Prevalence of Lynch syndrome in unselected patients with endometrial or ovarian cancer.

PubMed

Kast, Karin; Dobberschütz, Catharina; Sadowski, Carolin Eva; Pistorius, Steffen; Wimberger, Pauline

2016-11-01

Lynch syndrome is known by healthcare providers mainly for patients with colorectal cancer. Awareness of other associated tumors, such as endometrial or ovarian cancer, is low. This study aimed to analyze the prevalence of Lynch syndrome in unselected patients with endometrial or ovarian cancer. In addition, the willingness of patients and family members to undergo germline mutation testing was investigated. The medical records of all patients diagnosed with endometrial or ovarian cancer at the Department of Gynecology and Obsterics, University Hospital Dresden, between 1998 and 2012, were screened for a family history of HNPCC-associated cancer. Telephone interviews were used to screen, inform, and enroll patients in this genetic analysis study. Molecular analysis was performed by prescreening of tumor tissue, followed by germline mutation analysis. Two hundred and eighty-three patients were diagnosed with endometrial cancer, 291 with ovarian cancer, and 14 with both. A positive family history for tumors associated with Lynch syndrome was documented for 61 patients. Two pathogenic mutations in the genes MLH1 and MSH2 in nine genetic analyses had already been detected before. After genetic counseling, only 10 of 31 index patients (32.3 %) consented for mutation analysis. However, no additional pathogenic heterozygous mutations were found. In this retrospective cohort study in unselected patients with endometrial or ovarian cancer, only a small number of patients with suspected Lynch syndrome could be identified. Of those, acceptance of germline analyses was moderate, only. As a result, the rate of identified pathogenic germline mutations was lower than expected. Therefore, we are convinced that more information on cancer risks, options for predictive molecular testing and preventive procedures, needs to be provided to patients and gynecologists.

Lentiviral-mediated genetic correction of hematopoietic and mesenchymal progenitor cells from Fanconi anemia patients.

PubMed

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Lozano, M Luz; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-06-01

Previous clinical trials based on the genetic correction of purified CD34(+) cells with gamma-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34(+) cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34(+) cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34(-) mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs).

Lentiviral-mediated Genetic Correction of Hematopoietic and Mesenchymal Progenitor Cells From Fanconi Anemia Patients

PubMed Central

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Luz Lozano, M; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-01-01

Previous clinical trials based on the genetic correction of purified CD34+ cells with γ-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34+ cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34+ cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34− mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs). PMID:19277017

Strengths and weaknesses of 'real-world' studies involving non-vitamin K antagonist oral anticoagulants.

PubMed

Camm, A John; Fox, Keith A A

2018-01-01

Randomised controlled trials (RCTs) provide the reference standard for comparing the efficacy of one therapy or intervention with another. However, RCTs have restrictive inclusion and exclusion criteria; thus, they are not fully representative of an unselected real-world population. Real-world evidence (RWE) studies encompass a wide range of research methodologies and data sources and can be broadly categorised as non-interventional studies, patient registries, claims database studies, patient surveys and electronic health record studies. If appropriately designed, RWE studies include a patient population that is far more representative of unselected patient populations than those of RCTs, but they do not provide a robust basis for comparing treatment strategies. RWE studies can have very large sample sizes, can provide information on treatments in patient groups that are usually excluded from RCTs, are generally less expensive and quicker than RCTs, and can assess a broad range of outcomes. Limitations of RWE studies can include low internal validity, lack of quality control surrounding data collection and susceptibility to multiple sources of bias for comparing outcomes. RWE studies can complement the findings from RCTs by providing valuable information on treatment practices and patient characteristics among unselected patients. This information is necessary to guide treatment decisions and for reimbursement and payment decisions. RWE studies have been extensively applied in the postmarketing approval assessment of non-vitamin K antagonist oral anticoagulants since 2010. However, the benefits, costs, limitations and methodological challenges associated with the different types of RWE must be considered carefully when interpreting the findings.

Strengths and weaknesses of ‘real-world’ studies involving non-vitamin K antagonist oral anticoagulants

PubMed Central

Camm, A John; Fox, Keith A A

2018-01-01

Randomised controlled trials (RCTs) provide the reference standard for comparing the efficacy of one therapy or intervention with another. However, RCTs have restrictive inclusion and exclusion criteria; thus, they are not fully representative of an unselected real-world population. Real-world evidence (RWE) studies encompass a wide range of research methodologies and data sources and can be broadly categorised as non-interventional studies, patient registries, claims database studies, patient surveys and electronic health record studies. If appropriately designed, RWE studies include a patient population that is far more representative of unselected patient populations than those of RCTs, but they do not provide a robust basis for comparing treatment strategies. RWE studies can have very large sample sizes, can provide information on treatments in patient groups that are usually excluded from RCTs, are generally less expensive and quicker than RCTs, and can assess a broad range of outcomes. Limitations of RWE studies can include low internal validity, lack of quality control surrounding data collection and susceptibility to multiple sources of bias for comparing outcomes. RWE studies can complement the findings from RCTs by providing valuable information on treatment practices and patient characteristics among unselected patients. This information is necessary to guide treatment decisions and for reimbursement and payment decisions. RWE studies have been extensively applied in the postmarketing approval assessment of non-vitamin K antagonist oral anticoagulants since 2010. However, the benefits, costs, limitations and methodological challenges associated with the different types of RWE must be considered carefully when interpreting the findings. PMID:29713485

Degree of Stereotypic Responding by Hyperactive, Learning Disabled, and Unselected Children in a Computer-Controlled Task.

ERIC Educational Resources Information Center

Metzger, Mary Ann; Freund, Lisa

The present research assessed the ability to attend to relevant information in the presence of irrelevant distraction in hyperactive (H), learning disabled (LD), and unselected (US) children. A total of 20 LD, 20 H, and 20 US children divided into younger and older age groups participated in the study. Younger children were between 94 and 104…

Circulating neural antibodies in unselected children with new-onset seizures.

PubMed

Garcia-Tarodo, Stephanie; Datta, Alexandre N; Ramelli, Gian P; Maréchal-Rouiller, Fabienne; Bien, Christian G; Korff, Christian M

2018-05-01

The role of autoimmunity and neural antibodies is increasingly recognized in different forms of seizures and epilepsy. Their prevalence in new-onset epilepsy has also recently been the focus of several clinical cohorts in the adult and pediatric population, with positive titers in 10-11% of cases. Our aim was to determine the seropositivity at the first seizure onset in a non-selective group of children. We conducted a prospective multicenter cohort study recruiting children aged 0-16 years with new-onset seizures presenting at the In- and Outpatient Pediatric Neurology Departments of three Children's Hospitals in Switzerland between September 2013 and April 2016. Neural antibodies were screened within the first 6 months of a first seizure and when positive, repeated at 1 month and 6 months follow-up. A total of 103 children were enrolled with a mean age at presentation of 5 years (range 1 day-15 years 9 months). The majority (n = 75) presented with generalized seizures and 6 had status epilepticus lasting > 30 min. At the time of onset, 55% of patients had fever, 24% required emergency seizure treatment and 27% hospitalization. Epilepsy was diagnosed at follow-up in 18%. No specific antibody was found. Serum antibodies against the VGKC complex, without binding to the specific antigens LGI1 and CASPR2, were found in two patients. Four patients harbored not otherwise characterized antibodies against mouse neuropil. Specific neural antibodies are rarely found in an unselected population of children that present with a first seizure. Applying an extensive neuronal antibody profile in a child with new-onset seizures does not appear to be justified. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

N-terminal pro-B-type natriuretic peptide is an independent predictor of outcome in an unselected cohort of critically ill patients.

PubMed

Meyer, Brigitte; Huelsmann, Martin; Wexberg, Paul; Delle Karth, Georg; Berger, Rudolf; Moertl, Deddo; Szekeres, Thomas; Pacher, Richard; Heinz, Gottfried

2007-10-01

Natriuretic peptides emerged during recent years as potent prognostic markers in patients with heart failure and acute myocardial infarction. In addition, natriuretic peptides show strong predictive value in patients with pulmonary embolism, sepsis, renal failure, and shock. The present study tests the prognostic information of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in an unselected cohort of critically ill patients. Prospective, observational study. A tertiary intensive care unit in a university hospital. A total of 289 consecutive patients admitted to the intensive care unit during a 16-month period with the following data: age 64 +/- 14 yrs, male n = 191, Simplified Acute Physiology Score II of 52 +/- 24, mechanical ventilation n = 180 (62%), vasopressors n = 179 (62%), renal failure n = 24 (8%). None. Plasma NT-pro-BNP samples (Roche Diagnostics) were obtained on intensive care unit admission. Data are given as median [range]. Intensive care unit survivors had significantly lower NT-pro-BNP values compared with intensive care unit nonsurvivors (3394 [24-35,000] vs. 6776 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). Hospital survivors were characterized by significantly lower NT-pro-BNP values (2656 [24-35,000] vs. 8390 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). NT-pro-BNP levels were not significantly different in patients with primary cardiac diagnosis compared with those with a noncardiac admission diagnosis (4794 [26-35,000], n = 202 vs. 3349 [24-35,000], n = 87, cardiac vs. noncardiac, respectively, p = .28). In a logistic regression model, Simplified Acute Physiology Score II and NT-pro-BNP were independently associated with hospital survival (chi = 35.6, p = .0001 and chi = 11.3, p = .0008, Simplified Acute Physiology Score II and NT-pro-BNP, respectively). Areas under the receiver operating characteristic curves of NT-pro-BNP and Simplified Acute Physiology Score II were not statistically significant different regarding the prediction of outcome. NT-pro-BNP on admission is an independent prognostic marker of outcome in an unselected cohort of critically ill patients. A single measurement of NT-pro-BNP might facilitate triage of emergency and intensive care unit patients.

Impact of iso-osmolar versus low-osmolar contrast agents on contrast-induced nephropathy and tissue reperfusion in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the Contrast Media and Nephrotoxicity Following Primary Angioplasty for Acute Myocardial Infarction [CONTRAST-AMI] Trial).

PubMed

Bolognese, Leonardo; Falsini, Giovanni; Schwenke, Carsten; Grotti, Simone; Limbruno, Ugo; Liistro, Francesco; Carrera, Arcangelo; Angioli, Paolo; Picchi, Andrea; Ducci, Kenneth; Pierli, Carlo

2012-01-01

Conflicting data have been reported on the effects of low-osmolar and iso-osmolar contrast media on contrast-induced acute kidney injury (CI-AKI). In particular, no clinical trial has yet focused on the effect of contemporary contrast media on CI-AKI, epicardial flow, and microcirculatory function in patients with ST-segment elevation acute myocardial infarction who undergo primary percutaneous coronary intervention. The Contrast Media and Nephrotoxicity Following Coronary Revascularization by Angioplasty for Acute Myocardial Infarction (CONTRAST-AMI) trial is a prospective, randomized, single-blind, parallel-group, noninferiority study aiming to evaluate the effects of the low-osmolar contrast medium iopromide compared to the iso-osmolar agent iodixanol on CI-AKI and tissue-level perfusion in patients with ST-segment elevation acute myocardial infarction. Four hundred seventy-five consecutive, unselected patients who underwent primary percutaneous coronary intervention were randomized to iopromide (n = 239) or iodixanol (n = 236). All patients received high-dose N-acetylcysteine and hydration. The primary end point was the proportion of patients with serum creatinine (sCr) increases ≥25% from baseline to 72 hours. Secondary end points were Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, increase in sCr ≥50%, increase in sCr ≥0.5 or ≥1 mg/dl, and 1-month major adverse cardiac events. The primary end point occurred in 10% of the iopromide group and in 13% of the iodixanol group (95% confidence interval -9% to 3%, p for noninferiority = 0.0002). A TIMI myocardial perfusion grade of 0 or 1 was present in 14% of patients in the 2 groups. No differences between the 2 groups were found in any of the secondary analyses of sCr increase. No significant difference in 1-month major adverse cardiac events was found (8% vs 6%, p = 0.37). In conclusion, in a population of unselected patients with ST-segment elevation acute myocardial infarction who underwent primary percutaneous coronary intervention, iopromide was not inferior to iodixanol in the occurrence of CI-AKI; no significant differences were found in terms of tissue-level reperfusion and major adverse cardiac events between the 2 contrast agents. Copyright © 2012 Elsevier Inc. All rights reserved.

Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.

PubMed

Lowery, Maeve A; Wong, Winston; Jordan, Emmet J; Lee, Jonathan W; Kemel, Yelena; Vijai, Joseph; Mandelker, Diana; Zehir, Ahmet; Capanu, Marinela; Salo-Mullen, Erin; Arnold, Angela G; Yu, Kenneth H; Varghese, Anna M; Kelsen, David P; Brenner, Robin; Kaufmann, Erica; Ravichandran, Vignesh; Mukherjee, Semanti; Berger, Michael F; Hyman, David M; Klimstra, David S; Abou-Alfa, Ghassan K; Tjan, Catherine; Covington, Christina; Maynard, Hannah; Allen, Peter J; Askan, Gokce; Leach, Steven D; Iacobuzio-Donahue, Christine A; Robson, Mark E; Offit, Kenneth; Stadler, Zsofia K; O'Reilly, Eileen M

2018-02-28

Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board-approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Jakobi, Sina; Steetskamp, Joscha; Makris, Georgios; Sicking, Isabel; Weyer, Veronika; Schmidt, Marcus

2014-07-01

The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.

Clinical spectrum of Kawasaki disease in infants younger than 6 months of age.

PubMed

Burns, J C; Wiggins, J W; Toews, W H; Newburger, J W; Leung, D Y; Wilson, H; Glodé, M P

1986-11-01

We report an unselected series of eight patients younger than 6 months of age with Kawasaki disease evaluated between January 1982 and May 1984. The incidence of coronary artery aneurysms (six patients) and the mortality (two patients) were unusually high in this small series. Because of the confusing clinical presentation in three patients, diagnosis was delayed until pathologic or echocardiographic evidence of coronary vasculitis or aneurysm was discovered. The currently accepted clinical criteria for Kawasaki disease may not always identify patients with the pathologic findings of the syndrome who are younger than 6 months of age. The diagnosis of Kawasaki disease and echocardiographic evaluation of the coronary arteries should be considered in young infants with prolonged fever of unknown origin.

Prospective assessment of the occurrence of anemia in patients with heart failure: results from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry.

PubMed

Adams, Kirkwood F; Patterson, James H; Patterson, John H; Oren, Ron M; Mehra, Mandeep R; O'Connor, Christopher M; Piña, Ileana L; Miller, Alan B; Chiong, Jun R; Dunlap, Stephanie H; Cotts, William G; Felker, Gary M; Schocken, Douglas D; Schwartz, Todd A; Ghali, Jalal K

2009-05-01

Although a potentially important pathophysiologic factor in heart failure, the prevalence and predictors of anemia have not been well studied in unselected patients with heart failure. The Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry prospectively studied the prevalence of anemia and the relationship of hemoglobin to health-related quality of life and outcomes among patients with heart failure. A random selection algorithm was used to reduce bias during enrollment of patients seen in specialty clinics or clinics of community cardiologists with experience in heart failure. In this initial report, data on prevalence and correlates of anemia were analyzed in 1,076 of the 1,082 registry patients who had clinical characteristics and hemoglobin determined by finger-stick at baseline. Overall (n = 1,082), the registry patients were 41% female and 73% white with a mean age (+/-SD) of 64 +/- 14 years (68 +/- 13 years in community and 57 +/- 14 years in specialty sites, P < .001). Among the 1,076 patients in the prevalence analysis, mean hemoglobin was 13.3 +/- 2.1 g/dL (median 13.2 g/dL); and anemia (defined by World Health Organization criteria) was present in 34%. Age identified patients at risk for anemia, with 40% of patients >70 years affected. Initial results from the STAMINA-HFP Registry suggest that anemia is a common comorbidity in unselected outpatients with heart failure. Given the strong association of anemia with adverse outcomes in heart failure, this study supports further investigation concerning the importance of anemia as a therapeutic target in this condition.

Outcomes for patients with congenital hepatoblastoma.

PubMed

Trobaugh-Lotrario, Angela D; Chaiyachati, Barbara H; Meyers, Rebecka L; Häberle, Beate; Tomlinson, Gail E; Katzenstein, Howard M; Malogolowkin, Marcio H; von Schweinitz, Dietrich; Krailo, Mark; Feusner, James H

2013-11-01

Congenital hepatoblastoma, diagnosed in the first month of life, has been reported to have a poor prognosis; however, a comprehensive evaluation of this entity is lacking. We retrospectively reviewed two patients from the senior authors' personal series and 25 cases identified in the databases of several multicenter group studies (INT-0098, P9645, 881, P9346, HB 89, HB94, and HB 99). We compared this series with cases of congenital hepatoblastoma previously published in the literature. The 3-year survival in our case series was 86% (18/21) with a follow-up of 44-230 months (median 85.5 months). Presentation and treatment were not substantially different from hepatoblastoma cohorts unselected for age. Survival was comparable to the reported disease free survival for a similar cohort of hepatoblastoma patients unselected for age between 1986 and 2002 (82.5%) [von Schweinitz et al., Eur J Cancer 1997; 33:1243-1249]. The 2-year survival of cases reported in the literature was 0% (0/9) and 42% (10/24) for patients reported before and after 1990, respectively. Congenital hepatoblastoma does not appear to confer a worse prognosis. The improved survival of our current series of patients, collected from the past 20 years of German and American multicenter trials and personal series, suggests that the outcome of hepatoblastoma at this young age is much better than has been historically reported. More rigorous analysis should be conducted in future multicenter trials. It is possible that congenital hepatoblastoma should be treated like all other patients with hepatoblastoma provided that the child is stable enough to proceed with surgery and chemotherapy. Copyright © 2013 Wiley Periodicals, Inc.

Automatic management of atrial and ventricular stimulation in a contemporary unselected population of pacemaker recipients: the ESSENTIAL Registry.

PubMed

Biffi, Mauro; Bertini, Matteo; Saporito, Davide; Belotti, Giuseppina; Quartieri, Fabio; Piancastelli, Maurizio; Pucci, Angelo; Boggian, Giulio; Mazzocca, Gian Franco; Giorgi, Davide; Diotallevi, Paolo; Diemberger, Igor; Martignani, Cristian; Pancaldi, Stefano; Ziacchi, Matteo; Marcantoni, Lina; Toselli, Tiziano; Attala, Simone; Iori, Matteo; Bottoni, Nicola; Argnani, Selina; Tomasi, Corrado; Sassone, Biagio; Boriani, Giuseppe

2016-10-01

We investigated the applicability of the Ventricular Capture Control (VCC) and Atrial Capture Control (ACC) algorithms for automatic management of cardiac stimulation featured by Biotronik pacemakers in a broad, unselected population of pacemaker recipients. Ventricular Capture Control and Atrial Capture Control were programmed to work at a maximum adapted output voltage as 4.8 V in consecutive recipients of Biotronik pacemakers. Ambulatory threshold measurements were made 1 and 12 months after pacemaker implant/replacement in all possible pacing/sensing configurations, and were compared with manual measurements. Among 542 patients aged 80 (73-85) years, 382 had a pacemaker implant and 160 a pacemaker replacement. Ventricular Capture Control could work at long term in 97% of patients irrespectively of pacing indication, lead type, and lead service life, performance being superior with discordant pacing/sensing configurations. Atrial Capture Control could work in 93% of patients at 4.8 V maximum adapted voltage and at any pulse width, regardless of pacing indication, lead type, and service life. At 12-month follow-up, a ventricular threshold increase ≥1.5 V had occurred in 4.4% of patients uneventfully owing to VCC functioning. Projected pacemaker longevity at 1 month was strongly correlated with the 12-month estimate, and exceeded 13 years in >60% of patients. These algorithms for automatic management of pacing output ensure patient safety in the event of a huge increase of pacing threshold, while enabling maximization of battery longevity. Their applicability is quite broad in an unselected pacemaker population irrespectively of lead choice and service of life. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing

PubMed Central

Klemp, Jennifer R.; Kimler, Bruce F.; Mahnken, Jonathan D.; Geier, Larry J.; Khan, Qamar J.; Elia, Manana; Connor, Carol S.; McGinness, Marilee K.; Mammen, Joshua M. W.; Wagner, Jamie L.; Ward, Claire; Ranallo, Lori; Knight, Catherine J.; Stecklein, Shane R.; Jensen, Roy A.; Fabian, Carol J.; Godwin, Andrew K.

2014-01-01

NCCN guidelines recommend genetic testing for all triple-negative breast cancer (TNBC) patients aged ≤60 years. However, due to the lack of prospective information in unselected patients, these guidelines are not uniformly adopted by clinicians and insurance carriers. The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population. Stage I–IV TNBC patients were enrolled on a prospective registry at academic and community practices. All patients underwent BRCA1/2 testing. Significant family history (SFH) was defined >1 relative with breast cancer at age ≤50 or ≥1 relative with ovarian cancer. Mutation prevalence in the entire cohort and subgroups was calculated. 207 TNBC patients were enrolled between 2011 and 2013. Racial/ethnic distribution: Caucasian (80 %), African–American (14 %), Ashkenazi (1 %). Deleterious BRCA1/2 mutations were identified in 15.4 % (32/207) of patients (BRCA1:11.1 %, BRCA2:4.3 %). SFH reported by 36 % of patients. Mutation prevalence in patients with and without SFH was 31.6 and 6.1 %, respectively. When assessed by age at TNBC diagnosis, the mutation prevalences were 27.6 % (≤50 years), 11.4 % (51–60 years), and 4.9 % (≥61 years). Using SFH or age ≤50 as criteria, 25 and 34 % of mutations, respectively, were missed. Mutation prevalence in patients meeting NCCN guidelines was 18.3 % (32/175) and 0 % (0/32) in patients who did not meet guidelines (p = .0059). In this unselected academic and community population with negligible Ashkenazi representation, we observed an overall BRCA mutation prevalence rate of 15.4 %. BRCA testing based on NCCN guidelines identified all carriers supporting its routine application in clinical practice for TNBC. PMID:24807107

New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study

PubMed Central

Plaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Rita; Miller, Suzanne; Dann, Adela; Licence, Victoria; Webb, Hayley; Tan, Li Tee; Daly, Margaret; Ayers, Sarah; Rufford, Barnaby; Earl, Helena; Parkinson, Christine; Duncan, Timothy; Jimenez-Linan, Mercedes; Sagoo, Gurdeep S; Abbs, Stephen; Hulbert-Williams, Nicholas; Pharoah, Paul; Crawford, Robin; Brenton, James D; Tischkowitz, Marc

2016-01-01

Background Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. Objective To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Methods Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. Results 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. Conclusions The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice. PMID:27208206

NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study): Randomized Controlled Contrast-Enhanced Sonothrombolysis in an Unselected Acute Ischemic Stroke Population.

PubMed

Nacu, Aliona; Kvistad, Christopher E; Naess, Halvor; Øygarden, Halvor; Logallo, Nicola; Assmus, Jörg; Waje-Andreassen, Ulrike; Kurz, Kathinka D; Neckelmann, Gesche; Thomassen, Lars

2017-02-01

The NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study) aimed to assess effect and safety of contrast-enhanced ultrasound treatment in an unselected acute ischemic stroke population. Patients treated with intravenous thrombolysis within 4.5 hours after symptom onset were randomized 1:1 to either contrast-enhanced sonothrombolysis (CEST) or sham CEST. A visible arterial occlusion on baseline computed tomography angiography was not a prerequisite for inclusion. Pulse-wave 2 MHz ultrasound was given for 1 hour and contrast (SonoVue) as an infusion for ≈30 minutes. Magnetic resonance imaging and angiography were performed after 24 to 36 hours. Primary study end points were neurological improvement at 24 hours defined as National Institutes of Health Stroke Scale score 0 or reduction of ≥4 National Institutes of Health Stroke Scale points compared with baseline National Institutes of Health Stroke Scale and favorable functional outcome at 90 days defined as modified Rankin scale score 0 to 1. A total of 183 patients were randomly assigned to either CEST (93 patient) or sham CEST (90 patients). The rates of symptomatic intracerebral hemorrhage, asymptomatic intracerebral hemorrhage, or mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days was similar in the 2 groups both in the intention-to-treat analysis and in the per-protocol analysis. CEST is safe among unselected ischemic stroke patients with or without a visible occlusion on computed tomography angiography and with varying grades of clinical severity. There was, however, statistically no significant clinical effect of sonothrombolysis in this prematurely stopped trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01949961. © 2016 The Authors.

Significance of Large Vessel Intracranial Occlusion Causing Acute Ischemic Stroke and TIA

PubMed Central

Smith, Wade S.; Lev, Michael H.; English, Joey D.; Camargo, Erica C.; Chou, Maggie; Johnston, S. Claiborne; Gonzalez, Gilberto; Schaefer, Pamela W.; Dillon, William P.; Koroshetz, Walter J.; Furie, Karen L.

2009-01-01

Background: Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries- likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data has been reported on a cohort of unselected stroke and TIA patients, the clinical impact of LVO has been difficult to quantify. Methods: The STOP-Stroke Study is a prospective imaging-based study of stroke outcomes performed at two academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multi-modality CT/CTA were approached for consent for collection of clinical data and 6 month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin scores (mRS) were collected and combined with blinded interpretation of the CTA data. The odds ratio (OR) of each variable including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality was calculated using univariate and multivariate logistic regression. Results: Over a 33 month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as TIA. Among stroke patients, 267 (46%) had LVO accounting for the stroke and 13 (13%) of TIA patients had LVO accounting for TIA symptoms. LVO predicted six-month mortality (OR 4.5; 95% CI 2.7-7.3; p<0.001). Six-month good outcome (mRS≤ 2) was negatively predicted by LVO (0.33; 0.24-0.45; p<0.001). Based on multivariate analysis, the presence of basilar and internal carotid terminus occlusions, in addition to NIHSS and age, independently predicted outcome. Conclusion: Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers. In addition to age and baseline stroke severity, occlusion of either the basilar or internal carotid terminus segment is an independent predictor of outcome at 6 months. PMID:19834014

Phase II trial of everolimus in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma.

PubMed

Geiger, Jessica L; Bauman, Julie E; Gibson, Michael K; Gooding, William E; Varadarajan, Prakash; Kotsakis, Athanasios; Martin, Daniel; Gutkind, Jorge Silvio; Hedberg, Matthew L; Grandis, Jennifer R; Argiris, Athanassios

2016-12-01

Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC. This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway. Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue. Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1759-1764, 2016. © 2016 Wiley Periodicals, Inc.

Postabortal endometritis and isolation of Chlamydia trachomatis.

PubMed

Barbacci, M B; Spence, M R; Kappus, E W; Burkman, R C; Rao, L; Quinn, T C

1986-11-01

A prospective study of 505 unselected women presenting for induced abortion was undertaken to determine the prevalence of Chlamydia trachomatis and to determine if cervical isolation of C trachomatis before abortion increases the risk of postabortal endometritis. A comparison of direct fluorescent antibody (slide) test with tissue culture for diagnosing C trachomatis infection also was evaluated in this population. C trachomatis was identified by culture in 89 patients (17.6%) and by direct slide test in 85 patients (16.8%). Six of 17 patients with postabortal endometritis were culture positive for C trachomatis, with a significant correlation between C trachomatis infection and development of endometritis observed (P less than .05). These data suggest C trachomatis may play an important role in postabortal endometritis.

The risk of gastric cancer in carriers of CHEK2 mutations.

PubMed

Teodorczyk, Urszula; Cybulski, Cezary; Wokołorczyk, Dominika; Jakubowska, Anna; Starzyńska, Teresa; Lawniczak, Małgorzata; Domagała, Paweł; Ferenc, Katarzyna; Marlicz, Krzysztof; Banaszkiewicz, Zbigniew; Wiśniowski, Rafał; Narod, Steven A; Lubiński, Jan

2013-09-01

CHEK2 is a tumor suppressor gene whose functions are central to the induction of cell cycle arrest and apoptosis following DNA damage. Mutations in CHEK2 have been associated with cancers at many sites, including breast and prostate cancers, but the relationship between CHEK2 and gastric cancer has not been extensively studied. In Poland, there are four known founder alleles of CHEK2; three alleles are protein truncating (1100delC, IVS2G>A, del5395) and the other is a missense variant (I157T). We examined the frequencies of four Polish founder mutations in the CHEK2 gene in 658 unselected gastric cancer patients, in 154 familial gastric cancer patients and in 8,302 controls. A CHEK2 mutation was seen in 57 of 658 (8.7 %) unselected patients with gastric cancer compared to 480 of 8,302 (5.8 %) controls (OR 1.6, p = 0.004). A CHEK2 mutation was present in 19 of 154 (12.3 %) familial cases (OR = 2.3, p = 0.001). The odds ratio for early onset (<50 years) gastric cancer was higher (2.1, p = 0.01), than for cases diagnosed at age of 50 or above (OR 1.4, p = 0.05). Truncating mutations of CHEK2 were associated with higher risk (OR = 2.1, p = 0.02) than the missense mutation I157T (OR = 1.4, p = 0.04). CHEK2 mutations predispose to gastric cancer, in particular to young-onset cases.

External validity of the ARISTOTLE trial in real-life atrial fibrillation patients.

PubMed

Hägg, Lovisa; Johansson, Cecilia; Jansson, Jan-Håkan; Johansson, Lars

2014-10-01

Our primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility. We performed a cross-sectional study of an unselected population including 2274 patients in Skellefteå, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population. Among all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARISTOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria. Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life. © 2014 John Wiley & Sons Ltd.

Procalcitonin as a marker of micro-inflammation in hemodialysis.

PubMed

Conti, Giovanni; Amore, Alessandro; Chiesa, Monica; Mancuso, Domenico; Cirina, Paola; Mengozzi, Giulio; Santoro, Antonio; Coppo, Rosanna

2005-01-01

In searching for a rapid and sensitive test to detect micro-inflammation in patients on hemodialysis (HD), we measured serum procalcitonin (PCT) levels and made a comparison with other traditional markers such as C-reactive protein (CRP), serum amyloid (SAA) and homocysteine, considered related to vascular damage. We investigated 51 HD patients, without signs of infection, in basal conditions (during standard bicarbonate dialysis and unselected filters: X) and after 4 months of possibly more biocompatible treatments (on-line hemofiltration (HF) or HD with ultra-pure dialysate and biocompatible membranes: Y). Serum PCT (measured by immunoluminometric assay), CRP and SAA (nephelometric assay) and plasma homocysteine (measured by high performance liquid chromatography) concentrations were assessed at the beginning of dialysis (T0) and after 4 hr (T4). Patients on unselected dialysis displayed mean PCT values significantly increased after 4 hr of dialysis in comparison to those at the start of the sessions (XT4 1.56 +/- 3.93 vs. XT0 0.4 +/- 0.34 ng/mL; p < 0.05). The PCT levels detected after 4 hr of biocompatible treatments were significantly lower than those detected after 4 hr of unselected treatments (YT4 0.78 +/- 0.34 ng/mL; p < 0.05), even though the percentage of patients with positive PCT values (> 0.5 ng/mL) remained almost unchanged. No significant modification in mean levels or in the frequency of positive values was observed for CRP, SAA and homocysteine. After 4 months of highly biocompatible treatments, a reduction in intradialytic enhancements of all inflammation markers was detected. Our data support the conclusion that PCT is a more precise marker than other traditional tests to evaluate micro-inflammation and biocompatibility in HD.

Ex-vivo expansion of CFU-GM and BFU-E in unselected PBMC cultures with Flt3L is enhanced by autologous plasma.

PubMed

Guo, M; Miller, W M; Papoutsakis, E T; Patel, S; James, C; Goolsby, C; Winter, J N

1999-01-01

Previous ex-vivo expansion studies in our laboratory, comparing unselected and CD34(+)-selected PBMC, have shown no advantage for CD34(+) cell selection, in terms of the expansion achieved. Our goal was to develop procedures for consistent generation of large numbers of hematopoietic progenitor and post-progenitor cells from unselected PBMC. Unselected PBMC, collected from cancer patients undergoing apheresis prior to high-dose chemotherapy and autologous stem cell rescue, were expanded ex vivo in static cultures, without a stromal layer, in the presence of Flt3 ligand (Flt3L), a recombinant GM-CSF/IL-3 fusion protein (PIXY321), G-CSF and GM-CSF for 10 days. The addition of 2% autologous plasma to this cytokine combination enhanced expansion of total cell numbers (3.2 fold versus 1.9 fold; p < 0.01), colony-forming units granulocyte-macrophage (CFU-GM) (22.0 fold versus 8.1 fold, p < 0.01) and burst-forming units erythroid (BFU-E) (17.6 fold versus 7.0 fold, 0.01 < p < 0.02). The optimal seeding density for a given specimen was inversely related to the frequency of CD34(+) cells in the sample. CFU-GM expansion with the Flt3L-containing cytokine cocktail was equivalent to that obtained with IL-3, IL-6, G-CSF and SCF, whether or not the cultures were supplemented with autologous plasma. In plasma-free cultures, BFU-E expansion was significantly higher with IL-3, IL-6, G-CSF and SCF than with Flt3L, PIXY321, G-CSF and GM-CSF. In the presence of autologous plasma, however BFU-E expansion was higher in the Flt3L-containing media. In comparison studies, autologous plasma suppressed BFU-E expansion in SCF-containing cultures. Consistent with our colony assay results, dual-parameter flow cytometric analysis of the expanded cell population revealed that supplementation with autologous plasma yielded a significant increase in the numbers of myeloid progenitors in Flt3L-containing cultures. Unselected PBMC from cancer patients can be effectively expanded ex vivo in Flt3L, PIXY321, G-CSF and GM-CSF, supplemented with autologous plasma, yielding high numbers of myeloid and erythroid progenitors.

Written pretest information and germline BRCA1/2 pathogenic variant testing in unselected breast cancer patients: predictors of testing uptake.

PubMed

Nilsson, Martin P; Nilsson, Erik D; Silfverberg, Barbro; Borg, Åke; Loman, Niklas

2018-06-06

This study aimed to evaluate predictors of testing uptake among unselected breast cancer patients who were offered germline BRCA1/2 testing in a prospective study. Pretest information was provided by a standardized invitation letter instead of in-person counseling. Data was abstracted from medical records. Using multivariate logistic regressions, predictors of testing uptake were analyzed. The overall uptake of testing was 67% (539 of 805 patients). Low uptake rates were found for patients aged ≥80 years (33%), and patients born outside of Europe (37%). In adjusted analysis, age ≥80 years (odds ratio [OR] 0.10; P = 0.002), psychiatric disorders (OR 0.46; P = 0.006), occupation requiring at least 3 years of university or college education (OR 2.03; P = 0.003), and breast cancer or ovarian cancer in first-degree or second-degree relatives (OR 1.66; P = 0.02) were independently associated with uptake of BRCA1/2 testing. Somatic comorbidity in patients aged <70 years was associated with lower testing uptake. Testing uptake varies across different subgroups according to patient-related factors that are readily available in the medical records. Knowledge about these factors enables health care professionals to identify patients who are less likely to pursue genetic testing.

New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study.

PubMed

Plaskocinska, Inga; Shipman, Hannah; Drummond, James; Thompson, Edward; Buchanan, Vanessa; Newcombe, Barbara; Hodgkin, Charlotte; Barter, Elisa; Ridley, Paul; Ng, Rita; Miller, Suzanne; Dann, Adela; Licence, Victoria; Webb, Hayley; Tan, Li Tee; Daly, Margaret; Ayers, Sarah; Rufford, Barnaby; Earl, Helena; Parkinson, Christine; Duncan, Timothy; Jimenez-Linan, Mercedes; Sagoo, Gurdeep S; Abbs, Stephen; Hulbert-Williams, Nicholas; Pharoah, Paul; Crawford, Robin; Brenton, James D; Tischkowitz, Marc

2016-10-01

Over recent years genetic testing for germline mutations in BRCA1/BRCA2 has become more readily available because of technological advances and reducing costs. To explore the feasibility and acceptability of offering genetic testing to all women recently diagnosed with epithelial ovarian cancer (EOC). Between 1 July 2013 and 30 June 2015 women newly diagnosed with EOC were recruited through six sites in East Anglia, UK into the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. Eligibility was irrespective of patient age and family history of cancer. The psychosocial arm of the study used self-report, psychometrically validated questionnaires (Depression Anxiety and Stress Scale (DASS-21); Impact of Event Scale (IES)) and cost analysis was performed. 232 women were recruited and 18 mutations were detected (12 in BRCA1, 6 in BRCA2), giving a mutation yield of 8%, which increased to 12% in unselected women aged <70 years (17/146) but was only 1% in unselected women aged ≥70 years (1/86). IES and DASS-21 scores in response to genetic testing were significantly lower than equivalent scores in response to cancer diagnosis (p<0.001). Correlation tests indicated that although older age is a protective factor against any traumatic impacts of genetic testing, no significant correlation exists between age and distress outcomes. The mutation yield in unselected women diagnosed with EOC from a heterogeneous population with no founder mutations was 8% in all ages and 12% in women under 70. Unselected genetic testing in women with EOC was acceptable to patients and is potentially less resource-intensive than current standard practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Reduced length of hospital stay after the introduction of a rapid recovery protocol for primary THA procedures.

PubMed

den Hartog, Yvon M; Mathijssen, Nina M C; Vehmeijer, Stephan B W

2013-10-01

Rapid recovery protocols after total hip arthroplasty (THA) have been introduced worldwide in the last few years and they have reduced the length of hospital stay. We show the results of the introduction of a rapid recovery protocol for primary THA for unselected patients in our large teaching hospital. In a retrospective cohort study, we included all 1,180 patients who underwent a primary THA between July 1, 2008 and June 30, 2012. These patients were divided into 3 groups: patients operated before, during, and after the introduction of the rapid recovery protocol. There were no exclusion criteria. All complications, re-admissions, and reoperations were registered and analyzed. The mean length of hospital stay decreased from 4.6 to 2.9 nights after the introduction of the rapid recovery protocol. There were no statistically significant differences in the rate of complications, re-admissions, or reoperations between the 3 groups. In a large teaching hospital, the length of hospital stay decreased after introduction of our protocol for rapid recovery after THA in unselected patients, without any increase in complications, re-admissions, or reoperation rate.

Fifty-three years' experience with randomized clinical trials of emergency portacaval shunt for bleeding esophageal varices in Cirrhosis: 1958-2011.

PubMed

Orloff, Marshall J

2014-02-01

Emergency treatment of bleeding esophageal varices (BEV) consists mainly of endoscopic and pharmacologic measures, with transjugular intrahepatic portal-systemic shunt (TIPS) performed when bleeding is not controlled. Surgical shunt has been relegated to salvage. At the University of California, San Diego, Medical Center, our group has conducted 10 studies of emergency portacaval shunt (EPCS) during 46 years. To describe 2 randomized clinical trials (RCTs) conducted from 1988 to 2011 in unselected consecutive patients who received emergency treatment for BEV. In RCT No. 1, a total of 211 unselected consecutive patients with cirrhosis and acute BEV were randomized to emergency endoscopic sclerotherapy (EEST) (n=106) or EPCS (n=105). In RCT No. 2, a total of 154 unselected consecutive patients with cirrhosis and acute BEV were randomized to TIPS (n=78) or EPCS (n=76). Diagnostic workup was completed within 6 hours of initial contact, and primary treatment was initiated within 8 to 12 hours. Regular follow-up for up to 10 years was accomplished in 100% of the patients. In RCT No. 1, EEST or EPCS; in RCT No. 2, TIPS or EPCS. The 2 groups were compared with regard to survival, control of bleeding, portal-systemic encephalopathy, and direct cost of care. RESULTS Distribution in Child risk classes was almost identical. One-third of patients were in Child class C. Permanent control of bleeding was achieved by EEST in only 20% of the patients and by TIPS in only 22%. In contrast, EPCS permanently controlled bleeding in 97% and 100% of the patients in RCT No. 2 and RCT No. 1, respectively (P<.001). Survival was significantly greater following EPCS than after EEST and TIPS (P<.001). Median survival was more than 10 years following EPCS compared with 1.99 years after TIPS. Occlusion of TIPS was demonstrated in 84% of the patients, 63% of whom underwent TIPS revision, which failed in 80% of the cases. Recurrent portal-systemic encephalopathy developed in 35% of the patients who underwent EEST and 61% of those who received TIPS. In contrast, portal-systemic encephalopathy occurred in 15% of the patients who received EPCS in RCT No. 1 and 21% of those in RCT No. 2. Direct costs of care were 5 to 7 times greater in the EEST ($168100) and TIPS ($264800) groups than in the EPCS ($39000) group (P<.001). Emergency portacaval shunt permanently stopped variceal bleeding, almost never became occluded, accomplished 5 times the long-term survival than EEST or TIPS, and was much less costly than EEST or TIPS. The widespread practice of using EPCS mainly as salvage for failure of endoscopic therapy or TIPS is not supported by the definitive results of these long-term RCTs in unselected patients with cirrhosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00690027 and NCT00734227.

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru.

PubMed

Abugattas, J; Llacuachaqui, M; Allende, Y Sullcahuaman; Velásquez, A Arias; Velarde, R; Cotrina, J; Garcés, M; León, M; Calderón, G; de la Cruz, M; Mora, P; Royer, R; Herzog, J; Weitzel, J N; Narod, S A

2015-10-01

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation-positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Epidermal growth factor receptor in non-small cell lung cancer

PubMed Central

2015-01-01

Following the identification of a group of patients in the initial tyrosine kinase inhibitor (TKI) trials for lung cancer, there has been detailed focus on which patients may benefit from inhibitor therapy. This article reviews the background, genetics and prevalence of epidermal growth factor mutations in non-small cell lung cancer (NSCLC). Additionally, the prevalence in unselected patients is compared against various other reviews. PMID:25870793

Inductive learning of thyroid functional states using the ID3 algorithm. The effect of poor examples on the learning result.

PubMed

Forsström, J

1992-01-01

The ID3 algorithm for inductive learning was tested using preclassified material for patients suspected to have a thyroid illness. Classification followed a rule-based expert system for the diagnosis of thyroid function. Thus, the knowledge to be learned was limited to the rules existing in the knowledge base of that expert system. The learning capability of the ID3 algorithm was tested with an unselected learning material (with some inherent missing data) and with a selected learning material (no missing data). The selected learning material was a subgroup which formed a part of the unselected learning material. When the number of learning cases was increased, the accuracy of the program improved. When the learning material was large enough, an increase in the learning material did not improve the results further. A better learning result was achieved with the selected learning material not including missing data as compared to unselected learning material. With this material we demonstrate a weakness in the ID3 algorithm: it can not find available information from good example cases if we add poor examples to the data.

Absence of Bacteria on Coronary Angioplasty Balloons from Unselected Patients: Results with Use of a High Sensitivity Polymerase Chain Reaction Assay

PubMed Central

Hansen, Gorm Mørk; Nilsson, Martin; Nielsen, Claus Henrik; Holmstrup, Palle; Helqvist, Steffen; Tolker-Nielsen, Tim; Givskov, Michael; Hansen, Peter Riis

2015-01-01

Periodontitis is a chronic, bacterially-induced inflammatory disease of the tooth-supporting tissues, which may result in transient bacteremia and a systemic inflammatory response. Periodontitis is associated with coronary artery disease independently of established cardiovascular risk factors, and translocation of bacteria from the oral cavity to the coronary arteries may play a role in the development of coronary artery disease. Very few studies have used angioplasty balloons for in vivo sampling from diseased coronary arteries, and with varying results. Therefore, the aim of this study was to assess if bacterial DNA from primarily oral bacteria could be detected on coronary angioplasty balloons by use of an optimized sampling process combined with an internally validated sensitive polymerase chain reaction (PCR) assay. Coronary angioplasty balloons and control samples from a total of 45 unselected patients with stable angina, unstable angina/non-ST elevation myocardial infarction, and ST-elevation myocardial infarction (n = 15 in each group) were collected and analyzed using a PCR assay with high sensitivity and specificity for 16S rRNA genes of the oral microbiome. Despite elimination of extraction and purification steps, and demonstration of sensitivity levels of 25–125 colony forming units (CFU), we did not detect bacterial DNA from any of the coronary angioplasty balloons. A subsequent questionnaire indicated that the prevalence of periodontitis in the study cohort was at least 39.5%. Although coronary angioplasty balloons are unlikely to be useful for detection of bacteria with current PCR techniques in unselected patients with coronary artery disease, more studies are warranted to determine the extent to which bacteria contribute to atherosclerosis and its clinical manifestations and whether the presence of bacteria in the arteries is a transient phenomenon. PMID:26695491

Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA.

PubMed

Smith, Wade S; Lev, Michael H; English, Joey D; Camargo, Erica C; Chou, Maggie; Johnston, S Claiborne; Gonzalez, Gilberto; Schaefer, Pamela W; Dillon, William P; Koroshetz, Walter J; Furie, Karen L

2009-12-01

Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries-likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify. The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression. Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P<0.001). Six-month good outcome (modified Rankin Scale score

Injection related anxiety in insulin-treated diabetes.

PubMed

Zambanini, A; Newson, R B; Maisey, M; Feher, M D

1999-12-01

The presence of injection related anxiety and phobia may influence compliance, glycaemic control and quality of life in patients with insulin-treated diabetes. Unselected consecutive, insulin-treated patients attending a diabetes clinic for follow-up, completed a standardised questionnaire providing an injection anxiety score (IAS) and general anxiety score (GAS). A total of 115 insulin-treated (80 Type 1 and 35 Type 2) diabetic patients completed the questionnaire. Injections had been avoided secondary to anxiety in 14% of cases and 42% expressed concern at having to inject more frequently. An IAS > or = 3 was seen in 28% of patients and of these, 66% injected insulin one to two times/day, 45% had avoided injections, and 70% would be bothered by more frequent injections. A significant correlation between IAS and GAS was seen (Kendall's tau-a 0.30, 95% CI 0.19-0.41, P < 0.001). GAS was significantly associated with both previous injection avoidance and expressed concern at increased injection frequency. No significant correlation was seen with HbA1c and injection or general anxiety scores. Symptoms relating to insulin injection anxiety and phobia have a high prevalence in an unselected group of diabetic patients requiring insulin injections and are associated with higher levels of general anxiety.

Cognitive mediation of clinical improvement after intensive exposure therapy of agoraphobia and social phobia.

PubMed

Vögele, Claus; Ehlers, Anke; Meyer, Andrea H; Frank, Monika; Hahlweg, Kurt; Margraf, Jürgen

2010-03-01

The present study investigated cognitive mediation of clinical improvement in patients with agoraphobia (N=427) or social phobia (N=98) receiving high-density exposure therapy in a naturalistic clinical treatment setting. Patients were assessed before therapy, 6 weeks after the end of therapy, and 1 year thereafter, using a self-report assessment battery. Lower level mediation analyses provided support for the notion that cognitive changes partially mediate clinical improvement after exposure therapy. Changes in cognitions relating to physical catastrophes mediated treatment outcome only for patients with agoraphobia, whereas changes in cognitions about loss of control mediated outcome for both agoraphobia and social phobia patients. Changes in relationship satisfaction did not mediate symptomatic improvement. The results extend previous findings by demonstrating mediation in an unselected clinical sample and by providing evidence for the specificity of mediation effects. They further support the importance of cognitive changes in cognitive-behavior therapy. (c) 2009 Wiley-Liss, Inc.

Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

PubMed

Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

2012-04-01

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

Quality of Life Outcomes after Transcatheter Aortic Valve Replacement in an Unselected Population. A Report from the STS/ACC TVT Registry™

PubMed Central

Arnold, Suzanne V.; Spertus, John A.; Vemulapalli, Sreekanth; Li, Zhuokai; Matsouaka, Roland A.; Baron, Suzanne J.; Vora, Amit N.; Mack, Michael J.; Reynolds, Matthew R.; Rumsfeld, John S.; Cohen, David J.

2017-01-01

Importance In clinical trials, transcatheter aortic valve replacement (TAVR) has been shown to improve symptoms and quality of life. As this technology moves into general clinical practice, it is critical to evaluate the health status outcomes among unselected patients treated with TAVR. Design/Participants Observational study of patients with severe aortic stenosis treated with TAVR in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry. Main Outcomes Disease-specific health status was assessed at baseline and at 30 days (n=31,636) and 1 year after TAVR (n=7,014) with the Kansas City Cardiomyopathy Questionnaire-overall summary score (KCCQ-OS; range 0–100 points). We examined factors associated with health status at 1 year after TAVR using multivariable linear regression, with adjustment for baseline health status and accounting for clustering of patients within sites. Results Mean baseline KCCQ-OS was 42.3±23.7, indicating substantial health status impairment. Surviving patients had, on average, large improvements in health status at 30 days that persisted to 1 year, with a mean improvement in the KCCQ-OS of 27.6 points at 30 days and 31.9 points at 1 year. Worse baseline health status, older age, higher ejection fraction, lung disease, home oxygen, lower mean aortic valve gradient, prior stroke, diabetes, pacemaker, atrial fibrillation, slower gait speed, and non-femoral access were associated with worse health status at 1 year. Overall, 62.3% of patients had a favorable outcome at 1 year (alive with reasonable quality of life [KCCQ-OS ≥60] and no significant decline [≥10 points] from baseline) with the lowest rates seen among patients with severe lung disease (51.4%), on dialysis (47.7%), or with very poor baseline health status (49.2%). Conclusion In a national, contemporary clinical practice cohort of unselected patients, we found that improvement in health status following TAVR was similar to that seen in the pivotal clinical trials. While the health status results were favorable for the majority of patients, ~1 in 3 patients still had a poor outcome 1 year after TAVR. Continued efforts are needed to improve patient selection and procedural/post-procedural care in order to maximize health status outcomes of this evolving therapy. PMID:28146260

Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density.

PubMed

Weber, Thomas J; Koh, James; Thomas, Samantha M; Hogue, Joyce A; Scheri, Randall P; Roman, Sanziana A; Sosa, Julie A

2017-09-01

A subset of PHPT patients exhibit a more severe disease phenotype characterized by bone loss, fractures, recurrent nephrolithiasis, and other dysfunctions, but the underlying reasons for this disparity in clinical presentation remain unknown. We sought to identify new mechanistic indices that could inform more personalized management of PHPT. Pre-, peri-, and postoperative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT were collected. Univariate and partial Spearman correlation was used to estimate the association of parathyroid tumor calcium sensing capacity with select variables. An unselected series of 237 patients aged >18years and undergoing parathyroidectomy for PHPT were enrolled. Calcium sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an unselected series of 74 patients and assessed for association with clinical parameters. The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically autonomous parathyroid tumor behavior. Parathyroid tumors segregated into two distinct groups of calcium responsiveness (EC50<3.0 and ≥3.0mM). The low EC50 group (n=27) demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI): 2.43-2.54mM], consistent with reference normal activity. In contrast, the high EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48mM [95% CI: 3.41-3.55mM]. Retrospective analysis of the clinical registry data suggested that high calcium EC50 patients presented with a more significant preoperative bone mineral density (BMD) deficit with a t-score of -2.7, (95% CI: -3.4 to -1.9) versus 0.9, (95% CI: -2.1 to -0.4) in low EC50 patients (p<0.001). After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of -0.35 (p=0.02). Impaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density deficit. Assessment of parathyroid tumor biochemical behavior may be a useful predictor of disease severity as measured by bone mineral density in patients with PHPT. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effects and Costs of a Group-Based Education Programme for Self-Management of Patients with Type 2 Diabetes. A Community-Based Study

ERIC Educational Resources Information Center

Molsted, Stig; Tribler, Jane; Poulsen, Peter B.; Snorgaard, Ole

2012-01-01

The worldwide epidemic of Type 2 diabetes necessitates evidence-based self-management education programmes. The purpose of this study was to investigate the effects and costs of an empowerment-based structured diabetes self-management education programme in an unselected group of patients with Type 2 diabetes. Seven hundred and two patients…

Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.

PubMed

Schuetz, Philipp; Hausfater, Pierre; Amin, Devendra; Amin, Adina; Haubitz, Sebastian; Faessler, Lukas; Kutz, Alexander; Conca, Antoinette; Reutlinger, Barbara; Canavaggio, Pauline; Sauvin, Gabrielle; Bernard, Maguy; Huber, Andreas; Mueller, Beat

2015-10-29

Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting. We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin). During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) (p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender. Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes. ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.

Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study.

PubMed

Carling, Malin S; Jeppsson, Anders; Eriksson, Bengt I; Brisby, Helena

2015-03-28

There is a high prevalence of blood product transfusions in orthopedic surgery. The reported prevalence of red blood cell transfusions in unselected patients undergoing hip or knee replacement varies between 21% and 70%. We determined current blood loss and transfusion prevalence in total hip and knee arthroplasty when tranexamic acid was used as a routine prophylaxis, and further investigated potential predictors for excessive blood loss and transfusion requirement. In total, 193 consecutive patients undergoing unilateral hip (n = 114) or knee arthroplasty (n = 79) were included in a prospective observational study. Estimated perioperative blood loss was calculated and transfusions of allogeneic blood products registered and related to patient characteristics and perioperative variables. Overall transfusion rate was 16% (18% in hip patients and 11% in knee patients, p = 0.19). Median estimated blood loss was significantly higher in hip patients (984 vs 789 mL, p < 0.001). Preoperative hemoglobin concentration was the only independent predictor of red blood cell transfusion in hip patients while low hemoglobin concentration, body mass index, and operation time were independent predictors for red blood cell transfusion in knee patients. The prevalence of red blood cell transfusion was lower than previously reported in unselected total hip or knee arthroplasty patients. Routine use of tranexamic acid may have contributed. Low preoperative hemoglobin levels, low body mass index, and long operation increase the risk for red blood cell transfusion.

Evaluation of nasogastric tubes to enable differentiation between upper and lower gastrointestinal bleeding in unselected patients with melena.

PubMed

Kessel, Boris; Olsha, Oded; Younis, Aurwa; Daskal, Yaakov; Granovsky, Emil; Alfici, Ricardo

2016-02-01

Gastrointestinal (GI) bleeding is a common surgical problem. The aim of this study was to evaluate how insertion of the nasogastric tube may enable differentiation between upper and lower GI bleeding in patients with melena. A retrospective study involving patients admitted to our surgery division with a melena was carried out between the years 2010 and 2012. A total of 386 patients were included in the study. Of these, 279 (72.2%) patients had negative nasogastric aspirate. The sensitivity of examination of nasogastric aspirate to establish the upper GI as the source of bleeding was only 28% and the negative predictive value of a negative nasogastric aspirate was less than 1%. Most patients who initially presented with melena and were found to have upper GI bleeding had a negative nasogastric aspirate. Insertion of a nasogastric tube does not affect the clinical decision to perform upper endoscopy and should not be routinely carried out.

Significant prevalence of sickle cell disease in Southwest Germany: results from a birth cohort study indicate the necessity for newborn screening.

PubMed

Kunz, Joachim B; Awad, Saida; Happich, Margit; Muckenthaler, Lena; Lindner, Martin; Gramer, Gwendolyn; Okun, Jürgen G; Hoffmann, Georg F; Bruckner, Thomas; Muckenthaler, Martina U; Kulozik, Andreas E

2016-02-01

Children with sickle cell disease (SCD) benefit from newborn screening, because life-threatening complications can be prevented by pre-symptomatic diagnosis. In Germany, the immigration of people from endemic countries is steadily growing. Comprehensive data about the epidemiology and prevalence of SCD in Germany are however lacking, and SCD is not included in the national newborn screening program. We provide data on the prevalence of SCD in a population from both urban and rural areas in Southwest Germany. Anonymized dried blood spots from 37,838 unselected newborns were analyzed by allele-specific PCR for the HbS mutation. Samples tested positive were subjected to Sanger sequencing of the entire β-globin coding sequence firstly to validate the screening and secondly to identify compound heterozygous SCD patients with other mutations of the β-globin gene. We identified 83 carriers of the sickle cell trait, three compound heterozygous SCD patients (two with sickle cell-β-thalassemia, one with sickle cell-Hb Tianshui) but no homozygous SCD patients. The novel molecular method and strategy for newborn screening for SCD presented here compares favorably in terms of sensitivity (1.0 for homozygous HbS, 0.996 for heterozygous HbS), specificity (0.996), practicability, and costs with conventional biochemical screening. Our results demonstrate a significant prevalence of SCD of approximately 1:12,000 in an unselected urban and rural population in Southwest Germany. Together with previously published even higher results from exclusively urban populations in Berlin and Hamburg, our data provide the basis for the decision on a newborn screening program for SCD in Germany.

Nine-Months Clinical Outcome of Biodegradable Polymer Coated Sirolimus-eluting Stent System: A Multi-Centre "Real-World" Experience.

PubMed

Sarma, Raghava; Prajapati, Jayesh; Raheem, Asif; Thakkar, Kamlesh; Kothari, Shivani; Thakkar, Ashok

2015-08-01

The main culprit in first-generation drug eluting stents is 'durable' polymer, whose continuous presence may impair arterial healing and ultimately have a negative impact on late outcomes. The main enigma behind the biodegradable polymer usage is its degradation after elution of drug. This reduces adverse events in unselected patients with complex coronary artery lesions treated with biodegradable polymer coated sirolimus-eluting stents. The aim of the INDOLIMUS-G Registry was to evaluate safety and efficacy of the Indolimus (Sahajanand Medical Technologies Pvt. Ltd., Surat, India) sirolimus-eluting stents in large cohorts of unselected patients with complex coronary artery lesions. It is a multi-centre, non-randomized retrospective registry with a clear aim of evaluating safety and efficacy of the Indolimus sirolimus-eluting stents in consecutive patients enrolled between April 2012 and May 2014. The primary end-point of the study was major adverse cardiac events (MACE), which is a composite of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR) and stent thrombosis (ST) at the end of follow-up. Clinical follow-up were scheduled at the end of 30-days, 6-months, and 9-months period. The mean age of enrolled patients was 52.6 ± 11.0 years. A total of 1137 lesions were intervened successfully with 1242 stents (1.09 ± 0.30 stent per lesion). The average stent length and diameter was 27.42 ± 9.01 mm and 3.12 ± 0.36 mm respectively. There were 740 (73.40%) male patients, indicating their high prevalence. Diabetes, hypertension and totally occluded lesions were found in 372 (36.90%), 408 (40.47%) and 170 (16.86%) patients, respectively. This showed that study also included high risk complex lesions and not ideal recruited lesions. The incidence of MACE at 30-days, 6-months and 9-months were 3 (0.30%), 18 (1.80%) and 22 (2.20%) respectively. At 9-months, TLR was found in 6 (0.50%) patients. There were 2 (0.20%) cases of ST, 10 (1.0%) cases of MI and 4 (0.40%) cases of cardiac death at 9-month follow-up. The lower incidence of MACE, TLR and ST at 9-month follow-up clearly delineates safety and efficacy of Indolimus SES in large cohorts of unselected patients with complex coronary lesions.

Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma

PubMed Central

Johannesen, Tom B⊘rge; Berner, Aasmund; Haugland, Hans Kristian; Bjerkehagen, Bodil; B⊘hler, Per J.; Bruland, Øyvind S.

2015-01-01

Abstract Background This study describes time-trends on epidemiology, subtypes and histopathological entities of osteosarcoma (OS) in a nationwide and unselected cohort of OS patients in Norway between 1975 and 2009. Few nationwide studies are published, and we still have particularly limited knowledge regarding patients not included in clinical trials comprising about half of the OS population. Method Histologically verified skeletal OS for all subgroups were included, resulting in 473 eligible cases from a total of 702 evaluated patients. To ensure completeness, the present cohort was based on all cases reported to the Norwegian Cancer Registry, complemented with data from all Norwegian hospitals involved in sarcoma management. Survival analyses were performed with overall and sarcoma-specific survival as endpoints. Results Mean annual age-standard incidence amounted to about 3.8 per million in male and 2.8 per million in female with no clear time-trends. The male to female ratio was 1.4. Peak incidence was observed in the second decade for both genders. Conventional OS comprised 71.2% of all cases, while low grade OS represented 10.4% and telangiectatic OS only 1.3%. The most common primary site of OS was femur and tibia, respectively. The axial to appendicular ratio increased with the age. The overall 10-year survival did increase from about 30% during the late 1970s to around 50% 20 years later, with no subsequent improvement during the last two decades. Axial tumours, age above 40 years and overt metastatic disease at time of diagnosis were all negative prognostic factors. Conclusion No improvement in the overall survival for OS since the 1990s was documented. The survival rates are still poor for elderly people, patients with axial disease and in the primary metastatic setting. The average incidence rate of skeletal OS in Norway was in line with international figures. PMID:24957555

Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma.

PubMed

Berner, Kjetil; Johannesen, Tom Børge; Berner, Aasmund; Haugland, Hans Kristian; Bjerkehagen, Bodil; Bøhler, Per J; Bruland, Øyvind S

2015-01-01

This study describes time-trends on epidemiology, subtypes and histopathological entities of osteosarcoma (OS) in a nationwide and unselected cohort of OS patients in Norway between 1975 and 2009. Few nationwide studies are published, and we still have particularly limited knowledge regarding patients not included in clinical trials comprising about half of the OS population. Histologically verified skeletal OS for all subgroups were included, resulting in 473 eligible cases from a total of 702 evaluated patients. To ensure completeness, the present cohort was based on all cases reported to the Norwegian Cancer Registry, complemented with data from all Norwegian hospitals involved in sarcoma management. Survival analyses were performed with overall and sarcoma-specific survival as endpoints. Mean annual age-standard incidence amounted to about 3.8 per million in male and 2.8 per million in female with no clear time-trends. The male to female ratio was 1.4. Peak incidence was observed in the second decade for both genders. Conventional OS comprised 71.2% of all cases, while low grade OS represented 10.4% and telangiectatic OS only 1.3%. The most common primary site of OS was femur and tibia, respectively. The axial to appendicular ratio increased with the age. The overall 10-year survival did increase from about 30% during the late 1970s to around 50% 20 years later, with no subsequent improvement during the last two decades. Axial tumours, age above 40 years and overt metastatic disease at time of diagnosis were all negative prognostic factors. No improvement in the overall survival for OS since the 1990s was documented. The survival rates are still poor for elderly people, patients with axial disease and in the primary metastatic setting. The average incidence rate of skeletal OS in Norway was in line with international figures.

Direct immunofluorescence of normal skin in rheumatoid arthritis.

PubMed

Fitzgerald, O M; Barnes, L; Woods, R; McHugh, L; Barry, C; O'Loughlin, S

1985-11-01

The clinical significance of previously described immunoglobulin and complement deposition in the superficial dermal vessel walls of patients with rheumatoid arthritis is unknown. In the present study, skin biopsies were obtained from the normal forearm and buttock of 48 unselected patients with rheumatoid arthritis and were examined by direct immunofluorescence (IF) for the presence of immunoglobulin (IgG,A,M) and complement (C3) in the vessel walls. Deposits of C3, IgM or IgG were detected in 10 patients. Five patients had deposits at the forearm sample alone, four patients had deposits at both biopsy sites, while one patient was positive at the buttock alone. Clinical features were similar in patients with and without vessel IF. However, patients with IF were significantly more seropositive with lower levels of complement and raised levels of serum IgA and IgM. There was also an increased level of circulating IgG immune complexes in these patients. Further analysis following exclusion of seronegative patients revealed similar results. This study suggests that the presence of vessel IF identifies a subgroup of patients who have evidence of more severe immunological disturbance.

High-Frequency Oscillations and Seizure Generation in Neocortical Epilepsy

ERIC Educational Resources Information Center

Worrell, Greg A.; Parish, Landi; Cranstoun, Stephen D.; Jonas, Rachel; Baltuch, Gordon; Litt, Brian

2004-01-01

Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high-frequency (60--100 Hz) epileptiform oscillations…

Manipulation Detection and Preference Alterations in a Choice Blindness Paradigm

PubMed Central

Taya, Fumihiko; Gupta, Swati; Farber, Ilya; Mullette-Gillman, O'Dhaniel A.

2014-01-01

Objectives It is commonly believed that individuals make choices based upon their preferences and have access to the reasons for their choices. Recent studies in several areas suggest that this is not always the case. In choice blindness paradigms, two-alternative forced-choice in which chosen-options are later replaced by the unselected option, individuals often fail to notice replacement of their chosen option, confabulate explanations for why they chose the unselected option, and even show increased preferences for the unselected-but-replaced options immediately after choice (seconds). Although choice blindness has been replicated across a variety of domains, there are numerous outstanding questions. Firstly, we sought to investigate how individual- or trial-factors modulated detection of the manipulations. Secondly, we examined the nature and temporal duration (minutes vs. days) of the preference alterations induced by these manipulations. Methods Participants performed a computerized choice blindness task, selecting the more attractive face between presented pairs of female faces, and providing a typewritten explanation for their choice on half of the trials. Chosen-face cue manipulations were produced on a subset of trials by presenting the unselected face during the choice explanation as if it had been selected. Following all choice trials, participants rated the attractiveness of each face individually, and rated the similarity of each face pair. After approximately two weeks, participants re-rated the attractiveness of each individual face online. Results Participants detected manipulations on only a small proportion of trials, with detections by fewer than half of participants. Detection rates increased with the number of prior detections, and detection rates subsequent to first detection were modulated by the choice certainty. We show clear short-term modulation of preferences in both manipulated and non-manipulated explanation trials compared to choice-only trials (with opposite directions of effect). Preferences were altered in the direction that subjects were led to believe they selected. PMID:25247886

Non-optic glioma in adults and children with neurofibromatosis 1.

