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1
Oliveira, André Soares de, Daniel de Noronha Figueiredo Vieira da Cunha, José Maurício de Souza Campos, Sônia Maria Leite Ribeiro do Vale, and Anderson Jorge de Assis. "Identificação e quantificação de indicadores-referência de sistemas de produção de leite." Revista Brasileira de Zootecnia 36, no. 2 (April 2007): 507–16. http://dx.doi.org/10.1590/s1516-35982007000200030.
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Objetivou-se identificar e quantificar indicadores-referência de sistemas de produção de leite no Extremo Sul da Bahia. Analisaram-se o perfil tecnológico e os indicadores zootécnicos, econômicos e de tamanho de nove empresas. Foram determinados os coeficientes de correlação dos indicadores com a taxa de remuneração do capital investido. Após a identificação dos indicadores que apresentaram correlação, foram geradas equações de regressão para cada indicador em função da taxa de remuneração do capital investido para quantificar os indicadores-referência em quatro cenários de taxa de remuneração do capital investido (4, 6, 8 e 10% ao ano). Os indicadores correlacionados e seus respectivos valores nos quatro cenários foram: produção diária de leite (456, 538, 621 e 703 L/dia); produtividade da terra (733, 1.008, 1.284 e 1.559 L/ha/ano); vacas em lactação por área (0,37; 0,45; 0,54 e 0,62 vacas/ha); produtividade por total de vacas (3,01; 3,52; 4,03 e 4,54 L/vaca/dia); relação de vacas em lactação pelo total do rebanho (24, 27, 30 e 33%); produtividade da mão-de-obra (111, 124, 137 e 150 L/dia-homem), participação do custo operacional efetivo da atividade na renda bruta da atividade (60, 57, 54 e 51%); participação do custo operacional total da atividade na renda bruta da atividade (72, 66, 60, 54%); gasto com mão-de-obra em relação à renda bruta do leite (31, 27, 22 e 18%); capital investido na atividade em relação à produção diária de leite (2.093, 1.508, 924 e 339 R$/L-dia). A identificação de indicadores-referência em sistemas reais de produção de leite, caracterizando aqueles mais diretamente correlacionados à eficiência econômica, é uma importante ferramenta de apoio gerencial e pode trazer esclarecimentos para o debate sobre a viabilidade econômica de sistemas de produção de leite.
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Soverini, Simona, Caterina De Benedittis, Fausto Castagnetti, Gabriele Gugliotta, Manuela Mancini, Giorgina Specchia, Domenico Russo, et al. "BCR-ABL Mutations in Chronic Myeloid Leukemia (CML) Patients (pts) with Failure and Warning to First- and Second-Line Tyrosine Kinase Inhibitor (TKI) Therapy: What Is the Advantage of Next-Generation Sequencing (NGS) over Conventional Sequencing?" Blood 126, no. 23 (December 3, 2015): 346. http://dx.doi.org/10.1182/blood.v126.23.346.346.
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Abstract Background - Point mutations in the BCR-ABL kinase domain are associated with resistance to TKI therapy. The most recent (2013) European Leukemia Net (ELN) recommendations have re(de)fined the criteria for failure in pts receiving 1st-line and 2nd-line TKI therapy and introduced the concept of warning. Assessing in how many CML patients with failure and warning mutations can be identified, especially now that more sensitive NGS-based mutation screening methods are available, would advance our knowledge of the biology of TKI resistance as well as contribute useful data to revise the ELN recommendations as to when and how BCR-ABL mutation analysis should be performed. Aims - We aimed to determine the frequency of BCR-ABL mutations as assessed by NGS vs conventional Sanger sequencing (SS) in CML pts with failure and warning to 1st- or 2nd-line TKI therapy as per the latest, 2013 ELN definitions. Methods - Between May 2013 and June 2015, 298 consecutive CML pts on TKI therapy were referred to our laboratory for BCR-ABL mutation screening by SS. One hundred and fifty-eight cases had no clinical data available, or were not in CP, or were receiving ≥3rd-line TKI therapy, or had confirmed/suspected nonadherence, or had experienced dose reductions for toxicity - leaving 140 pts who could be included in this study. Pts who were negative for mutations as determined by SS (n=105/140) were retrospectively reanalyzed by NGS on a Roche GS Junior, using a protocol already set up and optimized in the framework of the IRON II (Interlaboratory RObustness of NGS) international consortium. Sequencing depth allowed to achieve a lower mutation detection limit of 1% in all samples. Results - Failures and warnings to 1st-line therapy (imatinib, n=57; nilotinib, n=22; dasatinib, n=13) were 63 and 29, respectively. BCR-ABL mutations were found in 15/63 (24%) failures and 3/29 (10%) warnings by SS (Table 1). NGS reanalysis of the 74 pts with no evidence of mutations by SS revealed low burden (median, 6.6%; range, 1.5-11.7%) mutations in 6 failures and 1 warning, so that, overall, 21/63 (33%) failures and 4/29 (14%) warnings turned out to have mutations (Table 1). Mutations were E462K, E279K, K262R, F359I, E255K, F317L, K378R, A399T, L364I, V280A. No compound mutation was detected. Failures and warnings to 2nd-line therapy (nilotinib, n=27; dasatinib, n=21) were 35 and 13, respectively. SS identified mutations in 13/35 (37%) failures and 2/13 (15%) warnings (Table 1). NGS reanalysis of the 33 pts with no evidence of mutations by SS revealed low burden (median, 5.4%; range, 1.9-10.0%) mutations in 5 failures and 2 warnings, so that, overall, 18/35 (51%) failures and 4/13 (31%) warnings turned out to have mutations (Table 1). Mutations were T315I, E255V, F317I, E258D, P480L, Y393C, W261L, L370P, V371A, L324Q, again with no compound mutations. Table.All ptsPts positive for mutations by SSAdditional pts positive for mutations by NGSTotal pts positive for mutations1ST -LINE FAILURESNo CyR @ 3 mo9101BCR-ABL>10% @ 6 mo9000mCyR @ 6 mo1101BCR-ABL>1% @ 12 mo10022No CCyR @ 12 mo2101Loss of CCyR7314Loss of MMR20639Loss of CHR2101Progression to BP3202Total6315 (24%)621 (33%)1ST -LINE WARNINGSBCR-ABL>10% @ 3 mo7101BCR-ABL>1% @ 6 mo10112BCR-ABL>0.1% @ 12 mo12101Total293 (10%)14 (14%)2ND -LINE FAILURESNo CyR @ 3 mo3112BCR-ABL>10% @ 6 mo10224Loss of CCyR7303Loss of MMR6123Loss of CHR4303Progression to BP5303Total3513 (37%)518 (51%)2ND -LINE WARNINGSBCR-ABL>10% @ 3 mo6202BCR-ABL>0.1% @ 12 mo7022Total132 (15%)24 (31%) Conclusions 1) NGS allowed to identify BCR-ABL mutations in a greater proportion of cases as compared to SS. Low burden mutations included a T315I mutation in 2 pts on 2nd-line therapy classified as warnings: this would have turned them into failures. 2) Still, a substantial proportion of cases was found to not harbor any mutation, even when using a more sensitive NGS-based method. In particular, non-optimal achievement of the key molecular response milestones (10%, 1%, 0.1%) on 1st-line therapy was mostly not associated with BCR-ABL mutations, indicating that other mechanisms of molecular disease persistence have to be investigated in an attempt to optimize therapeutic outcomes. A national, multicenter study ('NEXT-IN-CML') aimed at the prospective assessment of NGS for routine BCR-ABL mutation screening of CML patients has just started. Supported by ELN, AIL, AIRC, FP7 NGS-PTL project, Progetto Regione-Università 2010-12 (L. Bolondi) Disclosures Soverini: Bristol-Myers Squibb: Consultancy; Ariad: Consultancy; Novartis: Consultancy. Castagnetti:BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. Bonifacio:Ariad Pharmaceuticals: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Novartis Farma: Research Funding. Saglio:Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Novartis Pharmaceutical Corporation: Consultancy, Honoraria. Rosti:Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau. Baccarani:NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ARIAD Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Martinelli:Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau; ROCHE: Consultancy; BMS: Consultancy, Speakers Bureau; AMGEN: Consultancy; MSD: Consultancy; Ariad: Consultancy.
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Rea, Delphine, Hagop M. Kantarjian, Meir Wetzler, Franck E. Nicolini, Jeffrey H. Lipton, Luke Paul Akard, Hanna Jean Khoury, et al. "Post hoc analysis of sustained efficacy/tolerability of ≥12 cycles of omacetaxine mepesuccinate in chronic myeloid leukemia (CML)." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 7066. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.7066.
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7066 Background: Subcutaneous omacetaxine mepesuccinate (OMA), a first-in-class cephalotaxine, inhibits protein synthesis independent of Bcr-Abl signaling. It showed clinical activity in 2 phase II, open-label CML trials, 1 in patients with a T315I Bcr-Abl mutation failing imatinib, and 1 in patients failing ≥2 tyrosine kinase inhibitors (TKIs). Methods: This post hoc analysis pooled patients with chronic phase (CP) or accelerated phase (AP) from the 2 trials. 28-day cycles of OMA 1.25 mg/m2BID were given ≤14 days for induction, ≤7 days as maintenance with dose delay/change as needed. Primary endpoints were major cytogenetic response (MCyR) for CP and complete hematologic response (CHR) for AP. Adverse events (AEs) were assessed. Results: Of 108 CP and 51 AP patients from the 2 trials, 31 (29%) CP and 7 (14%) AP patients received ≥12 cycles (Table). At baseline in the ≥12-cycle groups, most CP (median age 59 y) and AP patients (median age 67 y) had received hydroxyurea (17/31, 4/7) and ≥2 TKIs (22/31, 5/7), were not in CHR (22/31, 5/7), and were T315I positive (23/31, 3/7). As of March 31, 2012, 9 CP and 2 AP patients continued OMA treatment. Overall, mean days dosed per cycle were 6.1 for CP, 9.7 for AP; 5.3 and 8.9 at cycle 12. Grade 3/4 AEs occurred in 35/38 patients in this post hoc analysis, most in early cycles; 15/31 CP, 2/7 AP had grade ≥3 AEs first occurring at ≥12 cycles. Across all cycles, most common grade ≥3 AEs were thrombocytopenia (24/31 CP, 5/7 AP), anemia (16/31, 7/7), and neutropenia (17/31, 3/7).Nine patients receiving ≥12 cycles (5/31, 4/7) discontinued, most commonly due to disease progression (n=2). Conclusions: In this post hoc analysis of heavily pretreated CML-CP and CML-AP patients who had failed prior TKI therapy, efficacy was often durable for those who received OMA for ≥12 cycles. Most grade 3/4 AEs were hematologic and declined with time. Support: Teva BPP R and D, Inc. Clinical trial information: NCT00375219, NCT00462943.
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Álvarez-Ortega, Sergio, Sergei A. Subbotin, and Reyes Peña-Santiago. "Morphological and molecular study of Californian species of the genus Aporcelaimellus Heyns, 1965 (Dorylaimida: Aporcelaimidae)." Nematology 15, no. 4 (2013): 431–49. http://dx.doi.org/10.1163/15685411-00002691.
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Several species of Aporcelaimellus collected in natural areas in California, USA, are characterised on the basis of morphological, morphometric and molecular data. Two new species are identified and described here. Aporcelaimellus californicus sp. n. is characterised by its body length of 2.46-3.42 mm, lip region offset by constriction and 24-26 μm broad, odontostyle 23-24 μm long, neck 611-765 μm long, pharyngeal expansion occupying 50-52% of total neck length, a dorsal cellular mass present at level of cardia, uterus simple and 246-408 μm long, V = 53-58, short conoid tail (43-50 μm, c = 56-71, c′ = 0.8-1.0) with a large hyaline portion occupying more than half of its total length, spicules 98 μm long, and 8-9 spaced ventromedian supplements. Aporcelaimellus salicinus sp. n. is distinguished by its body length of 1.45-1.94 mm, lip region offset by deep constriction and 16-18 μm broad, odontostyle 18-20 μm long, neck 393-521 μm long, pharyngeal expansion occupying 45-51% of total neck length, presence of a dorsal cellular mass at level of cardia, uterus simple and 21-45 μm long, V = 51-57, tail conical to conoid (31-38 μm, c = 39-59, c′ = 1.0-1.4), and male unknown. Measurements, sequences and taxonomic comments are provided for the other three Aporcelaimellus species. Californian Aporcelaimellus display a notable morphological homogeneity but a remarkable molecular diversity, putting into question the monophyly of this group.
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Kolenkiewicz, Małgorzata, Andrzej Włodarczyk, and Joanna Wojtkiewicz. "Diagnosis and Incidence of Spondylosis and Cervical Disc Disorders in the University Clinical Hospital in Olsztyn, in Years 2011–2015." BioMed Research International 2018 (2018): 1–7. http://dx.doi.org/10.1155/2018/5643839.
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Background. Disorders connected with the musculoskeletal and central nervous system dysfunction are the most significant clinical problem worldwide. Our earlier research has shown that back and spinal disorders and lumbar disc disorders were most frequently diagnosed using MRI scanner at the University Clinical Hospital (UCH) in Olsztyn in years 2011–2015. We have also observed that another two diseases of spinal column, spondylosis and cervical disc disorders, were also very prevalent. The main objective of this work was to analyze the prevalence of spondylosis and cervical disc disorders in the study population diagnosed at UCH in years 2011–2015. Methods. The digital database including patients’ diagnostic and demographic information was generated based on MRI reports from years 2011–2015 and analyzed using SPSS software. Results. Within the study group (n=13298) the most frequently MRI-diagnosed diseases were musculoskeletal group (M00–M99; n=7711; 57,98%) and cervical disc disorders (M50; n=1659; 12,47%) and spondylosis (M47, n=611; 4,59%). More women (67%) than men (33%) were enrolled in the study, and the largest fraction of the study population was in the range of 51–60 years, with about 1/3 of cases of both diseases diagnosed in early age range of 31–40 years. Conclusion. Significant number of patients presenting with either of the spine disorders at the young age of 31–40 years points to the necessity of introducing methods preventing disorders of the vertebral column at younger age, preferably at school age.
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Jones, Gareth-Rhys, Mathew Lyons, Nikolas Plevris, Philip W. Jenkinson, Cathy Bisset, Christopher Burgess, Shahida Din, et al. "IBD prevalence in Lothian, Scotland, derived by capture–recapture methodology." Gut 68, no. 11 (July 11, 2019): 1953–60. http://dx.doi.org/10.1136/gutjnl-2019-318936.
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ObjectiveIBD prevalence is estimated to be rising, but no detailed, recent UK data are available. The last reported prevalence estimate in the UK was 0.40% in 2003. We aimed to establish the current, and project future, prevalence in Lothian, Scotland.DesignWe conducted an all-age multiparameter search strategy using inpatient IBD international classification of disease (ICD-10) coding (K50/51)(1997–2018), IBD pathology coding (1990–2018), primary and secondary care prescribing data (2009–2018) and a paediatric registry, (1997–2018) to identify ‘possible’ IBD cases up to 31/08/2018. Diagnoses were manually confirmed through electronic health record review as per Lennard-Jones/Porto criteria. Autoregressive integrated moving average (ARIMA) regression was applied to forecast prevalence to 01/08/2028.ResultsIn total, 24 601 possible IBD cases were identified of which 10 499 were true positives. The point prevalence for IBD in Lothian on 31/08/2018 was 784/100 000 (UC 432/100 000, Crohn’s disease 284/100 000 and IBD unclassified (IBDU) 68/100 000). Capture–recapture methods identified an additional 427 ‘missed’ cases (95% CI 383 to 477) resulting in a ‘true’ prevalence of 832/100 000 (95% CI 827 to 837).Prevalence increased by 4.3% per year between 2008 and 2018 (95% CI +3.7 to +4.9%, p<0.0001). ARIMA modelling projected a point prevalence on 01/08/2028 of 1.02% (95% CI 0.97% to 1.07%) that will affect an estimated 1.53% (95% CI 1.37% to 1.69%) of those >80 years of age.ConclusionsWe report a rigorously validated IBD cohort with all-age point prevalence on 31/08/2018 of 1 in 125, one of the highest worldwide.
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Rathod, Girish, Nitin Raut, Pushkar Borole, Chandan Shetty, and Vijaykumar Gawali. "Single center, observational study to analyze correlation between vitamin D-3 deficiency and age in patients with orthopedic disorders." International Journal of Research in Orthopaedics 8, no. 1 (December 24, 2021): 64. http://dx.doi.org/10.18203/issn.2455-4510.intjresorthop20214963.
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<p><strong>Background:</strong> Vitamin D deficiency has been strongly associated with various health outcomes, including all-cause mortality. Chronic vitamin D deficiency in adults and in old age results in osteomalacia, osteoporosis, muscle weakness, and increased risk of fall and long bone fractures. <strong></strong></p><p><strong>Methods:</strong> We examined records of 1029 such patients and to analyze association of vitamin d-3 levels and categories of age groups (1-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 years). We categorized mild, moderate and severe cases age wise.</p><p><strong>Results: </strong>During the study period records for 1029 patients were evaluated, of which 347 (33.72%) male and 682 (66.27) were female the mean age with standard deviation for male was 38.25±15.64 years and for female was 41.43±15.23 years. Vitamin D deficiency (<20 ng/ml) was present in 623 patients (61%), 189 patients (18%) had vitamin D level 20-30 ng/ml and 217 patients (21%) had sufficient levels of vitamin D.</p><p><strong>Conclusions:</strong> Our study concludes that although there is high prevalence of vitamin D-3 deficiency across all age groups among orthopedic patients, age group 31-40 years, was found to be more affected.</p><p><strong> </strong></p>
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McGivern, Lauri, Leanne Shulman, Jan K. Carney, Steven Shapiro, and Elizabeth Bundock. "Death Certification Errors and the Effect on Mortality Statistics." Public Health Reports 132, no. 6 (November 2017): 669–75. http://dx.doi.org/10.1177/0033354917736514.
