properties of T current to be studied over a wide range of potentials. Analysis of the gating kinetics of this Ca2+ current indicate that T channel activation, inactivation, deactivation (closing), and reactivation (recovery from inactivation) each include voltage-independent transitions that become rate limiting at extreme voltages. Ca2+ current activated with voltage-dependent sigmoidal kinetics that were described by an m4 model. The activation time constant varied exponentially at test potentials between -30 and +10 mV, approaching a voltage-independent minimum of 1.6 ms. The inactivation time constant (tau i) also decreased exponentially to a minimum of 18.3 ms at potentials positive to 0 mV. T channel closing (deactivation) was faster at more negative voltages; the deactivation time constant (tau d) decreased from 8.14 +/- 0.7 to 0.48 +/- 0.1 ms at potentials between -40 and -150 mV. T channels inactivated by depolarization returned to the closed state along pathways that included two voltage-dependent time constants. tau rec-s ranged from 8.11 to 4.80 s when the recovery potential was varied from -50 to -90 mV, while tau rec-f decreased from 1.01 to 0.372 s. At potentials negative to -70 mV, both time constants approached minimum values. The low voltage-activated Ca2+ current in AZF cells was blocked by the T channel selective antagonist Ni2+ with an IC50 of 20 microM. At similar concentrations, Ni2+ also blocked cortisol secretion stimulated by adrenocorticotropic hormone. Our results indicate that bovine AZF cells are distinctive among secretory cells in expressing primarily or exclusively T-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)
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Ohanian, Maro, Guillermo Garcia-Manero, Mark J. Levis, Elias Jabbour, Naval Guastad Daver, Gautam Borthakur, Tapan M. Kadia, et al. "Sorafenib plus 5-azacytidine (AZA) in older untreated FLT3-ITD mutated AML." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 7029. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.7029.
Анотація:
7029 Background: Sorafenib plus 5-azacytidine (AZA) is observed to be safe and effective in relapsed / refractory FLT3-ITD mutated acute myeloid leukemia (AML) patients (pts). Hypothesis: Combining sorafenib with AZA is safe and effective in older untreated FLT3-ITD mutated AML pts. Methods: Eligibility included: untreated FLT3-ITD mutated AML (≥10% mutation burden), age ≥60 yrs, adequate organ function, and ECOG performance status ≤ 2. The regimen was: AZA 75 mg/m2daily x 7 days and sorafenib 400 mg twice daily for 28 days. Results: 26 pts with untreated AML [median age 73 (61-86)] were enrolled: 16 (62%) pts had normal karyotype, 2 (8%) complex karyotype, 4 (15%) other miscellaneous abnormalities, and 4 (15%) with insufficient metaphases. Prior to the initiation of treatment, FLT3-ITD was detected in all pts with a median allelic ratio of 0.3735 (0.009-0.885). The overall response rate (ORR) in 25 evaluable pts was (76%) [7 (28%) with CR, 10 (40%) CRi/CRp, and 2 (8%) PR]. Pts underwent a median of 3 (1-35) treatment cycles. The median number of cycles to response was 2 (1-4), and the median time to achieve response, 1.77 months (mos) (0.689-4.271 mos). The median duration of CR/CRp/CRi is 14.5 mos (1.18—28.74). Three (18%) responding pts (CR, CRp, CRi) have proceeded to allogeneic stem cell transplant. With a median follow-up of 6.8 mos (0.2-18.8), 6 pts are alive, 3 in remission (CR/CRP/CRi). The median overall survival (OS) for the entire group is 8.3 mos; 9.2 mos in 17 responders. Evaluable pts treated with AZA + sorafenib (n = 25) were compared to a matched cohort of historical FLT3-ITD mutated pts > 60 yrs, but treated with hypomethylator-based (HMA) therapy without sorafenib (n = 20); the respective ORR (CR, CRp, CRi, PR) (76% vs. 70%, p = 0.653) and median OS (8.3 and 9.4 mos, p = 0.69) were similar. The remission duration for the responding pts treated with AZA+sorafenib was significantly longer (14.5 mos) than those on other HMA regimens without sorafenib (3.8 mos) (p = 0.01). Adverse events possibly attributable to the regimen included: grade (Gr) 1/2 nausea (n = 3), Gr 1/2 diarrhea (n = 2), Gr 1 dyspnea (n = 1), and Gr 1 breast pain (n = 1). Conclusions: The combination of AZA and Sorafenib is both well tolerated and effective in older untreated FLT3-ITD mutated AML. Clinical trial information: NCT02196857;NCT01254890.
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Baraliakos, X., E. Pournara, D. D. Gladman, P. J. Mease, S. Jahandideh, and L. Coates. "POS1110 PATIENT CLUSTERS IDENTIFIED BY MACHINE LEARNING: DATA FROM A POOLED ANALYSIS OF PHASE-3 TRIALS OF SECUKINUMAB IN PSORIATIC ARTHRITIS, ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS WITH AXIAL MANIFESTATIONS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 879.1–879. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2975.