PubMed

Sellmer, Laura; Farschtschi, Said; Marangoni, Marco; Heran, Manraj K S; Birch, Patricia; Wenzel, Ralph; Friedman, Jan M; Mautner, Victor-Felix

2017-02-15

Non-optic gliomas occur in 5% of children with NF1, but little is known about these tumours in adults. We aimed to investigate progression, spontaneous regression and the natural history of non-optic gliomas in adults and compare these findings to the results found in children. One thousand seven hundred twenty-two brain MRI scans of 562 unselected individuals with NF1 were collected at the NF outpatient department of the University Hospital Hamburg-Eppendorf between 2003 and 2015. The number of scans per patient ranged from one to 12; patients were followed for a median of 3.7 years. We identified 24 patients (4.3%) with non-optic gliomas. Median age at first scan with glioma was 21.2 years, much higher than in previous publications. Only seven of the 24 non-optic glioma patients were symptomatic. Five of 24 patients had multiple non-optic gliomas. Four individuals developed a new tumour, and 4 cases showed progression. The risk of new tumour development was 0.19% (95% confidence interval 0.06% to 0.52%) per patient year of follow-up for patients over 10 years. The rate of progressing non-optic gliomas per patient year of follow-up in the first 5 years after tumour diagnosis was 4.7% (95% confidence interval 1.5% to 12%). Non-optic gliomas are twice as common in an unselected cohort of NF1 patients as previously reported. This is likely due to increased frequency of diagnosis of asymptomatic tumours when routine MRIs are performed and a higher prevalence in older individuals.

Lack of nephrotoxicity of gadodiamide in unselected hospitalized patients.

PubMed

Trivedi, Hariprasad; Raman, Lakshmi; Benjamin, Heather; Batwara, Ruchika

2009-09-01

The nephrotoxicity of gadolinium-based magnetic resonance contrast media has not been adequately studied. We evaluated the nephrotoxicity of gadolinium-based contrast media in hospitalized patients who underwent magnetic resonance imaging (MRI) as part of routine clinical care. Subjects who had a serum creatinine measurement during the 7 days before MRI and at least 1 other measurement 2 to 3 days after MRI were included. Patients who underwent noncontrasted MRI served as controls. There were 162 subjects (mean age, 57.8 +/- 16.9 years; 91 men and 71 women) and 125 controls (mean age, 64.6 +/- 18 years; 62 men and 63 women). All contrast-enhanced MRI studies utilized gadodiamide (Omniscan; GE Healthcare, Waukesha, WI). Subjects who received gadodiamide showed no difference in the incidence of acute renal insufficiency compared with controls (increase in serum creatinine >or= 25%, 11.1% vs 12.9%, respectively; P = 0.6; increase in serum creatinine by 0.5 mg/dL, 5.6% vs 3.2%, respectively; P = 0.4). There was no significant increase in serum creatinine baseline versus 48 hours in either the subjects who received gadodiamide (0.95 +/- 0.58 vs 0.96 +/- 0.65 mg/dL; P = 0.7) or controls (0.96 +/- 0.65 vs 0.88 +/- 0.43 mg/dL; P = 0.7). Our findings showed a lack of significant nephrotoxicity of gadodiamide in unselected hospitalized patients.

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer

PubMed Central

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-01-01

Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1 (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2. Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing. PMID:29348823

Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.

PubMed

Hirasawa, Akira; Imoto, Issei; Naruto, Takuya; Akahane, Tomoko; Yamagami, Wataru; Nomura, Hiroyuki; Masuda, Kiyoshi; Susumu, Nobuyuki; Tsuda, Hitoshi; Aoki, Daisuke

2017-12-22

Pathogenic germline BRCA1 , BRCA2 ( BRCA1/2 ), and several other gene variants predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma (OC), although variant frequency and relevance information is scarce in Japanese women with OC. Using targeted panel sequencing, we screened 230 unselected Japanese women with OC from our hospital-based cohort for pathogenic germline variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were identified in 41 (17.8%) women: 19 (8.3%; BRCA1 ), 8 (3.5%; BRCA2 ), 6 (2.6%; mismatch repair genes), 3 (1.3%; RAD51D ), 2 (0.9%; ATM ), 1 (0.4%; MRE11A ), 1 ( FANCC ), and 1 ( GABRA6 ). Carriers of BRCA1/2 or any other tested gene pathogenic variants were more likely to be diagnosed younger, have first or second-degree relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC). After adjustment for these variables, all 3 features were independent predictive factors for pathogenic variants in any tested genes whereas only the latter two remained for variants in BRCA1/2 . Our data indicate similar variant prevalence in Japanese patients with OC and other ethnic groups and suggest that HGSC and OC family history may facilitate genetic predisposition prediction in Japanese patients with OC and referring high-risk patients for genetic counseling and testing.

Outcomes of Patients Treated with the Everolimus- versus the Paclitaxel-Eluting Stents in a Consecutive Cohort of Patients at a Tertiary Medical Center.

PubMed

Shammas, Nicolas W; Shammas, Gail A; Nader, Elie; Jerin, Michael; Mrad, Luay; Ehrecke, Nicholas; Shammas, Waheeb J; Voelliger, Cara M; Hafez, Alexander; Kelly, Ryan; Reynolds, Emily

2013-09-01

In this study, we compare the outcomes of the paclitaxel-eluting stent (PES) versus the everolimus-eluting stent (EES) treated patients at a tertiary medical center and up to 2 years follow-up. Unselected consecutive patients were retrospectively recruited following stenting with PES (159 patients) or EES (189 patients). The primary endpoint of the study was target lesion failure (TLF), defined as the combined endpoint of cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization (TLR). Secondary endpoints included target vessel revascularization (TVR), TLR, target vessel failure (TVF), acute stent thrombosis (ST), total death, cardiac death, and nonfatal MI. Patients treated with the PES stent had less congestive heart failure and restenotic lesions, but a higher prevalence of longer lesions, nonleft main bifurcations, required more stents per patient (4.3 ± 2.8 vs. 2.9 ± 2.1). TLF occurred in 32.3% PES versus 21.5% EES (p = 0.027). The secondary unadjusted endpoints for PES versus EES, respectively, were TVF 38.6 versus 30.7% (p = 0.140), TVR 35.7 versus 26.5% (p = 0.079), definite and probable ST 1.2 versus 0.0%, nonfatal MI 4.5 versus 4.2%, and mortality 9.6 versus 4.0%. Logistic regression analysis showed that the numbers of stents per patient (p = 0.001), age (p = 0.01), and renal failure (p = 0.045) were independent predictors of TLF. Using univariate analysis, EES had lower TLF than PES in a cohort of unselected patients undergoing percutaneous coronary intervention at 2 years follow-up. Multivariate analysis showed that the numbers of stents per patient, age, and renal failure, but not stent type, were predictors of TLF.

Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands : Design and rationale of the Chronic Heart failure ESC guideline-based Cardiology practice Quality project (CHECK-HF) registry.

PubMed

Brugts, J J; Linssen, G C M; Hoes, A W; Brunner-La Rocca, H P

2018-05-01

Data from patient registries give insight into the management of patients with heart failure (HF), but actual data from unselected real-world HF patients are scarce. Therefore, we performed a cross sectional study of current HF care in the period 2013-2016 among more than 10,000 unselected HF patients at HF outpatient clinics in the Netherlands. In 34 participating centres, all 10,910 patients with chronic HF treated at cardiology centres were included in the CHECK-HF registry. Of these, most (96%) were managed at a specific HF outpatient clinic. Heart failure was typically diagnosed according to the ESC guidelines 2012, based on signs, symptoms and structural and/or functional cardiac abnormalities. Information on diagnostics, treatment and co-morbidities were recorded, with specific focus on drug therapy and devices. In our cohort, the mean age was 73 years (SD 12) and 60% were male. Frequent co-morbidities reported in the patient records were diabetes mellitus 30%, hypertension 43%, COPD 19%, and renal insufficiency 58%. In 47% of the patients, ischaemia was the origin of HF. In our registry, the prevalence of HF with preserved ejection fraction was 21%. The CHECK-HF registry will provide insight into the current, real world management of patient with chronic HF, including HF with reduced ejection fraction, preserved ejection fraction and mid-range ejection fraction, that will help define ways to improve quality of care. Drug and device therapy and guideline adherence as well as interactions with age, gender and co-morbidities will receive specific attention.

Exploiting Molecular and Immune Biology of Gastric and Gastroesophageal Adenocarcinomas to Discover Novel Therapeutic Targets.

PubMed

Elimova, Elena; Song, Shumei; Shimodaira, Yusuke; Lin, Quan; Ajani, Jaffer A

2016-11-01

Gastroesophageal carcinomas (GACs) are a significant problem worldwide, and despite many attempts to improve the outcomes of patients with these tumors, little progress has been made over the last several decades. In the past decade, only transtuzumab and ramucirumab, two drugs with marginal clinical benefit, have been approved for the treatment of patients with GACs. After second-line therapy, most treatment options are generally ineffective. Prior studies in this disease have been largely empiric, using unselected patient populations. More recently, detailed somatic genotyping, enrichment of patients based on biomarkers, and pharmacokinetic studies have opened new avenues for developing treatment options in patients with GAC.

Treatment, Outcome and Prognostic Factors in Renal Cell Carcinoma - A Single Center Study (2000-2010)

PubMed Central

Achermann, Christof; Stenner, Frank; Rothschild, Sacha I.

2016-01-01

In Switzerland efficient availability of novel drugs for renal cell cancer (RCC) has been granted early. Since the advent of the targeted agents for RCC the usage of these drugs has been reported to improve progression free survival. Here, we find that patients who are able to receive sequential targeted therapy, including tyrosine kinase inhibitors (TKI) and mTOR inhibitors (mTORi), have a largely better outcome than those who have less exposure to these agents. The value of the prognostic scores developed by Motzer and Heng is fully reflected by the outcomes according to prognostic risk groups in our unselected patient cohort. Also, the use of surgical intervention appears to be an important prognostic factor, however with a somehow diminished effect by novel systemic therapies. The importance of multiple lines of targeted therapies is underlined by this retrospective analysis. For patients with metastatic RCC not receiving targeted therapy the median OS was 22.6 months compared to those with one TKI 25.4 months. Patients receiving a second-line therapy (median overall survival 27.6 months) and those patients with three or more lines of therapy (43.8 months) have the greatest benefit. Also, exposure to a mTORi improves survival versus non-exposure to mTORi (63.3 vs. 22.3 months, p=0.038). In conclusion a trend towards improved survival is confirmed for an unselected population when the full variety of therapeutic options is available and can be used for the individual patient. PMID:27313782

Electrocardiographic screening for emphysema: the frontal plane P axis.

PubMed

Baljepally, R; Spodick, D H

1999-03-01

Because the most characteristic and sensitive electrocardiographic (ECG) correlate of pulmonary emphysema in adults is verticalization of the frontal plane P-wave vector (P axis), we investigated its strength as a lone criterion to screen for obstructive pulmonary disease (OPD) in an adult hospital population. In all, 954 consecutive unselected ECGs were required to yield 100 with P axis > or = +70 degrees (unequivocally negative P in a VL during sinus rhythm) and pulmonary function tests. and 100 with P axis < or = +50 degrees (unequivocally positive P-aVL). Obstructive pulmonary disease by both pulmonary function test and clinical criteria was present in 89 of 100 patients with vertical P axes and 4 of 100 patients without OPD. The high sensitivity (89% for this series) and high specificity (96%) makes vertical P axis a useful screening criterion. Its at-a-glance simplicity makes it "user-friendly."

Removal of restrictions following primary THA with posterolateral approach does not increase the risk of early dislocation.

PubMed

Gromov, Kirill; Troelsen, Anders; Otte, Kristian Stahl; Ørsnes, Thue; Ladelund, Steen; Husted, Henrik

2015-01-01

Patient education and mobilization restrictions are often used in an attempt to reduce the risk of dislocation following primary THA. To date, there have been no studies investigating the safety of removal of mobilization restrictions following THA performed using a posterolateral approach. In this retrospective non-inferiority study, we investigated the rate of early dislocation following primary THA in an unselected patient cohort before and after removal of postoperative mobilization restrictions. From the Danish National Health Registry, we identified patients with early dislocation in 2 consecutive and unselected cohorts of patients who received primary THA at our institution from 2004 through 2008 (n = 946) and from 2010 through 2014 (n = 1,329). Patients in the first cohort were mobilized with functional restrictions following primary THA whereas patients in the second cohort were allowed unrestricted mobilization. Risk of early dislocation (within 90 days) was compared in the 2 groups and odds ratio (OR)-adjusted for possible confounders-was calculated. Reasons for early dislocation in the 2 groups were identified. When we adjusted for potential confounders, we found no increased risk of early dislocation within 90 days in patients who were mobilized without restrictions. Risk of dislocation within 90 days was lower (3.4% vs 2.8%), risk of dislocation within 30 days was lower (2.1% vs 2.0%), and risk of multiple dislocations (1.8% vs 1.1%) was lower in patients who were mobilized without restrictions, but not statistically significantly so. Increasing age was an independent risk factor for dislocation. Removal of mobilization restrictions from the mobilization protocol following primary THA performed with a posterolateral approach did not lead to an increased risk of dislocation within 90 days.

Testicular tumours in prepubertal children: About eight cases.

PubMed

Khemakhem, Rachid; Ahmed, Yosra Ben; Jlidi, Said; Nouira, Faouzi; Fdhila, Faten; Charieg, Awatef; Ghorbel, Sofiene; Barsaoui, Sihem; Chaouachi, Béji

2013-01-01

To analyze the spectrum of testicular tumors in prepubertal children and the therapeutic resultants in an unselected population. Our hospital database was analyzed for testicular tumors from January 1995 to December 2010 concerning clinical presentation, treatment and therapeutic results. Eight patients were operated on because of testicular tumors. In six cases (75%) the tumor was benign: benign teratoma (four cases), epidermoid cyst (one case) and immature teratoma (one case). Two patients (25%) had a malignant tumour: yolk-sac tumour (two cases). All this children underwent surgery. Radical inguinal orchidectomy was performed in six cases and conservative surgery was performed in two cases. One patient has received adjuvant chemotherapy. Follow-up was uneventfully three years after primary surgery. In prepubertal children, most testicular tumours are benign. If tumour markers were negative testis-preserving surgery can be proposed, complete excision of the tumour should be ascertained. In the case of testicular teratoma, the possibility of contralateral tumour should be considered in the follow-up.

Cortical processing during smartphone text messaging.

PubMed

Tatum, William O; DiCiaccio, Benedetto; Yelvington, Kirsten H

2016-06-01

The objective of this study was to report the EEG features of text messaging using smartphones. One hundred twenty-nine patients were prospectively evaluated during video-EEG monitoring (VEM) over 16months. A reproducible texting rhythm (TR) present during active text messaging with a smartphone was compared with passive and forced audio telephone use, thumb/finger movements, cognitive testing/calculation, scanning eye movements, and speech/language tasks in patients with and without epilepsy. Statistical significance was set at p<0.05. Twenty-seven patients with a TR were identified from a cohort of 129 (93 female, mean age: 36; range: 18-71) unselected VEM patients. Fifty-three out of 129 patients had epileptic seizures (ES), 74/129 had nonepileptic seizures (NES), and 2/129 were dual-diagnosed. A reproducible TR was present in 27/129 (20.9%) specific to text messaging (p<0.0001) and present in 28% of patients with ES and 16% of patients with NES (p=NS). The TR was absent during independent tasks and audio cellular telephone use (p<0.0001). Age, gender, epilepsy type, MRI results, and EEG lateralization in patients with focal seizures were unrelated (p=NS). Our results suggest that the TR on scalp EEG represents a novel technology-specific neurophysiological alteration of brain networks. We propose that cortical processing in the contemporary brain is uniquely activated by the use of PEDs. These findings have practical implications that could impact industry and research in nonverbal communication. Copyright © 2016 Elsevier Inc. All rights reserved.

Medically unexplained conditions considered by patients in general practice.

PubMed

Tschudi-Madsen, Hedda; Kjeldsberg, Mona; Natvig, Bård; Ihlebaek, Camilla; Straand, Jørund; Bruusgaard, Dag

2014-04-01

Patients frequently present with multiple and 'unexplained' symptoms, often resulting in complex consultations. To better understand these patients is a challenge to health care professionals, in general, and GPs, in particular. In our research on symptom reporting, we wanted to explore whether patients consider that they may suffer from conditions commonly regarded as unexplained, and we explored associations between these concerns and symptom load, life stressors and socio-demographic factors. Consecutive, unselected patients in general practice completed questionnaires addressing eight conditions commonly regarded as unexplained (amalgam poisoning, Candida syndrome, fibromyalgia, food intolerance, electromagnetic hypersensitivity, burnout syndrome, chronic fatigue syndrome and irritable bowel syndrome). With logistic regression, we analysed associations with symptom load, burden of life stressors with negative impact on present health and socio-demographic variables. Out of the 909 respondents (response rate = 88.8%), 863 had complete data. In total, 39.6% of patients had considered that they may suffer from one or more unexplained conditions (UCs). These concerns were strongly and positively associated with recent symptom load and number of life stressors. If we excluded burnout and food intolerance, corresponding associations were found. Patients frequently considered that they may suffer from UCs. The likelihood of such concerns strongly increased with an increasing symptom load and with the number of life stressors with negative impact on present health. Hence, the number of symptoms may be a strong indicator of whether patients consider their symptoms part of such often controversial multisymptom conditions.

Gastro-oesophageal reflux in patients with chronic rhino-sinusitis investigated with multichannel impedance - pH monitoring.

PubMed

Katle, E J; Hatlebakk, J G; Grimstad, T; Kvaløy, J T; Steinsvåg, S K

2017-03-01

The pathophysiology of chronic rhinosinusitis (CRS) is unclear. It has been discussed for decades whether gastro-oesophageal reflux (GOR) may be a contributing factor for some patients. The aim of the present study was to evaluate the level of GOR in an unselected group of patients with CRS using multichannel impedance-pH monitoring. Consecutive patients with CRS diagnosed using the EPOS2012 criteria, completed questionnaires on GOR symptoms and were offered 24-h multichannel intraluminal impedance (MII)-pH monitoring. The results were compared with a group of healthy controls. Forty-six patients completed MII-pH-monitoring and were compared with 45 control subjects, with comparable age and gender distributions. The median number of reflux episodes in the patients was 56.5 compared with 33 in controls, while, the numbers of proximal reflux episodes was 27.5 versus 3, respectively. Thirty nine patients had abnormal pH-impedance recordings compared with five controls. The CRS patients had significantly higher incidences of gastro-oesophageal reflux compared with asymptomatic controls. The results of this study suggest that GOR may be a causative or contributing factor of CRS.

Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.

PubMed

Kishore, Amit; Vail, Andy; Majid, Arshad; Dawson, Jesse; Lees, Kennedy R; Tyrrell, Pippa J; Smith, Craig J

2014-02-01

Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity even within specified subgroups. Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Clinical significance of specific autoantibodies in juvenile dermatomyositis.

PubMed

Feldman, B M; Reichlin, M; Laxer, R M; Targoff, I N; Stein, L D; Silverman, E D

1996-10-01

To determine the prevalence and clinical association of myositis specific antibodies in an unselected group of patients with juvenile dermatomyositis (DM). The sera of 42 subjects, representing an unselected group of patients from a single center, with juvenile DM and 7 others with idiopathic inflammatory myopathy (IIM) were examined for the presence of myositis specific antibodies by immunodiffusion against calf thymus extract and immunoprecipitation with HeLa extract. Of the subjects with juvenile DM, only 2 had evidence of antibodies specific to myositis (anti-Mi2). Three other patients with juvenile DM had defined autoantibodies not usually considered to be specific to myositis. Two of the 3 subjects had anti-PM-Scl; both developed features of scleroderma after the juvenile DM remitted. The 5 subjects with defined autoantibodies did not differ clinically from the remainder of the subjects with the exception of the late development of scleroderma features in 2. Fourteen other subjects with juvenile DM had unidentified bands on immunoprecipitation, which may represent as yet undiscovered myositis specific antibodies. No myositis specific antibodies were detected in any of the 7 subjects with other IIM syndromes. Based on our findings, we do not recommend routine clinical testing for these antibodies in children with typical juvenile DM. Further study of the unidentified bands seen in our subjects may lead to better understanding of the clinical groupings and etiopathogenesis of childhood myositis.

Symptoms of gonadal dysfunction are more predictive of hypopituitarism than nonspecific symptoms in screening for pituitary dysfunction following moderate or severe traumatic brain injury.

PubMed

Cuesta, Martín; Hannon, Mark J; Crowley, Rachel K; Behan, Lucy Ann; Tormey, William; Rawluk, Daniel; Delargy, Mark; Agha, Amar; Thompson, Christopher J

2016-01-01

The economic and logistic burden of screening for hypopituitarism following moderate/severe traumatic brain injury (TBI) is considerable. A key recommendation in published guidelines is to prioritize for screening those patients with symptoms suggestive of pituitary dysfunction. The purpose of this study was to evaluate the utility of targeted screening for hypopituitarism in long-term survivors after moderate/severe TBI using referrals on the basis of symptoms. In group 1 (G1), consecutive, unselected patients were screened from the Irish National Neurosurgery Centre, whereas in group 2 (G2) patients were targeted based on the presence of symptoms suggestive of pituitary dysfunction. A total of 137 patients (113 male) were systematically screened (G1) and compared to 112 patients (77 male) referred for pituitary evaluation on the basis of suggestive symptoms (G2). The rate of GH, ACTH, gonadotrophin (GT), TSH and ADH deficiency was compared among groups. Patients referred with menstrual dysfunction had more GH (50% vs 11%, P = 0·001), ACTH (60% vs 14%, P < 0·0001), GT (90% vs 16%, P < 0·0001) deficiency and any pituitary hormone deficit (80% vs 33%, P = 0·003) than G1. Men with symptoms of hypogonadism had more GH (33% vs 11%, P = 0·003), GT (58% vs 16%, P < 0·0001) and TSH (16% vs 1%, P = 0·03) deficiency than G1. Patients with nonspecific symptoms were no more likely to have hypopituitarism than those consecutively screened. Symptoms of hypogonadism are sufficiently predictive of hypopituitarism to justify screening for hypopituitarism after moderate/severe TBI. Nonspecific symptoms of hypopituitarism are no more predictive than unselected screening. © 2015 John Wiley & Sons Ltd.

Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa.

PubMed

Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; van Wyk, Gavin; Vogt, Monica; Pahlana, Pearl; Nicol, Mark P; Meintjes, Graeme

2015-08-14

Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34-64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert). To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission. Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1-37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001). The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain.

BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer.

PubMed

Sakamoto, Ikuko; Hirotsu, Yosuke; Nakagomi, Hiroshi; Ouchi, Hidetaka; Ikegami, Atsushi; Teramoto, Katsuhiro; Amemiya, Kenji; Mochizuki, Hitoshi; Omata, Masao

2016-01-01

The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer. Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing. Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas). In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers. © 2015 American Cancer Society.

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

PubMed

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

A Danish population-based analysis of 105 mantle cell lymphoma patients: incidences, clinical features, response, survival and prognostic factors.

PubMed

Andersen, N S; Jensen, M K; de Nully Brown, P; Geisler, C H

2002-02-01

This study presents the first large clinical analysis of 105 unselected mantle cell lymphoma (MCL) patients diagnosed from 1992 to 2000 in a well-defined Danish population. The annual incidences were 0.7/100000 for men and 0.2/100000 for women, with no significant change during the study period. Of 97 evaluable cases, 43% achieved a complete response (CR) after initial therapy. The median disease-free (DFS) and overall survival (OS) rates were 15 and 30 months, respectively. In multivariate analysis, splenomegaly (P=0.002), anaemia (P=0.0001) and age (P=0.002), but not the international prognostic index (IPI) and the Ann Arbor staging system, had an independent impact on survival. Moreover, in a sub-analysis of 45 younger MCL patients (<65 years), a trend towards an OS plateau of 58% was observed in cases without splenomegaly and anaemia (n=29). Thus, in contrast to previously suggested prognostic factors, these variables may prove useful for clinical decisions in a significant subset of MCL patients.

Dynamic self-regulating prosthesis (protesi autoregolantesi dinamica): the long-term results in the treatment of primary inguinal hernias.

PubMed

Valenti, Gabriele; Baldassarre, Emanuele; Testa, Alessandro; Arturi, Alessandro; Torino, Giovanni; Campisi, Costantino; Capuano, Giorgio

2006-03-01

The dynamic self-regulating prosthesis (protesi autoregolantesi dinamica, PAD) is a double-layered prosthesi, in use since 1992 in inguinal hernia repair. In 1999, we published the short-term results on 500 patients and herein we report the long-term follow-up. Five hundred eighty-five PAD procedures were performed on 500 adult male, unselected patients. Hernias were unilateral in 415 patients, were bilateral in 85 patients, were direct in 197 patients (33.7%), were indirect in 269 patients (46.0%), and were combined in 119 patients (20.3%). Four hundred sixty-four patients were alive at the follow-up period of minimum 5 years, whereas 36 died (7.2%) of causes unrelated to the hernia. No information was available on 73 patients (14.6%). Therefore, the follow-up was consisted of 391 patients (78.2%) with 469 hernias. The recurrence and testicular atrophy rates were nil. Three patients (0.77%) presented chronic pain and 18 (4.6%) suffered persistent discomfort or paresthesia. A hydrocoele was observed in one patient (0.2%). The long-term data confirm the efficacy of the dynamic self-regulating posthesis hernioplasty. We propose it as a standard of care in all cases of primary inguinal hernia in adult males, retaining it as a definitive and comfortable solution.

Model of inter-cell interference phenomenon in 10 nm magnetic tunnel junction with perpendicular anisotropy array due to oscillatory stray field from neighboring cells

NASA Astrophysics Data System (ADS)

Ohuchida, Satoshi; Endoh, Tetsuo

2018-06-01

In this paper, we propose a new model of inter-cell interference phenomenon in a 10 nm magnetic tunnel junction with perpendicular anisotropy (p-MTJ) array and investigated the interference effect between a program cell and unselected cells due to the oscillatory stray field from neighboring cells by Landau–Lifshitz–Gilbert micromagnetic simulation. We found that interference brings about a switching delay in a program cell and excitation of magnetization precession in unselected cells even when no programing current passes through. The origin of interference is ferromagnetic resonance between neighboring cells. During the interference period, the precession frequency of the program cell is 20.8 GHz, which synchronizes with that of the theoretical precession frequency f = γH eff in unselected cells. The disturbance strength of unselected cells decreased to be inversely proportional to the cube of the distance from the program cell, which is in good agreement with the dependence of stray field on the distance from the program cell calculated by the dipole approximation method.

Use of prophylactic Saccharomyces boulardii to prevent Clostridium difficile infection in hospitalized patients: a controlled prospective intervention study.

PubMed

Carstensen, Jeppe West; Chehri, Mahtab; Schønning, Kristian; Rasmussen, Steen Christian; Anhøj, Jacob; Godtfredsen, Nina Skavlan; Andersen, Christian Østergaard; Petersen, Andreas Munk

2018-05-03

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 10 9 , Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.

BRCAsearch: written pre-test information and BRCA1/2 germline mutation testing in unselected patients with newly diagnosed breast cancer.

PubMed

Nilsson, Martin P; Törngren, Therese; Henriksson, Karin; Kristoffersson, Ulf; Kvist, Anders; Silfverberg, Barbro; Borg, Åke; Loman, Niklas

2018-02-01

To evaluate a simplified method of pre-test information and germline BRCA1/2 mutation testing. In a prospective, single-arm study, comprehensive BRCA1/2 testing was offered to unselected patients with newly diagnosed breast cancer at three hospitals in south Sweden (BRCAsearch, ClinicalTrials.gov Identifier: NCT02557776). Pre-test information was provided by a standardized invitation letter, but the patients could contact a genetic counselor for telephone genetic counseling if they felt a need for that. Noncarriers were informed about the test result through a letter. Mutation carriers were contacted and offered an appointment for in-person post-test genetic counseling. During the period Feb 2, 2015-Aug 26, 2016, eight hundred and eighteen patients were invited to participate in the study. Through Jan 31, 2017, five hundred and forty-two (66.2%) of them consented to analysis of BRCA1 and BRCA2. Eleven pathogenic mutations were found (BRCA1, n = 2; BRCA2, n = 9), corresponding to a mutation prevalence of 2.0%. Six out of 11 fulfilled the Swedish BRCA testing criteria, and 9 out of 11 fulfilled the NCCN testing criteria. None of the BRCA-associated tumors were of the luminal A-like subtype. Very few patients contacted us for telephone genetic counseling or practical questions, suggesting that a majority felt that the written pre-test information was sufficient for them to make a decision on testing. Streamlining the process of pre-test information, genetic testing, and delivery of test results was feasible and was associated with an uptake of genetic testing in 2/3 of the breast cancer patients.

Use of Diuretics is not associated with mortality in patients admitted to the emergency department: results from a cross-sectional study.

PubMed

Haider, Dominik G; Lindner, Gregor; Wolzt, Michael; Leichtle, Alexander Benedikt; Fiedler, Georg-Martin; Sauter, Thomas C; Fuhrmann, Valentin; Exadaktylos, Aristomenis K

2016-02-01

Patients with diuretic therapy are at risk for drug-induced adverse reactions. It is unknown if presence of diuretic therapy at hospital emergency room admission is associated with mortality. In this cross sectional analysis, all emergency room patients 2010 and 2011 at the Inselspital Bern, Switzerland were included. A multivariable logistic regression model was performed to assess the association between pre-existing diuretic medication and 28 day mortality. Twenty-two thousand two hundred thirty-nine subjects were included in the analysis. A total of 8.5%, 2.5%, and 0.4% of patients used one, two, or three or more diuretics. In univariate analysis spironolactone, torasemide and chlortalidone use were associated with 28 day mortality (all p < 0.05). In a multivariate cox regression model no association with mortality was detectable (p > 0.05). No difference existed between patients with or without diuretic therapy (P > 0.05). Age and creatinine were independent risk factors for mortaliy (both p < 0.05). Use of diuretics is not associated with mortality in an unselected cohort of patients presenting in an emergency room.

Bone breaking strength and apparent metabolisability of calcium and phosphorus in selected and unselected broiler chicken genotypes.

PubMed

McDevitt, R M; McEntee, G M; Rance, K A

2006-10-01

1. The present study examined the bone strength and apparent mineral metabolisability of a selected broiler chicken compared with those of a relatively unselected genotype. 2. Selected (SB) and unselected genotypes (UB) were reared under standard conditions and were fed on either a high quality (HQ) or a low quality (LQ) diet. Tibiotarsi samples were collected at 42 d from SB and compared to tibiotarsi from UB of the same age and the same body mass (BM). 3. Bones were assessed for: bone breaking strength (BBS), morphology (weight and length), and both organic (OM) and inorganic content (ASH). Apparent dry matter digestibility and the coefficient of apparent metabolisability of calcium and phosphorus were determined at the same BM. 4. The BBS of SB (214 +/- 9 N) was greater than that of same-age UB (119 +/- 8 N) but the same as that of same-BM UB (218 +/- 10 N). At the same age, the SB had stronger, heavier bones with more ash and organic matter per unit length of tibiotarsus than UB. At the same BM, the tibiotarsi of the SB were shorter and lighter, with a higher ash and a similar organic content than the bones of the UB. At the same BM, BBS was about 15% lower in both genotypes fed on the LQ compared to the HQ diet. 5. The coefficients of apparent metabolisability of calcium and phosphorus were the same in both genotypes when fed on the HQ diet, but were lower in the SB than in the UB genotype when the birds were given the LQ diet. 6. The tibiotarsi of the selected broilers were stronger, or at least as strong, as those of the unselected broiler genotype, which may be due to similar levels of apparent calcium metabolisability of the selected chickens.

Anosognosia for obvious visual field defects in stroke patients.

PubMed

Baier, Bernhard; Geber, Christian; Müller-Forell, Wiebke; Müller, Notger; Dieterich, Marianne; Karnath, Hans-Otto

2015-01-01

Patients with anosognosia for visual field defect (AVFD) fail to recognize consciously their visual field defect. There is still unclarity whether specific neural correlates are associated with AVFD. We studied AVFD in 54 patients with acute stroke and a visual field defect. Nineteen percent of this unselected sample showed AVFD. By using modern voxelwise lesion-behaviour mapping techniques we found an association between AVFD and parts of the lingual gyrus, the cuneus as well as the posterior cingulate and corpus callosum. Damage to these regions appears to induce unawareness of visual field defects and thus may play a significant role for conscious visual perception.

Impact of severe tricuspid regurgitation on accuracy of systolic pulmonary arterial pressure measured by Doppler echocardiography: Analysis in an unselected patient population.

PubMed

Fei, Beini; Fan, Ting; Zhao, Ling; Pei, Xiaoli; Shu, Xianhong; Fang, Xiaoyan; Cheng, Leilei

2017-07-01

Pulmonary arterial pressure is an important index in cardiovascular disorders, especially for pulmonary hypertension (PH). Doppler echocardiography (DE) is widely used as a noninvasive method to assess pulmonary arterial pressure. However, recent studies have found several hemodynamic factors that affect its accuracy in estimating systolic pulmonary arterial pressure (sPAP). But the effect of tricuspid regurgitation (TR) has not been investigated. Therefore, our study is aimed to determine whether the severity of TR will affect the accuracy of sPAP measured by DE in an unselected patient population. We retrospectively studied 177 patients who underwent DE and right heart catheterization (RHC) examinations. Patients were categorized into 3 groups according to the severity of TR (mild, moderate, and severe). The discrepancy in sPAP measured by DE and RHC was calculated and compared in each group. Determinants of discordant results between two methods were also evaluated. Age, gender, interval between DE and RHC, sequence of DE and RHC were similar among groups (all P>.05). Differences in sPAP, RAP, and tricuspid regurgitation pressure gradient (TR-PG) were similar in group 1 and 2 (all P>.05), while all significantly higher in group 3 (all P<.05). The difference in sPAP between DE and RHC was affected independently by severe TR and severe PH (both P<.05). Severe TR and severe PH affect the accuracy of sPAP measured by DE. Modification of echocardiographic sPAP measurements by taking into consideration of these factors may lead to reduced systemic errors. © 2017, Wiley Periodicals, Inc.

Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer

PubMed Central

Glenn, Wendy K.; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J.; Lawson, James S.

2012-01-01

Background The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. Materials and Methods All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). Results EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk – EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. Conclusions We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer. PMID:23183846

Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

PubMed

Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

2012-01-01

The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

Veress needle insertion into the left hypochondrium for creation of pneumoperitoneum: diagnostic value of tests to determine the position of the needle in unselected patients.

PubMed

Becker, Otávio Monteiro; Azevedo, João Luiz Moreira Coutinho; de Azevedo, Otávio Cansanção; Hypólito, Octávio Henrique Mendes; Miyahira, Susana Abe; Miguel, Gustavo Peixoto Soares; Machado, Afonso Cesar Cabral Guedes

2011-01-01

To assess the effectiveness of the Veress needle puncture in the left hypochondrium and the accuracy of the tests described for the intraperitoneal correct positioning of the tip of the Veress needle in an unselected population. Ninetyone patients consecutively scheduled for Videolaparoscopy had the abdominal wall punctured in the left hypochondrium. There were no exclusion criteria. The patients received general anesthesia and mechanical ventilation according to the protocol. After puncturing five tests were used to confirm the positioning of the needle tip within the peritoneal cavity: aspiration test--AT; resistance to infusion--Pres; recovery of the infused fluid--Prec, dripping test--DT, and test of initial intraperitoneal pressure--IIPP. The test results were compared with results from literature for groups with defined exclusion criteria. The results were used for calculating sensitivity (S) specificity (E), positive predictive value (PPV) and negative predictive value (NPV). Inferential statistical methods were used to analyze the findings. There were 13 failures. AT had E = 100% and NPV 100%. Pres had S = 100%, E = 0; PPV = 85.71%; NPV does not apply. Prec: S = 100%, E = 53.84%, PPV = 92.85%, NPV = 100%. DT: S = 100%, E = 61.53%, PPV = 93.97% NPV 100%. In IIPP, S, E, PPV and NPV were 100%. The puncture in the left hypochondrium is effective and the performed tests guide the surgeon regardless of sex, BMI, or previous laparotomy.

RAD50 germline mutations are associated with poor survival in BRCA1/2-negative breast cancer patients.

PubMed

Fan, Cong; Zhang, Juan; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

2018-05-04

RAD50 is a highly conserved DNA double-strand break (DSB) repair gene. However, the associations between RAD50 germline mutations and the survival and risk of breast cancer have not been fully elucidated. Here, we aimed to investigate the clinical impact of RAD50 germline mutations in a large cohort of unselected breast cancer patients. In this study, RAD50 germline mutations were determined using next-generation sequencing in 7657 consecutive unselected breast cancer patients without BRCA1/2 mutations. We also screened for RAD50 recurrent mutations (L719fs, K994fs, and H1269fs) in 5000 healthy controls using Sanger sequencing. We found that 26 out of 7657 (0.34%) patients had RAD50 pathogenic mutations, and 16 patients carried one of the three recurrent mutations (L719fs, n=6 cases; K994fs, n=5 cases; and H1269fs, n=5 cases); the recurrent mutation rate was 0.21%. The frequency of the three recurrent mutations in the 5000 healthy controls was 0.18% (9/5000). These mutations did not confer an increased risk of breast cancer in the studied patients [odds ratios (OR), 1.16; 95% confidence interval (CI), 0.51-2.63; P = 0.72]. Nevertheless, multivariate analysis revealed that RAD50 pathogenic mutations were an independent unfavourable predictor of recurrence-free survival (RFS) [adjusted hazard ratio (HR) 2.66; 95% CI, 1.18-5.98; P=0.018] and disease-specific survival (DSS) (adjusted HR 4.36; 95% CI, 1.58-12.03; P=0.004) in the entire study cohort. Our study suggested that RAD50 germline mutations are not associated with an increased risk of breast cancer, but patients with RAD50 germline mutations have unfavourable survival compared with patients without these mutations. This article is protected by copyright. All rights reserved. © 2018 UICC.

Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma.

PubMed Central

Griffiths, A P; Wyatt, J; Jack, A S; Dixon, M F

1994-01-01

A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions. Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%). This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma. PMID:7876391

Atherosclerotic renovascular disease – epidemiology, treatment and current challenges

PubMed Central

Vassallo, Diana

2017-01-01

The neutral results of recent large randomized controlled trials comparing renal revascularization with optimal medical therapy in patients with atherosclerotic renovascular disease (ARVD) have cast doubt on the role of revascularization in the management of unselected patients with this condition. However, these studies have strengthened the evidence base for the role of contemporary intensive medical vascular protection therapy and aggressive risk factor control in improving clinical outcomes in ARVD. Patients presenting with ‘high-risk’ clinical features such as uncontrolled hypertension, rapidly declining renal function or flash pulmonary oedema are underrepresented in these studies; hence these results may not be applicable to all patients with ARVD. In this ‘high-risk’ subgroup, conservative management may not be sufficient in preventing adverse events, and indeed, observational evidence suggests that this specific patient subgroup may gain benefit from timely renal revascularization. Current challenges include the development of novel diagnostic techniques to establish haemodynamic significance of a stenosis, patient risk stratification and prediction of post-revascularization outcomes to ultimately facilitate patient selection for revascularization. In this paper we describe the epidemiology of this condition and discuss treatment recommendations for this condition in light of the results of recent randomized controlled trials while highlighting important clinical unmet needs and challenges faced by clinicians managing this condition. PMID:29056991

Germline EMSY sequence alterations in hereditary breast cancer and ovarian cancer families.

PubMed

Määttä, Kirsi M; Nurminen, Riikka; Kankuri-Tammilehto, Minna; Kallioniemi, Anne; Laasanen, Satu-Leena; Schleutker, Johanna

2017-07-24

BRCA1 and BRCA2 mutations explain approximately one-fifth of the inherited susceptibility in high-risk Finnish hereditary breast and ovarian cancer (HBOC) families. EMSY is located in the breast cancer-associated chromosomal region 11q13. The EMSY gene encodes a BRCA2-interacting protein that has been implicated in DNA damage repair and genomic instability. We analysed the role of germline EMSY variation in breast/ovarian cancer predisposition. The present study describes the first EMSY screening in patients with high familial risk for this disease. Index individuals from 71 high-risk, BRCA1/2-negative HBOC families were screened for germline EMSY sequence alterations in protein coding regions and exon-intron boundaries using Sanger sequencing and TaqMan assays. The identified variants were further screened in 36 Finnish HBOC patients and 904 controls. Moreover, one novel intronic deletion was screened in a cohort of 404 breast cancer patients unselected for family history. Haplotype block structure and the association of haplotypes with breast/ovarian cancer were analysed using Haploview. The functionality of the identified variants was predicted using Haploreg, RegulomeDB, Human Splicing Finder, and Pathogenic-or-Not-Pipeline 2. Altogether, 12 germline EMSY variants were observed. Two alterations were located in the coding region, five alterations were intronic, and five alterations were located in the 3'untranslated region (UTR). Variant frequencies did not significantly differ between cases and controls. The novel variant, c.2709 + 122delT, was detected in 1 out of 107 (0.9%) breast cancer patients, and the carrier showed a bilateral form of the disease. The deletion was absent in 897 controls (OR = 25.28; P = 0.1) and in 404 breast cancer patients unselected for family history. No haplotype was identified to increase the risk of breast/ovarian cancer. Functional analyses suggested that variants, particularly in the 3'UTR, were located within regulatory elements. The novel deletion was predicted to affect splicing regulatory elements. These results suggest that the identified EMSY variants are likely neutral at the population level. However, these variants may contribute to breast/ovarian cancer risk in single families. Additional analyses are warranted for rare novel intronic deletions and the 3'UTR variants predicted to have functional roles.

Individual differences in circadian waveform of Siberian hamsters under multiple lighting conditions

PubMed Central

Evans, Jennifer A.; Elliott, Jeffrey A.; Gorman, Michael R.

2013-01-01

Because the circadian clock in the mammalian brain derives from a network of interacting cellular oscillators, characterizing the nature and bases of circadian coupling is fundamental to understanding how the pacemaker operates. Various phenomena involving plasticity in circadian waveform have been theorized to reflect changes in oscillator coupling; however, it remains unclear whether these different behavioral paradigms reference a unitary underlying process. To test if disparate coupling assays index a common mechanism, we examined whether there is co-variation among behavioral responses to various lighting conditions that produce changes in circadian waveform. Siberian hamsters, Phodopus sungorus, were transferred from long to short photoperiods to distinguish short photoperiod responders (SP-R) from non-responders (SP-NR). Short photoperiod chronotyped hamsters were subsequently transferred, along with unselected controls, to 24 h light:dark:light:dark cycles (LDLD) with dim nighttime illumination, a procedure that induces bifurcated entrainment. Under LDLD, SP-R hamsters were more likely to bifurcate their rhythms than SP-NR hamsters or unselected controls. After transfer from LDLD to constant dim light, SP-R hamsters were also more likely to become arrhythmic compared to SP-NR hamsters and unselected controls. In contrast, short photoperiod chronotype did not influence more transient changes in circadian waveform. The present data reveal a clear relationship in the plasticity of circadian waveform across three distinct lighting conditions, suggesting a common mechanism wherein individual differences reflect variation in circadian coupling. PMID:23010663

[Corifollitropin alfa in women stimulated for the first time in in vitro fertilization programme].

PubMed

Vraná-Mardešićová, N; Vobořil, J; Melicharová, L; Jelínková, L; Vilímová, Š; Mardešić, T

2017-01-01

To compare results after stimulation with corifollitropin alfa (Elonva) in unselected group of women entering for the first time in in vitro fertilization programme (IVF) with results from Phase III randomized trials with selected groups of women. Prospective study. Sanatorium Pronatal, Praha. 40 unselected women with adequat ovarian reserve entering for the first time in IVF programme were stimulated with corifollitropin alfa and GnRH antagonists. Avarage age in the study group was 32,8 years (29-42 years), women younger then 36 and less then 60 kg received Elonva 100 µg , all others (age > 36 let, weight > 60 kg) Elonva 150 µg. Five days after egg retrieval one blastocyst was transferred (single embryo transfer - eSET). Our results were compared with the resuls in higly selected groups of women from Phase III randomized trials. After stimulation with corifollitropin alfa and GnRH antagonists on average 10,6 (9,2 ± 4,2) eggs could be retrieved, among them 7,3 (6,6 ± 3,9) were M II oocytes (68,9%) and fertilisation rate was 84,6%. After first embryo transfer ("fresh" embryos and embryos from "freeze all" cycles) 14 pregnancies were achieved (37,8%), three pregnancies were achieved later from transfer of frozen-thawed embryos (cumulative pregnancy rate 45,9%). There were three abortions. No severe hyperstimulation syndrom occured. Our results in unselected group of women stimulated for the first in an IVF programme with corifollitropin alfa are fully comparable with results published in randomized trials with selected group of patiens. Corifollitropin alfa in combination with daily GnRH antagonist can be successfully used in normal-responder patients stimulated for the first time in an IVF programmeKeywords: corifollitropin alfa, GnRH antagonists, ovarian stimulation, pregnancy.

The effects of armodafinil on objective sleepiness and performance in a shift work disorder sample unselected for objective sleepiness.

PubMed

Howard, Ryan; Roth, Thomas; Drake, Christopher L

2014-06-01

Armodafinil is a medication used to treat excessive sleepiness in individuals with shift work disorder (SWD). In the present study, we investigate whether armodafinil can normalize nocturnal sleepiness in a group of typical SWD patients. Participants were 12 night workers (aged 33.8 ± 8.57 years, 7 female subjects) with excessive sleepiness (≥10 on the Epworth Sleepiness Scale; mean, 14.8 ± 3.16), meeting the International Classification of Sleep Disorders, Second Edition criteria for SWD, with no other sleep or medical disorders verified by polysomnogram. The multiple sleep latency test (MSLT) was not used as an entry criteria. Armodafinil was administered at 10:30 pm in a randomized, double-blind, placebo-controlled, crossover design with experimental nights separated by 1 week. Primary end point was the MSLT, with naps at 1:30, 3:30, 5:30, and 7:30 am. Other study measures included a sleepiness-alertness visual analog scale administered before each nap, and 2 computer-based performance tests evaluating attention and memory. Subjects with SWD had a mean MSLT of 5.3 ± 3.25 minutes, indicating a mean level of pathological sleepiness. Armodafinil significantly improved MSLT score to 11.1 ± 4.79 minutes (P = 0.006). Subjective levels of alertness on the visual analog scale also improved (P = 0.008). For performance, reaction time to central (P = 0.006) and peripheral (P = 0.003) stimuli and free recall memory (P = 0.05) were also improved. Armodafinil 150 mg administered at the beginning of a night shift normalizes nocturnal sleepiness in individuals with SWD unselected for objective sleepiness. Subjective measures of sleepiness and cognitive performance are also improved. This suggests that armodafinil can improve levels of nocturnal alertness to within normal daytime levels in the majority of patients with SWD.

Interactive videoconsultation is a feasible method for neurological in-patient assessment.

PubMed

Craig, J; Patterson, V; Russell, C; Wootton, R

2000-11-01

To evaluate the feasibility of interactive videoconsultation (IATV) as a means by which neurologists might assess patients admitted with neurological symptoms to hospitals distant from a neurological centre, we studied 25 unselected patients using interactive videoconsultation (IATV) and then validated the IATV diagnoses and management plans at a later face-to-face consultation. IATV consultation led to an eventual diagnosis in 23 out of 25 patients, with one diagnosis being changed and one remaining uncertain. The IATV management plans were felt to be appropriate for all patients in study. Twelve patients were able to be discharged from hospital on the same day as IATV on the advice of the neurologist. It is therefore practical to assess patients admitted with neurological symptoms to distant hospitals using IATV and this may result in more efficient use of in-patient resources.

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population.

PubMed

Brain, Keith L; Kay, Jonathan; Shine, Brian

2006-11-01

Despite the rarity of pheochromocytoma, diagnosis is important because of the dangers of uncontrolled severe hypertension and the availability of very effective surgical treatment. Urinary or plasma catecholamines or catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, and sex may better predict tumors in populations with a low pretest probability. We retrospectively studied outcomes of an unselected population (1819 patients) referred to a tertiary hospital laboratory for urinary metanephrine testing and investigated the usefulness of some simple derivative measures for detecting pheochromocytoma. We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range. We then compared pheochromocytoma prediction by the use of products of these normalized measures with the gold standard of biopsy-confirmed tumor. The product of the excretion of normalized metanephrine (nMAD) and normalized normetanephrine (nNMT) (nMAD.nNMT) was a highly sensitive (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%. ROC curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. The test for nMAD.nNMT gave higher sensitivity and specificity than the tests for either substance alone. The test for nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pretest probability.

Elevated carboxyhemoglobin: sources of carbon monoxide exposure.

PubMed

Buchelli Ramirez, Herminia; Fernández Alvarez, Ramón; Rubinos Cuadrado, Gemma; Martinez Gonzalez, Cristina; Rodriguez Jerez, Francisco; Casan Clara, Pere

2014-11-01

Inhalation of carbon monoxide (CO) can result in poisoning, with symptoms ranging from mild and nonspecific to severe, or even death. CO poisoning is often underdiagnosed because exposure to low concentrations goes unnoticed, and threshold values for normal carboxyhemoglobin vary according to different authors. The aim of our study was to analyze carboxyhemoglobin (COHb) levels in an unselected population and detect sources of CO exposure In a cross-sectional descriptive study, we analyzed consecutive arterial blood gas levels processed in our laboratory. We selected those with COHb≥2.5% in nonsmokers and ≥5% in smokers. In these cases a structured telephone interview was conducted. Elevated levels of COHb were found in 64 (20%) of 306 initial determinations. Of these, data from 51 subjects aged 65±12 years, 31 (60%) of which were men, were obtained. Mean COHb was 4.0%. Forty patients (78%) were non-smokers with mean COHb of 3.2%, and 11 were smokers with COHb of 6.7%. In 45 patients (88.2%) we detected exposure to at least one source of ambient CO other than cigarette smoke. A significant proportion of individuals from an unselected sample had elevated levels of COHb. The main sources of CO exposure were probably the home, so this possibility should be explored. The population should be warned about the risks and encouraged to take preventive measures. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Predictive Value of the Sequential Organ Failure Assessment Score for Mortality in a Contemporary Cardiac Intensive Care Unit Population.

PubMed

Jentzer, Jacob C; Bennett, Courtney; Wiley, Brandon M; Murphree, Dennis H; Keegan, Mark T; Gajic, Ognjen; Wright, R Scott; Barsness, Gregory W

2018-03-10

Optimal methods of mortality risk stratification in patients in the cardiac intensive care unit (CICU) remain uncertain. We evaluated the ability of the Sequential Organ Failure Assessment (SOFA) score to predict mortality in a large cohort of unselected patients in the CICU. Adult patients admitted to the CICU from January 1, 2007, to December 31, 2015, at a single tertiary care hospital were retrospectively reviewed. SOFA scores were calculated daily, and Acute Physiology and Chronic Health Evaluation (APACHE)-III and APACHE-IV scores were calculated on CICU day 1. Discrimination of hospital mortality was assessed using area under the receiver-operator characteristic curve values. We included 9961 patients, with a mean age of 67.5±15.2 years; all-cause hospital mortality was 9.0%. Day 1 SOFA score predicted hospital mortality, with an area under the receiver-operator characteristic curve value of 0.83; area under the receiver-operator characteristic curve values were similar for the APACHE-III score, and APACHE-IV predicted mortality ( P >0.05). Mean and maximum SOFA scores over multiple CICU days had greater discrimination for hospital mortality ( P <0.01). Patients with an increasing SOFA score from day 1 and day 2 had higher mortality. Patients with day 1 SOFA score <2 were at low risk of mortality. Increasing tertiles of day 1 SOFA score predicted higher long-term mortality ( P <0.001 by log-rank test). The day 1 SOFA score has good discrimination for short-term mortality in unselected patients in the CICU, which is comparable to APACHE-III and APACHE-IV. Advantages of the SOFA score over APACHE include simplicity, improved discrimination using serial scores, and prediction of long-term mortality. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Challenges of coronary angiography and intervention in patients previously treated by TAVI.

PubMed

Blumenstein, Johannes; Kim, Won-Keun; Liebetrau, Christoph; Gaede, Luise; Kempfert, Joerg; Walther, Thomas; Hamm, Christian; Möllmann, Helge

2015-08-01

Since the beginning of the transcatheter aortic valve implantation (TAVI) era, many prosthetic valves have entered clinical practice. TAVI prostheses differ regarding stent design and some may potentially interfere with diagnostic or interventional catheters. The aim of our analysis was to evaluate the feasibility of coronary angiography (CA) or percutaneous coronary intervention (PCI) in patients with prior TAVI. From 2011 to 2014, 1,000 patients were treated by TAVI at our center using eight different valve prostheses (Symetis ACURATE TA and ACURATE TF; Medtronic CoreValve and Engager; JenaValve, SJM Portico; Edwards Lifesciences SAPIEN and SAPIEN XT). In this analysis, all patients were included who underwent either CA or PCI after TAVI. CA or PCI were rated as fully feasible when coronary ostia could be fully intubated, partially feasible when coronary arteries could be displayed only unselectively or unfeasible when coronary arteries could not be displayed. A total of 35 patients underwent CA/PCI after TAVI at our hospital. In all patients with valves implanted in a subcoronary position (SAPIEN n = 19; JenaValve n = 1), selective intubation was feasible using standard catheters. Out of 15 patients with valve types that are placed over the coronary ostia (CoreValve n = 10, ACURATE n = 4, Portico n = 1), selective intubation of coronary arteries was not possible in 9 cases, even with the use of different diagnostic catheters. Full accessibility was possible only in 3 cases. In 2 cases, display of the right CA was only feasible using unselective aortography. In 1 case, coronary arteries could not be displayed at all immediately after a valve-in-valve procedure. CA or PCI after TAVI is usually feasible. Devices that are placed in a partially supracoronary position, however, can interfere with diagnostic or guiding catheters and impede straightforward intervention, especially when the prosthesis is not implanted in the correct position.

Prevalence of illicit drug use in pregnant women in a Wisconsin private practice setting.

PubMed

Schauberger, Charles W; Newbury, Emily J; Colburn, Jean M; Al-Hamadani, Mohammed

2014-09-01

We sought to measure the prevalence of illicit drug use in our obstetric population, to identify the drugs being used, and to determine whether a modified version of the 4Ps Plus screening tool could serve as an initial screen. In this prospective study, urine samples of 200 unselected patients presenting for initiation of prenatal care in a Wisconsin private practice were analyzed for evidence of the use of illicit drugs. Of 200 patients, 26 (13%) had evidence of drugs of abuse in their urine samples. Marijuana (7%) and opioids (6.5%) were the most commonly identified drugs. Adding 5 questions about drug or alcohol use to the obstetric intake questionnaire proved sensitive in identifying patients with high risks of having a positive drug screen. The rate of drug use in our low-risk population was higher than expected and may reflect increasing rates of drug use across the United States. Enhanced screening should be performed to identify patients using illicit drugs in pregnancy to improve their care. Medical centers and communities may benefit from periodic testing of their community prevalence rates to aid in appropriate care planning. Copyright © 2014 Mosby, Inc. All rights reserved.

A homozygous mutation in the endothelin-3 gene associated with a combined Waardenburg type 2 and Hirschsprung phenotype (Shah-Waardenburg syndrome).

PubMed

Hofstra, R M; Osinga, J; Tan-Sindhunata, G; Wu, Y; Kamsteeg, E J; Stulp, R P; van Ravenswaaij-Arts, C; Majoor-Krakauer, D; Angrist, M; Chakravarti, A; Meijers, C; Buys, C H

1996-04-01

Hirschsprung disease (HSCR) or colonic aganglionosis is a congenital disorder characterized by an absence of intramural ganglia along variable lengths of the colon resulting in intestinal obstruction. The incidence of HSCR is 1 in 5,000 live births. Mutations in the RET gene, which codes for a receptor tyrosine kinase, and in EDNRB which codes for the endothelin-B receptor, have been shown to be associated with HSCR in humans. The lethal-spotted mouse which has pigment abnormalities, but also colonic aganglionosis, carries a mutation in the gene coding for endothelin 3 (Edn3), the ligand for the receptor protein encoded by EDNRB. Here, we describe a mutation of the human gene for endothelin 3 (EDN3), homozygously present in a patient with a combined Waardenburg syndrome type 2 (WS2) and HSCR phenotype (Shah-Waardenburg syndrome). The mutation, Cys159Phe, in exon 3 in the ET-3 like domain of EDN3, presumably affects the proteolytic processing of the preproendothelin to the mature peptide EDN3. The patient's parents were first cousins. A previous child in this family had been diagnosed with a similar combination of HSCR, depigmentation and deafness. Depigmentation and deafness were present in other relatives. Moreover, we present a further indication for the involvement of EDNRB in HSCR by reporting a novel mutation detected in one of 40 unselected HSCR patients.

Stent thrombosis and bleeding complications after implantation of sirolimus-eluting coronary stents in an unselected worldwide population: a report from the e-SELECT (Multi-Center Post-Market Surveillance) registry.

PubMed

Urban, Philip; Abizaid, Alexandre; Banning, Adrian; Bartorelli, Antonio L; Baux, Ana Cebrian; Džavík, Vladimír; Ellis, Stephen; Gao, Runlin; Holmes, David; Jeong, Myung Ho; Legrand, Victor; Neumann, Franz-Josef; Nyakern, Maria; Spaulding, Christian; Worthley, Stephen

2011-03-29

The aim of this study was to ascertain the 1-year incidence of stent thrombosis (ST) and major bleeding (MB) in a large, unselected population treated with sirolimus-eluting stents (SES). Stent thrombosis and MB are major potential complications of drug-eluting stent implantation. Their relative incidence and predisposing factors among large populations treated worldwide are unclear. The SES were implanted in 15,147 patients who were entered in a multinational registry. We analyzed the incidence of: 1) definite and probable ST as defined by the Academic Research Consortium; and 2) MB, with the STEEPLE (Safety and efficacy of Enoxaparin in PCI) definition, together with their relation to dual antiplatelet therapy (DAPT) and to 1-year clinical outcomes. The mean age of the sample was 62 ± 11 years, 30.4% were diabetic, 10% had a Charlson comorbidity index ≥3, and 44% presented with acute coronary syndrome or myocardial infarction. At 1 year, the reported compliance with DAPT as recommended by the European Society of Cardiology guidelines was 86.3%. Adverse event rates were: ST 1.0%, MB 1.0%, mortality 1.7%, myocardial infarction 1.9%, and target lesion revascularization 2.3%. Multivariate analysis identified 9 correlates of ST and 4 correlates of MB. Advanced age and a high Charlson index were associated with an increased risk of both ST and MB. After ST, the 7-day and 1-year all-cause mortality was 30% and 35%, respectively, versus 1.5% and 10% after MB. Only 2 of 13,749 patients (0.015%) experienced both MB and ST during the entire 1-year follow-up period. In this worldwide population treated with ≥1 SES, the reported compliance with DAPT was good, and the incidence of ST and MB was low. Stent thrombosis and MB very rarely occurred in the same patient. (The e-SELECT Registry: a Multicenter Post-Market Surveillance; NCT00438919). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

EGFR Amplification as a Target in Gastroesophageal Adenocarcinoma: Do Anti-EGFR Therapies Deserve a Second Chance?

PubMed

Strickler, John H

2018-06-01

Anti-EGFR therapies have failed to improve survival for unselected patients with metastatic gastroesophageal cancer, but in a subset of patients, EGFR amplification may predict treatment benefit. Maron and colleagues report the clinical activity of anti-EGFR therapies in a cohort of patients with EGFR -amplified metastatic gastroesophageal cancer and utilize serial blood and tumor tissue collection to identify molecular drivers of treatment sensitivity and resistance. Their insights offer a path to overcome technical limitations associated with EGFR amplification and facilitate molecularly targeted therapeutic strategies. Cancer Discov; 8(6); 679-81. ©2018 AACR See related article by Maron et al., p. 696 . ©2018 American Association for Cancer Research.

Propranolol reduces the anxiety associated with day case surgery.

PubMed

Mealy, K; Ngeh, N; Gillen, P; Fitzpatrick, G; Keane, F B; Tanner, A

1996-01-01

To find out if propranolol, a non-cardioselective beta-blocker, can reduce the anxiety associated with day case surgery. Prospective randomized double blind trial. University hospital, Ireland. An unselected group of 53 patients undergoing day case surgery. Subjects randomised to receive either propranolol (10 mg) or placebo on the morning of operation. Blood pressure; pulse, anxiety, pain score and patient satisfaction. Mean (SD) Hospital Anxiety and Depression score was significantly lower in the propranolol group than in the control group (2.5 (0.7) compared with 4.6 (0.7), p < 0.0001) before discharge. A low dose of propranolol given on the morning of day case surgery significantly reduced patients' anxiety.

Detecting re-infection in patients after an initial diagnosis of gonorrhoea: is routine recall for re-screening useful?

PubMed

Fernando, K A; Fowler, T; Harding, J; Flew, S; Caley, M; Phattey, J; Ross, Jdc

2015-08-01

To assess the outcome of routine sexually transmitted infection re-screening after a three-month interval in unselected patients diagnosed with gonorrhoea, we sought to assess whether this active approach would result in an increase in the number of people attending clinic and subsequently diagnosed with gonorrhoea re-infection, compared with normal re-presentation rates. A recall group of patients were invited for re-screening three months after their initial diagnosis of gonorrhoea. Permission was sought to send a reminder two weeks prior to their scheduled recall appointment. Comparisons were made with a historical control group of patients with gonorrhoea in the absence of any formal recall. Of the 242 patients in the intervention arm, 96 (40%) re-attended within six months, and 15 (6%) tested gonorrhoea positive. Two hundred and two patients were assessed in the control group, of whom 45 (22%) re-attended within six months, and 13 (6%) tested gonorrhoea positive. Women were more likely than men to re-attend following active recall, but they were not at higher risk of re-attending while re-infected with gonorrhoea. Active recall following a gonorrhoea diagnosis significantly increases re-attendance rates for repeat screening but did not result in an increased number of subsequent gonorrhoea diagnoses. © The Author(s) 2014.

The consequences of balanced harvesting of fish communities

PubMed Central

Jacobsen, Nis S.; Gislason, Henrik; Andersen, Ken H.

2014-01-01

Balanced harvesting, where species or individuals are exploited in accordance with their productivity, has been proposed as a way to minimize the effects of fishing on marine fish communities and ecosystems. This calls for a thorough examination of the consequences balanced harvesting has on fish community structure and yield. We use a size- and trait-based model that resolves individual interactions through competition and predation to compare balanced harvesting with traditional selective harvesting, which protects juvenile fish from fishing. Four different exploitation patterns, generated by combining selective or unselective harvesting with balanced or unbalanced fishing, are compared. We find that unselective balanced fishing, where individuals are exploited in proportion to their productivity, produces a slightly larger total maximum sustainable yield than the other exploitation patterns and, for a given yield, the least change in the relative biomass composition of the fish community. Because fishing reduces competition, predation and cannibalism within the community, the total maximum sustainable yield is achieved at high exploitation rates. The yield from unselective balanced fishing is dominated by small individuals, whereas selective fishing produces a much higher proportion of large individuals in the yield. Although unselective balanced fishing is predicted to produce the highest total maximum sustainable yield and the lowest impact on trophic structure, it is effectively a fishery predominantly targeting small forage fish. PMID:24307676

Impact of extent of resection and recurrent surgery on clinical outcome and overall survival in a consecutive series of 170 patients for glioblastoma in intraoperative high field magnetic resonance imaging.

PubMed

Coburger, Jan; Wirtz, Christian R; König, Ralph W

2017-06-01

In patients with a glioblastoma (GBM), few unselected data exists using actual standard adjuvant treatment and contemporary surgical techniques like iMRI. Aim of study is to assess impact of EoR and recurrent surgery on survival and outcome. We assessed a consecutive unselected series of 170 surgeries for GBM (2008-2014) applying intraoperative MRI (iMRI). All patients received adjuvant radio-chemo-therapy. Overall-survival (OS), progression free survival (PFS), complications and new permanent neurological deficits (nPND) were assessed. Uni- and multivariate-cox-regression-models were calculated. Mean follow-up was 40mo. GTR was intended in 82% and achieved in 77% of these cases. A nPND was found in 7% of patients. In multivariate cox-regression, GTR (HR:0.6, P<0.024) and absence of MGMT methylation (HR:1.6, P<0.042) was significantly associated with PFS. We found no difference in PFS after primary surgery and recurrent surgery. Concerning OS, in multivariate assessment an un-methylated MGMT-promotor (HR2.0, P<0.01) and presence of a complication (HR1.7, P<0.06) were negative prognosticators. Only GTR was significantly beneficial for OS (HR0.4, P<0.028) compared to a failed GTR and a STR. Repeated surgery for recurrent disease was positively associated with OS (HR0.6, P<0.06). Surgery in a contemporary setup using iMRI, brain mapping and modern adjuvant treatment, has a higher OS and lower complication rates as previously published. A maximum but safe resection should be the goal of surgery since a perioperative complication significantly decreases OS. Recurrent surgery has a beneficial effect on OS without an increase of complications.

Impact of the introduction of a standardised ICD programming protocol: real-world data from a single centre.