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Objective: Errors in cause and manner of death on death certificates are common and affect families, mortality statistics, and public health research. The primary objective of this study was to characterize errors in the cause and manner of death on death certificates completed by non–Medical Examiners. A secondary objective was to determine the effects of errors on national mortality statistics. Methods: We retrospectively compared 601 death certificates completed between July 1, 2015, and January 31, 2016, from the Vermont Electronic Death Registration System with clinical summaries from medical records. Medical Examiners, blinded to original certificates, reviewed summaries, generated mock certificates, and compared mock certificates with original certificates. They then graded errors using a scale from 1 to 4 (higher numbers indicated increased impact on interpretation of the cause) to determine the prevalence of minor and major errors. They also compared International Classification of Diseases, 10th Revision (ICD-10) codes on original certificates with those on mock certificates. Results: Of 601 original death certificates, 319 (53%) had errors; 305 (51%) had major errors; and 59 (10%) had minor errors. We found no significant differences by certifier type (physician vs nonphysician). We did find significant differences in major errors in place of death ( P < .001). Certificates for deaths occurring in hospitals were more likely to have major errors than certificates for deaths occurring at a private residence (59% vs 39%, P < .001). A total of 580 (93%) death certificates had a change in ICD-10 codes between the original and mock certificates, of which 348 (60%) had a change in the underlying cause-of-death code. Conclusions: Error rates on death certificates in Vermont are high and extend to ICD-10 coding, thereby affecting national mortality statistics. Surveillance and certifier education must expand beyond local and state efforts. Simplifying and standardizing underlying literal text for cause of death may improve accuracy, decrease coding errors, and improve national mortality statistics.
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Sarpatwari, Ameet, Shirley Watson, Howard Anderson, Drew Provan, and Adrian Newland. "Health-Related Lifestyle among Adult & Pediatric Patients with Idiopathic Thrombocytopenic Purpura in the United Kingdom." Blood 112, no. 11 (November 16, 2008): 3435. http://dx.doi.org/10.1182/blood.v112.11.3435.3435.
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Abstract Idiopathic thrombocytopenic purpura (ITP) is an autoimmune condition characterized by autoantibody-mediated platelet destruction and suboptimal megakaryocytic production. Primarily acute (< 6 months) in duration among children, ITP manifests predominantly chronically among adults, increasing susceptibility to bleeding events. Despite recent growth, published literature on health-related quality of life in ITP remains limited. The objective of our investigation was to identify lifestyle concerns associated with ITP among adult and pediatric patients in the United Kingdom. In collaboration with ITP specialists, a 43 question, closed-field lifestyle survey was developed, addressing social engagement, work and school performance, sports and activities, treatment, and travel. Patient members of the United Kingdom ITP Support Association (N = 1,767) were asked to complete and return mailed surveys. Pearson’s chi-square and Fisher’s exact tests were used to evaluate differences in dichotomized variables between groups. 790 (45%) completed surveys were returned. As illustrated in the table below, roughly one-quarter of adults (≥ 16 years) and one-fifth of children reported ‘always’, ‘sometimes’, or ‘often’ missing school or work owing to fatigue and having encountered difficulty obtaining insurance. Nearly one-third of adults further revealed having an elective surgery delayed owing to a low platelet count. Disparities were noted across gender with regard to bruise concealment (adults: p < 0.01; children: p = 0.03) and suspicions of subjection to violence (adults: p < 0.01; children: p = 0.49). In contrast with adults, pediatric patients reported being more likely to having requests for referral denied (p = 0.03). This study represents the largest quality of life investigation of ITP to date. Although the survey utilized remains to be validated, its findings nonetheless successfully highlight avenues for future investigation. Subgroups: ‘Yes’ % Adults Children Question Total ‘Yes’ % N = 790 Male N = 199 Female N = 497 Male N = 51 Female N = 43 [1] Total number of responses recorded for the given question. Have you ever been unable to go to work or school because of tiredness and fatigue? 29% 710[1] 26% 186 31% 435 20% 49 30% 40 Have you had difficulty obtaining or been refused travel and life insurance? 29% 611 30% 540 18% 71 Have you ever had surgery (other than splenectomy for ITP) postponed or delayed because of a low platelet count? 30% 620 34% 158 30% 391 13% 39 19% 32 Do you try to hide your bruises? 29% 756 10% 190 37% 475 20% 50 42% 41 Are people ever suspicious that the bruises are a result of physical violence? 17% 750 5% 193 19% 468 31% 49 38% 40 Have you ever been refused a referral to an ITP specialist or hospital of 5% 574 3% 144 4% 358 10% 41 10% 31
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Davies, Angela M., Kari Chansky, Derick H. M. Lau, Bryan R. Leigh, Laurie E. Gaspar, Geoffrey R. Weiss, Antoinette J. Wozniak, John J. Crowley, and David R. Gandara. "Phase II Study of Consolidation Paclitaxel After Concurrent Chemoradiation in Poor-Risk Stage III Non–Small-Cell Lung Cancer: SWOG S9712." Journal of Clinical Oncology 24, no. 33 (November 20, 2006): 5242–46. http://dx.doi.org/10.1200/jco.2006.07.0268.
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Purpose A previous Southwest Oncology Group (SWOG) study (S9429) demonstrated efficacy and tolerability of concurrent chemoradiotherapy in poor-risk stage III non–small-cell lung cancer (NSCLC). This study evaluated adding consolidation paclitaxel after chemoradiotherapy for a similar patient cohort. Patients and Methods Patients with histologically/cytologically determined stage III NSCLC were eligible based on performance status (PS) 2 and either low albumin or weight loss more than 10%, poor pulmonary function, or comorbidities precluding cisplatin use. Treatment was carboplatin 200 mg/m2 days 1, 3, 29, and 31, and etoposide 50 mg/m2 days 1 through 4, and 29 to 32. Beginning day 1, thoracic radiation was delivered at 1.8 Gy in 25 fractions plus 16-Gy boost (total dose, 61 Gy). Patients without disease progression received paclitaxel 175 mg/m2 every 21days for three cycles. Results Characteristics of 87 eligible patients were age 51 to 82 years; 57% PS 0 to 1, 43% PS 2; and 51% stage IIIA, 49% stage IIIB. Toxicities of concurrent chemoradiotherapy included grade 3 esophagitis (7%) and grade 3/4 neutropenia (43%). Fifty-four assessable patients received paclitaxel consolidation. Four treatment-related deaths occurred during chemoradiotherapy and four occurred during consolidation. Overall response rate was 53%. Median progression free- and overall survival were 6.1 and 10.2 months, respectively. One- and 2-year survival rates were 43% and 25%. Conclusion Compared with a previous SWOG trial in a similar patient population, the addition of consolidation paclitaxel after chemoradiotherapy resulted in increased toxicity without a survival advantage. More PS 2 patients (43% v 18%) enrolled onto S9712, which may explain increased toxicity and lack of benefit. The optimal chemoradiotherapy approach for poor-risk patients remains to be defined.
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Burchert, W., M. Schäfers, W. Schaefer, and O. Lindner. "Myokard-Perfusions-Szintigraphie 2012 in Deutschland." Nuklearmedizin 53, no. 01 (2014): 13–18. http://dx.doi.org/10.3413/nukmed-0612-13-07.
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SummaryAim: The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 6th survey on myocardial perfusion scintigraphy (MPS) of the reporting year 2012. Method: 278 questionnaires (177 private practices (PP), 78 hospitals (HO), 23 university hospitals (UH)) were evaluated. Results: MPS of 105,941 patients were reported. 95% [2005 = 80%] of MPS studies were conducted with 99mTc perfusion radiopharmaceuticals and only 5% with 201Tl. 79% [2009 = 76%] of the MPS were performed in PP, 15% [2009 = 17%] in HO, and 6% [2009 = 7%] in UH. Data from 108 centres which participated in all surveys from 2005 to 2012 showed an increase in MPS numbers of 4.0% (PP +6.1%, HO +18.2%, UH –18.3%). 29% of all participants (27% of PP, 31% of HO, and 26% of UH) noticed no change and 26% of all participants (28% of PP, 17% of HO and 35% of UH) an increase in their MPS requests since the 2009 query. The type of stress was pharmacological in 39% [2009 = 31%]. Of these 61% with adenosine (39% with exercise), 22% with regadenoson (51% with exercise), 14% with dipyridamole (60% with exercise), and 3% with dobutamine. Gated SPECT was performed in 73% [2009 = 56%] of all rest, in 70% [2009 = 56%] of all stress and in 67% [47%] of all stress and rest MPS. Only 36% [2009 = 33%] of the centres performed a quantification of all their studies with scores, whereas 41% [2009 = 52%] did not apply any quantification. 60% [2009 = 49%] of the MPS were requested by ambulatory care cardiologists. Conclusion: The survey on MPS in Germany reveals a good conformity of imaging procedures with the current guideline. A positive development in MPS practice and referral can be stated. However, there is still some potential of MPS processing considering the quantitative perfusion analysis.
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Dreyfus, Julien, Michele Flagiello, Baptiste Bazire, Florian Eggenspieler, Florence Viau, Elisabeth Riant, Yannick Mbaki, et al. "Isolated tricuspid valve surgery: impact of aetiology and clinical presentation on outcomes." European Heart Journal 41, no. 45 (September 25, 2020): 4304–17. http://dx.doi.org/10.1093/eurheartj/ehaa643.
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Abstract Aims The aim of this study was to identify determinants of in-hospital and mid-term outcomes after isolated tricuspid valve surgery (ITVS) and more specifically the impact of tricuspid regurgitation (TR) mechanism and clinical presentation. Methods and results Among 5661 consecutive adult patients who underwent a tricuspid valve (TV) surgery at 12 French tertiary centres in 2007–2017 collected from a mandatory administrative database, we identified 466 patients (8% of all tricuspid surgeries) who underwent an ITVS. Most patients presented with advanced disease [47% in New York Heart Association (NYHA) III/IV, 57% with right-sided heart failure (HF) signs]. Tricuspid regurgitation was functional in 49% (22% with prior left-sided heart valve surgery and 27% isolated) and organic in 51% (infective endocarditis in 31% and other causes in 20%). In-hospital mortality and major complications rates were 10% and 31%, respectively. Rates of survival and survival free of HF readmission were 75% and 62% at 5 years. Patients with functional TR incurred a worse in-hospital mortality than those with organic TR (14% vs. 6%, P = 0.004), but presentation was more severe. Independent determinants of outcomes were NYHA Class III/IV [odd ratios (OR) = 2.7 (1.2–6.1), P = 0.01], moderate/severe right ventricular dysfunction [OR = 2.6 (1.2–5.8), P = 0.02], lower prothrombin time [OR = 0.98 (0.96–0.99), P = 0.008], and with borderline statistical significance, right-sided HF signs [OR = 2.4 (0.9–6.5), P = 0.06] while TR mechanism was not [OR = 0.7 (0.3–1.8), P = 0.88]. Conclusion Isolated TV surgery was associated with high mortality and morbidity, both in hospital and during follow-up, predicted by the severity of the presentation but not by TR mechanism. Our results suggest that TV intervention should be performed earlier in the course of the disease.
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Dillman, R. O., R. K. Oldham, K. W. Tauer, D. W. Orr, N. M. Barth, G. Blumenschein, J. Arnold, R. Birch, and W. H. West. "Continuous interleukin-2 and lymphokine-activated killer cells for advanced cancer: a National Biotherapy Study Group trial." Journal of Clinical Oncology 9, no. 7 (July 1991): 1233–40. http://dx.doi.org/10.1200/jco.1991.9.7.1233.
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We conducted a multicenter, phase II trial of continuous-infusion recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells. Patients had advanced cancer, measurable disease, and a good performance level. Treatment included a 5-day continuous infusion of 18 x 10(6) IU/m2/d of rIL-2 followed by 1 day of rest, 4 days of leukapheresis to collect cells for in vitro augmentation of cellular cytotoxicity, and 5 more days of rIL-2 infusion with reinfusion of LAK cells for 3 successive days. Therapy was repeated after 2 weeks. There were 117 patients enrolled: 63% were males, with a median age of 51 years. Eighty-two percent were managed in oncology units, and 18% were in intensive care units. Six patients died within 1 month of initiating therapy. In renal cell carcinoma, the response rate was one of 31 patients (3%), with a median survival of 10.7 months. In melanoma, the response rate was four of 33 patients (12%), with a median survival of 6.1 months. For all other histologies, response rate was three of 53 patients (5%), with a median survival of 7.4 months. All responders were asymptomatic when therapy was initiated. This trial confirms the feasibility of administering continuous rIL-2 and LAK cells outside the intensive care unit environment. Antitumor activity in melanoma was similar to that seen in multicenter trials of bolus rIL-2 and LAK cells. Activity in renal cell cancer was disappointing.
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Riaz, Lubna, Waqas Ali Khan, Shamayal Mandokhel, Asfand Tariq, Neelam Faryad, and Shazia Irum. "Relation of Parents Economical, Educational and Awareness on Immunization Status of Children." Pakistan Journal of Medical and Health Sciences 15, no. 5 (May 30, 2021): 965–67. http://dx.doi.org/10.53350/pjmhs21155965.
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Aim: To determine the immunization status of children 0 to 2 years and factors leading to low vaccination status in children visiting tertiary care center. Study design: Cross-sectional study Place and duration of study: Department of Paediatrics Shaikh Zayed Hospital Lahore from 1st November 2019 to 31st April 2020. Methodology: Five hundred children age between 0-2 years were enrolled after fulfilling inclusion and exclusion criteria. Results: The mean age was 9.9±6.1 months, with mean weight of 7.4±3.4 kg and 200 (40%) were male and 300 (60%) were female patients. Sixty (12%) were not vaccinated, 145 (29%) partially vaccinated and 295 (59%) fully vaccinated. In the distribution by income level 255 (51%),180 (36%) and 65 (13%) parents were having low, middle and high income respectively; By education level,155 (31%) with no education, 140 (28%) some education and 205 (41%) with high education, regarding knowledge of immunization, 50 (10%) had no knowledge, 215 (43% )had wrong perception of immunization and 235 (47%) were fully aware.295 (59%) had up-to-date immunization Conclusion: More than half of the study populations were upto date about immunization status. It is also concluded that majority of parents of low-income level and uneducated were unknown about immunization status and majority of middle and high-income level and educated people were partial known or up-to-date about immunization status Keywords: Economical level, Educational level, Awareness level, Immunization status
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Rotta, Johanna, Valentina Perosa, Renat Yakupov, Hugo J. Kuijf, Frank Schreiber, Laura Dobisch, Jan Oltmer, et al. "Detection of Cerebral Microbleeds With Venous Connection at 7-Tesla MRI." Neurology 96, no. 16 (March 2, 2021): e2048-e2057. http://dx.doi.org/10.1212/wnl.0000000000011790.
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ObjectiveCerebral microbleeds (MBs) are a common finding in patients with cerebral small vessel disease (CSVD) and Alzheimer disease as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein.Methods7-Tesla (7T) MRI was conducted and MBs were counted on quantitative susceptibility mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein.ResultsA total of 51 people (mean age [SD] 70.5 [8.6] years, 37% female) participated in the study: 20 had CSVD (cerebral amyloid angiopathy [CAA] with strictly lobar MBs [n = 8], hypertensive arteriopathy [HA] with strictly deep MBs [n = 5], or mixed lobar and deep MBs [n = 7], 72.4 [6.1] years, 30% female) and 31 were healthy controls (69.4 [9.9] years, 42% female). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. Patients with CAA showed the highest ratio of venous to total MBs (19%) (HA = 9%, mixed = 18%, controls = 5%).ConclusionOur findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathologic studies are needed to confirm our observations.
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Ajayi, Bisola, Alex J. Trompeter, Shamim Umarji, Priyanshu Saha, Magnus Arnander, and Darren F. Lui. "Catching the second wave: clinical characteristics and nosocomial infection rates in major trauma and orthopaedic patients during the COVID-19 pandemic." Bone & Joint Open 2, no. 8 (August 1, 2021): 661–70. http://dx.doi.org/10.1302/2633-1462.28.bjo-2021-0078.r1.