Анотація:
BackgroundUniversally acceptable criteria to define axial psoriatic arthritis (PsA) are lacking. Machine learning (ML) algorithms can detect patterns from large clinical datasets and identify clusters with potential therapeutic or prognostic significance in PsA patients (pts) with axial manifestations.[1]ObjectivesTo identify pt clusters based on baseline (BL) demographics and clinical indicators to support characterisation of the axial PsA phenotype within the spondyloarthritis (SpA) spectrum.MethodsPooled BL demographics and clinical data of secukinumab (SEC)-treated pts from 10 Phase-3 studies: FUTURE 1–5 (PsA), MEASURE 1–4 (ankylosing spondylitis, AS) and MAXIMISE (PsA with axial manifestations) were analysed to identify pt clusters by ML.[2]Finite mixture model methodology was applied to the pooled dataset. Longitudinal responses of SEC 300 mg vs 150 mg were explored across the identified clusters and clinical indicators tender joint counts (TJC), swollen joint counts (SJC) and enthesitis.ResultsEight distinct clusters were identified (n=3907,Figure 1 and Table 1). Pts with PsA with axial manifestations (MAXIMISE) were overrepresented in clusters 6–8. Pts in cluster 6 (mean age 48 yrs; 46% male) were overweight with pronounced psoriasis (PsO), and high articular burden in large joints. Pts in cluster 7 (mean age 47 yrs; 53% male) were less overweight with lower polyarticular joint counts (mean 11 joints) and tenderness focused on the feet, wrists and hands. Pts in cluster 8 were mostly pts with AS (mean age 43 yrs; 64% male), less overweight with oligoarthritis and high prevalence of spinal pain. Pts with PsA (FUTURE) were overrepresented in clusters 1–5. Longitudinal analysis showed significant improvements with SEC 300 mg vs 150 mg in clusters 6 and 8 for TJC, and cluster 7 for SJC.ConclusionPsA clusters obtained by ML in the pooled dataset indicate phenotypical heterogeneity of pts with PsA with axial manifestations and overlapping features across the SpA spectrum.References[1]Pournara E et al. RMD Open 2021;7:e00184[2]Baraliakos X et al. Arthritis Rheumatol 2022; 74 (suppl 9)Table 1.Pt characteristics by clusterH-SWO/TENACH (++)M-SWO/TENACH (+)L-SWO/TENPsO (+)M-SWO/TENPsO (+)L-SWO/TENACH (-)L-SWO/TENACH (+)PsO (++)L-SWO/ M-TENDAC (-)VL-TEN-SWOACH/DAC/PsO (-)Variables, mean (SD) unless specifiedCluster 1 (n=567)Cluster 2 (n=420)Cluster 3 (n=164)Cluster 4 (n=452)Cluster 5 (n=403)Cluster 6 (n=408)Cluster 7 (n=193)Cluster 8 (n=1300)Pt demographicsMale, n (%)225 (39.7)183 (43.6)98 (59.8)193 (42.7)239 (59.3)187 (45.8)103 (53.4)829 (63.8)BMI (kg/m2)30.0 (7.05)29.6 (6.53)28.5 (5.40)30.3 (6.68)28.1 (5.39)30.2 (6.15)28.6 (5.09)27.3 (5.41)Age (yrs)51.3 (11.58)47.8 (12.01)46.5 (11.59)49.9 (11.93)48.4 (12.20)48.2 (12.22)46.9 (11.67)42.9 (12.14)Clinical indicatorsSJC14.6 (8.44)7.2 (4.49)4.0 (1.93)8.8 (4.00)5.5 (2.80)5.0 (2.43)3.7 (2.78)0.9 (1.30)TJC29.0 (7.22)16.0 (4.87)7.2 (2.67)15.1 (4.48)7.5 (3.21)8.6 (2.76)10.9 (3.12)2.5 (2.40)ACH tendon*1 (0.91)0.9 (0.90)0.4 (0.66)0.5 (0.76)0.2 (0.57)0.7 (0.88)0.5 (0.75)0.3 (0.64)DAC, n (%)247 (43.6)156 (37.1)76 (46.3)171 (37.8)139 (34.5)150 (36.8)48 (24.9)206 (15.9)PsO, n (%)254 (44.9)185 (44.0)85 (51.8)233 (51.5)197 (48.9)252 (61.8)84 (43.5)410 (31.5)CRP >5 mg/L, n (%)278 (49.0)213 (50.7)71 (43.3)227 (50.2)155 (38.5)228 (55.9)86 (44.6)665 (51.2)Spinal pain, n (%)184 (32.5)176 (41.9)62 (37.8)138 (30.5)100 (24.8)162 (39.7)104 (53.9)1035 (79.6)StudiesTotal, n (%)FUTURE2453 (62.8)493 (87.0)323 (76.9)130 (79.3)386 (85.4)354 (87.8)303 (74.3)121 (62.7)343 (26.4)MAXIMISE485 (12.4)45 (7.9)43 (10.2)19 (11.6)45 (10.0)29 (7.2)65 (15.9)40 (20.7)199 (15.3)MEASURE969 (24.8)29 (5.1)54 (12.9)15 (9.2)21 (4.7)20 (5.0)40 (9.8)32 (16.6)758 (58.3)*ACH tendon enthesitis for right or left footACH, Achilles; DAC, Dactylitis; H, high; L, low; M, medium; n, number of evaluable pts; SWO, swollen; TEN, tender; VL, very lowAcknowledgements:NIL.Disclosure of InterestsXenofon Baraliakos Consultant of: Abbvie, Amgen, Chugai, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Grant/research support from: Abbvie, Amgen, Chugai, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Effie Pournara Shareholder of: Novartis, Employee of: Novartis, Dafna D Gladman Consultant of: Amgen, AbbVie, BMS, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, BMS, Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, BMS, Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB, Samad Jahandideh Employee of: Novartis, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB.