PubMed

Sunderland, Nicholas; Kaura, Amit; Li, Anthony; Kamdar, Ravi; Petzer, Ed; Dhillon, Para; Murgatroyd, Francis; Scott, Paul A

2016-09-01

Randomised trials have shown that empiric ICD programming, using long detection times and high detection zones, reduces device therapy in ICD recipients. However, there is less data on its effectiveness in a "real-world" setting, especially secondary prevention patients. Our aim was to evaluate the introduction of a standardised programming protocol in a real-world setting of unselected ICD recipients. We analysed 270 consecutive ICD recipients implanted in a single centre-135 implanted prior to protocol implementation (physician-led group) and 135 after (standardised group). The protocol included long arrhythmia detection times (30/40 or equivalent) and high rate detection zones (primary prevention lower treatment zone 200 bpm). Programming in the physician-led group was at the discretion of the implanter. The primary endpoint was time-to-any therapy (ATP or shocks). Secondary endpoints were time-to-inappropriate therapy and time-to-appropriate therapy. The safety endpoints were syncopal episodes, hospital admissions and death. At 12 months follow-up, 47 patients had received any ICD therapy (physician-led group, n = 31 vs. standardised group, n = 16). There was a 47 % risk reduction in any device therapy (p = 0.04) and an 86 % risk reduction in inappropriate therapy (p = 0.009) in the standardised compared to the physician-led group. There was a non-significant 30 % risk reduction in appropriate therapy (p = 0.32). Results were consistent across primary and secondary prevention patients. There were no significant differences in the rates of syncope, hospitalisation, and death. In unselected patients in a real-world setting, introduction of a standardised programming protocol, using long detection times and high detection zones, significantly reduces the burden of ICD therapy without an increase in adverse outcomes.

Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

PubMed Central

van den Broek, Alexandra J; de Ruiter, Karen; van 't Veer, Laura J; Tollenaar, Rob A E M; van Leeuwen, Flora E; Verhoef, Senno; Schmidt, Marjanka K

2015-01-01

In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974–2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a ‘triple-negative breast cancer' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria. PMID:25138101

Cell-based strategies to manage leukemia relapse: efficacy and feasibility of immunotherapy approaches.

PubMed

Rambaldi, A; Biagi, E; Bonini, C; Biondi, A; Introna, M

2015-01-01

When treatment fails, the clinical outcome of acute leukemia patients is usually very poor, particularly when failure occurs after transplantation. A second allogeneic stem cell transplant could be envisaged as an effective and feasible salvage option in younger patients having a late relapse and an available donor. Unmanipulated or minimally manipulated donor T cells may also be effective in a minority of patients but the main limit remains the induction of severe graft-versus-host disease. This clinical complication has brought about a huge research effort that led to the development of leukemia-specific T-cell therapy aiming at the direct recognition of leukemia-specific rather than minor histocompatibility antigens. Despite a great scientific interest, the clinical feasibility of such an approach has proven to be quite problematic. To overcome this limitation, more research has moved toward the choice of targeting commonly expressed hematopoietic specific antigens by the genetic modification of unselected T cells. The best example of this is represented by the anti-CD19 chimeric antigen receptor (CD19.CAR) T cells. As a possible alternative to the genetic manipulation of unselected T cells, specific T-cell subpopulations with in vivo favorable homing and long-term survival properties have been genetically modified by CAR molecules. Finally, the use of naturally cytotoxic effector cells such as natural killer and cytokine-induced killer cells has been proposed in several clinical trials. The clinical development of these latter cells could also be further expanded by additional genetic modifications using the CAR technology.

Analytical evaluation of point of care cTnT and clinical performances in an unselected population as compared with central laboratory highly sensitive cTnT.

PubMed

Dupuy, Anne Marie; Sebbane, Mustapha; Roubille, François; Coste, Thibault; Bargnoux, Anne Sophie; Badiou, Stéphanie; Kuster, Nils; Cristol, Jean Paul

2015-03-01

To report the analytical performances of the Radiometer AQT90 FLEX® cTnT assay (Neuilly-Plaisance, France) and to evaluate the concordance with hs-cTnT results from central laboratory for the diagnosis of acute myocardial infarction (AMI) at baseline and during a short follow-up among unselected patients admitted in emergency room or cardiology department. Analytical performances of AQT90 FLEX® cTnT immunoassay included imprecision study with determination of a coefficient of variation at 10% and 20%, linearity, and limit of detection. The concordance study was based on samples obtained from 170 consecutive patients with chest pain suggestive of acute coronary syndrome (ACS) admitted in the emergency room or cardiology department. The kinetic study (within 62 additional samples 3h later) was based on absolute delta criterion and the combination of relative change of 30% with absolute change of 7ng/L. The cTnT assay from Radiometer was evaluated as clinically usable, although less sensitive than the Roche hs-cTnT assay as demonstrated by the concordance and the kinetic studies. In non-selected population, the cTnT AQT Flex© assay on AQT90© with kinetic change at 3h, provides similar clinical classification of patients, particularly for AMI group as compared to central laboratory hs-cTnT assay and could be suitable for clinical use. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Neglecting the Left Side of a City Square but Not the Left Side of Its Clock: Prevalence and Characteristics of Representational Neglect

PubMed Central

Guariglia, Cecilia; Palermo, Liana; Piccardi, Laura; Iaria, Giuseppe; Incoccia, Chiara

2013-01-01

Representational neglect, which is characterized by the failure to report left-sided details of a mental image from memory, can occur after a right hemisphere lesion. In this study, we set out to verify the hypothesis that two distinct forms of representational neglect exist, one involving object representation and the other environmental representation. As representational neglect is considered rare, we also evaluated the prevalence and frequency of its association with perceptual neglect. We submitted a group of 96 unselected, consecutive, chronic, right brain-damaged patients to an extensive neuropsychological evaluation that included two representational neglect tests: the Familiar Square Description Test and the O'Clock Test. Representational neglect, as well as perceptual neglect, was present in about one-third of the sample. Most patients neglected the left side of imagined familiar squares but not the left side of imagined clocks. The present data show that representational neglect is not a rare disorder and also support the hypothesis that two different types of mental representations (i.e. topological and non-topological images) may be selectively damaged in representational neglect. PMID:23874416

The Dysexecutive Questionnaire advanced: item and test score characteristics, 4-factor solution, and severity classification.

PubMed

Bodenburg, Sebastian; Dopslaff, Nina

2008-01-01

The Dysexecutive Questionnaire (DEX, , Behavioral assessment of the dysexecutive syndrome, 1996) is a standardized instrument to measure possible behavioral changes as a result of the dysexecutive syndrome. Although initially intended only as a qualitative instrument, the DEX has also been used increasingly to address quantitative problems. Until now there have not been more fundamental statistical analyses of the questionnaire's testing quality. The present study is based on an unselected sample of 191 patients with acquired brain injury and reports on the data relating to the quality of the items, the reliability and the factorial structure of the DEX. Item 3 displayed too great an item difficulty, whereas item 11 was not sufficiently discriminating. The DEX's reliability in self-rating is r = 0.85. In addition to presenting the statistical values of the tests, a clinical severity classification of the overall scores of the 4 found factors and of the questionnaire as a whole is carried out on the basis of quartile standards.

Bile acid malabsorption: an under-investigated differential diagnosis in patients presenting with diarrhea predominant irritable bowel syndrome type symptoms.

PubMed

Kurien, Matthew; Evans, Kate E; Leeds, John S; Hopper, Andy D; Harris, Andrew; Sanders, David S

2011-07-01

Bile acid malabsorption (BAM) has been reported as a possible cause of diarrhea predominant irritable bowel syndrome (D-IBS) type symptoms. We aimed to determine how commonly patients with D-IBS type symptoms had a diagnosis of BAM as demonstrated by a positive SeHCAT (75 Selenium-homocholic acid taurine) test (retention <10% at seven days). A retrospective analysis was undertaken of patient's records for all patients who underwent a SeHCAT test between 2001 and 2009 in a tertiary hospital (Group A). Concurrently, a cohort of patients with Rome II D-IBS type symptoms was examined to determine the potential utility of SeHCAT test (Group B). In Group A 39.2% (n = 107/273) of patients had a positive SeHCAT result. The median time from first hospital visit to SeHCAT result was 30 weeks. Predictive factors for BAM: terminal ileal Crohn's disease (p < 0.01), terminal ileal resection (p < 0.01), and previous cholecystectomy (p < 0.01). 33.6% of patients who had a positive SeHCAT also had Rome II D-IBS. In Group B the D-IBS control cohort only 1.9% of patients had undergone a SeHCAT scan (p < 0.001 compared to Group A). BAM is common and should be considered earlier when investigating unselected patients with D-IBS type symptoms.

Potential source of cerebral embolism in migraine with aura: a transcranial Doppler study.

PubMed

Anzola, G P; Magoni, M; Guindani, M; Rozzini, L; Dalla Volta, G

1999-05-12

The recently found association between patent foramen ovale (PFO) and transient global amnesia (TGA) has suggested that paradoxical microembolization in the terminal vertebrobasilar territory might underlie at least some TGA cases. Migraine with visual aura is another paroxysmal disturbance in which a sudden dysfunction of cortical areas fed by the terminal branches of the basilar artery is believed to trigger the attack. Therefore we investigated the prevalence of PFO in a consecutive unselected cohort of migraine patients. To investigate the prevalence of PFO in a consecutive unselected cohort of migraine patients to search for a possible mechanism for the reported association of migraine with stroke. A total of 113 patients, consecutively referred by the Headache Outpatient Clinic for migraine with aura (MA+, mean age 34+/-12 years) were compared with 53 patients with migraine without aura (MA-, mean age 36+/-13 years) and with 25 age-matched nonmigraine subjects (mean age 31+/-10 years) selected from the hospital staff. PFO was assessed with transcranial Doppler sonography with IV injection of agitated saline, a technique that is 90% sensitive and 100% specific. The prevalence of PFO was 48% (54/113) in MA+ patients, 23% (12/53) in MA- patients, and 20% (5/25) in control subjects. The difference between MA+ and MA- patients was significant (odds ratio [OR] = 3.13, 95% confidence interval [CI] = 1.41 to 7.04, chi2 = 9.52,p = 0.002) as was the difference between MA+ patients and controls (OR = 3.66, 95% CI = 1.21 to 13.25, chi2 = 6.46, p = 0.01), whereas MA- patients did not differ from controls (OR = 1.17, 95% CI = 0.32 to 4.45, chi2 = 0.07). MRI was negative in 22 MA+ and 8 MA- patients. Patency of the foramen ovale is associated with migraine with aura but not with migraine without aura. The increased risk of stroke found in epidemiologic studies in patients with migraine with aura may be explained by an increased propensity to paradoxical cerebral embolism.

High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial.

PubMed

Azoulay, Elie; Lemiale, Virginie; Mokart, Djamel; Nseir, Saad; Argaud, Laurent; Pène, Frédéric; Kontar, Loay; Bruneel, Fabrice; Klouche, Kada; Barbier, François; Reignier, Jean; Stoclin, Anabelle; Louis, Guillaume; Constantin, Jean-Michel; Mayaux, Julien; Wallet, Florent; Kouatchet, Achille; Peigne, Vincent; Perez, Pierre; Girault, Christophe; Jaber, Samir; Oziel, Johanna; Nyunga, Martine; Terzi, Nicolas; Bouadma, Lila; Lebert, Christine; Lautrette, Alexandre; Bigé, Naike; Raphalen, Jean-Herlé; Papazian, Laurent; Rabbat, Antoine; Darmon, Michael; Chevret, Sylvie; Demoule, Alexandre

2018-03-05

Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO 2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated. This is a multicenter, open-label, randomized controlled superiority trial in 30 intensive care units, part of the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH). Inclusion criteria will be: (1) adults, (2) known immunosuppression, (3) ARF, (4) oxygen therapy ≥ 6 L/min, (5) written informed consent from patient or proxy. Exclusion criteria will be: (1) imminent death (moribund patient), (2) no informed consent, (3) hypercapnia (PaCO 2 ≥ 50 mmHg), (4) isolated cardiogenic pulmonary edema, (5) pregnancy or breastfeeding, (6) anatomical factors precluding insertion of a nasal cannula, (7) no coverage by the French statutory healthcare insurance system, and (8) post-surgical setting from day 1 to day 6 (patients with ARF occurring after day 6 of surgery can be included). The primary outcome measure is day-28 mortality. Secondary outcomes are intubation rate, comfort, dyspnea, respiratory rate, oxygenation, ICU length of stay, and ICU-acquired infections. Based on an expected 30% mortality rate in the standard oxygen group, and 20% in the HFNO group, error rate set at 5%, and a statistical power at 90%, 389 patients are required in each treatment group (778 patients overall). Recruitment period is estimated at 30 months, with 28 days of additional follow-up for the last included patient. The HIGH study will be the largest multicenter, randomized controlled trial seeking to demonstrate that survival benefits from HFNO reported in unselected patients also apply to a large immunocompromised population. ClinicalTrials.gov, ID: NCT02739451 . Registered on 15 April 2016.

Recurrent ischemia across the spectrum of acute coronary syndromes: prevalence and prognostic significance of (re-)infarction and ST-segment changes in a large contemporary registry.

PubMed

Yan, Andrew T; Steg, Philippe Gabriel; Fitzgerald, Gordon; Feldman, Laurent J; Eagle, Kim A; Gore, Joel M; Anderson, Frederick A; López-Sendón, Jose; Gurfinkel, Enrique P; Brieger, David; Goodman, Shaun G

2010-11-05

There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia (RI) in unselected patients with acute coronary syndromes(ACS). We examined the clinical features and treatment associated with, and the differential prognostic impact of, the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era. The Global Registry of Acute Coronary Events (GRACE) was a prospective, multinational registry of patients hospitalized for ACS. Data were collected on standardized case report forms. Of the 29,400 ACS patients enrolled in May 2000-March 2007, 21% developed RI; 2.4%, 4.9%, and 16% had myocardial (re-)infarction [(re-)MI], RI with ST-segment changes, and RI without ST-segment changes (not mutually exclusive), respectively. Rates of in-hospital mortality and complications, and 6-month mortality were significantly higher among patients with RI compared to those without; the rates were highest for patients who developed (re-)MI, followed by those with RI and ST-segment changes. After adjusting for other validated prognosticators in the GRACE risk score, all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality. Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI (P for interaction=0.003). Despite the current use of intensive medical therapies, RI remains a common and serious consequence across the spectrum of ACS. Different types of RI confer a variable adverse prognostic impact. Re-MI is associated with the worst outcome, which appears to be mitigated by early revascularization. Our findings underscore the persistent need to improve the treatment of ACS. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Costs and resource utilization for diagnosis and treatment during the initial year in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom Study.

PubMed

Burisch, Johan; Vardi, Hillel; Pedersen, Natalia; Brinar, Marko; Cukovic-Cavka, Silvja; Kaimakliotis, Ioannis; Duricova, Dana; Bortlik, Martin; Shonová, Olga; Vind, Ida; Avnstrøm, Søren; Thorsgaard, Niels; Krabbe, Susanne; Andersen, Vibeke; Dahlerup, Jens F; Kjeldsen, Jens; Salupere, Riina; Olsen, Jónger; Nielsen, Kári R; Manninen, Pia; Collin, Pekka; Katsanos, Konstantinnos H; Tsianos, Epameinondas V; Ladefoged, Karin; Lakatos, Laszlo; Bailey, Yvonne; OʼMorain, Colm; Schwartz, Doron; Lupinacci, Guido; De Padova, Angelo; Jonaitis, Laimas; Kupcinskas, Limas; Turcan, Svetlana; Barros, Louisa; Magro, Fernando; Lazar, Daniela; Goldis, Adrian; Nikulina, Inna; Belousova, Elena; Fernandez, Alberto; Pineda, Juan R; Almer, Sven; Halfvarson, Jonas; Tsai, Her-Hsin; Sebastian, Shaji; Friger, Michael; Greenberg, Dan; Lakatos, Peter L; Langholz, Ebbe; Odes, Selwyn; Munkholm, Pia

2015-01-01

No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe. The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (€) using the Danish Health Costs Register. One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was €5,408,174 (investigations: €2,042,990 [38%], surgery: €1,427,648 [26%], biologicals: €781,089 [14%], and standard treatment: €1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations €1803 (€2160) (P = 0.44), surgery €11,489 (€13,973) (P = 0.14), standard treatment €1027 (€824) (P = 0.51), and biologicals €7376 (€8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations €1189 ( €1518) (P < 0.01), surgery €18,414 ( €12,395) (P = 0.18), standard treatment €896 ( €798) (P < 0.05), and biologicals €5681 ( €72) (P = 0.51). In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.

Polymorphisms in nonhomologous end-joining genes associated with breast cancer risk and chromosomal radiosensitivity.

PubMed

Willems, Petra; Claes, Kathleen; Baeyens, Ans; Vandersickel, Veerle; Werbrouck, Joke; De Ruyck, Kim; Poppe, Bruce; Van den Broecke, Rudy; Makar, Amin; Marras, Emanuela; Perletti, Gianpaolo; Thierens, Hubert; Vral, Anne

2008-02-01

As enhanced chromosomal radiosensitivity (CRS) results from non- or misrepaired double strand breaks (DSBs) and is a hallmark for breast cancer and single nucleotide polymorphisms (SNPs) in DSB repair genes, such as non homologous end-joining (NHEJ) genes, could be involved in CRS and genetic predisposition to breast cancer. In this study, we investigated the association of five SNPs in three different NHEJ genes with breast cancer in a population-based case-control setting. The total patient population composed of a selected group of patients with a family history of the disease and an unselected group, consisting mainly of sporadic cases. SNP analysis showed that the c.2099-2408G>A SNP (XRCC5Ku80) [corrected] has a significant, positive odds ratio (OR) of 2.81 (95% confidence interval (CI): 1.30-6.05) for the heterozygous (He) and homozygous variant (HV) genotypes in the selected patient group. For the c.-1310 C>G SNP (XRCC6Ku70)[corrected] a significant OR of 1.85 (95%CI: 1.01-3.41) was found for the He genotype in the unselected patient group. On the contrary, the HV genotype of c.1781G>T (XRCC6Ku70) [corrected] displays a significant, negative OR of 0.43 (95%CI: 0.18-0.99) in the total patient population. The He+HV genotypes of the c.2099-2408G>A SNP (XRCC5Ku80) [corrected] also showed high and significant ORs in the group of "radiosensitive," familial breast cancer patients. In conclusion, our results provide preliminary evidence that the variant allele of c.-1310C>G (XRCC6Ku70) [corrected]and c.2099-2408G>A (XRCC5Ku80) [corrected] are risk alleles for breast cancer as well as CRS. The HV genotype of c.1781G>T (XRCC6Ku70) [corrected] on the contrary, seems to protect against breast cancer and ionizing radiation induced micronuclei. (c) 2007 Wiley-Liss, Inc.

Anti-tumour activity of platinum compounds in advanced prostate cancer-a systematic literature review.

PubMed

Hager, S; Ackermann, C J; Joerger, M; Gillessen, S; Omlin, A

2016-06-01

For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents. To systematically identify and analyse clinical trials that have evaluated platinum agents in advanced prostate cancer patients. PubMed was searched to identify published clinical trials of platinum agents in advanced prostate cancer. The PRIMSA statement was followed for the systematic review process. Identified trials are analysed for study design, statistical plan, assessments of anti-tumour activity and the potential value of predictive biomarkers. A total of 163 references were identified by the literature search and 72 publications that met the selection criteria were included in this review; of these 33 used carboplatin, 27 cisplatin, 6 satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall, anti-tumour activity varies in the range of 10%-40% for objective response and 20%-70% for PSA decline ≥50%. Response seemed highest for the combinations of carboplatin with taxanes or oxaliplatin with gemcitabine. The interpretation of the clinical data is limited by differences in response criteria used and patient populations studied. Platinum compounds have moderate anti-tumour activity in molecularly unselected patients with advanced prostate cancer. Translational evidence of DNA repair deficiency should be leveraged in future studies to select prostate cancer patients most likely to benefit from platinum-based therapy. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Deficit in automatic sound-change detection may underlie some music perception deficits after acute hemispheric stroke.

PubMed

Kohlmetz, C; Altenmüller, E; Schuppert, M; Wieringa, B M; Münte, T F

2001-01-01

Music perception deficits following acute neurological damage are thought to be rare. By a newly devised test battery of music-perception skills, however, we were able to identify among a group of 12 patients with acute hemispheric stroke six patients with music perception deficits (amusia) while six others had no such deficits. In addition we recorded event-related brain potentials (ERPs) in a passive listening task with frequent standard and infrequent pitch deviants designed to elicit the mismatch negativity (MMN). The MMN in the patients with amusia was grossly reduced, while the non-amusic patients and control subjects had MMNs of equal size. These data show that amusia is quite common in unselected stroke patients. The MMN reduction suggests that amusia is related to unspecific automatic stimulus classification deficits in these patients.

Serial MRIs provide novel insight into natural history of optic pathway gliomas in patients with neurofibromatosis 1.

PubMed

Sellmer, Laura; Farschtschi, Said; Marangoni, Marco; Heran, Manraj K S; Birch, Patricia; Wenzel, Ralph; Mautner, Victor-Felix; Friedman, Jan M

2018-04-23

Optic pathway gliomas (OPGs) are present in 20% of children with neurofibromatosis 1 (NF1) but are less frequently observed in adults. Our goal was to determine the natural history of OPGs in children and adults with NF1. We analyzed the features of OPGs and other intracranial lesions on 1775 head MRI scans of 562 unselected adults and children with NF1 collected between 2003 and 2015. 52 (9.3%) of 562 patients in this study had an OPG diagnosed on their MRI. The median age at first scan with an OPG present was 12.7 years. Of the 52 OPG patients, the intraorbital optic nerves were affected in 29 patients (56%), the prechiasmatic optic nerves were affected in 32 patients (62%), the optic chiasm was affected in 17 patients (33%) and the optic radiations were affected in 19 patients (37%). 29 patients had two or more areas affected. One patient had a newly-appearing OPG, and 1 patient showed progression. The rate of progression over 5 years was 2.4% (95% CI: 0.4% to 16%). Four patients showed partial regression of their OPGs, but we observed no case of complete regression during this study. The rate of regression over 5 years was 8.9% (95% confidence intervals: 2.8% to 26%). We found the presence of UBOs and the presence of OPGs in individual patients to be highly associated (p = 0.0061). OPGs are more common in older adults with NF1 than previously thought. The occurrences of unidentified bright objects (UBOs) and asymptomatic OPGs are associated with each other. This suggests the possibility that OPGs that remain asymptomatic may differ pathogenically from those that become symptomatic.

Precancerous lesions of the cervix uteri in infertile women.

PubMed Central

Holst, N; Abyholm, T

1983-01-01

A study of 318 patients with tubal infertility and a control group of 200 unselected infertile women yielded 14 (4.4%) and 1 (0.5%), respectively, with precancerous lesions of the cervix uteri. The one patient in the control group with severe dysplasia was later shown to have tubal infertility. The overall incidence of premalignant lesions of the cervix uteri as reported to the National Cancer Registry of Norway was 0.1% for the age group and period studied. Women with tubal infertility represent a small but comparatively high risk group for the development of precancerous lesions of the cervix uteri. PMID:6412931

Brown Nail-bed Arcs and Chronic Renal Disease

PubMed Central

Stewart, W. K.; Raffle, E. J.

1972-01-01

A brown arc affecting the distal part of the fingernail-bed, just proximal to the point of separation of the nail from its bed, has been found in 12 out of 34 patients with chronic renal disease (35%) compared with an incidence of less than 2% in a series of unselected patients. It represents a distinctive form of pigmentation, possibly due to lipochromes. No decisive association could be found between the presence or absence of the pigmented nail arc and the level of impaired renal function. Nevertheless it seems that renal disease predisposes towards the development of brown nail arcs. Imagesp786-a PMID:5014252

Randomized Phase II Trial of Seribantumab in Combination With Paclitaxel in Patients With Advanced Platinum-Resistant or -Refractory Ovarian Cancer

PubMed Central

Ray-Coquard, Isabelle; Selle, Frederic; Poveda, Andrés M.; Cibula, David; Hirte, Hal; Hilpert, Felix; Raspagliesi, Francesco; Gladieff, Laurence; Harter, Philipp; Siena, Salvatore; del Campo, Josep Maria; Tabah-Fisch, Isabelle; Pearlberg, Joseph; Moyo, Victor; Riahi, Kaveh; Nering, Rachel; Kubasek, William; Adiwijaya, Bambang; Czibere, Akos; Naumann, R. Wendel; Coleman, Robert L.; Vergote, Ignace; MacBeath, Gavin; Pujade-Lauraine, Eric

2016-01-01

Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) –mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab. Patients and Methods Patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned at a ratio of two to one to receive seribantumab plus paclitaxel or paclitaxel alone. Patients underwent pretreatment core needle biopsy; archival tumor samples were also obtained to support biomarker analyses. Results A total of 223 patients were randomly assigned (seribantumab plus paclitaxel, n = 140; paclitaxel alone, n = 83). Median PFS in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741 to 1.425; P = .864). Among patients whose tumors had detectable HRG mRNA and low HER2 (n = 57 [38%] of 151 with available biomarker data), increased treatment benefit was observed in those receiving seribantumab plus paclitaxel compared with paclitaxel alone (PFS HR, 0.37; 95% CI, 0.18 to 0.76; P = .007). The HR in patients not meeting these criteria was 1.80 (95% CI, 1.08 to 2.98; P = .023). Conclusion The addition of seribantumab to paclitaxel did not result in improved PFS in unselected patients. Exploratory analyses suggest that detectable HRG and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for HRG expression and focus on cancers with low HER2 levels. PMID:27998236

Randomized Phase II Trial of Seribantumab in Combination With Paclitaxel in Patients With Advanced Platinum-Resistant or -Refractory Ovarian Cancer.

PubMed

Liu, Joyce F; Ray-Coquard, Isabelle; Selle, Frederic; Poveda, Andrés M; Cibula, David; Hirte, Hal; Hilpert, Felix; Raspagliesi, Francesco; Gladieff, Laurence; Harter, Philipp; Siena, Salvatore; Del Campo, Josep Maria; Tabah-Fisch, Isabelle; Pearlberg, Joseph; Moyo, Victor; Riahi, Kaveh; Nering, Rachel; Kubasek, William; Adiwijaya, Bambang; Czibere, Akos; Naumann, R Wendel; Coleman, Robert L; Vergote, Ignace; MacBeath, Gavin; Pujade-Lauraine, Eric

2016-12-20

Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) -mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab. Patients and Methods Patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned at a ratio of two to one to receive seribantumab plus paclitaxel or paclitaxel alone. Patients underwent pretreatment core needle biopsy; archival tumor samples were also obtained to support biomarker analyses. Results A total of 223 patients were randomly assigned (seribantumab plus paclitaxel, n = 140; paclitaxel alone, n = 83). Median PFS in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741 to 1.425; P = .864). Among patients whose tumors had detectable HRG mRNA and low HER2 (n = 57 [38%] of 151 with available biomarker data), increased treatment benefit was observed in those receiving seribantumab plus paclitaxel compared with paclitaxel alone (PFS HR, 0.37; 95% CI, 0.18 to 0.76; P = .007). The HR in patients not meeting these criteria was 1.80 (95% CI, 1.08 to 2.98; P = .023). Conclusion The addition of seribantumab to paclitaxel did not result in improved PFS in unselected patients. Exploratory analyses suggest that detectable HRG and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for HRG expression and focus on cancers with low HER2 levels.

Surgery in Jehovah's Witnesses – our experience

PubMed Central

Kujawski, Ryszard; Mik, Michał; Berut, Maciej; Dziki, Łukasz; Dziki, Adam

2015-01-01

Introduction Surgeons face a special challenge in treating Jehovah's Witnesses who refuse blood transfusion. Aim To present our surgical experience with this group of patients operated on in our department. Material and methods A retrospective study of 16 unselected Jehovah's Witnesses patients was conducted between October 2004 and February 2012. We analysed gender, age, haemogram before and after surgery, types of surgery, postoperative complications and the need for blood transfusion, and/or other drugs stimulating erythrogenesis. Results Eighty-one percent of patients were women; the average age of all patients was 57.3 years. Mean haemoglobin level, preoperative, postoperative, and on the day of discharge from hospital, was 12.5 g/dl, 9.7 g/dl, and 9.29 g/dl, respectively. Over the same time period, mean red blood cell count was 4.53 mln/µl, 3.58 mln/µl, and 3.37 mln/µl, respectively. Two out of 16 patients agreed to have blood transfusion. Drugs used for erythropoiesis stimulation included rEPO, ferrum, and folic acid. No surgical death was noted. Conclusions We found that abdominal surgery was safe in our small group of Jehovah's Witness patients. However, all Jehovah's Witness patients should be fully informed about the type of procedure and possible consequences of blood transfusion refusal. Two of our patients agreed to blood transfusion in the face of risk of death. PMID:25960813

Salpingitis Isthmica Nodosa: Technical Success and Outcome of Fluoroscopic Transcervical Fallopian Tube Recanalization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houston, J. Graeme; Machan, Lindsay S.

1998-01-15

Purpose: To evaluate the technical success and outcome of fallopian tube recanalization (FTR) in salpingitis isthmica nodosa (SIN). Methods: SIN is a well-recognized pathological condition affecting the proximal fallopian tube and is associated with infertility and ectopic pregnancy. We reviewed the presentations, films, and case records of all patients attending for FTR for infertility from 1990 to 1994. Technical success and total, intrauterine, and ectopic pregnancy rates at follow-up were determined. Results: SIN was observed in 22 of 349 (6%) patients. FTR was attempted in 34 tubes in these 22 patients. Technical success was achieved in 23 of 34 (68%)more » tubes affected by SIN. In 5 of the 11 failed recanalizations, failure was due to distal obstruction. At least one tube was patent on selective postprocedural salpingography in 17 of 22 (77%) patients. There were no recorded perforations or complications. At follow-up (mean 14 months), total, intrauterine, and ectopic pregnancy rates were 23%, 18%, and 4.5%, respectively. Conclusion: FTR in SIN is technically successful and, compared with previously reported results in unselected infertility patients, is associated with only a slightly less favorable intrauterine pregnancy rate and a comparable ectopic pregnancy rate. The findings of SIN at FTR should not discourage attempted fluoroscopic transcervical recanalization.« less

How do medical students engaging in elective courses on acupuncture and homeopathy differ from unselected students? A survey.

PubMed

Jocham, Alexandra; Kriston, Levente; Berberat, Pascal O; Schneider, Antonius; Linde, Klaus

2017-03-09

We aimed to investigate whether students at German medical schools participating in elective courses on acupuncture and homeopathy differ from an unselected group of students regarding attitudes and personality traits. Elective courses on acupuncture and homeopathy in the academic half-year 2013/14 all over Germany were identified and participants invited to fill in a questionnaire including nineteen questions on attitudes towards Complementary and Alternative Medicine (CAM), orientation towards science, care and status orientation, and a short validated instrument (Big-Five-Inventory-10) to measure personality traits (extraversion, neuroticism, openness, conscientiousness, and agreeableness). Participants of a mandatory family medicine course at one university served as unselected control group. Two hundred twenty and 113 students from elective courses on acupuncture and homeopathy, respectively, and 315 control students participated (response rate 93%). Students participating in elective courses had much more positive attitudes towards CAM, somewhat lower science and status orientation, and somewhat higher care orientation than control group students (all p-values for three-group comparisons < 0.001). There were no differences between the three groups regarding personality traits with the exception of lower values for agreeableness in controls (p = 0.009). The findings of this study show that attitudes of students participating in elective courses on acupuncture or homeopathy at German medical schools differ to a considerable degree from the attitudes of unselected students.

Degree of facial and body terminal hair growth in unselected black and white women: toward a populational definition of hirsutism.

PubMed

DeUgarte, Catherine Marin; Woods, K S; Bartolucci, Alfred A; Azziz, Ricardo

2006-04-01

Hirsutism (i.e. facial and body terminal hair growth in a male-like pattern in women) is the principal clinical sign of hyperandrogenism, although its definition remains unclear. The purposes of the present study were to define 1) the degree of facial and body terminal hair, as assessed by the modified Ferriman-Gallwey (mFG) score, in unselected women from the general population; 2) the effect of race (Black and White) on the same; and 3) the normative cutoff values. We conducted a prospective observational study at a tertiary academic medical center. Participants included 633 unselected White (n = 283) and Black (n = 350) women presenting for a preemployment physical exam. Interventions included history and physical examination. Terminal body hair growth was assessed using the mFG scoring system; nine body areas were scored from 0-4 for terminal hair growth distribution. The mFG scores were not normally distributed; although cluster analysis failed to identify a natural cutoff value or clustering of the population, principal component and univariate analyses denoted two nearly distinct clusters that occurred above and below an mFG value of 2, with the bulk of the scores below. Overall, an mFG score of at least 3 was observed in 22.1% of all subjects (i.e. the upper quartile); of these subjects, 69.3% complained of being hirsute, compared with 15.8% of women with an mFG score below this value, and similar to the proportion of women with an mFG score of at least 8 who considered themselves to be hirsute (70.0%). Overall, there were no significant differences between Black and White women. Our data indicate that the prevalence and degree of facial and body terminal hair growth, as assessed by the mFG score, is similar in Black and White women and that an mFG of at least 3 signals the population of women whose hair growth falls out of the norm.

Predictors and outcomes of acute pancreatitis in critically ill patients presenting to the emergency department of a tertiary referral centre in Australia.

PubMed

Sundararajan, Krishnaswamy; Schoeman, Tom; Hughes, Lara; Edwards, Suzanne; Reddi, Benjamin

2017-04-01

To provide a current review of the clinical characteristics, predictors and outcomes in critically ill patients presenting to the ED with acute pancreatitis and subsequently admitted to an intensive care unit (ICU) of a tertiary referral centre in Australia. A retrospective single-centre study of adult patients admitted with pancreatitis. Severe acute pancreatitis defined by Bedside Index of Severity in Acute Pancreatitis (BISAP) score ≥2. Eighty-seven patients fulfilled criteria for inclusion during the study period, representing 0.9% of all ICU admissions. The median age of patients was 54. Survival was independent of patients' age, sex, aetiology and comorbidities. Mortality was 30.8% for both inpatient referrals to the ICU and for direct referrals via the ED. Higher mortality was identified among patients requiring mechanical ventilation (74.2 vs 24.6% in survivors; P < 0.0001), vasopressor support (85.7 vs 33.8% in survivors; P < 0.0001) or renal replacement therapy (60 vs 16.9% in survivors; P < 0.002). BISAP score surpasses Ranson's and Acute Physiological and Chronic Health Examination (APACHE) II scores in discriminating between survivors and non-survivors among unselected patients with acute pancreatitis admitted to ICU, whereas APACHE II discriminates better in the cohort admitted from ED. Severe acute pancreatitis is associated with high mortality. Aetiology and comorbidity did not predict adverse outcomes in this population. BISAP score is non-inferior to APACHE II score as a prognostic tool in critically ill patients with acute pancreatitis and could be used to triage admission. Evidence of persistent organ dysfunction and requirements for organ support reliably identify patients at high-risk of death. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

The effect of endometrial scratch on natural-cycle cryopreserved embryo transfer outcomes: a randomized controlled study.

PubMed

Mak, Jennifer Sze Man; Chung, Cathy Hoi Sze; Chung, Jacqueline Pui Wah; Kong, Grace Wing Shan; Saravelos, Sotirios H; Cheung, Lai Ping; Li, Tin-Chiu

2017-07-01

The benefit of endometrial scratch (ES) prior to embryo transfer is controversial. Systemic analysis has confirmed its potential benefit, especially in women with repeated IVF failures, yet most studies have focused on fresh embryo transfer, and its effect on vitrified-warmed embryo transfer (FET) cycles is yet to be explored. We hereby present our prospective, double-blind, randomized controlled study on the evaluation of the implantation and pregnancy rate after ES prior to natural-cycle FET. A total of 299 patients underwent natural-cycle FET and were randomized to receive ES (n = 115) or endocervical manipulation as control (n = 114) prior to FET cycle, and a total of 196 patients had embryo transfer (93 patients in each group). Our study showed no significant difference in the implantation and pregnancy rate, as well as the clinical and ongoing pregnancy or live birth rates between the two groups. It appears that ES does not have any beneficial effect on an unselected group of women undergoing FET in natural cycles. Further studies on its effect in women with recurrent implantation failure after IVF are warranted. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population

PubMed Central

Brain, Keith L.; Kay, Jonathan; Shine, Brian

2009-01-01

Background Despite the rarity of pheochromocytoma, the dangers of uncontrolled severe hypertension and the very effective surgical treatment of this condition mean that diagnosis is important. Urinary or plasma catecholamines or catecholamine-derivatives are commonly used to screen for pheochromocytomas prior to imaging. This study investigates whether derived measures obtained from 24-hour urinary metanephrine results, patient age and sex can better predict tumors in populations with a low pre-test probability. Methods This study takes a pragmatic approach by retrospectively studying the outcomes of an unselected population referred for urinary metanephrine testing (1819 patients) to a tertiary hospital laboratory, and investigates the usefulness of some simple derivative measures for detecting pheochromocytoma. Urinary 24-hour excretion of metanephrine, normetanephrine and 3-methoxytyramine were normalized by dividing by an age- and sex- specific reference range. The ability of products of these normalized measures to predict pheochromocytomas was assessed, compared to a gold standard of biopsy-confirmed tumor. Results The normalized product of urinary metanephrine and normetanephrine excretion (nMAD.nNMT) proved to be a highly sensitive (100%) and specific (99.1%) measure yielding a positive predictive value 82%. Receiver-operator characteristic curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. nMAD.nNMT gave higher sensitivity and specificity than either test alone. Conclusion We suggest that nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pre-test probability. PMID:16990424

Novel BRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland.

PubMed

Sobczak, K; Kozłowski, P; Napierała, M; Czarny, J; Woźniak, M; Kapuścińska, M; Lośko, M; Koziczak, M; Jasińska, A; Powierska, J; Braczkowski, R; Breborowicz, J; Godlewski, D; Mackiewicz, A; Krzyzosiak, W

1997-10-09

Three different novel BRCA1 mutations, five independent cases of the same 12 bp insertion-duplication in intron-20 and two novel rare BRCA1 sequence variants were identified among 122 Polish women with positive, in most cases moderate family history of breast and/or ovarian cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in intron-20 were first found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT-PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and significance of different BRCA1 variants and mutations.

Urine output on ICU entry is associated with hospital mortality in unselected critically ill patients.

PubMed

Zhang, Zhongheng; Xu, Xiao; Ni, Hongying; Deng, Hongsheng

2014-02-01

Urine output (UO) is routinely measured in the intensive care unit (ICU) but its prognostic value remains debated. The study aimed to investigate the association between day 1 UO and hospital mortality. Clinical data were abstracted from the Multiparameter Intelligent Monitoring in Intensive Care II (version 2.6) database. UO was recorded for the first 24 h after ICU entry, and was classified into three categories: UO >0.5, 0.3-0.5 and ≤0.3 ml/kg per hour. The primary endpoint was the hospital mortality. Four models were built to adjust for the hazards ratio of mortality. A total of 21,207 unselected ICU patients including 2,401 non-survivors and 18,806 survivors were included (mortality rate 11.3 %). Mortality rate increased progressively across UO categories: >0.5 (7.67 %), 0.3-0.5 (11.27 %) and ≤0.3 ml/kg/h (18.29 %), and this relationship remained statistically significant after rigorous control of confounding factors with the Cox proportional hazards regression model. With UO >0.5 as the referent group, the hazards ratios for UO 0.3-0.5 and UO ≤0.3 were 1.41 (95 % CI 1.29-1.54) and 1.52 (95 % CI 1.38-1.67), respectively. UO obtained on ICU entry is an independent predictor of mortality irrespective of diuretic use. It would be interesting to examine whether strategies to increase UO would improve clinical outcome.

Lasting impact of an implemented self-management programme for people with type 2 diabetes referred from primary care: a one-group, before-after design.

PubMed

Fløde, Mari; Iversen, Marjolein M; Aarflot, Morten; Haltbakk, Johannes

2017-12-01

Research interventions in uniform clinical settings and in patients fulfilling well-defined inclusion criteria might show a more pronounced effect than implementing the same intervention in existing practice. Diabetes Self-Management Education (DSME) is complex, and should be assessed in existing practice as it is an intervention widely implemented. To examine the impact of an established group-based DSME in unselected people with type 2 diabetes referred from primary care. A one-group, before-after design was used for assessments before, immediately after, and 3 months after participation in a group-based DSME programme conducted at two Learning and Mastering Centres in Norway between November 2013 and June 2014. Participants completed a questionnaire before (n = 115), immediately after (n = 95) and 3 months after (n = 42) the DSME programme. Primary outcome measure was diabetes knowledge (Michigan Diabetes Knowledge Test). Also patient activation (Patient Activation Measure [PAM]) and self-efficacy (General Self-Efficacy scale [GSE]) were measured. Changes in outcome measures were analysed using paired t-tests for normally distributed data and Wilcoxon signed-rank test for skewed data. Mean knowledge improved significantly from baseline (p < 0.001). Changes persisted at the 3-month assessment. Mean PAM scores improved significantly from baseline (p < 0.001), and changes persisted for 3 months. Mean GSE scores improved from baseline (p = 0.022) and persisted for 3 months. However, when results were stratified for participants who responded at all three time points, GSE showed no change during the study period. The complexity self-management in the individual is challenging to reflect in DSME. This implemented DSME programme for people with type 2 diabetes improved levels of diabetes knowledge and patient activation, persisting for at least 3 months. Hence, the DSME programme appears to be robust beyond standardised research settings, in educating unselected diabetes patients referred from primary care. © 2017 Nordic College of Caring Science.

What is the evidence base to guide surgical treatment of infected hip prostheses? systematic review of longitudinal studies in unselected patients

PubMed Central

2012-01-01

Background Prosthetic joint infection is an uncommon but serious complication of hip replacement. There are two main surgical treatment options, with the choice largely based on the preference of the surgeon. Evidence is required regarding the comparative effectiveness of one-stage and two-stage revision to prevent reinfection after prosthetic joint infection. Methods We conducted a systematic review to identify randomised controlled trials, systematic reviews and longitudinal studies in unselected patients with infection treated exclusively by one- or two-stage methods or by any method. The Embase, MEDLINE and Cochrane databases were searched up to March 2011. Reference lists were checked, and citations of key articles were identified by using the ISI Web of Science portal. Classification of studies and data extraction were performed independently by two reviewers. The outcome measure studied was reinfection within 2 years. Data were combined to produce pooled random-effects estimates using the Freeman-Tukey arc-sine transformation. Results We identified 62 relevant studies comprising 4,197 patients. Regardless of treatment, the overall rate of reinfection after any treatment was 10.1% (95% CI = 8.2 to 12.0). In 11 studies comprising 1,225 patients with infected hip prostheses who underwent exclusively one-stage revision, the rate of reinfection was 8.6% (95% CI = 4.5 to 13.9). After two-stage revision exclusively in 28 studies comprising 1,188 patients, the rate of reinfection was 10.2% (95% CI = 7.7 to 12.9). Conclusion Evidence of the relative effectiveness of one- and two-stage revision in preventing reinfection of hip prostheses is largely based on interpretation of longitudinal studies. There is no suggestion in the published studies that one- or two stage methods have different reinfection outcomes. Randomised trials are needed to establish optimum management strategies. PMID:22340795

Immunophenotypic analysis of adult patients with T-cell lymphoblastic lymphoma treated with hyper-CVAD.

PubMed

Kato, Harumi; Yamamoto, Kazuhito; Kodaira, Takeshi; Higuchi, Yusuke; Yamamoto, Hideyuki; Saito, Toko; Taji, Hirofumi; Yatabe, Yasushi; Nakamura, Shigeo; Kinoshita, Tomohiro

2018-03-01

Immunophenotype is an important prognostic factor for childhood and adult T-cell acute lymphoblastic leukemia. However, immunophenotypic data from adult patients with T-cell lymphoblastic lymphoma (T-LBL) are scarcely available. Subjects were unselected adult patients with T-LBL who were treated with intensive chemotherapy. Immunophenotyping of tumor cells was performed according to standard techniques. A total of eight patients with a median age of 31 years were analyzed who received hyper-CVAD treatment for LBL. Immunophenotypic analysis showed that the most common tumor type was cortical T-cell type [early T (n = 2), cortical T (n = 4), and medullary T (n = 2)]. Two patients diagnosed with early T-cell type had early disease progression. Assessment of T-cell differentiation stages in malignant T lymphoblasts would be important in choosing treatment strategies for adult patients with T-LBL.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mast, Mirjam E., E-mail: m.mast@mchaaglanden.nl; Heijenbrok, Mark W.; Petoukhova, Anna L.

Purpose: Breast cancer radiotherapy has been associated with an increased risk of cardiac toxicity. However, no data are available on the probability of developing coronary artery disease (CAD) in breast cancer patients when compared with healthy women. Therefore, baseline coronary artery calcium (CAC) scores, as an accepted tool to predict CAD, were determined and compared with the CAC scores of a healthy, asymptomatic cohort, the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Methods and Materials: Eighty consecutive patients with ductal carcinoma in situ or infiltrative breast cancer referred for radiotherapy after breast-conserving surgery were included in our study. Their cardiovascular riskmore » profile was registered, and a 64 multislice CT scan was performed. The CAC scores of an unselected (Caucasian only) Radiotherapy Centre West (RCWEST) cohort, as well as of those of a selected (comorbidity and race adjusted) RCWEST cohort, were determined. The scores of both cohorts were compared with those of the female (Caucasian only) MESA cohort. Results: For the unselected RCWEST cohort (n = 62) we found significant (p < .01) higher scores for women in the 55-64 age category compared with those of the MESA cohort. In the selected cohort (n = 55) the CAC scores of the women in the age category 55-64 were significantly (p = .02) higher compared with the MESA cohort. No significant differences were noted in the other age categories. Conclusion: Both cohorts revealed that CAC scores in the 55-64 age category were significantly higher than the CAC scores in the asymptomatic (female) MESA population. These data suggest that breast cancer patients bear a higher risk of developing coronary heart disease before the start of radiotherapy. Therefore, measures to decrease cardiac dose further in breast cancer radiotherapy are even more important.« less

Prevalence, awareness, treatment, and control rate of hypertension in HIV-infected patients: the HIV-HY study.

PubMed

De Socio, Giuseppe Vittorio; Ricci, Elena; Maggi, Paolo; Parruti, Giustino; Pucci, Giacomo; Di Biagio, Antonio; Calza, Leonardo; Orofino, Giancarlo; Carenzi, Laura; Cecchini, Enisia; Madeddu, Giordano; Quirino, Tiziana; Schillaci, Giuseppe

2014-02-01

We aimed to assess the prevalence of hypertension in an unselected human immunodeficiency virus (HIV)-infected population and to identify factors associated with hypertension prevalence, treatment, and control. We used a multicenter, cross-sectional, nationwide study that sampled 1,182 unselected, consecutive, HIV-infected patients. Office blood pressure was accurately measured with standard procedures. Patients were 71% men and 92% white, with a median age of 47 years (range = 18-78); 6% were antiretroviral treatment naive. The overall prevalence of hypertension was 29.3%; high-normal pressure accounted for an additional 12.3%. Among hypertensive subjects, 64.9% were aware of their hypertensive condition, 52.9% were treated, and 33.0% were controlled (blood pressure < 140/90 mm Hg). Blood pressure-lowering medications were used in monotherapy in 54.3% of the subjects. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were the most frequently used drugs (76.1%: monotherapy = 39.1%, combination treatment = 37.0%). In multivariable regression models, hypertension was independently predicted by traditional risk factors, including age ≥50 years, male sex, family history of cardiovascular disease, body mass index ≥25 kg/m2, previous cardiovascular events, diabetes, central obesity, and metabolic syndrome, as well as by duration of HIV infection, duration of antiretroviral therapy, and nadir CD4+ T-cell count <200/μl. The choice of protease inhibitors vs. nonnucleoside reverse transcriptase inhibitors as a third antiretroviral drug was irrelevant. Hypertension affects nearly 30% of HIV adult outpatients in Italy. More than one-third of the hypertensive subjects are unaware of their condition, and more than two-thirds are uncontrolled. A higher level of attention to the diagnosis and treatment of hypertension is mandatory in this setting.

The Spectrum of Renal Allograft Failure

PubMed Central

Chand, Sourabh; Atkinson, David; Collins, Clare; Briggs, David; Ball, Simon; Sharif, Adnan; Skordilis, Kassiani; Vydianath, Bindu; Neil, Desley; Borrows, Richard

2016-01-01

Background Causes of “true” late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. Methods We evaluated all unselected graft failures from 2008–2014 (n = 171; 0–36 years post-transplantation) by contemporary classification of indication biopsies “proximate” to failure, DSA assessment, clinical and biochemical data. Results The spectrum of graft failure changed markedly depending on the timing of allograft failure. Failures within the first year were most commonly attributed to technical failure, acute rejection (with T-cell mediated rejection [TCMR] dominating antibody-mediated rejection [ABMR]). Failures beyond a year were increasingly dominated by ABMR and ‘interstitial fibrosis with tubular atrophy’ without rejection, infection or recurrent disease (“IFTA”). Cases of IFTA associated with inflammation in non-scarred areas (compared with no inflammation or inflammation solely within scarred regions) were more commonly associated with episodes of prior rejection, late rejection and nonadherence, pointing to an alloimmune aetiology. Nonadherence and late rejection were common in ABMR and TCMR, particularly Acute Active ABMR. Acute Active ABMR and nonadherence were associated with younger age, faster functional decline, and less hyalinosis on biopsy. Chronic and Chronic Active ABMR were more commonly associated with Class II DSA. C1q-binding DSA, detected in 33% of ABMR episodes, were associated with shorter time to graft failure. Most non-biopsied patients were DSA-negative (16/21; 76.1%). Finally, twelve losses to recurrent disease were seen (16%). Conclusion This data from an unselected population identifies IFTA alongside ABMR as a very important cause of true late graft failure, with nonadherence-associated TCMR as a phenomenon in some patients. It highlights clinical and immunological characteristics of ABMR subgroups, and should inform clinical practice and individualised patient care. PMID:27649571

CHEK2 mutations and the risk of papillary thyroid cancer.

PubMed

Siołek, Monika; Cybulski, Cezary; Gąsior-Perczak, Danuta; Kowalik, Artur; Kozak-Klonowska, Beata; Kowalska, Aldona; Chłopek, Małgorzata; Kluźniak, Wojciech; Wokołorczyk, Dominika; Pałyga, Iwona; Walczyk, Agnieszka; Lizis-Kolus, Katarzyna; Sun, Ping; Lubiński, Jan; Narod, Steven A; Góźdż, Stanisław

2015-08-01

Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age- and sex-matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 + 1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non-carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid. © 2015 UICC.

Individual polyp detection rate in routine daily endoscopy practice depends on case-mix.

PubMed

Loffeld, R J L F; Liberov, B; Dekkers, P E P

2015-07-01

The adenoma detection rate (ADR), a marker of endoscopic quality, is confounded by selection bias. It is not known what the ADR is in normal daily practice. To study the polyp detection rate (PDR) in different endoscopists in the course of years. All consecutive endoscopies of the colon done in 11 years were included. Endoscopies in the regular surveillance programme after polyp removal and after surgery because of colorectal cancer or diverticular disease were scored separately. The number of yearly procedures per endoscopist and presence of polyps, anastomoses, surveillance and cancer were noted. In the period of 11 years, 14,908 consecutive endoscopies of colon and rectum were done by four endoscopists. Two endoscopists had a significantly lower PDR than the other two (p < 0.001), these two had the longest careers in endoscopy. The two younger endoscopists did significantly less often procedures in patients with anastomoses and because of surveillance (p < 0.001, respectively). One endoscopist detected significantly less colorectal cancers than the other three endoscopists (p < 0.001). This study presents the PDR in normal routine daily endoscopy practice. It can be concluded that the PDR, implicating the ADR, in unselected patients can be lower in individual endoscopists than recommended in the literature. This highly depends on the case-mix of patients presented for endoscopy. This result debates the use of the ADR as quality indicator for individual endoscopists.

Incidence and diagnosis of anosognosia for hemiparesis revisited

PubMed Central

Baier, B; Karnath, H

2005-01-01

Background: In previous studies, the incidence of anosognosia for hemiparesis has varied between 17% and 58% in samples of brain damaged patients with hemiparesis. Objective: To determine whether this wide variation might be explained by the different criteria used for diagnosing anosognosia. Methods: 128 acute stroke patients with hemiparesis or hemiplegia were tested for anosognosia for hemiparesis using the anosognosia scale of Bisiach et al. Results: 94% of the patients who were rated as having "mild anosognosia"—that is, they did not acknowledge their hemiparesis spontaneously following a general question about their complaints—suffered from, and mentioned, other neurological deficits such as dysarthria, ptosis, or headache. However, they immediately acknowledged their paresis when they were asked about the strength of their limbs. Their other deficits clearly had a greater impact. These patients had significantly milder paresis than those who denied their disorder even when asked directly about their limbs. Conclusions: Patients who do not mention their paresis spontaneously but do so when questioned about it directly should not be diagnosed having "anosognosia." If this more conservative cut off criterion is applied to the data of the present as well as previous studies, a frequency of between 10% and 18% for anosognosia for hemiparesis is obtained in unselected samples of acute hemiparetic stroke patients. The incidence thus seems smaller than previously assumed. PMID:15716526

[Institutional Prevalence and Context of Severe Sleep Disorders in Psychosomatic Rehabilitation].

PubMed

Linden, Michael

2015-07-01

In cases of burnout, chronic fatigue, depression, somatization, overtaxation, or impairment in wellbeing and work capacity, the cause can be sleep problems. Goal of the present study was to estimate the prevalence of sleep problems in psychosomatic inpatients. Included were 1325 unselected patients from a psychosomatic rehabilitation hospital. They filled in the SCL-90, the PSQI and were assessed in respect to their clinical, social and occupational status. At admission 13.4% of patients had a PSQI score of 5 at maximum (no sleep problem), 34.6% 6 to 10 (moderate sleep problem) und 52.1% over 10 (severe sleep problem). At discharge there was a reduction of sleep problems with 32.7% of patients over 10. Sleep problems were significantly associated with more severe mental problems, older age, women, lower socioeconomic status, and also incapacity to work or early retirement. Mental disorders can cause sleep problems and sleep problems mental disorders and incapacity to work, with a negative interaction. The high rate of severe sleep problems in rehabilitation patients shows that this problem is in need of special diagnostic and therapeutic attention. Also, the equipment of hospitals and the qualification of therapists should allow adequate care. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical presentation and management of stable coronary artery disease in Austria.

PubMed

Pichlhöfer, Otto; Maier, Manfred; Badr-Eslam, Roza; Ristl, Robin; Zebrowska, Magdalena; Lang, Irene M

2017-01-01

Cardiovascular disease is the main cause of death in Austria. However, no systematic information exists regarding characteristics and treatments of contemporary patients with stable coronary artery disease (CAD) in Austria. We assembled two retrospective physicians' databases to describe demographics, clinical profiles, and therapeutic strategies in patients with stable CAD. In addition, we compared patient profiles of secondary care internists and hospital-based cardiologists with those of general practitioners in a primary care setting outside of hospital. The study population was identified from retrospective chart review of 1020 patients from 106 primary care physicians in Austria (ProCor II registry), and was merged with a previous similar database of 1280 patients under secondary care (ProCor I registry) to yield a total patient number of 2300. Female patients with stable CAD were older, had more angina and/or heart failure symptoms, and more depression than males. Female gender, type 2 diabetes mellitus, higher CCS class and asthma/COPD were predictors of elevated heart rate, while previous coronary events/revascularization predicted a lower heart rate in multivariate analysis. There were no significant differences with regard to characteristics and management of patients of general practitioners in the primary care setting versus internists in secondary care. Characteristics and treatments of unselected patients with stable ischemic heart disease in Austria resemble the pattern of large international registries of stable ischemic heart disease, with the exception that diabetes and systemic hypertension were more prevalent.

Construct validity and frequency of euphoria sclerotica in multiple sclerosis.

PubMed

Fishman, Inna; Benedict, Ralph H B; Bakshi, Rohit; Priore, Roger; Weinstock-Guttman, Bianca

2004-01-01

Using the Neuropsychiatric Inventory (NPI), we studied euphoria and other behavioral changes in 75 consecutive, unselected multiple sclerosis (MS) patients and 25 healthy controls. We also assessed disease duration, clinical course, physical disability, personality, depression, insight, cognition, and caregiver distress. Factor analysis identified a cluster of symptoms--labeled euphoria/disinhibition--similar to the euphoria sclerotica syndrome originally described by Charcot and others. The euphoria/disinhibition factor score was elevated in 9% of patients and associated with secondary-progressive course, low agreeableness, poor insight, impaired cognition, and high caregiver distress. Thus, we used the NPI to validate the euphoria syndrome in multiple sclerosis (MS) and determined its frequency, and its neurological and psychological correlates.

Impact of P2Y12 inhibition by clopidogrel on cardiovascular mortality in unselected patients treated by percutaneous coronary angioplasty: a prospective registry.

PubMed

El Ghannudi, Soraya; Ohlmann, Patrick; Meyer, Nicolas; Wiesel, Marie-Louise; Radulescu, Bogdan; Chauvin, Michel; Bareiss, Pierre; Gachet, Christian; Morel, Olivier

2010-06-01

The aim of this study was to determine whether low platelet response to the P2Y(12) receptor antagonist clopidogrel as assessed by Vasodilator-stimulated phosphoprotein flow cytometry test (VASP- FCT) predicts cardiovascular events in a high-risk population undergoing percutaneous coronary intervention (PCI). Impaired platelet responsiveness to clopidogrel is thought to be a determinant of cardiovascular events after PCI. The platelet VASP-FCT is a new assay specific to the P2Y(12) adenosine diphosphate receptor-pathway. In this test, platelet activation is expressed as platelet reactivity index (PRI). Four-hundred sixty-one unselected patients undergoing urgent (n = 346) or planned (n = 115) PCI were prospectively enrolled. Patients were classified as low-response (LR) and response (R) to clopidogrel, depending on their PRI. Optimal PRI cutoff was determined by receiver-operator characteristic curve analysis to 61% (LR: PRI > or =61% and R: PRI <61%). Follow-up was obtained at a mean of 9 +/- 2 months in 453 patients (98.3%). At follow-up, total cardiac mortality rates and possible and total stent thrombosis were higher in LR patients. Multivariate analysis identified creatinine clearance (hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.93 to 0.98, p < 0.001), drug-eluting stent (HR: 5.73; 95% CI: 1.40 to 23.43, p = 0.015), C-reactive protein (HR: 1.01; 95% CI: 1.001 to 1.019, p = 0.024), and LR to clopidogrel (HR: 4.00; 95% CI: 1.08 to 14.80, p = 0.037) as independent predictors of cardiac death. The deleterious impact of LR to clopidogrel on cardiovascular death was significantly higher in patients implanted with drug-eluting stent. In patients undergoing PCI, LR to clopidogrel assessed by VASP-FCT is an independent predictor of cardiovascular death at the PRI cutoff value of > or =61%. The LR clinical impact seems to be dependent on the type of stent implanted. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Prognosis and guideline-adherent antithrombotic treatment in patients with atrial fibrillation and atrial flutter: implications of undertreatment and overtreatment in real-life clinical practice; the Loire Valley Atrial Fibrillation Project.

PubMed

Gorin, Laurent; Fauchier, Laurent; Nonin, Emilie; Charbonnier, Bernard; Babuty, Dominique; Lip, Gregory Y H

2011-10-01

In patients with atrial fibrillation (AF), adherence to guidelines for antithrombotic treatment is poorly followed, and undertreatment (or nonadherence with guidelines) is associated with a worse prognosis. The study objective was to evaluate whether this was also the case in a large contemporary series of unselected patients with AF in real-world clinical practice. All patients with AF or atrial flutter seen in our institution between 2000 and 2007 were identified in a database and followed up for mortality and stroke. Antithrombotic guideline adherence was assessed according to the 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines. We reviewed outcomes in 3,646 consecutive patients with AF or atrial flutter (aged 71 ± 14 years; mean CHADS(2) [congestive heart failure, hypertension, aged ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score, 1.5 ± 1.1). Antithrombotic treatment was in agreement with the guidelines in 53% of patients, whereas 31% were classified as undertreated and 16% as overtreated. Among other parameters, nonpermanent AF and atrial flutter were independently associated with an increased risk of undertreatment. After a follow-up of 953 ± 767 days (median, 771 days; interquartile range, 1,286 days), guideline adherence was associated with a lower risk of adverse events (death from all causes or stroke) compared with undertreatment (relative risk, 0.47; 95% CI, 0.40-0.55; P < .0001). Overtreatment was associated with a lower risk of adverse events compared with the guideline-adherent population (relative risk, 0.40; 95% CI, 0.28-0.58; P < .0001). Factors independently associated with increased risk of mortality or stroke were antithrombotic undertreatment, older age, heart failure, renal failure, diabetes, male sex, and previous history of stroke. Guideline nonadherence and undertreatment with antithrombotic agents in unselected real-world patients with AF or atrial flutter are independently associated with a high risk of stroke and mortality.

CHEK2 1100delC and male breast cancer in the Netherlands.

PubMed

Wasielewski, Marijke; den Bakker, Michael A; van den Ouweland, Ans; Meijer-van Gelder, Marion E; Portengen, Henk; Klijn, Jan G M; Meijers-Heijboer, Hanne; Foekens, John A; Schutte, Mieke

2009-07-01

Mutations in the breast cancer susceptibility genes BRCA1, BRCA2, and CHEK2 are known risk factors for female breast cancer. Mutations in BRCA1 and BRCA2 also are associated with male breast cancer (MBC). Similarly, it had been suggested in the original CHEK2 identification report that the CHEK2 1100delC mutation confers an increased risk for MBC. Here, we have evaluated the risk of CHEK2 1100delC for MBC by genotyping CHEK2 1100delC in 23 familial and 71 unselected Dutch MBC cases. None of the 23 familial MBC cases carried the CHEK2 1100delC mutation. In contrast, CHEK2 1100delC was present in 3 of the 71 (4.2%) unselected MBC cases, which was significantly more prevalent than the 1.1% Dutch population frequency assessed in 1,692 individuals (P = 0.05, OR = 4.1, 95% CI 1.2-14.3). Our data suggest that, in the Netherlands, CHEK2 1100delC is associated with an increased risk for MBC.

The Spectrum of Paraneoplastic Cutaneous Vasculitis in a Defined Population

PubMed Central

Loricera, Javier; Calvo-Río, Vanesa; Ortiz-Sanjuán, Francisco; González-López, Marcos A.; Fernández-Llaca, Hector; Rueda-Gotor, Javier; Gonzalez-Vela, Maria C.; Alvarez, Lino; Mata, Cristina; González-Lamuño, Domingo; Martínez-Taboada, Victor M.; González-Gay, Miguel A.; Blanco, Ricardo

2013-01-01

Abstract Cutaneous vasculitis may be associated with malignancies, and may behave as a paraneoplastic syndrome. This association has been reported in a variable proportion of patients depending on population selection. We conducted the current study to assess the frequency, clinical features, treatment, and outcome of paraneoplastic vasculitis in a large unselected series of 766 patients with cutaneous vasculitis diagnosed at a single university hospital. Sixteen patients (10 men and 6 women; mean age ± standard deviation, 67.94 ± 14.20 yr; range, 40–85 yr) presenting with cutaneous vasculitis were ultimately diagnosed as having an underlying malignancy. They constituted 3.80% of the 421 adult patients. There were 9 hematologic and 7 solid underlying malignancies. Skin lesions were the initial clinical presentation in all of them, and the median interval from the onset of cutaneous vasculitis to the diagnosis of the malignancy was 17 days (range, 8–50 d). The most frequent skin lesions were palpable purpura (15 patients). Other clinical manifestations included constitutional syndrome (10 patients) and arthralgia and/or arthritis (4 cases). Hematologic cytopenias (11 cases) as well as immature peripheral blood cells (6 cases) were frequently observed in the full blood cell count, especially in those with vasculitis associated with hematologic malignancies. Specific treatment for vasculitis was prescribed in 10 patients; nonsteroidal antiinflammatory drugs (4 patients), corticosteroids (3 patients), chloroquine (1 patient), antihistamines (1 patient), and cyclophosphamide (1 patient). Ten patients died due to the malignancy and 6 patients recovered following malignancy therapy. Patients with paraneoplastic vasculitis were older, more frequently had constitutional syndrome, and less frequently had organ damage due to the vasculitis than the remaining patients with cutaneous vasculitis. In summary, cutaneous paraneoplastic vasculitis is an entity not uncommonly encountered by clinicians. The most common underlying malignancy is generally hematologic. In these cases the presence of cytopenias and immature cells may be red flags for the diagnosis of cancer. In patients with paraneoplastic cutaneous vasculitis, the prognosis depends on the underlying neoplasia. PMID:24145696

Laparoscopic Cholecystectomy and Incidental Carcinoma of the Extrahepatic Biliary Tree

PubMed Central

Raparelli, Luigi; Jover Navalon, Jose' Maria; Gomez, Ana Serantes; Azcoita, Mariano Moreno; Materia, Alberto; Basso, Nicola

2002-01-01

Background and Objectives: Gallbladder carcinoma is found in 0.2 % to 5% of patients undergoing cholecystectomy, and gallstones are found in 70% to 98% of patients with gallbladder carcinoma. Early diagnosis of carcinoma is difficult because of the absence of specific symptoms and the frequent association with chronic cholecystitis and gallstones. At present, laparoscopic cholecystectomy is the gold standard for the surgical treatment of symptomatic cholelithiasis and other benign gallbladder diseases. The aims of this study were to evaluate retrospectively the incidence of occasional and occult gallbladder carcinomas to ascertain the effect of laparoscopy on diagnosis and treatment of unexpected extrahepatic biliary tree carcinomas and to assess possible guidelines that can be taken into consideration when the problem is encountered. Methods: Clinical records of 3900 patients undergoing laparoscopic cholecystectomy were reviewed. Patients with occasional (intraoperative = Group A) or occult (postoperative = Group B) diagnosis of gallbladder or common bile duct carcinoma entered the study group. Follow-up data were obtained in June 2000. Results: A total of 14 patients (0.35%), 3 men and 11 women, mean age 60.8 years (range 37 to 73) with extra-hepatic biliary tree carcinoma were found. Occasional carcinomas occurred in 8 patients, occult carcinomas in 6. No deaths occurred in either group. The overall survival at mean follow-up of 30.5 months is 50%. Five patients are disease free, and 2 are alive with evidence of recurrence. Discussion: In 2 large series of unselected consecutive laparoscopic cholecystectomy, only 14 unsuspected malignant tumors of the extrahepatic biliary tree were found (0.35%). The limits of the preoperative workup and the difficult diagnosis of biliary tract carcinoma during laparoscopic cholecystectomy, has led to the present retrospective study and several significant recommendations. PMID:12500833

Predictive value of the baseline electrocardiogram ST-segment pattern in cardiogenic shock: Results from the CardShock Study.