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Aims The new COVID-19 variant was reported by the authorities of the UK to the World Health Organization (WHO) on 14 December 2020. We aim to describe the clinical characteristics and nosocomial infection rates in major trauma and orthopaedic patients comparing the first and second wave of COVID-19 infection. Methods A retrospective analysis of a prospectively collected trauma database was reviewed at a level 1 major trauma centre from 1 December 2020 to 18 February 2021 looking at demographics, clinical characteristics, and nosocomial infections and compared to our previously published first wave data (26 January 2020 to 14 April 2020). Results From 1 December 2020 to 18 February 2021, 522 major trauma patients were identified with a mean age of 54.6 years, and 53.4% (n = 279) were male. Common admissions were falls (318; 60.9%) and road traffic accidents (RTAs; 71 (13.6%); 262 of these patients (50.2%) had surgery. In all, 75 patients (14.4%) tested positive for COVID-19, of which 51 (68%) were nosocomial. Surgery on COVID-19 patients increased to 46 (61.3%) in the second wave compared to 13 (33.3%) in the first wave (p = 0.005). ICU admissions of patients with COVID-19 infection increased from two (5.1%) to 16 (20.5%), respectively (p = 0.024). Second wave mortality was 6.1% (n = 32) compared to first wave of 4.7% (n = 31). Cardiovascular (CV) disease (35.9%; n = 14); p = 0.027) and dementia (17.9%; n = 7); p = 0.030) were less in second wave than the first. Overall, 13 patients (25.5%) were Black, Asian and Minority ethnic (BAME), and five (9.8%) had a BMI > 30 kg/m2. The mean time from admission to diagnosis of COVID-19 was 13.9 days (3 to 44). Overall, 12/75 (16%) of all COVID-19 patients died. Conclusion During the second wave, COVID-19 infected three-times more patients. There were double the number of operative cases, and quadruple the cases of ICU admissions. The patients were younger with less dementia and CV disease with lower mortality. Concomitant COVID-19 and the necessity of major trauma surgery showed 13% mortality in the second wave compared with 15.4% in the first wave. In contrast to the literature, we showed a high percentage of nosocomial infection, normal BMI, and limited BAME infections. Cite this article: Bone Jt Open 2021;2(8):661–670.
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Fomina, L. V., A. M. Dashchuk, and E. I. Dobrzhanska. "Study of clinical features of patients with chronic eczema." Ukrainian Journal of Dermatology, Venerology, Cosmetology, no. 4 (December 8, 2021): 23–27. http://dx.doi.org/10.30978/ujdvk2021-4-23.
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Objective — s to study the clinical features of chronic eczema (CE) in 96 patients aged 18 to 78 years.
Materials and methods. The study was carried out in the city clinical dermatovenerological dispensary No. 5 in Kharkov. All patients gave written informed consent to participate in the study.The majority of them (66.7 %) were between 31 and 50 years old. The duration of dermatosis in 6.3 % of the surveyed persons ranged from 6 months to 1 year, in 33.3 % — from 1 year to 5 years, in 42.7 % — from 5 to 10 years, in 17.7 % — over 10 years. The most frequent causes of exacerbation in 51.1 % were neuropsychiatric trauma and stress, in 15.6 % — diseases of internal organs and acute respiratory diseases, in 13.5 % — contact with chemicals. In all patients, dermatosis was recurrent. Most often, the surveyed patients complained of moderate intensity itching (51 %) and severe sleep disturbances (66.7 %). Moderate leukocytosis and accelerated ESR were found in 21.9 % of patients, eosinophilia — in 5.1 %.
Results and discussion. 96 patients with chronic eczema aged 18 to 78 years were under observation. The diagnosis of chronic eczema was based on anamnestic data, patients’ complaints of itchy skin of varying intensity, objective examination of the patient, as well as recurrences of dermatosis for more than 1 year. The largest number of patients had dermatosis from 5 to 10 years. Chronic eczema in the observed patients was recurrent. The duration of remission was (4.9 ± 0.2) months. The duration of exacerbation was (6.1 ± 0.2) weeks. To characterize the severity of chronic eczema, a scoring system was used, according to which the average severity was (2.63 ± 0.08) points.According to the degree of skin lesions, the forms of dermatosis were limited and widespread. Patients complained of skin itching of varying intensity: more often itching of moderate intensity, periodic; painful, persistent, with an insurmountable need to scratch; short-term; no itching.Also, patients noted sleep disturbance in the form of difficulty falling asleep, sudden awakening at night and lack of a feeling of rest after waking up in the morning. 39 patients had bad habits (smoking, alcohol abuse).Сlinical analysis of blood revealed moderate leukocytosis, accelerated ESR, eosinophilia, signs of secondary infection.
Conclusions. The average age of the patients ranged from 31 to 50 years. All examined patients had recurrent dermatosis. The average degree of its severity was (2.63 ± 0.08) points. Most often, patients complained of moderate intensity itching (51 %) and severe sleep disturbances (66.7 %). In 21.9 % of the examined patients moderate leukocytosis and accelerated ESR were revealed, in 5.1 % — eosinophilia.
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Muharraran, Firdha, Ivan Elisabeth Purba, and Donal Nababan. "RELATIONSHIP OF LEADER SUPPORT WITH EMPLOYEE WORK ACHIEVEMENT AT SEI SUKA DISTRICT PUSKESMAS SEI SUKA BATU BARA DISTRICT 2019." International Journal of Research -GRANTHAALAYAH 9, no. 12 (January 10, 2022): 251–58. http://dx.doi.org/10.29121/granthaalayah.v9.i12.2021.4444.
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Background: The national health system is essentially an order that reflects the efforts of the Indonesian people to increase their ability to achieve health status. Puskesmas is a leading health service organization unit that provides comprehensive and integrated health services to the community. Human resource management is a planning, organizing, coordinating, implementing, and supervising the procurement, development, provision of remuneration, integration, maintenance, and separation of workers in order to achieve organizational goals. One way to improve resource management is leadership support for outstanding employees.
Purpose: This study aims to determine the relationship between leadership support and employee performance at the Sei Suka Health Center, Sei Suka District, Batu Bara Regency in 2019.
Method: This research was conducted cross sectional with data collection method (questionnaire). Each group with an age range of 20-30 years, 31-40, 41-50, 51-60 was given a questionnaire to fill out. Determination of the relationship between leadership support and employee performance can be seen from the results obtained after filling out the questionnaire, then the data is analyzed using the chi-square test.
Results: The results obtained that the most respondents in the category of good leadership support as many as 16 people (48.5%) had poor work performance and the least was good leadership support 2 people (6.1%) had good work performance after being tested with the chi test square can be seen that the value of Significancy p value = 0.003 (P <0.005) which shows that the relationship between leadership support and employee performance is significant.
Conclusion: there is a significant relationship between leadership support and employee performance.
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Krenn, Kurt, and Le Thi Thu Huong. "Fluid characteristics from shallow magmatic environments: A contribution to danburite bearing Luc Yen pegmatites, northern Vietnam." VIETNAM JOURNAL OF EARTH SCIENCES 41, no. 1 (January 8, 2019): 1–9. http://dx.doi.org/10.15625/0866-7187/41/1/13541.
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Danburite as a member of the Luc Yen pegmatite mineral assemblage has been studied using fluid inclusion microthermometry and Raman spectroscopy. Data characterize well-preserved fluid inclusions which originate from primary large tubular inclusions as result of necking down. Same modifications underwent a second inclusion generation that evolved during healing of a later crack. Both generations of fluid inclusions show the same chemistry (H2O-CO2) characterizing 3-phase inclusions with additional solids (calcite, sassolite and danburite). Inclusions consist of pure CO2 and H2O with additional NaCl ± KCl comprising a salinity of about 4.5 mass%. Internal fluid inclusion pressures as well as bulk inclusion densities have been calculated using the fermi diad split method of pure CO2 at clathrate melting temperatures of the system and total homogenization temperatures, respectively. Mean internal pressures of ca. 4.5 MPa as well as a bulk density around 0.60 g/cm3 represent a low-dense fluid with XH2O~0.86 and XCO2~0.14 in composition that was present during formation of danburite. Data characterize danburite as a late stage crystallization member of the pegmatite in a shallow magmatic environment.ReferencesAnovitz L.M. and Grew, E.S., 1996. Mineralogy, petrology and geochemistry of boron: An introduction. In L.M. Anovitz and E.S. Grew, Eds., Boron: Mineralogy, Petrology, and Geochemistry, Reviews in Mineralogy, Vol. 33, Mineralogical Society of America, Washington DC, USA, 1–40.Bakker, R.J., 1997. Clathrates: computer programs to calculate fluid inclusion V–X properties using clathrate melting temperatures. Computer & Geosciences, 23, 1-18.Bakker R.J., Diamond L.W., 2000. Determination of the composition and molar volume of H2O–CO2 fluid inclusions by microthermometry. Geochimica et Cosmochimica Acta, 64, 1753-1764.Bodnar R.J., 1993. Revised equation and table for determining the freezing point depression of H2O-NaCl solutions. Geochimica et Cosmochimica Acta, 57, 683-684.Chauviré B., Rondeau B., Fritsch E., Ressigeac P., Devidal J.-L., 2015. Blue spinel from the Luc Yen District of Vietnam. Gems & Gemology, 51, 1, 2–17.Diamond L., 2003. Glossary: Terms and symbols used in fluid inclusion studies, In: Samson, I., Anderson, A., Marshall, D. (Eds.), Fluid Inclusions: Analysis and Interpretation. Mineralogical Association of Canada Short Course Series, 32, 365-374.Duan Z., Møller N., Weare J.H., 1996. A general equation of state for supercritical fluid mixtures and molecular dynamics simulation of mixture PVTX properties. Geochimica et Cosmochimica Acta, 60, 1209-1216.Davis D.W., Lowenstein T.K., Spencer R.J., 1990. Melting behavior of fluid inclusions in laboratory-grown halite crystals in the systems NaCl-H2O, NaCl-KCl-H2O, NaCl-MgC12-H2O, and NaCl-CaCl2-H2O. Geochimica et Cosmochimica Acta, 54, 591-601.Fall A., Tattrich B., Bodnar R.J., 2011. Combined microthermometric and Raman spectroscopic technique to determine the salinity of H2O-CO2-NaCl fluid inclusions based on clathrate melting. Geochimica et Cosmochimica Acta, 75, 951-964.Garnier V., Ohnenstetter D., Giuliani G., Maluski H., Deloule E., Phan Trong T., Pham Van L., Hoang Quang V., 2005. Age and significance of ruby bearing marble from the Red River shear zone, northern Vietnam. Canadian Mineralogist, 43(4), 1315-1329.Goldstein R.H., Reynolds T.J., 1994. Systematics of fluid inclusions in diagenetic minerals. SEPM Short Course, 31.Kurshakova L.D., 1982. Temperature regime and geochemical conditions of formation of danburite. International Geology Review 24, 3, 367–371.Roedder E. 1984. Fluid Inclusions. Reviews in Mineralogy, 12, 646.Tattitch B.C., Candela P.A., Piccoli P.M., Bodnar R.J., 2015. Copper partitioning between felsic melt and H2O-CO2 bearing saline fluids. Geochim.
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Shroff, Rachna T., Mitesh J. Borad, Lianchun Xiao, Ahmed Omar Kaseb, Gauri R. Varadhachary, Robert A. Wolff, Kanwal Pratap Singh Raghav, et al. "A phase II trial of gemcitabine (G), cisplatin (C), and nab-paclitaxel (N) in advanced biliary tract cancers (aBTCs)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 4018. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.4018.
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4018 Background: BTCs are often diagnosed at an advanced stage and have a poor prognosis. The standard therapy for aBTCs is the combination of GC. However, the median overall survival (mOS) is dismal at 11.7 months (mos) with a median progression free survival (mPFS) of 8 mos. Methods: A single arm, phase II study was conducted at MD Anderson and Mayo Clinic Arizona. Patients (pts) with aBTC were treated at initial dose level of G/C/N (in mg/m2) at 1000/25/125 (n = 27) which was reduced to lower doses due to grade 3/4 hematological (heme) toxicity (tox) - G/C/N: 800/25/100 (n = 33). Cycles were q21 days with restaging q3 cycles until progression. PFS was the primary endpoint (endpt). Using a Bayesian hypothesis test-based design, we assumed mPFS of 8 mos under the null hypothesis (H0), 10 mos under the alternative (H1). Secondary endpts included mOS, RECIST v1.1 response rate (RR), safety and CA19-9 response. Results: 60 pts were enrolled with data on 51 available as of the time of this abstract (age: median 60 yrs [range 31-77], ECOG PS 0/1 (17/34), M/F (30/21), intrahepatic cholangiocarcinoma/extrahepatic/gallbladder (32/8/11). Median follow-up was 11.5 mos and median number of treatment (trmt) cycles = 5. Pts at initial dose level had significant grade 3/4 heme tox: neutropenia, febrile neutropenia, anemia, and thrombocytopenia leading to trmt discontinuation in 6/27 pts. After dose reduction to G/C/N (in mg/m2) at 800/25/100, trmt was better tolerated with only 4 pts experiencing grade 4 heme tox. Non-heme tox were grade 3 in 10 pts: nausea/vomiting, diarrhea, thromboembolic event/CVA, hypokalemia, constipation, cystitis, LFT elevations. In the initial 51 pts, mPFS = 11.4 mos (95% CI: 6.1, not reached) and mOS not reached (estimated > 20 mos, 1-year survival rate 66.7%; 95%CI: 65.9-92.2%). 34 pts evaluable for response: disease control rate (PR+CR+SD)-82.3% and RR-32.3%. 3 unresectable cases were operated post trmt with 1 pathologic CR. Conclusions: The combination of GCN was well tolerated at adjusted doses and demonstrates encouraging preliminary efficacy having met its mPFS endpt and a 1-year survival rate higher than historical control. These results merit evaluating GC +/-N in a randomized controlled study. Clinical trial information: NCT02392637.
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Omran, Heyder, Rupert Bauersachs, Siegfried Rübenacker, Franz Goss, and Christoph Hammerstingl. "The HAS-BLED score predicts bleedings during bridging of chronic oral anticoagulation." Thrombosis and Haemostasis 108, no. 07 (2012): 65–73. http://dx.doi.org/10.1160/th11-12-0827.
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SummaryPatients who receive long-term oral anticoagulant (OAC) therapy often require interruption of OAC for an elective invasive procedure. Current guidelines allow bridging therapy with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Apart from the risk of embolism, bleeding is an important complication in this setting and the optimal perioperative management of such patients is still under discussion. The aims of this prospective, observational, multicentre registry of patients treated by cardiologists were: 1) to evaluate current practice of perioperative management of OAC in a large outpatient cohort, 2) to document embolic and haemorrhagic events, and 3) to identify risk factors predicting adverse events. In the years 2009 and 2010, 1,000 invasive procedures (cardiac catheterisation n=533, pacemaker implantation n = 128, surgery n = 194, other n = 145) were performed in patients with OAC. Sixty- one (6.1%) of those patients did not receive bridging therapy during interruption of OAC, 937 (93.7%) patients were treated with LMWH, two patients (0.2%) received UFH. In 22 patients (2.2%) LMWHs were given in prophylactic dose, 727 patients (72.7%) were treated with halved therapeutic (i.e. weight-adapted) LMWH doses and 188 (18.8%) received full therapeutic LMWH doses. Four thromboembolic complications were observed during 30 days of follow-up (two retinal embolisms, one stroke, one myocardial infarction; 0.4%). One major bleeding (0.1%) and 35 clinically relevant bleedings (3.5%) occurred. Rehospitalisation after bleedings was necessary in 20 patients. Independent predictors for bleedings were history of mechanical heart valve replacement (MVR) (p=0.0002) and the HAS-BLED score (<0.0001), with a cut off value ≥3 being the most predictive variable for haemorrhage (hazard ratio 11.8, 95% confidence interval 5.6–24.9, p<0.0001). A total of 527 patients with atrial fibrillation and a CHADS2 score ≤2 received halved therapeutic or full therapeutic dosages of LMWH despite a low embolic risk, whereas 49 of the patients with heart valve replacement (51%) did not receive dosages of bridging therapy as recommended in guidelines. In conclusion, in this registry of patients treated by cardiologists, 94% of patients who required interruption of OAC before invasive procedures received LMWH as a bridging therapy, of whom 73% were treated with halved therapeutic LMWH-dosages. Guideline recommendations were followed in only 31% of cases. Importantly, 69% of patients with AF were over-treated while 51% of patients with heart valve replacement were under-treated with LMWHs. A HASB-BLED score ≥3 was highly predictive of bleeding events.
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Shroff, Rachna T., Milind M. Javle, Lianchun Xiao, Ahmed Omar Kaseb, Gauri R. Varadhachary, Robert A. Wolff, Kanwal Pratap Singh Raghav, et al. "A phase II trial of gemcitabine (G), cisplatin (C), and nab-paclitaxel (N) in advanced biliary tract cancers (aBTCs): Updated survival analysis." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 350. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.350.
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350 Background: BTCs are often diagnosed at an advanced stage and have a poor prognosis. The standard therapy for aBTCs is the combination of GC. However, the median overall survival (mOS) is dismal at 11.7 months (mos) with a median progression free survival (mPFS) of 8 mos. Methods: A single arm, phase II study was conducted at MD Anderson and Mayo Clinic Arizona. Patients (pts) with aBTC were treated at initial dose level of G/C/N (in mg/m2) at 1000/25/125 (n = 30) which was reduced to lower doses due to grade 3/4 hematological (heme) toxicity (tox) - G/C/N: 800/25/100 (n = 30). Cycles were q21 days with restaging q3 cycles until progression. PFS was the primary endpoint (endpt). Using a Bayesian hypothesis test-based design, we assumed mPFS of 8 mos under the null hypothesis (H0), 10 mos under the alternative (H1). Secondary endpts included mOS, RECIST v1.1 response rate (RR), safety and CA19-9 response. Results: 60 pts were enrolled with 51 being response-evaluable having received more than 1 cycle of therapy (age: median 60 yrs [range 31-77], ECOG PS 0/1 (22/38), M/F (33/27), intrahepatic cholangiocarcinoma/extrahepatic/gallbladder (38/9/13). Median follow-up was 14 mos and median number of treatment (trmt) cycles = 5.24. Pts at initial dose level had significant grade 3/4 heme tox: neutropenia, febrile neutropenia, anemia, and thrombocytopenia leading to trmt discontinuation in 6/30 pts. After dose reduction to G/C/N (in mg/m2) at 800/25/100, trmt was better tolerated with only 3 pts experiencing grade 4 heme tox. Non-heme tox were grade 3 in 19 pts: nausea/vomiting, diarrhea, thromboembolic event/CVA, hypokalemia, constipation, cystitis, LFT elevations. The mPFS = 11.4 mos (95% CI: 6.1, 16.1) and mOS = 19.2 (95%CI: 13.6, NA), 1-year survival rate 67.6%. 51 pts evaluable for response: disease control rate (PR+CR+SD)-84.3% and RR-39%. 12 unresectable cases were operated post trmt with 1 pathologic CR. Conclusions: The combination of GCN was well tolerated at adjusted doses and demonstrates encouraging efficacy having met its mPFS endpt and an impressive mOS higher than historical control. These results merit evaluating GC +/-N in a randomized controlled study. Clinical trial information: NCT02392637.