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Rodríguez-Abreu, Delvys, Maximillian Hochmair, Byoung Chul Cho, Tibor Csőszi, Talia Shentzer Kutiel, Veronika Müller, Myung-Ju Ahn, et al. "Abstract CT253: Results from KEYNOTE-B99: Phase 2 study of first-line (1L) pembrolizumab (pembro) plus investigational agents and chemotherapy (chemo) for extensive-stage small-cell lung cancer (ES-SCLC)." Cancer Research 84, no. 7_Supplement (April 5, 2024): CT253. http://dx.doi.org/10.1158/1538-7445.am2024-ct253.
Анотація:
Abstract Background: ES-SCLC is an aggressive cancer with substantial mortality. Current 1L treatments include anti-PD-(L)1 + etoposide-platinum chemo (EP), but with minimal improvements in OS vs chemo. In the phase 3 KEYNOTE-604 study, pembro + EP significantly improved PFS (P = 0.0023) but not OS vs placebo + EP; ORR was also improved (71% vs 62%). We present data from the phase 2 KEYNOTE-B99 study (NCT04924101) of 1L pembro + investigational agents (MK-4830, anti-ILT4; boserolimab, anti-CD27; or lenvatinib), and EP for ES-SCLC. Methods: In this open-label platform study, patients (pts) were aged ≥18 y with previously untreated histologically or cytologically confirmed stage IV ES-SCLC (per AJCC v8) and ECOG PS 0 or 1. Pts were randomized 1:1:1 to receive MK-4830 800 mg Q3W (35 cycles; arm A), boserolimab 30 mg Q6W (18 cycles; arm B), or lenvatinib 8 mg (induction)/20 mg (maintenance) QD (arm C). All pts received pembro 200 mg Q3W (35 cycles) + etoposide 100 mg/m2 Q3W and cisplatin 75 mg/m2 Q3W or carboplatin AUC 5 mg/mL/min Q3W (4 cycles). Primary endpoints were ORR and PFS at 6 mo, both assessed per RECIST v1.1 by BICR. Secondary endpoints included DOR, PFS, OS, and safety. Results: 122 pts received ≥1 dose of study treatment (arm A, 43; B, 41; C, 38). At data cutoff (Sep 15, 2023), median follow-up was 14.1 (range, 6.1-25.7) mo. ORR was 65%, 71%, and 74% in arms A, B, and C, respectively; median DOR was 6.8, 4.7, and 7.1 mo. 6-mo PFS rates were 45%, 38%, and 54%, respectively (Table). AEs (any cause) occurred in 98% of pts in arm A and all pts in arms B and C; most commonly neutropenia and anemia. Serious AEs occurred in 30%, 37%, and 55%; grade ≥3 AEs in 86%, 83%, and 87% of pts; and grade 5 AEs in 5%, 7%, and 21%, respectively. Conclusions: 1L ES-SCLC treatment with pembro + EP and MK-4830, boserolimab, or lenvatinib was associated with similar antitumor activity as in KEYNOTE-604 with pembro + EP. No new safety signals were identified. TABLE 1. NAND Group A MK-4830 + Pembro + EP(n = 43) Group B boserolimab + Pembro + EP(n = 41) Group C Lenvatinib + Pembro + EP(n = 38) ORR (95% CI), % 65.1 (49.1-79.0) 70.7 (54.5-83.9) 73.7 (56.9-86.6) Median DOR (range), mo 6.8 (2.4-13.9) 4.7 (1.4+ to 16.4+) 7.1 (1.8 to 18.4+) PFS - 6-mo PFS rate (95% CI), % 45.2 (29.9-59.4) 37.8 (22.7-52.7) 54.2 (35.8-69.4) - Median PFS (95% CI), mo 5.5 (4.2-8.3) 5.5 (4.0-6.7) 7.2 (5.4-NR) Median OS (95% CI), mo 15.5 (8.3-NR) NR (13.2-NR) 15.8 (7.2-NR) ‘+’, no PD at the time of last disease assessment. NR, not reached. Citation Format: Delvys Rodríguez-Abreu, Maximillian Hochmair, Byoung Chul Cho, Tibor Csőszi, Talia Shentzer Kutiel, Veronika Müller, Myung-Ju Ahn, Dariusz Kowalski, Michele Maio, Vladimir Moiseyenko, Alejandro Navarro, Jianxin Niu, Andrea S. Fung, Carolin Lips, Heng Zhou, Bin Zhao, Humberto Lara-Guerra, Nir Peled. Results from KEYNOTE-B99: Phase 2 study of first-line (1L) pembrolizumab (pembro) plus investigational agents and chemotherapy (chemo) for extensive-stage small-cell lung cancer (ES-SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT253.
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Božič, Luka. "Numbers, distribution and nest site characteristics of Jackdaw Corvus monedula in Slovenia and its conservation status." Acrocephalus 37, no. 170-171 (December 1, 2016): 123–50. http://dx.doi.org/10.1515/acro-2016-0007.