PubMed

Javanainen, Tuija; Tolppanen, Heli; Lassus, Johan; Nieminen, Markku S; Sionis, Alessandro; Spinar, Jindrich; Silva-Cardoso, José; Greve Lindholm, Matias; Banaszewski, Marek; Harjola, Veli-Pekka; Jurkko, Raija

2018-05-30

The most common aetiology of cardiogenic shock (CS) is acute coronary syndrome (ACS), but even up to 20%-50% of CS is caused by other disorders. ST-segment deviations in the electrocardiogram (ECG) have been investigated in patients with ACS-related CS, but not in those with other CS aetiologies. We set out to explore the prevalence of different ST-segment patterns and their associations with the CS aetiology, clinical findings and 90-day mortality. We analysed the baseline ECG of 196 patients who were included in a multinational prospective study of CS. The patients were divided into 3 groups: (a) ST-segment elevation (STE). (b) ST-segment depression (STDEP). (c) No ST-segment deviation or ST-segment impossible to analyse (NSTD). A subgroup analysis of the ACS patients was conducted. ST-segment deviations were present in 80% of the patients: 52% had STE and 29% had STDEP. STE was associated with the ACS aetiology, but one-fourth of the STDEP patients had aetiology other than ACS. The overall 90-day mortality was 41%: in STE 47%, STDEP 36% and NSTD 33%. In the multivariate mortality analysis, only STE predicted mortality (HR 1.74, CI 95 1.07-2.84). In the ACS subgroup, the patients were equally effectively revascularized, and no differences in the survival were noted between the study groups. ST-segment elevation is associated with the ACS aetiology and high mortality in the unselected CS population. If STE is not present, other aetiologies must be considered. When effectively revascularized, the prognosis is similar regardless of the ST-segment pattern in ACS-related CS. © 2018 Wiley Periodicals, Inc.

Body dysmorphic concerns, social adaptation, and motivation for psychotherapeutic support in dermatological outpatients.

PubMed

Ritter, Viktoria; Fluhr, Joachim W; Schliemann-Willers, Sibylle; Elsner, Peter; Strauß, Bernhard; Stangier, Ulrich

2016-09-01

Dermatologists are increasingly confronted with patients affected by body dysmorphic disorder (BDD). BDD is characterized by excessive preoccupation with one or more perceived defect(s) or flaw(s) in physical appearance which are not observable or appear slight to others. So far, there have been only few studies examining the prevalence of BDD in dermatological outpatients. In addition, the need for psychotherapeutic support in dermatological outpatients with body dysmorphic concerns has not yet been systematically examined. The objective of the present study was therefore to investigate the frequency of body dysmorphic concerns as well as social adaptation and the need for psychotherapeutic support in the aforementioned patient group. A total of 252 dermatological outpatients seen at a German university hospital were consecutively enrolled, and examined using the Dysmorphic Concerns Questionnaire, the Social Adaptation Self-Evaluation Scale, and the German version of the University of Rhode Island Change Assessment Scale. 7.9 % of all outpatients (unselected sample) showed positive test results, suggesting clinically relevant body dysmorphic concerns. Patients with clinically relevant body dysmorphic concerns exhibited poor social adaptation. Contrary to expectations, these patients revealed a high motivation for change, indicating the necessity for psychotherapeutic support. Our findings confirm previous prevalence rates of BDD in dermatological outpatients, and highlight the need for providing psychotherapeutic support to dermatological patients. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression.

PubMed

Dicker, Frank; Schnittger, Susanne; Haferlach, Torsten; Kern, Wolfgang; Schoch, Claudia

2006-11-01

Compared with fluorescence in situ hybridization (FISH), conventional metaphase cytogenetics play only a minor prognostic role in chronic lymphocytic leukemia (CLL) so far, due to technical problems resulting from limited proliferation of CLL cells in vitro. Here, we present a simple method for in vitro stimulation of CLL cells that overcomes this limitation. In our unselected patient population, 125 of 132 cases could be successfully stimulated for metaphase generation by culture with the immunostimulatory CpG-oligonucleotide DSP30 plus interleukin 2. Of 125 cases, 101 showed chromosomal aberrations. The aberration rate is comparable to the rate detected by parallel interphase FISH. In 47 patients, conventional cytogenetics detected additional aberrations not detected by FISH analysis. A complex aberrant karyotype, defined as one having at least 3 aberrations, was detected in 30 of 125 patients, compared with only one such case as defined by FISH. Conventional cytogenetics frequently detected balanced and unbalanced translocations. A significant correlation of the poor-prognosis unmutated IgV(H) status with unbalanced translocations and of the likewise poor-prognosis CD38 expression to balanced translocations and complex aberrant karyotype was found. We demonstrate that FISH analysis underestimates the complexity of chromosomal aberrations in CLL. Therefore, conventional cytogenetics may define subgroups of patients with high risk of progression.

Derivation and external validation of a case mix model for the standardized reporting of 30-day stroke mortality rates.

PubMed

Bray, Benjamin D; Campbell, James; Cloud, Geoffrey C; Hoffman, Alex; James, Martin; Tyrrell, Pippa J; Wolfe, Charles D A; Rudd, Anthony G

2014-11-01

Case mix adjustment is required to allow valid comparison of outcomes across care providers. However, there is a lack of externally validated models suitable for use in unselected stroke admissions. We therefore aimed to develop and externally validate prediction models to enable comparison of 30-day post-stroke mortality outcomes using routine clinical data. Models were derived (n=9000 patients) and internally validated (n=18 169 patients) using data from the Sentinel Stroke National Audit Program, the national register of acute stroke in England and Wales. External validation (n=1470 patients) was performed in the South London Stroke Register, a population-based longitudinal study. Models were fitted using general estimating equations. Discrimination and calibration were assessed using receiver operating characteristic curve analysis and correlation plots. Two final models were derived. Model A included age (<60, 60-69, 70-79, 80-89, and ≥90 years), National Institutes of Health Stroke Severity Score (NIHSS) on admission, presence of atrial fibrillation on admission, and stroke type (ischemic versus primary intracerebral hemorrhage). Model B was similar but included only the consciousness component of the NIHSS in place of the full NIHSS. Both models showed excellent discrimination and calibration in internal and external validation. The c-statistics in external validation were 0.87 (95% confidence interval, 0.84-0.89) and 0.86 (95% confidence interval, 0.83-0.89) for models A and B, respectively. We have derived and externally validated 2 models to predict mortality in unselected patients with acute stroke using commonly collected clinical variables. In settings where the ability to record the full NIHSS on admission is limited, the level of consciousness component of the NIHSS provides a good approximation of the full NIHSS for mortality prediction. © 2014 American Heart Association, Inc.

Glaucoma incidence in an unselected cohort of diabetic patients: is diabetes mellitus a risk factor for glaucoma? DARTS/MEMO collaboration. Diabetes Audit and Research in Tayside Study. Medicines Monitoring Unit.

PubMed

Ellis, J D; Evans, J M; Ruta, D A; Baines, P S; Leese, G; MacDonald, T M; Morris, A D

2000-11-01

To evaluate whether diabetes mellitus is a risk factor for the development of primary open angle glaucoma or ocular hypertension (OHT). A historical cohort study of an unselected population comprising all residents of the Tayside region of Scotland was performed using record linkage techniques followed by case note review. Ascertainment of prevalent diabetes was achieved using the Diabetes Audit and Research in Tayside Study (DARTS) validated regional diabetes register. Glaucoma and treated OHT were defined by encashment of community prescriptions and the statutory surgical procedure coding database. The study population comprised 6631 diabetic subjects and 166 144 non-diabetic subjects aged >40 years without glaucoma or OHT at study entry. 65 patients with diabetes and 958 without diabetes were identified as new cases of glaucoma or treated OHT during the 24 month study period, yielding a standardised morbidity ratio of 127 (95% CI, 96-158). Case note review demonstrated non-differential misclassification of prevalent glaucoma and OHT as incident disease (diabetic cohort 20%, non-diabetic cohort 24%; p=0.56) primarily as a result of non-compliance in medically treated disease. Removing misclassified cases and adjusting for age yielded an incidence of primary open angle glaucoma in diabetes of 1.1/1000 patient years (95% CI, 0.89-1. 31) compared to 0.7/1000 patient years (95% CI, 0.54-0.86) in the non-diabetic cohort; RR 1.57 (95% CI, 0.99-2.48). This study failed to confirm an association between diabetes mellitus and primary open angle glaucoma and ocular hypertension. A non-significant increase in diagnosed and treated disease in the diabetic population was observed, but evidence was also found that detection bias contributes to this association.

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.

PubMed

Besser, Michal J; Shapira-Frommer, Ronnie; Treves, Avraham J; Zippel, Dov; Itzhaki, Orit; Schallmach, Ester; Kubi, Adva; Shalmon, Bruria; Hardan, Izhar; Catane, Raphael; Segal, Eran; Markel, Gal; Apter, Sara; Nun, Alon Ben; Kuchuk, Iryna; Shimoni, Avichai; Nagler, Arnon; Schachter, Jacob

2009-05-01

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Health care utilization history, GOLD guidelines, and respiratory medication prescriptions in patients with COPD.

PubMed

Seaman, Joseph; Leonard, Anthony C; Panos, Ralph J

2010-04-07

The relationship between prior health care utilization and respiratory medication prescriptions in an unselected population of patients with COPD is not known. We determined the prescribed respiratory medications and respiratory and nonrespiratory health care encounters in 523 Veterans with COPD at the Cincinnati Veterans Affairs Medical Center between 2000 and 2005. Prescribed treatments were compared with the GOLD guidelines and each patient was classified as receiving less medications than recommended in the guidelines (G). Respiratory medications were G for 14% of the patients studied. For GOLD stages 1 and 2, G patients the most prior respiratory encounters during a 12 month period (0.31 +/- 0.073 (0.21, 0.47), 0.75 +/- 0.5 (0.37, 1.5), 1.1 +/- 0.27 (0.74, 1.6) visits/person/year, G, respectively, mean + standard error of mean (SEM) (95% confidence limits) 2 degrees of freedom (df) ANOVA P < 0.001 for prescription effect). For GOLD stages 3 and 4, G respectively, 2 df ANOVA P = 0.096) or for GOLD stages 3 and 4 (3.6 +/- 0.25 (3.2, 4.1) and 4.0 +/- 0.44 (3.3, 4.9) visits/person/year,

Alcohol septal ablation in obstructive hypertrophic cardiomyopathy: four years of experience at a reference center.

PubMed

Fiarresga, António; Cacela, Duarte; Galrinho, Ana; Ramos, Ruben; de Sousa, Lídia; Bernardes, Luís; Patrício, Lino; Cruz Ferreira, Rui

2014-01-01

We describe our center's initial experience with alcohol septal ablation (ASA) for the treatment of obstructive hypertrophic cardiomyopathy. The procedure, its indications, results and clinical outcomes will be addressed, as will its current position compared to surgical myectomy. To assess the results of ASA in all patients treated in the first four years of activity at our center. We retrospectively studied all consecutive and unselected patients treated by ASA between January 2009 and February 2013. In the first four years of experience 40 patients were treated in our center. In three patients (7.5%) the intervention was repeated. Procedural success was 84%. Minor complications occurred in 7.5%. Two patients received a permanent pacemaker for atrioventricular block (6% of those without previous pacemaker). The major complication rate was 5%. There were no in-hospital deaths; during clinical follow-up (22 ± 14 months) cardiovascular mortality was 2.5% and overall mortality was 5%. The results presented reflect the initial experience of our center with ASA. The success rate was high and in line with published results, but with room to improve with better patient selection. ASA was shown to be safe, with a low complication rate and no procedure-related mortality. Our experience confirms ASA as a percutaneous alternative to myectomy for the treatment of symptomatic patients with obstructive hypertrophic cardiomyopathy refractory to medical treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Positive view and increased likely uptake of follow-up testing with analysis of cell-free fetal DNA as alternative to invasive testing among Danish pregnant women.

PubMed

Miltoft, Caroline B; Rode, Line; Tabor, Ann

2018-05-01

The aim of this study was to investigate the attitude (view, likely uptake and preferred strategy) towards cell-free fetal DNA (cfDNA) testing among pregnant women before a first-trimester risk assessment for trisomy 21 (unselected women) and after obtaining a high risk. Unselected and high-risk women attending first-trimester screening (Rigshospitalet, Copenhagen University Hospital) were invited to fill out the questionnaire Antenatal testing for Down syndrome as an online survey. The survey included 203 unselected and 50 high-risk women (response rates of 74.8% and 84.7%, respectively). Nearly all considered cfDNA testing a positive development in antenatal care, and 97.2% would like it to be offered. Offering cfDNA testing as an alternative to invasive testing would increase the uptake of follow-up testing compared with invasive testing alone (98.8% vs. 90.7%, p < 0.001). Women who would only accept follow up by cfDNA testing were more likely to continue an affected pregnancy (30.0% vs. 3.6%, p < 0.001) or have doubts about termination (50.0% vs. 32.1%, p < 0.001). Offering cfDNA testing would likely increase the uptake of follow-up testing without a corresponding rise in the termination rate of affected fetuses as some women test for information only. However, both unselected and high-risk women had overwhelmingly positive views underlining attention to avoid routinization. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

ATM/RB1 mutations predict shorter overall survival in urothelial cancer.

PubMed

Yin, Ming; Grivas, Petros; Emamekhoo, Hamid; Mendiratta, Prateek; Ali, Siraj; Hsu, JoAnn; Vasekar, Monali; Drabick, Joseph J; Pal, Sumanta; Joshi, Monika

2018-03-30

Mutations of DNA repair genes, e.g. ATM/RB1 , are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

Trace element analysis by PIXE in several biomedical fields

NASA Astrophysics Data System (ADS)

Weber, G.; Robaye, G.; Bartsch, P.; Collignon, A.; Beguin, Y.; Roelandts, I.; Delbrouck, J. M.

1984-04-01

Since 1980 in the University of Liége trace element analysis by PIXE has been developed in several directions, among these: the elemental composition of lung parenchyma, hilar lymph nodes, blood content in hematological disorders and renal insufficiency. The content in trace elements of lung tumor and surrounding tissue is measured and compared to similar content previously obtained on unselected patients of comparable ages. The normalization of the bromine deficiency observed in hemodialized patients is achieved by using a dialyzing bath doped with NaBr in order to obtain a normal bromine level of 5.7 μg/ml. The content of Cu, Zn, Br and Se in blood serum from more than 100 patients suffering from malignant hemopathy has been measured. The results are compared with a reference group. These oligoelements have also been measured sequentially for patients under intensive chemotherapy in acute myeloid leukemia.

The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization: a randomized controlled trial.

PubMed

Yeung, Tracy Wing Yee; Chai, Joyce; Li, Raymond Hang Wun; Lee, Vivian Chi Yan; Ho, Pak Chung; Ng, Ernest Hung Yu

2014-11-01

Does endometrial injury in the cycle preceding ovarian stimulation for in vitro fertilization (IVF) improve the ongoing pregnancy rate in unselected subfertile women? Endometrial injury induced by endometrial aspiration in the preceding cycle does not improve the ongoing pregnancy rate in unselected subfertile women undergoing IVF. Implantation failure remains one of the major limiting factors for IVF success. Mechanical endometrial injury in the cycle preceding ovarian stimulation of IVF treatment has been shown to improve implantation and pregnancy rates in women with repeated implantation failures. There is limited data on unselected subfertile women, especially those undergoing their first IVF treatment. This randomized controlled trial recruited 300 unselected subfertile women scheduled for IVF/ICSI treatment between March 2011 and August 2013. Subjects were randomized into endometrial aspiration (EA) (n = 150) and non-EA (n = 150) groups according to a computer-generated randomization list. Subjects were recruited and randomized in the assisted reproductive unit at the University of Hong Kong. In the preceding cycle, women in the EA group underwent endometrial aspiration using a Pipelle catheter in mid-luteal phase. All women were treated with a cycle of IVF/ICSI. Pregnancy outcomes were compared. There were no significant differences in baseline or cycle characteristics between the groups. There were 209 subjects (69.7%) who were undergoing their first IVF cycle and 91 (30.3%) subjects who had repeated cycles. There was no significant difference in ongoing pregnancy rates [26.7% (40/150) versus 32.0% (48/150); RR 0.833 (95% CI 0.585-1.187), P = 0.375] in the EA and non-EA groups. The implantation rates [32.8% (67/204) versus 29.7% (68/229); RR 1.080 (95% CI 0.804-1.450), P = 0.120], clinical pregnancy rates [34.0% (51/150) versus 38.0 (57/150); RR 0.895 (95% CI 0.661-1.211), P = 0.548], miscarriage rates [30.3% (17/56) versus 18.6% (11/59), RR 1.628 (95% CI 0.838-3.164), P = 0.150] and multiple pregnancy rates [31.3% (16/51) versus 19.3% (11/57), RR 1.626 (95% CI 0.833-3.172), P = 0.154] were all comparable between the EA and non-EA groups. Subgroup analysis in women having first embryo transfer (n = 209) also demonstrated no significant difference in ongoing pregnancy rates, but for women undergoing repeated cycles (n = 91), the on-going pregnancy rate was significantly lower in the EA group than in the non-EA group. The study aimed at assessing an unselected population of subfertile women by recruiting consecutive women attending our fertility clinic. However, since the majority of the recruited women (69.7%) were having their first IVF treatments, the results may not be generalizable to all women undergoing IVF. Previous RCTs and meta-analyses have suggested improved pregnancy rates after pretreatment endometrial injury in women with repeated implantation failure. A recent RCT also showed increased pregnancy rates in unselected subfertile women after endometrial injury, although that study was terminated early and thus underpowered. Our study showed with adequate power that no significant improvement in pregnancy rates was observed after endometrial injury in unselected women undergoing IVF treatment. The study was supported by the Small Project Funding 201309176012 of the Committee on Research and Conference Grants, University of Hong Kong. The authors have nothing to disclose. HKCTR-1646 and NCT 01977976. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Molecular evidence of simian virus 40 infections in children

NASA Technical Reports Server (NTRS)

Butel, J. S.; Arrington, A. S.; Wong, C.; Lednicky, J. A.; Finegold, M. J.

1999-01-01

Recent studies have detected simian virus 40 (SV40) DNA in certain human tumors and normal tissues. The significance of human infections by SV40, which was first discovered as a contaminant of poliovirus vaccines used between 1955 and 1963, remains unknown. The occurrence of SV40 infections in unselected hospitalized children was evaluated. Polymerase chain reaction and DNA sequence analyses were done on archival tissue specimens from patients positive for SV40 neutralizing antibody. SV40 DNA was identified in samples from 4 of 20 children (1 Wilms' tumor, 3 transplanted kidney samples). Sequence variation among SV40 regulatory regions ruled out laboratory contamination of specimens. This study shows the presence of SV40 infections in pediatric patients born after 1982.

Increasing rates of contralateral prophylactic mastectomy - a trend made in USA?

PubMed

Güth, U; Myrick, M E; Viehl, C T; Weber, W P; Lardi, A M; Schmid, S M

2012-04-01

Numerous recent studies conducted in the USA reported a considerable rise in the rates of contralateral prophylactic mastectomy (CPM) in early-stage breast cancer (BC). However, this aggressive surgical approach only showed an evidence-based improvement in prognosis for a small subgroup of high-risk BC patients. We present the first European study reporting CPM rates in an unselected cohort of patients with BC. The data of 881 patients (≤ 80 years) who underwent surgery for stage I-III BC from 1995 to 2009 at the University of Basel Breast Center was analyzed. CPM was performed in 23 of 881 patients (2.6%). Of the entire patient population, 37.5% underwent ipsilateral mastectomy and of those, only 7.0% chose to undergo CPM. Importantly, there was no trend over time in the rate of CPM. Women who chose CPM were significantly younger (54 vs. 60 years, p < 0.001), had more often a positive family history (39.1% vs. 24.4%, p = 0.032) and tumors of lobular histology (30.5% vs. 13.9%, p = 0.035). Our analysis of CPM rates in BC patients, conducted at a European University breast center, does not show the considerably rising CPM rates observed in the USA. We hypothesize that different medico-social and cultural factors, which are highlighted by a different public perception of BC and a different attitude toward plastic surgery, determine the varying CPM rates between the USA and Europe. © 2011 Elsevier Ltd. All rights reserved.

Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI.

PubMed

Delgado, Julio; Doubek, Michael; Baumann, Tycho; Kotaskova, Jana; Molica, Stefano; Mozas, Pablo; Rivas-Delgado, Alfredo; Morabito, Fortunato; Pospisilova, Sarka; Montserrat, Emili

2017-04-01

Rai and Binet staging systems are important to predict the outcome of patients with chronic lymphocytic leukemia (CLL) but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients' outcome. We devised a biomarkers-only CLL prognostic system based on the two most important prognostic parameters in CLL (i.e., IGHV mutational status and fluorescence in situ hybridization [FISH] cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV + no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either unmutated IGHV or adverse FISH cytogenetics) and (3) high-risk (unmutated IGHV + adverse FISH cytogenetics). In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76%-88%), 52% (45%-62%), and 27% (17%-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials. © 2017 Wiley Periodicals, Inc.

Predisposing cardiac conditions, interventional procedures, and antibiotic prophylaxis among patients with infective endocarditis.

PubMed

Chirillo, Fabio; Faggiano, Pompilio; Cecconi, Moreno; Moreo, Antonella; Squeri, Angelo; Gaddi, Oscar; Cecchi, Enrico

2016-09-01

Efficacy and safety of antibiotic prophylaxis (AP) for prevention of infective endocarditis (IE) in patients with predisposing cardiac condition (PCC) undergoing invasive procedures is still debated. We sought to assess the prevalence of PCC, the type of interventional procedures preceding the onset of symptoms, and the usefulness of AP in a large cohort of consecutive patients with definite IE. We examined 677 (median age 65.34 years; male 492 [73%]) consecutive patients with IE enrolled from July 2007 through 2010 into the Italian Registry of Infective Endocarditis. Predisposing cardiac condition was present in 341 patients (50%).Thirty-two patients (4.7%) underwent dental procedures. Of 20 patients with PCC undergoing dental procedure, 13 had assumed AP. Viridans group streptococci were isolated from blood cultures in 8 of 20 patients with PCC and prior dental procedure. Nondental procedures preceded IE in 139 patients (21%). They were significantly older and had more comordibities compared with patients undergoing dental procedures. Predisposing cardiac condition was identified in 91 patients. Perioperative antimicrobial prophylaxis was administered to 67 patients. Staphylococcus aureus was the most frequent causative agent. Cardiac surgery was necessary in 85 patients (20 with prior dental and 65 with nondental procedure). Surgical mortality (12% vs 0%, P = .03) and hospital mortality (23% vs 3%, P = .001) were significantly larger among patients with nondental procedures. In a large unselected cohort of patients with IE, the incidence of preceding dental procedures was minimal. The number of cases potentially preventable by means of AP was negligible. Nondental procedures were more frequent than dental procedures and were correlated with poorer prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Developmental differences according to age at onset in juvenile bipolar disorder.

PubMed

Masi, Gabriele; Perugi, Giulio; Millepiedi, Stefania; Mucci, Maria; Toni, Cristina; Bertini, Nicoletta; Pfanner, Chiara; Berloffa, Stefano; Pari, Cinzia

2006-12-01

This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome. A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study. Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups. Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.

Somatic mutations in early onset luminal breast cancer

PubMed Central

de Lyra, Eduardo Carneiro; Hirata Katayama, Maria Lucia; Maistro, Simone; de Vasconcellos Valle, Pedro Wilson Mompean; de Lima Pereira, Gláucia Fernanda; Rodrigues, Lívia Munhoz; de Menezes Pacheco Serio, Pedro Adolpho; de Gouvêa, Ana Carolina Ribeiro Chaves; Geyer, Felipe Correa; Basso, Ricardo Alves; Pasini, Fátima Solange; del Pilar Esteves Diz, Maria; Brentani, Maria Mitzi; Guedes Sampaio Góes, João Carlos; Chammas, Roger; Boutros, Paul C.; Koike Folgueira, Maria Aparecida Azevedo

2018-01-01

Breast cancer arising in very young patients may be biologically distinct; however, these tumors have been less well studied. We characterized a group of very young patients (≤ 35 years) for BRCA germline mutation and for somatic mutations in luminal (HER2 negative) breast cancer. Thirteen of 79 unselected very young patients were BRCA1/2 germline mutation carriers. Of the non-BRCA tumors, eight with luminal subtype (HER2 negative) were submitted for whole exome sequencing and integrated with 29 luminal samples from the COSMIC database or previous literature for analysis. We identified C to T single nucleotide variants (SNVs) as the most common base-change. A median of six candidate driver genes was mutated by SNVs in each sample and the most frequently mutated genes were PIK3CA, GATA3, TP53 and MAP2K4. Potential cancer drivers affected in the present non-BRCA tumors include GRHL2, PIK3AP1, CACNA1E, SEMA6D, SMURF2, RSBN1 and MTHFD2. Sixteen out of 37 luminal tumors (43%) harbored SNVs in DNA repair genes, such as ATR, BAP1, ERCC6, FANCD2, FANCL, MLH1, MUTYH, PALB2, POLD1, POLE, RAD9A, RAD51 and TP53, and 54% presented pathogenic mutations (frameshift or nonsense) in at least one gene involved in gene transcription. The differential biology of luminal early-age onset breast cancer needs a deeper genomic investigation. PMID:29854292

Attentional bias to threat in the general population is contingent on target competition, not on attentional control settings.

PubMed

Wirth, Benedikt Emanuel; Wentura, Dirk

2018-04-01

Dot-probe studies usually find an attentional bias towards threatening stimuli only in anxious participants. Here, we investigated under what conditions such a bias occurs in unselected samples. According to contingent-capture theory, an irrelevant cue only captures attention if it matches an attentional control setting. Therefore, we first tested the hypothesis that an attentional control setting tuned to threat must be activated in (non-anxious) individuals. In Experiment 1, we used a dot-probe task with a manipulation of attentional control settings ('threat' - set vs. control set). Surprisingly, we found an (anxiety-independent) attentional bias to angry faces that was not moderated by attentional control settings. Since we presented two stimuli (i.e., a target and a distractor) on the target screen in Experiment 1 (a necessity to realise the test of contingent capture), but most dot-probe studies only employ a single target, we conducted Experiment 2 to test the hypothesis that attentional bias in the general population is contingent on target competition. Participants performed a dot-probe task, involving presentation of a stand-alone target or a target competing with a distractor. We found an (anxiety-independent) attentional bias towards angry faces in the latter but not the former condition. This suggests that attentional bias towards angry faces in unselected samples is not contingent on attentional control settings but on target competition.

Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic non-small cell lung cancer Spanish patients and its association with histological subtypes and clinical features: The Spanish REASON study.

PubMed

Esteban, E; Majem, M; Martinez Aguillo, M; Martinez Banaclocha, N; Dómine, M; Gómez Aldaravi, L; Juan, O; Cajal, R; Gonzalez Arenas, M C; Provencio, M

2015-06-01

The aim of the REASON study is to determine the frequency of EGFR mutation in advanced non-small cell lung cancer (aNSCLC) patients in Spain (all histologies), and to better understand the clinical factors (gender, smoking habits and histological subtypes) that may be associated with EGFR mutations, in an unselected sample of aNSCLC patients. All newly diagnosed aNSCLC patients from 40 selected centers in Spain were prospectively included for a 6-month period. Patient characteristics were obtained from clinical records. Mutation testing was performed on available tumor samples. Exploratory analyses were performed to characterize the clinico-pathological factors associated with presence of EGFR mutations. From March 2010 to March 2011, 1113 patients were included in the study, of which 1009 patients provided sample for EGFR mutation analysis (90.7%). Mutation analysis was not feasible in 146/1113 patients (13.1%) due to either sample unavailability (79/1113; 7.1%) or sample inadequacy (67/1113; 6.0%). Twenty-five out of 1113 patients (2.3%) were excluded due to unavailable information. Most patients (99.5%) were Caucasian, 74.5% were male, and predominantly were current (38.1%) or former smokers (44.0%). Median age was 66 years (range 25-90) and 70.7% of patients had non-squamous histology (57.8% adenocarcinoma, 1.8% bronchoalveolar, 11.1% large-cell carcinoma). Exon 19 deletions and the exon 21 L858R point mutation were analyzed in 942/1009 (93.4%) samples. Mutation rate was 11.6% (82.6% exon 19 dels and 17.4% L858R). To be never smoker (38.1%), female (25.4%), with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was associated with a higher prevalence of EGFR mutations. Exons 18, 20 and 21 (excluding L858R) were analyzed in 505/942 samples, and EGFR mutations were found in 22/505 samples (4.4%). The estimated prevalence of sensitizing EGFR mutations (exon 19 del, exon 21 L858R) in an unselected samples of newly diagnosed aNSCLC patients in Spain (all histologies) is consistent with previous published data in Caucasian patients. When a sample is available, EGFR mutation testing is feasible in over 90% of cases, and may therefore be suitable for routine clinical practice. CLINICALTRIALS. NCT01081496. Copyright © 2015 Elsevier Ltd. All rights reserved.

Opportunistic screening of atrial fibrillation by automatic blood pressure measurement in the community.

PubMed

Omboni, Stefano; Verberk, Willem J

2016-04-12

Timely detection of atrial fibrillation (AF) may effectively prevent cardiovascular consequences. However, traditional diagnostic tools are either poorly reliable (pulse palpation) or not readily accessible (ECG) in general practice. We tested whether an automatic oscillometric blood pressure (BP) monitor embedded with an algorithm for AF detection might be effective for opportunistic screening of asymptomatic AF in the community. A community-based screening campaign in an unselected population to verify the feasibility of AF screening with a Microlife WatchBP Office BP monitor with a patented AFIB algorithm. When possible AF was detected (≥2 of 3 BP measurements reporting AF), a doctor immediately performed a single-lead ECG in order to confirm or exclude the presence of the arrhythmia. The main demographic and clinical data were also collected. 220 consecutive participants from an unselected sample of individuals in a small Italian community. Number of patients detected with AF and diagnosed risk factors for AF. In 12 of 220 participants, the device detected possible AF during the BP measurement: in 4 of them (1.8%), the arrhythmia was confirmed by the ECG. Patients with AF were more likely to be older (77.0±1.2 vs 57.2±15.2 years, p=0.010), obese (50.0 vs 14.4%, p=0.048) and to suffer from a cardiovascular disease (50.0 vs 10.6%, p=0.014) than patients without AF. Participants with a positive BP AF reading and non-AF arrhythmias (n=8) did not differ in their general characteristics from participants with a negative BP AF reading and were younger than patients with AF (mean age 56.4±14.8, p=0.027; 5 of 8 participants aged <65 years). Opportunistic screening of AF by BP measurement is feasible to diagnose this arrhythmia in unaware participants, particularly in those older than 65 years, who are the target patient group recommended by current AF screening guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Behavioral effects of bidirectional selection for behavior towards human in virgin and lactate Norway rats.

PubMed

Konoshenko, Maria Yu; Plyusnina, Irina Z

2012-06-01

Although numerous studies have demonstrated strong differences in behavioral, hormonal and neurobiological characteristics between male rats selected for elimination (tame) and enhancement (aggressive) of aggressiveness towards humans, few studies have examined changes in female behavior under this selection. The objective of the current work was to evaluate the effects of bidirectional selection for aggressiveness towards humans on behavioral profiles of virgin and lactating rats compared with the behavior in tame, aggressive and unselected (wild-type) females. The behavior of virgin females was studied using the light-dark box, the startle response test and the modified glove test. Tame females were less anxious and more tolerant towards humans than unselected and aggressive rats. Principal component analysis of all behavioral parameters produced three independent factors, explaining 66.37% of the total variability. The measures of behavior towards humans and the measures of anxiety mainly loaded on PC1 (first principal component) which separated the tame females from the unselected and aggressive ones. These data suggest the genetic correlation between the selected behavior towards humans and anxiety-related behavior in virgin rats. No significant effect of line was found for PC2 scores, associated with risk assessment behavior. Measurements of freezing behavior mainly loaded on PC3, and this component separated rats of different genetic groups from each other. The behavior of lactating rats was studied in maternal defense and pup retrieval tests. Females of selected lines did not significantly differ in behavioral measurements of these tests and were characterized by higher maternal motivation than unselected rats. It is suggested that long-term breeding of tame and aggressive rats in captivity has reduced the threshold for maternal behavior. Copyright © 2012 Elsevier B.V. All rights reserved.

The Focus of Attention in Visual Working Memory: Protection of Focused Representations and Its Individual Variation.

PubMed

Heuer, Anna; Schubö, Anna

2016-01-01

Visual working memory can be modulated according to changes in the cued task relevance of maintained items. Here, we investigated the mechanisms underlying this modulation. In particular, we studied the consequences of attentional selection for selected and unselected items, and the role of individual differences in the efficiency with which attention is deployed. To this end, performance in a visual working memory task as well as the CDA/SPCN and the N2pc, ERP components associated with visual working memory and attentional processes, were analysed. Selection during the maintenance stage was manipulated by means of two successively presented retrocues providing spatial information as to which items were most likely to be tested. Results show that attentional selection serves to robustly protect relevant representations in the focus of attention while unselected representations which may become relevant again still remain available. Individuals with larger retrocueing benefits showed higher efficiency of attentional selection, as indicated by the N2pc, and showed stronger maintenance-associated activity (CDA/SPCN). The findings add to converging evidence that focused representations are protected, and highlight the flexibility of visual working memory, in which information can be weighted according its relevance.

Diagnosis of unstable angina pectoris has declined markedly with the advent of more sensitive troponin assays.

PubMed

D'Souza, Maria; Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S; Gerke, Oke; Larsen, Torben B; Diederichsen, Axel C P; Jangaard, Nikolaj; Diederichsen, Søren Z; Hosbond, Susanne; Hove, Jens; Thygesen, Kristian; Mickley, Hans

2015-08-01

Since the arrival of the universal definition of myocardial infarction more sensitive troponin assays have been developed. How these occurrences have influenced the proportions and clinical features of the components of acute coronary syndrome have not been studied prospectively in unselected hospital patients. During 2010 we evaluated all patients in whom cardiac troponin I had been measured at a single university hospital. The diagnosis of acute myocardial infarction (ST-elevation myocardial infarction [STEMI] or non-ST-elevation myocardial infarction [NSTEMI]) was established in cases of a rise and/or fall of cardiac troponin I together with cardiac ischemic features. Patients with unstable chest discomfort and cardiac troponin I values below the decision limit of myocardial infarction were diagnosed as having unstable angina pectoris. The definition of acute coronary syndrome included unstable angina pectoris, NSTEMI, and STEMI. Mortality data were obtained from the Danish Civil Personal Registration System. Of 3762 consecutive patients, 516 had acute coronary syndrome. Unstable angina pectoris was present in 7%, NSTEMI in 67%, and STEMI in 26%. The NSTEMI patients were older, more frequently women, and had more comorbidities than patients with unstable angina pectoris and STEMI. At median follow-up of 3.2 years 195 patients had died: 14% of unstable angina pectoris, 45% of NSTEMI, and 25% of STEMI patients. Age-adjusted log-rank statistics revealed differences in mortality: NSTEMI vs unstable angina pectoris (P = .0091) and NSTEMI vs STEMI (P = .0045). The application of the universal definition together with the use of a contemporary troponin assay seems to have reduced the proportion of patients with unstable angina pectoris to the benefit of patients with NSTEMI. Despite this, NSTEMI patients have a sustained higher mortality than patients with STEMI. Copyright © 2015 Elsevier Inc. All rights reserved.

Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.

PubMed

Pritchard, Colin C; Mateo, Joaquin; Walsh, Michael F; De Sarkar, Navonil; Abida, Wassim; Beltran, Himisha; Garofalo, Andrea; Gulati, Roman; Carreira, Suzanne; Eeles, Rosalind; Elemento, Olivier; Rubin, Mark A; Robinson, Dan; Lonigro, Robert; Hussain, Maha; Chinnaiyan, Arul; Vinson, Jake; Filipenko, Julie; Garraway, Levi; Taplin, Mary-Ellen; AlDubayan, Saud; Han, G Celine; Beightol, Mallory; Morrissey, Colm; Nghiem, Belinda; Cheng, Heather H; Montgomery, Bruce; Walsh, Tom; Casadei, Silvia; Berger, Michael; Zhang, Liying; Zehir, Ahmet; Vijai, Joseph; Scher, Howard I; Sawyers, Charles; Schultz, Nikolaus; Kantoff, Philip W; Solit, David; Robson, Mark; Van Allen, Eliezer M; Offit, Kenneth; de Bono, Johann; Nelson, Peter S

2016-08-04

Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established. We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis. We isolated germline DNA and used multiplex sequencing assays to assess mutations in 20 DNA-repair genes associated with autosomal dominant cancer-predisposition syndromes. A total of 84 germline DNA-repair gene mutations that were presumed to be deleterious were identified in 82 men (11.8%); mutations were found in 16 genes, including BRCA2 (37 men [5.3%]), ATM (11 [1.6%]), CHEK2 (10 [1.9% of 534 men with data]), BRCA1 (6 [0.9%]), RAD51D (3 [0.4%]), and PALB2 (3 [0.4%]). Mutation frequencies did not differ according to whether a family history of prostate cancer was present or according to age at diagnosis. Overall, the frequency of germline mutations in DNA-repair genes among men with metastatic prostate cancer significantly exceeded the prevalence of 4.6% among 499 men with localized prostate cancer (P<0.001), including men with high-risk disease, and the prevalence of 2.7% in the Exome Aggregation Consortium, which includes 53,105 persons without a known cancer diagnosis (P<0.001). In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair processes among men with metastatic prostate cancer was 11.8%, which was significantly higher than the incidence among men with localized prostate cancer. The frequencies of germline mutations in DNA-repair genes among men with metastatic disease did not differ significantly according to age at diagnosis or family history of prostate cancer. (Funded by Stand Up To Cancer and others.).

Is the pencil point spinal needle a better choice in younger patients? A comparison of 24G Sprotte with 27G Quincke needles in an unselected group of general surgical patients below 46 years of age.

PubMed

Brattebø, G; Wisborg, T; Rodt, S A; Røste, I

1995-05-01

Reports have indicated that there are less postoperative complaints after the use of pencil pointed spinal needles. We compared a 24G Sprotte needle with a 27G Quincke needle in a randomised study of 200 healthy patients (49% females), aged 15-46 years. Four patients (2%) reported postdural puncture headache, three with the 24G Sprotte needle and one with the 27G Quincke needle. Thirteen patients (7%) suffered with nonspecific headache, with no significant difference between the two groups. Of the 57 (29%) who reported backpain, a significantly higher proportion had received spinal anaesthesia with the Sprotte needle (OR = 2.06). There was a significantly higher incidence of insufficient blocks after dural puncture with the Sprotte needle. Ease of needle insertion and number of puncture attempts was the same for both needle types.

VCAM-1 serum levels are associated with arthropathy in hereditary haemochromatosis.

PubMed

Nell-Duxneuner, Valerie; Axmann, Roland; Husar-Memmer, Emma; Dallos, Tomás; Datz, Christian; Stadlmayr, Andreas; Aigner, Elmar; Englbrecht, Matthias; Schett, Georg; Zwerina, Jochen

2013-12-01

The aim of this study was to assess the role of vascular adhesion molecule 1 (VCAM-1) in patients with hereditary haemochromatosis (HH) with or without arthropathy. Sera from a large cross-sectional cohort of unselected HH patients (n=147) were obtained and compared to an age-matched and sex-matched control group. Serum levels of VCAM-1 were measured by ELISA and were correlated with clinical measures. VCAM-1 serum levels were elevated in HH patients as compared to matched controls (mean 913±456 vs 654±451 ng/ml, p<0.0001). Within the HH patient group, VCAM-1 levels were much higher in patients with arthropathy and joint replacement surgery. VCAM-1 levels correlated well with radiographic measures of HH arthropathy (r=0.36, p<0.0001). Multivariate regression analysis confirmed a highly significant association of VCAM-1 serum levels and the presence of HH arthropathy, independent from diabetes, body mass index and age. VCAM-1 serum levels emerge as a biomarker for haemochromatosis arthropathy.

Challenging the wisdom of puncture at the calyceal fornix in percutaneous nephrolithotripsy: feasibility and safety study with 137 patients operated via a non-calyceal percutaneous track.

PubMed

Kyriazis, Iason; Kallidonis, Panagiotis; Vasilas, Marinos; Panagopoulos, Vasilios; Kamal, Wissam; Liatsikos, Evangelos

2017-05-01

To present our experience with a central, non-calyceal puncture protocol for percutaneous nephrolithotripsy (PCNL) in an attempt to challenge the opinion of worldwide adopted calyceal puncture as the less traumatic site of percutaneous entrance into the collecting system. During 2012, a total of 137 consecutive, unselected patients were subjected to PCNL in our department. Non-calyceal punctures were performed to all cases and followed by subsequent track dilations up to 30 Fr. Perioperative and postoperative data were prospectively collected and analyzed. Mean operative time (from skin puncture to nephrostomy tube placement) was 48 min. Patients with single, multiple and staghorn stones had primary stone-free rates of 89.2, 80.4 and 66.7 % after PCNL, respectively. The overall complication rate was 10.2 %, while bleeding complications were minimal. Only 4 patients (2.9 %) required blood transfusion. Five patients (3.6 %) had Clavien Grade IIIa complications requiring an intervention for their management and none Grade IV or V. Despite the absence of evidence that non-calyceal percutaneous tracts could be a risk factor for complications, the concept of calyceal puncture has been worldwide adopted by PCNL surgeons as the sole safe percutaneous entrance into the collective system. Based on our experience, other pathways than the worldwide recognized rule, calyceal puncture, are possible and probably not as dangerous as has been previously stated.

Enhanced broadband absorption in nanowire arrays with integrated Bragg reflectors

NASA Astrophysics Data System (ADS)

Aghaeipour, Mahtab; Pettersson, Håkan

2018-05-01

A near-unity unselective absorption spectrum is desirable for high-performance photovoltaics. Nanowire (NW) arrays are promising candidates for efficient solar cells due to nanophotonic absorption resonances in the solar spectrum. The absorption spectra, however, display undesired dips between the resonance peaks. To achieve improved unselective broadband absorption, we propose to enclose distributed Bragg reflectors (DBRs) in the bottom and top parts of indium phosphide (InP) NWs, respectively. We theoretically show that by enclosing only two periods of In0.56Ga0.44As/InP DBRs, an unselective 78% absorption efficiency (72% for NWs without DBRs) is obtained at normal incidence in the spectral range from 300 nm to 920 nm. Under oblique light incidence, the absorption efficiency is enhanced up to about 85% at an incidence angle of 50°. By increasing the number of DBR periods from two to five, the absorption efficiency is further enhanced up to 95% at normal incidence. In this work, we calculated optical spectra for InP NWs, but the results are expected to be valid for other direct band gap III-V semiconductor materials. We believe that our proposed idea of integrating DBRs in NWs offers great potential for high-performance photovoltaic applications.

The derivation and validation of a simple model for predicting in-hospital mortality of acutely admitted patients to internal medicine wards.

PubMed

Sakhnini, Ali; Saliba, Walid; Schwartz, Naama; Bisharat, Naiel

2017-06-01

Limited information is available about clinical predictors of in-hospital mortality in acute unselected medical admissions. Such information could assist medical decision-making.To develop a clinical model for predicting in-hospital mortality in unselected acute medical admissions and to test the impact of secondary conditions on hospital mortality.This is an analysis of the medical records of patients admitted to internal medicine wards at one university-affiliated hospital. Data obtained from the years 2013 to 2014 were used as a derivation dataset for creating a prediction model, while data from 2015 was used as a validation dataset to test the performance of the model. For each admission, a set of clinical and epidemiological variables was obtained. The main diagnosis at hospitalization was recorded, and all additional or secondary conditions that coexisted at hospital admission or that developed during hospital stay were considered secondary conditions.The derivation and validation datasets included 7268 and 7843 patients, respectively. The in-hospital mortality rate averaged 7.2%. The following variables entered the final model; age, body mass index, mean arterial pressure on admission, prior admission within 3 months, background morbidity of heart failure and active malignancy, and chronic use of statins and antiplatelet agents. The c-statistic (ROC-AUC) of the prediction model was 80.5% without adjustment for main or secondary conditions, 84.5%, with adjustment for the main diagnosis, and 89.5% with adjustment for the main diagnosis and secondary conditions. The accuracy of the predictive model reached 81% on the validation dataset.A prediction model based on clinical data with adjustment for secondary conditions exhibited a high degree of prediction accuracy. We provide a proof of concept that there is an added value for incorporating secondary conditions while predicting probabilities of in-hospital mortality. Further improvement of the model performance and validation in other cohorts are needed to aid hospitalists in predicting health outcomes.

Peritonitis remains the major clinical complication of peritoneal dialysis: the London, UK, peritonitis audit 2002-2003.

PubMed

Davenport, Andrew

2009-01-01

Over the past two decades, the rate of peritonitis in patients treated by peritoneal dialysis (PD) has been significantly reduced. However, peritonitis remains a major complication of PD, accounting for considerable mortality and hospitalization among PD patients. To compare the outcome of peritonitis in a large unselected group of PD patients with that from single-center and selected groups. We audited the outcome of peritonitis in PD patients attending the 12 PD units in the Thames area in 2002 and 2003. There were 538 patients on continuous ambulatory PD (CAPD) and 325 patients on automated PD (APD) and/or continuous cycling PD (CCPD) at the end of 2002, and 635 CAPD and 445 APD/CCPD patients at the end of 2003. There were 1467 episodes of PD peritonitis during the 2-year period, including 129 recurrent episodes, with the average number of months between peritonitis episodes being 14.7 for CAPD and 18.1 for APD/CCPD, p < 0.05. However there was considerable variation between units. Coagulase-negative staphylococcus (CoNS) was the most common cause, accounting for around 30% of all peritonitis episodes, including recurrences, followed by non-pseudomonas gram negatives and Staphylococcus aureus. Cure rates were 77.2% for CoNS, 46.6% for S. aureus, and 7.7% for methicillin-resistant S. aureus. The cure rate for pseudomonas was 21.4%, and other gram negatives 56.7%. In total, there were 351 episodes of culture-negative peritonitis, with an average cure rate of 76.9%. Cure rates were higher for those centers that used a combination of intraperitoneal gentamicin and cephalosporins than those centers that used oral-based regimes. A total of 296 PD catheters were removed as a direct consequence of PD peritonitis: 121 due to gram-positive and 123 due to gram-negative organisms. Only 49 catheters were reinserted and the patients returned to PD. 52 patients died during or subsequent to their episode of PD peritonitis, with an overall mortality rate of 3.5%. This audit showed that, in a large unselected population of PD patients, the incidence of peritonitis was significantly greater than that reported in single-center short-term studies, and varied from unit to unit. Similarly, the success of treating PD peritonitis varied not only with the cause of the infection but also from unit to unit. PD peritonitis remains a major cause of patients discontinuing PD and switching to hemodialysis.

Surgical restoration of vas continuity after vasectomy: further clinical evaluation of a new operation technique.

PubMed

Pardanani, D S; Kothari, M L; Pradhan, S A; Mahendrakar, M N

1974-04-01

20 unselected former vasectomy patients were subjected to scrotal exploration and vas recanalization operation. Anastomosis was carried out using a large diameter silicone rubber splint; the splint was removed 7 days postoperatively. No complications or side effects were encountered, and there were no patient complaints of discomfort or pain. 92.3% of the men considered satisfactory candidates for recanalization had successful results, and 30.8% of their wives became pregnant. The low fertility rate following successful vas recanalization is not understood. The 2 conditions which were found to be unfavorable for vas recanalization were a vasectomy where a long segment of the vas had been excised or where the vas section had been made very low and involved its convoluted segment.

Understanding the Key to Targeting the IGF Axis in Cancer: A Biomarker Assessment

PubMed Central

Lodhia, Kunal Amratlal; Tienchaiananda, Piyawan; Haluska, Paul

2015-01-01

Type 1 insulin like growth factor receptor (IGF-1R) targeted therapies showed compelling pre-clinical evidence; however, to date, this has failed to translate into patient benefit in Phase 2/3 trials in unselected patients. This was further complicated by the toxicity, including hyperglycemia, which largely results from the overlap between IGF and insulin signaling systems and associated feedback mechanisms. This has halted the clinical development of inhibitors targeting IGF signaling, which has limited the availability of biopsy samples for correlative studies to understand biomarkers of response. Indeed, a major factor contributing to lack of clinical benefit of IGF targeting agents has been difficulty in identifying patients with tumors driven by IGF signaling due to the lack of predictive biomarkers. In this review, we will describe the IGF system, rationale for targeting IGF signaling, the potential liabilities of targeting strategies, and potential biomarkers that may improve success. PMID:26217584

Prevalence of pathogenic yeasts and humoral antibodies to candida in diabetic patients.

PubMed Central

Odds, F C; Evans, E G; Taylor, M A; Wales, J K

1978-01-01

The prevalence of oral yeasts and humoral precipitating antibodies to candida was estimated in 204 unselected diabetic patients (172 outpatients and 32 inpatients). Yeasts, mainly Candida albicans, were isolated from the mouths of 41% of the outpatients and precipitins were found in 17.5% although none of the patients had clinically overt candidiasis. The extent of oral yeast colonisation and incidence of antibodies was not related to their antidiabetic treatment or to the duration of their diabetes. It was, however, related to the blood glucose and urine sugar levels at the time they were sampled, the highest incidence being among the diabetic inpatients with high blood glucose levels at the time of sampling and the lowest among outpatients with normal blood glucose levels at the time of sampling. There was no such correlation when diabetic control over the previous 12-month period was considered. PMID:711913

[Family study of patients with aspirin intolerance and rhinosinusitis].

PubMed

May, A; Wagner, D; Langenbeck, U; Weber, A

2000-09-01

The high prevalence of aspirin intolerance in asthmatics and patients with nasal polyps as well as reports of familial clustering suggest a genetic disposition of this disease. Our study aimed at obtaining further evidence of hereditary factors in this disease. We included 33 unselected patients from 28 families with aspirin intolerance and rhinosinusitis in this study. Controls were recruited from individuals treated in our ENT clinic for diseases other than aspirin intolerance (n = 52). A questionnaire focused on family histories as well as reports on diseases of the upper respiratory tract or allergies. ASS intolerance was verified either by bronchial or nasal provocation tests. We found cases of aspirin intolerance among parents, siblings, and children of ASS intolerant probands. The children of probands had nasal polyps and rhinosinusitis more often than the children of controls. We propose that ASS intolerance with nasal polyps and asthma represents a complex phenotype, with genetic and environmental factors contributing to its manifestation.

Intravitreal aflibercept versus intravitreal ranibizumab in patients with age-related macular degeneration: a comparative effectiveness study.

PubMed

Smit, Cornelis; Wiertz-Arts, Karin; van de Garde, Ewoudt Mw

2018-06-01

A hospital-wide, unselected switch of ranibizumab to aflibercept in treatment of age-related macular degeneration (AMD) allowed us to compare the clinical effectiveness of these agents. In a single-center before-after, observational study design new AMD-patients started with aflibercept treatment in 2013-2014 were compared with a control group of AMD-patients on ranibizumab before the switch. The mean difference in visual acuity (in logMAR units) after 1 year was comparable (+0.012 [aflibercept, n = 37] vs +0.17 [ranibizumab, n = 30], p = 0.154). However, the aflibercept-group did receive more intravitreal injections (5.8 vs 4.7 injections, p = 0.004) and were treated longer (265.7 vs 197.7 days; p = 0.011). With no difference in clinical effectiveness, longer treatment intervals for aflibercept should be investigated.

Anti-Type VII Collagen Antibodies Are Identified in a Subpopulation of Bullous Pemphigoid Patients With Relapse

PubMed Central

Giusti, Delphine; Gatouillat, Grégory; Le Jan, Sébastien; Plée, Julie; Bernard, Philippe; Antonicelli, Frank; Pham, Bach-Nga

2018-01-01

Bullous pemphigoid (BP) is an autoimmune bullous skin disease characterized by anti-BP180 and anti-BP230 autoantibodies (AAbs). Mucous membrane involvement is an uncommon clinical feature of BP which may evoke epidermolysis bullosa acquisita, another skin autoimmune disease characterized by anti-type VII collagen AAbs. We therefore evaluated the presence of anti-type VII collagen AAbs in the serum of BP patients with and without mucosal lesions at time of diagnosis and under therapy. Anti-BP180, anti-BP230, and anti-type VII collagen AAbs were measured by ELISA in the serum of unselected patients fulfilling clinical and histo/immunopathological BP criteria at baseline (n = 71) and at time of relapse (n = 24). At baseline, anti-type VII collagen AAbs were detected in 2 out of 24 patients with BP presenting with mucosal involvement, but not in patients without mucosal lesions (n = 47). At the time of relapse, 10 out of 24 BP patients either displayed a significant induction or increase of concentrations of anti-type VII collagen AAbs (P < 0.01), independently of mucosal involvement. Those 10 relapsing BP patients were also characterized by a sustained high concentration of anti-BP180 AAb, whereas the serum anti-BP230 AAb concentrations did not vary in BP patients with relapse according to the presence of anti-type VII collagen AAbs. Thus, our study showed that anti-type VII collagen along with anti-BP180 AAbs detection stratified BP patients at time of relapse, illustrating a still dysregulated immune response that could reflect a potential epitope spreading mechanism in those BP patients. PMID:29619029

Blood pressure control in patients with chronic renal insufficiency in Spain: a cross-sectional study.

PubMed

Marín, Rafael; Fernández-Vega, Francisco; Gorostidi, Manuel; Ruilope, Luis M; Díez, Javier; Praga, Manuel; Herrero, Pablo; Alcázar, Jose M; Laviades, Concepción; Aranda, Pedro

2006-02-01

Despite therapeutic advances, strict control of hypertension remains elusive in patients with chronic renal insufficiency (CRI). The present study was designed for assessment of control rates of blood pressure in patients with CRI. Secondary objectives included evaluation of the control rates of proteinuria and cardiovascular comorbidities. A multicenter and cross-sectional survey of unselected patients with CRI attending outpatient nephrology clinics in Spain between April and September 2003 was performed. Fifty-two centers recruited 2501 patients with a mean age 64.8 years (65.7% men). The prevalence of previous cardiovascular disease was 55%. The two most prevalent renal diseases were vascular (38.9%) and diabetic nephropathy (20.1%). Blood pressure below 130/80 mmHg was observed in 435 patients (17.4%). A poor blood pressure control was associated with older age, greater proteinuria and higher low-density lipoprotein cholesterol levels. Proteinuria less than 0.5 g/day was observed in 1209 cases (48.3%). A total of 1899 patients (75.9%) were receiving drugs suppressing the activity of the renin-angiotensin system and 1048 patients (41.9%) were being treated with three or more antihypertensive drugs. Lipid-lowering agents and antiplatelet therapy were used in 49.3 and 38.1% of patients, respectively. The control rate of blood pressure in patients with CRI is inadequate despite frequent use of combination therapy that most commonly included an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Greater emphasis should be made to increase the number and dose of antihypertensive drugs and the need for using a statin as well as antiplatelet therapy in order to improve renal and cardiovascular outcomes.

The Identity Crisis of Osteoarthritis in General Practice: A Qualitative Study Using Video-Stimulated Recall.

PubMed

Paskins, Zoe; Sanders, Tom; Croft, Peter R; Hassell, Andrew B

2015-11-01

Patients and doctors report marked disenchantment with primary care consultation experiences relating to osteoarthritis. This study aimed to observe and analyze interactions between general practitioners (GPs) and patients presenting with osteoarthritis (OA) to identify how to improve care for OA. We conducted an observational study in general practices in the United Kingdom using video-recorded real-life consultations of unselected patients and their GPs. Postconsultation interviews were conducted using video-stimulated recall. Both consultations and interviews were analyzed thematically. Three key themes were identified in an analysis of 19 OA consultations and the matched GP and patient interviews: complexity, dissonance, and prioritization. The topic of osteoarthritis arises in the consultation in complex contexts of multimorbidity and multiple, often not explicit, patient agendas. Dissonance between patient and doctor was frequently observed and reported; this occurred when GPs normalized symptoms of OA as part of life and reassured patients who were not seeking reassurance. GPs used wear and tear in preference to osteoarthritis or didn't name the condition at all. GPs subconsciously made assumptions that patients did not consider OA a priority and that symptoms raised late in the consultation were not troublesome. The lack of a clear illness profile results in confusion between patients and doctors about what OA is and its priority in the context of multimorbidity. This study highlights generic communication issues regarding the potential negative consequences of unsought reassurance and the importance of validation of symptoms and raises new arguments for tackling OA's identity crisis by developing a clearer medical language with which to explain OA. © 2015 Annals of Family Medicine, Inc.

The TP53 gene polymorphisms and survival of sporadic breast cancer patients.

PubMed

Bišof, V; Salihović, M Peričić; Narančić, N Smolej; Skarić-Jurić, T; Jakić-Razumović, J; Janićijević, B; Rudan, P

2012-06-01

The TP53 gene polymorphisms, Arg72Pro and PIN3 (+16 bp), can have prognostic and predictive value in different cancers including breast cancer. The aim of the present study is to investigate a potential association between different genotypes of these polymorphisms and clinicopathological variables with survival of breast cancer patients in Croatian population. Ninety-four women with sporadic breast cancer were retrospectively analyzed. Median follow-up period was 67.9 months. The effects of basic clinical and histopathological characteristics of tumor on survival were tested by Cox's proportional hazards regression analysis. The TNM stage was associated with overall survival by Kaplan-Meier analysis, univariate, and multivariate Cox's proportional hazards regression analysis, while grade was associated with survival by Kaplan-Meier analysis and univariate Cox's proportional hazards regression analysis. Different genotypes of the Arg72Pro and PIN3 (+16 bp) polymorphisms had no significant impact on survival in breast cancer patients. However, in subgroup of patients treated with chemotherapy without anthracycline, the A2A2 genotype of the PIN3 (+16 bp) polymorphism was associated with poorer overall survival than other genotypes by Kaplan-Meier analysis (P = 0.048). The TP53 polymorphisms, Arg72Pro and PIN3 (+16 bp), had no impact on survival in unselected sporadic breast cancer patients in Croatian population. However, the results support the role of the A2A2 genotype of the PIN3 (+16 bp) polymorphism as a marker for identification of patients that may benefit from anthracycline-containing chemotherapy.

Open tension-free hernioplasty using a novel lightweight self-gripping mesh: medium-term experience from two institutions.

PubMed

Pedano, Nicolás; Pastor, Carlos; Arredondo, Jorge; Poveda, Ignacio; Ruiz, Jaime; Montón, Soledad; Molina, María; Hernández-Lizoain, José Luis

2012-02-01

The process of mesh fixation and the potential risk of associated chronic pain are always surgeon's main concerns in hernia surgery. A wide variety of lightweight mesh models are currently available on the market to overcome some of these problems showing good preliminary results, but no data representing the medium- or long-term results. The present study aims to report the clinical outcomes of two institutional series of patients who underwent hernia repair using a partially absorbable auto adherent mesh (Parietene™ Progrip™--PP). A prospective analysis was performed including unselected patients with primary groin hernia who underwent a standardized Lichtenstein procedure using the PP mesh at two tertiary institutions. During the 2-year study period, 181 patients (167 males; 14 females) with a median age of 63 years (19-85 years) were operated on at both centers. Short-term complications occurred in 27 patients (15%), the most commonly seen being urinary retention (6%) followed by hematoma (5%) and acute orchitis (2%). With a median follow-up of 17 months (12-29 months), 4 patients (2%) had a feeling of a foreign body in the groin, and 7 (4%) developed chronic pain. A total of four patients (2%) developed recurrence. In our experience, the use of the PP mesh for hernioplasties offers a potential benefit not only in the short-term period but also in a medium-term follow-up with low recurrence and late chronic pain rates. However, this particular mesh does not fully prevent all complications and chronic pain and recurrent hernias have been reported for the first time.

Undiagnosed long-term cognitive impairment in acutely hospitalised older medical patients with delirium: a prospective cohort study.

PubMed

Jackson, Thomas A; MacLullich, Alasdair M J; Gladman, John R F; Lord, Janet M; Sheehan, Bart

2016-07-01

delirium and dementia are common in the general hospital, being present in nearly 50% of older unselected admissions to hospital. Cognitive impairment is a risk factor for delirium, but the prevalence of previously undiagnosed cognitive impairment (dementia or mild cognitive impairment) in patients with delirium is unknown. we performed a prospective cohort study of people over 70 years admitted to hospital with delirium to establish the prevalence of previously unrecognised prior cognitive impairment. Delirium was diagnosed at baseline using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Mild cognitive impairment and dementia were diagnosed 3 months following recruitment in survivors using the International Working Group on Mild Cognitive Impairment criteria and DSM-IV criteria, respectively. delirium was identified in 17.9% of older patients, and 82 participants with delirium were assessed at 3 months: 5 (6%) had persistent delirium, 14 (17%) had mild cognitive impairment and 47 (57%) had dementia. In 17 participants with prior dementia and 14 with prior mild cognitive impairment, the diagnosis had been unrecognised, amounting to 31/82 (38%) of all patients with delirium having some form of previously undiagnosed cognitive impairment. given that over 1/3 of older patients with delirium were found to have a previously undiagnosed cognitive impairment, the development and evaluation of services to follow-up and manage patients with delirium are warranted. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data.

PubMed

Fornaro, Lorenzo; Vivaldi, Caterina; Cereda, Stefano; Leone, Francesco; Aprile, Giuseppe; Lonardi, Sara; Silvestris, Nicola; Santini, Daniele; Milella, Michele; Caparello, Chiara; Musettini, Gianna; Pasquini, Giulia; Falcone, Alfredo; Brandi, Giovanni; Sperduti, Isabella; Vasile, Enrico

2015-12-23

After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far. We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings. A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months). The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.

A Novel Assay for the Identification of NOTCH1 PEST Domain Mutations in Chronic Lymphocytic Leukemia

PubMed Central

Petroni, Roberta Cardoso; Muto, Nair Hideko; Sitnik, Roberta; de Carvalho, Flavia Pereira; Bacal, Nydia Strachman; Velloso, Elvira Deolinda Rodrigues Pereira; Oliveira, Gislaine Borba; Pinho, João Renato Rebello; Torres, Davi Coe; Mansur, Marcela Braga; Hassan, Rocio; Lorand-Metze, Irene Gyongyvér Heidemarie; Chiattone, Carlos Sérgio; Hamerschlak, Nelson; Mangueira, Cristovão Luis Pitangueira

2016-01-01

Aims. To develop a fast and robust DNA-based assay to detect insertions and deletions mutations in exon 34 that encodes the PEST domain of NOTCH1 in order to evaluate patients with chronic lymphocytic leukemia (CLL). Methods. We designed a multiplexed allele-specific polymerase chain reaction (PCR) combined with a fragment analysis assay to detect specifically the mutation c.7544_7545delCT and possibly other insertions and deletions in exon 34 of NOTCH1. Results. We evaluated our assay in peripheral blood samples from two cohorts of patients with CLL. The frequency of NOTCH1 mutations was 8.4% in the first cohort of 71 unselected CLL patients. We then evaluated a second cohort of 26 CLL patients with known cytogenetic abnormalities that were enriched for patients with trisomy 12. NOTCH1 mutations were detected in 43.7% of the patients with trisomy 12. Conclusions. We have developed a fast and robust assay combining allele-specific PCR and fragment analysis able to detect NOTCH1 PEST domain insertions and deletions. PMID:28074183

Prevalence of anterior pituitary dysfunction in patients following traumatic brain injury in a German multi-centre screening program.

PubMed

Berg, C; Oeffner, A; Schumm-Draeger, P-M; Badorrek, F; Brabant, G; Gerbert, B; Bornstein, S; Zimmermann, A; Weber, M; Broecker-Preuss, M; Mann, K; Herrmann, B L

2010-02-01

We determined the prevalence of anterior pituitary dysfunction in a multi-centre screening program across five German endocrine centres in patients rehabilitating from TBI (GCS<13). 246 patients (39+/-14 yrs; 133 males, 12+/-8 months after TBI) underwent a series of baseline endocrine tests with central assessment of TSH, free T4, prolactin, LH, FSH, testosterone (m), estradiol (f), cortisol, GH, and IGF-I. If IGF-I was <-2 SDS dynamic testing was performed. GHD was defined according to BMI-dependent cut-off values for GH response to GHRH+arginine of <4.2, <8.0 and <11.5 ng/ml in obese, overweight and lean subjects, respectively, or <3 micro g/l in ITT. Hypocortisolism was suggested when basal cortisol was <200 nmol/l and confirmed by ITT (peak<500 nmol/l). In TBI patients some degree of impaired pituitary function was shown in 21% (n=52/246). Total, multiple and isolated deficits were present in 1%, 2% and 18%, respectively. 19% had an IGF-I of <-1 SDS, 9% of <-2 SDS. In 5% GHD was confirmed. 9% had hypogonadism. 4% had hypocortisolism and 1% of patients had confirmed ACTH-deficiency. 12% had TSH-deficiency. In summary, in this large series carried out on an unselected group of TBI survivors we have found hypopituitarism in every fifth patient with predominantly secondary hypogonadism and hypothyreosis. Regarding somatotrope insufficiency IGF-I is decreased in 50% of GHD patients. These findings strongly suggest that patients who suffer head trauma should routinely undergo endocrine evaluation. J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart. New York.