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Teng, N. N., M. K. Cheung, A. Husain, K. Osann, J. S. Berek, D. S. Kapp, and J. K. Chan. "The significance of the ratio of metastatic to examined lymph nodes in endometrioid uterine cancer." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 15043. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.15043.
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15043 Background: To determine the impact benign to positive lymph node ratio (LNR) on the disease-specific survival of women with advanced endometrioid corpus cancer. Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results Program from 1988–2001 and analyzed using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of the 1,222 women diagnosed with stage IIIC-IV endometrioid uterine cancer with nodal disease, the median age was 64 (range: 28–93). 1,025 (83.9%) were White, 75 (6.1%) Black, 91 (7.5%) were Asian and 31 (2.5%) were Other. All patients underwent surgical staging including a lymph node assessment and were found to have nodal metastases. 639 (52.3%) had stage IIIC, 24 (2.0%) IVA, and 559 (45.7%) IVB disease. Furthermore, 123 (10.1%), 466 (38.1%), and 581 (47.6%) women had grade 1, 2, and 3 disease, respectively. Grade information was unavailable for 51 (4.2%) patients. The benign to positive lymph node ratios (LNR) were divided in four subgroups: ≤5%, >5% to ≤10%, >10% to ≤20%, and >20% to determine impact of LNR on disease-specific survival. Increasing LNR (≤5%, >5% to ≤10%, >10% to ≤20%, and >20%) was associated with a decrease in disease-specific survival at 83.8%, 73.2%, 62.4%, and 50.8%, respectively (p < 0.0001). More specifically, LNR was an important factor only in patients with 11–20 and >20 lymph nodes removed but not for those with less than 10 nodes resected. Women with higher (LNR) received significantly more adjuvant radiotherapy at 72.0%, 69.7%, 61.1%, and 52.6%, respectively. On multivariate analysis, age, stage, grade, and lymph node ratio were significant independent prognostic factors for survival. Adjuvant radiation was not an important independent prognostic factor in multivariate analysis. Conclusion: The ratio of metastatic to examined lymph nodes in endometrioid uterine cancer is an important prognostic factor. Clinical trials on adjuvant therapy should be designed with consideration of this significant prognosticator. No significant financial relationships to disclose.
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Singhal, Rishi, Victor Roth Cardoso, Tom Wiggins, Jonathan Super, Christian Ludwig, Georgios V. Gkoutos, Kamal Mahawar, et al. "30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data." International Journal of Obesity 46, no. 4 (December 15, 2021): 750–57. http://dx.doi.org/10.1038/s41366-021-01048-1.
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Abstract Background There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts. Materials and methods This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien–Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups. Results In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07). Conclusions This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts.
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Keating, Michael J., Susan O’Brien, Maher Albitar, Susan Lerner, William Wierda, and Hagop Kantarjian. "Extended Follow-Up of a Chemo-Immunotherapy Regimen FCR (Fludarabine, F; Cyclophosphamide, C; and Rituximab, R) as Initial Therapy for Chronic Lymphocytic Leukemia (CLL)." Blood 106, no. 11 (November 16, 2005): 2118. http://dx.doi.org/10.1182/blood.v106.11.2118.2118.
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Abstract Combination regimens are increasingly being used in CLL. The addition of R to F±C has increased the complete response (CR) rate in previously untreated patients (pts) with CLL. FCR was given to 300 previously untreated pts with CLL; 70.3% male, 33% Rai stage III-IV, with median value and ranges for age − 57 years (17–86), hemoglobin − 12.5G% (6.1–18.7), white cell count − 76 x 103/μl (2.1–620), platelets − 154 x 103/μl (8–406). 51% had splenomegaly. All pts fulfilled the NCIWG indications for therapy. 72% achieved CR, 10% nodular partial remission (NPR), and 12% PR. The pretreatment characteristic most strongly associated with CR was the beta-2-microglobulin level (P<.001) with significant differences between those with a value less than twice normal versus higher values. Advanced age (≥ 70 yrs), advanced stage, low hemoglobin (<11G%), low albumin (<3.6G%), and elevated BUN (>23mg%) were all significantly associated with a lower CR rate (P<.01). CD38 was not associated with CR. Mutation status, ZAP70, and FISH cytogenetics were not routinely measured. Median follow-up was 43 months (18–73). Several characteristics were associated with remission duration (R Dur). Multivariate analysis showed that (1) PCR for IgVH, (2) NCIWG response, and (3) flow responses were all independently associated with R Dur. PCR negativity for IgVH was most strongly correlated with R Dur. Seven of 79 PCR negative pts have relapsed at 31, 39, 43, 44, 62, 64, and 67 months. Response Patients 4-Yr. R Dur Θ 4-Year Surv. Flow CR† PCR Neg.$ *P<.01;𝛉Projected;†Marrow CD5+CD19<1%;$PCR IgVH CR 217 83%* 84%* 165/208 (79%) 69/160 (43%) NPR 31 64% 84% 10/27 (37%) 7/19 (37%) PR 37 38% 50% 10/26 (38%) 3/13 (23%) Overall 300 77% (CR+PR) 83% 185/261 (71%) NA There was no significant difference in survival between CR and NPR pts despite a significantly shorter R Dur (P<.01) for NPR pts. Survival was similar for progressive Rai 0-II and III-IV pts with projected four-year survival of >80%. The median survival for the 300 patients and various prognostic subgroups has not been reached. Second cancers occurred in 53 cases (20 with non-melanomatous skin cancers). Three cases of AML and 3 additional cases of myelodysplastic syndrome occurred. Autoimmune hemolytic anemia (AIHA) or red cell aplasia (RCA) occurred in 25 and 6 cases respectively. These complications remain a significant clinical problem in CLL. There was no significant difference in the IgA or IgM levels over time but a lower mean initial IgG (837±567mg%) versus 690±338mg% six months after FCR was completed (P<.005) was noted. 56/72 (78%) who failed or relapsed have been started on salvage therapy. The salvage response rate on retreatment with FCR+alemtuzumab was 9/17 (53%). More pts failing after initial CR or NPR claimed a second response (17/29, 59%) compared with the PR or refractory pts (3/20, 16%; P=.002). Multivariate analysis of characteristics associated with CR rate and survival for FCR and preceding non-R protocols demonstrated a significant advantage for FCR (P<.001). Conclusion When compared with other completed chemotherapy protocols without R, FCR significantly improved CR rate, time-to-progression and treatment failure, and overall survival establishing FCR as the most successful protocol which we have conducted to date.
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Alves, Kelle Karolina Ariane Ferreira, Lívia Menezes Borralho, Ítalo de Macedo Bernardino, and Tânia Maria Ribeiro Monteiro de Figueiredo. "Análise temporal da incidência da tuberculose na população privada de liberdade." ARCHIVES OF HEALTH INVESTIGATION 9, no. 6 (December 28, 2020): 655–60. http://dx.doi.org/10.21270/archi.v9i6.4907.
Full textAbstract:
Objetivo: verificar o comportamento da incidência da tuberculose na população privada de liberdade e estimando sua tendência. Materiais e métodos: Trata-se de um estudo ecológico de série temporal com análise de tendência da incidência da tuberculose na população privada de liberdade. Utilizou-se de dados secundários provenientes do Sistema de Informações e Agravos de Notificação. A população foi composta por todas as notificações de Tuberculose da população privada de liberdade de unidades masculinas e femininas no período de 2007 a 2016. Na análise de tendência temporal foi realizada através da criação de modelos de regressão polinomial e testados os modelos linear; quadrático; exponencial. Resultados: A tendência da incidência na população privada de liberdade geral e no sexo masculino foi considerada estável, ambas com (p=0,180), e no sexo feminino decrescente (p= 0,040). Conclusão: É necessário avanços na condução do controle da tuberculose nas unidades prisionais.
Descritores: Tuberculose; Epidemiologia; Prisioneiros; Incidência; Saúde Pública.
Referências
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Alves JP, Brazil JM, Nery AA, Vilela ABA, Filho IEM. Perfil Epidemiológico de pessoas privadas de liberdade. Rev enferm UFPE on line. 2017;11(supl.10):4036-44.
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Demetrio, D., A. Magalhaes, M. Oliveira, R. Santos, and R. Chebel. "11 Invivo-derived embryo pregnancy rates at Maddox Dairy from 2008 to 2018." Reproduction, Fertility and Development 32, no. 2 (2020): 130. http://dx.doi.org/10.1071/rdv32n2ab11.
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Maddox Dairy, located in Riverdale, CA, USA, is a Holstein herd that milks 3500 cows with a 305-day mature-equivalent milk production of 12 800 kg, and they have been producing high genetic animals by embryo transfer (ET) since the early 1980s. Invivo-derived embryos from Holstein donors were transferred fresh (grade 1 or 2) or frozen (grade 1), at morula (4), early blastocyst (5), or blastocyst (6) stage, to virgin heifers (VH, natural oestrus, 13-15 months old) or lactating cows (LC, Presynch-Ovsynch, 86 days in milk, first or second lactation) 6 to 9 days after oestrus. Pregnancy diagnosis was done by transrectal ultrasonography at 32-46 days in VH and by the IDEXX PAG test at 30 days in LC. June, July, August, September, and October were called critical months (first service AI conception rate drops below 44%) and compared with the other months. The data from 32 503 ETs between January 2008 and December 2018 are summarised on Table 1. Pregnancy rates (PR) are lower for LC recipients than for VH. Embryo transfers performed 7 or 8 days after oestrus had higher PR in both types of recipients and embryos, but Day 6 and 9 oestrus are also used with fair results. The season does not seem to affect PR. There is not enough difference in the combination of stage and days from oestrus for invivo-derived embryos. These numbers do not belong to a planned experiment. Several management changes during the years were made, which make it very difficult to apply statistical methods to analyse the data correctly. They are used as a tool to make decisions in an attempt to improve future results. Table 1.Pregnancy rate (PR) of virgin heifers (top) and lactating cows (bottom)-fresh (SH) and frozen (OZ) invivo-derived embryo transfer1 Heat-months SH-ST4 SH-ST5 SH-ST6 SH-All OZ-ST4 OZ-ST5 OZ-ST6 OZ-All PR% n PR% n PR% n PR% n PR% n PR% n PR% n PR% n Heifers 6 d-CM 62 934 66 243 68 69 63 1246 56 473 58 219 62 42 57 734 6 d-OM 62 1623 67 489 69 211 64 2323 56 600 55 296 48 137 55 1033 6 d-T 62 2557 67 732 69 280 63 3569 56 1073 57 515 51 179 56 1767 7 d-CM 64 1506 68 495 67 221 65 2222 60 822 62 340 63 156 61 1318 7 d-OM 66 2723 68 1021 69 510 67 4254 57 1120 59 581 57 231 58 1932 7 d-T 66 4229 68 1516 69 731 67 6476 58 1942 60 921 60 387 59 3250 8 d-CM 65 1348 64 518 67 322 65 2188 59 595 64 258 63 108 61 961 8 d-OM 66 2166 68 886 70 510 67 3562 61 770 60 364 51 130 60 1264 8 d-T 66 3514 67 1404 69 832 66 5750 60 1365 62 622 56 238 60 2225 9 d-CM 60 109 56 43 70 20 60 172 60 5 33 6 50 4 47 15 9 d-OM 58 129 63 57 60 40 60 226 63 16 50 18 75 4 58 38 9 d-T 59 238 60 100 63 60 60 398 62 21 46 24 63 8 55 53 All-CM 64 3897 66 1299 67 632 65 5828 58 1895 61 823 63 310 60 3028 All-OM 65 6641 67 2453 69 1271 66 10 365 58 2506 58 1259 53 502 58 4267 All-T 65 10 538 67 3752 69 1903 66 16 193 58 4401 60 2082 57 812 59 7295 Lactating cows 6 d-CM 54 265 48 86 50 12 53 363 38 141 31 77 50 10 36 228 6 d-OM 49 463 52 203 45 56 50 723 46 101 48 54 59 27 48 182 6 d-T 51 728 51 289 46 68 51 1086 41 242 38 131 57 37 42 410 7 d-CM 54 755 59 274 56 103 55 1137 43 928 48 450 43 192 45 1570 7 d-OM 55 914 66 367 54 109 58 1393 46 1052 45 564 47 353 46 1969 7 d-T 55 1669 63 641 55 212 57 2530 45 1980 46 1014 46 545 45 3539 8 d-CM 63 252 68 82 76 33 65 368 48 219 56 80 42 33 50 332 8 d-OM 61 257 64 161 53 47 61 466 50 191 53 77 56 16 51 284 8 d-T 62 509 65 243 63 80 63 834 49 410 55 157 47 49 50 616 All-CM 56 1272 58 442 60 148 57 1868 44 1288 47 607 43 235 45 2130 All-OM 55 1634 62 731 51 212 56 2582 47 1344 46 695 48 396 47 2435 All-T 55 2906 60 1173 55 360 57 4450 45 2632 47 1302 46 631 46 4565 1ST=stage; CM=critical months (June, July, August, September, and October); OM=other months.
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Sood, Mona, Fayaz A. Bhat, Shariq R. Masoodi, Fayaz Ahmad Sofi, Yasmin Sultana Rahman, Moomin Hussain Bhat, Arshad Iqbal Wani, Mir Iftikhar Bashir, M. Ashraf Ganie, and Abdul Hamid Zargar. "A Comparative Analysis of Spectrum and Outcome of Common bacterial Infections in Patients with and without Diabetes-a Prospective Hospital Based Study." JMS SKIMS 21, no. 2 (January 3, 2019): 84–90. http://dx.doi.org/10.33883/jms.v21i2.358.
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Objective: In this prospective study we analyzed clinical spectrum of infections and there outcome in patients with diabetes mellitus and compared it with nondiabeticcontrols admitted in Endocrinology division of a tertiary care hospital.Methods: This was a prospective, longitudinal study of 242 diabetic and non-diabetic subjects. Patients were studied in terms of clinical picture, biochemical, hematological and microbiological profile, type and severity of infection, treatment received, and final outcome. There were 142 diabetic patients in group 1 and 100 nondiabetic patients in group 2 served as control. Study subjects were followed for a median period of one year (52 weeks in diabetics, 65 weeks in non-diabetics) after discharge from the ward.Results: Diabetic patients admitted because of infections were older than their non-diabetic counterparts (74% vs 51%> 50 years; p<0.001) and mounted a less inflammatory response in terms of fever and leucocytosis(55% vs 82%:P<0.001).Urinary tract infections were the commonest infections observed among in-hospital diabetic as well as non-diabetic patients (36% vs. 30%; P>0.3). Diabetics contract some specific infections exclusively, like emphysematous pyelonephritis and foot infections, while respiratory infections were more commonly seen in nondiabetic patients (31% vs. 11%; P<0.001).Staphylococcus aureus was the commonest organism involved in soft tissue and diabetic foot infections (32% vs. 19%; P<0.03). Though mean hospital stay was equal in either group it was significantly longer in diabetic subjects when statistically adjusted for APACHE score.Comparative mortality rates were higher in non-diabetics with in-hospital deaths, followup deaths and total deaths of11%, 6.1% and 17.2% vs 4.9%, 4% and 9.1% respectively but re-infections on follow-up occurred more in diabetics (15% vs.2.6%; P=0.005).Conclusion: Poor glycaemic control and less inflammatory response in terms of fever and leucocytosis, longer hospital stay with increased chances of reinfections are poor prognostic indicators for outcomes in diabetic patients admitted with infections. Urinary tract infections and soft tissue infections particularly foot infectionsare causes of concern in our diabetic patients. JMS 2018: 21 (2):84-90
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Prasad, Narayan, Amit Gupta, Archana Sinha, Anurag Singh, Raj Kumar Sharma, and Anupama Kaul. "Impact of Stratification of Comorbidities on Nutrition Indices and Survival in Patients on Continuous Ambulatory Peritoneal Dialysis." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 29, no. 2_suppl (February 2009): 153–57. http://dx.doi.org/10.1177/089686080902902s30.