Анотація:
Abstract In 2008, a coordinated census of Jackdaw Corvus monedula was carried out to assess breeding population, distribution and nest site selection in Slovenia. Data collection continued for unsurveyed areas in the 2009-2011 period, including information on former colonies and threats. A total of 663-794 Jackdaw pairs were recorded at 86 sites, while total Slovene breeding population was estimated to be in the range of 700-900 pairs. Over one third of pairs were recorded in Central Slovenia, notably the largest city Ljubljana (20.8%), followed by almost a quarter in the Podravje region. Most colonies numbered between 2 and 5 pairs, the largest occupying the Bežigrad district of Ljubljana (82-87 pairs). Large-scale density in geographically more or less uniform areas ranged from 3.65 pairs/10 km2 in the Sava plain to 0.15 pairs/10 km2 in mostly mountainous area in northern Slovenia. The majority of Jackdaws selected buildings for nesting (82.2% of pairs), while nesting in trees occurred less frequently (14.7%) and was almost entirely confined to the two easternmost regions of Slovenia. Nesting in cliffs was recorded at just two sites in Slovene Istria (3.1%). Average colony size differed significantly in relation to nest site type, with colonies in rock walls being on average the largest (median = 9.5 pairs), followed by colonies on buildings (6) and those in trees the smallest (3). Among pairs nesting on buildings, multi-storey residential buildings predominated (34.2%). A substantial percentage of population nested also on churches and tower blocks (14.4% and 13.5%, respectively). The highest percentage of pairs utilised holes in roofs (26.9%), followed by eaves (18.0%) and chimney pots (14.7%). Tree-nesting pairs occupied mostly small woods situated in open agricultural landscape. The most commonly used tree species was Beech Fagus sylvatica (53.1% of pairs) which hosted 14 of the total 16 forest colonies. For Jackdaws nesting in urban parks and avenues, plane trees Platanus sp. were the most important (30.6% of pairs). Their population stronghold was in lowlands, with 88.1% of pairs recorded at elevations under 400 m and the highest living colony in Slovenia at 578 m a.s.l. Jackdaws occurred on at least 54 specific sites in the past but became extinct there or declined severely by the time of this study. A minimum of 217-254 pairs were estimated lost at these sites, constituting a decline of 24% in c. 10-20 years. According to the IUCN criteria, Jackdaw would qualify as Vulnerable (VU) on the Red List of Slovenia. The commonest known cause of extinction/decline is renovation of buildings, a threat that is projected to escalate in the near future.
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Mollah, Mahabubur R., Dale J. Unwin, Glenn J. Fitzgerald, and Everard J. Edwards. "A CO2 Injection System Inside an Open-Top Chamber Enclosing Mature Field-Grown Grapevines: Design and Performance." Transactions of the ASABE 61, no. 4 (2018): 1231–39. http://dx.doi.org/10.13031/trans.12576.
Анотація:
Abstract. Global mean temperature is likely to rise by more than 2°C by the end of the century and carbon dioxide concentration ([CO2]) is expected to increase from 408 µmol mol-1 in 2018 to 650 µmol mol-1 by 2060-2070. Previous studies and industry experience suggest that there has already been an effect of warmer temperatures on grapevine phenology; harvest dates have advanced and vintages have become shorter over the past 30 years in Australia. In addition, increasing [CO2] in the atmosphere will likely alter grapevine growth, development, and grape quality. Understanding the interactive effects of [CO2] and temperature on grapevines is essential to determine the potential impact of future climate on grape phenology, grape composition, and final wine quality. Open-top chambers (OTC), capable of maintaining air temperature 2°C above ambient throughout the diurnal cycle using an active heating system and fan-assisted air circulation, were established in an experimental vineyard managed to current commercial practice. A system was then developed to elevate atmospheric [CO2] to 650 µmol mol-1 around the grapevines within the OTC. The main engineering goal of the system was to maintain an even temporal and spatial distribution of CO2. Monitoring showed that the mean daytime [CO2] at the center of each OTC varied between 620 and 665 µmol mol-1, maintaining [CO2] at or above 95.4% of the target [CO2] and not exceeding the target by more than 2.3%, meeting the performance criteria of within ±10% of the target concentration. Both the temporal and spatial distributions of [CO2] were more even in heated OTCs than non-heated OTCs. In all heated OTCs, the [CO2] was at or above 90% of the target and within ±10% of the target at all locations assessed (spatial distribution). The mean [CO2] was between 80% and 86% of the target at 40% of locations in OTCs without heating; however, the overall mean [CO2] in the OTCs was 97.5% of the target. The system performed satisfactorily over a wide range of temperatures (20°C to 50°C), with overall standard deviation varying between 85 and 112 µmol mol-1. This indicates that the CO2 injection system showed satisfactory performance in controlling [CO2] at the center of each OTC and providing confidence in the results that will be generated from experiments using the system. On average, the heating system maintained a higher temperature (about 2.0°C in both day and night) than the ambient control plots. Keywords: Australia, CO2 injection in grapevines, Elevated CO2, Grapevines, Open-top chamber, Temperature.