[Cytoprotection with amifostine in radiotherapy or radio-chemotherapy of head and neck tumors].

PubMed

Altmann, S; Hoffmanns, H

1999-11-01

A considerable amount of experimental and clinical data prove the cytoprotective effect of amifostine on normal tissue exposed to different types of antineoplastic treatments. The present study examines its influence on the short-term toxicity of either radiotherapy alone or combined radio-chemotherapy in patients with advanced head and neck cancer. Twenty-three patients with advanced head and neck cancer, mainly Stage III and IV, were treated with preoperative radiation (n = 1), pre- as well as postoperative radiotherapy (n = 5), postoperative radiation (n = 9) or combined postoperative radio-chemotherapy (n = 6). Before each radiation application a total dose of 500 mg amifostine was administered intravenously over 15 minutes. The documentation of this unselected patient group was compared retrospectively to a historical control group comprising 17 patients. In 15 patients (65%) of the amifostine group, therapy induced side effects such as mucositis and dermatitis of WHO Grade < or = 2 were detected, requiring interruptions of the radiotherapy (mean: 6.5, maximum 17 days). No mucosa or dermatologic toxicity of WHO Grade 3 or 4 was observed in this group. Significantly more acute toxicity was detected in the historical control group. Stomatitis or epitheliolysis of WHO Grade 3 occurred in 7 patients (41%). The side effects induced by the antineoplastic therapy caused an interruption of treatment in 15 patients (88%) (mean: 16, maximum 40 days; p = 0.0016). The application of amifostine before each radiation treatment seems to result in a distinct reduction of short-term toxicity of radiotherapy or combined radio-chemotherapy in patients with head and neck cancer, allowing for a better adherence to the planned radiation time schedule.

Mortality and Rates of Secondary Intervention After EVAR in an Unselected Population: Influence of Simple Clinical Categories and Implications for Surveillance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammond, Christopher J., E-mail: christopherhammond@nhs.net; Shah, Asim H.; Snoddon, Andrew

IntroductionPost-EVAR surveillance has a major impact upon patients, carers and healthcare resources. We hypothesised that elective indication, on-IFU anatomy, use of a modern device or normal first CTA, or a combination of these categories, might predict a rate of secondary intervention low enough to alter current surveillance protocols.MethodsPatients undergoing EVAR in our institution between 01.05.2007 and 28.02.2013 were assessed. Data on indication (elective, emergency), anatomy relative to IFU, device, first month CTA result, secondary intervention and mortality were obtained. Kaplan–Meier charts of mortality and freedom from secondary intervention were produced. Statistical analysis was by log-rank test and Cox proportional hazardmore » modelling.Results234 patients underwent EVAR (188 elective, 208 on-IFU). Most implants were Endurant (106) or Talent (98). 151 patients had a normal first CTA. By median follow-up of 38.6 months, 39 patients underwent secondary intervention. A normal first CTA and elective indication were significantly associated with reduced risk of secondary intervention (p < 0.001 and p = 0.042 respectively), but device type and placement on- or off-IFU were not. Elective placement with a normal first CTA was 93 % predictive of freedom from secondary intervention by 32 months post-EVAR. Of nine patients undergoing secondary intervention in this group, eight presented symptomatically.DiscussionIn optimal procedural circumstances with normal post-procedural imaging, only 7 % of patients undergoing EVAR require secondary intervention, a minority of which is driven by surveillance. These data support a change to surveillance more tailored to the individual patient, and highlight the need for further qualitative and quantitative research.« less

A recurrent CHEK2 p.H371Y mutation is associated with breast cancer risk in Chinese women.

PubMed

Liu, Yin; Liao, Ji; Xu, Ye; Chen, Weiqiu; Liu, Dongyun; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xu, Xingzhi; Xie, Yuntao

2011-09-01

The association between the CHEK2 and breast cancer risk in Chinese women is unknown. Here, we screened the full CHEK2 coding sequence in 118 Chinese familial breast cancer cases who are negative for mutations in BRCA1 and BRCA2, one recurrent mutation, CHEK2 c.1111C>T (p.H371Y), was identified in five index cases in this cohort. Functional analysis suggested that CHEK2 p.H371Y was a pathogenic mutation that resulted in decreased kinase activity. We further screened the CHEK2 p.H371Y mutation in 909 unselected breast cancer cases and 1,228 healthy individuals. The frequencies of the CHEK2 p.H371Y in familial and unselected breast cancer cases and controls were 4.24% (5/118), 1.76% (16/909), and 0.73% (9/1228), respectively. The p.H371Y mutation was significantly associated with increased breast cancer risk in unselected breast cancer (odds ratio [OR] 2.43, 95% confidence interval [CI] 1.07-5.52, P = 0.034). Our results indicate that the recurrent mutation, p.H371Y, confers a moderate risk of breast cancer in Chinese women. © 2011 Wiley-Liss, Inc.

Influence of Honey Bee Genotype and Wintering Method on Wintering Performance of Varroa destructor (Parasitiformes: Varroidae)-Infected Honey Bee (Hymenoptera: Apidae) Colonies in a Northern Climate.

PubMed

Bahreini, Rassol; Currie, Robert W

2015-08-01

The objective of this study was to assess the effectiveness of a cooperative breeding program designed to enhance winter survival of honey bees (Apis mellifera L.) when exposed to high levels of varroa (Varroa destructor Anderson and Trueman) in outdoor-wintered and indoor-wintered colonies. Half of the colonies from selected and unselected stocks were randomly assigned to be treated with late autumn oxalic acid treatment or to be left untreated. Colonies were then randomly assigned to be wintered either indoors (n = 37) or outdoors (n = 40). Late autumn treatment with oxalic acid did not improve wintering performance. However, genotype of bees affected colony survival and the proportion of commercially viable colonies in spring, as indicated by greater rates of colony survival and commercially viable colonies for selected stock (43% survived and 33% were viable) in comparison to unselected stock (19% survived and 9% were viable) across all treatment groups. Indoor wintering improved spring bee population score, proportion of colonies surviving, and proportion of commercially viable colonies relative to outdoor wintering (73% of selected stock and 41% of unselected stock survived during indoor wintering). Selected stock showed better "tolerance" to varroa as the selected stock also maintained higher bee populations relative to unselected stock. However, there was no evidence of "resistance" in selected colonies (reduced mite densities). Collectively, this experiment showed that breeding can improve tolerance to varroa and this can help minimize colony loss through winter and improve colony wintering performance. Overall, colony wintering success of both genotypes of bees was better when colonies were wintered indoors than when colonies were wintered outdoors. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Engineering information on an Analog Signal to Discrete Time Interval Converter (ASDT-IC)

NASA Technical Reports Server (NTRS)

Schwarz, F. C.

1974-01-01

An electronic control system for nondissipative dc power converters is presented which improves (1) the routinely attainable static output voltage accuracy to the order of + or - 1% for ambient temperatures from -55 to 100 C and (2) the dynamic stability by utilizing approximately one tenth of the feedback gain needed otherwise. Performance is due to a functional philosophy of deterministic pulse modulation based on pulse area control and to an autocompensated signal processing principle. The system can be implemented with commercially available unselected components.

Temporal trends in sperm count: a systematic review and meta-regression analysis.

PubMed

Levine, Hagai; Jørgensen, Niels; Martino-Andrade, Anderson; Mendiola, Jaime; Weksler-Derri, Dan; Mindlis, Irina; Pinotti, Rachel; Swan, Shanna H

2017-11-01

Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality. To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group. PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981-2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973-2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group ('Unselected by fertility' versus 'Fertile'), geographic group ('Western', including North America, Europe Australia and New Zealand versus 'Other', including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models. SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models -0.70 million/ml/year; 95% CI: -0.72 to -0.69; P < 0.001; slope in adjusted meta-regression models = -0.64; -1.06 to -0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (-1.38; -2.02 to -0.74; P < 0.001) and among Fertile Western (-0.68; -1.31 to -0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (-5.33 million/year, -7.56 to -3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (-2.06 million/ml, -3.38 to -0.74; P = 0.004 and -8.12 million, -13.73 to -2.51, P = 0.006, respectively). This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Epidemiology of coeliac disease in a single centre in Southern Derbyshire 1958–2014

PubMed Central

Holmes, Geoffrey K T; Muirhead, A

2017-01-01

Objective To determine trends in diagnosis of coeliac disease (CD) in patients attending a single centre 1958–2014 and provide figures for prevalence and incidence in those born in Derby city over 4 decades. To explore a link between deprivation and prevalence and characteristics of CD in Asians. Design An unselected, consecutive series of 2410 adult patients with CD diagnosed in the catchment area of the Derby hospitals was identified. 1077 born within Derby city identified by postcodes was used to determine changes in prevalence and incidence over 4 decades. 191 patients were Asian. Population numbers were obtained from National Census information. Results In the quinquennium 2010–2014, 20 times more patients were diagnosed than during 1975–1979. 27% were diagnosed at ≥60 years. A paucity of diagnoses in young men was observed. Women were diagnosed most often in age band ≥35<45, 15 years earlier than men. The largest increase in diagnosis rates occurred in young women and the elderly. In 2014, overall prevalence was 1:188; women 1:138. 4.6% of the variation was attributed to deprivation. Diagnosis rates in Asians increased markedly although only 5% were diagnosed at ≥60 years, much lower than for whites. Conclusions The dramatic increase in number of patients with CD presents challenges for follow-up and new models of care need to be explored. Healthcare workers should be alert to the diagnosis in young men and elderly Asians. A dedicated coeliac clinic is an excellent facility to increase diagnosis rates. PMID:28761688

Genomic Profiling on an Unselected Solid Tumor Population Reveals a Highly Mutated Wnt/β-Catenin Pathway Associated with Oncogenic EGFR Mutations.

PubMed

Jiang, Jingrui; Protopopov, Alexei; Sun, Ruobai; Lyle, Stephen; Russell, Meaghan

2018-04-09

Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to mutations, oncogenic shift, alternative signaling, and other potential mechanisms. To further understand the genetic alterations associated with oncogenic EGFRs and to provide further insight into optimal and personalized therapeutic strategies, we applied a proprietary comprehensive next-generation sequencing (NGS)-based assay of 435 genes to systematically study the genomic profiles of 1565 unselected solid cancer patient samples. We found that activating EGFR mutations were predominantly detected in lung cancer, particularly in non-small cell lung cancer (NSCLC). The mutational landscape of EGFR-driven tumors covered most key signaling pathways and biological processes. Strikingly, the Wnt/β-catenin pathway was highly mutated (48 variants detected in 46% of the EGFR-driven tumors), and its variant number topped that in the TP53/apoptosis and PI3K-AKT-mTOR pathways. Furthermore, an analysis of mutation distribution revealed a differential association pattern of gene mutations between EGFR exon 19del and EGFR L858R. Our results confirm the aggressive nature of the oncogenic EGFR-driven tumors and reassure that a combinational strategy should have advantages over an EGFR-targeted monotherapy and holds great promise for overcoming drug resistance.

Prevalence of gastroesophageal reflux symptoms in a large unselected general population in Japan

PubMed Central

Yamagishi, Hatsushi; Koike, Tomoyuki; Ohara, Shuichi; Kobayashi, Shigeyuki; Ariizumi, Ken; Abe, Yasuhiko; Iijima, Katsunori; Imatani, Akira; Inomata, Yoshifumi; Kato, Katsuaki; Shibuya, Daisuke; Aida, Shigemitsu; Shimosegawa, Tooru

2008-01-01

AIM: To examine the prevalence of gastroesophageal reflux disease (GERD) symptoms in a large unselected general population in Japan. METHODS: In Japan, mature adults are offered regular check-ups for the prevention of gastric cancer. A notice was sent by mail to all inhabitants aged > 40 years. A total of 160 983 Japanese (60 774 male, 100 209 female; mean age 61.9 years) who underwent a stomach check up were enrolled in this study. In addition, from these 160 983 subjects, we randomly selected a total of 82 894 (34 275 male, 48 619 female; mean age 62.4 years) to evaluate the prevalence of abdominal pain. The respective subjects were prospectively asked to complete questionnaires concerning the symptoms of heartburn, dysphagia, and abdominal pain for a 1 mo period. RESULTS: The respective prevalences of the symptoms in males and females were: heartburn, 15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among these symptoms, heartburn was significantly high compared with the other symptoms, and the prevalence of heartburn was significantly more frequent in females than in males in the 60-89-year age group. Dysphagia was also significantly more frequent in female patients. CONCLUSION: The prevalence of typical GERD symptoms (heartburn) was high, at about 20% of the Japan population, and the frequency was especially high in females in the 60-89 year age group. PMID:18322948

The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients.

PubMed

Riis, Lene; Vind, Ida; Vermeire, Severine; Wolters, Frank; Katsanos, Kostas; Politi, Patrizia; Freitas, João; Mouzas, Ioannis A; O'Morain, Colm; Ruiz-Ochoa, Victor; Odes, Selwyn; Binder, Vibeke; Munkholm, Pia; Moum, Bjørn; Stockbrügger, Reinhold; Langholz, Ebbe

2007-01-01

The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north-south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD cohort. Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files. Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north-south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype. The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.

A pretest prognostic score to assess patients undergoing exercise or pharmacological stress testing

PubMed Central

Morise, Anthony; Evans, Matthew; Jalisi, Farrukh; Shetty, Rajendra; Stauffer, Marc

2007-01-01

Objective A previously developed pretest score was validated to stratify patients presenting for exercise testing with suspected coronary disease according to the presence of angiographic coronary disease. Our goal was to determine how well this pretest score risk stratified patients undergoing pharmacological and exercise stress tests concerning prognostic endpoints. Design Retrospective cohort analysis. Setting University hospital stress laboratory. Patients 7452 unselected ambulatory patients with symptoms of suspected coronary disease undergoing stress testing between 1995 and 2004. Main outcomes measures All‐cause death, cardiac death and non‐fatal myocardial infarction. Results The rate of all‐cause death was 5.5% (CI 5.0 to 6.1) with 4.3 (SD 2.4) years of follow‐up (Exercise 2.8% (CI 2.3 to 3.2) v Pharmacological group 11.9% (CI 10.5 to 13.3); p<0.001). The rate of cardiac death/myocardial infarction was 2.6% (CI 2.2 to 3.0) (Exercise 1.4% (CI 1.1 to 1.8) v Pharmacological group 5.3% (CI 4.3 to 6.2); p<0.001). In both groups, stratification by pretest score was significant for all‐cause death and the combined endpoint. However, stratification was more effective in the pharmacological group using the combined endpoint rather than all‐cause death. Pharmacological stress patients in intermediate and high risk groups were at higher risk than their respective exercise test cohorts. Referral for pharmacological stress testing was found to be an independent predictor of time to death (2.7 (CI 2.0 to 3.6); p<0.001). Conclusion A pretest score previously validated to stratify according to angiographic outcomes, effectively risk stratified pharmacological and exercise stress patients according to the combined endpoint of cardiac death/myocardial infarction. PMID:17228070

Patient reported outcome in posttraumatic pituitary deficiency: results from The Danish National Study on posttraumatic hypopituitarism.

PubMed

Klose, Marianne; Stochholm, Kirstine; Janukonyté, Jurgita; Christensen, Louise Lehman; Cohen, Arieh S; Wagner, Aase; Laurberg, Peter; Christiansen, Jens Sandahl; Andersen, Marianne; Feldt-Rasmussen, Ulla

2015-06-01

Posttraumatic pituitary hormone deficiency is often suggested. The impact of these predominantly mild and often irreproducible deficiencies on outcome is less clear. The aim of the present study was to describe patient reported outcome in a national a priori unselected cohort of patients with traumatic brain injury (TBI) in relation to deficiencies identified upon pituitary assessment. We conducted a nationwide population-based cohort study. Participants were Danish patients with a head trauma diagnosis recorded in the Danish Board of Health diagnostic code registry; 439 patients (and 124 healthy controls) underwent assessment of anterior pituitary function 2.5 years (median) after TBI. Questionnaires on health-related quality of life (QoL) (SF36, EuroQoL-5D, QoL assessment of GH deficiency in adults) and fatigue (MFI-20) were completed in parallel to pituitary assessment. Patients with TBI had significant detriments in QoL. Impairment (mainly physical scales) related to pituitary deficiency, although only partially confirmed after adjustment for demographic differences. Hypogonadotropic hypogonadism related to several QoL scores. Increasing impairments were observed with declining total testosterone concentrations (men), but not free testosterone concentrations or any other hormone concentrations. Total testosterone was not independently related to impaired QoL and fatigue, after adjustment for demographics, and treatment with antidiabetics, opioids, antidepressants, and anticonvulsants. Only a very limited relationship between pituitary hormone deficiencies and QoL/fatigue was demonstrated. Due to the dominating influence of concurrent comorbidities, pituitary deficiencies were not independently related to QoL/fatigue. Causality is still to be shown, and whether substitution therapy could be of additional relevance in selected patients needs to be proven. © 2015 European Society of Endocrinology.

Gender, socioeconomic position, revascularization procedures and mortality in patients presenting with STEMI and NSTEMI in the era of primary PCI. Differences or inequities?

PubMed

Gnavi, Roberto; Rusciani, Raffaella; Dalmasso, Marco; Giammaria, Massimo; Anselmino, Monica; Roggeri, Daniela Paola; Roggeri, Alessandro

2014-10-20

Several studies have reported gender and socioeconomic differences in the use of revascularization procedures in patients with acute myocardial infarction. However, it is not clear whether these differences influence patients' survival. Moreover, most of the studies neither considered STEMI and NSTEMI separately, nor included primary PCI, which nowadays is the treatment of choice in case of AMI. In an unselected population of patients admitted to hospital with a first episode of STEMI and NSTEMI we examined gender and socioeconomic differences in the use of cardiac invasive procedures and in one-year mortality. Subjects hospitalized with a first episode of STEMI (n=3506) or NSTEMI (n=2286) were selected from the Piedmont (Italy) hospital discharge database. We considered the percentage of patients undergoing PCI, primary PCI and CABG, and in-hospital mortality. Out of hospital mortality was calculated through record linkage with the regional register. The relation between outcomes and gender or educational level was investigated using appropriate multivariate regression models adjusting for available confounders. After adjustment for age, comorbidity and hospital characteristics, women and low educated patients had a lower probability of undergoing revascularization procedures. However, neither in-hospital, nor 30-day, nor 1-year mortality showed gender or social disparities. Despite gender and socioeconomic differences in the use of revascularization, no differences emerged in in-hospital and 1-year mortality. These findings could suggest that patients are differently, but equitably, treated; differences are more likely due to an inability to fully adjust for clinical conditions rather than to a selection process at admission. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1.

PubMed

Gorin, Laurent; Fauchier, Laurent; Nonin, Emilie; de Labriolle, Axel; Haguenoer, Ken; Cosnay, Pierre; Babuty, Dominique; Charbonnier, Bernard

2010-04-01

In patients with atrial fibrillation (AF) and an intermediate risk of stroke (CHADS2 score =1), available evidence from clinical trials is inconclusive and the present guidelines for the management of AF indicate that the choice between oral anticoagulant and aspirin in these patients is open. Our goal was to evaluate whether, in patients with AF and only one moderate risk factor for thromboembolism, treatment with an oral anticoagulant is appreciably more beneficial than treatment with an antiplatelet agent. Among 6,517 unselected patients with AF, 1,012 of them (15.5%) had a CHADS2 score of 1 and were liable to treatment with an antiplatelet agent or an anticoagulant. An oral anticoagulant was prescribed for 606 patients (59.9%) and an antiplatelet agent or no antithrombotic treatment for 406 (40.1%). During follow-up (median=793 days, interquartile range=1,332 days), 105 deaths (10.4%) and 19 strokes (1.9%) were recorded. The administration of an anticoagulant was associated with a lower rate of events (relative risk=0.42, 95% confidence interval 0.29-0.60, p<0.0001) than when no anticoagulant was prescribed. Results remained similar after adjustment for age and other confounding factors. In contrast, prescription of an antiplatelet agent was not associated with a lower risk of events. Factors independently associated with an increased risk of events were older age (p<0.0001), concomitant heart failure (p=0.0002), diabetes (p=0.0025), lack of prescription of an anticoagulant (p<0.0001) and permanent AF (p=0.04). Thus, prescription of an anticoagulant is independently associated with a decreased risk of death or stroke among patients with AF and a CHADS2 score =1.

Influence of manual thrombus aspiration on left ventricular diastolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

PubMed

Ilić, Ivan; Stanković, Ivan; Vidaković, Radosav; Janićijević, Aleksandra; Cerović, Milivoje; Jovanović, Vladimir; Aleksić, Aleksandar; Obradović, Gojko; Nikolajević, Ivica; Kafedzić, Srdjan; Milicević, Dusan; Kusić, Jovana; Putniković, Biljana; Nesković, Aleksandar N

2016-01-01

Data on effects of thrombus aspiration on left ventricular diastolic function in ST-elevation myocardial infarction (STEMI) population are scarce. We sought to compare echocardiographic indices of the diastolic function and outcomes in STEMI patients treated with and without manual thrombus aspiration, in an academic, high-volume percutaneous coronary intervention (PCI) center. A total of 433 consecutive patients who underwent primary PCI in 2011-2012 were enrolled in the study. Patients were not eligible for the study if they already suffered a myocardial infarction, had been previously revascularized, received thrombolytics, presented with cardiogenic shock, had significant valvular disease, atrial fibrillation or had previously implanted pacemaker. Comprehensive echocardiogram was performed within 48 hours. During follow-up patients'status was assessed by an office visit or telephone interview. Patients treated with thrombus aspiration (TA+, n=216) had similar baseline characteristics as those without thrombus aspiration (TA-, n = 217). Groups had similar total ischemic time (319 ± 276 vs. 333 ± 372 min; p = 0.665), but TA+ group had higher maximum values of troponin I (39.5 ± 30.5 vs. 27.6 ± 26.9 ng/ml; p < 0.001). The echocardiography revealed similar left ventricular volumes and systolic function, but TA+ group had significantly higher incidence of E/e' > 15, as a marker of severe diastolic dysfunction' (TA+ 23.1% vs. TA- 15.2%; p = 0.050). During average follow-up of 14 ± 5 months, major adverse cardiac/cerebral events occurred at the similar rate (log rank p = 0.867). Thrombus aspiration is associated with a greater incidence of severe diastolic dysfunction in unselected STEMI patients treated with primary PCI, but it doesn't influence the incidence of major adverse cardiovascular events.

Item Selection, Evaluation, and Simple Structure in Personality Data

PubMed Central

Pettersson, Erik; Turkheimer, Eric

2010-01-01

We report an investigation of the genesis and interpretation of simple structure in personality data using two very different self-reported data sets. The first consists of a set of relatively unselected lexical descriptors, whereas the second is based on responses to a carefully constructed instrument. In both data sets, we explore the degree of simple structure by comparing factor solutions to solutions from simulated data constructed to have either strong or weak simple structure. The analysis demonstrates that there is little evidence of simple structure in the unselected items, and a moderate degree among the selected items. In both instruments, however, much of the simple structure that could be observed originated in a strong dimension of positive vs. negative evaluation. PMID:20694168

[Analysis of Foetal Heart Rate Data using Complex Software: Comparison of Recurrence Plot of Foetal Heart Rate with the Course of Pregnancy -].

PubMed

Jörn, H; Morgenstern, B; Wassenberg, B; Rath, W

2004-08-01

Is it useful to further analyse foetal heart rate to improve the prediction of pregnancy complications? The analysis of the foetal heart rate is usually based on the variability of the heart rate, i. e. the more variable the heart rate presents - except a decrease - the better the condition of the foetus is. The same concept is applied in our own analysis which differs only in the presentation of the data. We analysed 25 non-stress-tests from unselected third trimester pregnancies using sophisticated software. The recurrence plot (RP) is able to rearrange data from foetal heart rate monitoring in order to make the heart rate variability visible. We developed criteria for a normal and an abnormal test result describing the structure of the diagram to predict an uneventful and a high-risk pregnancy, respectively. 11 out of 11 patients with uneventful course and outcome of pregnancy showed a coarse and blurred RP pattern. 12 out of 14 (86 %) patients developing either intrauterine growth retardation or preeclampsia and requiring caesarean section because of foetal heart rate abnormalities showed a fine and clear RP pattern. Our preliminary results show that it makes sense to further evaluate foetal heart rate variability in order to predict pregnancy complications. Computer programs including the algorithms needed (calculation of the recurrence plot) are not expensive and easy to handle. A widespread use of these programs represents the basis requirement for large controlled clinical trials.

Role of rituximab in treatment of patients with primary central nervous system lymphoma: a retrospective analysis of the Czech lymphoma study group registry.

PubMed

Mocikova, Heidi; Pytlik, Robert; Sykorova, Alice; Janikova, Andrea; Prochazka, Vit; Vokurka, Samuel; Berkova, Adela; Belada, David; Campr, Vit; Buresova, Lucie; Trneny, Marek

2016-12-01

We have investigated whether the addition of rituximab to methotrexate, procarbazine, vincristine, radiotherapy and cytarabine was associated with improved outcome of primary central nervous system lymphomas (PCNSL). Of 164 patients, 49 received rituximab. Median age was 63 years, median Karnofsky performance score (KPS) was 60 and median follow-up of living patients was 59.5 months. 1- and 2-year PFS were 49.7 and 37.9%, 1- and 2-year OS were 57.0 and 45.3%. Median progression-free survival (PFS), but not overall survival (OS) was significantly better for patients treated with rituximab (22.9 vs. 10.9 months, p = 0.037). In multivariate analysis, age ≤70 years and KPS ≥90 were predictive for PFS and OS, rituximab was an independent prognostic factor for PFS only. In landmark analyses, rituximab was not found beneficial for long-term survivors and no group particularly benefited from rituximab. In conclusion, addition of rituximab was associated with improved PFS, but not OS in this unselected cohort of PCNSL patients.

Hospital Anxiety and Depression Scale: Factor Structure, Internal Consistency and Convergent Validity in Patients with Dizziness.

PubMed

Piker, Erin G; Kaylie, David M; Garrison, Douglas; Tucci, Debara L

2015-01-01

Psychiatric comorbidities, particularly anxiety-related pathologies, are often observed in dizzy patients. The Hospital Anxiety and Depression Scale (HADS) is a widely used self-report instrument used to screen for anxiety and depression in medical outpatient settings. The purpose of this study was to assess the factor structure, internal consistency and convergent validity of the HADS in an unselected group of patients with dizziness. The HADS and the Dizziness Handicap Inventory (DHI) were administered to 205 dizzy patients. An exploratory factor analysis was conducted and indicated a 3-factor structure, inconsistent with the 2-subscale structure (i.e. anxiety and depression) of the HADS. The total scale was found to be internally consistent, and convergent validity, as assessed using the DHI, was acceptable. Overall findings suggest that the HADS should not be used as a tool for psychiatric differential diagnosis, but rather as a helpful screener for general psychiatric distress in the two domains of psychiatric illness most germane in dizzy patients. © 2015 S. Karger AG, Basel.

Reporting Severe Hypoglycemia in Type 1 Diabetes: Facts and Pitfalls.

PubMed

Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2017-10-28

To describe potential factors influencing reporting of severe hypoglycemia in adult patients with type 1 diabetes and to analyze their effect on reported rates of severe hypoglycemia. Reported rates of severe hypoglycemia defined as need for third party assistance vary between 0.3-3.0 events per patient-year in unselected cohorts, corresponding to a yearly prevalence range of 10-53%. When defined as need for parenteral therapy with glucose or glucagon or need for admission to an emergency unit or hospitalization, incidence and prevalence rates of severe hypoglycemia are 0.02-0.5 events per patient-year and 1-29%, respectively. When subjects with recurrent severe hypoglycemia in the past or suffering from impaired hypoglycemia awareness are excluded from participation in studies, lower rates are reported. Studies applying anonymous reporting or reporting by partners report higher rates of severe hypoglycemia. There is a large variation between studies reporting incidence and prevalence of severe hypoglycemia in patients with type 1 diabetes, mainly explained by definition of severity, methods of reporting, and patient selection. These findings call for consensus about hypoglycemia definition and reporting in future research.

Transbulbar B-Mode Sonography in Multiple Sclerosis: Clinical and Biological Relevance.

PubMed

De Masi, Roberto; Orlando, Stefania; Conte, Aldo; Pasca, Sergio; Scarpello, Rocco; Spagnolo, Pantaleo; Muscella, Antonella; De Donno, Antonella

2016-12-01

Optic nerve sheath diameter quantification by transbulbar B-mode sonography is a recently validated technique, but its clinical relevance in relapse-free multiple sclerosis patients remains unexplored. In an open-label, comparative, cross-sectional study, we aimed to assess possible differences between patients and healthy controls in terms of optic nerve sheath diameter and its correlation with clinical/paraclinical parameters in this disease. Sixty unselected relapse-free patients and 35 matched healthy controls underwent transbulbar B-mode sonography. Patients underwent routine neurologic examination, brain magnetic resonance imaging and visual evoked potential tests. The mean optic nerve sheath diameter 3 and 5 mm from the eyeball was 22-25% lower in patients than controls and correlated with the Expanded Disability Status Scale (r = -0.34, p = 0.048, and r = -0.32, p = 0.042, respectively). We suggest that optic nerve sheath diameter quantified by transbulbar B-mode sonography should be included in routine assessment of the disease as an extension of the neurologic examination. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Quality assurance in surgical oncology. Colorectal cancer as an example.

PubMed

Gunnarsson, Ulf

2003-02-01

Quality assurance in surgical oncology is a field of growing importance. National, regional and local systems have been built up in many countries. Often the quality assurance projects are linked to different registers. The advantage of such a link is the possibility of obtaining population-based data from unselected health care institutions. Few discussions of results from such projects have been published. Quality assurance of colorectal cancer surgery implies the development and use of systems for improvement all the way from detection of the cancer to the outcome as survival and patient satisfaction. To achieve this we must know what methods are being used and the outcome of our treatments. Designing processes for improvement necessitates careful planning, including decisions about end-points. Some crucial issues are discussed step-by-step in the present paper. In addition to auditing and providing collegial feedback, quality assurance is a tool for closing the gap between clinical practice and evidence based medicine and for creating new evidences as well as monitoring the introduction of new techniques and their effects.

Optimizing Early Rule-Out Strategies for Acute Myocardial Infarction: Utility of 1-Hour Copeptin.

PubMed

Hillinger, Petra; Twerenbold, Raphael; Jaeger, Cedric; Wildi, Karin; Reichlin, Tobias; Rubini Gimenez, Maria; Engels, Ulrike; Miró, Oscar; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Röthlisberger, Michèle; Ernst, Susanne; Rentsch, Katharina; Mueller, Christian

2015-12-01

Combined testing of high-sensitivity cardiac troponin T (hs-cTnT) and copeptin at presentation provides a very high-although still imperfect-negative predictive value (NPV) for the early rule-out of acute myocardial infarction (AMI). We hypothesized that a second copeptin measurement at 1 h might further increase the NPV. In a prospective diagnostic multicenter study, we measured hs-cTnT and copeptin concentrations at presentation and at 1 h in 1439 unselected patients presenting to the emergency department with suspected AMI. The final diagnosis was adjudicated by 2 independent cardiologists blinded to copeptin concentrations. We investigated the incremental value of 1-h copeptin in the rule-out setting (0-h hs-cTnT negative and 0-h copeptin negative) and the intermediate-risk setting (0-h hs-cTnT negative and 0-h copeptin positive). The adjudicated diagnosis was AMI in 267 patients (18.6%). For measurements obtained at presentation, the NPV in the rule-out setting was 98.6% (95% CI, 97.4%-99.3%). Whereas 1-h copeptin did not increase the NPV significantly, 1-h hs-cTnT did, to 99.6% (95% CI, 98.7%-99.9%, P = 0.008). Similarly, in the intermediate-risk setting (NPV 92.8%, 95% CI, 88.7%-95.8%), 1-h copeptin did not significantly increase the NPV (P = 0.751), but 1-h hs-cTnT did, to 98.6 (95% CI, 96%-99.7%, P < 0.001). One-hour copeptin increased neither the safety of the rule-out process nor the NPV in the intermediate-risk setting. In contrast, the incremental value of 1-h hs-cTnT was substantial in both settings. ClinicalTrials.gov/NCT00470587. © 2015 American Association for Clinical Chemistry.

Studies on strain sensitivity of Trichomonas vaginalis to metronidazole.

PubMed Central

Meingassner, J G; Havelec, L; Mieth, H

1978-01-01

Ninety-four strains of Trichomonas vaginalis isolated from unselected patients in Vienna during the period from November 1975 to November 1975 were subjected to sensitivity tests against metronidazole in vitro and in vivo. Nearly 90% of the isolates examined showed in vitro growth inhibition at concentrations of 0.4 to 1.6 microgram metronidazole/ml and only about 10% at concentrations of less than 0.4 microgram/ml. All isolates showed some inhibition of growth after incubation for 48 hours with 3.2 microgram metroidazole/ml. Tests on treatment carried out on experimentally infected mice revealed that all strains of T. vaginalis examined were sensitive to metronidazole (MDE: less than 3 x 35 mg/kg peroral). PMID:305807

Validation of the GRACE Risk score for hospital mortality in patients with acute coronary syndrome in the Arab Middle East.

PubMed

Yusufali, Afzalhussein; Zubaid, Mohammad; Al-Zakwani, Ibrahim; Alsheikh-Ali, Alawi A; Al-Mallah, Mouaz H; Al Suwaidi, Jassim; AlMahmeed, Wael; Rashed, Wafa; Sulaiman, Kadhim; Amin, Haitham

2011-07-01

Our objective was to validate the Global Registry of Acute Coronary Events (GRACE) risk score for in-hospital mortality in a Middle Eastern acute coronary syndrome (ACS) population enrolled in the Gulf Registry of Acute Coronary Events (Gulf RACE). Out of 8176, unselected, consecutive patients with ACS, during 6 months in 2006 and 2007 from 63 hospitals in 6 Arab countries in the Middle East Gulf region, 7709 (94.3%) with available data were included. The main outcome measures were discriminatory performance (using C-index) and calibration of the GRACE risk score (in-hospital mortality predicted by GRACE risk score versus the actual mortality). In-hospital mortality in the Gulf RACE was 3.09% (n = 238). The discriminatory performance of the GRACE risk scores in the Gulf RACE was good overall (C-index = 0.86). Observed and predicted risk corresponded well in each stratum of risk of in-hospital mortality. This suggests its suitability for clinical use in this patient population.

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: study by the Nagasaki CML Study Group.

PubMed

Itonaga, Hidehiro; Tsushima, Hideki; Imanishi, Daisuke; Hata, Tomoko; Doi, Yuko; Mori, Sayaka; Sasaki, Daisuke; Hasegawa, Hiroo; Matsuo, Emi; Nakashima, Jun; Kato, Takeharu; Horai, Makiko; Taguchi, Masataka; Matsuo, Masatoshi; Taniguchi, Hiroaki; Makiyama, Junnya; Sato, Shinya; Horio, Kensuke; Ando, Koji; Moriwaki, Yuji; Sawayama, Yasushi; Ogawa, Daisuke; Yamasaki, Reishi; Takasaki, Yumi; Imaizumi, Yoshitaka; Taguchi, Jun; Kawaguchi, Yasuhisa; Yoshida, Shinichiro; Joh, Tatsuro; Moriuchi, Yukiyoshi; Nonaka, Hiroaki; Soda, Hisashi; Fukushima, Takuya; Nagai, Kazuhiro; Kamihira, Shimeru; Tomonaga, Masao; Yanagihara, Katsunori; Miyazaki, Yasushi

2014-01-01

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Low-dose omega-3 fatty acids as lipid lowering agents in the practice. A field study of ambulatory patients in general practice].

PubMed

Zakaria, B; Bertsch, S

1992-04-10

BASICS: Clinical trials have shown that omega-3 fatty acids are also effective at smaller doses than those so far recommended for lowering lipid concentrations. Testing this finding in a large number of unselected outpatients. Open multicentric trial involving 197 patients with dyslipoproteinemia. Treatment comprised omega-3 fatty acids, 1.1 to 1.4 g per day administered for a period of 12 weeks. After 12 weeks of treatment, serum triglycerides decreased on average by about 23%, total cholesterol by about 10%, and LDL cholesterol by about 5%. HDL cholesterol rose by an average of 16%. The fish oil preparation (Eicosapen, Nycomed, Munich) was well tolerated; a fishy taste and mild gastrointestinal complaints led to discontinuation of treatment in only four cases. It was also found that the effect of omega-3 fatty acids was appreciably greater in hypertensives than in patients with normal blood pressure--not only on systolic and diastolic blood pressure, but also on serum triglycerides and HDL.

Does addition of low-level laser therapy (LLLT) in conservative care of knee arthritis successfully postpone the need for joint replacement?

PubMed

Ip, David

2015-12-01

The current study evaluates whether the addition of low-level laser therapy into standard conventional physical therapy in elderly with bilateral symptomatic tri-compartmental knee arthritis can successfully postpone the need for joint replacement surgery. A prospective randomized cohort study of 100 consecutive unselected elderly patients with bilateral symptomatic knee arthritis with each knee randomized to receive either treatment protocol A consisting of conventional physical therapy or protocol B which is the same as protocol A with added low-level laser therapy. The mean follow-up was 6 years. Treatment failure was defined as breakthrough pain which necessitated joint replacement surgery. After a follow-up of 6 years, patients clearly benefited from treatment with protocol B as only one knee needed joint replacement surgery, while nine patients treated with protocol A needed surgery (p < 0.05). We conclude low-level laser therapy should be incorporated into standard conservative treatment protocol for symptomatic knee arthritis.

Novel drugs in clinical development for hepatocellular carcinoma.

PubMed

Waidmann, Oliver; Trojan, Jörg

2015-01-01

Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Within recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development either due to toxicity or lack of benefit. This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC. In unselected patients with advanced HCC, disappointing results have been reported from several large trials. However, in two subgroups encouraging results have been achieved. Treatment with the MET inhibitor tivantinib resulted in a substantial survival benefit in the subgroup of MET overexpressing tumors in a randomized Phase II trial. Furthermore, the vascular endothelial growth factor receptor 2 antibody ramucirumab resulted in improved overall survival in patients with baseline α-fetoprotein (AFP) ≥ 400 ng/ml in a Phase III trial. These two agents, and several others, will be further developed in HCC. Moreover, immunotherapeutics such as checkpoint inhibitors, programmed death receptor-1 blocking antibodies and oncolytic viruses are under investigation in advanced HCC.

A pretest prognostic score to assess patients undergoing exercise or pharmacological stress testing.

PubMed

Morise, Anthony; Evans, Matthew; Jalisi, Farrukh; Shetty, Rajendra; Stauffer, Marc

2007-02-01

A previously developed pretest score was validated to stratify patients presenting for exercise testing with suspected coronary disease according to the presence of angiographic coronary disease. Our goal was to determine how well this pretest score risk stratified patients undergoing pharmacological and exercise stress tests concerning prognostic endpoints. Retrospective cohort analysis. University hospital stress laboratory. 7452 unselected ambulatory patients with symptoms of suspected coronary disease undergoing stress testing between 1995 and 2004. All-cause death, cardiac death and non-fatal myocardial infarction. The rate of all-cause death was 5.5% (CI 5.0 to 6.1) with 4.3 (SD 2.4) years of follow-up (Exercise 2.8% (CI 2.3 to 3.2) v Pharmacological group 11.9% (CI 10.5 to 13.3); p<0.001). The rate of cardiac death/myocardial infarction was 2.6% (CI 2.2 to 3.0) (Exercise 1.4% (CI 1.1 to 1.8) v Pharmacological group 5.3% (CI 4.3 to 6.2); p<0.001). In both groups, stratification by pretest score was significant for all-cause death and the combined endpoint. However, stratification was more effective in the pharmacological group using the combined endpoint rather than all-cause death. Pharmacological stress patients in intermediate and high risk groups were at higher risk than their respective exercise test cohorts. Referral for pharmacological stress testing was found to be an independent predictor of time to death (2.7 (CI 2.0 to 3.6); p<0.001). A pretest score previously validated to stratify according to angiographic outcomes, effectively risk stratified pharmacological and exercise stress patients according to the combined endpoint of cardiac death/myocardial infarction.

Prognostic value of plasma midregional pro-adrenomedullin and C-terminal-pro-endothelin-1 in chronic heart failure outpatients.

PubMed

Adlbrecht, Christopher; Hülsmann, Martin; Strunk, Guido; Berger, Rudolf; Mörtl, Deddo; Struck, Joachim; Morgenthaler, Nils G; Bergmann, Andreas; Jakowitsch, Johannes; Maurer, Gerald; Lang, Irene M; Pacher, Richard

2009-04-01

The identification of chronic heart failure (CHF) patients at high risk of adverse outcome remains a challenge. New peptides are emerging that may give additional information. In CHF patients, endothelin (ET) levels predict mortality risk. Adrenomedullin has been shown to predict mortality in ischaemic heart failure, but not in unselected or non-ischaemic CHF patients. Moreover, ADM and ET have never been assessed in one model. The aim of the present study was to assess the prognostic value of midregional-pro-adrenomedullin (MR-proADM) and C-terminal-pro-endothelin-1 (CT-proET-1) in outpatients with CHF. We measured plasma MR-proADM and CT-proET-1 levels in 786 consecutive CHF outpatients and compared them with B-type natriuretic peptide (BNP) levels. At 24-month follow-up, 233 patients had died. A stepwise forward Cox regression model with age, sex, estimated glomerular filtration rate, NYHA > II, left ventricular ejection fraction (LVEF), MR-proADM, CT-proET-1, and BNP as possible predictors revealed that MR-proADM levels [hazard ratio (HR) = 1.77, P < 0.001] in addition to age (HR = 1.02, P = 0.004), ejection fraction (HR = 0.98, P = 0.004), and NYHA > II (HR = 1.86, P < 0.001) were predictors of death at 24 months. When the analysis was repeated dependent on NYHA-stage, MR-proADM (HR = 2.12, P < 0.001) and LVEF (HR = 0.96, P = 0.006) were significant markers, but only in patients with mild/moderate CHF. Our data suggest that MR-proADM may be an important prognostic humoral marker, especially in mild/moderately symptomatic and non-ischaemic CHF patients.

Weight gain following treatment of hyperthyroidism.

PubMed

Dale, J; Daykin, J; Holder, R; Sheppard, M C; Franklyn, J A

2001-08-01

Patients frequently express concern that treating hyperthyroidism will lead to excessive weight gain. This study aimed to determine the extent of, and risk factors for, weight gain in an unselected group of hyperthyroid patients. We investigated 162 consecutive hyperthyroid patients followed for at least 6 months. Height, weight, clinical features, biochemistry and management were recorded at each clinic visit. Documented weight gain was 5.42 +/- 0.46 kg (mean +/- SE) and increase in BMI was 8.49 +/- 0.71%, over a mean 24.2 +/- 1.6 months. Pre-existing obesity, Graves' disease causing hyperthyroidism, weight loss before presentation and length of follow-up each independently predicted weight gain. Patients treated with thionamides or radioiodine gained a similar amount of weight (thionamides, n = 87, 5.16 +/- 0.63 kg vs. radioiodine, n = 62, 4.75 +/- 0.57 kg, P = 0.645), but patients who underwent thyroidectomy (n = 13) gained more weight (10.27 +/- 2.56 kg vs. others, P = 0.007). Development of hypothyroidism (even transiently) was associated with weight gain (never hypothyroid, n = 102, 4.57 +/- 0.52 kg, transiently hypothyroid, n = 29, 5.37 +/- 0.85 kg, on T4, n = 31, 8.06 +/- 1.42 kg, P = 0.014). This difference remained after correcting for length of follow-up. In the whole cohort, weight increased by 3.95 +/- 0.40 kg at 1 year (n = 144) to 9.91 +/- 1.62 kg after 4 years (n = 27) (P = 0.008), representing a mean weight gain of 3.66 +/- 0.44 kg/year. We have demonstrated marked weight gain after treatment of hyperthyroidism. Pre-existing obesity, a diagnosis of Graves' disease and prior weight loss independently predicted weight gain and weight continued to rise with time. Patients who became hypothyroid, despite T4 replacement, gained most weight.

Enhanced treatment of secondary municipal wastewater effluent: comparing (biological) filtration and ozonation in view of micropollutant removal, unselective effluent toxicity, and the potential for real-time control.

PubMed

Chys, Michael; Demeestere, Kristof; Ingabire, Ange Sabine; Dries, Jan; Van Langenhove, Herman; Van Hulle, Stijn W H

2017-07-01

Ozonation and three (biological) filtration techniques (trickling filtration (TF), slow sand filtration (SSF) and biological activated carbon (BAC) filtration) have been evaluated in different combinations as tertiary treatment for municipal wastewater effluent. The removal of 18 multi-class pharmaceuticals, as model trace organic contaminants (TrOCs), has been studied. (Biological) activated carbon filtration could reduce the amount of TrOCs significantly (>99%) but is cost-intensive for full-scale applications. Filtration techniques mainly depending on biodegradation mechanisms (TF and SSF) are found to be inefficient for TrOCs removal as a stand alone technique. Ozonation resulted in 90% removal of the total amount of quantified TrOCs, but a post-ozonation step is needed to cope with an increased unselective toxicity. SSF following ozonation showed to be the only technique able to reduce the unselective toxicity to the same level as before ozonation. In view of process control, innovative correlation models developed for the monitoring and control of TrOC removal during ozonation, are verified for their applicability during ozonation in combination with TF, SSF or BAC. Particularly for the poorly ozone reactive TrOCs, statistically significant models were obtained that correlate TrOC removal and reduction in UVA 254 as an online measured surrogate parameter.

Online attentional bias modification training targeting anxiety and depression in unselected adolescents: Short- and long-term effects of a randomized controlled trial.

PubMed

de Voogd, E L; Wiers, R W; Prins, P J M; de Jong, P J; Boendermaker, W J; Zwitser, R J; Salemink, E

2016-12-01

Based on information processing models of anxiety and depression, we investigated the efficacy of multiple sessions of online attentional bias modification training to reduce attentional bias and symptoms of anxiety and depression, and to increase emotional resilience in youth. Unselected adolescents (N = 340, age: 11-18 years) were randomly allocated to eight sessions of a dot-probe, or a visual search-based attentional training, or one of two corresponding placebo control conditions. Cognitive and emotional measures were assessed pre- and post-training; emotional outcome measures also at three, six and twelve months follow-up. Only visual search training enhanced attention for positive information, and this effect was stronger for participants who completed more training sessions. Symptoms of anxiety and depression reduced, whereas emotional resilience improved. However, these effects were not especially pronounced in the active conditions. Thus, this large-scale randomized controlled study provided no support for the efficacy of the current online attentional bias modification training as a preventive intervention to reduce symptoms of anxiety or depression or to increase emotional resilience in unselected adolescents. However, the absence of biased attention related to symptomatology at baseline, and the large drop-out rates at follow-up preclude strong conclusions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Quantitative structural MRI for early detection of Alzheimer’s disease

PubMed Central

McEvoy, Linda K; Brewer, James B

2011-01-01

Alzheimer’s disease (AD) is a common progressive neurodegenerative disorder that is not currently diagnosed until a patient reaches the stage of dementia. There is a pressing need to identify AD at an earlier stage, so that treatment, when available, can begin early. Quantitative structural MRI is sensitive to the neurodegeneration that occurs in mild and preclinical AD, and is predictive of decline to dementia in individuals with mild cognitive impairment. Objective evidence of ongoing brain atrophy will be critical for risk/benefit decisions once potentially aggressive, disease-modifying treatments become available. Recent advances have paved the way for the use of quantitative structural MRI in clinical practice, and initial clinical use has been promising. However, further experience with these measures in the relatively unselected patient populations seen in clinical practice is needed to complete translation of the recent enormous advances in scientific knowledge of AD into the clinical realm. PMID:20977326

The role of randomized cluster crossover trials for comparative effectiveness testing in anesthesia: design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial.

PubMed

Spence, Jessica; Belley-Côté, Emilie; Lee, Shun Fu; Bangdiwala, Shrikant; Whitlock, Richard; LeManach, Yannick; Syed, Summer; Lamy, Andre; Jacobsohn, Eric; MacIsaac, Sarah; Devereaux, P J; Connolly, Stuart

2018-07-01

Increasingly, clinicians and researchers recognize that studies of interventions need to evaluate not only their therapeutic efficacy (i.e., the effect on an outcome in ideal, controlled settings) but also their real-world effectiveness in broad, unselected patient groups. Effectiveness trials inform clinical practice by comparing variations in therapeutic approaches that fall within the standard of care. In this article, we discuss the need for studies of comparative effectiveness in anesthesia and the limitations of individual patient randomized-controlled trials in determining comparative effectiveness. We introduce the concept of randomized cluster crossover trials as a means of answering questions of comparative effectiveness in anesthesia, using the design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial (Clinicaltrials.gov identifier NCT03053869).

Somatic mutations in the transcriptional corepressor gene BCORL1 in adult acute myelogenous leukemia.

PubMed

Li, Meng; Collins, Roxane; Jiao, Yuchen; Ouillette, Peter; Bixby, Dale; Erba, Harry; Vogelstein, Bert; Kinzler, Kenneth W; Papadopoulos, Nickolas; Malek, Sami N

2011-11-24

To further our understanding of the genetic basis of acute myelogenous leukemia (AML), we determined the coding exon sequences of ∼ 18 000 protein-encoding genes in 8 patients with secondary AML. Here we report the discovery of novel somatic mutations in the transcriptional corepressor gene BCORL1 that is located on the X-chromosome. Analysis of BCORL1 in an unselected cohort of 173 AML patients identified a total of 10 mutated cases (6%) with BCORL1 mutations, whereas analysis of 19 AML cell lines uncovered 4 (21%) BCORL1 mutated cell lines. The majority (87%) of the mutations in BCORL1 were predicted to inactivate the gene product as a result of nonsense mutations, splice site mutation, or out-of-frame insertions or deletions. These results indicate that BCORL1 by genetic criteria is a novel candidate tumor suppressor gene, joining the growing list of genes recurrently mutated in AML.

[Evaluation of DCA vantage for rapid in-clinic measurement of HbA1c on capillary blood in young type 1 diabetic patients].

PubMed

El Arabi, H; Willems, D; Mélot, C; Dorchy, H

2013-01-01

Rapid in clinic measurement of glycated hemoglogin (HbA1c) allows to determine the level of metabolic control within a few minutes on capillary blood. We have evaluated the new DCA Vantage (Siemens) based on an immunological technique, replacing the DCA 2000+ (Siemens). The study included 120 unselected young type 1 diabetic patients, with different degrees of metabolic control. The DCA Vantage was compared with the HPLC system (Menarini HA 8160) whose deviation from the DCCT was < 0.1% across the clinical range. The mean underestimation of the DCA Vantage was -0.40%. The agreement limits (+/- 1.96 SD) were between 0.14% and -0.93%; this means +/- 0.53% around -0.40%. In conclusion, the DCA Vantage underestimates HbA1c levels; however it met the acceptance criteria of having a coefficient of variation < 3%.

Distinguishing rational from irrational applications of pharmacogenetic synergies from the bench to clinical trials.

PubMed

Hucl, Tomas; Gallmeier, Eike; Kern, Scott E

2007-06-01

Single therapeutic agents very often fail in unselected patients. It is therefore commonplace to combine an agent specifically with a selected patient subgroup or with another agent. To support such efforts, it is useful to clarify the distinctions between the terms and the mathematical models used in analyzing combinations. To incorporate molecular disease classifications, the familiar concept of the therapeutic window is modified to define a pharmacogenetic window, which is an unambiguous numerical measure of the magnitude of interaction produced by a combination, and to define a test of pharmacogenetic synergy. In contrast, certain common comparative methods, such as vertical windows (comparing effects at a given dose) and animal models of mutational targets may be dominated by undesirable features. Although this discussion is oriented towards cancer therapy, an extension of these concepts to other comparative biologic assays is feasible and advisable.

Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

PubMed

Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

2016-04-01

With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

Long-term safety and real-world effectiveness of fingolimod in relapsing multiple sclerosis

PubMed Central

Druart, Charlotte; El Sankari, Souraya; van Pesch, Vincent

2018-01-01

With a growing number of disease-modifying therapies becoming available for relapsing multiple sclerosis, there is an important need to gather real-world evidence data regarding long-term treatment effectiveness and safety in unselected patient populations. Although not providing as high a level of evidence as randomized controlled trials, and prone to bias, real-world studies from observational studies or registries nevertheless provide crucial information on real-world outcomes of a given therapy. In addition, evaluation of treatment satisfaction and impact on quality of life are increasingly regarded as complementary outcome measures. Fingolimod was the first oral disease-modifying therapy approved for relapsing multiple sclerosis. This review aims to summarize current knowledge on the long-term effectiveness and safety outcomes of multiple sclerosis patients on fingolimod. Impact on treatment satisfaction and quality of life will be discussed according to available data. PMID:29317850

Follicular flushing during oocyte retrieval: a systematic review and meta-analysis.

PubMed

Roque, Matheus; Sampaio, Marcos; Geber, Selmo

2012-11-01

The purpose of this systematic review and meta-analysis was to examine the literature and identify randomized controlled trials (RCTs), in order to answer if performing follicular flushing during the oocyte retrieval may improve the assisted reproductive technologies (ART) outcomes. An exhaustive electronic search was performed using MEDLINE and EMBASE databases. Only RCTs comparing follicular flushing to aspiration only during ART, were included. We included 5 trials, with a total of 482 patients randomized, with median ages ranging from 30.5 to 37.1. The data analyses did not show significant differences regarding live birth rate, clinical pregnancies rates, and the number of oocytes retrieved. The duration of oocyte retrieval was significantly increased in the follicular flushing group. The results from this systematic review and meta-analysis suggest that there is no advantage to use of routine follicular flushing during OR in an unselected group of patients.

Impact of history of heart failure on diagnostic and prognostic value of BNP: results from the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study.

PubMed

Boldanova, Tujana; Noveanu, Markus; Breidthardt, Tobias; Potocki, Mihael; Reichlin, Tobias; Taegtmeyer, Anne; Christ, Michael; Laule, Kirsten; Stelzig, Claudia; Mueller, Christian

2010-07-23

This study aimed to examine the influence of history of heart failure (HF) on circulating levels, diagnostic accuracy and prognostic value of B-type natriuretic peptide (BNP) in patients presenting with all cause dyspnea at the emergency department. BNP has been shown to be very helpful in diagnosis and prognosis of HF. Due to chronically elevated cardiac filling pressures, patients with a history of HF might have higher BNP levels and therefore diagnostic and prognostic properties of BNP may be affected. We analyzed circulating levels, diagnostic accuracy and prognostic value of BNP in 388 patients without a previous history of HF and compared these to data to 64 patients with a history of HF included in the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) Study. Baseline BNP levels were higher in patients with a history of HF (median 814 pg/ml [353-1300 pg/ml] vs. 216 pg/ml [45-801 pg/ml], p<0.001). Diagnostic accuracy of BNP to identify HF was comparable in patients with (AUC=0.804; 95% CI 0.628-0.980) and in patients without history of HF (AUC=0.883; 95% CI 0.848-0.919, p=0.389). Prognostic ability of BNP to predict one-year mortality was lower in overall patients with history of HF (AUC=0.458; 95%CI 0.294-0.622) compared to patients without history of HF (AUC=0.710; 95% CI 0.653-0.768, p<0.05). In patients with history of HF, BNP levels retain diagnostic accuracy. Ability to predict one-year mortality was decreased in unselected patients, but not in patients with acute HF-induced dyspnea. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Implementation of high sensitivity cardiac troponin T measurement in the emergency department.

PubMed

Christ, Michael; Popp, Steffen; Pohlmann, Hella; Poravas, Michail; Umarov, Dina; Bach, Ruth; Bertsch, Thomas

2010-12-01

we examined the diagnostic performance of high sensitivity cardiac troponin T (cTnThs) measurement and its ability to predict risk in unselected patients presenting to the emergency department with acute chest pain. we conducted a retrospective analysis of 137 consecutive patients with chest pain (age range, 66 ± 16 years; 64% male). A final diagnosis of acute myocardial infarction was made using the "old" (cTnT fourth-generation assay, ≥ 0.04 microg/L) or the "new" cutpoint (cTnThs ≥ 0.014 microg/L). the adjudicated final diagnosis of acute myocardial infarction significantly increased from 20 to 35 patients (a 75% increase) and troponin-positive nonvascular cardiac chest pain from 10 to 30 (a 200% increase) using cTnThs. The number of patients with unstable angina or troponin-negative nonvascular cardiac chest pain significantly decreased (P <.05). Diagnostic performance of cTnThs levels at admission was significantly higher compared to cTnT levels (area under the curve [AUC] 0.85 vs AUC 0.70; P <.05). cTnThs levels below the detection limit (<0.003 microg/L) had a negative predictive value of 100% to exclude acute myocardial infarction. The event rate during 6 months of follow-up was low in patients with cTnThs levels <0.014 microg/L, while patients with cTnT levels ≥ 0.04 μg/L were at increased, and patients with cTnThs ≥ 0.014 μg/L and cTnT <0.04 microg/L at intermediate risk of death or recurrent myocardial infarction (P = .002). Risk was highest in chest pain patients with dynamic changes of cTnThs levels >30%. the introduction of cTnThs assay displays an excellent diagnostic performance for the workup of patients with chest pain at the time of their initial presentation. Even small increases of cTnThs indicate increased risk for death or myocardial infarction during follow-up. © 2010 Elsevier Inc. All rights reserved.

Specific IgG4 antibodies to cow's milk proteins in pediatric patients with eosinophilic esophagitis.

PubMed

Schuyler, Alexander J; Wilson, Jeffrey M; Tripathi, Anubha; Commins, Scott P; Ogbogu, Princess U; Kruzsewski, Patrice G; Barnes, Barrett H; McGowan, Emily C; Workman, Lisa J; Lidholm, Jonas; Rifas-Shiman, Sheryl L; Oken, Emily; Gold, Diane R; Platts-Mills, Thomas A E; Erwin, Elizabeth A

2018-04-18

Allergen-specific IgG 4 (sIgG 4 ) antibodies are often associated with tolerance, but sIgG 4 antibodies to causally relevant foods have been reported recently in adults with eosinophilic esophagitis (EoE). Prevalence and levels of food sIgG 4 are not well established in the general pediatric population. We sought to investigate serum food sIgG 4 with component diagnostics in children with EoE and children from an unselected birth cohort and to explore the effects of sex, age, and milk consumption on sIgG 4 levels. Sera from 71 pediatric patients with EoE and 210 early adolescent children from an unselected birth cohort (Project Viva) were assayed for sIgG 4 and specific IgE (sIgE) to major cow's milk (CM) proteins (α-lactalbumin, β-lactoglobulin, and caseins) and to wheat, soy, egg, and peanut proteins. In the EoE cohort high-titer sIgG 4 (≥10 μg/mL) to CM proteins was more common than in control sera and achieved odds ratios for EoE ranging from 5.5 to 8.4. sIgE levels to CM proteins were mostly 4 IU/mL or less in patients with EoE, such that sIgG 4 /sIgE ratios were often 10,000 or greater. When adjusted for age and milk consumption, high-titer sIgG 4 to CM proteins was strongly associated with EoE, with an odds ratio of greater than 20 to all 3 CM proteins in boys. sIgG 4 to CM proteins are common and high titer in children with EoE. Although it is not clear that this response is pathogenic, sIgG 4 levels imply that these antibodies are an important feature of the local immune response that gives rise to EoE. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Genetic alterations and tumor immune attack in Yo paraneoplastic cerebellar degeneration.

PubMed

Small, Mathilde; Treilleux, Isabelle; Couillault, Coline; Pissaloux, Daniel; Picard, Géraldine; Paindavoine, Sandrine; Attignon, Valery; Wang, Qing; Rogemond, Véronique; Lay, Stéphanie; Ray-Coquard, Isabelle; Pfisterer, Jacobus; Joly, Florence; Du Bois, Andreas; Psimaras, Dimitri; Bendriss-Vermare, Nathalie; Caux, Christophe; Dubois, Bertrand; Honnorat, Jérôme; Desestret, Virginie

2018-04-01

Paraneoplastic cerebellar degenerations with anti-Yo antibodies (Yo-PCD) are rare syndromes caused by an auto-immune response against neuronal antigens (Ags) expressed by tumor cells. However, the mechanisms responsible for such immune tolerance breakdown are unknown. We characterized 26 ovarian carcinomas associated with Yo-PCD for their tumor immune contexture and genetic status of the 2 onconeural Yo-Ags, CDR2 and CDR2L. Yo-PCD tumors differed from the 116 control tumors by more abundant T and B cells infiltration occasionally organized in tertiary lymphoid structures harboring CDR2L protein deposits. Immune cells are mainly in the vicinity of apoptotic tumor cells, revealing tumor immune attack. Moreover, contrary to un-selected ovarian carcinomas, 65% of our Yo-PCD tumors presented at least one somatic mutation in Yo-Ags, with a predominance of missense mutations. Recurrent gains of the CDR2L gene with tumor protein overexpression were also present in 59% of Yo-PCD patients. Overall, each Yo-PCD ovarian carcinomas carried at least one genetic alteration of Yo-Ags. These data demonstrate an association between massive infiltration of Yo-PCD tumors by activated immune effector cells and recurrent gains and/or mutations in autoantigen-encoding genes, suggesting that genetic alterations in tumor cells trigger immune tolerance breakdown and initiation of the auto-immune disease.

Does anatomy of the pubic arch interfere with the maintaining of erection?

PubMed

Paul, Jean François; Virag, Ronald

2013-03-01

There are men who suffer from unsustainable erections without any identified cause of erectile dysfunction, raising the question if anatomical alterations could be involved. Since early anatomical studies, it has been proposed that to achieve full penile rigidity, the blood must be blocked inside the penis by compression of the deep dorsal vein (DDV), the main venous collector under pubic symphysis. Using a recently developed caverno computed tomography (CT) scan technique, allowing the evaluation of the venous drainage of the corpora cavernosa (CC) during erection, we have studied some anatomical conditions of this important part of the erectile phenomenon. Puboischial rami angles were measured in axial CT images and calculated strictly on the upper insertion point of the CC, using axial submillimeter slices in 37 patients divided into 3 groups depending on the results of the caverno CT scan: (i) no leak; (ii) superficial veins leaking; and (iii) drainage through the DDV and/or preprostatic plexus. In addition same angles were measured in two randomly unselected populations of men (N = 30), and women (N = 23) who underwent pelvic CT scan for various reasons, unrelated to their sexual or genital condition. The angles made by both puboischial rami were measured in patients with and without veno-occlusive dysfunction and in unselected samples of men and women. There is a significantly wider angle made by both puboischial rami in men without complete erection and without evidence of anomalous venous drainage (group 3) (72.2° ± 4.7° standard deviation [SD]), compared with both men with normal erection (group 1) (57.5 ± 5° SD) P < 0.00001, and men with incomplete erection and evidence of anomalous drainage (group 2) (57.7 ± 6° SD) P < 0.00001. If confirmed in larger samples, these results raise new questions on the mechanism and the role of these significant anatomical variations, yet unknown, in maintaining or not full rigid erections. © 2012 International Society for Sexual Medicine.

A perspective on the use of an enhanced recovery program in open, non-instrumented day surgery for degenerative lumbar and cervical spinal conditions.

PubMed

Venkata, Hari K; van Dellen, James R

2018-06-01

A means of significantly shortening patients' length of hospital stay, improving their outcome and thereby also reducing costs is to use an enhanced recovery program (ERP) which is increasingly being used in a number of surgical sub-specialties. This paper provides a perspective on its prospective use in a wide-ranging, unselected cohort of patients undergoing open spinal surgery for degenerative lumbar and cervical spinal conditions. Selected spinal cases undergoing day surgery have been increasingly reported. A prospective, unselected, consecutive cohort of 246 cases, over an 18-month period, undergoing open, non-instrumented decompression spinal surgery and using ERP (and the concept of "bundles of care") was analyzed. Nine cases could not be included as they did not fully meet the entry criteria. No routine follow-up was arranged for the study group. The ages ranged widely, from 23-90 years (mean 57). In 187 the surgery for degenerative conditions was lumbar and in 50 cervical. The ASA (American Association of Anesthesiologists) ratings were 108=1; 107=2 and 22=3. Using the United Kingdom (UK) National Health Service (NHS) definitions of length of stay 225 (95%) could be finally classified as "ambulatory" and 12 (5%) were "short stay". A sub-cohort of 126 (53.2%) were "day cases". The follow-up was >1 year for all. There were no wound infections reported; 5 postdischarge cases (2.1%) needed to be seen in the Accident and Emergency (A&E) Department (less than 4 days postsurgery), but none needed re-admission; and there were 7 re-admissions (2.5%), between 4 and 30 days, and of these 6 required a further surgical procedure. There were no long-term instability complications reported in this cohort. ERP can be used for spinal surgery. There were identifiable and correctable medical and social factors found on analysis which could significantly increase the "day cases" number to over 90%.

Identification of men with low-risk biopsy-confirmed prostate cancer as candidates for active surveillance.

PubMed

Lin, Daniel W; Crawford, E David; Keane, Thomas; Evans, Brent; Reid, Julia; Rajamani, Saradha; Brown, Krystal; Gutin, Alexander; Tward, Jonathan; Scardino, Peter; Brawer, Michael; Stone, Steven; Cuzick, Jack

2018-06-01

A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10 -5 ). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS. Copyright © 2018 Elsevier Inc. All rights reserved.

Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis: A Systematic Review and Meta-Analysis

PubMed Central

Kunutsor, Setor K.; Whitehouse, Michael R.; Blom, Ashley W.; Beswick, Andrew D.

2015-01-01

Background The two-stage revision strategy has been claimed as being the “gold standard” for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option; however, its effectiveness in comparison to the two-stage strategy remains uncertain. Objective To compare the effectiveness of one- and two-stage revision strategies in treating prosthetic hip infection, using re-infection as an outcome. Design Systematic review and meta-analysis. Data Sources MEDLINE, EMBASE, Web of Science, Cochrane Library, manual search of bibliographies to March 2015, and email contact with investigators. Study Selection Cohort studies (prospective or retrospective) conducted in generally unselected patients with prosthetic hip infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision. No clinical trials were identified. Review Methods Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection from 38 one-stage studies (2,536 participants) and 60 two-stage studies (3,288 participants) were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics. Results In one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0–10.8). The corresponding re-infection rate after two-stage revision was 7.9% (6.2–9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no strong evidence of publication bias among contributing studies. Conclusion Evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision among unselected patients. More detailed analyses under a broader range of circumstances and exploration of other sources of heterogeneity will require collaborative pooling of individual participant data. Systematic Review Registration PROSPERO 2015: CRD42015016559 PMID:26407003

Comparison of the Multiattribute Utility Instruments EQ-5D and SF-6D in a Europe-Wide Population-Based Cohort of Patients with Inflammatory Bowel Disease 10 Years after Diagnosis.

PubMed

Huppertz-Hauss, Gert; Aas, Eline; Lie Høivik, Marte; Langholz, Ebbe; Odes, Selwyn; Småstuen, Milada; Stockbrugger, Reinhold; Hoff, Geir; Moum, Bjørn; Bernklev, Tomm

2016-01-01

Background. The treatment of chronic inflammatory bowel disease (IBD) is costly, and limited resources call for analyses of the cost effectiveness of therapeutic interventions. The present study evaluated the equivalency of the Short Form 6D (SF-6D) and the Euro QoL (EQ-5D), two preference-based HRQoL instruments that are broadly used in cost-effectiveness analyses, in an unselected IBD patient population. Methods. IBD patients from seven European countries were invited to a follow-up visit ten years after their initial diagnosis. Clinical and demographic data were assessed, and the Short Form 36 (SF-36) was employed. Utility scores were obtained by calculating the SF-6D index values from the SF-36 data for comparison with the scores obtained with the EQ-5D questionnaire. Results. The SF-6D and EQ-5D provided good sensitivities for detecting disease activity-dependent utility differences. However, the single-measure intraclass correlation coefficient was 0.58, and the Bland-Altman plot indicated numerous values beyond the limits of agreement. Conclusions. There was poor agreement between the measures retrieved from the EQ-5D and the SF-6D utility instruments. Although both instruments may provide good sensitivity for the detection of disease activity-dependent utility differences, the instruments cannot be used interchangeably. Cost-utility analyses performed with only one utility instrument must be interpreted with caution.

Comparison of the Multiattribute Utility Instruments EQ-5D and SF-6D in a Europe-Wide Population-Based Cohort of Patients with Inflammatory Bowel Disease 10 Years after Diagnosis

PubMed Central

Aas, Eline; Odes, Selwyn; Småstuen, Milada; Stockbrugger, Reinhold; Hoff, Geir; Moum, Bjørn; Bernklev, Tomm

2016-01-01

Background. The treatment of chronic inflammatory bowel disease (IBD) is costly, and limited resources call for analyses of the cost effectiveness of therapeutic interventions. The present study evaluated the equivalency of the Short Form 6D (SF-6D) and the Euro QoL (EQ-5D), two preference-based HRQoL instruments that are broadly used in cost-effectiveness analyses, in an unselected IBD patient population. Methods. IBD patients from seven European countries were invited to a follow-up visit ten years after their initial diagnosis. Clinical and demographic data were assessed, and the Short Form 36 (SF-36) was employed. Utility scores were obtained by calculating the SF-6D index values from the SF-36 data for comparison with the scores obtained with the EQ-5D questionnaire. Results. The SF-6D and EQ-5D provided good sensitivities for detecting disease activity-dependent utility differences. However, the single-measure intraclass correlation coefficient was 0.58, and the Bland-Altman plot indicated numerous values beyond the limits of agreement. Conclusions. There was poor agreement between the measures retrieved from the EQ-5D and the SF-6D utility instruments. Although both instruments may provide good sensitivity for the detection of disease activity-dependent utility differences, the instruments cannot be used interchangeably. Cost-utility analyses performed with only one utility instrument must be interpreted with caution. PMID:27630711

Dopamine D3 receptor gene locus: Association with schizophrenia, as well age of onset

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nimgsonkar, V.L.; Zhang, X.R.; Brar, J.S.

Genetic factors are clearly involved in the etiology of schizophrenia, but their specific nature is unknown. If the genetic etiology is multifactorial or polygenic, the role of specific genes as susceptibility factors can be directly evaluated by examining allelic variation at these loci among cases in comparison with controls. Two studies have independently demonstrated an association of schizophrenia with homozygosity at the dopamine D3 receptor gene (D3RG) locus, using a biallelic polymorphism in the first exon of D3RG. These results are important because D3RG is a favored candidate gene. Three other studies have identified associations among sub-groups of patients, butmore » the majority were negative. The present study involved patients with schizophrenia (DSM-III-R criteria) of Caucasian or African-American ethnicity (n=130). Two groups of controls, matched for ethnicity, were used: adults screened for schizophrenia (n=128) and unselected neonates (n=160). Multivariate analysis revealed an association between allele no. 1 homozygosity and schizophrenia in comparison with adult, but not neonatal controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.7, C.I. 1.8, 104.3). An association of the D3RG locus with age of onset (AOO) was also noted. The discrepancies in earlier studies may due to variations in control groups, differencies in mean AOO among different cohorts, or ethnic variations in susceptibility attributable to D3RG.« less

Computer-aided system for diabetes care in Berlin, G.D.R.

PubMed

Thoelke, H; Meusel, K; Ratzmann, K P

1990-01-01

In the Centre of Diabetes and Metabolic Disorders of Berlin, G.D.R., a computer-aided care system has been used since 1974, aiming at relieving physicians and medical staff from routine tasks and rendering possible epidemiological research on an unselected diabetes population of a defined area. The basis of the system is the data bank on diabetics (DB), where at present data from approximately 55,000 patients are stored. DB is used as a diabetes register of Berlin. On the basis of standardised criteria of diagnosis and therapy of diabetes mellitus in our dispensary care system, DB facilitates representative epidemiological analyses of the diabetic population, e.g. prevalence, incidence, duration of diabetes, and modes of treatment. The availability of general data on the population or the selection of specified groups of patients serves the management of the care system. Also, it supports the computer-aided recall of type II diabetics, treated either with diet alone or with diet and oral drugs. In this way, the standardised evaluation of treatment strategies in large populations of diabetics is possible on the basis of uniform metabolic criteria (blood glucose plus urinary glucose). The system consists of a main computer in the data processing unit and of personal computers in the diabetes centre which can be used either individually or as terminals to the main computer. During 14 years of experience, the computer-aided out-patient care of type II diabetics has proved efficient in a big-city area with a large population.

A prospective assessment of cytomegalovirus infection in active inflammatory bowel disease.

PubMed

de Saussure, P; Lavergne-Slove, A; Mazeron, M-C; Alain, S; Matuchansky, C; Bouhnik, Y

2004-12-01

The prevalence and clinical significance of cytomegalovirus infection is reportedly high in patients with refractory inflammatory bowel disease but is unknown in unselected patients with active disease. In patients admitted for active inflammatory bowel disease, we prospectively studied the presence and significance of cytomegalovirus infection using anti-cytomegalovirus antibodies, cytomegalovirus viraemia and antigenaemia and cytomegalovirus inclusions and cytomegalovirus immunochemistry staining in ileocolonic biopsies. A total of 64 patients were included (ulcerative colitis, n = 23; Crohn's disease, n = 41), 18 of whom had been on high-dose oral steroids and 11 on immunosuppressants. Anti-cytomegalovirus IgG and IgM were positive in 42 (66%) and 3 (5%) patients respectively. Blood or urine cytomegalovirus replication markers were found in 4 (6%) patients, all of whom had ulcerative colitis. Three patients had cytomegalovirus viraemia and received anti-viral treatment with ganciclovir. Only one of these patients had cytomegalovirus antigenaemia and also associated biopsy-proven cytomegalovirus colitis, probably as a primary cytomegalovirus infection. This patient is the only one who benefitted from anti-viral therapy. Cytomegalovirus infection is infrequent in in-patients with active inflammatory bowel disease. Systematic search of cytomegalovirus replication markers should not be performed. Isolated viraemia without associated antigenaemia or direct demonstration of cytomegalovirus in ileocolonic biopsies does not warrant anti-viral therapy.

Management of patients during hunger strike and refeeding phase.

PubMed

Eichelberger, M; Joray, M L; Perrig, M; Bodmer, M; Stanga, Z

2014-01-01

Hunger strikers resuming nutritional intake may develop a life-threatening refeeding syndrome (RFS). Consequently, hunger strikers represent a core challenge for the medical staff. The objective of the study was to test the effectiveness and safety of evidence-based recommendations for prevention and management of RFS during the refeeding phase. This was a retrospective, observational data analysis of 37 consecutive, unselected cases of prisoners on a hunger strike during a 5-y period. The sample consisted of 37 cases representing 33 individual patients. In seven cases (18.9%), the hunger strike was continued during the hospital stay, in 16 episodes (43.2%) cessation of the hunger strike occurred immediately after admission to the security ward, and in 14 episodes (37.9%) during hospital stay. In the refeed cases (n = 30), nutritional replenishment occurred orally, and in 25 (83.3%) micronutrients substitutions were made based on the recommendations. The gradual refeeding with fluid restriction occurred over 10 d. Uncomplicated dyselectrolytemia was documented in 12 cases (40%) within the refeeding phase. One case (3.3%) presented bilateral ankle edemas as a clinical manifestation of moderate RFS. Intensive medical treatment was not necessary and none of the patients died. Seven episodes of continued hunger strike were observed during the entire hospital stay without medical complications. Our data suggested that seriousness and rate of medical complications during the refeeding phase can be kept at a minimum in a hunger strike population. This study supported use of recommendations to optimize risk management and to improve treatment quality and patient safety in this vulnerable population. Copyright © 2014 Elsevier Inc. All rights reserved.

Are treatment results for eating disorders affected by ADHD symptoms? A one-year follow-up of adult females.

PubMed

Svedlund, Nils Erik; Norring, Claes; Ginsberg, Ylva; von Hausswolff-Juhlin, Yvonne

2018-05-02

To explore the influence of self-reported Attention Deficit Hyperactivity Disorder (ADHD) symptoms on recovery rate at 1-year follow-up in an unselected group of patients in a specialized eating disorder (ED) clinic. Four hundred forty-three adult females with an ED were assessed with the ADHD Self-Report Scale for Adults (ASRS-screener), and for demographic variables and ED symptoms. Recovery was registered at 1-year follow-up. A high degree of ADHD symptoms at baseline was predictive for nonrecovery of ED at 1-year follow-up in patients with loss of control over eating, bingeing, or purging. The presence of inattentive ADHD symptoms was stronger associated with nonrecovery than hyperactive/impulsive symptoms. A high degree of ADHD symptoms may have a negative impact on recovery in ED. Screening/diagnostic evaluation of ADHD in all loss of control over eating/bingeing/purging ED patients and studies of the effect of implementing ADHD-treatment strategies in this patient group are recommended. Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.

Lyral has been included in the patch test standard series in Germany.

PubMed

Geier, Johannes; Brasch, Jochen; Schnuch, Axel; Lessmann, Holger; Pirker, Claudia; Frosch, Peter J

2002-05-01

Lyral 5% pet. was tested in 3245 consecutive patch test patients in 20 departments of dermatology in order (i) to check the diagnostic quality of this patch test preparation, (ii) to examine concomitant reactions to Lyral and fragrance mix (FM), and (iii) to assess the frequency of contact allergy to Lyral in an unselected patch test population of German dermatological clinics. 62 patients reacted to Lyral, i.e. 1.9%. One third of the positive reactions were + + and + + +. The reaction index was 0.27. Thus, the test preparation can be regarded a good diagnostic tool. Lyral and fragrance mix (FM) were tested in parallel in 3185 patients. Of these, 300 (9.4%) reacted to FM, and 59 (1.9%) to Lyral. In 40 patients, positive reactions to both occurred, which is 13.3% of those reacting to FM, and 67.8% of those reacting to Lyral. So the concordance of positive test reactions to Lyral and FM was only slight. Based on these results, the German Contact Dermatitis Research Group (DKG) decided to add Lyral 5% pet. to the standard series.

A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS).

PubMed

Nacu, Aliona; Kvistad, Christopher E; Logallo, Nicola; Naess, Halvor; Waje-Andreassen, Ulrike; Aamodt, Anne Hege; Solhoff, Ragnar; Lund, Christian; Tobro, Håkon; Rønning, Ole Morten; Salvesen, Rolf; Idicula, Titto T; Thomassen, Lars

2015-07-11

Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients. Acute ischaemic stroke patients ≥ 18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable ≤ 4(½) hours after symptom onset, are included in NOR-SASS. NOR-SASS is superimposed on a separate trial randomising patients with acute ischemic stroke to either tenecteplase or alteplase (The Norwegian Tenecteplase Stroke Trial NOR-TEST). The NOR-SASS trial has two arms: 1) the thrombolysis-arms (NOR-SASS A and B) includes patients given intravenous thrombolysis (tenecteplase or alteplase), and 2) the no-thrombolysis-arm (NOR-SASS C) includes patients with contraindications to thrombolysis. First step randomisation of NOR-SASS A is embedded in NOR-TEST as a 1:1 randomisation to either tenecteplase or alteplase. Second step NOR-SASS randomisation is 1:1 to either contrast enhanced sonothrombolysis (CEST) or sham CEST. Randomisation in NOR-SASS B (routine alteplase group) is 1:1 to either CEST or sham CEST. Randomisation of NOR-SASS C is 1:1 to either contrast enhanced sonolysis (CES) or sham CES. Ultrasound is given for one hour using a 2-MHz pulsed-wave diagnostic ultrasound probe. Microbubble contrast (SonoVue®) is given as a continuous infusion for ~30 min. Recanalisation is assessed at 60 min after start of CEST/CES. Magnetic resonance imaging and angiography is performed after 24 h of stroke onset. Primary study endpoints are 1) major neurological improvement measured with NIHSS score at 24 h and 2) favourable functional outcome defined as mRS 0-1 at 90 days. NOR-SASS is the first randomised controlled trial designed to test the superiority of contrast enhanced ultrasound treatment given ≤ 4(½) hours after stroke onset in an unselected acute ischaemic stroke population eligible or not eligible for intravenous thrombolysis, with or without a defined arterial occlusion on CTA. If a positive effect and safety can be proven, contrast enhanced ultrasound treatment will be an option for all acute ischaemic stroke patients. EudraCT No 201200032341; www.clinicaltrials.gov NCT01949961.

Genetic diversity of European cattle breeds highlights the conservation value of traditional unselected breeds with high effective population size.

PubMed

Medugorac, Ivica; Medugorac, Ana; Russ, Ingolf; Veit-Kensch, Claudia E; Taberlet, Pierre; Luntz, Bernhard; Mix, Henry M; Förster, Martin

2009-08-01

In times of rapid global and unforeseeable environmental changes, there is an urgent need for a sustainable cattle breeding policy, based on a global view. Most of the indigenous breeds are specialized in a particular habitat or production system but are rapidly disappearing. Thus, they represent an important resource to meet present and future breeding objectives. Based on 105 microsatellites, we obtained thorough information on genetic diversity and population structure of 16 cattle breeds that cover a geographical area from the domestication centre near Anatolia, through the Balkan and alpine regions, to the North-West of Europe. Breeds under strict artificial selection and indigenous breeds under traditional breeding schemes were included. The overall results showed that the genetic diversity is widespread in Busa breeds in the Anatolian and Balkan areas, when compared with the alpine and north-western European breeds. Our results reflect long-term evolutionary and short-term breeding events very well. The regular pattern of allele frequency distribution in the entire cattle population studied clearly suggests conservation of rare alleles by conservation of preferably unselected traditional breeds with large effective population sizes. From a global and long-term conservation genetics point of view, the native and highly variable breeds closer to the domestication centre could serve as valuable sources of genes for future needs, not only for cattle but also for other farm animals.

Diclofenac Does Not Reduce the Risk of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Low-Risk Units.

PubMed

Rainio, Mia; Lindström, Outi; Udd, Marianne; Louhimo, Johanna; Kylänpää, Leena

2017-08-01

Nonsteroidal anti-inflammatory drugs have an inhibitory role in pathogenesis of pancreatitis. Guidelines from the European Society of Gastrointestinal Endoscopy recommend routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP for all patients without contraindications. Our aim was to evaluate the effect of diclofenac in preventing post-ERCP pancreatitis (PEP) in a high-volume, low-PEP-risk ERCP unit. The rate and severity of PEP were compared in groups of 1000 historical controls prior to the routine use of diclofenac and in 1000 patients receiving 100 mg diclofenac before ERCP. PEP occurred in 56 (2.8%) of the 2000 patients, and the rate of the pancreatitis was 2.8% in control group and 2.8% in diclofenac group (p = 1.000). The PEP rate among the native papilla patients was 3.9% in control group and 3.6% in diclofenac group (p = 0.803). In subgroup analysis of patients with a high risk of PEP, diclofenac neither prevented PEP nor made its course milder. In an unselected patient population in a center with a low incidence of PEP, diclofenac seems to have no beneficial effect.

Trends in survival of multiple myeloma: a thirty-year population-based study in a single institution.

PubMed

Ríos-Tamayo, Rafael; Sánchez, María José; Puerta, José Manuel; Sáinz, Juan; Chang, Daysi-Yoe-Ling; Rodríguez, Teresa; López, Pilar; de Pablos, José María; Navarro, Pilar; de Veas, José Luís García; Romero, Antonio; Garrido, Pilar; Moratalla, Lucía; Alarcón-Payer, Carolina; López-Fernández, Elisa; González, Pedro Antonio; Jiménez-Moleón, José Juan; Calleja-Hernández, Miguel Ángel; Jurado, Manuel

2015-10-01

Despite the progress made in recent years, multiple myeloma is still considered an incurable disease. Most survival data come from clinical trials. Little is known about the outcome in unselected real-life patients. Overall survival was analyzed in a cohort of newly diagnosed symptomatic multiple myeloma patients, over the last three decades, in a single institution population-based study. 582 consecutive myeloma patients were included in the study. Survival increased over time in patients younger than 65 years but did not reach statistical significance in patients with 65 years or older. The prognostic factors associated with overall survival were the International Staging System, the serum lactate dehydrogenase level, the renal impairment, the realization of autologous stem cell transplantation, and the presence of concomitant amyloidosis. Overall survival shows a steady improvement over time. The survival of myeloma is improving progressively in real-life patients, particularly after the widespread use of the novel agents. A comprehensive assessment of comorbidity can help to explain the huge heterogeneity of myeloma outcome. The optimization of current therapeutic resources as well as the incorporation of new drugs will allow further improvement of survival in the coming years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stereotactic Radiosurgery versus Natural History in Patients with Growing Vestibular Schwannomas.

PubMed

Tu, Albert; Gooderham, Peter; Mick, Paul; Westerberg, Brian; Toyota, Brian; Akagami, Ryojo

2015-08-01

Objective To describe our experience with stereotactic radiosurgery and its efficacy on growing tumors, and then to compare this result with the natural history of a similar cohort of non-radiation-treated lesions. Study Design A retrospective chart review and cohort comparison. Methods The long-term control rates of patients having undergone radiosurgery were collected and calculated, and this population was then compared with a group of untreated patients from the same period of time with growing lesions. Results A total of 61 patients with growing vestibular schwannomas treated with radiosurgery were included. After a mean of 160 months, we observed a control rate of 85.2%. When compared with a group of 36 patients with growing tumors who were yet to receive treatment (previously published), we found a corrected control rate or relative risk reduction of only 76.8%. Conclusion Radiosurgery for growing vestibular schwannomas is less effective than previously reported in unselected series. Although radiosurgery still has a role in managing this disease, consideration should be given to the actual efficacy that may be calculated when the natural history is known. We hope other centers will similarly report their experience on this cohort of patients.

Stereotactic Radiosurgery versus Natural History in Patients with Growing Vestibular Schwannomas

PubMed Central

Tu, Albert; Gooderham, Peter; Mick, Paul; Westerberg, Brian; Toyota, Brian; Akagami, Ryojo

2015-01-01

Objective To describe our experience with stereotactic radiosurgery and its efficacy on growing tumors, and then to compare this result with the natural history of a similar cohort of non-radiation–treated lesions. Study Design A retrospective chart review and cohort comparison. Methods The long-term control rates of patients having undergone radiosurgery were collected and calculated, and this population was then compared with a group of untreated patients from the same period of time with growing lesions. Results A total of 61 patients with growing vestibular schwannomas treated with radiosurgery were included. After a mean of 160 months, we observed a control rate of 85.2%. When compared with a group of 36 patients with growing tumors who were yet to receive treatment (previously published), we found a corrected control rate or relative risk reduction of only 76.8%. Conclusion Radiosurgery for growing vestibular schwannomas is less effective than previously reported in unselected series. Although radiosurgery still has a role in managing this disease, consideration should be given to the actual efficacy that may be calculated when the natural history is known. We hope other centers will similarly report their experience on this cohort of patients. PMID:26225318

Use of healthcare, patient satisfaction and burden of care in Guillain-Barre syndrome.

PubMed

Forsberg, Anette; de Pedro-Cuesta, Jesús; Widén Holmqvist, Lotta

2006-07-01

The aim of this study was to investigate, in an unselected sample of patients with Guillain-Barré syndrome in Sweden, the utilization of healthcare resources, satisfaction with these resources, informal help and the burden of care on family caregivers during the first 2 years after onset. Forty-four patients were enrolled from 8 hospitals, and 42 of them were followed for 2 years. Data on the utilization of hospital inpatient and outpatient care, primary care and community-based services were collected via computerized registry information, medical records and a specific protocol. Patient satisfaction and the burden on family caregivers were studied using questionnaires. Forty-one patients required inpatient hospitalization for a mean of 82 days. Patients with persistent dependency during activities of daily living had significantly longer hospital stays and more days of outpatient rehabilitation. The majority of patients were satisfied with their care, but dissatisfaction was found regarding information and finances. At 2 years after onset, 26% of patients still depended on informal help. The spouses expressed increased concern and responsibility for household and family. Patients with persistent disability due to Guillain-Barré syndrome were found to have long-term need for services from the healthcare system and informal help.

Symptom severity scale of the DSM5 for schizophrenia, and other psychotic disorders: diagnostic validity and clinical feasibility.

PubMed

Ritsner, Michael S; Mar, Maria; Arbitman, Marina; Grinshpoon, Alexander

2013-06-30

Innovations in DSM5 include dimensional diagnosis of schizophrenia (SZ) and other psychotic (OP) disorders using the symptom severity scale (SS-DSM5). We evaluated the psychometric properties and diagnostic validity of the SS-DSM5 scale using a cross-sectional design and an unselected convenience unselected sample of 314 inpatients and outpatients with SZ/OP and mood disorders who received standard care in routine clinical practice. The SS-DSM5 scale, the Clinical Global Impression-Severity scale (CGI-S), the Positive and Negative Syndrome Scale (PANSS), and the Bech-Rafaelsen Mania Scale (BRMS) were administered. Factor structure, reliability, internal consistency, convergent and diagnostic ability of the DSM5-SS were evaluated. Factor analysis indicated two latent factors underlying the SS-DSM5 (Psychotic and Deficit sub-scales). Cronbach's alpha was >0.70. Convergent validity of the SS-DSM5 was highly significant. Patients with SZ/PO disorders were correctly diagnosed (77.9%) using the SS-DSM5 scale (72% using PANSS). The agreement of the diagnostic decisions between the SS-DSM5 and PANSS was substantial for SZ/PO disorders (Kappa=0.75). Classifying participants with SZ/PO versus mood disorders using SS-DSM5 provided a sensitivity of 95%, and specificity of 34%. Thus, this study suggests that the SS-DSM5 has acceptable psychometric properties and that its use in clinical practice and research is feasible in clinical settings. The dimensional option for the diagnosis of schizophrenia and related disorders using SS-DSM5 is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Psychometric properties of the dimensional anxiety scales for DSM-V in an unselected sample of German treatment seeking patients.

PubMed

Beesdo-Baum, Katja; Klotsche, Jens; Knappe, Susanne; Craske, Michelle G; Lebeau, Richard T; Hoyer, Jürgen; Strobel, Anja; Pieper, Lars; Wittchen, Hans-Ulrich

2012-12-01

Dimensional assessments are planned to be included as supplements to categorical diagnoses in DSM-V. The aim of this study was to examine the unidimensionality, reliability, validity, and clinical sensitivity of brief self-rated scales for specific anxiety disorders in an unselected German sample of consecutive attendees to a psychological clinic. These scales use a common template to assess core constructs of fear and anxiety. Dimensional scales for social anxiety disorder, specific phobia, agoraphobia, panic disorder, and generalized anxiety disorder were administered along with established scales to 102 adults seeking treatment for mental health problems at a German university outpatient clinic for psychotherapy. The computer-assisted clinical version of the Munich-Composite International Diagnostic Interview was used to assess mental disorders according to DSM-IV criteria. Dimensionality and scale reliability were examined using confirmatory factor analyses. Convergent and discriminant validity were examined by testing differences in the size of correlations between each dimensional anxiety scale and each of the previously validated scales. Each dimensional scale's ability to correctly differentiate between individuals with versus without an anxiety diagnosis was examined via the area under the curve. Analyses revealed unidimensionality for each scale, high reliability, and convergent and discriminant validity. Classification performance was good to excellent for all scales except for specific phobia. The application of the dimensional anxiety scales may be an effective way to screen for specific anxiety disorders and to supplement categorical diagnoses in DSM-V, although further evaluation and refinement of the scales (particularly the specific phobia scale) is needed. © 2012 Wiley Periodicals, Inc.

A survey on features of allergic rhinitis in children.

PubMed

Zicari, A M; Indinnimeo, L; De Castro, G; Incorvaia, C; Frati, F; Dell'Albani, I; Puccinelli, P; Scolari, M; Duse, M

2013-05-01

A number of epidemiologic studies evaluated the prevalence of allergic rhinitis (AR), but few data are available on its different clinical presentations. We addressed this survey to assess the features of AR in children and adolescents. Thirty-five centers in Italy included 2623 pediatric patients with rhinitis, of whom 2319 suffered from AR, while 304 had other kinds of rhinitis. For each patient a standardized questionnaire was filled in, including ARIA classification, the duration of symptoms, the allergen identified as clinically relevant, the co-morbidities, the kind of treatment, the response to treatment, the satisfaction with the treatment, and the feasibility of allergen immunotherapy (AIT). Of the 2319 patients, 597 (25.7%) had mild intermittent, 701 (30.2%) mild persistent, 174 (7.5%) moderate-severe intermittent, and 773 (33.3%) moderate-severe persistent AR. The allergens most relevant were grass pollen and dust mites. The most frequently used drugs were oral antihistamines (83.1%) and topical corticosteroids (63.5%). The response to treatment was judged as excellent in 13.5%, good in 45.1%, fair in 30.8%, poor in 10%, and very bad in 0.6% of cases. The satisfaction with treatment was judged as very satisfactory in 15.2%, satisfactory in 61.8%, unsatisfactory in 22.4%, and very unsatisfactory in 0.5% of cases. AIT was considered indicated in 53.1% of patients with mild intermittent, 79.2% of moderate-severe intermittent, 72.6% of mild persistent, and 82.7% of moderate-severe persistent AR. The limitation of this study is that the population was not unselected and this prevents epidemiological significance. These results offer confirmation of the adequacy of ARIA guidelines in classifying patients with AR and of the association of severe phenotype with lack of success of drug treatment.

[Peripheral lymphadenopathy in childhood--recommendations for diagnostic evaluation].

PubMed

Benesch, M; Kerbl, R; Wirnsberger, A; Stünzner, D; Mangge, H; Schenkeli, R; Deutsch, J

2000-01-01

Enlargement of peripheral lymph nodes most commonly caused by a local inflammatory process is frequently seen in childhood. The aim of the present study was to analyze the most common causes of peripheral lymphadenopathy and to develop a simple algorithm for the primary diagnostic evaluation of peripheral lymph node enlargement in this age group. Between April and September 1999 87 unselected children (median age: 5 1/2 years) with peripheral lymphadenopathy were referred to the Department of Pediatrics, University of Graz, for further investigation. EBV infection was diagnosed in 20 (23.0%) children. 19 (21.8%) patients had acute bacterial lymphadenitis. In 21 (24.1%) patients lymph node enlargement was classified as "post/parainfectious (viral)". Four patients each had toxoplasmosis and cat scratch disease. In 11 (12.6%) patients neither physical nor laboratory examinations revealed pathologic results. Among the remaining 8 children sarcoidosis and Hodgkin disease was diagnosed in one patient each. Small, soft, mobile, nontender, cervical, axillary or inguinal lymph nodes do not require further investigations. In case of enlarged, tender lymph nodes with overlying skin erythema and fever diagnostic evaluation should include complete blood count, erythrocyte sedimentation rate and/or c-reactive protein level, supplemented by appropriate antibody testing (EBV, CMV, Toxoplasma gondii, Bartonella henselae). Firm, enlarged, painless lymph nodes which are matted together and fixed to the skin or underlying tissues necessitate a more detailed diagnostic evaluation in order to exclude malignant or granulomatous diseases. Our study demonstrated that primary diagnostic evaluation of childhood peripheral lymphadenopathy is mainly based on clinical grounds. In most cases a small number of additionally performed laboratory tests allow to correctly identify the cause of the peripheral lymph node enlargement.

Derivation and Validation of a Risk Standardization Model for Benchmarking Hospital Performance for Health-Related Quality of Life Outcomes after Acute Myocardial Infarction

PubMed Central

Arnold, Suzanne V.; Masoudi, Frederick A.; Rumsfeld, John S.; Li, Yan; Jones, Philip G.; Spertus, John A.

2014-01-01

Background Before outcomes-based measures of quality can be used to compare and improve care, they must be risk-standardized to account for variations in patient characteristics. Despite the importance of health-related quality of life (HRQL) outcomes among patients with acute myocardial infarction (AMI), no risk-standardized models have been developed. Methods and Results We assessed disease-specific HRQL using the Seattle Angina Questionnaire at baseline and 1 year later in 2693 unselected AMI patients from 24 hospitals enrolled in the TRIUMPH registry. Using 57 candidate sociodemographic, economic, and clinical variables present on admission, we developed a parsimonious, hierarchical linear regression model to predict HRQL. Eleven variables were independently associated with poor HRQL after AMI, including younger age, prior CABG, depressive symptoms, and financial difficulties (R2=20%). The model demonstrated excellent internal calibration and reasonable calibration in an independent sample of 1890 AMI patients in a separate registry, although the model slightly over-predicted HRQL scores in the higher deciles. Among the 24 TRIUMPH hospitals, 1-year unadjusted HRQL scores ranged from 67–89. After risk-standardization, HRQL scores variability narrowed substantially (range=79–83), and the group of hospital performance (bottom 20%/middle 60%/top 20%) changed in 14 of the 24 hospitals (58% reclassification with risk-standardization). Conclusions In this predictive model for HRQL after AMI, we identified risk factors, including economic and psychological characteristics, associated with HRQL outcomes. Adjusting for these factors substantially altered the rankings of hospitals as compared with unadjusted comparisons. Using this model to compare risk-standardized HRQL outcomes across hospitals may identify processes of care that maximize this important patient-centered outcome. PMID:24163068

N-terminal pro-brain natriuretic peptide and high-sensitivity troponin T exhibit additive prognostic value for the outcome of critically ill patients.

PubMed

Lenz, Max; Krychtiuk, Konstantin A; Goliasch, Georg; Distelmaier, Klaus; Wojta, Johann; Heinz, Gottfried; Speidl, Walter S

2018-04-01

Patients treated at medical intensive care units suffer from various pathologies and often present with elevated troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Both markers may reflect different forms of cardiac involvement in critical illness. Therefore, the aim of our study was to examine the synergistic prognostic potential of NT-proBNP and high-sensitivity TnT (hs)TnT in unselected critically ill patients. We included all consecutive patients admitted to our intensive care unit within one year, excluding those suffering from acute myocardial infarction or undergoing cardiac surgery and measured NT-proBNP and TnT plasma levels on the day of admission and 72 hours thereafter. Of the included 148 patients, 52% were male, mean age was of 64.2 ± 16.8 years and 30-day mortality was 33.2%. Non-survivors showed significantly higher NT-proBNP and TnT plasma levels as compared with survivors ( p<0.01). An elevation of both markers exhibited an additive effect on mortality, as those with both NT-proBNP and TnT levels above the median had a 30-day mortality rate of 51.0%, while those with both markers below the median had a 16.7% mortality rate (hazard ratio 3.7). These findings were independent of demographic and clinical parameters ( p<0.05). Our findings regarding the individual predictive properties of NT-proBNP and TnT are in line with literature. However, we were able to highlight that they exhibit additive prognostic potential which exceeds their individual value. This might be attributed to a difference in underlying pathomechanisms and an assessment of synergistic risk factors.

Advanced ECG in 2016: is there more than just a tracing?

PubMed

Reichlin, Tobias; Abächerli, Roger; Twerenbold, Raphael; Kühne, Michael; Schaer, Beat; Müller, Christian; Sticherling, Christian; Osswald, Stefan

2016-01-01

The 12-lead electrocardiogram (ECG) is the most frequently used technology in clinical cardiology. It is critical for evidence-based management of patients with most cardiovascular conditions, including patients with acute myocardial infarction, suspected chronic cardiac ischaemia, cardiac arrhythmias, heart failure and implantable cardiac devices. In contrast to many other techniques in cardiology, the ECG is simple, small, mobile, universally available and cheap, and therefore particularly attractive. Standard ECG interpretation mainly relies on direct visual assessment. The progress in biomedical computing and signal processing, and the available computational power offer fascinating new options for ECG analysis relevant to all fields of cardiology. Several digital ECG markers and advanced ECG technologies have shown promise in preliminary studies. This article reviews promising novel surface ECG technologies in three different fields. (1) For the detection of myocardial ischaemia and infarction, QRS morphology feature analysis, the analysis of high frequency QRS components (HF-QRS) and methods using vectorcardiography as well as ECG imaging are discussed. (2) For the identification and management of patients with cardiac arrhythmias, methods of advanced P-wave analysis are discussed and the concept of ECG imaging for noninvasive localisation of cardiac arrhythmias is presented. (3) For risk stratification of sudden cardiac death and the selection of patients for medical device therapy, several novel markers including an automated QRS-score for scar quantification, the QRS-T angle or the T-wave peak-to-end-interval are discussed. Despite the existing preliminary data, none of the advanced ECG markers and technologies has yet accomplished the transition into clinical practice. Further refinement of these technologies and broader validation in large unselected patient cohorts are the critical next step needed to facilitate translation of advanced ECG technologies into clinical cardiology.

The horizontal computerized rotational impulse test.

PubMed

Furman, Joseph M; Shirey, Ian; Roxberg, Jillyn; Kiderman, Alexander

2016-01-01

Whole-body impulsive rotations were used to overcome several limitations associated with manual head impulse testing. A computer-controlled rotational chair delivered brief, whole-body, earth-vertical axis yaw impulsive rotations while eye movements were measured using video-oculography. Results from an unselected group of 20 patients with dizziness and a group of 22 control subjects indicated that the horizontal computerized rotational head impulse test (crHIT) is well-tolerated and provides an estimate of unidirectional vestibulo-ocular reflex gain comparable to results from caloric testing. This study demonstrates that the horizontal crHIT is a new assessment tool that overcomes many of the limitations of manual head impulse testing and provides a reliable laboratory-based measure of unilateral horizontal semicircular canal function.

Effect of Using the HEART Score in Patients With Chest Pain in the Emergency Department: A Stepped-Wedge, Cluster Randomized Trial.

PubMed

Poldervaart, Judith M; Reitsma, Johannes B; Backus, Barbra E; Koffijberg, Hendrik; Veldkamp, Rolf F; Ten Haaf, Monique E; Appelman, Yolande; Mannaerts, Herman F J; van Dantzig, Jan-Melle; van den Heuvel, Madelon; El Farissi, Mohamed; Rensing, Bernard J W M; Ernst, Nicolette M S K J; Dekker, Ineke M C; den Hartog, Frank R; Oosterhof, Thomas; Lagerweij, Ghizelda R; Buijs, Eugene M; van Hessen, Maarten W J; Landman, Marcel A J; van Kimmenade, Roland R J; Cozijnsen, Luc; Bucx, Jeroen J J; van Ofwegen-Hanekamp, Clara E E; Cramer, Maarten-Jan; Six, A Jacob; Doevendans, Pieter A; Hoes, Arno W

2017-05-16

The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score is an easy-to-apply instrument to stratify patients with chest pain according to their short-term risk for major adverse cardiac events (MACEs), but its effect on daily practice is unknown. To measure the effect of use of the HEART score on patient outcomes and use of health care resources. Stepped-wedge, cluster randomized trial. (ClinicalTrials.gov: NCT01756846). Emergency departments in 9 Dutch hospitals. Unselected patients with chest pain presenting at emergency departments in 2013 and 2014. All hospitals started with usual care. Every 6 weeks, 1 hospital was randomly assigned to switch to "HEART care," during which physicians calculated the HEART score to guide patient management. For safety, a noninferiority margin of a 3.0% absolute increase in MACEs within 6 weeks was set. Other outcomes included use of health care resources, quality of life, and cost-effectiveness. A total of 3648 patients were included (1827 receiving usual care and 1821 receiving HEART care). Six-week incidence of MACEs during HEART care was 1.3% lower than during usual care (upper limit of the 1-sided 95% CI, 2.1% [within the noninferiority margin of 3.0%]). In low-risk patients, incidence of MACEs was 2.0% (95% CI, 1.2% to 3.3%). No statistically significant differences in early discharge, readmissions, recurrent emergency department visits, outpatient visits, or visits to general practitioners were observed. Physicians were hesitant to refrain from admission and diagnostic tests in patients classified as low risk by the HEART score. Using the HEART score during initial assessment of patients with chest pain is safe, but the effect on health care resources is limited, possibly due to nonadherence to management recommendations. Netherlands Organisation for Health Research and Development.

Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3.

PubMed

Modest, D P; Denecke, T; Pratschke, J; Ricard, I; Lang, H; Bemelmans, M; Becker, T; Rentsch, M; Seehofer, D; Bruns, C J; Gebauer, B; Modest, H I; Held, S; Folprecht, G; Heinemann, V; Neumann, U P

2018-01-01

The FIRE-3 trial investigated combination chemotherapy plus either cetuximab or bevacizumab in patients with untreated metastatic colorectal cancer (mCRC) not scheduled for upfront surgery. We aimed to determine the number of patients who present with potentially resectable disease during systemic first-line therapy and to compare the findings with study reports concerning resections and outcome. This evaluation of 448 patients was performed as central review blinded for treatment, other reviewers' evaluations and conducted interventions. Resectability was defined if at least 50% of the reviewers recommended surgical-based intervention. Overall survival was assessed by Kaplan-Meier method. Resectability increased from 22% (97/448) at baseline before treatment to 53% (238/448) at best response (P < 0.001), compared with an actual secondary resection rate for metastases of 16% (72/448). At baseline (23% versus 20%) and best response (53% versus 53%), potential resectability of metastases in this molecular unselected population was similar in cetuximab-treated patients versus bevacizumab-treated patients and not limited to patients with one-organ disease. The actual resection rate of metastases was significantly associated with treatment setting (P = 0.02; university hospital versus hospital/practice). Overall survival was 51.3 months (95% confidence interval [CI] 35.9-66.7) in patients with resectable disease who received surgery, 30.8 months (95% CI 26.6-34.9) in patients with resectable disease without surgery and 18.6 months (95% CI 15.8-21.3) in patients with unresectable disease (P < 0.001). Our findings illustrate the potential for conversion to resectability in mCRC, certain reluctance towards metastatic resections in clinical practice and the need for pre-planned and continuous evaluation for metastatic resection in high-volume centres. CLINICALTRIALS. NCT00433927. Copyright © 2017 Elsevier Ltd. All rights reserved.

Screening for germline mutations of MLH1, MSH2, MSH6 and PMS2 genes in Slovenian colorectal cancer patients: implications for a population specific detection strategy of Lynch syndrome.

PubMed

Berginc, Gasper; Bracko, Matej; Ravnik-Glavac, Metka; Glavac, Damjan

2009-01-01

Microsatellite instability (MSI) is present in more than 90% of colorectal cancers of patients with Lynch syndrome, and is therefore a feasible marker for the disease. Mutations in MLH1, MSH2, MSH6 and PMS2, which are one of the main causes of deficient mismatch repair and subsequent MSI, have been linked to the disease. In order to establish the role of each of the 4 genes in Slovenian Lynch syndrome patients, we performed MSI analysis on 593 unselected CRC patients and subsequently searched for the presence of point mutations, larger genomic rearrangements and MLH1 promoter hypermethylation in patients with MSI-high tumours. We detected 43 (7.3%) patients with MSI-H tumours, of which 7 patients (1.3%) harboured germline defects: 2 in MLH1, 4 in MSH2, 1 in PMS2 and none in MSH6. Twenty-nine germline sequence variations of unknown significance and 17 deleterious somatic mutations were found. MLH1 promoter methylation was detected in 56% of patients without detected germline defects and in 1 (14%) suspected Lynch syndrome. Due to the minor role of germline MSH6 mutations, we adapted the Lynch syndrome detection strategy for the Slovenian population of CRC patients, whereby germline alterations should be first sought in MLH1 and MSH2 followed by a search for larger genomic rearrangements in these two genes. When no germline mutations are found tumors should be further tested for the presence of germline defects in PMS2 and MSH6. The choice about which gene should be tested first can be guided more accurately by the immunohistochemical analysis. Our study demonstrates that the incidence of MMR mutations in a population should be known prior to the application of one of several suggested strategies for detection of Lynch syndrome.

The influence of social environment in early life on the behavior, stress response, and reproductive system of adult male Norway rats selected for different attitudes to humans.

PubMed

Gulevich, R G; Shikhevich, S G; Konoshenko, M Yu; Kozhemyakina, R V; Herbeck, Yu E; Prasolova, L A; Oskina, I N; Plyusnina, I Z

2015-05-15

The influence of social disturbance in early life on behavior, response of blood corticosterone level to restraint stress, and endocrine and morphometric indices of the testes was studied in 2-month Norway rat males from three populations: not selected for behavior (unselected), selected for against aggression to humans (tame), and selected for increased aggression to humans (aggressive). The experimental social disturbance included early weaning, daily replacement of cagemates from days 19 to 25, and subsequent housing in twos till the age of 2months. The social disturbance increased the latent period of aggressive behavior in the social interaction test in unselected males and reduced relative testis weights in comparison to the corresponding control groups. In addition, experimental unselected rats had smaller diameters of seminiferous tubules and lower blood testosterone levels. In the experimental group, tame rats had lower basal corticosterone levels, and aggressive animals had lower hormone levels after restraint stress in comparison to the control. The results suggest that the selection in two directions for attitude to humans modifies the response of male rats to social disturbance in early life. In this regard, the selected rat populations may be viewed as a model for investigation of (1) neuroendocrinal mechanisms responsible for the manifestation of aggression and (2) interaction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems in stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Retrospective study evaluating the performance of a first-trimester combined screening for trisomy 21 in an Italian unselected population

PubMed Central

Padula, Francesco; Cignini, Pietro; Giannarelli, Diana; Brizzi, Cristiana; Coco, Claudio; D’Emidio, Laura; Giorgio, Elsa; Giorlandino, Maurizio; Mangiafico, Lucia; Mastrandrea, Marialuisa; Milite, Vincenzo; Mobili, Luisa; Nanni, Cinzia; Raffio, Raffaella; Taramanni, Cinzia; Vigna, Roberto; Mesoraca, Alvaro; Bizzoco, Domenico; Gabrielli, Ivan; Di Giacomo, Gianluca; Barone, Maria Antonietta; Cima, Antonella; Giorlandino, Francesca Romana; Emili, Sabrina; Cupellaro, Marina; Giorlandino, Claudio

2014-01-01

Objectives to assess the performance of a combined first-trimester screening for trisomy 21 in an unselected Italian population referred to a specialized private center for prenatal medicine. Methods a retrospective validation of first-trimester screening algorithms [risk calculation based on maternal age and nuchal translucency (NT) alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both] for fetal aneuploidies evaluated in an unselected Italian population at Artemisia Fetal-Maternal Medical Centre in Rome. All measurements were performed between 11+0 and 13+6 weeks of gestation, between April 2007 and December 2008. Results of 3,610 single fetuses included in the study, we had a complete follow-up on 2,984. Fourteen of 17 cases of trisomy 21 were detected when a cut-off of 1:300 was applied [detection rate (DR) 82.4%, 95% confidence interval (CI) 64.2–100; false-positive rate (FPR) 4.7%, 95% CI 3.9–5.4; false-negative rate (FNR) 17.6%, 95% CI 0–35.8%]. Conclusion in our study population the detection rate for trisomy 21, using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free β-hCG levels, was superior to the application of either parameter alone. The algorithm has been validated for first trimester screening in the Italian population. PMID:26266002

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants

PubMed Central

Buchanan, Adam H; Manickam, Kandamurugu; Meyer, Michelle N; Wagner, Jennifer K; Hallquist, Miranda L G; Williams, Janet L; Rahm, Alanna Kulchak; Williams, Marc S; Chen, Zong-Ming E; Shah, Chaitali K; Garg, Tullika K; Lazzeri, Amanda L; Schwartz, Marci L B; Lindbuchler, D'Andra M; Fan, Audrey L; Leeming, Rosemary; Servano, Pedro O; Smith, Ashlee L; Vogel, Victor G; Abul-Husn, Noura S; Dewey, Frederick E; Lebo, Matthew S; Mason-Suares, Heather M; Ritchie, Marylyn D; Davis, F Daniel; Carey, David J; Feinberg, David T; Faucett, W Andrew; Ledbetter, David H; Murray, Michael F

2018-01-01

Purpose The clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility. Methods Whole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient–participants and their clinicians. We queried patient–participants’ electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient–participants of eligible age who had begun risk management. Results Thirty-seven MyCode patient–participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer—including a stage 1C fallopian tube cancer—via these procedures. Conclusion Screening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility. PMID:29261187

Effect of Artificial Selection on Runs of Homozygosity in U.S. Holstein Cattle

PubMed Central

Kim, Eui-Soo; Cole, John B.; Huson, Heather; Wiggans, George R.; Van Tassell, Curtis P.; Crooker, Brian A.; Liu, George; Da, Yang; Sonstegard, Tad S.

2013-01-01

The intensive selection programs for milk made possible by mass artificial insemination increased the similarity among the genomes of North American (NA) Holsteins tremendously since the 1960s. This migration of elite alleles has caused certain regions of the genome to have runs of homozygosity (ROH) occasionally spanning millions of continuous base pairs at a specific locus. In this study, genome signatures of artificial selection in NA Holsteins born between 1953 and 2008 were identified by comparing changes in ROH between three distinct groups under different selective pressure for milk production. The ROH regions were also used to estimate the inbreeding coefficients. The comparisons of genomic autozygosity between groups selected or unselected since 1964 for milk production revealed significant differences with respect to overall ROH frequency and distribution. These results indicate selection has increased overall autozygosity across the genome, whereas the autozygosity in an unselected line has not changed significantly across most of the chromosomes. In addition, ROH distribution was more variable across the genomes of selected animals in comparison to a more even ROH distribution for unselected animals. Further analysis of genome-wide autozygosity changes and the association between traits and haplotypes identified more than 40 genomic regions under selection on several chromosomes (Chr) including Chr 2, 7, 16 and 20. Many of these selection signatures corresponded to quantitative trait loci for milk, fat, and protein yield previously found in contemporary Holsteins. PMID:24348915

Humans identify negative (but not positive) arousal in silver fox vocalizations: implications for the adaptive value of interspecific eavesdropping.

PubMed

Filippi, Piera; Gogoleva, Svetlana S; Volodina, Elena V; Volodin, Ilya A; de Boer, Bart

2017-08-01

The ability to identify emotional arousal in heterospecific vocalizations may facilitate behaviors that increase survival opportunities. Crucially, this ability may orient inter-species interactions, particularly between humans and other species. Research shows that humans identify emotional arousal in vocalizations across multiple species, such as cats, dogs, and piglets. However, no previous study has addressed humans' ability to identify emotional arousal in silver foxes. Here, we adopted low- and high-arousal calls emitted by three strains of silver fox-Tame, Aggressive, and Unselected-in response to human approach. Tame and Aggressive foxes are genetically selected for friendly and attacking behaviors toward humans, respectively. Unselected foxes show aggressive and fearful behaviors toward humans. These three strains show similar levels of emotional arousal, but different levels of emotional valence in relation to humans. This emotional information is reflected in the acoustic features of the calls. Our data suggest that humans can identify high-arousal calls of Aggressive and Unselected foxes, but not of Tame foxes. Further analyses revealed that, although within each strain different acoustic parameters affect human accuracy in identifying high-arousal calls, spectral center of gravity, harmonic-to-noise ratio, and F0 best predict humans' ability to discriminate high-arousal calls across all strains. Furthermore, we identified in spectral center of gravity and F0 the best predictors for humans' absolute ratings of arousal in each call. Implications for research on the adaptive value of inter-specific eavesdropping are discussed.

Epigenetic Alterations in Density Selected Human Spermatozoa for Assisted Reproduction.

PubMed

Yu, Bolan; Zhou, Hua; Liu, Min; Zheng, Ting; Jiang, Lu; Zhao, Mei; Xu, Xiaoxie; Huang, Zhaofeng

2015-01-01

Epidemiological evidence indicates that assisted reproductive technologies (ART) may be associated with several epigenetic diseases such as Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS). Selection of sperm by density-gradients in ART has improved DNA integrity and sperm quality; however, epigenetic alterations associated with this approach are largely unknown. In the present study, we investigated DNA methylation and histone retention profiles in raw sperm and selected sperm derived from the same individual and separated by using density-gradients. Results from a study group consisting of 93 males demonstrated that both global DNA methylation and histone retention levels decreased in density selected sperm. Compared to unselected raw sperm, histone transition rates decreased by an average of 27.2% in selected sperm, and the global methylation rate was 3.8% in unselected sperm and 3.3% in the selected sperm. DNA methylation and histone retention location profiling analyses suggested that these alterations displayed specific location patterns in the human genome. Changes in the pattern of hypomethylation largely occurred in transcriptional factor gene families such as HOX, FOX, and GATA. Histone retention increased in 67 genes, whereas it was significantly clustered in neural development-related gene families, particularly the olfactory sensor gene family. Although a causative relationship could not be established, the results of the present study suggest the possibility that sperm with good density also possess unique epigenetic profiles, particularly for genes involved in neural and olfactory development. As increasing evidence demonstrates that epigenetics plays a key role in embryonic development and offspring growth characteristics, the specific epigenetic alterations we observed in selected sperm may influence the transcriptional process and neural development in embryos.

Epigenetic Alterations in Density Selected Human Spermatozoa for Assisted Reproduction

PubMed Central

Yu, Bolan; Zhou, Hua; Liu, Min; Zheng, Ting; Jiang, Lu; Zhao, Mei; Xu, Xiaoxie; Huang, Zhaofeng

2015-01-01

Epidemiological evidence indicates that assisted reproductive technologies (ART) may be associated with several epigenetic diseases such as Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS). Selection of sperm by density-gradients in ART has improved DNA integrity and sperm quality; however, epigenetic alterations associated with this approach are largely unknown. In the present study, we investigated DNA methylation and histone retention profiles in raw sperm and selected sperm derived from the same individual and separated by using density-gradients. Results from a study group consisting of 93 males demonstrated that both global DNA methylation and histone retention levels decreased in density selected sperm. Compared to unselected raw sperm, histone transition rates decreased by an average of 27.2% in selected sperm, and the global methylation rate was 3.8% in unselected sperm and 3.3% in the selected sperm. DNA methylation and histone retention location profiling analyses suggested that these alterations displayed specific location patterns in the human genome. Changes in the pattern of hypomethylation largely occurred in transcriptional factor gene families such as HOX, FOX, and GATA. Histone retention increased in 67 genes, whereas it was significantly clustered in neural development-related gene families, particularly the olfactory sensor gene family. Although a causative relationship could not be established, the results of the present study suggest the possibility that sperm with good density also possess unique epigenetic profiles, particularly for genes involved in neural and olfactory development. As increasing evidence demonstrates that epigenetics plays a key role in embryonic development and offspring growth characteristics, the specific epigenetic alterations we observed in selected sperm may influence the transcriptional process and neural development in embryos. PMID:26709917

The impact of prophylactic fresh-frozen plasma and cryoprecipitate on the incidence of central nervous system thrombosis and hemorrhage in children with acute lymphoblastic leukemia receiving asparaginase.

PubMed

Abbott, Lesleigh S; Deevska, Mariana; Fernandez, Conrad V; Dix, David; Price, Victoria E; Wang, Hao; Parker, Louise; Yhap, Margaret; Fitzgerald, Colleen; Barnard, Dorothy R; Berman, Jason N

2009-12-10

Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG). Potential toxicities include central nervous system thrombosis (CNST) and hemorrhage. Historical practice at the Izaak Walton Killam Health Centre (IWK) involves measuring AT and FG levels after ASP administration and transfusing fresh-frozen plasma (FFP) or cryoprecipitate (CRY) to prevent thrombotic and hemorrhagic complications. To determine whether this reduced these complications in children with acute lymphoblastic leukemia (ALL), incidence, outcome, and clinical characteristics of ASP-related CNST in ALL patients at IWK were compared with a similar cohort from BC Children's Hospital (BCCH), where prophylaxis was not performed. Costs associated with preventative versus expectant management were estimated. From 1990 to 2005, 240 patients were treated at IWK and 479 at BCCH. Seven BCCH patients developed venous CNST (1.5%), compared with none at IWK. CNST occurred exclusively during induction. Six patients received anticoagulation and continued ASP. All 7 patients remain in remission. National Cancer Institute high-risk ALL predicted CNST risk (P = .02), whereas sex, age, race, and body mass index did not. Neither FFP nor CRY protected against CNST, suggesting prophylaxis is unwarranted for unselected ALL patients. However, prophylactic replacement for HR patients in induction may be cost-effective.

Tumor necrosis factor-α promoter -308/238 polymorphism association with less severe disease in ankylosing spondylitis is unrelated to serum TNF-α and does not predict TNF inhibitor response.

PubMed

Nossent, Johannes C; Sagen-Johnsen, Sylvia; Bakland, Gunnstein

2014-08-01

Despite the clinical efficacy of tumor necrosis factor inhibitors (TNFi), the manner in which TNF-α contributes to disease in patients with ankylosing spondylitis (AS) remains unresolved. We investigated the relationship between TNF-α gene promoter region polymorphism, serum TNF-α levels, and clinical phenotype. We did a cross-sectional and longitudinal cohort study in TNFi-naive patients with AS (n = 335). Clinical data and biological samples were collected during a research visit with genotyping for TNF-α -238 A/G and -308 A/G performed by Taqman RT-PCR and TNF levels determined by sandwich ELISA. Longitudinal TNF levels were monitored in unselected patients (n = 61). TNF-α -308 GA/AA genotype was present in 14% and TNF-α -238 GA/AA genotype in 1% of patients. TNF-α -308 GA/AA genotype was associated with a reduced risk of uveitis and better spinal function, while TNF-α -238 GA/AA genotype was associated with later age of onset and lower erythrocyte sedimentation rate (ESR). Serum TNF-α level was lower in patients with AS (151 pg/ml) than in controls (263 pg/ml), because more patients with AS had undetectable serum TNF-α (66 vs 25%, p < 0.001). TNFi treatment did not influence serum TNF-α. There was no effect of TNF-α -308/-238 or HLA-B27 genotype on serum TNF-α or subsequent initiation of TNFi. TNF-α -238 or -308 GA/AA genotypes in patients with AS are associated with signs of less severe disease. Serum TNF-α is, however, undetectable in two-thirds of patients with AS and is not influenced by TNF-α promoter genotype or TNFi therapy. These data suggest a more significant role for TNF-α at local sites of inflammation in AS than through systemic effects.

Predictive value of anaemia for tuberculosis in HIV-infected patients in sub-Saharan Africa: an indication for routine microbiological investigation using new rapid assays

PubMed Central

Kerkhoff, Andrew D.; Wood, Robin; Vogt, Monica; Lawn, Stephen D.

2014-01-01

Background The relationship between anaemia and undiagnosed tuberculosis (TB) in patients living with HIV in sub-Saharan Africa is incompletely defined. We assessed the prevalence of TB among those with HIV-related anaemia and evaluated new means of rapid TB diagnosis. Methodology Blood haemoglobin levels were measured in unselected antiretroviral treatment (ART)-naïve patients in Cape Town, South Africa, and anaemia was classified according to WHO criteria. All patients were screened for TB by testing paired sputum samples using liquid culture (reference standard), fluorescence microscopy and Xpert MTB/RIF. Urine samples were tested for lipoarabinomannan (LAM) using the Determine TB-LAM diagnostic assay. Results Of 602 adults screened, 485 had complete results. Normal haemoglobin levels were found in 44.5% (n=216) of patients and mild, moderate or severe anaemia were present in 24.9% (n=121), 25.4% (n=123) and 5.2% (n=25) of patients, respectively. Culture-confirmed pulmonary TB was diagnosed in 8.8% (19/216) of those without anaemia compared to 16.5% (20/121), 26.0% (32/123) and 40.0% (10/25) with mild, moderate or severe anaemia, respectively (p<0.001). Anaemia was a strong independent predictor of TB. The sensitivities of diagnostic assays were much higher among those with moderate/severe anaemia compared to those with no/mild anaemia using sputum microscopy (42.9% vs 15.4%); urine LAM (54.8% vs 0%); sputum microscopy plus urine LAM (71.4% vs 15.4%) and sputum Xpert (73.8% vs 41.0%) (P<0.01 for all). Conclusions A very high prevalence of undiagnosed TB was found in patients with moderate or severe anaemia. Such patients should be prioritized for routine microbiological investigation using rapid diagnostic assays. PMID:24346639

Invasive strategy and frailty in very elderly patients with acute coronary syndromes.

PubMed

Llaó, Isaac; Ariza-Solé, Albert; Sanchis, Juan; Alegre, Oriol; López-Palop, Ramon; Formiga, Francesc; Marín, Francisco; Vidán, María T; Martínez-Sellés, Manuel; Sionis, Alessandro; Vives-Borrás, Miguel; Gómez-Hospital, Joan Antoni; Gómez-Lara, Josep; Roura, Gerard; Díez-Villanueva, Pablo; Núñez-Gil, Iván; Maristany, Jaume; Asmarats, Lluis; Bueno, Héctor; Abu-Assi, Emad; Cequier, Àngel

2018-04-03

Current guidelines recommend an early invasive strategy in patients with non-ST segment elevation acute coronary syndromes (NSTEACS). The role of an invasive strategy in frail elderly patients remains controversial. The LONGEVO-SCA registry included unselected NSTEACS patients aged ≥80 years. A geriatric assessment was performed during hospitalization, including frailty. We evaluated the impact of an invasive strategy during the admission on the incidence of cardiac death, reinfarction or new revascularisation at 6-months. From 531 patients included, 145 (27.3%) were frail. Mean age was 84.3 years. Most patients underwent an invasive strategy (407/531, 76.6%). Patients undergoing an invasive strategy were younger and had lower proportion of frailty (23.3% vs 40.3%, p<0.001). The incidence of cardiac events was more common in patients managed conservatively, after adjusting for confounding factors (sub-Hazard ratio (sHR) 2.32, 95% confidence interval (CI) 1.26-4.29, p=0.007). This association remained significant in non-frail patients (sHR 3.85, 95% CI 2.13-6.95, p=0.001), but was not significant in patients with established frailty criteria (sHR 1.40, 95% CI 0.72-2.75, p=0.325). The interaction invasive strategy-frailty was significant (p=0.032) Conclusions: An invasive strategy was independently associated with better outcomes in very elderly patients with NSTEACS. This association was different according to frailty status.

Acoustic (loudspeaker) facial EMG monitoring: II. Use of evoked EMG activity during acoustic neuroma resection.

PubMed

Prass, R L; Kinney, S E; Hardy, R W; Hahn, J F; Lüders, H

1987-12-01

Facial electromyographic (EMG) activity was continuously monitored via loudspeaker during eleven translabyrinthine and nine suboccipital consecutive unselected acoustic neuroma resections. Ipsilateral facial EMG activity was synchronously recorded on the audio channels of operative videotapes, which were retrospectively reviewed in order to allow detailed evaluation of the potential benefit of various acoustic EMG patterns in the performance of specific aspects of acoustic neuroma resection. The use of evoked facial EMG activity was classified and described. Direct local mechanical (surgical) stimulation and direct electrical stimulation were of benefit in the localization and/or delineation of the facial nerve contour. Burst and train acoustic patterns of EMG activity appeared to indicate surgical trauma to the facial nerve that would not have been appreciated otherwise. Early results of postoperative facial function of monitored patients are presented, and the possible value of burst and train acoustic EMG activity patterns in the intraoperative assessment of facial nerve function is discussed. Acoustic facial EMG monitoring appears to provide a potentially powerful surgical tool for delineation of the facial nerve contour, the ongoing use of which may lead to continued improvement in facial nerve function preservation through modification of dissection strategy.

Elevated total plasma homocysteine and 667C{r_arrow}T mutation of the 5,10-methylenetetrahydrofolate reductase gene in thrombotic vascular disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Franchis, R.; Sebastio, G.; Andria, G.

1996-07-01

Moderate elevation of total plasma homocysteine (tHcy) has been reported as an independent risk factor for thrombotic vascular disease, a well-known multifactorial disorder. Possible genetic causes of elevated tHcy include defects of the sulfur-containing amino acids metabolism due to deficiencies of cystathionine {Beta}-synthase, of 5,10-methylenetetrahydrofolate reductase (MTHFR), and of the enzymes of cobalamin metabolism. An impaired activity of MTHFR due to a thermolabile form of the enzyme has been observed in {le}28% of hyperhomocysteinemic patients with premature vascular disease. More recently, the molecular basis of such enzymatic thermolability has been related to a common mutation of the MTHFR gene, causingmore » a C-to-T substitution at nt 677 (677C{r_arrow}T). This mutation was found in 38% of unselected chromosomes from 57 French Canadian individuals. The homozygous state for the mutation was present in 12% of these subjects and correlated with significantly elevated tHcy. Preliminary evidence indicates that the frequency of homozygotes for the 677C{r_arrow}T mutation may vary significantly in populations from different geographic areas. 5 refs., 2 tabs.« less

Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PubMed

Helbig, Katherine L; Farwell Hagman, Kelly D; Shinde, Deepali N; Mroske, Cameron; Powis, Zöe; Li, Shuwei; Tang, Sha; Helbig, Ingo

2016-09-01

To assess the yield of diagnostic exome sequencing (DES) and to characterize the molecular findings in characterized and novel disease genes in patients with epilepsy. In an unselected sample of 1,131 patients referred for DES, overall results were compared between patients with and without epilepsy. DES results were examined based on age of onset and epilepsy diagnosis. Positive/likely positive results were identified in 112/293 (38.2%) epilepsy patients compared with 210/732 (28.7%) patients without epilepsy (P = 0.004). The diagnostic yield in characterized disease genes among patients with epilepsy was 33.4% (105/314). KCNQ2, MECP2, FOXG1, IQSEC2, KMT2A, and STXBP1 were most commonly affected by de novo alterations. Patients with epileptic encephalopathies had the highest rate of positive findings (43.4%). A likely positive novel genetic etiology was proposed in 14/200 (7%) patients with epilepsy; this frequency was highest in patients with epileptic encephalopathies (17%). Three genes (COQ4, DNM1, and PURA) were initially reported as likely positive novel disease genes and were subsequently corroborated in independent peer-reviewed publications. DES with analysis and interpretation of both characterized and novel genetic etiologies is a useful diagnostic tool in epilepsy, particularly in severe early-onset epilepsy. The reporting on novel genetic etiologies may further increase the diagnostic yield.Genet Med 18 9, 898-905.

Prevalence of obstructive sleep apnea in patients with chronic wounds.

PubMed

Patt, Brian T; Jarjoura, David; Lambert, Lynn; Roy, Sashwati; Gordillo, Gayle; Schlanger, Richard; Sen, Chandan K; Khayat, Rami N

2010-12-15

Chronic non-healing wounds are a major human and economic burden. Obstructive sleep apnea (OSA) is prevalent in patients with obesity, diabetes, aging, and cardiovascular disease, all of which are risk factors for chronic wounds. We hypothesized that OSA would have more prevalence in patients of a wound center than the general middle-aged population. Consecutive patients of the Ohio State University Comprehensive Wound Center (CWC) were surveyed with the Berlin and Epworth questionnaires. In the second stage of the protocol, 50 consecutive unselected CWC patients with lower extremity wounds underwent home sleep studies. In 249 patients of the CWC who underwent the survey study, OSA had been previously diagnosed in only 22%. The prevalence of high-risk status based on questionnaires for OSA was 46% (95% CI 40%, 52%). In the 50 patients who underwent home sleep studies, and using an apnea hypopnea index of 15 events per hour, the prevalence of OSA was 57% (95% CI 42%, 71%). There was no difference between the Berlin questionnaire score and weight between patients with OSA and those without. The prevalence of OSA in patients with chronic wounds exceeds the estimated prevalence of OSA in the general middle aged population. This study identifies a previously unrecognized population with high risk for OSA. Commonly used questionnaires were not sufficiently sensitive for the detection of high risk status for OSA in this patient population.