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Background Case-mix comorbidities and malnutrition influence outcome in continuous ambulatory peritoneal dialysis (CAPD) patients. In the present study, we analyzed the influence of stratified comorbidities on nutrition indices and survival in CAPD patients. Patients and Methods We categorized 373 CAPD patients (197 with and 176 without diabetes) into three risk groups: low—age under 70 years and no comorbid illness; medium—age 70 – 80 years, or any age with 1 comorbid illness, or age under 70 years with diabetes; high—age over 80 years, or any age with 2 comorbid illnesses. We then compared nutrition indices and malnutrition by subjective global assessment (SGA) between the three groups. Survival was compared using Kaplan–Meier survival analysis. Results Mean daily calorie and protein intakes in the low-risk group (21 ± 6.7 Kcal/kg, 0.85 ± 0.28 g/kg) were significantly higher than in the medium- (17.6 ± 5.2 Kcal/kg, 0.79 ± 0.25 g/kg) and high-risk (17.5 ± 6.1 Kcal/kg, 0.78 ± 0.26 g/kg) groups ( p = 0.001 and p = 0.04 respectively). Relative risk (RR) of malnutrition was less in the low-risk group (103/147, 70.06%) than in the medium-risk group [135/162, 83.3%; RR: 2.0; 95% confidence interval (CI): 2.1 to 3.4; p = 0.01] or the high-risk group (54/64, 84.4%; RR: 2.3; 95% CI: 2.1 to 4.9; p = 0.03). Mean survivals of patients in the low-, medium-, and high-risk groups were 51 patient–months (95% CI: 45.6 to 56.4 patient–months), 43.3 patient–months (95% CI: 37.8 to 48.7 patient–months), and 29.7 patient–months (95% CI: 23 to 36.4 patient–months) respectively (log-rank: 35.9 patient–months; p = 0.001). The 1-, 2-, 3-, 4-, and 5-year patient survivals in the low-, medium-, and high-risk groups were 96%, 87%, 79%, 65%, and 56%; 89%, 67%, 54%, 43%, and 34%; and 76%, 48%, 31%, 30%, and 30% respectively. Conclusions Intake of calories and protein was significantly lower in the medium-risk and high-risk groups than in the low-risk group. Survival was significantly better in low-risk patients than in medium- and high-risk patients.
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Hassan, Raffit, Thierry Marie Jahan, Hedy Lee Kindler, Lyudmila Bazhenova, Martin Reck, Ira Pastan, Alison Ellis, et al. "Amatuximab, a chimeric monoclonal antibody to mesothelin, in combination with pemetrexed and cisplatin in patients with unresectable pleural mesothelioma: Results of a multicenter phase II clinical trial." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 7030. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.7030.
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7030 Background: Amatuximab (MORAb-009) is a chimeric monoclonal antibody to mesothelin, a cell surface glycoprotein highly expressed in many cancers including malignant mesothelioma (MM). Based on safety of amatuximab in phase I clinical trial and pre-clinical studies showing synergy in combination with chemotherapy, a single arm phase II study of amatuximab plus pemetrexed (P) and cisplatin (C) was initiated in pts. with MM. Methods: Eligibility criteria included pts. with unresectable epithelial or biphasic pleural MM, no prior chemotherapy and KPS > 70%. Pts. received amatuximab 5 mg/kg on days 1 and 8 with P 500 mg/m2 and C 75 mg/m2 (PC) given on day 1, of each 21 day cycle for 6 cycles. Pts. with objective response or stable disease received amatuximab monotherapy until disease progression. Primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were overall survival (OS), objective response rate and safety of amatuximab with PC. Results: From 2/2009 to 10/2010, 89 pts. were enrolled at 26 sites. Pt. characteristics: median age 67 yrs. (range 46-80), 78% male, 70% with KPS >90%, 89% epithelial MM, 11% biphasic MM and 88% had stage III/IV disease. Median number of PC plus amatuximab cycles was 5 (range 1-6) and 56 (63%) pts. received single agent amatuximab. In addition to the expected toxicity from PC, hypersensitivity reactions (12.4%; Grade 3/4=4.5%) from amatuximab were noted. By independent radiological review 30 (39%) pts. had partial response and 39 (51%) had stable disease. PFS at 6 months was 52% (95% CI: 39.5-63.5) with a median PFS of 6.1 months (95% CI: 5.4-6.5). As of 1/10/12 the median OS was 14.5 months (95% CI: 12.4-18.5) with 31 pts. still alive and 7 pts. receiving maintenance amatuximab. Conclusions: Amatuximab in combination with PC was generally well-tolerated in this study with 90% of pts. having an objective tumor response or stable disease by independent radiological review. Although PFS is not significantly different from historical results of PC alone, the median OS is 14.5 months with 35% of pts. still alive. Updated OS and biomarker data will be presented at the meeting.
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Secondino, Simona, Andrea Necchi, Giovanni Rosti, Manuela Badoglio, Daniele Raggi, Patrizia Giannatempo, Francesco Lanza, and Paolo Pedrazzoli. "Incidence of secondary malignancies (SM) in patients (pts) with germ cell tumors (GCT) who received high-dose chemotherapy (HDCT): A retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) database." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 4549. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.4549.
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4549 Background: Little is still known about the incidence of SM in young adult pts with GCT after HDCT, owing to the rarity of the disease, and the need for registries with long term follow-up (FUP) data. In Europe, the EBMT may provide a suitable platform for such retrospective analyses. Methods: Criteria for patient selection included diagnosis of GCT, adult male gender, ≥2yr of FUP after the administration of HDCT. Summary statistics were used to describe pt characteristics and outcomes. χ2 tests were used to compare groups according to the length of FUP. Kaplan-Meier estimates were used to estimate overall survival (OS). Univariable Cox regression analyses examined clinical factors potentially associated with OS. Survival times were calculated from the HDCT administration date. To estimate the probability of developing SM, the cumulative incidence of SM was calculated for all pts. Results: From 1981 to 2014, 9,153 autografts, accounting for 5,100 pts, have been registered. Of them, 1,855 had ≥2yr of FUP. Among the latter, a total of 56 cases of SM were identified (3.0%). 28 (50%) had solid SM, 22 (39.3%) hematologic (hem) SM (5 had uncoded SM). Median age at first HDCT was 34 years (IQR: 30-42), median age at development of SM was 42 (37-51). 26 pts (46.4%) received single HDCT cycle, 22 (39.3%) multiple HDCT cycles (8 unknown). 31 pts had ≥5 yr FUP, 25 pts 2-5 yr FUP. The median latency of SM was 3.3yrs (IQR: 1.8-6.1) for hem SM and 5.6yrs (IQR: 1.2-10.8) for solid SM. Median FUP was 6.4yrs. Univariably, the type of SM (solid vs. hem) was significantly associated with OS. Hem vs solid SM: HR: 2.17 (95%CI: 1.19-4.97, p = 0.020). Median OS of pts who developed solid SM was 13.3yrs compared to 4.1yrs of those with hem SM. The retrospective nature of the data is the major limitation. Conclusions: In the largest European database of SM in GCT pts, we observed different trends for SM development according to the SM type. This information may be important for FUP guidelines of these pts. Dataset implementation is ongoing and we will compare the SM incidence from EBMT database with SM rates in the general EU population.
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Takahashi, S., T. Kinoshita, N. Saito, M. Sugitoh, and A. Ochiai. "Assessment of influence of hepatitis B or C virus (HBV or HCV) infection on occurence of colorectal liver metastasis (CLM)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 14559. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.14559.
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14559 Background: Rare occurrence of CLM was reported in patients (pts) with HBV or HCV infection, or liver cirrhosis (LC). However, it is obscure whether HBV or HCV infection itself influence occurrence of CLM irrespective of liver cirrhosis (LC). The aim of this retrospective study was to evaluate correlation between HBV or HCV infection and occurrence of CLM. Methods: Subjects of this study were colorectal carcinomas treated by curative resection at our institution between Nov ’92 and Dec ’01 and fulfilled the following criteria; TNM Stage I-III, histologically confirmed colorectal adenocarcinoma, having definitive results of preoperative tests for HB surface antigen (HBsAg) and HCV antibody, and no LC. Results: A total of 1040 pts met the recruitment criteria. Eleven and 60 pts were positive for HBsAg and HCV antibody respectively. Both HBsAg and HCV antibody were negative in the remaining 969 pts. Comparing characteristics between the infection group and the non-infection group, stage (I/II/III: 19/31/21, 305/306/358), lymph node metastasis (present/absent: 51/20, 607/362), histological type (well, mod/por, others: 62/9, 895/74) depth of tumor (T1,T2/T3,T4: 21/50, 358/611), and preoperative CEA level (ng/ml: 6.5±7.5, 9.2±24.6) did not differ between two groups significantly by the chi-square test (stage, lymph node metastasis, histological type, and depth of tumor) and Mann-Whitney’s U test (CEA). Hepatic function of the infection group was slightly worse than those of the non-infection group by student t-test; alb (g/dl: 3.8±0.5, 4.0±0.4, p<0.01), t-bil (mg/dl: 0.8±0.4, 0.7±0.3, p<0.01). When correlations between hepatic recurrence-free survival and clinicopathological factors were examined, depth of tumor (T3.T4), lymph node metastasis, and alb < 3.8g/dl were the independent poor prognostic factors by the Cox regression model. HBV or HCV infection did not correlate with hepatic recurrence-free survival, recurrence- free survival, or overall survival. Conclusions: HBV or HCV infection does not influence on occurrence of CLM. No significant financial relationships to disclose.
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Meigs, James B., Martin G. Larson, Melvin E. Clouse, David M. Nathan, and Peter WF Wilson. "Coronary Artery Calcification in Type 2 Diabetes and Insulin Resistance: the Framingham Offspring Study." Circulation 103, suppl_1 (March 2001): 1344. http://dx.doi.org/10.1161/circ.103.suppl_1.9999-2.
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0002 Risk for clinical atherosclerosis is increased in people with type 2 diabetes (DM). We assessed subclinical atherosclerosis (SCA) of the coronary arteries using electron beam computed tomography (EBCT) in subjects classified with normal or impaired glucose tolerance (NGT or IGT) or DM, or with or without insulin resistance (IR). Glucose tolerance was categorized by DM therapy (diagnosed [Dx] DM) or with an oral glucose tolerance test (IGT and new DM; 1997 ADA criteria) and IR as >90th percentile fasting insulin in subjects with NGT, in subjects of the Framingham Offspring Study attending the 5th exam (1991-95). A subset free of clinical CVD were selected for EBCT in 1998-99 from age-stratified sex-specific quintiles of the Framingham coronary heart disease risk score. Coronary SCA was quantified by Agatston scores, with the top quartile of score distributions defined as presence of SCA. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for IGT and DM (Dx, new, or both), or IR, predicting SCA. Models were adjusted for age and sex, these and smoking, total/HDL cholesterol ratio and systolic blood pressure, and finally for IGT and DM together with IR. Of 325 subjects aged 31-73 years, 51% were men; 11.2% had IGT and 9.9% had DM (2.8% Dx DM); 14.5% had IR. Compared with NGT, subjects with IGT tended to be more likely (adjusted OR 1.5, 95% CI 0.7-3.4) and those with DM were significantly more likely (2.7, 1.2-6.1) to have coronary SCA. In age-,sex-adjusted models those with IR were more likely to have coronary SCA compared with those without IR (2.1, 1.0-4.2), but further risk factor adjustment weakened this effect. In adjusted models including IR, DM remained associated with risk for coronary SCA, (2.8, 1.2-6.7); Dx DM (6.0, 1.4-25.2) having a larger effect than new DM (2.1, 0.8-5.5). We conclude that subjects with DM have an elevated burden of coronary SCA independent of IR. IR or CVD risk factors may partially explain effects of new DM. Although sample size limits analytic power, there was a trend for subjects with subclinical glucose intolerance to have increased coronary SCA, supporting the hypothesis of a common DM/CVD risk state.
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Brunstein, Claudio G., Daniela Setubal, Marcie Tomblyn, Todd DeFor, Mukta Arora, Linda J. Burns, Jeffrey S. Miller, Daniel J. Weisdorf, and John E. Wagner. "Umbilical Cord Blood Transplant after Reduced Intensity Conditioning Provides Outcomes Comparable HLA-Matched Siblings for Patients with High Risk and Advanced Acute Myeloid Leukemia." Blood 108, no. 11 (November 16, 2006): 606. http://dx.doi.org/10.1182/blood.v108.11.606.606.
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Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is a standard treatment for patients with high risk or advanced AML. However, older age and of co-morbidities frequently limit its use due to high risk of regimen related toxicities (RRT) after a myeloablative regimen. While the inception of RIC regimens has been very successful at reducing RRT, lack of available HLA matched sibling or unrelated donors has become the principal limiting factor. We hypothesized that UCB would increase the utilization of HSCT in patients with AML who lacked a HLA-matched, medically suitable sibling donor. Therefore, we evaluated the various transplant outcomes in 64 AML patients treated with RIC followed by transplantation with HLA-matched sibling PBSC (n=21) and 4–6/6 HLA matched UCB (n=43). All pts received Fludarabine (Flu, 200 mg/kg) and total body irradiation (TBI 200 cGy) with either cyclophosphamide (Cy 50 mg/kg, n=49) or Busulfan (Bu 8 mg/kg, n=15). All pts received cyclosporine A and mycophenolate mofetil GVHD prophylaxis. UCB grafts were composed of 1 (n=15) or 2 (n=28) units to achieve the minimum cell dose. Patients with good and intermediate risk cytogenetics in first complete remission (CR1) were classified as standard risk; others were classified as high risk. Multivariate models considered: donor type, age, disease status, weight, CMV serostatus, cytogenetic risk, disease risk, acute GVHD, conditioning regimen, and time from diagnosis to HSCT. The proportion of engraftment (88% vs. 100%, p=0.10), the incidence of grade II–IV GVHD at day 100 (51% vs. 62%, p=0.85) and TRM at 1 year (28% vs 38%, p=0.43) did not differ between UCB and PBSC recipients. Similarly, relapse at 2 years (UCB 35% vs SIB 35%, p=0.72) and 2 year survival (UCB 31% vs SIB 32%, p=0.62) were comparable. In multivariate analysis, only disease risk group was associated with increased relative risk (RR) of relapse (RR 2.9, 95%CI, 1.3–6.2, p<0.01) and death (RR 2.6, 95%CI, 1.1–5.5, p=0.02). These results demonstrate that partially HLA matched UCB after RIC markedly extends the availability of HSCT with results comparable to those observed with PBSC from HLA matched sibling donors. Variable UCB (n=43) SIB PBSC (n=21) p value * Cell doses of double UCB grafts=combined cell dose. Age in years - median (range) 53 (22–68) 54 (19–69) 0.77 Weight in kg - median (range) 75 (53–120) 72 (51–112) 0.24 Recipient/Donor CMV + 20 (47%)/− 13 (62%)/8 (38%) <0.01 HLA-match 6/6* 5 (7%) 21 (100%) HLA-match 4–5/6* 66 (93%) Zero Disease status CR1 18 (43%) 14 (67%) Cytogenetics good/intermediate 32 (84%) 10 (48%) 0.31 Cytogenetics poor risk 7 (16%) 10 (48%) TNC X10 7/kg median (range)* 3.6 (1.6–5.9) 93.4 (64.8–212.3) CD34 X105/kg median (range)* 4.9 (1.1–18.8) 52.2 (14.1–153.7) Median follow-up in years 2.7 (0.7–5.5) 1.3 (0.7–6.1)
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Johnson, Stephen A., Kamal Shouman, Shahar Shelly, Paola Sandroni, Sarah E. Berini, P. James B. Dyck, Ernest Matthew Hoffman, et al. "Small Fiber Neuropathy Incidence, Prevalence, Longitudinal Impairments, and Disability." Neurology 97, no. 22 (October 27, 2021): e2236-e2247. http://dx.doi.org/10.1212/wnl.0000000000012894.
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Background and ObjectivesThere are limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbid conditions, longitudinal impairments, and disabilities.MethodsTest-confirmed patients with SFN in Olmsted, Minnesota, and adjacent counties were compared 3:1 to matched controls (January 1, 1998–December 31, 2017).ResultsNinety-four patients with SFN were identified, with an incidence of 1.3/100,000/y that increased over the study period and a prevalence of 13.3 per 100,000. Average follow-up was 6.1 years (0.7–43 years), and mean onset age was 54 years (range 14–83 years). Female sex (67%), obesity (body mass index mean 30.4 vs 28.5 kg/m2), insomnia (86% vs 54%), analgesic-opioid prescriptions (72% vs 46%), hypertriglyceridemia (180 mg/dL mean vs 147 mg/dL), and diabetes (51% vs 22%, p < 0.001) were more common (odds ratio 3.8–9.0, all p < 0.03). Patients with SFN did not self-identify as disabled with a median modified Rankin Scale score of 1.0 (range 0–6) vs 0.0 (0–6) for controls (p = 0.04). Higher Charlson comorbid conditions (median 6, range 3–9) occurred vs controls (median 3, range 1–9, p < 0.001). Myocardial infarctions occurred in 46% vs 27% of controls (p < 0.0001). Classifications included idiopathic (70%); diabetes (15%); Sjögren disease (2%); AL-amyloid (1%); transthyretin-amyloid (1%); Fabry disease (1%); lupus (1%); postviral (1%); Lewy body (1%), and multifactorial (5%). Foot ulcers occurred in 17, with 71% having diabetes. Large fiber neuropathy developed in 36%, on average 5.3 years (range 0.2–14.3 years) from SFN onset. Median onset Composite Autonomic Severity Score (CASS) was 3 (change per year 0.08, range 0–2.0). Median Neuropathy Impairment Scale (NIS) score was 2 at onset (range 0–8, change per year 1.0, range −7.9 to +23.3). NIS score and CASS change >1 point per year occurred in only AL-amyloid, hereditary transthyretin-amyloid, Fabry, uncontrolled diabetes, and Lewy body. Death after symptom onset was higher in patients with SFN (19%) vs controls (12%, p < 0.001), 50% secondary to diabetes complications.DiscussionIsolated SFN is uncommon but increasing in incidence. Most patients do not develop major neurologic impairments and disability but have multiple comorbid conditions, including cardiovascular ischemic events, and increased mortality from SFN onsets. Development of large fiber involvements and diabetes are common over time. Targeted testing facilitates interventional therapies for diabetes but also rheumatologic and rare genetic forms.