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Pilié, Patrick Glen, Rebecca Slack Tidwell, Paul Vincent Viscuse, Sumit Kumar Subudhi, Paul Gettys Corn, Shi-Ming Tu, John C. Araujo, et al. "Randomized phase II study of olaparib (Ola) maintenance following cabazitaxel-carboplatin induction chemotherapy (CabCarb) in men with aggressive variant prostate cancer (AVPC)." Journal of Clinical Oncology 41, no. 6_suppl (February 20, 2023): 196. http://dx.doi.org/10.1200/jco.2023.41.6_suppl.196.
Анотація:
196 Background: An aggressive subset of prostate cancers (AVPC) respond poorly to androgen signaling inhibitors, have limited therapeutic options and a dismal prognosis. Preclinical models of AVPC display functional alterations in DNA damage response (DDR) pathways linked to platinum and PARP inhibitor (PARPi) sensitivity. We hypothesized that PARPi (ola) maintenance following CabCarb would improve the progression free survival (PFS) of men with AVPC. We performed a tissue-rich randomized trial for men with AVPC to address this hypothesis and unravel the heterogeneity of AVPC by linking genomic and transcriptomic analyses with clinical outcomes. Methods: In a single-institution study, men with CRPC meeting ≥ 1 of 9 AVPC criteria and ECOG performance status (PS) of 0-2 received 6 cycles of Cab 20-25mg/m2 and Carbo (AUC 3-4). Men completing 6 cycles without progressive disease (PD) were randomized 2:1 to Ola 300mg BID vs. observation (Obs). The primary endpoint is to estimate PFS in those randomized and we aimed to detect a difference of 3.9 vs. 7.8 months. Subgroup comparisons between patients who had PD prior to randomization (platinum-resistant) vs. those randomized (platinum sensitive) were made with chi-square tests for categorical baseline characteristics, and Kruskal-Wallis test for continuous measures. Results: 96 patients started CabCarb. Their median age was 67 years (43-86), most were white/non-Hispanic (74%), had an ECOG score of 0 (64%), bone metastases (79%), and no prior docetaxel therapy (59%). Of the 96, 7 (7.3%) went off study for reasons unrelated to PD and 36 (37.5%) had PD prior to randomization. Patients with PD prior to randomization were more likely at baseline to have received prior docetaxel (59% vs. 29%; p=0.004), have bone metastases (92% vs. 71%; p=0.03), have lower hemoglobin (11.4 vs. 12. 4; p=0.02), higher LDH (359 vs. 260; p=0.01), lower albumin (4.0 vs. 4.2; p=0.04), and higher AlkPhos (181.5 vs. 98.5; p=0.01) compared to patients who went on to randomization. With a median follow up time of 38.9 months post randomization, the median PFS was 2.3 months (95% confidence interval: 1.3, 4.6 months) for Observation and 4.9 (3.5, 6.3) months with Olaparib (p=0.12). The median OS was 16.2 (6.8, 26.4) for observation and 15.3 (10.2, 28.4) months with Olaparib (p=0.56). Conclusions: These data highlight the heterogeneity within the AVPC subset. Ongoing molecular analyses of sequential liquid and tumor tissue will illuminate the underpinnings of this heterogeneity and identify targets for additional combinatorial strategies. Clinical trial information: NCT03263650 .
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Masarova, Lucia, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Sherry Pierce, Taghi Manshouri, Jorge E. Cortes, Hagop M. Kantarjian, and Srdan Verstovsek. "Do Patients with Post-Essential Thrombocythemia and Post-Polycythemia Vera Differ from Patients with Primary Myelofibrosis?" Blood 126, no. 23 (December 3, 2015): 4069. http://dx.doi.org/10.1182/blood.v126.23.4069.4069.