Brain Gut Microbiome Interactions and Functional Bowel Disorders

PubMed Central

Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

2014-01-01

Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

Minimal Residual Disease Assessment and Risk-based Therapy in Acute Lymphoblastic Leukemia.

PubMed

Bassan, Renato; Intermesoli, Tamara; Scattolin, Annamaria; Viero, Piera; Maino, Elena; Sancetta, Rosaria; Carobolante, Francesca; Gianni, Francesca; Stefanoni, Paola; Tosi, Manuela; Spinelli, Orietta; Rambaldi, Alessandro

2017-07-01

The study of minimal residual disease (MRD) in adult patients with acute lymphoblastic leukemia (ALL) allows a greater refinement of the individual risk classification and is the best support for risk-specific therapy with or without allogeneic hematopoietic cell transplantation (HCT). Using case-specific sensitive molecular probes or multiparametric flow cytometry on marrow samples obtained from the end of induction until midconsolidation, MRD assays can detect up to 1 leukemic cell of 10,000 total mononuclear cells (sensitivity, 0.01%; ie, ≥10 4 ). This cutoff, presently bound to technical limitations and subject to improvement, reflects the individual chemosensitivity and is strongly correlated with treatment outcome. The chance for cure is approximately 70% in the MRD-negative subset but only 20% to 30% in MRD-positive patients, in any diagnostic and risk subset. As shown by prospective trials from Germany, Italy, Spain, and France-Switzerland-Belgium, approximately 50% to 70% of unselected adult patients with Philadelphia-negative ALL achieve and maintain an early MRD response, whereas the remainder do not, including a substantial proportion of clinically standard-risk patients, and require an HCT to avert at least partially the risk of relapse. Along with the diffusion of more effective "pediatric-inspired" chemotherapy programs, the MRD analysis is an integral part of a modern management strategy, guiding the decision process to transplant or not, in which case nonrelapse mortality using HCT in first remission-still 10% to 20%-is totally abolished. The use of new agents such as monoclonal antibodies, small inhibitors, and chimeric antigen receptor T cells is opening a new era of MRD-directed therapies, that will further increase survival rates. Copyright © 2017 Elsevier Inc. All rights reserved.

Suicide and other causes of mortality in bipolar disorder: a longitudinal study.

PubMed

Dutta, Rina; Boydell, Jane; Kennedy, Noel; VAN Os, Jim; Fearon, Paul; Murray, Robin M

2007-06-01

The high risk of suicide in bipolar disorder is well recognized, but may have been overestimated. There is conflicting evidence about deaths from other causes and little known about risk factors for suicide. We aimed to estimate suicide and mortality rates in a cohort of bipolar patients and to identify risk factors for suicide. All patients who presented for the first time with a DSM-IV diagnosis of bipolar I disorder in a defined area of southeast London over a 35-year period (1965-1999) were identified. Mortality rates were compared with those of the 1991 England and Wales population, indirectly standardized for age and gender. Univariate and multivariate analyses were used to test potential risk factors for suicide. Of the 239 patients in the cohort, 235 (98.3%) were traced. Forty-two died during the 4422 person-years of follow-up, eight from suicide. The standardized mortality ratio (SMR) for suicide was 9.77 [95% confidence interval (CI) 4.22-19.24], which, although significantly elevated compared to the general population, represented a lower case fatality than expected from previous literature. Deaths from all other causes were not excessive for the age groups studied in this cohort. Alcohol abuse [hazard ratio (HR) 6.81, 95% CI 1.69-27.36, p=0.007] and deterioration from pre-morbid level of functioning up to a year after onset (HR 5.20, 95% CI 1.24-21.89, p=0.024) were associated with increased risk of suicide. Suicide is significantly increased in unselected bipolar patients but actual case fatality is not as high as previously claimed. A history of alcohol abuse and deterioration in function predict suicide in bipolar disorder.

Clinical application of inert gas Multiple Breath Washout in children and adolescents with asthma.

PubMed

Zwitserloot, Annelies; Fuchs, Susanne I; Müller, Christina; Bisdorf, Kornelia; Gappa, Monika

2014-09-01

Children with asthma often have normal spirometry despite significant disease. The pathology of the small airways in asthma may be assessed using Multiple Breath Washout (MBW) and calculating the Lung Clearance Index (LCI). There are only few studies using MBW in children with asthma and existing data regarding bronchodilator effect are contradictory. The aim of the present pilot study was to compare LCI in asthma and controls and assess the effect of salbutamol in children with asthma on the LCI. Unselected patients with a diagnosis of asthma visiting the outpatient department of our hospital between 04-2010 and 03-2011 were recruited and compared to a healthy control group. MBW was performed as inert gas MBW using sulfurhexafluorid (SF6) as the tracer gas. Clinical data were documented and spirometry and MBW (EasyOne Pro, MBW module, NDD Switzerland) were performed before and after the use of salbutamol (200-400 μg). Healthy controls performed baseline MBW only. 32 children diagnosed with asthma (4.7-17.4 years) and 42 controls (5.3-20.8) were included in the analysis. LCI differed between patients and controls, with a mean LCI (SD) of 6.48 (0.48) and 6.21 (0.38) (P = 0.008). Use of salbutamol had no significant effect on LCI for the group. These pilot data show that clinically stable asthma patients and controls both have a LCI in the normal range. However, in patients the LCI is significantly higher indicating that MBW may have a role in assessing small airways disease in asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.

High frequency of genes' promoter methylation, but lack of BRAF V600E mutation among Iranian colorectal cancer patients.

PubMed

Naghibalhossaini, Fakhraddin; Hosseini, Hamideh Mahmoodzadeh; Mokarram, Pooneh; Zamani, Mozhdeh

2011-12-01

Gene silencing due to DNA hypermethylation is a major mechanism for loss of tumor suppressor genes function in colorectal cancer. Activating V600E mutation in BRAF gene has been linked with widespread methylation of CpG islands in sporadic colorectal cancers. The aim of the present study was to evaluate the methylation status of three cancer-related genes, APC2, p14ARF, and ECAD in colorectal carcinogenesis and their association with the mutational status of BRAF and KRAS among Iranian colorectal cancer patients. DNA from 110 unselected series of sporadic colorectal cancer patients was examined for BRAF V600E mutation by PCR-RFLP. Promoter methylation of genes in tumors was determined by methylation specific PCR. The frequency of APC2, E-CAD, and p14 methylation was 92.6%, 40.4% and 16.7%, respectively. But, no V600E mutation was identified in the BRAF gene in any sample. No association was found in cases showing epigenetic APC, ECAD, and p14 abnormality with the clinicopathological parameters under study. The association between KRAS mutations and the so called methylator phenotype was previously reported. Therefore, we also analyzed the association between the hot spot KRAS gene mutations in codons of 12 and 13 with genes' promoter hypermethylation in a subset of this group of patients. Out of 86 tumors, KRAS was mutated in 24 (28%) of tumors, the majority occurring in codon 12. KRAS mutations were not associated with genes' methylation in this tumor series. These findings suggest a distinct molecular pathway for methylation of APC2, p14, and ECAD genes from those previously described for colorectal cancers with BRAF or KRAS mutations.

Cancer incidence and mortality for all causes in HIV-infected patients over a quarter century: a multicentre cohort study.

PubMed

Raffetti, Elena; Albini, Laura; Gotti, Daria; Segala, Daniela; Maggiolo, Franco; di Filippo, Elisa; Saracino, Annalisa; Ladisa, Nicoletta; Lapadula, Giuseppe; Fornabaio, Chiara; Castelnuovo, Filippo; Casari, Salvatore; Fabbiani, Massimiliano; Pierotti, Piera; Donato, Francesco; Quiros-Roldan, Eugenia

2015-03-12

We aimed to assess cancer incidence and mortality for all-causes and factors related to risk of death in an Italian cohort of HIV infected unselected patients as compared to the general population. We conducted a retrospective (1986-2012) cohort study on 16 268 HIV infected patients enrolled in the MASTER cohort. The standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were computed using cancer incidence rates of Italian Cancer Registries and official national data for overall mortality. The risk factors for death from all causes were assessed using Poisson regression models. 1,195 cancer cases were diagnosed from 1986 to 2012: 700 AIDS-defining-cancers (ADCs) and 495 non-AIDS-defining-cancers (NADCs). ADC incidence was much higher than the Italian population (SIR = 30.8, 95% confidence interval 27.9-34.0) whereas NADC incidence was similar to the general population (SIR = 0.9, 95% CI 0.8-1.1). The SMR for all causes was 11.6 (11.1-12.0) in the period, and it decreased over time, mainly after 1996, up to 3.53 (2.5-4.8) in 2012. Male gender, year of enrolment before 1993, older age at enrolment, intravenous drug use, low CD4 cell count, AIDS event, cancer occurrence and the absence of antiretroviral therapy were all associated independently with risk of death. In HIV infected patients, ADC but not NADC incidence rates were higher than the general population. Although overall mortality in HIV infected subjects decreased over time, it is about three-fold higher than the general population at present.

A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer

PubMed Central

Cybulski, C; Wokołorczyk, D; Huzarski, T; Byrski, T; Gronwald, J; Górski, B; Dębniak, T; Masojć, B; Jakubowska, A; Gliniewicz, B; Sikorski, A; Stawicka, M; Godlewski, D; Kwias, Z; Antczak, A; Krajka, K; Lauer, W; Sosnowski, M; Sikorska‐Radek, P; Bar, K; Klijer, R; Zdrojowy, R; Małkiewicz, B; Borkowski, A; Borkowski, T; Szwiec, M; Narod, S A; Lubiński, J

2006-01-01

Background Germline mutations in the Chek2 kinase gene (CHEK2) have been associated with a range of cancer types. Recently, a large deletion of exons 9 and 10 of CHEK2 was identified in several unrelated patients with breast cancer of Czech or Slovak origin. The geographical and ethnic extent of this founder allele has not yet been determined. Participants and methods We assayed for the presence of this deletion, and of three other CHEK2 founder mutations, in 1864 patients with prostate cancer and 5496 controls from Poland. Results The deletion was detected in 24 of 5496 (0.4%) controls from the general population, and is the most common CHEK2 truncating founder allele in Polish patients. The deletion was identified in 15 of 1864 (0.8%) men with unselected prostate cancer (OR 1.9; 95% CI 0.97 to 3.5; p = 0.09) and in 4 of 249 men with familial prostate cancer (OR 3.7; 95% CI 1.3 to 10.8; p = 0.03). These ORs were similar to those associated with the other truncating mutations (IVS2+1G→A, 1100delC). Conclusion A large deletion of exons 9 and 10 of CHEK2 confers an increased risk of prostate cancer in Polish men. The del5395 founder deletion might be present in other Slavic populations, including Ukraine, Belarus, Russia, Baltic and Balkan countries. It will be of interest to see to what extent this deletion is responsible for the burden of prostate cancer in other populations. PMID:17085682

Measurement of antinuclear antibodies and their fine specificities: time for a change in strategy?

PubMed

Otten, Henny G; Brummelhuis, Walter J; Fritsch-Stork, Ruth; Leavis, Helen L; Wisse, Bram W; van Laar, Jacob M; Derksen, Ronald H W M

2017-01-01

The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients. In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes). Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation. We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.

Pituitary Adenoma With Paraganglioma/Pheochromocytoma (3PAs) and Succinate Dehydrogenase Defects in Humans and Mice

PubMed Central

Xekouki, Paraskevi; Szarek, Eva; Bullova, Petra; Giubellino, Alessio; Quezado, Martha; Mastroyannis, Spyridon A.; Mastorakos, Panagiotis; Wassif, Christopher A.; Raygada, Margarita; Rentia, Nadia; Dye, Louis; Cougnoux, Antony; Koziol, Deloris; Sierra, Maria de La Luz; Lyssikatos, Charalampos; Belyavskaya, Elena; Malchoff, Carl; Moline, Jessica; Eng, Charis; Maher, Louis James; Pacak, Karel; Lodish, Maya

2015-01-01

Context: Germline mutations in genes coding succinate dehydrogenase (SDH) subunits A, B, C, and D have been identified in familial paragangliomas (PGLs)/pheochromocytomas (PHEOs) and other tumors. We described a GH-secreting pituitary adenoma (PA) caused by SDHD mutation in a patient with familial PGLs. Additional patients with PAs and SDHx defects have since been reported. Design: We studied 168 patients with unselected sporadic PA and with the association of PAs, PGLs, and/or pheochromocytomas, a condition we named the 3P association (3PAs) for SDHx germline mutations. We also studied the pituitary gland and hormonal profile of Sdhb+/− mice and their wild-type littermates at different ages. Results: No SDHx mutations were detected among sporadic PA, whereas three of four familial cases were positive for a mutation (75%). Most of the SDHx-deficient PAs were either prolactinomas or somatotropinomas. Pituitaries of Sdhb+/− mice older than 12 months had an increased number mainly of prolactin-secreting cells and several ultrastructural abnormalities such as intranuclear inclusions, altered chromatin nuclear pattern, and abnormal mitochondria. Igf-1 levels of mutant mice tended to be higher across age groups, whereas Prl and Gh levels varied according to age and sex. Conclusion: The present study confirms the existence of a new association that we termed 3PAs. It is due mostly to germline SDHx defects, although sporadic cases of 3PAs without SDHx defects also exist. Using Sdhb+/− mice, we provide evidence that pituitary hyperplasia in SDHx-deficient cells may be the initial abnormality in the cascade of events leading to PA formation. PMID:25695889

DIAGNOSIS OF ENDOCRINE DISEASE: Prevalence of hypercortisolism in type 2 diabetes patients: a systematic review and meta-analysis.

PubMed

Steffensen, Charlotte; Pereira, Alberto M; Dekkers, Olaf M; Jørgensen, Jens Otto L

2016-12-01

Type 2 diabetes (T2D) and Cushing's syndrome (CS) share clinical characteristics, and several small studies have recorded a high prevalence of hypercortisolism in T2D, which could have therapeutic implications. We aimed to assess the prevalence of endogenous hypercortisolism in T2D patients. Systematic review and meta-analysis of the literature. A search was performed in SCOPUS, MEDLINE, and EMBASE for original articles assessing the prevalence of endogenous hypercortisolism and CS in T2D. Data were pooled in a random-effect logistic regression model and reported with 95% confidence intervals (95% CI). Fourteen articles were included, with a total of 2827 T2D patients. The pooled prevalence of hypercortisolism and CS was 3.4% (95% CI: 1.5-5.9) and 1.4% (95 CI: 0.4-2.9) respectively. The prevalence did not differ between studies of unselected patients and patients selected based on the presence of metabolic features such as obesity or poor glycemic control (P = 0.41 from meta-regression). Imaging in patients with hypercortisolism (n = 102) revealed adrenal tumors and pituitary tumors in 52 and 14% respectively. Endogenous hypercortisolism is a relatively frequent finding in T2D, which may have therapeutic implications. © 2016 European Society of Endocrinology.

Spatial working memory function in twins with schizophrenia and bipolar disorder.

PubMed

Pirkola, Tiia; Tuulio-Henriksson, Annamari; Glahn, David; Kieseppä, Tuula; Haukka, Jari; Kaprio, Jaakko; Lönnqvist, Jouko; Cannon, Tyrone D

2005-12-15

Family studies are in conflict as to whether schizophrenia and bipolar disorder have independent genetic etiologies. Given the relatively low prevalence (approximately 1%) of these disorders, the use of quantitative endophenotypic markers of genetic liability might provide a more sensitive strategy for evaluating their genetic overlap. We have previously demonstrated that spatial working memory deficits increase in a dose-dependent fashion with increasing genetic proximity to a proband among the unaffected co-twins of schizophrenic patients. Here, we evaluated whether such deficits might also mark genetic susceptibility to bipolar disorder. The Wechsler Memory Scale-Revised Visual Memory Span and Digit Span subtests were administered to 46 schizophrenic patients, 32 of their unaffected co-twins, 22 bipolar patients, 16 of their unaffected co-twins, and 100 control twins, representing unselectively nationwide twin samples. Schizophrenic patients and their unaffected co-twins performed significantly worse than control subjects on the spatial working memory task, whereas only the schizophrenic patients performed significantly below the control subjects on the verbal working memory task. Neither bipolar patients nor their unaffected co-twins differed from control subjects on these measures. Our findings support the hypothesis that impairment in spatial working memory might effectively reflect an expression of genetic liability to schizophrenia but less clearly to bipolar disorder.

Five year follow-up after autologous peripheral blood hematopoietic stem cell transplantation for refractory, chronic, corticosteroid-dependent systemic lupus erythematosus: effect of conditioning regimen on outcome.

PubMed

Burt, Richard K; Han, Xiaoqiang; Gozdziak, Paula; Yaung, Kim; Morgan, Amy; Clendenan, Allison M; Henry, Jacquelyn; Calvario, Michelle A; Datta, Syamal K; Helenowski, Irene; Schroeder, James

2018-05-31

Some patients with systemic lupus erythematosus (SLE) are refractory to traditional therapies, dependent on chronic corticosteroids, have organ damage, and are at high risk of mortality. In this group of patients, we report outcome at a median of five years after autologous hematopoietic stem cell transplant (HSCT) using two different non-myeloablative regimens. Four patients received a conditioning regimen of cyclophosphamide (200 mg/kg) and alemtuzumab (60 mg), while 26 patients underwent conditioning with cyclophosphamide (200 mg/kg), rATG (Thymoglobulin) (5.5 mg/kg), and rituximab 1000 mg. Unselected peripheral blood stem cells were infused on day 0. There were no treatment related deaths. Of the four patients treated with cyclophosphamide and alemtuzumab, none entered remission. For the 26 patients treated with cyclophosphamide, rATG, and rituximab, disease remission defined as no immune suppressive drugs except hydroxychloroquine and/or 10 mg or less of prednisone a day was 92% at 6 months, 92% at one year, 81% at 2 years, 71% at 3 years, and 62% at 4 and 5 years post-HSCT. Autologous HSCT outcome is dependent on the conditioning regimen but prior organ damage may cause lingering symptoms.

Serum adipokines and HIV viral replication in patients undergoing antiretroviral therapy

PubMed Central

Aramă, Victoria; Tilişcan, Cătălin; Ion, Daniela Adriana; Mihăilescu, Raluca; Munteanu, Daniela; Streinu-Cercel, Anca; Tudor, Ana Maria; Hristea, Adriana; Leoveanu, Viorica; Olaru, Ioana; Aramă, Ştefan Sorin

2012-01-01

Introduction Several studies have reported that cytokines secreted by adipose tissue (adipokines) may be linked to HIV replication. The aim of the study was to evaluate the relationship between HIV replication and serum levels of adipokines, in a Caucasian HIV-infected population of men and women undergoing complex antiretroviral therapy. Methods A cross-sectional study was conducted in an unselected sample of 77 HIV-1-positive patients. Serum adipokines levels were measured including circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Patients were divided into two groups: Group 1 - with undetectable viral load and Group 2 - with persistent HIV viral replication. Differences between groups ? were tested using independent-sample t-test for Gaussian variables and Mann–Whitney–Wilcoxon test for non-parametric variables. Pearson's chi-squared test was used for correlation analysis. Results A total of 77 patients (age range: 17-65, mean: 32.5 years) including 44 men (57.1% men, age range: 17–63 years, mean: 34.1 years) and 33 women (42.9% women age range: 19–65 years, mean: 30.3 years) were included in the study. TNF-alpha had significantly higher serum levels in patients with detectable viral load (16.89 vs. 9.35 pg/mL), (p=0.043), but correlation analysis lacked statistical significance. Adiponectin had median serum levels of 9.22 ìg/mL in Group 1 vs. 16.50 ìg/mL in Group 2 but the results lacked statistical significance (p=0.059). Higher leptin, IL-6 and resistin serum levels were noted in patients with undetectable HIV viral load, without statistical significance. Conclusions The present study reported higher TNF-alpha serum levels in patients with persistent HIV viral load. We found no statistically significant correlations between adiponectin, leptin, resistin and IL-6 and HIV viral load in our Caucasian HIV-positive study population, undergoing antiretroviral therapy. PMID:24432258

Intrinsic Limitations to Unilateral Parathyroid Exploration

PubMed Central

Moore, Francis D.; Mannting, Finn; Tanasijevic, Milenko

1999-01-01

Objective To evaluate a method of limited parathyroid exploration for primary hyperparathyroidism. Summary Background Data Although preoperative localization of parathyroid adenomas has become sensitive enough for clinical practice, it has not achieved success as the basis for limited parathyroid exploration, because multiglandular disease is routinely underdiagnosed. The rapid intraoperative parathyroid hormone assay is sensitive for multiglandular disease, because hormone levels will not fall within 10 minutes of adenoma removal if additional abnormal tissue is present. A combination technique in which the exploration is limited according to the localization studies and the success is confirmed with the parathyroid hormone assay has promise for producing a high rate of curative limited parathyroid explorations. Methods Forty-eight consecutive patients with primary hyperparathyroidism and indications for surgery underwent preoperative localization. After tests, 45 patients underwent unilateral parathyroid exploration and confirmation of the success of unilateral exploration during surgery using the rapid parathyroid hormone assay. The intraoperative management of these patients and their follow-up to 3 months was recorded. Results Thirty-two of the 48 patients (67%) had successful unilateral exploration as gauged by a marked drop in parathyroid hormone levels during the procedure and by 3-month clinical follow-up. Of the 16 patients who ultimately underwent bilateral exploration, 7 had parathyroid hormone levels that did not fall after adenoma removal. Of these seven, five were found to have a second adenoma and two had slow metabolism of hormone with no additional abnormal tissue found. In 5 of the 16 patients, bilateral exploration was performed for erroneous localization. Four additional patients underwent bilateral exploration for improved exposure or negative results on localization tests. Conclusions These results show that unilateral parathyroid exploration is limited by the intrinsic 15% rate of multiglandular primary hyperparathyroidism, combined with the imperfections of preoperative localizing techniques. Although an 85% rate of unilateral exploration can theoretically be obtained for unselected cases, the other vagaries of the technique make a 70% rate a more reasonable expectation. PMID:10493485

Diabetic muscle infarction in end-stage renal disease: A scoping review on epidemiology, diagnosis and treatment

PubMed Central

Yong, Tuck Yean; Khow, Kareeann Sok Fun

2018-01-01

Diabetic muscle infarction (DMI) refers to spontaneous ischemic necrosis of skeletal muscle among people with diabetes mellitus, unrelated to arterial occlusion. People with DMI may have coexisting end-stage renal disease (ESRD) but little is known about its epidemiology and clinical outcomes in this setting. This scoping review seeks to investigate the characteristics, clinical features, diagnostic evaluation, management and outcomes of DMI among people with ESRD. Electronic database (PubMed/MEDLINE, CINAHL, SCOPUS and EMBASE) searches were conducted for (“diabetic muscle infarction” or “diabetic myonecrosis”) and (“chronic kidney disease” or “renal impairment” or “dialysis” or “renal replacement therapy” or “kidney transplant”) from January 1980 to June 2017. Relevant cases from reviewed bibliographies in reports retrieved were also included. Data were extracted in a standardized form. A total of 24 publications with 41 patients who have ESRD were included. The mean age at the time of presentation with DMI was 44.2 years. Type 2 diabetes was present in 53.7% of patients while type 1 in 41.5%. In this cohort, 60.1% were receiving hemodialysis, 21% on peritoneal dialysis and 12.2% had kidney transplantation. The proximal lower limb musculature was the most commonly affected site. Muscle pain and swelling were the most frequent manifestation on presentation. Magnetic resonance imaging (MRI) provided the most specific findings for DMI. Laboratory investigation findings are usually non-specific. Non-surgical therapy is usually used in the management of DMI. Short-term prognosis of DMI is good but recurrence occurred in 43.9%. DMI is an uncommon complication in patients with diabetes mellitus, including those affected by ESRD. In comparison with unselected patients with DMI, the characteristics and outcomes of those with ESRD are generally similar. DMI may also occur in kidney transplant recipients, including pancreas-kidney transplantation. MRI is the most useful diagnostic investigation. Non-surgical treatment involving analgesia, optimization of glycemic control and initial bed rest can help to improve recovery rate. However, recurrence of DMI is relatively frequent. PMID:29527509

Inadequate Diagnostic Evaluation in Young Patients Registered with a Diagnosis of Dementia: A Nationwide Register-Based Study

PubMed Central

Salem, Lise Cronberg; Andersen, Birgitte Bo; Nielsen, T. Rune; Stokholm, Jette; Jørgensen, Martin Balslev; Waldemar, Gunhild

2014-01-01

Background Establishing a diagnosis of dementia in young patients may be complex and have significant implications for the patient. The aim of this study was to evaluate the quality of the diagnostic work-up in young patients diagnosed with dementia in the clinical routine. Methods Two hundred patients were randomly selected from 891 patients aged ≤65 years registered with a diagnosis of dementia for the first time in 2008 in Danish hospitals, and 159 medical records were available for review. Three raters evaluated their medical records for the completeness of the diagnostic work-up on which the diagnosis of dementia had been based, using evidence-based guidelines for the diagnostic evaluation of dementia as reference standards. Results According to the rater review, only 111 (70%) patients met the clinical criteria for dementia. An acceptable diagnostic work-up including all items of recommended basic diagnostic evaluation was performed in only 24%, although more often (28%) in the subgroup of patients where dementia was confirmed by raters. Conclusion This first nationwide study of unselected young patients registered with a diagnosis of dementia indicated that the concept of dementia may be misinterpreted by clinicians and that a diagnosis of dementia in the young is only rarely based on a complete basic diagnostic work-up, calling for increased competency. PMID:24711812

Risk of ischemic stroke after an acute myocardial infarction in patients with diabetes mellitus.

PubMed

Jakobsson, Stina; Bergström, Lisa; Björklund, Fredrik; Jernberg, Tomas; Söderström, Lars; Mooe, Thomas

2014-01-01

Incidence, any trend over time, and predictors of ischemic stroke after an acute myocardial infarction (AMI) in diabetic patients are unknown. Data for 173,233 unselected patients with an AMI, including 33,503 patients with diabetes mellitus, were taken from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) during 1998 to 2008. Ischemic stroke events were recorded during 1 year of follow-up. Patients with diabetes mellitus more often had a history of cardiovascular disease, received less reperfusion therapy, and were treated with acetylsalicylic acid, P2Y12 inhibitors, and statins to a lesser extent compared with patients without diabetes mellitus. However, the use of evidence-based therapies increased markedly in both groups during the study period. The incidence of ischemic stroke during the first year after AMI decreased from 7.1% to 4.7% in patients with diabetes mellitus and from 4.2% to 3.7% in patients without diabetes mellitus. Risk reduction was significantly larger in the diabetic subgroup. Reperfusion therapy, acetylsalicylic acid, P2Y12 inhibitors, and statins were independently associated with the reduced stroke risk. Ischemic stroke is a fairly common complication after an AMI in patients with diabetes mellitus, but the risk of stroke has decreased during recent years. The increased use of evidence-based therapies contributes importantly to this risk reduction, but there is still room for improvement.

The effect of queen pheromone status on Varroa mite removal from honey bee colonies with different grooming ability.

PubMed

Bahreini, Rassol; Currie, Robert W

2015-07-01

The objective of this study was to assess the effects of honey bees (Apis mellifera L.) with different grooming ability and queen pheromone status on mortality rates of Varroa mites (Varroa destructor Anderson and Trueman), mite damage, and mortality rates of honey bees. Twenty-four small queenless colonies containing either stock selected for high rates of mite removal (n = 12) or unselected stock (n = 12) were maintained under constant darkness at 5 °C. Colonies were randomly assigned to be treated with one of three queen pheromone status treatments: (1) caged, mated queen, (2) a synthetic queen mandibular pheromone lure (QMP), or (3) queenless with no queen substitute. The results showed overall mite mortality rate was greater in stock selected for grooming than in unselected stock. There was a short term transitory increase in bee mortality rates in selected stock when compared to unselected stock. The presence of queen pheromone from either caged, mated queens or QMP enhanced mite removal from clusters of bees relative to queenless colonies over short periods of time and increased the variation in mite mortality over time relative to colonies without queen pheromone, but did not affect the proportion of damaged mites. The effects of source of bees on mite damage varied with time but damage to mites was not reliably related to mite mortality. In conclusion, this study showed differential mite removal of different stocks was possible under low temperature. Queen status should be considered when designing experiments using bioassays for grooming response.

Patterns of disease control and survival in patients with melanoma brain metastases undergoing immune-checkpoint blockade.

PubMed

Milsch, Laura; Gesierich, Anja; Kreft, Sophia; Livingstone, Elisabeth; Zimmer, Lisa; Goebeler, Matthias; Schadendorf, Dirk; Schilling, Bastian

2018-06-12

Immune-checkpoint blockers (ICBs) significantly prolong overall survival (OS) in patients with advanced melanoma. Limited data are available on the efficacy and clinical benefit in patients with melanoma brain metastases (MBMs). The aim of this study was to determine whether ICB is active in an unselected cohort treated of patients with known brain metastases and if disease control correlates with the survival. A total of 385 patients with metastatic malignant melanoma treated with ICB as monotherapy between 2005 and 2017 in two tertiary referral centres were included. Patient records were searched for the development of brain metastases. Demographic and clinical data of all patients were collected retrospectively. We identified 177 patients with MBM who received ICBs (ipilimumab, nivolumab, pembrolizumab). Patients with and without brain metastases received similar ICB regimens. Prognosis was inferior in patients with brain metastases; patients with >1 brain metastasis showed even poorer survival. For extracranial (ec) metastases, disease control was associated with improved survival. However, when comparing patients with intracranial (ic) disease control during immunotherapy to patients with ic disease progression, no difference in OS could be observed. In our study, ec disease control was the dominant predictive factor for OS in both patients with or without melanoma brain metastases. These data indicate that clinical trials in melanoma patients with brain metastases should address end-points such as symptom control, quality of life or OS in addition to ic response rates. Copyright © 2018 Elsevier Ltd. All rights reserved.

An inherited NBN mutation is associated with poor prognosis prostate cancer

PubMed Central

Cybulski, C; Wokołorczyk, D; Kluźniak, W; Jakubowska, A; Górski, B; Gronwald, J; Huzarski, T; Kashyap, A; Byrski, T; Dębniak, T; Gołąb, A; Gliniewicz, B; Sikorski, A; Świtała, J; Borkowski, T; Borkowski, A; Antczak, A; Wojnar, Ł; Przybyła, J; Sosnowski, M; Małkiewicz, B; Zdrojowy, R; Sikorska-Radek, P; Matych, J; Wilkosz, J; Różański, W; Kiś, J; Bar, K; Bryniarski, P; Paradysz, A; Jersak, K; Niemirowicz, J; Słupski, P; Jarzemski, P; Skrzypczyk, M; Dobruch, J; Domagała, P; Narod, S A; Lubiński, J

2013-01-01

Background: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. Methods: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). Results: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ⩽60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. Conclusion: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment. PMID:23149842

Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.

PubMed

Tutt, Andrew; Tovey, Holly; Cheang, Maggie Chon U; Kernaghan, Sarah; Kilburn, Lucy; Gazinska, Patrycja; Owen, Julie; Abraham, Jacinta; Barrett, Sophie; Barrett-Lee, Peter; Brown, Robert; Chan, Stephen; Dowsett, Mitchell; Flanagan, James M; Fox, Lisa; Grigoriadis, Anita; Gutin, Alexander; Harper-Wynne, Catherine; Hatton, Matthew Q; Hoadley, Katherine A; Parikh, Jyoti; Parker, Peter; Perou, Charles M; Roylance, Rebecca; Shah, Vandna; Shaw, Adam; Smith, Ian E; Timms, Kirsten M; Wardley, Andrew M; Wilson, Gregory; Gillett, Cheryl; Lanchbury, Jerry S; Ashworth, Alan; Rahman, Nazneen; Harries, Mark; Ellis, Paul; Pinder, Sarah E; Bliss, Judith M

2018-05-01

Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative 'BRCAness' subgroups-tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes-may also be sensitive to platinum. We assessed the efficacy of carboplatin and another mechanistically distinct therapy, docetaxel, in a phase 3 trial in subjects with unselected advanced TNBC. A prespecified protocol enabled biomarker-treatment interaction analyses in gBRCA-BC and BRCAness subgroups. The primary endpoint was objective response rate (ORR). In the unselected population (376 subjects; 188 carboplatin, 188 docetaxel), carboplatin was not more active than docetaxel (ORR, 31.4% versus 34.0%, respectively; P = 0.66). In contrast, in subjects with gBRCA-BC, carboplatin had double the ORR of docetaxel (68% versus 33%, respectively; biomarker, treatment interaction P = 0.01). Such benefit was not observed for subjects with BRCA1 methylation, BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay. Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup. We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations, but not BRCA1 methylation or Myriad HRD analyses, to inform choices on platinum-based chemotherapy. Additionally, gene expression analysis of basal-like cancers may also influence treatment selection.

Diagnostic testing for celiac disease among patients with abdominal symptoms: a systematic review.

PubMed

van der Windt, Daniëlle A W M; Jellema, Petra; Mulder, Chris J; Kneepkens, C M Frank; van der Horst, Henriëtte E

2010-05-05

The symptoms and consequences of celiac disease usually resolve with a lifelong gluten-free diet. However, clinical presentation is variable and most patients presenting with abdominal symptoms in primary care will not have celiac disease and unnecessary diagnostic testing should be avoided. To summarize evidence on the performance of diagnostic tests for identifying celiac disease in adults presenting with abdominal symptoms in primary care or similar settings. A literature search via MEDLINE (beginning in January 1966) and EMBASE (beginning in January 1947) through December 2009 and a manual search of references for additional relevant studies. Diagnostic studies were selected if they had a cohort or nested case-control design, enrolled adults presenting with nonacute abdominal symptoms, the prevalence of celiac disease was 15% or less, and the tests used included gastrointestinal symptoms or serum antibody tests. Quality assessment using the Quality Assessment of Diagnostic Accuracy Studies tool and data extraction were performed by 2 reviewers independently. Sensitivities and specificities were calculated for each study and pooled estimates were computed using bivariate analysis if there was clinical and statistical homogeneity. Sixteen studies were included in the review (N = 6085 patients). The performance of abdominal symptoms varied widely. The sensitivity of diarrhea, for example, ranged from 0.27 to 0.86 and specificity from 0.21 to 0.86. Pooled estimates for IgA antiendomysial antibodies (8 studies) were 0.90 (95% confidence interval [CI], 0.80-0.95) for sensitivity and 0.99 (95% CI, 0.98-1.00) for specificity (positive likelihood ratio [LR] of 171 and negative LR of 0.11). Pooled estimates for IgA antitissue transglutaminase antibodies (7 studies) were 0.89 (95% CI, 0.82-0.94) and 0.98 (95% CI, 0.95-0.99), respectively (positive LR of 37.7 and negative LR of 0.11). The IgA and IgG antigliadin antibodies showed variable results, especially for sensitivity (range, 0.46-0.87 and range, 0.25-0.93, respectively). One recent study using diamidated gliadin peptides showed good specificity (> or = 0.94), but evidence is limited in this target population. Among adult patients presenting with abdominal symptoms in primary care or other unselected populations, IgA antitissue transglutaminase antibodies and IgA antiendomysial antibodies have high sensitivity and specificity for diagnosing celiac disease.

Genomic Alterations in Advanced Esophageal Cancer May Lead to Subtype-Specific Therapies

PubMed Central

Forde, Patrick M.

2013-01-01

The development of targeted agents for metastatic esophageal or gastroesophageal junction (GEJ) tumors has been limited when compared with that for other common tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2) antibody, trastuzumab, in combination with chemotherapy, is the only approved novel agent for these cancers, and its use is limited to the small population of patients whose tumors overexpress HER-2. Despite recent progress in the field, median overall survival remains only 8–12 months for patients with stage IV esophageal or GEJ cancer. In this article, we examine the molecular aberrations thought to drive the development and spread of esophageal cancer and identify promising targets for specific tumor inhibition. Data from clinical studies of targeted agents are reviewed, including epidermal growth factor receptor antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth factor-directed therapy. Current and future targets include MET, fibroblast growth factor receptor, and immune-based therapies. Evidence from trials to date suggests that molecularly unselected patient cohorts derive minimal benefit from most target-specific agents, suggesting that future collaborative investigation should focus on preselected molecular subgroups of patients with this challenging heterogeneous disease. PMID:23853247

Common medium versus advanced IVF medium for cryopreserved oocytes in heterologous cycles.

PubMed

Poverini, R; Lisi, R; Lisi, F; Berlinghieri, V; Bielli, W; Carfagna, P; Costantino, A; Iacomino, D; Nicodemo, G

2018-12-01

Granulocyte-macrophage colony-stimulation factor plays different crucial roles during embryo implantation and subsequent development. Here we aimed to evaluate the effects of embryo cell culture medium, with the inclusion of granulocyte-macrophage colony-stimulation factor (GM-CSF), on embryo development and pregnancy rate. To this end, we took advantage of our retrospective observational study to correlate the outcomes from two different culture media. We included in this study 25 unselected patient from our IVF Center that underwent heterologous IVF cycle with crypreserved oocytes. We analyze the fertilization rate, pregnancy rate, and embryo quality at different day of transfer obtained from two different media composition. Our results show that the rate of fertilization and the pregnancy rate were increased using medium added with this particular type of cytokines (GM-CSF).

Somatic mutations in the transcriptional corepressor gene BCORL1 in adult acute myelogenous leukemia

PubMed Central

Li, Meng; Collins, Roxane; Jiao, Yuchen; Ouillette, Peter; Bixby, Dale; Erba, Harry; Vogelstein, Bert; Kinzler, Kenneth W.

2011-01-01

To further our understanding of the genetic basis of acute myelogenous leukemia (AML), we determined the coding exon sequences of ∼ 18 000 protein-encoding genes in 8 patients with secondary AML. Here we report the discovery of novel somatic mutations in the transcriptional corepressor gene BCORL1 that is located on the X-chromosome. Analysis of BCORL1 in an unselected cohort of 173 AML patients identified a total of 10 mutated cases (6%) with BCORL1 mutations, whereas analysis of 19 AML cell lines uncovered 4 (21%) BCORL1 mutated cell lines. The majority (87%) of the mutations in BCORL1 were predicted to inactivate the gene product as a result of nonsense mutations, splice site mutation, or out-of-frame insertions or deletions. These results indicate that BCORL1 by genetic criteria is a novel candidate tumor suppressor gene, joining the growing list of genes recurrently mutated in AML. PMID:21989985

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

NASA Technical Reports Server (NTRS)

Wu, C. L.; Denq, J. C.; Harper, C. M.; O'Brien, P. C.; Low, P. A.

1998-01-01

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

ALCOHOLIC VERSUS NONALCOHOLIC CIRRHOSIS IN A RANDOMIZED CONTROLLED TRIAL OF EMERGENCY THERAPY OF BLEEDING VARICES

PubMed Central

Orloff, Marshall J.; Isenberg, Jon I.; Wheeler, Henry O.; Haynes, Kevin S.; Jinich-Brook, Horacio; Rapier, Roderick; Vaida, Florin; Hye, Robert J.; Orloff, Susan L.

2010-01-01

Background It has been proposed that portal-systemic shunts be avoided in alcoholic cirrhotics because survival rate is allegedly lower in alcoholics than in nonalcoholics. We examined this issue in a randomized controlled trial. Methods 211 unselected, consecutive patients with cirrhosis and bleeding esophageal varices were randomized to endoscopic sclerotherapy (EST) (n=106) or emergency portacaval shunt (EPCS) (105). Treatment was initiated within 8 hours. EST failure was treated by rescue PCS. 10-yr follow-up was 96%. Results Results strongly favored EPCS over EST (p<0.001). Among EPCS patients, 83% were alcoholic and 17% nonalcoholic. Outcomes were (1) permanent control of bleeding 100% vs. 100%; (2) 5-yr survival 71% vs.78%; (3) encephalopathy 14% vs. 19%; (4) yearly charges $38,300 vs. $43,000. Conclusions EPCS results were similar in alcoholic and nonalcoholic cirrhotics. EPCS is an effective first line emergency treatment in all forms of cirrhosis, including alcoholic. PMID:21195430

Evidence of SV40 infections in hospitalized children

NASA Technical Reports Server (NTRS)

Butel, J. S.; Jafar, S.; Wong, C.; Arrington, A. S.; Opekun, A. R.; Finegold, M. J.; Adam, E.

1999-01-01

Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.

[Single embryo transfer: is Scandinavian model valuable in France?].

PubMed

Belaisch-Allart, J; Mayenga, J-M; Grefenstette, I; Chouraqui, A; Serkine, A-M; Abirached, F; Kulski, O

2008-11-01

The aim of infertility treatment is clearly to obtain one healthy baby. If the transfer of a top quality single embryo could provide a baby to all the patients, there would be no more discussion. The problem is that, nowadays, French pregnancy rates after fresh embryo or frozen embryo transfer are not the same as in Nordic countries. All studies show that in unselected patients, single embryo transfer decreases twin pregnancy rate but decreases pregnancy rate too. Pregnancy rate is dependent on embryo quality, women's age, rank of IVF attempt (clear data) but also on body mass index, ovarian reserve, smoking habits. All these data cannot be taken into account in a law. That is the reason why a flexible policy of transfer adapted to each couple is preferable. Each couple and each IVF team are unique and must keep the freedom to choose how many embryos must be transferred to obtain healthy babies, and to avoid twin pregnancies but without demonizing them.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ausborn, Natalie L.; Le, Quynh Thu; Bradley, Jeffrey D.

Therapeutic decisions in non-small cell lung cancer (NSCLC) have been mainly based on disease stage, performance status, and co-morbidities, and rarely on histological or molecular classification. Rather than applying broad treatments to unselected patients that may result in survival increase of only weeks to months, research efforts should be, and are being, focused on identifying predictive markers for molecularly targeted therapy and determining genomic signatures that predict survival and response to specific therapies. The availability of such targeted biologics requires their use to be matched to tumors of corresponding molecular vulnerability for maximum efficacy. Molecular markers such as epidermal growthmore » factor receptor (EGFR), K-ras, vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and anaplastic lymphoma kinase (ALK) represent potential parameters guide treatment decisions. Ultimately, identifying patients who will respond to specific therapies will allow optimal efficacy with minimal toxicity, which will result in more judicious and effective application of expensive targeted therapy as the new paradigm of personalized medicine develops.« less

Prognostic value of 6-minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation.

PubMed

Rostagno, Carlo; Olivo, Giuseppe; Comeglio, Marco; Boddi, Vieri; Banchelli, Michela; Galanti, Giorgio; Gensini, Gian Franco

2003-06-01

The study was designed to evaluate the prognostic value of the 6-min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF). Two hundred and fourteen patients (119 men and 95 women, mean age 64 years) were followed for a mean period of 34 months to assess event-free survival (death, heart transplantation). Sixty-six patients (34%) died (63 cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart transplantation. For patients who walked <300 m during the 6MWT, survival was 62% compared with 82% in patients who walked 300-450 m or>450 m. With univariate analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001), aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT distance (P<0.01) were all significantly related to survival. No significant relationship was found between survival, peak oxygen consumption or anaerobic threshold. Multivariate analysis using the Cox-stepwise regression model showed that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the strongest prognostic markers. A 6MWT distance of <300 m is a simple and useful prognostic marker of subsequent cardiac death in unselected patients with mild to moderate CHF.

Impairments in proverb interpretation following focal frontal lobe lesions☆

PubMed Central

Murphy, Patrick; Shallice, Tim; Robinson, Gail; MacPherson, Sarah E.; Turner, Martha; Woollett, Katherine; Bozzali, Marco; Cipolotti, Lisa

2013-01-01

The proverb interpretation task (PIT) is often used in clinical settings to evaluate frontal “executive” dysfunction. However, only a relatively small number of studies have investigated the relationship between frontal lobe lesions and performance on the PIT. We compared 52 patients with unselected focal frontal lobe lesions with 52 closely matched healthy controls on a proverb interpretation task. Participants also completed a battery of neuropsychological tests, including a fluid intelligence task (Raven’s Advanced Progressive Matrices). Lesions were firstly analysed according to a standard left/right sub-division. Secondly, a finer-grained analysis compared the performance of patients with medial, left lateral and right lateral lesions with healthy controls. Thirdly, a contrast of specific frontal subgroups compared the performance of patients with medial lesions with patients with lateral frontal lesions. The results showed that patients with left frontal lesions were significantly impaired on the PIT, while in patients with right frontal lesions the impairments approached significance. Medial frontal patients were the only frontal subgroup impaired on the PIT, relative to healthy controls and lateral frontal patients. Interestingly, an error analysis indicated that a significantly higher number of concrete responses were found in the left lateral subgroup compared to healthy controls. We found no correlation between scores on the PIT and on the fluid intelligence task. Overall our results suggest that specific regions of the frontal lobes contribute to the performance on the PIT. PMID:23850600

Do attendees at sexual health and HIV clinics prefer to be called in by name or number?

PubMed

Dabis, R; Nightingale, P; Kumar, V; Jaffer, K; Radcliffe, K

2014-06-01

Calling patients in from the waiting area is an important aspect of the initial medical encounter. According to national and international guidelines, clinics should decide on an appropriate way of calling patients in from the waiting room for consultations; however, no preference is actually recommended. A survey was carried out to see if patients were happy to be called in by number, first name, surname, full name, or title (Mr/Mrs/Miss/Ms) followed by surname. One hundred unselected patients were drawn from each clinic including; a genito-urinary medicine (GUM), a co-located GUM (cGUM) and co-located reproductive health (cRH), an HIV and a reproductive health (RH) clinic. Patients from the GUM, cGUM, cRH and RH clinics preferred to be called in by number rather than full name or title. Patients from the cRH clinic also preferred number to first name. In contrast, patients from the HIV clinics preferred to be called in by first name rather than number, surname, full name or title. Following this survey it would appear that number would be the most popular method of calling patients in sexual and reproductive health clinics and first name is the choice in HIV clinics. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Gender and age influence the relationship between serum GH and IGF-I in patients with acromegaly.

PubMed

Parkinson, C; Renehan, A G; Ryder, W D J; O'Dwyer, S T; Shalet, S M; Trainer, P J

2002-07-01

In patients with acromegaly serum IGF-I is increasingly used as a marker of disease activity. As a result, the relationship between serum GH and IGF-I is of profound interest. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and women with GH deficiency require 30-50% more exogenous GH to maintain the same serum IGF-I as GH-deficient men. In a selected cohort of patients with active acromegaly, studied off medical therapy using a single fasting serum GH and IGF-I measurement, we have reported previously that, for a given GH level, women have significantly lower circulating IGF-I. To evaluate the influence of age and gender on the relationship between serum GH and IGF-I in an unselected cohort of patients with acromegaly independent of disease control and medical therapy. Sixty (34 male) unselected patients with acromegaly (median age 51 years (range 24-81 years) attending a colonoscopy screening programme were studied. Forty-five had previously received pituitary radiotherapy. Patients had varying degrees of disease control and received medical therapy where appropriate. Mean serum GH was calculated from an eight-point day profile (n = 45) and values obtained during a 75-g oral glucose tolerance test (n = 15). Serum IGF-I, IGFBP-3 and acid-labile subunit were measured and the dependency of these factors on covariates such as log10 mean serum GH, sex, age and prior radiotherapy was assessed using regression techniques. The median calculated GH value was 4.7 mU/l (range 1-104). A significant linear association was observed between serum IGF-I and log10 mean serum GH for the cohort (R = 0.5, P < 0.0001). After simultaneous adjustment of the above covariates a significant difference in the relationship between mean serum GH and IGF-I was observed for males and females. On average, women had serum IGF-I levels 11.44 nmol/l lower than men with the same mean serum GH (P = 0.03, 95% CI 1.33-21.4 nmol/l). Age significantly influenced the relationship and for a given serum GH, IGF-I was estimated to fall by 0.37 nmol/l per year (P = 0.04, 95% CI 0.015-0.72). In keeping with previous observations of relative GH resistance in normal and GH-deficient females we have observed lower serum IGF-I levels for equivalent mean serum GH levels in females patients with acromegaly. This gender-dependent difference is independent of disease activity and the use of concomitant medical therapy. Additionally, we have demonstrated that for a given serum GH level, age significantly influences IGF-I concentrations in patients with acromegaly. These data have important implications for the use of serum IGF-I and GH as markers of disease activity in acromegaly.

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

PubMed

Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

2016-02-01

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

Real-world clopidogrel utilization in acute coronary syndromes: patients selection and outcomes in a single-center experience.

PubMed

Castini, Diego; Persampieri, Simone; Cazzaniga, Sara; Ferrante, Giulia; Centola, Marco; Lucreziotti, Stefano; Salerno-Uriarte, Diego; Sponzilli, Carlo; Carugo, Stefano

2017-12-01

With this study, we sought to identify patient characteristics associated with clopidogrel prescription and its relationship with in-hospital adverse events in an unselected cohort of ACSs patients. We studied all consecutive patients admitted at our institution for ACSs from 2012 to 2014. Patients were divided into two groups based on clopidogrel or novel P2Y12 inhibitors (prasugrel or ticagrelor) prescription and the relationship between clopidogrel use and patient clinical characteristics and in-hospital adverse events was evaluated using logistic regression analysis. The population median age was 68 years (57-77 year) and clopidogrel was prescribed in 230 patients (46%). Patients characteristics associated with clopidogrel prescription were older age, female sex, non-ST-elevation ACS diagnosis, the presence of diabetes mellitus and anemia, worse renal and left ventricular functions and a higher Killip class. Patients on clopidogrel demonstrated a significantly higher incidence of in-hospital mortality (4.8%) than prasugrel and ticagrelor-treated patients (0.4%), while a nonstatistically significant trend emerged considering bleeding events. However, on multivariable logistic regression analysis female sex, the presence of anemia and Killip class were the only variables independently associated with in-hospital death. Patients treated with clopidogrel showed a higher in-hospital mortality. However, clinical variables associated with its use identify a population at high risk for adverse events and this seems to play a major role for the higher in-hospital mortality observed in clopidogrel-treated patients.

Accuracy of risk scales for predicting repeat self-harm and suicide: a multicentre, population-level cohort study using routine clinical data.

PubMed

Steeg, Sarah; Quinlivan, Leah; Nowland, Rebecca; Carroll, Robert; Casey, Deborah; Clements, Caroline; Cooper, Jayne; Davies, Linda; Knipe, Duleeka; Ness, Jennifer; O'Connor, Rory C; Hawton, Keith; Gunnell, David; Kapur, Nav

2018-04-25

Risk scales are used widely in the management of patients presenting to hospital following self-harm. However, there is evidence that their diagnostic accuracy in predicting repeat self-harm is limited. Their predictive accuracy in population settings, and in identifying those at highest risk of suicide is not known. We compared the predictive accuracy of the Manchester Self-Harm Rule (MSHR), ReACT Self-Harm Rule (ReACT), SAD PERSONS Scale (SPS) and Modified SAD PERSONS Scale (MSPS) in an unselected sample of patients attending hospital following self-harm. Data on 4000 episodes of self-harm presenting to Emergency Departments (ED) between 2010 and 2012 were obtained from four established monitoring systems in England. Episodes were assigned a risk category for each scale and followed up for 6 months. The episode-based repeat rate was 28% (1133/4000) and the incidence of suicide was 0.5% (18/3962). The MSHR and ReACT performed with high sensitivity (98% and 94% respectively) and low specificity (15% and 23%). The SPS and the MSPS performed with relatively low sensitivity (24-29% and 9-12% respectively) and high specificity (76-77% and 90%). The area under the curve was 71% for both MSHR and ReACT, 51% for SPS and 49% for MSPS. Differences in predictive accuracy by subgroup were small. The scales were less accurate at predicting suicide than repeat self-harm. The scales failed to accurately predict repeat self-harm and suicide. The findings support existing clinical guidance not to use risk classification scales alone to determine treatment or predict future risk.

Evidence of shared Epstein-Barr viral isolates between sexual partners, and low level EBV in genital secretions.

PubMed

Thomas, Ranjit; Macsween, Karen F; McAulay, Karen; Clutterbuck, Daniel; Anderson, Richard; Reid, Stuart; Higgins, Craig D; Swerdlow, Anthony J; Harrison, Nadine; Williams, Hilary; Crawford, Dorothy H

2006-09-01

Epstein-Barr virus is present in the saliva of most persistently infected individuals and is generally thought to be spread by close oral contact. However, there are now several reports of EBV in genital secretions, suggesting the possibility of sexual transmission between adults. The present study was undertaken to investigate the risk of sexual transmission of EBV. PCR analysis was used to examined the degree to which a group (n = 11) of patients with infectious mononucleosis (IM) shared the same viral isolates as their sexual partners, and compare this to the extent of isolate sharing among a different group (n = 18) of IM patients and their non-sexual contacts. There was significantly more sharing of EBV isolates among the IM/sexual-contact pairs than among the IM/non-sexual-contact pairs (P = 0.0012). Female cervical (n = 84), male urethral (n = 55), and semen (n = 30) samples from asymptomatic, unselected volunteers were analyzed for the presence of EBV DNA, revealing 7%, 5%, and 3% to be EBV positive, respectively. Fractionation of cervical and urethral samples into cellular and supernatant fluid components showed EBV to be mainly cell-associated. Quantitation of EBV in these samples gave levels of below 10 EBV genomes per microg of DNA. Overall the findings support the possibility that EBV could on occasions be transmitted sexually, however, the low levels detected in genital secretions compared to saliva suggest that this is not a major transmission route. The finding of small quantities of cell-associated virus suggests a latent infection; thus EBV is probably in the B lymphocyte rather than in the epithelial cell component of the secretions.

Rapid Automated Quantification of Cerebral Leukoaraiosis on CT Images: A Multicenter Validation Study.

PubMed

Chen, Liang; Carlton Jones, Anoma Lalani; Mair, Grant; Patel, Rajiv; Gontsarova, Anastasia; Ganesalingam, Jeban; Math, Nikhil; Dawson, Angela; Aweid, Basaam; Cohen, David; Mehta, Amrish; Wardlaw, Joanna; Rueckert, Daniel; Bentley, Paul

2018-05-15

Purpose To validate a random forest method for segmenting cerebral white matter lesions (WMLs) on computed tomographic (CT) images in a multicenter cohort of patients with acute ischemic stroke, by comparison with fluid-attenuated recovery (FLAIR) magnetic resonance (MR) images and expert consensus. Materials and Methods A retrospective sample of 1082 acute ischemic stroke cases was obtained that was composed of unselected patients who were treated with thrombolysis or who were undergoing contemporaneous MR imaging and CT, and a subset of International Stroke Thrombolysis-3 trial participants. Automated delineations of WML on images were validated relative to experts' manual tracings on CT images, and co-registered FLAIR MR imaging, and ratings were performed by using two conventional ordinal scales. Analyses included correlations between CT and MR imaging volumes, and agreements between automated and expert ratings. Results Automated WML volumes correlated strongly with expert-delineated WML volumes at MR imaging and CT (r 2 = 0.85 and 0.71 respectively; P < .001). Spatial-similarity of automated maps, relative to WML MR imaging, was not significantly different to that of expert WML tracings on CT images. Individual expert WML volumes at CT correlated well with each other (r 2 = 0.85), but varied widely (range, 91% of mean estimate; median estimate, 11 mL; range of estimated ranges, 0.2-68 mL). Agreements (κ) between automated ratings and consensus ratings were 0.60 (Wahlund system) and 0.64 (van Swieten system) compared with agreements between individual pairs of experts of 0.51 and 0.67, respectively, for the two rating systems (P < .01 for Wahlund system comparison of agreements). Accuracy was unaffected by established infarction, acute ischemic changes, or atrophy (P > .05). Automated preprocessing failure rate was 4%; rating errors occurred in a further 4%. Total automated processing time averaged 109 seconds (range, 79-140 seconds). Conclusion An automated method for quantifying CT cerebral white matter lesions achieves a similar accuracy to experts in unselected and multicenter cohorts. © RSNA, 2018 Online supplemental material is available for this article.

Effect of early oral feeding on length of hospital stay following gastrectomy for gastric cancer: a Japanese multicenter, randomized controlled trial.

PubMed

Shimizu, Nobuyuki; Oki, Eiji; Tanizawa, Yutaka; Suzuki, Yutaka; Aikou, Susumu; Kunisaki, Chikara; Tsuchiya, Takashi; Fukushima, Ryoji; Doki, Yuichiro; Natsugoe, Shoji; Nishida, Yasunori; Morita, Masaru; Hirabayashi, Naoki; Hatao, Fumihiko; Takahashi, Ikuo; Choda, Yasuhiro; Iwasaki, Yoshiaki; Seto, Yasuyuki

2018-05-02

This multicenter, randomized controlled study evaluates the safety of early oral feeding following gastrectomy, and its effect on the length of postoperative hospital stay. The subjects of this study were patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for gastric cancer between January 2014 and December 2015. Patients were randomly assigned to the early oral feeding group (intervention group) or the conventional postoperative management group (control group) for each procedure. We evaluated the length of postoperative hospital stay and the incidence of postoperative complications in each group. No significant differences in length of postoperative stay were found between the intervention and control groups of the patients who underwent DG. The incidence of postoperative complications was significantly greater in the DG intervention group. In contrast, the length of postoperative stay was significantly shorter in the TG intervention group, although the TG group did not attain the established target sample size. Early oral feeding did not shorten the postoperative hospital stay after DG. The higher incidence of postoperative complications precluded the unselected adoption of early oral feeding for DG patients. Further confirmative studies are required to definitively establish the potential benefits of early oral feeding for TG patients.

A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer

PubMed Central

Santa-Maria, Cesar August; Kato, Taigo; Park, Jae-Hyun; Kiyotani, Kazuma; Rademaker, Alfred; Shah, Ami N.; Gross, Leeaht; Blanco, Luis Z.; Jain, Sarika; Flaum, Lisa; Tellez, Claudia; Stein, Regina; Uthe, Regina; Gradishar, William J.; Cristofanilli, Massimo; Nakamura, Yusuke; Giles, Francis J.

2018-01-01

Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline. Eighteen evaluable patients were accrued (11 ER-positive; seven TNBC). Only three patients had a response (ORR = 17%), thus the study did not proceed to the second stage. Responses were only observed in patients with TNBC (ORR = 43%). Responders versus non-responders had upregulation of CD8, granzyme A, and perforin 1 gene expression, and higher mutational and neoantigen burden. Patients with TNBC had an oligoclonal shift of the most abundant TCR-beta clonotypes compared to those with ER-positive disease, p = 0.004. We conclude responses are low in unselected metastatic breast cancer, however, higher rates of clinical benefit were observed in TNBC. Immunogenomic dynamics may help identify phenotypes most likely to respond to immunotherapy. PMID:29721177

Perceived cognitive function in coronary artery disease--an unrecognised predictor of unemployment.

PubMed

Kiessling, Anna; Henriksson, Peter

2005-08-01

We aimed to assess whether perceived cognitive function influences employment and return to work in patients with coronary artery disease (CAD). Prospective longitudinal cohort study. Health care system of Södertälje, Stockholm County, Sweden. We included consecutive unselected patients less than 65 years of age with CAD and followed them during 2 years. Gainful employment and return to work in patients with CAD. We found that perceived cognitive function predicts both prevalence of unemployment [OR 2.06 (95% CI: 1.36-3.13); p = 0.0006] and early retirement and sick leave due to coronary artery disease [OR 1.59 (95% CI: 1.12-2.25)] both at baseline and 2 years later. Furthermore, perceived cognitive function predicted return to work after an acute coronary event [OR 2.28 (95% CI: 1.08-4.84)]. Covariates such as age, sex, prevalence and degree of angina (CCS grade), cardiovascular risk factors and events did not change the predictive power. Perceived cognitive function is a hitherto unrecognised independent predictor of unemployment, sick leave and return to work in patients with coronary artery disease. Perceived cognitive function adds a new perspective on ability to gainful employment in patients with CAD. The findings might have significance both to individual care and to society.

Bone histomorphometry in de novo renal transplant recipients indicates a further decline in bone resorption 1 year posttransplantation.

PubMed

Evenepoel, Pieter; Behets, Geert J; Viaene, Liesbeth; D'Haese, Patrick C

2017-02-01

Renal transplantation is believed to have a major impact on bone health. The present prospective observational bone biopsy study aimed to define the natural history of bone histomorphometry parameters in contemporaneous de novo renal transplant recipients. Paired bone biopsies were performed at the time of transplantation and at one-year posttransplantation in an unselected cohort of 36 patients referred for deceased kidney replacement. Parameters of mineral metabolism and circulating bone turnover markers were monitored as well. Static parameters of bone formation and especially bone resorption being already low-normal in the majority of patients at the time of renal transplantation, further declined during the first posttransplant year. However, interindividual variation was substantial, and significance was reached only for bone resorption parameters. Bone mineralization and trabecular bone volume were within the normal range at the time of transplantation (83.3% and 91.7% of graft recipients, respectively) and showed little change one-year posttransplantation. Changes in osteoclast number were paralleled by changes in circulating tartrate-resistant acid phosphatase 5b levels. Finally, cumulative glucocorticoid dose, but not the posttransplantation parathyroid hormone level, associated with trabecular bone loss. Thus, the impact of renal transplantation on bone histomorphometry is limited with only bone resorption, being already low at the time of transplantation, showing a further decline. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Determinants of quality of life in stroke survivors and their informal caregivers.

PubMed

Jönsson, Ann-Cathrin; Lindgren, Ingrid; Hallström, Björn; Norrving, Bo; Lindgren, Arne

2005-04-01

We examined longitudinal changes of quality of life (QOL) covering physical and mental factors in an unselected group of stroke patients and their informal caregivers. Our hypothesis was that informal caregivers would have better QOL than patients at both follow-ups, and that changes, if any, would be related to the patients' status. QOL of 304 consecutive stroke patients and their 234 informal caregivers from the population-based Lund Stroke Register was assessed 4 months after stroke onset with the Short Form 36 (SF-36) questionnaire. SF-36 was repeated for both groups after 16 months together with Mini Mental State Examination (MMSE) and Geriatric Depression Scale (GDS-20) for patients. The patients' mean QOL scores improved between 4 and 16 months after stroke in the socio-emotional and mental SF-36 domains and decreased in the domain physical function. Multivariate analyses showed that the patients' most important determinants of QOL after 16 months were GDS-20 score, functional status, age, and gender. Informal caregivers had better QOL than patients except for the domain role emotional and the mental component summary. The caregivers' most important determinants of QOL were their own age and the patients' functional status. Our study highlights depressive symptoms in determining QOL of stroke patients. Despite self-perceived deterioration in physical function over time, several other components of QOL improved, suggesting internal adaptation to changes in their life situations. Informal caregivers of stroke patients may be under considerable strain as suggested by their lower emotional-mental scores.

Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

PubMed

Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

2016-03-01

DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

Lead-related complications after DDD pacemaker implantation.

PubMed

Dębski, Maciej; Ulman, Mateusz; Ząbek, Andrzej; Boczar, Krzysztof; Haberka, Kazimierz; Kuniewicz, Marcin; Lelakowski, Jacek; Małecka, Barbara

2018-04-10

Pacing leads remain the weakest link in pacemaker systems despite advances in manufacturing technology. To assess the long-term pacing lead performance in an unselected real-life cohort following primary DDD pacing system implantation. A single-centre retrospective analysis of patients who underwent DDD pacing system implantation between October 1984 and December 2014 and were followed up until August 2016 was conducted. The inclusion criterion was at least one follow-up visit following post-implant discharge. The performance of each atrial and ventricular lead implanted was evaluated during the follow-up period, and the incidence of and predictive factors for lead dislodgement and failure were analysed. The data of 3771 patients and 24431.8 patient-years of follow-up were analysed. The mean follow-up of patients was 77.7 ± 61.8 months. During the study period, 7887 transvenous atrial and right ventricular pacing leads were implanted. Lead dislodgement occurred in 94 (1.2%) leads [92 (2.4%) patients], perforation in 11 (0.1%) leads [10 (0.3%) patients] and lead failure in 329 (4.2%) leads [275 (7.3%) patients]. Atrial lead position was a predictive factor for lead dislodgement, while age at implantation, polyurethane 80A insulation, subclavian vein access, unipolar lead construction and lead manufacturer were multivariate predictors of lead failure. Leads with polyurethane 80A insulation, unipolar construction and implantation via subclavian vein puncture exhibited the worst long-term performance.

Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age.

PubMed

Malphettes, Marion; Carcelain, Guislaine; Saint-Mezard, Pierre; Leblond, Véronique; Altes, Hester Korthals; Marolleau, Jean-Pierre; Debré, Patrice; Brouet, Jean-Claude; Fermand, Jean-Paul; Autran, Brigitte

2003-03-01

Immunodeficiency following autologous CD34+-purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to thymus irradiation. Aiming to assess the role of irradiated thymus in T-cell repopulation, we studied 32 adults with multiple myeloma, randomly assigned to receive high-dose therapy including total body irradiation (TBI) followed by autologous transplantation with either unselected or CD34+-selected PBSCs. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 x 10(6)/kg; P =.002). Lymphocyte subset counts were evaluated from month 3 to 24 after grafting. Naive CD4+ T cells were characterized both by phenotype and by quantification of T-cell receptor rearrangement excision circles (TRECs). The reconstitution of CD3+ and CD4+ T cells was significantly delayed in the CD34+-selected group, but eventually led to counts similar to those found in the unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+ subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells appear to be CD62L-. Age was identified as an independent adverse factor for CD4+ and CD62L+CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing PBSCs depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.