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Schiffer, Charles A., Jorge E. Cortes, Giuseppe Saglio, Philipp D. le Coutre, Kimmo Porkka, Satu Mustjoki, Hesham Mohamed, and Neil P. Shah. "The Association Of Dasatinib-Induced Lymphocytosis With Treatment Outcome In Patients With Chronic Myeloid Leukemia (CML)." Blood 122, no. 21 (November 15, 2013): 2741. http://dx.doi.org/10.1182/blood.v122.21.2741.2741.
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Abstract Background Clonal proliferation of T/NK cells has been noted after the treatment of CML patients with dasatinib. Previous reports have suggested that persistent expansion of clonal cytotoxic T cells or NK cells in dasatinib-treated patients may be associated with higher response rates and increased occurrence of pleural effusions. This retrospective study analyzed the incidence of lymphocytosis and its association with response, progression-free survival (PFS) and overall survival (OS), and pleural effusion in a large sample of dasatinib-treated patients. Methods Analyses were conducted using dasatinib-treated patients from three large studies with ≥3 years of follow-up: CA180-056 (DASISION), which included 258 dasatinib-treated patients with newly diagnosed CML in chronic phase (CML-CP); CA180-034, which included 662 dasatinib-treated patients with CML-CP who were previously treated with imatinib; and CA180-035, which included 316 dasatinib-treated patients with CML in accelerated phase (CML-AP) and 148 dasatinib-treated patients with CML in myeloid blast phase (CML-MBP) who were previously treated with imatinib. Results Lymphocytosis, as defined by ≥2 consecutive lymphocyte counts > 3600/µl after 28 days of treatment, was present in 33% of patients (85/258) with newly diagnosed CML-CP in DASISION (median time to onset, 4.6 months) and 31% of patients (206/662) with imatinib-resistant or -intolerant CML-CP in CA180-034 (median time to onset, 3.0 months). The median on-treatment follow-up times were 36.8 months and 29.3 months for DASISION and CA180-034, respectively. For CA180-035, the median on-treatment follow-up time was 6.1 months, and lymphocytosis developed in 35% of patients (110/316) with CML-AP and 34% of patients (51/148) with CML-MBP. Lymphocytosis persisted for >12 months in 64% of patients (54/85) with newly diagnosed CML-CP, in 52% of patients (107/206) with imatinib-resistant or -intolerant CML-CP, in 42% (46/110) with CML-AP, and in 18% (9/51) with CML-MBP. The proportion of newly diagnosed patients with complete cytogenetic response (CCyR) or major molecular response (MMR) at any time was higher among those with vs. without lymphocytosis: 89% (76/85) vs. 80% (138/173) for confirmed CCyR and 74% (63/85) vs. 67% (116/173) for MMR. Patients who developed lymphocytosis during treatment with second-line dasatinib were more likely to achieve CCyR, regardless of disease phase; the proportion of patients who achieved CCyR with vs. without lymphocytosis was 62% (127/206) vs. 49% (222/456) for CML-CP, 46% (51/110) vs. 27% (55/206) for CML-AP, and 31% (16/51) vs. 14% (14/97) for CML-MBP. In landmark analyses of patients with CML-CP in DASISION who were still on first-line dasatinib at 3 or 8 months, lymphocytosis status did not significantly affect PFS or OS. Similar results were found in the second-line studies, when considering patients with CML-CP, -AP, or -MBP who were still on study treatment (second-line dasatinib) at 3 months. Pleural effusions (all grades) developed more often in newly diagnosed patients with lymphocytosis (28% [24/85] vs. 16% [27/173] without lymphocytosis) and in imatinib-resistant or -intolerant patients with CML-CP (38% [79/206] vs. 30% [136/456]) or CML-AP (53% [58/110] vs. 31% [64/206]). The proportion of patients with CML-MBP developing pleural effusions was 27%, regardless of the presence of lymphocytosis (14/51 with lymphocytosis and 26/97 without lymphocytosis). Conclusions Lymphocytosis develops very commonly after treatment with dasatinib and persists for >1 year in an appreciable fraction of patients. Immunophenotyping was not done, but it can be presumed that this represents a large granular lymphocyte proliferation in most patients, based on other studies. Lymphocytosis was associated with higher CCyR rates in all stages of CML, as well as higher rates of pleural effusions in CML-CP and -AP. Lymphocytosis was also associated with higher MMR rates in patients with CML-CP receiving first-line dasatinib. There appears to be no significant association, however, between lymphocytosis and PFS or OS in this analysis. Prospective studies are warranted to more carefully characterize the functional activity of these cells and to help assess whether an immunologic effect against CML is detectable in some patients, particularly advanced phase patients with unexpected long responses to treatment with dasatinib alone. Disclosures: Schiffer: Novartis: Consultancy, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Teva: Consultancy; Eisai: Consultancy; Ariad: Research Funding; Pfizer: Research Funding. Cortes:Ariad: Consultancy, Grant to institution Other, Honoraria; BMS: Grant to institution, Grant to institution Other; Novartis: Grant to institution, Grant to institution Other; Pfizer: Consultancy, Grant to institution, Grant to institution Other, Honoraria; Teva: Consultancy, Grant to institution Other, Honoraria; Tragara: Membership on an entity’s Board of Directors or advisory committees; Ambit: Grants/grants pending for institution Other; Astellas: Grants/grants pending for institution, Grants/grants pending for institution Other; Incyte: Grants/grants pending for institution, Grants/grants pending for institution Other; Arog: Grants/grants pending for institution Other; Celgene: Grants/grants pending for institution, Grants/grants pending for institution Other; sanofi: Grants/grants pending for institution, Grants/grants pending for institution Other. Saglio:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. le Coutre:Novartis: Honoraria, Research Funding; BMS: Honoraria; Pfizer: Honoraria. Porkka:BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Mustjoki:BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Mohamed:BMS: Employment, Stock/stock options; travel/accommodations/meeting expenses unrelated to activities listed Other. Shah:BMS: Consultancy, Grants/grants pending to institution for costs related to clinical research Other; Ariad: Consultancy, Grants/grants pending to institution for costs related to clinical research, Grants/grants pending to institution for costs related to clinical research Other.
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Prasad, Vinod K., Premjit Gill, Richard Vinesett, Suhag H. Parikh, Paul Szabolcs, Timothy A. Driscoll, Kristin M. Page, et al. "Single Donor 4/6 Matched Banked Unrelated Cord Blood Is An Effective Graft Source for Children Undergoing Myeloablative Transplantation for Malignant and Nonmalignant Disorders: Single Center Analysis of 318 Patients." Blood 112, no. 11 (November 16, 2008): 1975. http://dx.doi.org/10.1182/blood.v112.11.1975.1975.
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Abstract Background: Despite millions of donors in unrelated registries, many patients, in particular those belonging to ethnic minorities can not find a suitable donor in a timely fashion. In contrast, with an inventory of 250,000 banked cord blood unit, almost every patient will find a 4/6 cord blood unit matched by low resolution HLA-A and –B and high resolution –DRB1 typing. The current study evaluates the outcomes of umbilical cord blood transplants (UCBT) performed using a 4/6 matched donor treated at a single center. Methods: Between August 1993 and November 2007 a total of 318 consecutive pediatric patients (under 21 years old) underwent UCBT from a single 4/6 unit after myeloablative conditioning regimen. The patients were a median of 6.1 (range 0.05–20.33) years and weighed a median of 21.2 (range 3.27–118.4) kg at transplant. Overall, 36.5% (n=116) were girls and 39.2% (n=123) were CMV seropositive. A significant proportion (34.6%) of patient identified as belonging to ethnic and racial minorities. Sixty-five percent (n=205) of the patients had malignant diseases including acute lymphoblastic leukemia (n=87), acute myeloid leukemia (n=58), infant leukemia (n=14), and others (n=46). The nonmalignant patients (n=113) included inherited metabolic disorders (n=75), primary immunodeficiency diseases (n=16), bone marrow failure syndromes (n=11), and others (n=11). The cellular composition of the donor cord blood unit showed a median pre-cryopreservation total nucleated cell (TNC) dose of 6.2×107/kg (range 0.9–38.2), infused TNC of 4.8×107/kg (range 0.5–27.4), infused CD34 of 1.8×105/kg (range 0.02–104.8), and infused CFU of 3.6×104/kg (range 0.0–49.9). Kaplan-Meier estimates of survival were calculated using log-rank test. Descriptive statistics were used for other analyses. Results: The median time to engraftment (ANC>500/mm3 and platelets>50K/uL) were 25 and 83 days. By day 42, 87.4% had achieved ANC>500/mm3 and by day 180, 74.7% had achieved platelets>50K/uL. Acute grades III/IV GvHD developed in 15.5% while the incidence of extensive chronic GvHD at 2 years was 15.2% in evaluable patients. A total of 9.7% of patients had either primary graft failure (n=19) or autologous recovery (n=12). The probabilities of overall survival (OS) are presented in the table. N 1-yr OS 3-yr OS 5-yr OS Diagnosis Group Malignant 205 52% 44% 43% Nonmalignant 113 59% 51% 46% Patient CMV status Positive 123 45% 38% 38% Negative 190 62% 52% 49% TNC cryopreserved x107/Kg <2.5 29 31% 24% 24% 2.5 – 4.99 92 51% 43% 43% 5.0 – 7.5 79 56% 50% 48% > 7.5 118 63% 53% 48% Conclusions: A 4/6 single donor unit is an effective graft source for patients younger than 21 yrs and should be seriously considered if the cryopreserved cell dose is more than 2.5×107TNC/kg. The use of 4/6 matched units will make transplant accessible to many more patients in particular those of ethnic and racial minorities who are unable to find a suitable adult unrelated donor.
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Ансарін Алі Акбар and Джаваді Шалал. "Маскований семантичний/ асоціативний та перекладний праймінг у різних мовах." East European Journal of Psycholinguistics 5, no. 1 (June 30, 2018): 7–15. http://dx.doi.org/10.29038/eejpl.2018.5.1.ans.
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Статтю присвячено спробі дослідити двомовний ментальний лексикон. Головне питання дослідження – встановити, чи персько-англійські білінгви можуть досягнути ефекту семантичного / асоціативного або перекладацького праймінгу. Для відповіді на це питання було застосовано масковану праймінгову парадигму як техніку, що відображає автоматичні когнітивні процеси, що тривають під час семантичної обробки, а не стратегічного використання прайму. Із метою вирішення лексичного завдання було сформовано чотири типи цільових пар праймінгу (перекладацькі еквіваленти, семантично подібні, асоціативно та семантично пов’язані пари). Загалом у дослідженні взяло участь 85 персько-англійських білінгвів. Хоча ефекту праймінгу не було виявлено для перших трьох груп, респонденти із семантично пов’язаних пар (найміцніше пов’язаних слів) відповіли приблизно на 29 мс швидше. Результати засвідчили, що білінгви мають спільні уявлення для асоціативних семантично пов’язаних слів. Отже, навчання новим словам другої мови, шляхом поєднання їх із асоціативно пов’язаними словами першої мови, може привести до кращих результатів.
Література
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Sorror, Mohamed L., Barry Storer, Brenda M. Sandmaier, Leanthe Braunert, Ginna G. Laport, Thomas Chauncey, Christopher Bredeson, et al. "Impacts of Cytogenetic Abnormalities and Prior Alemtuzumab on Outcomes of Patients (pts) with High-Risk Chronic Lymphocytic Leukemia (CLL) Given Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation (HCT)." Blood 116, no. 21 (November 19, 2010): 2364. http://dx.doi.org/10.1182/blood.v116.21.2364.2364.
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Abstract Abstract 2364 Allogeneic HCT using nonmyeloablative regimens may provide long-term remission in high-risk relapsed CLL. Here, we investigated the impact of histology, disease status, lymph node (LN) size, genomic aberrations, donor type, and prior alemtuzumab on outcomes. Pts (n=136) were conditioned with 2Gy TBI alone (12%) or 2Gy TBI plus 90 mg/m2 fludarabine (88%). Median age was 56 (range 42–72) years and median number of prior regimens was 4. Ninety percent of pts had fludarabine-refractory CLL. Incidences of grades II, III, and IV acute GVHD were 39%, 14%, and 2% respectively, and chronic extensive GVHD was 51%. Complete (CR) and partial remissions (PR) were seen in 55% and 15% of pts, respectively. Estimated 5-years rates of non-relapse mortality (NRM), progression/relapse, OS, and progression-free survival (PFS) were 32%, 36%, 41%, and 32%, respectively. Overall, 58 pts are alive; 45 in CR, 5 in PR, 5 with stable disease, and 3 with progression (PD)/relapse. Univariate outcomes (Table 1) were not statistically significantly different between donor types for NRM (p=0.37), relapse (p=0.17), or PFS (p=0.88). Pts with CLL and SLL had comparable rates of relapse and PFS. Disease status at HCT had no impact on NRM (p=0.75), relapse (p=0.31), or PFS (p=0.27). Relapse (p=0.51) and PFS (p=0.45) were not statistically significantly different among the 6 groups of cytogenetic abnormalities (Table 1). Both alemtuzumab within 12 months before HCT (53% vs. 31%, p=0.007, Figure) and LN size ≥5 cm (59% vs. 28%, p=0.003) were associated with increased rates of relapse. In Cox regression model for outcomes, prior alemtuzumab (HR: 2.20, p=0.02) and LN size ≥5 cm (HR: 2.21, p=0.02) were independently associated with increased relapse; while donor type, cytogenetic abnormalities, and disease status were not. PFS was also worse for pts with prior alemtuzumab (HR: 1.55, p=0.09) and LN size ≥5 cm (HR: 1.64, p=0.06). In multivariate models, pts who had alemtuzumab within 3 months prior to HCT appeared to have the highest relapse risk (Table 2). Prior alemtuzumab had no impact on CD3 donor chimerism following HCT. Further studies are warranted to explore whether the negative impact of alemtuzumab on relapse was due to unrecognized high-risk disease features or hampering the quality of graft-versus-tumor effects such as by deletion of host dendritic cells (Blood. 2002; 99: 2586). Allogeneic nonmyeloablative HCT is associated with graft-versus-leukemia effects even against chemo-refractory and high cytogenetic-risk diseases. We currently are studying novel approaches to better debulk disease before HCT and/or to augment graft-versus-leukemia effects after HCT for CLL pts with large LN size. Table 1: Univariate outcomes in 136 patients with CLL receiving nonmyeloablative HCT 5 year outcomes (%) Factor Group N NRM Rel PFS Donor HLA-matched related 75 26 43 31 HLA-matched unrelated 53 42 24 34 HLA-antigen mismatched 8 15 56 29 p-value 0.37 0.17 0.88 Disease status at HCT Chemo-responsive 55 31 32 38 Chemo-refractory 72 32 41 27 Untested relapse 9 36 22 42 p-value 0.75 0.31 0.27 Cytogenetic abnormalities Normal 39 42 25 34 Del17p 24 49 32 18 Del11q 19 31 40 29 Tri12 10 20 40 40 Del13q 18 17 43 40 Other 26 21 47 33 p-value 0.25 0.51 0.45 Alemtuzumab within 12 months before HCT No 103 34 31 35 Yes 33 22 53 25 p-value 0.80 0.01 0.07 LN size <5 cm 36 30 28 39 ≥5 cm 100 33 59 11 p-value 0.95 0.003 0.01 Note: p-values reflect underlying hazard ratios over all follow-up period. Table 2: Impact of prior alemtuzumab on relapse after allogeneic HCT Alemtuzumab prior to HCT Number of pts Relapse rate at 5-years, % Univariate HR p-value Multivariate HR* p-value No or beyond 12 months 103 31 1.0 1.0 Within 3 months 11 58 2.49 0.04 3.36 0.02 Within 3.1-6 months 13 46 2.43 0.07 2.29 0.10 Within 6.1-12 months 9 49 2.2 0.14 1.32 0.65 * Adjusted for genomic features, lymph node size, disease status at HCT, and donor type. Figure: Relapse rate of 53% vs. 31% (p=0.007) among 136 CLL pts who did or did not receive alemtuzumab within 12 months prior to nonmyeloablative HCT. Adjustment for pre-transplant risk factors did not change the significant difference in relapse rate between the two groups. Figure:. Relapse rate of 53% vs. 31% (p=0.007) among 136 CLL pts who did or did not receive alemtuzumab within 12 months prior to nonmyeloablative HCT. Adjustment for pre-transplant risk factors did not change the significant difference in relapse rate between the two groups. Disclosures: Off Label Use: All discussions about therapeutics used for HCT preparative regimens are off-label.
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Søndergaard, Jens, Helene Nordahl Christensen, Rikke Ibsen, Dorte Ejg Jarbøl, and Jakob Kjellberg. "Healthcare resource use and costs of opioid-induced constipation among non-cancer and cancer patients on opioid therapy: A nationwide register-based cohort study in Denmark." Scandinavian Journal of Pain 15, no. 1 (April 1, 2017): 83–90. http://dx.doi.org/10.1016/j.sjpain.2017.01.006.