Анотація:
Abstract Introduction: Clinical characteristics of post-essential thrombocythemia/polycythemia vera myelofibrosis "post ET/PV-MF" are not well defined as for primary myelofibrosis "MF". Objective: We aimed to identify morphological, clinical and prognostic characteristics of patients with post ET/PV-MF seen at our center. Methods: Retrospective chart review of 1120 patients with MF - 766 primary MF, 354 post ET/PV-MF, who were referred to our institution between years 1984-2013 was performed; 92% presented after the year of 2000. Fisher's exact and Mann-Whitney test were used for categorical and continuous variables; Cox proportional hazard model and Kaplan-Meier curves with log rank test for correlation between the variables and survival. Survival analysis were calculated after censoring patients for stem cell transplantation "SCT" (n=92). Results: Overall median follow up was 36 months (0-411), 51% (n=573) patients had died. Progression to AML after median time of 32 months was not different between groups and occurred in 9.5% (n=106) patients over observation period of 5180 persons-years. Incidence rate was 3.4 cases per 100 persons-year. Causes of death were known in 55% of patients, and included progression of MF in 38% (n=122), infection in 27% (n=86), and other reasons with less than 10% occurrence (complications post SCT; secondary malignancy; other medical conditions). Demographics and disease characteristics are depicted in a table. 92% of patients were evaluable for karyotype; abnormalities were detected in 39% (n=404), of which 53% were unfavorable with monosomal (23%), complex (43%) and trisomy 8 (18%) being the most common. Molecularly high risk mutations "MHR" in genes ASXL1, EZH2, and IDH1/2 were positive in 35% of tested patients (n=161) regardless of presence of driver mutation. IPSS and DIPSS plus scores were similar between MF and post ET/PV-MF (with IPSS low in 8.7%, intermediate 1 in 19%, intermediate 2 in 28%, and high in 44%). By multivariate analysis, higher risk categories of IPSS and DIPSSplus predicted shorter overall survival "OS" for both cohorts (by DIPSSplus - high risk: HR 2.7, 95% CI 2.1-3.5; int-2: HR 1.6; 95% CI 1.3-2.0). Median OS stratified by IPSS was 160 (HR 1.8, 95%CI 1.0-3.0), 116 (HR 1.5, 95%CI 1.0 -1.5), 78 (HR 1.4, 95%CI 1.2-1.7) and 54 months, p=0.001. Univariate analysis identified age over 65, anemia, trombocytopenia, leukopenia, increased blasts, splenomegaly, constitutional symptoms, unfavorable karyotype, JAK2 mutation and triple negativity as predictors for inferior survival. Age over 65; hemoglobin below 10, platelets below 100 and peripheral blasts ≥1% showed significance for predicting OS by multivariate analysis. When stratified according to diagnosis, higher age, anemia, thrombocytopenia, high blasts, JAK2 positivity and triple negativity retained prognostic significance for MF whereas anemia, thrombocytopenia, and JAK2 mutation for post ET/PV-MF. Median OS was 73 months (range, 0.1-210) without difference between MF and post ET/PV-MF. Conclusion: Post ET/PV-MF does not appear to have substantial different clinical characteristics than primary MF. Table. Characteristics Total, number or median (% or range) MF, number or median (% or range) PET/PV-MF, number or median (% or range) Age 65 (20-89) 64 (20-88) 64 (27-89) Age > 65 552 (49) 367 (48) 185 (53) Males 675 (60%) 494 (65) 181 (51)* WBC 9.6 (0.4-361) 17.3 (5-19) 16.7 (5-18) WBC > 24 203 (18) 133 (18) 70 (20) WBC < 4 160 (14) 130 (17) 30 (8.5)* Plt 204 (3-2690) 237 (1-1364) 354 (6-2690)* Plt < 100 276 (25) 220 (29) 56 (16)* Hgb 10.5 (5-18) 10 (5-18) 11 (5-19)* Hgb < 10 462 (42) 329 (43) 133 (38)* Transfusion dependency 265 (24) 203 (27) 62 (18)* Blasts ≥ 1% 523 (47) 371 (49) 152 (43) Splenomegaly 668 (60) 459 (63) 209 (65) Symptoms 793 (71) 537 (70) 256 (73) LDH 1246 (189-10343) 1248 (189-10353) 1261 (205-8476) LDH > 620 958 (86) 640 (85) 318 (90)* JAK2 positive 586 (57) 371 (63) 215 (37)* MPL positive 19 (1.9) 16 (84) 3 (16)* CARL positive 53 (5) 27 (51) 26 (49)* Triple negative 26 (2.5) 21 (81) 5 (19)* *statistically significant differences (p<0.05) Disclosures Pemmaraju: Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Teva: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; ARIAD Pharmaceuticals Inc.: Consultancy, Research Funding.
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Montesinos, Pau, Concepcion Rivas, Consuelo Rayon, Edo Vellenga, Javier de la Serna, Juan Bergua, Ricardo Parody, Salud Brunet, Gustavo Milone, and Miguel Sanz. "Prognostic Value of Immunophenotype Analysis in Patients with Acute Promyelocytic Leukemia (APL) Treated with All-Transretinoic Acid and Anthracyclin Monochemotherapy." Blood 108, no. 11 (November 1, 2006): 2345. http://dx.doi.org/10.1182/blood.v108.11.2345.2345.
Анотація:
Abstract Introduction: The prognostic significance of the expression pattern of certain cell surface markers in APL is controversial. Objectives: Analyse the impact of the expression of certain cell surface markers on complete remission rate (CR), overall survival (OS) and relapse free survival (RFS) in patients with APL included in multicenter trials PETHEMA LPA96 y LPA99. Material and methods: Between 1996 and 2005, 734 patients were included in these 2 consecutive trials. Induction therapy consisted of ATRA and idarubicin, followed by three consolidation courses of anthracycline monochemotherapy with or without ATRA and followed by maintenance. Bone marrow immunophenotype analysis was performed at local or reference laboratories. Positivity was defined as more than 20% blasts expressing a specific antigen for the following antigens: CD34 (527 patients), CD33 (521), CD15 (520), CD13 (513), HLA-DR (495), CD2 (443), CD19 (433), CD7 (403), CD117 (395), CD56 (392), y CD11b (335). We performed univariate analysis to establish the impact of antigen positivity on CR rate, OS and RFS. Significant values were included in the multivariate analysis. Results: A total of 664 patients (90%) achieved CR. The following variables were associated with decreased CR rate: WBC > 10x109/L, serum level creatinine > 1.4 mg/dl, age > 60 years, ECOG > 1, M3v and male gender. None of the cell surface antigens were significantly associated with CR rate. WBC, creatinine, age and gender were found to be independent prognostic factors for CR. Median follow up was 55 months. OS at 8 years was inferior in those patients with WBC > 10x109/L (67% vs 85%, p < 0.01), M3v (70% vs 83%, p < 0.01), age > 60 (56% vs 86%, p < 0.01), male gender (78% vs 83%, p=0.03), LPA96 trial (74% vs 84%, p=0.01) and CD2+ (76% vs 84%, p=0.04). Age, WBC and gender were independent factors for OS. RFS was inferior in those patients with WBC > 10x109/L (69% vs 93%, p < 0.01), high vs intermediate vs low risk (69% vs 91% vs 95%, p < 0.01), M3v (76% vs 88%, p < 0.01), BCR2 vs BCR3 vs BCR1 transcript (71% vs 81% vs 89%, p < 0.01), male gender (83% vs 90%, p=0.03), LPA96 trial (82% vs 87%, p=0.02) and CD2+ (75% vs 91%, p < 0.01). The risk of relapse category was the only independent factor for RFS. CD2+ APL (115/443 patients) was significantly associated with WBC > 10x109/L, M3v, BCR3, CD34+, CD56+, CD7+, and HLA-DR negative. Conclusion: Of all the cell surface antigens analysed, only expression of CD2 was associated with an lower OS and RFS, due to its association with WBC > 10x109/L. In patients taking part in PETHEMA trials, immunophenotype analysis at presentation does not give additional prognostic impact from the previously established risk factors.