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AbstractBackground and aimOpioid analgesics are often effective for pain management, but may cause constipation. The aim of this study was to determine healthcare resource use and costs in non-cancer and cancer patients with opioid-induced constipation (OIC).MethodsThis was a nationwide register-based cohort study including patients ≥18years of age initiating ≥4 weeks opioid therapy (1998–2012) in Denmark. Ameasure of OIC was constructed based on data from Danish national health registries, and defined as ≥1 diagnosis of constipation, diverticulitis, mega colon, ileus/subileus, abdominal pain/acute abdomen or haemorrhoids and/or ≥2 subsequent prescription issues of laxatives. Total healthcare resource utilization and costs (including pharmacy dispense, inpatient-, outpatient-, emergency room- and primary care) were estimated according to OIC status, opioid treatment dosage and length, gender, age, marital status, and comorbidities using Generalised Linear Model.ResultsWe identified 97 169 eligible opioid users (77 568 non-cancer and 19 601 patients with a cancer diagnosis). Among non-cancer patients,15% were classified with OIC,10% had previous constipation, and 75% were without OIC. Patients characteristics of non-cancer OIC patients showed a higher frequency of strong opioid treatment (69% versus 41%), long-term opioid treatment (1189 days versus 584 days), advanced age (73 years versus 61 years), and cardiovascular disease (31%versus 19%) compared to those without OIC (P < 0.001 for all comparisons). Non-cancer patients with OIC had 34% higher total healthcare costs compared to those without OIC (P < 0.001) after adjusting for age, gender, opioid usage, marital status and comorbidities. Among cancer patients, 35% were classified with OIC,14% had previous constipation, and 51% were without OIC. A higher proportion of cancer patients with OIC were continuous opioid users (85% versus 83%) and strong opioid users (97% versus 85%), compared to those without OIC (P <0.001 for both comparisons). Further, the mean number of days on opioids were higher for cancer patients with versus without OIC (329 days versus 238 days, P < 0.001). Total healthcare costs were 25% higher for cancer patients with versus without OIC (P < 0.001) after adjusting for age, gender, opioid usage, marital status and comorbidities.ConclusionsThe results of this nationwide study based on real life data suggested that both non-cancer patients and cancer patients suffering from opioid-induced constipation (OIC) may have higher healthcare resource utilization and higher associated costs compared to those without OIC.ImplicationsReducing the number of OIC patients has potential cost savings for the health care system. Special attention should be on patients at potential high risk of OIC, such as strong and long-term opioid treatment, advanced age, and concomitant cardiovascular disease.
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Olthof, Nick A., Michel W. Coppieters, G. Lorimer Moseley, Michele Sterling, Dylan J. Chippindall, and Daniel S. Harvie. "Modernising tactile acuity assessment; clinimetrics of semi-automated tests and effects of age, sex and anthropometry on performance." PeerJ 9 (October 25, 2021): e12192. http://dx.doi.org/10.7717/peerj.12192.
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Background Reduced tactile acuity has been observed in several chronic pain conditions and has been proposed as a clinical indicator of somatosensory impairments related to the condition. As some interventions targeting these impairments have resulted in pain reduction, assessing tactile acuity may have significant clinical potential. While two-point discrimination threshold (TPDT) is a popular method of assessing tactile acuity, large measurement error has been observed (impeding responsiveness) and its validity has been questioned. The recently developed semi-automated ‘imprint Tactile Acuity Device’ (iTAD) may improve tactile acuity assessment, but clinimetric properties of its scores (accuracy score, response time and rate correct score) need further examination. Aims Experiment 1: To determine inter-rater reliability and measurement error of TPDT and iTAD assessments. Experiment 2: To determine internal consistencies and floor or ceiling effects of iTAD scores, and investigate effects of age, sex, and anthropometry on performance. Methods Experiment 1: To assess inter-rater reliability (ICC(2,1)) and measurement error (coefficient of variation (CoV)), three assessors each performed TPDT and iTAD assessments at the neck in forty healthy participants. Experiment 2: To assess internal consistency (ICC(2,k)) and floor or ceiling effects (skewness z-scores), one hundred healthy participants performed the iTAD’s localisation and orientation tests. Balanced for sex, participants were equally divided over five age brackets (18–30, 31–40, 41–50, 51–60 and 61–70). Age, sex, body mass index (BMI) and neck surface area were assessed to examine their direct (using multiple linear regression analysis) and indirect (using sequential mediation analysis) relationship with iTAD scores. Results Mean ICC(2,1) was moderate for TPDT (0.70) and moderate-to-good for the various iTAD scores (0.65–0.86). The CoV was 25.3% for TPDT and ranged from 6.1% to 16.5% for iTAD scores. Internal consistency was high for both iTAD accuracy scores (ICC(2,6) = 0.84; ICC(2,4) = 0.86). No overt floor or ceiling effects were detected (all skewness z-scores < 3.29). Accuracy scores were only directly related to age (decreasing with increasing age) and sex (higher for men). Discussion Although reliability was similar, iTAD scores demonstrated less measurement error than TPDT indicating a potential for better responsiveness to treatment effects. Further, unlike previously reported for TPDT, iTAD scores appeared independent of anthropometry, which simplifies interpretation. Additionally, the iTAD assesses multiple aspects of tactile processing which may provide a more comprehensive evaluation of tactile acuity. Taken together, the iTAD shows promise in measuring tactile acuity, but patient studies are needed to verify clinical relevance.
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Eggermont, Alexander M., Andrey Meshcheryakov, Victoria Atkinson, Christian U. Blank, Mario Mandalà, Georgina V. Long, Catherine Barrow, et al. "Crossover and rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-MG/Keynote-054 phase 3 trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 9500. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9500.
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9500 Background: The phase 3 double-blind EORTC 1325/KEYNOTE-054 trial evaluated pembrolizumab (pembro) vs placebo in stage III cutaneous melanoma patients (pts) with complete resection of lymph nodes. Pembro improved RFS (hazard ratio [HR] 0.57) and DMFS (HR 0.60) (Eggermont, NEJM 2018, TLO 2021). In the pembro group, the incidence of immune related AE (irAE) grade 1-5 was 37%, and of grade 3-5 was 7%. We present the safety profile, response rate and PFS for the subset of pts who had a recurrence and crossed over or were rechallenged with pembrolizumab, within protocol. Methods: Pts were randomized to receive iv. pembro 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year). Upon recurrence with no brain metastases, pts with an ECOG PS 0-2 were eligible to enter part 2 of the study, i.e. to receive pembro 200 mg iv. every 3 weeks for a maximum of 2 years, for crossover (those who received placebo) or rechallenge (those who recurred ≥6 months after completing one year of pembro therapy). Treatment was stopped in case of disease progression (RECIST 1.1) or unacceptable toxicity. Results: At the clinical cut-off (16-Oct-2020), 298 (59%) pts had a disease recurrence in the placebo group; 155 pts participated in the crossover part 2 of the trial. A total of 297 (58%) pts completed the 1-yr pembro adjuvant treatment, of whom 47 had a recurrence ≥6 mths from the stop of treatment and 20 entered in the rechallenge part of the trial. Among 175 pts who started pembro in Part 2, 160 discontinued due to completion of therapy (N=24), disease progression (N=88), toxicity (N=20), investigator's decision (N=21), or other reason (N=7); 15 pts were still on-treatment. Results for the 2 groups are provided in the table. The median number of doses was 12 and 5.5, respectively (resp), and the median follow-up was 41 and 19 mts, resp. Among the 175 pts, 51 (29%) had a grade 1-4 irAE (by group: 47 [30%] and 4 [20%] resp) and 11 (6%) a grade 3-4 irAE. Conclusions: Pembrolizumab treatment after crossover yielded a 39% ORR in evaluable pts and an overall 3-yr PFS of ̃32%, but after rechallenge the efficacy was lower. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA The median PFS (95% CI) from start of Part 2 was 14 (5-27) and 8 (5-15) mts for stage III-resected and III/IV various, resp. Among the 80 stage IV crossover pts with evaluable disease, 31 (39%) had an objective response: 14 (18%) CR, 17 (21%) PR. The 2-yr PFS rate from response was 69% (95% CI 48-83%). For these 80 pts, the median PFS was 6.1 mts and the 3-yr PFS rate was 31% (95% CI 21-41%). Among 9 stage IV rechallenged pts with an evaluable disease, 1 (11%) reached CR, 3 had SD and 5 PD. Clinical trial information: NCT02362594. [Table: see text]
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Sultana, S., Z. Zeba, A. Hossain, A. Khaleque, R. Zinnat, and L. Ali. "Serum Proinsulin in Bangladeshi Subjects with Impaired Glucose Tolerance." Bangladesh Journal of Medical Biochemistry 7, no. 2 (February 26, 2015): 41–46. http://dx.doi.org/10.3329/bjmb.v7i2.22411.
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Hyperproinsulinemia is commonly present in subjects with impaired glucose tolerance. The present study was undertaken to investigate the proinsulin level in Bangladeshi IGT subjects and to explore its association with insulin resistance. This observational study was conducted under a case-control design with IGT subjects (n=50) and controls (n=44). IGT was diagnosed following the WHO Study Group Criteria. Serum glucose was measured by glucose-oxidase method, serum lipid profile by enzymatic method and serum insulin and serum proinsulin were measured by ELISA method. Insulin secretory capacity (HOMA%B) and insulin sensitivity (HOMA%S) were calculated from fasting serum glucose and fasting serum insulin by homeostasis model assessment. The study subjects were age- and BMI- matched. Mean (±SD) age (yrs) of the control and IGT subjects were 40±6 and 40±5 respectively (p=0.853). Mean (±SD) BMI of the control and IGT subjects were 23±3 and 22±2 respectively (p=0.123). Fasting glucose was not significantly higher in IGT subjects, but serum glucose 2 hours after 75 gm glucose load was significantly higher in IGT subjects. Median (Range) value of fasting serum glucose (mmol/l) of control and IGT subjects were 5.3 (3.8-6) and 5.2 (4-12) respectively; (p=0.297). Median (Range) value of serum glucose (mmol/l) 2 hours after 75 gm glucose load of control and IGT subjects were 6.1 (3-7.8) and 7.9 (5- 21) respectively; (p=0.001). Fasting TG was significantly higher in IGT subjects and LDL-c was significantly lower in IGT subjects. Serum Total cholesterol and HDL-c were not significantly different between the IGT and control subjects. Median (Range) value of fasting serum TG (mg/dl) of control and IGT subjects were 119 (51-474) and 178 (82-540) respectively; (p=0.001). Median (Range) value of fasting serum T chol (mg/dl) of control and IGT subjects were 180 (65-272) and 186 (140-400) respectively; (p=0.191). Median (Range) value of fasting serum HDL-C (mg/dl) of control and IGT subjects were 29 (19-45) and 31 (15-78) respectively; (p=0.914). Median (Range) value of fasting serum LDL-C (mg/dl) of control and IGT subjects were 117(29-201) and 111(41- 320) respectively; (p=0.001). Fasting serum proinsulin was significantly higher in IGT subjects. Median (Range) value of fasting serum proinsulin (pmol/l) of control and IGT subjects were 9.2(1.8-156) and 17(3-51) respectively; (p=0.001). Insulin secretory capacity (HOMA%B) was higher but insulin sensitivity (HOMA%S) was significantly lower in case of IGT subjects. Median (Range) value of HOMA%B of control and IGT subjects were 97(46-498) and 164(17-300) respectively; (p=0.001). Median (Range) value of HOMA%S of control and IGT subjects were 68(19-270) and 39(15-110) respectively (p=0.001). In multiple regression analysis a significant negative association was found between fasting proinsulin and insulin sensitivity (p=0.037). The data led to the following conclusions: a) Insulin resistance is the predominant defect in Bangladeshi IGT subjects. b) Basal proinsulin level is significantly increased in IGT subjects. c) Insulin resistance is negatively associated with serum proinsulin in IGT subjects. DOI: http://dx.doi.org/10.3329/bjmb.v7i2.22411 Bangladesh J Med Biochem 2014; 7(2): 41-46
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Cappellini, Maria Domenica, Mohsen Saleh Elalfy, Antonis Kattamis, John F. Seymour, Chan Lee Lee, John B. Porter, Amal El-Beshlawy, et al. "Efficacy and Safety of Once-Daily, Oral Iron Chelator Deferasirox (Exjade®) in a Large Group of Regularly Transfused Patients with β-Thalassemia Major." Blood 112, no. 11 (November 16, 2008): 3878. http://dx.doi.org/10.1182/blood.v112.11.3878.3878.
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Abstract Background: The 1-year, prospective, multicenter EPIC trial, the largest ever conducted for an iron-chelating agent, evaluated the efficacy and safety of the once-daily, oral chelator deferasirox (Exjade®) in patients (pts) with transfusion-dependent anemias. 54% of 1744 pts had β-thalassemia major, providing one of the largest data sets assessing the use of deferasirox in this group. Data from this subgroup are presented. Methods: Pts (≥2 years old) with transfusional iron overload due to β-thalassemia and serum ferritin (SF) levels of ≥1000 ng/mL or <1000 ng/mL but with a history of multiple transfusions (>20 transfusions or 100 mL/kg of blood) and R2 MRI-confirmed liver iron concentration >2 mg Fe/g dry weight, received an initial deferasirox dose of 10–30 mg/kg/day dependent on transfusion requirements. Protocol-specified dose adjustments in steps of 5–10 mg/kg/day (range 0–40 mg/kg/day) were done every 3 months based on SF trends and safety markers. The change at week 52 from baseline (BL) was the primary efficacy endpoint. Results: 937 pts with β-thalassemia major, 450 males and 487 females (mean age 18.4±10.8 years), were enrolled. Median BL SF was 3157 ng/mL (range 462–22320). In the year prior to enrollment, pts received a mean of 189.8 mL/kg of blood (range 0–1768). Most pts (n=625; 66.7%) had received deferoxamine (DFO); 234 (25.0%) DFO/deferiprone combination, 12 (1.3%) deferiprone alone and four (0.4%) other therapy; 66 (7.0%) were chelation naive. 798 pts (85%) started on ≤20 mg/kg/day and 139 (15%) on >20 mg/kg/day. 51% required a dose increase at a median of 24 weeks after treatment initiation (range 2–53). After 1 year, median SF significantly decreased from BL by 129 ng/mL (P=0.0007) at an average actual dose of 24.2±5.6 mg/kg/day. Pts receiving an average actual dose of ≥30 mg/kg/day achieved a significant reduction in SF at 1 year. Pts receiving an average actual dose of <20 or ≥20–<30 mg/kg/day maintained their iron balance. SF change by mean actual dose received is shown in Table 1. The magnitude of reduction in SF was reflective of dose adjustments throughout the study. Table 1. Median change from BL in SF (ng/mL) by average actual dose received BL End of study Average actual dose categories Mean iron intake, mg/kg/day n Median SF n Median change from BL in SF P -value versus BL <20 mg/kg/day 0.38 193 2318 187 −14 0.67 ≥20–<30 mg/kg/day 0.46 614 3108 611 −45 0.56 ≥30 mg/kg/day 0.35 130 5154 130 −962 <0.0001 All pts 0.43 937 3157 928 −129 0.0007 Only 9.5% of pts (n=89) discontinued therapy. Reasons for withdrawal were AEs (n=31, 3.3%), consent withdrawal (n=24, 2.6%), unsatisfactory therapeutic effect (n=12, 1.3%), lost to follow-up (n=5, 0.5%), death (n=4, 0.4%, three due to cardiac failure and one to septicemia following surgery, none treatment related by investigators’ assessment) and other (n=13, 1.4%). The most common investigator-assessed drug-related AEs were rash (n=115, 12.3%), diarrhea (n=76, 8.1%) and abdominal pain (n=50, 5.3%). The majority of AEs were mild-to-moderate (>95%). Thirty-seven pts (3.9%) had serum creatinine >33% above BL and the upper limit of normal (ULN) on two consecutive visits; there were no progressive increases. Five (0.5%) pts had an increase in alanine aminotransferase >10×ULN on two consecutive visits; levels were already elevated in four pts. Conclusions: These data confirm that in heavily iron-loaded pts with β-thalassemia major, higher deferasirox doses are needed to achieve significant reductions in SF, while lower doses are able to maintain iron balance. The starting dose guided by the rate of iron intake from blood transfusions and current iron burden should be titrated individually and promptly (at 3 months) according to SF trends and safety markers. Deferasirox treatment in this subgroup was generally well tolerated (including doses ≥30 mg/kg/day) with a low discontinuation rate.
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Schneider, Friederike, Annika Dufour, Tobias Benthaus, Stephanie Schneider, Gudrun Mellert, Evelyn Zellmeier, Stefan K. Bohlander, et al. "A New Molecular and Clinical Prognostic Score for Risk Stratification in CN-AML." Blood 114, no. 22 (November 20, 2009): 2635. http://dx.doi.org/10.1182/blood.v114.22.2635.2635.
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Abstract Abstract 2635 Poster Board II-611 Background: Cytogenetically normal acute myeloid leukemia (CN-AML) is associated with an intermediate outcome. A number of clinical and molecular risk factors have been characterized pointing to the heterogeneity of this group. The purpose of the study was to define a prognostic model based on pre-treatment patient characteristics to facilitate choice of therapy by definition of patient groups with different prognoses. Patients and methods: We evaluated four molecular markers (mutations of NPM1, CEBPA, MLL-PTD; FLT3-ITD mutant level; interaction term NPM1 and FLT3-ITD mutant level) and nine clinical parameters (white blood count (WBC), platelet count, hemoglobin level, lactase dehydrogenase (LDH) level, bone marrow blasts, de novo AML vs. non de novo AML, performance status, sex and age) at initial diagnosis in 648 patients with CN-AML treated in the AMLCG (German AML Cooperative Group) 1999 trial. The outcome parameter overall survival (OS) was calculated from randomization to death from any cause or to the latest follow-up date. Event-free survival (EFS) was defined as the period from the start of therapy until lack of a complete remission (CR), relapse of AML after CR or death without relapse. Relapse-free survival (RFS) was determined for responders from the first day of a CR until relapse or death without relapse. Univariate and multivariate Cox regression analyses for OS were performed. All parameters with p'0.05 in multivariate analyses after backward elimination and their regression coefficients were applied in the prognostic score. The minimal p-value approach was used to identify the risk groups with the greatest differences in OS. Results: In our patient cohort 84% had de novo AML. Median age was 60 years (17–85 years) and 70% had an ECOG score ≤1. Median platelet count was 57 G/l (5–643 G/l), median WBC was 18 G/l (0.1–798 G/l) and median hemoglobin level was 9.2 g/dl (4.2–16.4 g/dl). Mutations of NPM1, FLT3-ITD, MLL-PTD and CEBPA were present in 51%, 27%, 8% and 10% of patients, respectively. Median FLT3-ITD mutant level in FLT3-ITD mutated patients was 0.42 (0.02–1.00). Of 648 patients 377 had died. Median OS was 20 months with a median follow-up of 45 months. In the multivariate analyses for OS, the following parameters were significant: age (+10, years, HR: 1.3, p<0.001), WBC (10 fold, ×109/l, HR: 1.4, p<0.001), NPM1 (mutation vs. wild-type, HR: 0.35, p<0.001), CEBPA (mutation vs. wild-type, HR: 0.47, p=0.001), interaction term NPM1/FLT3-ITD mutant level (+1, HR: 4.5, p=0.006), performance status (ECOG 0,1 vs. ECOG 2-4, HR: 1.4, p=0.006) and platelet count (10 fold, ×109/l, HR: 0.70, p=0.016). After calculation of the prognostic score for each patient and definition of two cutpoints, we could identify three risk groups (median OS (N=590): not reached (n=169) vs. 22.7 months (n=220) vs. 8.4 months (n=201), p<0.001; median EFS (N=583): 42.3 months (n=168) vs. 7.6 months (n=216) vs. 3.2 months (n=199), p<0.001; median RFS (N=383): not reached (n=136) vs. 15.3 months (n=143) vs. 7.6 months (n=104), p<0.001). Furthermore this model was valid in both age subgroups (<60 years / ≥60 years). Interestingly, a subset of 31% of patients within the molecular favorable NPM1+/FLT3-ITD- risk group were assigned to the intermediate group according to our prognostic score and 31% of the low risk group were not NPM1+/FLT3-ITD-. Conclusions: We propose a new prognostic score based on pre-therapeutic clinical and well-established molecular markers that could be easily applied in the routine patient care setting for risk stratification and risk-adapted therapy. Further prospective validation is required to confirm the clinical relevance of this score. Disclosures: Unterhalt: Roche: travel support. Hoster:Roche: travel support.
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Sharma, Sanjeevan, Uday Yanamandra, Mir Moslem, Rajan Kapoor, Suman Pramanik, Rajiv Kumar, Harshit Khurana, et al. "Ph Positive ALL: Real World Experience from a Tertiary Care Center in North India." Blood 132, Supplement 1 (November 29, 2018): 5901. http://dx.doi.org/10.1182/blood-2018-99-117861.
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Abstract Introduction: The outcomes of Philadelphia positive acute lymphoblastic leukemia(Ph-ALL) have improved significantly after the introduction of tyrosine kinase inhibitors (TKI). The presence of Philadelphia positivity once considered as poor prognosis mandating transplantation, now even can be managed with TKI added to steroids. The data is scarce on Ph-ALL from real-world settings with resource constraints. Objective: To study the characteristics and outcomes of Ph+ve ALL from real world settings. Methodology: It is a retrospective observational study wherein the data of all patients of Ph-ALL managed at a tertiary care center in North India over the last 14 years (2004-2018) were analyzed. All case records of the Ph-ALL were perused, digitalized and their survival statistics derived. Results:Amongst a total of 611 ALL case records, 55 (9%) were Ph-ALL. Ph-ALL cases with complete data (n-51) were analysed for overall survival. The mean age of the patients was 31± 2.41 years (range 3-76) (Fig. 1A). Males constituted 74.5% (n-38) and females, 25.4% (n-13) of our cohort. On risk stratification, 11 (21.5%), 5 (9.8%), and 35 (68.6%) patients were classified as standard, intermediate and high risk. Twenty five percent patients had associated complex karyotype in addition to the Ph positivity. Of these 24 patients (47.05%) received adult ALL (GMALL protocol), 15 patients (29.4%) received paediatric BFM protocol, and12 patients (23.5%) received Hyper-CVAD. Week 4 Bone marrow evaluation was in CR in 87.2% of patients. L-Asparaginase was given in only 60% of the patients. An interruption in the therapy of more than 2 weeks for various reasons was present in 23.4% of the patients, mainly secondary to infections. Prophylactic cranial irradiation was given in 34.7% of the patients and high dose methotrexate was given in 30.4% of the patients. Relapse was seen in 22% of the patients. CNS disease was present in 17.6% of the patients. Only 19.6% of the patients were subjected to transplant. All patients received TKI, of which 44% received high dose imatinib and 56% patients received dasatinib. A total of 19.6% patients succumbed to the illness at various stages of the therapy. The cumulative overall survival at 1y (1y-OS) was 95.68% with 3y and 5y OS being 72.09% and 63.07% (Fig. 1B). The survival was not statistically different between patients with and without complex karyotype (p-0.52),based on type of TKI administered (Dasatinib Vs high dose Imatinib) (p-0.76), males and females (p-0.41), risk category (p-0.41) or by the presence of CNS disease (p-0.21) (Fig. 1C-G). The survivals based on the type of protocol was statistically different with the best survival with GMALL protocol and the least survival with Hyper-CVAD therapy (log rank p<0.001)(Fig. 1H). Conclusion: We have demonstrated in this study the improved outcomes of Ph-ALL who usually present late in resource constraint settings. There was no additional benefit of dasatinib over high dose imatinib in this cohort. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
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Castagna, Luca, Sabine Furst, Thomas Prébet, Jean El Cheikh, Aude Charbonnier, Catherine Faucher, Mohamad Mohty, Norbert Vey, and Didier Blaise. "Tandem Auto-Allo in Acute Myeloid Leukemia (AML) Patients in First Complete Remission (CR)." Blood 114, no. 22 (November 20, 2009): 3355. http://dx.doi.org/10.1182/blood.v114.22.3355.3355.
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Abstract Abstract 3355 Poster Board III-243 Background. High and intermediate risk AML can benefit by allogeneic stem cell transplantation in first CR. The use of reduced intensity conditioning regimens (ALLO-RIC) decreases the toxicity even if the relapse rate is more pronounced. To contrast the high relapse rate we hypothyzed that if a better quality of remission could be achieved, the relapse incidence could be lowered. Patients and methods. From 2001 to 2008, 31 AML patients in first CR received a tandem auto-allo program. The median number of white blood cell was 3 × 10e9/l (range 0.9-235), 13% of patients have extramedullary localisations. In 13% AML was secondary to previous CT treatment. Cytogenetic was abnormal in 36% of pts. After one or two induction chemotherapies (CT), all but two patients received a consolidation course with high-dose cytarabine (HD-ARAC) CT, followed by autologous stem cell harvest. Then, HD melphalan (HD-PAM 140 mg/m2) followed by autologous stem cells reinfusion was administered, followed by ALLO-RIC. RIC consisted of fludarabine plus (2 Gy) TBI (3 pts) or fludarabine, oral or intravenous busulfan (8 mg/kg) in two days, and anti thymocyte globulin (2.5 or 5 mg/kg). Graft versus host disease (GVHD) prophylaxis was cyclosporine (CyA) plus mycofenolate mofetil (3 pts) or CyA alone (28 pts). Donors were all but one HLA identical sibling. The median number of allogeneic CD34+ and CD3+ cells was 6.1 × 10e6/Kg (range 1.9-11) and 315 (range 166-609). Prognostic scores (HCT-CI, PAM, EBMT) were retrospectively calculated for each patient. All pts have a performance status ≥ 90%. Results. The median follow-up was from diagnosis and ALLO-RIC 40 and 34 months, respectively. The median time between last CT and HD-PAM was 51 days (range 30-77) and HD-PAM and ALLO-RIC was 69 days (55-176). Treatment related mortality after HD-PAM was null. Prognostic scores were: HCT-CI score 0-2= 53% (16 pts), ≥3= 47% (14 pts), 1 pt not evaluable; PAM score 9-16= 30% (10 pts), 17-23= 67% (19 pts), 24-30= 3% (1 pt); EBMT score 1= 9% (3 pts), 2= 78% (24 pts), 3= 13% (4 pts). At last follow-up, 42% of pts (n= 13) died: 5 due to disease relapse and 8 because of toxicity. Grade II-IV acute GVHD and chronic GVHD incidence were respectively 26% and 65% (extensive 84%). GVHD was the cause of death in seven pts. Six pts (19%) reactived CMV, without disease, and 1 pt not survived to an interstitial pneumonitis. The 5-year overall survival (OS), relapse free survival (RFS), and 1-year TRM were 60%, 60%, and 15%, respectively. In multivariate analysis, prognostic scores did not influence TRM and OS. Conclusions. This report showed that i) tandem auto-allo is feasible in AML pts; ii) acute GVHD incidence is not increased iii) prognostic score did not impact on TRM and survival; iv) the TRM is quite low with GVHD as main cause of death. A retrospective comparison with a cohort of pts not receiving HD-PAM is on going. Disclosures: No relevant conflicts of interest to declare.
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Gastinne, Thomas, Xavier Leleu, Anne-Sophie Moreau, Joris Andrieux, Jean-Luc Lai, Valérie Coiteux, Ibrahim Yakoub-Agha, et al. "Plasma Cell Proliferation Using Ki67 Antigen Expression Defines Subgroups Related to Short Survival in Multiple Myeloma Especially with Low Beta-2 Microglobulin." Blood 108, no. 11 (November 16, 2006): 5031. http://dx.doi.org/10.1182/blood.v108.11.5031.5031.
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Abstract Background: The current most powerful prognosis model in Multiple Myeloma (MM) combines beta-2 microglobulin (b2m) with albumin, corresponding to the International Staging System (ISS). However, the prognosis of patients within the group I of ISS (high albumin and low b2m) may vary. Proliferative activity of plasma cells has been previously related to prognosis in MM, but methods proposed so far are difficult to apply in routine practice. Ki-67 is a nuclear protein associated with cell proliferation, and its expression is reported as a powerful prognosis marker in solid tumours and several hematological malignancies. We retrospectively evaluated the % of bone marrow plasma cells (BMPC) expressing Ki-67 antigen (Ki67 index) in a series of 174 untreated patients with MM at diagnosis and we looked for its prognostic value on survival in MM. Method: Ki-67 index was determined after double immunocytochemistry on PC from BM cytospins (ABC peroxidase to identify cells expressing Ki-67, and alkaline phosphatase to identify PC expressing either Kappa or Lambda light chain). Conventional cytogenetic study and interphase FISH (research of Rb1 gene deletion) were performed in 114 and in 128 pts respectively. Results: Median survival (± se; months) for pts with stage III, II, and stage I of ISS score were 20 (± 3), 41 (± 3), 51 (± 3) months, respectively (p<0.001). Median Ki-67 index (± se) was of 3.0% (± 1.2), 6.1% (± 1.2), and 6.5% (± 1.4) in ISS stage I, stage II, and stage III patients, respectively (p< 0.004). Independently of the ISS staging system, Ki-67 index ≥ 4% was highly predictive of adverse prognosis, with a median survival of 26 ± 4 months and of 49 ± 10 months over and under that value, respectively (p < 0.0001). B2m (threshold at 3 mg/L) gave identical results than Ki-67 index (p < 0.001), whereas chromosome 13 deletion (del 13) was less powerful (p< 0.02). Ki-67 index correlated well with several markers of intrinsic malignancy, with markers of tumour burden, but it was unrelated to age, serum creatinine and b2m. There was a strong relationship between hypodiploidy and BMPC proliferation: within the group of pts displaying Ki-67 index ≥ 4%, 93% pts were found hypodiploid (p < 0.0001). Within ISS stage I, median survival [± se; RR of death (95%CI)] was of 31 ± 4 months [2.65 (1.5–4.6)] and of 67 ± 6 months in patients with Ki-67 index ≥ 4% and < 4%, respectively (p < 0.001). Chromosome 13 deletion also delineated two groups within ISS stage I pts, but the difference did not reach statistical significance (p = 0.243). Finally, the combination of Ki-67 to b2m produced an efficient prognostic model that appeared the most effective in our series compared to known models such as b2m/chr 13 deletion and ISS. The -2Log (likelihood) scores calculated on 155 patients were 1107.885, 1113.256 and 1116.829 for Ki-67/b2m model, ISS model and b2m/del13 model, respectively. Conclusion: Ki-67 index is easy to perform in routine practice, and is a good prognostic marker, which provides additional survival prognostic information to b2m into the ISS model.
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Graham, George G., William C. MacLean, Kenneth H. Brown, Enrique Morales, Jorge Lembcke, and Arturo Gastañaduy. "Protein Requirements of Infants and Children: Growth During Recovery From Malnutrition." Pediatrics 97, no. 4 (April 1, 1996): 499–505. http://dx.doi.org/10.1542/peds.97.4.499.
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Objective. To evaluate the adequacy of protein intakes now recommended as safe for infants and toddlers. Methods. Subjects were recovering malnourished infants, age 5.3 to 17.9 months, length age (LA) 2.5 to 6.4 months, weight age (WA) 1.5 to 5.2 months, weight/length (W/L) 78% to 100% of National Center for Health Statistics data; and toddlers age 11.4 to 31.6 months, LA 6.1 to 17.9 months, WA 3.9 to 12.0 months, W/L 79% to 99%. Infants were assigned at random to formulas with 5.5%, 6.7%, or 8.0% energy as 60:40 whey:casein protein. The 5.5% was based on FAO-WHO-UNU safe protein and average energy for ages 2.5 to 6.0 months. Toddlers received 4.7% (recommended for 6 to 18 months), 6.4%, or 8.0%. Identical concentrations (weight/kcal) of other nutrients were maintained; intakes were adjusted weekly to reach, in 90 days, the 50th percentile of weight for a LA 3 months greater than the initial one. Results. Infants consumed 125 ± 11 (SD), 116 ± 10, and 126 ± 14 kcal and 1.7 ± 0.1, 1.9 ± 0.2, and 2.5 ± 0.3 g protein Kg-1· d-1; gained 2.4 ± 0.7, 2.9 ± 0.7, and 2.6 ± 0.5 months in LA, and reached a W/L of 105 ± 5, 103 ± 6, and 105 ± 5% of reference. Sum of four fat-folds (Σ FF) grew 13.1 ± 6.9, 10.4 ± 4.8, and 11.7 ± 5.3 mm to 32.5 ± 5.2, 31.7 ± 4.7, and 30.5 ± 5.5 mm; arm muscle areas (AMA) 57%, 51%, 70% to 1004 ± 109, 1017 ± 110, and 1004 ± 116 mm2, still low; arm fat areas (AFA) 93%, 66%, and 93% to higher-than-normal 598 ± 105, 610 ± 101, and 541 ± 116 mm2. Regression of intake on weight gain estimated energy for maintenance + activity to be 81.0 ± 7.5 (SEM) kcal · kg-1· d-1, and cost of gain (storage + metabolic cost) as 7.6 ± 1.7 kcal/g, with no significant effect of % protein. Toddlers consumed 107 ± 9, 103 ± 12, and 105 ± 10 kcal and 1.3 ±0.1, 1.6 ± 0.2, and 2.1 ± 0.2 g protein kg-1 · d-1; gained 3.3 ± 0.7, 2.9 ± 0.6, and 3.3 ± 0.7 months in LA; to a W/L of 102 ± 1, 102 ± 3, and 101 ± 4%. Σ FF grew 9.2 ± 4.0, 7.4 ± 4.3, and 6.0 ± 3.8 to 28.9 ± 5.2, 30.5 ± 3.7, and 27.0 ± 2.7 mm; AMA 31%, 33%, and 34% to 1121 ± 115, 1124 ± 110, and 1117 ± 120 mm2; AFA 53%, 44%, and 45% to higher-than-normal 578 ± 106, 636 ± 99, and 569 ± 68 mm2. Cost of maintenance + activity was 70.8 ± 3.8 (SEM) kcal · kg-1 · d-1, that of weight gain 9.7 ± 1.35 kcal/g, with no effect of % protein. Conclusions. Within age groups, there were no significant protein-related differences in growth. In both infants and toddlers, high-energy intakes resulted in mild obesity, with lean body mass still deficient. Protein intakes two SD below the means in the lowest protein/energy cells, 1.5 g · kg-1 · d-1 for infants and 1.1 g · Kg-1 · d-1 for toddlers, should still be safe for nearly all children of comparable biological ages.
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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.
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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.