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Nasonov, E., A. Avdeeva, A. Misiyuk, A. Satybaldyev, V. Sorotskaya, O. Fomina, A. Babaeva, N. Lapkina, and A. Lila. "AB0328 SIMILAR EFFICACY OF TOFACITINIB THERAPY IN BIOLOGIC NAIVE AND HAD PRIOR BIOLOGIC USE HISTORY PATIENTS WITH RHEUMATOID ARTHRITIS (OREL REGISTER)." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1462.3–1463. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3052.
Анотація:
Objectives:To evaluate the efficacy of tofacitinib therapy (TOFA) in biologic naive and had prior biologic use history patients with rheumatoid arthritis (RA) according to OREL registerMethods:Were analyzed the data from Russian national register of patients with RA - OREL treated with TOFA. 138 patients (118 woman, Me;IQR age 55.0 (43.0-63.0) years, disease duration 128.0 (84.0-213.0) months, mean DAS 28 5.5 (4.6-6.2), SDAI 30.5 (21.4-42.9), positive for ACCP (73%)/RF (77%), who were non-responders to MTX at least 15 mg/week and/or other synthetic DMARDs) who received TOFA therapy for more than 1 year were selected for statistical analysis. TOFA used in 26 (18.8%) pts without DMARDs, combination with MTX in 82 (59.4%) pts, leflunomide in 21 (15.2%). Low-dose oral corticosteroids (<10 mg/day prednisone or equivalent) were received by 43 (31.2%) pts. TOFA therapy was started in all pts in dose 5 mg BID per os with dose escalation to 10 mg BID in (86%) pts.Results:The use of TOFA was accompanied by a decrease in the disease activity and the level of acute phase reactants (CRP and ESR) after 12, 24 and 48 weeks of therapy, p<0.05, table 1. Depending on the previous treatment with biological DMARDs, all patients were divided into two groups: had prior biologic use history pts (group 1) (n=51) and biologic naïve pts (group 2) (n=87), table 1.Table 1.Baseline vs month 1ParametersWeeksAll patients (n=138)Had prior biologic use history (group 1) (n=51)Biologic naive (group 2) (n=87)DAS28baseline5,5 (4,6-6,2)5,1 (4,5-5,9)5,7 (4,8-6,5)$week 124,2 (3,1-4,8)*3,9 (2,8-4,8)*4,4 (3,7-4,8)*week 243,4 (2,7-4,4)*3,5 (2,4-4,3)*3,4 (2,8-4,5)*week 483,3 (2,5-4,4)*3,2 (2,4-4,2)*3,4 (2,7-4,4)*SDAIbaseline30,5 (21,4-42,9)28,6 (18,1-36,6)33,1 (22,6-45,9)week 1214,5 (7,1-23,3)*13,1 (5,1-19,1)*16,3 (9,3-25,6)*week 2410,5 (5,1-19,0)*11,0 (5,5-17,6)*9,1 (4,7-20,4)*week 4810,3 (4,9-17,7)*10,2 (3,4-15,8)*10,9 (6,2-18,1)*CDAIbaseline28,2 (20,0-37,1)25,7 (17,0-33,7)30,0 (21,5-40,5)week 1214,9 (8,0-22,5)*13,0 (6,8-18,7)*16,6 (9,0-24,0)*week 2410,0 (5,0-18,0)*11,0 (4,7-16,0)*9,3 (5,0-18,0)*week 4810,1 (5,8-17,0)*10,4 (4,0-16,0)*10,0 (6,0-17,0)*CRP, mg/lbaseline15,6 (6,5-38,0)15,6 (6,0-38,1)15,4 (6,9-36,7)week 125,5 (1,7-12,1)*6,4 (2,7-10,4)*5,2 (1,3-12,8)*week 244,5 (1,0-10,0)*5,0 (0,8-9,8)*4,2 (1,0-10,0)*week 484,0 (0,7-9,0)*2,9 (0,6-9,6)*4,0 (0,8-8,9)*ESR, mm/hbaseline32,0 (23,0-48,0)29,0 (16,0-37,0)32,0 (23,0-49,0)$week 1221,0 (17,0-33,0)*20,0 (12,0-33,0)21,0 (17,0-33,0)*week 2421,0 (12,0-31,0)*13,0 (9,0-28,0)21,0 (12,0-31,0)*week 4816,0 (10,0-27,0)*16,0 (7,0-30,0)*16,0 (10,0-27,0)**p<0.05 from baseline; $p<0.05 between the groups 1 and 2Patients of the second group had a higher disease activity and ESR before therapy. The use of TOFA was accompanied by a decrease in the disease activity and the level of acute phase reactants (CRP and ESR) in both groups of patients. By week 48 of treatment, no significant difference between the groups according to the disease activity was detected.In the first and the second group of pts on the 48-th week of therapy remission/low disease activity was achieved on DAS 28 in 51% and 43% (р=0.57), high disease activity on DAS 28 in 12% and 8% (p=0.48).Conclusion:An analysis of the data from the Russian national register of patients with RA demonstrated similar efficacy of TOFA among patients who received and did not receive previous biological therapy.Disclosure of Interests:Evgeny Nasonov Speakers bureau: Lilly, AbbVie, Pfizer, Biocad, R-Pharm, Anastasia Avdeeva: None declared, Anna Misiyuk: None declared, Azamat Satybaldyev: None declared, Valentina Sorotskaya: None declared, Oxana Fomina: None declared, Aida Babaeva: None declared, N Lapkina: None declared, Alexander Lila: None declared
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Conaghan, P. G., L. Abraham, P. Graham-Clarke, L. Viktrup, J. C. Cappelleri, C. Beck, A. G. Bushmakin, N. Hatchell, E. Clayton, and J. Jackson. "OP0190 UNDERSTANDING CURRENT PRESCRIPTION DRUG TREATMENT PARADIGMS FOR PATIENTS WITH OSTEOARTHRITIS IN EUROPE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 118.2–118. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4776.
Анотація:
Background:Joint pain is the most prevalent symptom for sufferers of osteoarthritis (OA). Pharmacological management of OA is restricted by limited efficacy and considerable toxicity, with growing fears about opioid use.Objectives:To understand the current real-world prescribed drug treatment paradigm related to OA disease severity for patients in 5 EU countries; France, Germany, Italy, Spain and the UK.Methods:Data were drawn from the Adelphi OA Disease Specific Programme (2017-18), a point-in-time study of physicians and their patients. Physicians classified their patients as currently having mild, moderate or severe disease severity, and provided details on currently prescribed OA therapy and physician satisfaction with therapy, rated from very satisfied to very dissatisfied. Patients were excluded from these analyses if they suffered from back and neck OA only, and shoulder OA that had not been diagnosed by X-ray. Comparisons among disease severity groups were made using analysis of variance and chi-squared tests.Results:The study included 489 physicians (primary care physicians, rheumatologists, orthopaedists) reporting on 3596 of their OA patients: 24% mild (n=874), 53% moderate (n=1904), and 23% severe (n=818). Overall, 73% patients were prescribed at least one drug for their OA (65% of mild; 76% of moderate; 77% of severe patients [<0.001]). Paracetamol (34%) was the most commonly prescribed OA treatment. NSAIDs (31%) and opioids (27%) were also frequently prescribed treatments, and worsening severity was associated with an increase in opioid use (11% of mild; 26% of moderate, 47% of severe patients [<0.001]), but not NSAID (Table 1). The mean number of prescription medications increased (0.9 for mild; 1.4 for moderate; 1.6 for severe patients [<0.001]) and physician satisfaction with treatment decreased (86% for mild; 70% for moderate; 41% for severe [<0.001]) with worsening OA disease severity.Table 1.Prescribed treatment by physician-reported OA severityMild(n=874)Moderate(n=1904)Severe(n=818)Current class of medication prescribed for OA, n (%)Paracetamol186 (21.3)663 (34.8)313 (38.3)NSAIDs267 (30.5)605 (31.8)237 (29.0)Any opioid93 (10.6)501 (26.3)386 (47.2)Weak opioid82 (9.4)407 (21.4)255 (31.2)Strong opioid11 (1.3)99 (5.2)146 (17.8)Opioid + analgesic (combined)6 (0.7)15 (0.8)7 (0.9)Corticosteroid31 (3.5)150 (7.9)92 (11.2)Glycosaminoglycan50 (5.7)149 (7.8)62 (7.6)Viscosupplement12 (1.4)93 (4.9)42 (5.1)Number of currently prescribed drug classes, mean (SD)0.9 (0.8)1.4 (1.1)1.6 (1.2)Conclusion:Physicians reported decreasing satisfaction with treatment for their OA patients as disease severity increased, despite increasing use of opioids and numbers of classes of prescribed drugs.Disclosure of Interests:Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Lucy Abraham Shareholder of: Pfizer, Employee of: Pfizer, Peita Graham-Clarke Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Craig Beck Shareholder of: Pfizer, Employee of: Pfizer, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Niall Hatchell: None declared, Emily Clayton: None declared, James Jackson: None declared