Estimated home ranges can misrepresent habitat relationships on patchy landscapes

USGS Publications Warehouse

Mitchell, M.S.; Powell, R.A.

2008-01-01

Home ranges of animals are generally structured by the selective use of resource-bearing patches that comprise habitat. Based on this concept, home ranges of animals estimated from location data are commonly used to infer habitat relationships. Because home ranges estimated from animal locations are largely continuous in space, the resource-bearing patches selected by an animal from a fragmented distribution of patches would be difficult to discern; unselected patches included in the home range estimate would bias an understanding of important habitat relationships. To evaluate potential for this bias, we generated simulated home ranges based on optimal selection of resource-bearing patches across a series of simulated resource distributions that varied in the spatial continuity of resources. For simulated home ranges where selected patches were spatially disjunct, we included interstitial, unselected cells most likely to be traveled by an animal moving among selected patches. We compared characteristics of the simulated home ranges with and without interstitial patches to evaluate how insights derived from field estimates can differ from actual characteristics of home ranges, depending on patchiness of landscapes. Our results showed that contiguous home range estimates could lead to misleading insights on the quality, size, resource content, and efficiency of home ranges, proportional to the spatial discontinuity of resource-bearing patches. We conclude the potential bias of including unselected, largely irrelevant patches in the field estimates of home ranges of animals can be high, particularly for home range estimators that assume uniform use of space within home range boundaries. Thus, inferences about the habitat relationships that ultimately define an animal's home range can be misleading where animals occupy landscapes with patchily distributed resources.

Maternal use of probiotics during pregnancy and effects on their offspring's health in an unselected population.

PubMed

Rutten, Nicole; Van der Gugten, Anne; Uiterwaal, Cuno; Vlieger, Arine; Rijkers, Ger; Van der Ent, Kors

2016-02-01

Probiotics are used by women in the perinatal period and may improve balance of microbiota, with possible health benefits for both mother and baby. Characteristics and (health) behaviour patterns of mothers using probiotics during pregnancy, and health effects on their offspring, were investigated. Differences between mothers using probiotics during pregnancy and those who did not, were assessed. In total, 341 out of 2491 (13.7%) mothers reported use of probiotics during pregnancy. There were no significant differences in maternal features (gestation, age, ethnicity, education) between users and non-users. Logistic regression analyses showed that consumption of probiotics was significantly associated with use of homeopathic products [odds ratio (OR) 1.65, 95% confidence interval (CI) 1.17-2.33, p = 0.005], maternal history of smoking (OR 1.72, 95% CI 1.25-2.37, p = 0.001) and paternal history of smoking (OR 1.39, 95% CI 1.01-1.89, p = 0.05). Common disease symptoms during the first year of life in the offspring did not differ between both groups. The use of probiotics or other health-related products without doctor's prescription during pregnancy might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not seem to induce positive health effects in the offspring in an unselected population. Aberrant microbiota compositions have been detected during critical periods when early programming occurs including pregnancy and early neonatal life. Probiotics modulate intestinal microbiota composition and are associated with positive health effects. The use of probiotics or other health-related products without doctor's prescription during pregnancy is associated with and might point to compensation for types of less favourable behaviour. Probiotic use during pregnancy does not induce positive health effects in the offspring in this unselected population.

Impact of ELN recommendations in the management of first-line treated chronic myeloid leukaemia patients: a French cross-sectional study.

PubMed

Etienne, Gabriel; Huguet, Francoise; Guerci-Bresler, Agnès; Nicolini, Franck E; Maloisel, Frédéric; Coiteux, Valérie; Dauriac, Charles; Carpentier, Nathalie; Bourdeix, Isabelle; Tulliez, Michel; Cony-Makhoul, Pascale

2016-07-01

The availability of tyrosine kinase inhibitors has extended therapeutic options for chronic myeloid leukaemia (CML) patients. Monitoring recommendations and clinical response goals have recently been updated. The objective of this study was to describe the profile of CML patients in chronic phase currently receiving first-line therapy, including treatment, monitoring and response kinetics. A multicentre, cross-sectional, epidemiological survey in unselected chronic phase CML patients in France attending consultations during a one-month period was performed. 438 of 697 (62·8%) reported patients were currently receiving first-line treatment and were analysed. Imatinib was the most frequently received treatment (72·4% of patients). Retrospective cytogenetic and molecular assessments at 3, 6, 12 or 18 months were available in 88·4% of patients. At the 12-month assessment, 32·2% were not in major molecular response (MMR). At last assessment, among 355 patients with duration of treatment ≥ 12 months, 91·5% had achieved MMR and 66·5% were in deep molecular response. This study, performed in everyday practice population of CML patients, suggests that monitoring of molecular responses in real-life practice is aligned with European LeukaemiaNet recommendations. The majority of patients still receiving first-line treatment are in optimal response, with a few being classified as in the warning area or responding to failure. © 2016 John Wiley & Sons Ltd.

Antineutrophil Cytoplasmic Antibodies Associated With Infective Endocarditis

PubMed Central

Langlois, Vincent; Lesourd, Anais; Girszyn, Nicolas; Ménard, Jean-Francois; Levesque, Hervé; Caron, Francois; Marie, Isabelle

2016-01-01

Abstract To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with infective endocarditis (IE) in internal medicine; and to compare clinical and biochemical features and outcome between patients exhibiting IE with and without ANCA. Fifty consecutive patients with IE underwent ANCA testing. The medical records of these patients were reviewed. Of the 50 patients with IE, 12 exhibited ANCA (24%). ANCA-positive patients with IE exhibited: longer duration between the onset of first symptoms and IE diagnosis (P = 0.02); and more frequently: weight loss (P = 0.017) and renal impairment (P = 0.08), lower levels of C-reactive protein (P = 0.0009) and serum albumin (P = 0.0032), involvement of both aortic and mitral valves (P = 0.009), and longer hospital stay (P = 0.016). Under multivariate analysis, significant factors for ANCA-associated IE were: longer hospital stay (P = 0.004), lower level of serum albumin (P = 0.02), and multiple valve involvement (P = 0.04). Mortality rate was 25% in ANCA patients; death was because of IE complications in all these patients. Our study identifies a high prevalence of ANCA in unselected patients with IE in internal medicine (24%). Our findings further underscore that ANCA may be associated with a subacute form of IE leading to multiple valve involvement and more frequent renal impairment. Because death was due to IE complications in all patients, our data suggest that aggressive therapy may be required to improve such patients’ outcome. PMID:26817911

Sleep disruption is related to poor response inhibition in individuals with obsessive-compulsive and repetitive negative thought symptoms.

PubMed

Nota, Jacob A; Schubert, Jessica R; Coles, Meredith E

2016-03-01

Obsessive-compulsive (OC) symptoms and repetitive negative thinking (RNT) are associated with poor inhibitory control. Sleep disruptions may partially mediate these relations and/or act as a "second hit" to individuals with OC symptoms and RNT. Models including habitual (past month) hours slept and bedtimes were tested. We employed a go/no-go task that allowed us to examine the relation between sleep and inhibition with various task contingencies. Sixty-seven unselected individuals were recruited from the participant pool at a public university. Bias-corrected bootstrap estimates did not show that sleep disruption mediated the relation between OC symptoms and response inhibition nor the relation between RNT and response inhibition. Multiple linear regression analyses found significant interactions between hours slept and OC symptom severity and between RNT and hours slept to predict poor response inhibition. Hours slept significantly negatively predicted commission errors when OC symptoms and RNT levels were relatively heightened but not when OC symptoms and RNT levels were relatively low. These effects were present in blocks where task contingencies were designed to shape a no-go bias. No significant relations were found with habitual bedtimes. The cross-sectional study design precludes testing the temporal precedence of symptoms in the "second hit" model. The unselected sample also limits generalization to clinical samples. These findings support a "second hit" model of interaction between sleep disruption and perseverative thoughts and behaviors. Further research on the mechanisms of the relation between sleep disruption and perseverative thought symptoms (OC and RNT) is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study designs for identification of rare disease variants in complex diseases: the utility of family-based designs.

PubMed

Ionita-Laza, Iuliana; Ottman, Ruth

2011-11-01

The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for association testing of rare variants in family-based designs or designs based on unselected affected individuals. This framework allows us to quantify the enrichment in rare disease variants in families containing multiple affected individuals and to investigate the optimal design of studies aiming to identify rare disease variants in complex traits. We show that for many complex diseases with small values for the overall sibling recurrence risk ratio, such as Alzheimer's disease and most cancers, sequencing affected individuals with a positive family history of the disease can be extremely advantageous for identifying rare disease variants. In contrast, for complex diseases with large values of the sibling recurrence risk ratio, sequencing unselected affected individuals may be preferable.

A Membrane-Free Neutral pH Formate Fuel Cell Enabled by a Selective Nickel Sulfide Oxygen Reduction Catalyst.

PubMed

Yan, Bing; Concannon, Nolan M; Milshtein, Jarrod D; Brushett, Fikile R; Surendranath, Yogesh

2017-06-19

Polymer electrolyte membranes employed in contemporary fuel cells severely limit device design and restrict catalyst choice, but are essential for preventing short-circuiting reactions at unselective anode and cathode catalysts. Herein, we report that nickel sulfide Ni 3 S 2 is a highly selective catalyst for the oxygen reduction reaction in the presence of 1.0 m formate. We combine this selective cathode with a carbon-supported palladium (Pd/C) anode to establish a membrane-free, room-temperature formate fuel cell that operates under benign neutral pH conditions. Proof-of-concept cells display open circuit voltages of approximately 0.7 V and peak power values greater than 1 mW cm -2 , significantly outperforming the identical device employing an unselective platinum (Pt) cathode. The work establishes the power of selective catalysis to enable versatile membrane-free fuel cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heterogeneous Photocatalysis and Photoelectrocatalysis: From Unselective Abatement of Noxious Species to Selective Production of High-Value Chemicals.

PubMed

Augugliaro, Vincenzo; Camera-Roda, Giovanni; Loddo, Vittorio; Palmisano, Giovanni; Palmisano, Leonardo; Soria, Javier; Yurdakal, Sedat

2015-05-21

Heterogeneous photocatalysis and photoelectrocatalysis have been considered as oxidation technologies to abate unselectively noxious species. This article focuses instead on the utilization of these methods for selective syntheses of organic molecules. Some promising reactions have been reported in the presence of various TiO2 samples and the important role played by the amorphous phase has been discussed. The low solubility of most of the organic compounds in water limits the utilization of photocatalysis. Dimethyl carbonate has been proposed as an alternative green organic solvent. The recovery of the products by coupling photocatalysis with pervaporation membrane technology seems to be a solution for future industrial applications. As far as photoelectrocatalysis is concerned, a decrease in recombination of the photogenerated pairs occurs, enhancing the rate of the oxidation reactions and the quantum yield. Another benefit is to avoid reaction(s) between the intermediates and the substrate, as anodic and cathodic reactions take place in different places.

High-dose interleukin 2 in patients with metastatic renal cell carcinoma with sarcomatoid features

PubMed Central

Arjunan, Ananth; Wang, Hong; Saul, Melissa; Davar, Diwakar; Appleman, Leonard J.; Friedland, David; Parikh, Rahul A.

2017-01-01

Background High-dose interleukin-2 (HD IL-2) is used in the treatment of metastatic renal cell carcinoma (mRCC) and has an overall response rate (ORR) of 12–20% and a complete response rate (CR) of 8% in unselected populations with predominantly clear cell type renal cell carcinoma. Nearly 10–15% of patients with renal cell carcinoma exhibit sarcomatoid differentiation, a feature which correlates with a median overall survival (OS) of 9 months and overall poor prognosis. We report a single institution experience with 21 patients with mRCC with sarcomatoid features post-nephrectomy who were treated with HD IL-2. Methods Twenty one patients with mRCC with sarcomatoid features post-nephrectomy who underwent therapy with HD IL-2 were identified at the University of Pittsburgh Medical Center from 2004 to 2016. Baseline patient characteristics, HD IL-2 cycles, time to progression, and subsequent therapies were evaluated. OS and progression-free survival (PFS) in the cohort were calculated using the Kaplan-Meier method. Disease characteristics were evaluated for significance using the Fischer′s exact test and Wilcoxon rank sum test. Results Patients were predominantly Caucasian males with a median age of 54 years. A majority, 86% of these patients, had metastatic disease at time of initial presentation, primarily with lung and lymph node involvement. The ORR and CR with HD IL-2 was 10% and 5%, respectively. Initial localized disease presentation is the only variable that was significantly associated with response to HD IL-2 (p = 0.0158). Number of HD IL-2 doses did not correlate with response with a mean of 16.5 and 15.0 total doses in responders and non-responders, respectively (p = 0.53). Median PFS with HD IL-2 was 7.9 months (95% CI, 5.0–21.3). Median OS was 30.5 months (95% CI 13.3–57.66). Within the subset of patients who had progression on IL-2, median OS was 19.4 months (95% CI, 13.3–35.3). In patients who received second-line therapy, median PFS was 7.9 months (95% CI 2.4–10.2). Conclusion In patients with mRCC with sarcomatoid features, use of HD IL-2 was associated with a modest ORR and a higher survival compared to historical controls (patients with mRCC and sarcomatoid features). Thus, HD IL-2 may have a role in treating selected patients with mRCC with sarcomatoid features. PMID:29261796

High-dose interleukin 2 in patients with metastatic renal cell carcinoma with sarcomatoid features.

PubMed

Achkar, Tala; Arjunan, Ananth; Wang, Hong; Saul, Melissa; Davar, Diwakar; Appleman, Leonard J; Friedland, David; Parikh, Rahul A

2017-01-01

High-dose interleukin-2 (HD IL-2) is used in the treatment of metastatic renal cell carcinoma (mRCC) and has an overall response rate (ORR) of 12-20% and a complete response rate (CR) of 8% in unselected populations with predominantly clear cell type renal cell carcinoma. Nearly 10-15% of patients with renal cell carcinoma exhibit sarcomatoid differentiation, a feature which correlates with a median overall survival (OS) of 9 months and overall poor prognosis. We report a single institution experience with 21 patients with mRCC with sarcomatoid features post-nephrectomy who were treated with HD IL-2. Twenty one patients with mRCC with sarcomatoid features post-nephrectomy who underwent therapy with HD IL-2 were identified at the University of Pittsburgh Medical Center from 2004 to 2016. Baseline patient characteristics, HD IL-2 cycles, time to progression, and subsequent therapies were evaluated. OS and progression-free survival (PFS) in the cohort were calculated using the Kaplan-Meier method. Disease characteristics were evaluated for significance using the Fischer's exact test and Wilcoxon rank sum test. Patients were predominantly Caucasian males with a median age of 54 years. A majority, 86% of these patients, had metastatic disease at time of initial presentation, primarily with lung and lymph node involvement. The ORR and CR with HD IL-2 was 10% and 5%, respectively. Initial localized disease presentation is the only variable that was significantly associated with response to HD IL-2 (p = 0.0158). Number of HD IL-2 doses did not correlate with response with a mean of 16.5 and 15.0 total doses in responders and non-responders, respectively (p = 0.53). Median PFS with HD IL-2 was 7.9 months (95% CI, 5.0-21.3). Median OS was 30.5 months (95% CI 13.3-57.66). Within the subset of patients who had progression on IL-2, median OS was 19.4 months (95% CI, 13.3-35.3). In patients who received second-line therapy, median PFS was 7.9 months (95% CI 2.4-10.2). In patients with mRCC with sarcomatoid features, use of HD IL-2 was associated with a modest ORR and a higher survival compared to historical controls (patients with mRCC and sarcomatoid features). Thus, HD IL-2 may have a role in treating selected patients with mRCC with sarcomatoid features.

National Early Warning Score (NEWS) as an emergency department predictor of disease severity and 90-day survival in the acutely dyspneic patient - a prospective observational study.

PubMed

Bilben, Bente; Grandal, Linda; Søvik, Signe

2016-06-02

National Early Warning Score (NEWS) was designed to detect deteriorating patients in hospital wards, specifically those at increased risk of ICU admission, cardiac arrest, or death within 24 h. NEWS is not validated for use in Emergency Departments (ED), but emerging data suggest it may be useful. A criticism of NEWS is that patients with chronic poor oxygenation, e.g. severe chronic obstructive pulmonary disease (COPD), will have elevated NEWS also in the absence of acute deterioration, possibly reducing the predictive power of NEWS in this subgroup. We wanted to prospectively evaluate the usefulness of NEWS in unselected adult patients emergently presenting in a Norwegian ED with respiratory distress as main symptom. In respiratory distressed patients, NEWS was calculated on ED arrival, after 2-4 h, and the next day. Manchester Triage Scale (MTS) category, age, gender, comorbidity (ASA score), ICU-admission, ventilatory support, and discharge diagnoses were noted. Survival status was tracked for >90 days through the Population Registry. Data are medians (25-75th percentiles). Factors predicting 90-day survival were analysed with multiple logistic regression. We included 246 patients; 71 years old (60-80), 89 % home-dwelling, 74 % ASA 3-4, 72 % MTS 1-2, 88 % admitted to hospital. NEWS on arrival was 5 (3-7). NEWS correlated closely with MTS category and maximum in-hospital level of care (ED, ward, high-dependency unit, ICU). Sixteen patients died in-hospital, 26 died after discharge within 90 days. Controlled for age, ASA score, and COPD, a higher NEWS on ED arrival predicted poorer 90-day survival. Increased NEWS also correlated with decreased 30-day- and in-hospital survival and a decreased probability for home-dwelling patients to be discharged directly home. In respiratory distressed patients, NEWS on ED arrival correlated closely with triage category and need of ICU admission and predicted long-term out-of-hospital survival controlled for age, comorbidity, and COPD. NEWS should be explored in the ED setting to determine its role in clinical decision-making and in communication along the acute care chain.

Fecal incontinence after minor anorectal surgery.

PubMed

Zbar, A P; Beer-Gabel, M; Chiappa, A C; Aslam, M

2001-11-01

Fecal leakage after open lateral internal anal sphincterotomy for chronic anal fissure is common, but underreported. The aim of this study was to prospectively assess the physiologic and morphologic effects of sphincterotomy, comparing continent and incontinent patients after surgery. This group was further compared with an unselected group of patients presenting with incontinence after hemorrhoidectomy. Between January 1997 and June 1999, 23 patients were prospectively followed up through internal sphincterotomy with conventional and vector volume anorectal manometry, parametric assessment of the rectoanal inhibitory reflex, and endoanal magnetic resonance imaging. Fourteen continent patients were compared with 9 incontinent postoperative cases, 9 patients referred with incontinence after hemorrhoidectomy, and 33 healthy volunteers without anorectal disease. Significant differences were noted between continent and incontinent postsphincterotomy cases for all resting conventional and vector volume parameters and for some squeeze parameters. Although there was a significant reduction in postoperative high pressure zone length at rest, there were no differences between the postoperative groups. There was an increase in sphincter asymmetry of 6.7 percent (+/- 3.5 percent) in incontinent postsphincterotomy patients and a decrease of 2.8 percent (+/- 3.2 percent) in continent cases. Significant differences were noted for resting parameters between incontinent postsphincterotomy and posthemorrhoidectomy patients, with a higher resting sphincter asymmetry in the latter group. The area under the rectoanal inhibitory curve was smaller in postsphincterotomy incontinent patients when compared with continent cohorts over the distal and intermediate sphincter zones at rest with a reduced latency of inhibition. There was no difference in the magnetic resonance images of the sphincterotomy site between incontinent and continent postsphincterotomy cases and no posthemorrhoidectomy case had evidence of sphincteric damage. There are complex significant differences in the postoperative physiology of patients undergoing lateral internal sphincterotomy who become incontinent when compared with those who maintain continence. These physiologic changes are not reflected in detectable morphologic sphincteric differences. It is unknown whether these changes predict for long-term incontinence, and it is suggested that postoperative incontinence after minor anorectal surgery is not necessarily related either to a preexisting sphincter defect or inadvertent intraoperative sphincter injury.

The a´ velocity in the tissue Doppler predicts S/D ratio <1 in patients with a normal ejection fraction.

PubMed

Johansson, Benny; Lundin, Fredrik; Tegeback, Rolf; Bojö, Leif

2018-04-13

To compare the ability of the a´ velocity and the e´ velocity in predicting a dominant diastolic pulmonary vein flow (S/D ratio <1) in patients with normal ejection fraction. We retrospectively evaluated the diastolic function according to the ASE/EACVI guidelines, the S/D ratio and the septal, lateral and average a´ velocity in 293 unselected in-hospital patients, aged 39-86 years, in sinus rhythm and with no or mild valve disease, having a normal systolic function (EF >50%). There was a good linear correlation between the S/D ratio and the a´ velocity, but a tendency towards a negative correlation between the S/D ratio and the e´ velocity. S/D ratio <1 was seen in 43 patients. These patients had a significantly lower a´ velocity compared to those with S/D-ratio ≥1, septal (6,1 ± 2,4 v 8,8 ± 2,1 cm/s; p < .001) and lateral (6,0 ± 2,6 v 9,3 ± 2,5 cm/s; p < .001) No significant difference was seen in the septal e´ velocity (6,8 ± 2,4 v 6,8 ± 2,1 cm/s), lateral e´ velocity (9,4 ± 2,6 v 9,1 ± 2,8 cm/s) or in the ejection fraction (58,6 ± 4,4% v 58,7 ± 4,0%). A diastolic dysfunction was present in 62 patients, normal diastolic function in 231 patients. The a´ velocity was significantly lower in patients with S/D ratio <1 in both groups (p < .01). The a´ velocity is superior to the e´ velocity in predicting S/D ratio <1 in patients with normal ejection fraction regardless the ASE/EACVI diastolic classification. A failing left atrium seems to be the explanation.

Characteristics and care pathways of advanced cancer patients in a palliative-supportive care unit and an oncological ward.

PubMed

Mercadante, Sebastiano; Marchetti, Paolo; Adile, Claudio; Caruselli, Amanda; Ferrera, Patrizia; Costanzi, Andrea; Casuccio, Alessandra

2018-06-01

A supportive palliative care unit (SPCU) may have a positive impact on patients' care. The aim of this study was to compare the pattern of patients admitted to a specialized SPCU and to a traditional oncologic ward (OW) in a consecutive sample of advanced cancer patients. Data on patients demographics, reasons for and kind of admission, care-giver, anticancer treatments, being on/off treatment or uncertain, origin setting, who proposed hospital admission, the use of opioids, and hospitalization were gathered. The same parameters were recorded at discharge. A follow-up was performed by phone 1 month after discharge. Two-hundred patients were surveyed. Awareness of disease was more complete in OW patients (P = 0.001). Uncontrolled pain and symptoms were the prevalent reasons for admission to SPCU (P < 0.0005). Toxicity from chemotherapy was more frequently reported by OW patients (P = 0.001). SPCU patients received higher doses of opioids (P = 0.004). More SPCU patients were referred from home and were discharged home (P < 0.0005 and P = 0.018, respectively). Emergency admissions were more frequently reported in OW patients (P < 0.0005). One month after, more SPCU patients were at home and were still on active treatment (P = 0.002, and P = 0.05, respectively). More OW patients died within 1 month (P = 0.001). SPCU allows a better planning admission to hospital and a better care trajectory in advanced cancer patients in comparison to a busy OW, where unselected emergencies more frequently occur.

[Treatment of acromegaly with octreotide LAR].

PubMed

Sosa, Ernesto; Espinosa-de-los-Monteros, Ana Laura; González, Baldomero; Vargas, Guadalupe; Mier, Fernando; Mercado, Moisés

2008-01-01

Treatment of acromegaly with somastostatin analogues, albeit highly effective, is not curative and its elevated cost represents a major disadvantage. Hereby we describe our Center's experience using a fixed, 20 mg q.4 weeks- dose of octreotide LAR. 97 patients, 69 females, 71 with macroadenomas, treated with 20-mg im injections of octreotide LAR every 4 weeks, in 23 as primary therapy. No dose escalation was allowed. Patients were evaluated with GH and IGF-1 levels at 4 weeks after the third injection; thereafter, assessments occurred at 3 to 6 months intervals. In 27 unselected patients, evaluations were also performed 6 weeks after the SA injection. A GH concentration < 2.5 ng/mL was reached by 71%, 75% and 83% of patients at the 3rd , 6th and 12th months of follow up respectively, whereas over 30% achieved an IGF-1 index < or = 1.0 at each of these time points, and both biochemical goals were achieved by 30%, 33% and 32% of patients at the same time points. Biochemical success was the same for those patients treated primarily and those treated secondarily and prior radiation made no difference. A baseline GH level > 10 ng/mL was associated with a poor response. A biochemical control rate comparable with other published series it is feasible to reach with the treatment with a fixed dose of 20 mg.

Ovarian Epithelial Inclusions With Mucinous Differentiation: A Clinicopathologic Study of 42 Cases.

PubMed

Seidman, Jeffrey D; Krishnan, Jayashree

2017-07-01

Ovarian epithelial inclusions lined by mucinous epithelium are rare and of uncertain origin. Ovaries containing such inclusions were studied in 42 women. The inclusions were divided into 3 groups: serous epithelial lined with typical ciliated morphology but with distinct basophilic cytoplasmic mucin in some or all of the lining cells, those lined by typical mucinous epithelium, and those lined by a combination of typical mucinous epithelium and serous epithelium. The mean patient age was 61.5 years. Pure mucinous inclusions were found in 27 patients, serous-type inclusions with cytoplasmic mucin in 20, and mixed type in 10. All 3 types of inclusions were found in 1 patient. Two types of inclusions were found in 13. Four patients had associated mucinous neoplasms (1 mucinous cystadenoma, 1 atypical proliferative seromucinous tumor, and 2 seromucinous cystadenomas), and 11 patients (26%) had endometriosis. The fallopian tubes in 4 patients (9.5%) also displayed mucinous metaplasia; this was not significantly different from the 3.1% we found in our previously reported series of unselected tubes from the same population. These findings suggest that mucinous inclusions may arise as a direct metaplastic change in serous-type inclusions. Other possible origins of mucinous inclusions in the ovarian cortex include endometriosis and Brenner (transitional cell) nests. Whether such inclusions can be a source of mucinous ovarian neoplasms as are Brenner tumors and mature cystic teratomas is unknown and may warrant further investigation.

Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type.

PubMed

Hutton, Saunie M; Spritz, Richard A

2008-10-01

Oculocutaneous albinism (OCA) is a genetically heterogeneous group of disorders characterized by absent or reduced pigmentation of the skin, hair, and eyes. In humans, four genes have been associated with "classical" OCA and another 12 genes with syndromic forms of OCA. To assess the prevalence of different forms of OCA and different gene mutations among non-Hispanic Caucasian patients, we performed DNA sequence analysis of the four genes associated with "classical" OCA (TYR, OCA2, TYRP1, SLC45A2), the two principal genes associated with syndromic OCA (HPS1, HPS4), and a candidate OCA gene (SILV), in 121 unrelated, unselected non-Hispanic/Latino Caucasian patients carrying the clinical diagnosis of OCA. We identified apparent pathologic TYR gene mutations in 69% of patients, OCA2 mutations in 18%, SLC45A2 mutations in 6%, and no apparent pathological mutations in 7% of patients. We found no mutations of TYRP1, HPS1, HPS4, or SILV in any patients. Although we observed a diversity of mutations for each gene, a relatively small number of different mutant alleles account for a majority of the total. This study demonstrates that, contrary to long-held clinical lore, OCA1, not OCA2, is by far the most frequent cause of OCA among Caucasian patients.

Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals.

PubMed

Fitzpatrick, J M; Biswas, J S; Edgeworth, J D; Islam, J; Jenkins, N; Judge, R; Lavery, A J; Melzer, M; Morris-Jones, S; Nsutebu, E F; Peters, J; Pillay, D G; Pink, F; Price, J R; Scarborough, M; Thwaites, G E; Tilley, R; Walker, A S; Llewelyn, M J

2016-03-01

Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (p <0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Rome Foundation-Asian working team report: Asian functional gastrointestinal disorder symptom clusters.

PubMed

Siah, Kewin Tien Ho; Gong, Xiaorong; Yang, Xi Jessie; Whitehead, William E; Chen, Minhu; Hou, Xiaohua; Pratap, Nitesh; Ghoshal, Uday C; Syam, Ari F; Abdullah, Murdani; Choi, Myung-Gyu; Bak, Young-Tae; Lu, Ching-Liang; Gonlachanvit, Sutep; Boon, Chua Seng; Fang, Fan; Cheong, Pui Kuan; Wu, Justin C Y; Gwee, Kok-Ann

2018-06-01

Functional gastrointestinal disorders (FGIDs) are diagnosed by the presence of a characteristic set of symptoms. However, the current criteria-based diagnostic approach is to some extent subjective and largely derived from observations in English-speaking Western patients. We aimed to identify latent symptom clusters in Asian patients with FGID. 1805 consecutive unselected patients with FGID who presented for primary or secondary care to 11 centres across Asia completed a cultural and linguistic adaptation of the Rome III Diagnostic Questionnaire that was translated to the local languages. Principal components factor analysis with varimax rotation was used to identify symptom clusters. Nine symptom clusters were identified, consisting of two oesophageal factors (F6: globus, odynophagia and dysphagia; F9: chest pain and heartburn), two gastroduodenal factors (F5: bloating, fullness, belching and flatulence; F8 regurgitation, nausea and vomiting), three bowel factors (F2: abdominal pain and diarrhoea; F3: meal-related bowel symptoms; F7: upper abdominal pain and constipation) and two anorectal factors (F1: anorectal pain and constipation; F4: diarrhoea, urgency and incontinence). We found that the broad categorisation used both in clinical practice and in the Rome system, that is, broad anatomical divisions, and certain diagnoses with long historical records, that is, IBS with diarrhoea, and chronic constipation, are still valid in our Asian societies. In addition, we found a bowel symptom cluster with meal trigger and a gas cluster that suggests a different emphasis in our populations. Future studies to compare a non-Asian cohort and to match to putative pathophysiology will help to verify our findings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Autobiographical memory and structural brain changes in chronic phase TBI.

PubMed

Esopenko, Carrie; Levine, Brian

2017-04-01

Traumatic brain injury (TBI) is associated with a range of neuropsychological deficits, including attention, memory, and executive functioning attributable to diffuse axonal injury (DAI) with accompanying focal frontal and temporal damage. Although the memory deficit of TBI has been well characterized with laboratory tests, comparatively little research has examined retrograde autobiographical memory (AM) at the chronic phase of TBI, with no prior studies of unselected patients drawn directly from hospital admissions for trauma. Moreover, little is known about the effects of TBI on canonical episodic and non-episodic (e.g., semantic) AM processes. In the present study, we assessed the effects of chronic-phase TBI on AM in patients with focal and DAI spanning the range of TBI severity. Patients and socioeconomic- and age-matched controls were administered the Autobiographical Interview (AI) (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) a widely used method for dissociating episodic and semantic elements of AM, along with tests of neuropsychological and functional outcome. Measures of episodic and non-episodic AM were compared with regional brain volumes derived from high-resolution structural magnetic resonance imaging (MRI). Severe TBI (but not mild or moderate TBI) was associated with reduced recall of episodic autobiographical details and increased recall of non-episodic details relative to healthy comparison participants. There were no significant associations between AM performance and neuropsychological or functional outcome measures. Within the full TBI sample, autobiographical episodic memory was associated with reduced volume distributed across temporal, parietal, and prefrontal regions considered to be part of the brain's AM network. These results suggest that TBI-related distributed volume loss affects episodic autobiographical recollection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Two-year follow-up of low-level laser therapy for elderly with painful adhesive capsulitis of the shoulder

PubMed Central

Ip, David; Fu, Nga-Yue

2015-01-01

Introduction This paper reports on the medium-term mean 2-year prospective follow-up of a patient cohort of 35 unselected elderly patients with mean age of 65 years who visited our tertiary referral pain center for painful adhesive capsulitis of the shoulder managed with low-level laser therapy (LLLT). Materials and methods All patients in this prospective cohort study had documentation of the diagnosis by contrast-enhanced magnetic resonance imaging before study entry and all had failed to respond to a combination of conventional physical therapy and nonsteroidal anti-inflammatory medications for not fewer than 4 weeks. LLLT, at a wavelength of 810 nm emitted from a GaAIAs semiconductor laser device with 5.4 J per point and a power density of 20 mW/cm2, was employed to irradiate six predetermined anatomic points and two acupuncture points. The treatment regimen consisted of three sessions of treatment per week for 8 consecutive weeks. Each treatment session lasted 180 seconds. Serial clinical assessment was undertaken using the Constant–Murley shoulder score. Results A total of 50 painful shoulder joints were treated, as a number of elderly presented with bilateral symptoms. All but four painful shoulders showed significant improvement in Constant–Murley shoulder score at the end of 8-weeks’ LLLT treatment and, surprisingly, the improvement was found maintained at follow-up assessments at 1 year and 2 years. Conclusion We conclude that LLLT is a viable option in the conservative treatment of shoulder pain arising from adhesive capsulitis of the shoulder in the elderly, with a positive clinical result of more than 90% and with clinical efficacy both in the short-term and the medium-term. PMID:26045677

Differences in patient selection and outcomes between SilverHawk atherectomy and laser ablation in the treatment of femoropopliteal in-stent restenosis: a retrospective analysis from a single center.

PubMed

Shammas, Nicolas W; Shammas, Gail A; Jerin, Michael

2013-12-01

To analyze differences in the application and outcomes of SilverHawk atherectomy (SH) and excimer laser ablation (ELA) in the treatment of femoropopliteal in-stent restenosis (ISR) in an unselected cohort of patients treated at a single center. Between January 2005 and June 2010, 81 consecutive patients (46 men; mean age 69.1 years, range 43-86) underwent directional atherectomy (41 SH, 40 ELA) for femoropopliteal ISR lesions. Data were reviewed retrospectively on procedural outcomes, major adverse events, and 1-year target lesion revascularization (TLR) obtained from medical records and supplemented with telephone calls. The primary endpoint was symptom-driven TLR at 1 year; secondary endpoints were death and amputation. ELA was utilized more frequently than SH in longer lesions (210.4±104 vs. 126.2±79.3 mm, respectively; p=0.001), subacute presentation (55% vs. 14.6%, p=0.001), TASC D lesions (47.5% vs. 12.2%), and in patients with more angiographic thrombus (42.5% vs. 4.9%, p=0.001). Final angiographic success (<30% residual narrowing post final treatment) was similar between ELA and SH (92.5% vs. 100%, respectively, p=0.12). Bailout stenting was significantly higher with ELA vs. SH (50.0% vs. 24.4%, p=0.022). At 1 year, TLR had occurred in 48.7% of the ELA patients vs. 31.7% of the SH cases (p=0.171). Regression analysis confirmed that SH was a predictor of TLR at 1 year (hazard ratio 2.679, 95% CI 1.015 to 7.073, p=0.047). Both SH and ELA continue to have a high TLR rate in treating ISR of the femoral and popliteal arteries. A higher rate of delayed failure is seen with SH and an earlier, steeper loss of TLR-free survival is seen with ELA.

2D XD-GRASP provides better image quality than conventional 2D cardiac cine MRI for patients who cannot suspend respiration

PubMed Central

Piekarski, Eve; Chitiboi, Teodora; Ramb, Rebecca; Latson, Larry A; Bhatla, Puneet; Feng, Li; Axel, Leon

2017-01-01

Object Residual respiratory motion degrades image quality in conventional cardiac cine MRI (CCMR). We evaluated whether a free-breathing (FB) radial imaging CCMR sequence with compressed sensing reconstruction (eXtra-Dimension (e.g. cardiac and respiratory phases) Golden-angle RAdial Sparse Parallel, or XD-GRASP) could provide better image quality than a conventional Cartesian breath-held (BH) sequence, in an unselected population of patients undergoing clinical CCMR. Material and Methods 101 patients who underwent BH and FB imaging in a mid-ventricular short-axis plane at a matching location were included. Visual and quantitative image analysis was performed by two blinded experienced readers, using a 5-point qualitative scale to score overall image quality and visual signal-to-noise ratio (SNR) grade, with measures of noise and sharpness. End-diastole (ED) and end-systole (ES) left-ventricular areas were also measured and compared for both BH and FB images. Results Image quality was generally better with the BH cines (overall quality grade BH vs FB: 4 vs 2.9, p<0.001; noise 0.06 vs 0.08 p< 0.001; SNR grade: 4.1 vs 3, p<0.001), except for sharpness (p=0.48). There were no significant differences between BH and FB images regarding ED or ES areas (p=0.35 and 0.12). 18 of the 101 patients had impaired BH image quality (grades 1 or 2). In this subgroup, image quality of the FB images was better (p=0.0032), as was the SNR grade (p=0.003), but there were no significant differences regarding noise and sharpness (p=0.45, p=0.47). Conclusion Although FB XD-GRASP CCMR was visually inferior to conventional BH cardiac cine in general, it provided improved image quality in the subgroup of patients presenting respiratory motion-induced artifacts on breath-held images. PMID:29067539

Acute respiratory distress syndrome: an audit of incidence and outcome in Scottish intensive care units.

PubMed

Hughes, M; MacKirdy, F N; Ross, J; Norrie, J; Grant, I S

2003-09-01

This prospective audit of incidence and outcome of the acute respiratory distress syndrome was conducted as part of the national audit of intensive care practice in Scotland. All patients with acute respiratory distress syndrome in 23 adult intensive care units were identified using the diagnostic criteria defined by the American-European Consensus Conference. Daily data collection was continued until death or intensive care unit discharge. Three hundred and sixty-nine patients were diagnosed with acute respiratory distress syndrome over the 8-month study period. The frequency of acute respiratory distress syndrome in the intensive care unit population was 8.1%; the incidence in the Scottish population was estimated at 16.0 cases.100,000(-1).year(-1). Intensive care unit mortality for acute respiratory distress syndrome was 53.1%, with a hospital mortality of 60.9%. In our national unselected population of critically ill patients, the overall outcome is comparable with published series (Acute Physiology and Chronic Health Evaluation II standardised mortality ratio = 0.99). However, mortality from acute respiratory distress syndrome in Scotland is substantially higher than in recent other series suggesting an improvement in outcome in this condition.

Sexual Orientation in Adolescents Who Commit Suicide.

ERIC Educational Resources Information Center

Shaffer, David; And Others

1995-01-01

Examined relationship between suicidal behavior and homosexuality in adolescence in an unselected, matched sample. Found no evidence that suicide is a common characteristic of gay youth, or that when suicide does occur among gay teenagers, that it is a direct consequence of stigmatization or lack of support. (JBJ)

An Evaluation of the Navy’s Health Promotion Videotapes

DTIC Science & Technology

1990-04-30

1263. Fisher, L., Rowley, P. T., & Lipkin. M. (1981). Genetic counseling for beta- thalassemia trait following health screening in a health maintenence...counseling for x, ta- thalassemia trait in a population unselected for interest: Effects on knowledge and m ,ood. American Journal of Human Genetics

Brief time course of trait anxiety-related attentional bias to fear-conditioned stimuli: Evidence from the dual-RSVP task.

PubMed

Booth, Robert W

2017-03-01

Attentional bias to threat is a much-studied feature of anxiety; it is typically assessed using response time (RT) tasks such as the dot probe. Findings regarding the time course of attentional bias have been inconsistent, possibly because RT tasks are sensitive to processes downstream of attention. Attentional bias was assessed using an accuracy-based task in which participants detected a single digit in two simultaneous rapid serial visual presentation (RSVP) streams of letters. Before the target, two coloured shapes were presented simultaneously, one in each RSVP stream; one shape had previously been associated with threat through Pavlovian fear conditioning. Attentional bias was indicated wherever participants identified targets in the threat's RSVP stream more accurately than targets in the other RSVP stream. In 87 unselected undergraduates, trait anxiety only predicted attentional bias when the target was presented immediately following the shapes, i.e. 160 ms later; by 320 ms the bias had disappeared. This suggests attentional bias in anxiety can be extremely brief and transitory. This initial study utilised an analogue sample, and was unable to physiologically verify the efficacy of the conditioning. The next steps will be to verify these results in a sample of diagnosed anxious patients, and to use alternative threat stimuli. The results of studies using response time to assess the time course of attentional bias may partially reflect later processes such as decision making and response preparation. This may limit the efficacy of therapies aiming to retrain attentional biases using response time tasks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Automated point-of-care testing for ABO agglutination test: proof of concept and validation.

PubMed

El Kenz, H; Corazza, F

2015-07-01

ABO-incompatible red blood cell transfusions still represent an important hazard in transfusion medicine. Therefore, some countries have introduced a systematic bedside ABO agglutination test checking that the right blood is given to the right patient. However, this strategy requires an extremely time-consuming learning programme and relies on a subjective interpretation of ABO test cards agglutination. We developed a prototype of a fully automated device performing the bedside agglutination test that could be completed by reading of a barcoded wristband. This POCT checks the ABO compatibility between the patient and the blood bag. Proof of concept and analytical validation of the prototype has been completed on 451 blood samples: 238 donor packed red blood cells, 137 consecutive unselected patients for whom a blood group determination had been ordered and on 76 patient samples selected with pathology that could possibly interfere with or impair performances of the assay. We observed 100% concordance for ABO blood groups between the POCT and the laboratory instrument. These preliminary results demonstrate the feasibility of ABO determination with a simple POCT device eliminating manipulation and subjective interpretation responsible for transfusion errors. This device should be linked to the blood bank system allowing all cross-check of the results. © 2015 International Society of Blood Transfusion.

[Critical appraisal of organ procurement under Maastricht 3 condition].

PubMed

Puybasset, L; Bazin, J-E; Beloucif, S; Bizouarn, P; Crozier, S; Devalois, B; Eon, B; Fieux, F; Gisquet, E; Guibet-Lafaye, C; Kentish, N; Lienhart, A; Nicolas-Robin, A; Otero Lopez, M; Pelluchon, C; Roussin, F; Beydon, L

2012-05-01

The ethics committee of the French Society of Anesthesia and Intensive Care (Sfar) has been requested by the French Biomedical Agency to consider the issue of organ donation in patients after a decision of withdrawing life supporting therapies has been taken. This category of organ donation is performed in the USA, Canada, United Kingdom, the Netherlands and Belgium. The three former countries have published recommendations, which formalize procedures and operations. The Sfar ethics committee has considered this issue and envisioned the different aspects of the whole process. Consequently, it sounds a note of caution regarding the applicability of this type of organ procurement in unselected patient following a decision to withdraw life supporting therapies. According to the French regulation concerning organ procurement in brain dead patients, the committee stresses the need to restrict this specific way of procurement to severely brain injured patients, once confirmatory investigations predicting a catastrophic prognosis have been performed. It suggests that the nature of the confirmatory investigation required should be formalized by the French Biomedical Agency on behalf of the French parliamentarians. This should help preserving population trust regarding organ procurement and provide a framework to medical decision. This text has been endorsed by the Sfar. Copyright © 2012. Published by Elsevier SAS.

The value of radiology in predicting gallstone type when selecting patients for medical treatment.

PubMed Central

Bell, G D; Dowling, R H; Whitney, B; Sutor, D J

1975-01-01

Since medical treatment of gallstones is confined to cholesterol-rich stones, the ability of clinical radiographs to predict gallstone type was tested prospectively by comparing the preoperative radiological appearance of gallstones from 57 unselected patients with cholelithiasis coming to cholecystectomy with the subsequent analysis of the stones both by X-ray diffraction and by chemical techniques. Fifty-two per cent of the patients had 'non-functioning' gallbladders which failed to opacify after at least two contrast examinations and 25 out of 50 had radioopaque stones. Of the 25 patients with radiolucent stones, the stones in 20 ((80%) were predominantly cholesterol in type but radiology was misleading in five; three contained 40-55% calcium salts but were still radiolucent while two were amorphous and contained less than 10% cholesterol by weight on chemical analysis. While radiology was sometimes misleading when the stones were small and irregular, large radiolucent stones with a smooth profile were invariably cholesterol-rich stones. The results also show that in men calcified stones were commoner than in women and that in older women the gallstones contained more calcium salts and less cholesterol than in younger women less than 50 yr). This paper analyses critically the value and limitations of clinical radiology in predicting gallstone type. PMID:1140634

Survival After Relapse of Medulloblastoma.

PubMed

Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

2016-05-01

Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations.

The prevalence of BRCA1 and BRCA2 mutations among young Mexican women with triple-negative breast cancer

PubMed Central

Villarreal-Garza, C.; Weitzel, J. N.; Llacuachaqui, M.; Sifuentes, E.; Magallanes-Hoyos, M. C.; Gallardo, L.; Alvarez-Gómez, R. M.; Herzog, J.; Castillo, D.; Royer, R.; Akbari, Mohammad; Lara-Medina, F.; Herrera, L. A.; Mohar, A.

2015-01-01

Various guidelines recommend that women with triple-negative breast cancer should be tested for BRCA1 mutations, but the prevalence of mutations may vary with ethnic group and with geographic region, and the optimal cutoff age for testing has not been established. We estimated the frequencies of BRCA1 and BRCA2 (BRCA) mutations among 190 women with triple-negative breast cancer, unselected for family history, diagnosed at age 50 or less at a single hospital in Mexico City. Patients were screened for 115 recurrent BRCA mutations, which have been reported previously in women of Hispanic origin, including a common large rearrangement Mexican founder mutation (BRCA1 ex9-12del). A BRCA mutation was detected in 44 of 190 patients with triple-negative breast cancer (23 %). Forty-three mutations were found in BRCA1 and one mutation was found in BRCA2. Seven different mutations accounted for 39 patients (89 % of the total mutations). The Mexican founder mutation (BRCA1 ex9-12del) was found 18 times and accounted for 41 % of all mutations detected. There is a high prevalence of BRCA1 mutations among young triple-negative breast cancer patients in Mexico. Women with triple-negative breast cancer in Mexico should be screened for mutations in BRCA1. PMID:25716084

Analysis of polymorphic patterns in candidate genes in Israeli patients with prostate cancer.

PubMed

Figer, Arie; Friedman, Tal; Manguoglu, Ayse Esra; Flex, Dov; Vazina, Amnon; Novikov, Ilia; Shtrieker, Avi; Sidi, A Ami; Tichler, Thomas; Sapir, Einat Even; Baniel, Jack; Friedman, Eitan

2003-10-01

The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known. To evaluate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters. Jewish Israeli prostate cancer patients (n = 224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters. The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner. In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.

Mutation frequency in 15 common cancer genes in high-risk head and neck squamous cell carcinoma.

PubMed

McBride, Sean M; Rothenberg, S Michael; Faquin, William C; Chan, Annie W; Clark, John R; Ellisen, Leif W; Wirth, Lori J

2014-08-01

With prior studies having looked at unselected cohorts, we sought to explore the mutational landscape in a high-risk group of head and neck squamous cell carcinoma (HNSCC) tumors. A multiplexed polymerase chain reaction (PCR) assay evaluating 68 loci in 15 genes was performed on 64 patients with high-risk HNSCC. Because of the frequent PIK3CA and AKT1 mutations in patients with oropharyngeal carcinoma, we evaluated the relationship between mutation status and both clinical/pathologic variables and tumor control in this subgroup. Seventeen of 64 patients harbored mutations in the assayed loci: 16% in PIK3CA, 9% in TP53, 2% in AKT1, and 2% in epidermal growth factor receptor (EGFR). The frequency of PIK3CA/AKT1 mutations in oropharyngeal and sinonasal primaries was increased compared to other primary sites (35% vs 6%; p = .005). There was no relationship between mutation status and overall survival (OS), disease-specific death, or progression in the oropharyngeal cohort. We identified frequent PIK3CA mutations in patients with high-risk HNSCC confined predominantly to the oropharyngeal and sinonasal subsites; for the first time, mutation in AKT1 has been identified in HNSCC. Copyright © 2014 Wiley Periodicals, Inc.

Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy.

PubMed

Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

2015-07-01

Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy.Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-β2 glycoprotein 1 antibody (aβ2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test.Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), aβ2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology.The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment.

Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy

PubMed Central

Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

2015-01-01

Abstract Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy. Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-β2 glycoprotein 1 antibody (aβ2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test. Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), aβ2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology. The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment. PMID:26131823

Clinical impact of defibrillation testing at the time of implantable cardioverter-defibrillator insertion.

PubMed

Hadid, Claudio; Atienza, Felipe; Strasberg, Boris; Arenal, Ángel; Codner, Pablo; González-Torrecilla, Esteban; Datino, Tomás; Percal, Tamara; Almendral, Jesús; Ortiz, Mercedes; Martins, Raphael; Martinez-Alzamora, Nieves; Fernandez Aviles, Francisco

2015-01-01

Ventricular fibrillation is routinely induced during implantable cardioverter-defibrillator insertion to assess defibrillator performance, but this strategy is experiencing a progressive decline. We aimed to assess the efficacy of defibrillator therapies and long-term outcome in a cohort of patients that underwent defibrillator implantation with and without defibrillation testing. Retrospective observational series of consecutive patients undergoing initial defibrillator insertion or generator replacement. We registered spontaneous ventricular arrhythmias incidence and therapy efficacy, and mortality. A total of 545 patients underwent defibrillator implantation (111 with and 434 without defibrillation testing). After 19 (range 9-31) months of follow-up, the death rate per observation year (4% vs. 4%; p = 0.91) and the rate of patients with defibrillator-treated ventricular arrhythmic events per observation year (with test: 10% vs. without test: 12%; p = 0.46) were similar. The generalized estimating equations-adjusted first shock probability of success in patients with test (95%; CI 88-100%) vs. without test (98%; CI 96-100%; p = 0.42) and the proportion of successful antitachycardia therapies (with test: 87% vs. without test: 80%; p = 0.35) were similar between groups. There was no difference in the annualized rate of failed first shock per patient and per shocked patient between groups (5% vs. 4%; p = 0.94). In this observational study, that included an unselected population of patients with a defibrillator, no difference was found in overall mortality, first shock efficacy and rate of failed shocks regardless of whether defibrillation testing was performed or not.

Impairments in proverb interpretation following focal frontal lobe lesions.

PubMed

Murphy, Patrick; Shallice, Tim; Robinson, Gail; MacPherson, Sarah E; Turner, Martha; Woollett, Katherine; Bozzali, Marco; Cipolotti, Lisa

2013-09-01

The proverb interpretation task (PIT) is often used in clinical settings to evaluate frontal "executive" dysfunction. However, only a relatively small number of studies have investigated the relationship between frontal lobe lesions and performance on the PIT. We compared 52 patients with unselected focal frontal lobe lesions with 52 closely matched healthy controls on a proverb interpretation task. Participants also completed a battery of neuropsychological tests, including a fluid intelligence task (Raven's Advanced Progressive Matrices). Lesions were firstly analysed according to a standard left/right sub-division. Secondly, a finer-grained analysis compared the performance of patients with medial, left lateral and right lateral lesions with healthy controls. Thirdly, a contrast of specific frontal subgroups compared the performance of patients with medial lesions with patients with lateral frontal lesions. The results showed that patients with left frontal lesions were significantly impaired on the PIT, while in patients with right frontal lesions the impairments approached significance. Medial frontal patients were the only frontal subgroup impaired on the PIT, relative to healthy controls and lateral frontal patients. Interestingly, an error analysis indicated that a significantly higher number of concrete responses were found in the left lateral subgroup compared to healthy controls. We found no correlation between scores on the PIT and on the fluid intelligence task. Overall our results suggest that specific regions of the frontal lobes contribute to the performance on the PIT. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

Pegylated interferon-alpha2b plus ribavirin therapy in patients with hepatitis C and psychiatric disorders: results of a cohort study.

PubMed

Lang, Jean-Philippe; Melin, Pascal; Ouzan, Denis; Rotily, Michel; Fontanges, Thierry; Marcellin, Patrick; Chousterman, Michel; Cacoub, Patrice

2010-01-01

Hepatitis C antiviral therapies have significant psychiatric side effects. It is therefore believed that they might exacerbate mental illness in patients with pre-existing psychiatric disorders, resulting in poor adherence and response to antiviral treatment. We aimed to assess adherence to treatment, virological outcomes and mental safety in psychiatric patients, compared with non-psychiatric patients, treated for hepatitis C. A cohort study involved unselected hepatitis C patients on scheduled therapy with pegylated interferon-alpha2b and ribavirin, between 2002 and 2005 in France, and followed-up until 6 months after the end of treatment. Virological response was reported by the physician according to standard definitions and adverse events were monitored. Adherence to treatment was assessed by patient report. Among 1,860 patients, 403 (22%) had pre-existing psychiatric disorders, mostly depressive and anxiety disorders. Strict adherence was similar in psychiatric and non-psychiatric patients (35% versus 39%; P=0.20) as was the rate of sustained virological response (52% versus 51%; P=0.75). Conversely the rate of mental adverse events was higher in psychiatric patients (78% versus 57%; P<0.001). Baseline characteristics independently associated with the risk of later mental adverse events were history of depression, initial pegylated interferon-alpha2b dose and female gender. Antiviral therapy in hepatitis C patients with associated psychiatric disease appears as effective as in other patients but results in a higher rate of mental adverse events, emphasizing the need for close monitoring of these psychiatric patients.

Repeatability of measurements of removal of mite-infested brood to assess Varroa Sensitive Hygiene

USDA-ARS?s Scientific Manuscript database

Varroa Sensitive Hygiene is a useful resistance trait that bee breeders could increase in different populations with cost-effective and reliable tests. We investigated the reliability of a one-week test estimating the changes in infestation of brood introduced into highly selected and unselected co...

Selection signature analysis in Holstein cattle identified genes known to affect reproduction

USDA-ARS?s Scientific Manuscript database

Using direct comparison of 45,878 SNPs between a group of Holstein cattle unselected since 1964 and contemporary Holsteins that on average take 30 days longer for successful conception than the 1964 Holsteins, we conducted selection signature analyses to identify genomic regions associated with dair...

Outcomes of Cardiopulmonary Resuscitation and Estimation of Healthcare Costs in Potential ‘Do Not Resuscitate’ Cases

PubMed Central

Ahmad, Akhwand S.; Mudasser, Sayed; Khan, Muhammad N.; Abdoun, Hafiz N. H.

2016-01-01

Objectives: Cardiopulmonary resuscitation (CPR) is a life-saving procedure which may fail if applied unselectively. ‘Do not resuscitate’ (DNR) policies can help avoid futile life-saving attempts among terminally-ill patients. This study aimed to assess CPR outcomes and estimate healthcare costs in potential DNR cases. Methods: This retrospective study was carried out between March and June 2014 and included 50 adult cardiac arrest patients who had undergone CPR at Sultan Qaboos Hospital in Salalah, Oman. Medical records were reviewed and treating teams were consulted to determine DNR eligibility. The outcomes, clinical risk categories and associated healthcare costs of the DNR candidates were assessed. Results: Two-thirds of the potential DNR candidates were ≥60 years old. Eight patients (16%) were in a vegetative state, 39 (78%) had an irreversible terminal illness and 43 (86%) had a low likelihood of successful CPR. Most patients (72%) met multiple criteria for DNR eligibility. According to clinical risk categories, these patients had terminal malignancies (30%), recent massive strokes (16%), end-stage organ failure (30%) or were bed-bound (50%). Initial CPR was unsuccessful in 30 patients (60%); the remaining 20 patients (40%) were initially resuscitated but subsequently died, with 70% dying within 24 hours. These patients were ventilated for an average of 5.6 days, with four patients (20%) requiring >15 days of ventilation. The average healthcare cost per patient was USD $1,958.9. Conclusion: With careful assessment, potential DNR patients can be identified and futile CPR efforts avoided. Institutional DNR policies may help to reduce healthcare costs and improve services. PMID:26909209

Critical Dysphagia is Common in Parkinson Disease and Occurs Even in Early Stages: A Prospective Cohort Study.

PubMed

Pflug, Christina; Bihler, Moritz; Emich, Katharina; Niessen, Almut; Nienstedt, Julie Cläre; Flügel, Till; Koseki, Jana-Christiane; Plaetke, Rosemarie; Hidding, Ute; Gerloff, Christian; Buhmann, Carsten

2018-02-01

To assess the prevalence of dysphagia and its typical findings in unselected "real-world" Parkinson patients using an objective gold-standard method. This was a prospective, controlled, cross-sectional study conducted in 119 consecutive Parkinson patients of all stages independent of subjective dysphagia. Patients and 32 controls were clinically and endoscopically examined by flexible endoscopic evaluation of swallowing (FEES) to evaluate the deglutition with regard to three consistencies (water, biscuit, and bread). Typical findings of dysphagia like penetration and aspiration, residues, and leakage were assessed. Dysphagia was common in Parkinson patients and occurred in all, even early, disease stages. Only 5% (6/119) of patients showed a completely unremarkable deglutition. Aspiration was seen in 25% (30/119) of patients and always related to water. Residues occurred in 93% (111/119), most commonly for bread. Leakage was much less frequent and was found in only 3-18%, depending on consistency. In a significant fraction of patients, objective dysphagia was not subjectively perceived. A total of 16% of asymptomatic patients suffered from critical aspiration. Significant swallowing deficiencies already occurred in early disease. Aspiration was found in 4 of 20 (20%) patients with disease duration of less than 2 years. Seven of 57 patients (12%) with Hoehn and Yahr stage 2 suffered from severe aspiration. Given the high frequency of critical aspiration in Parkinson disease, these patients should be evaluated early for dysphagia to avoid complications and recommend an adequate therapy. FEES is a simple, cost efficient, minimally invasive method that is ideally suited for this purpose.

Exposure to well water and pesticides in Parkinson's disease: a case-control study in the Madrid area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jimenez-Jimenez, F.J.; Mateo, D.; Gimenez-Roldan, S.

1992-01-01

Past exposure to well water and pesticides was assessed in 128 unselected Parkinson's disease (PD) patients and 256 age and sex-matched controls. All were residents in a defined urban area of Madrid, Spain. In keeping with other reports, we found that exposure to well water might be a factor associated with the likelihood of developing PD, though only prolonged exposures of 30 years or longer were significantly different between PD and controls (p less than 0.02). In contrast, past exposure to pesticides did not appear to be associated with an increased risk of developing PD. Prolonged well water drinking antedatingmore » the development of PD was not associated with early onset of the disease, nor did such cases progress to greater disability. Future case-control studies addressing prolonged well water consumption as a risk factor in PD should look for differences in the content of substances other than pesticides in the water as determined by the source of water to which patients may have been specifically exposed.« less

Cerebellar damage impairs the self-rating of regret feeling in a gambling task

PubMed Central

Clausi, Silvia; Coricelli, Giorgio; Pisotta, Iolanda; Pavone, Enea Francesco; Lauriola, Marco; Molinari, Marco; Leggio, Maria

2015-01-01

Anatomical, clinical, and neuroimaging evidence implicates the cerebellum in processing emotions and feelings. Moreover recent studies showed a cerebellar involvement in pathologies such as autism, schizophrenia and alexithymia, in which emotional processing have been found altered. However, cerebellar function in the modulation of emotional responses remains debated. In this study, emotions that are involved directly in decision-making were examined in 15 patients (six males; age range 17–60 years) affected by cerebellar damage and 15 well matched healthy controls. We used a gambling task, in which subjects’ choices and evaluation of outcomes with regard to their anticipated and actual emotional impact were analyzed. Emotions, such as regret and relief, were elicited, based on the outcome of the unselected gamble. Interestingly, despite their ability to avoid regret in subsequent choices, patients affected by cerebellar lesions were significantly impaired in evaluating the feeling of regret subjectively. These results demonstrate that the cerebellum is involved in conscious recognizing of negative feelings caused by the sense of self-responsibility for an incorrect decision. PMID:25999829

Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia.

PubMed

Lazarevic, Vladimir; Hörstedt, Ann-Sofi; Johansson, Bertil; Antunovic, Petar; Billström, Rolf; Derolf, Åsa; Lehmann, Sören; Möllgård, Lars; Peterson, Stefan; Stockelberg, Dick; Uggla, Bertil; Vennström, Lovisa; Wahlin, Anders; Höglund, Martin; Juliusson, Gunnar

2015-05-01

Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80 yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Systematic follow-up after curative surgery for colorectal cancer in Norway: a population-based audit of effectiveness, costs, and compliance.

PubMed

Körner, Hartwig; Söreide, Kjetil; Stokkeland, Pål J; Söreide, Jon Arne

2005-03-01

In this study, we analyzed the Norwegian guidelines for systematic follow-up after curative colorectal cancer surgery in a large single institution. Three hundred fourteen consecutive unselected patients undergoing curative surgery for colorectal cancer between 1996 and 1999 were studied with regard to asymptomatic curable recurrence, compliance with the program, and cost. Follow-up included carcinoembryonic antigen (CEA) interval measurements, colonoscopy, ultrasonography of the liver, and radiography of the chest. In 194 (62%) of the patients, follow-up was conducted according to the Norwegian guidelines. Twenty-one patients (11%) were operated on for curable recurrence, and 18 patients (9%) were disease free after curative surgery for recurrence at evaluation. Four metachronous tumors (2%) were found. CEA interval measurement had to be made most frequently (534 tests needed) to detect one asymptomatic curable recurrence. Follow-up program did not influence cancer-specific survival. Overall compliance with the surveillance program was 66%, being lowest for colonoscopy (55%) and highest for ultrasonography of the liver (85%). The total program cost was 228,117 euro (US 280,994 dollars), translating into 20,530 euro (US 25,289 dollars) for one surviving patient after surgery for recurrence. The total diagnosis yield with regard to disease-free survival after surgery for recurrence was 9%. Compliance was moderate. Whether the continuing implementation of such program and cost are justified should be debated.

Clinical Outcomes from Unselected "Real-World" Patients with Long Coronary Lesion Receiving 40 mm Biodegradable Polymer Coated Sirolimus-Eluting Stent.

PubMed

Polavarapu, Anurag; Polavarapu, Raghava Sarma; Prajapati, Jayesh; Thakkar, Kamlesh; Raheem, Asif; Mayall, Tamanpreet; Thakkar, Ashok

2015-01-01

Background. Long lesions being implanted with drug-eluting stents (DES) are associated with relatively high restenosis rates and higher incidences of adverse events. Objectives. We aimed to examine the safety and efficacy of the long (40 mm) biodegradable polymer coated Indolimus sirolimus-eluting stent (SES) in real-world patients with long coronary lesions. Methods. This study was observational, nonrandomized, retrospective, and carried out in real-world patients. A total of 258 patients were enrolled for the treatment of long coronary lesions, with 40 mm Indolimus. The primary endpoints in the study were incidence of major adverse cardiac events (MACE), a miscellany of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) or target vessel revascularization (TVR), and stent thrombosis (ST) up to 6-month follow-up. Results. The study population included higher proportion of males (74.4%) and average age was 53.2 ± 11.0 years. A total of 278 lesions were intervened successfully with 280 stents. The observed MACE at 6-month follow-up was 2.0%, which included 0.8% cardiac death and 1.2% MI. There were no TLR or TVR and ST observed during 6-month follow-up. Conclusions. The long (40 mm) Indolimus stent demonstrated low MACE rate and was proven to be safe and effective treatment for long lesions in "real-world" patients.

Outcome of physiotherapy as part of a multidisciplinary rehabilitation in an unselected polio population with one-year follow-up: an uncontrolled study.

PubMed

Bertelsen, Merete; Broberg, Susse; Madsen, Ellen

2009-01-01

The aim of this study was to evaluate the outcome of physiotherapy as part of a multidisciplinary rehabilitation. Prospective uncontrolled intervention study. Fifty patients with late effects of polio, first time referred to physiotherapy at the Danish Society of Polio and Accident Victims (PTU) Rehabilitation Centre. The intervention was physiotherapy as an essential part of an individually planned multidisciplinary rehabilitation. The outcome measures Six-Minute Walk Test and Timed-Stands Test were used to assess the functional capacity. Quality of life was evaluated by Medical Outcome Survey Short Form (SF-36) and fatigue by Multidimensional Fatigue Inventory (MFI-20). Patients were tested at baseline; 3 months after the start of rehabilitation and at one-year follow-up. The patients showed significantly better functional capacity on all measurements 3 months after start of intervention and at one-year follow-up. The patients showed significant improvement in 3 of the SF-36 dimensions regarding quality of life, but only the improvement in "general health" remained after one year. This study shows that patients with late effects of polio, who experience new problems related to polio, can benefit from an individually planned multidisciplinary intervention with emphasis on physiotherapy, and the improvement in physical capacity and general health can remain at one-year follow-up.

Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment.

PubMed

Osman, Faizel; Franklyn, Jayne A; Daykin, Jacqueline; Chowdhary, Saqib; Holder, Roger L; Sheppard, Michael C; Gammage, Michael D

2004-08-15

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

Progression of abnormal MIB-1 staining patterns of reserve cells in cervical smears from women ultimately developing high grade squamous intraepithelial lesions.

PubMed

Siemens, Frederike C; van Haaften, Carolien; Kuijpers, Johan C; Helmerhorst, Theo J M; Boon, Mathilde E

2006-01-01

To assess, in a longitudinal study in women diagnosed with high grade squamous epithelial lesion (HSIL), the progression over time of proliferative activity in reserve cells using population screening cervical cytology specimens. Twenty consecutive, unselected patients with HSIL lesions were part of the national cervical screening program. From the archives, for each patient, the last prior normal population screening smear was included in the study. Concurrent sets of cervical smears from 80 age-matched women without pathology formed the controls. The original slides were stained using MIB-1 monoclonal antibody. The fraction of MIB-1-positive reserve cells was assessed using systematic random sampling and running progressive means assessment to ensure a sufficient sample size. The proliferation fraction in reserve cells of HSIL patients was significantly raised (mean, 65.0%; range, 53.5-94.1%; p < 0.01) as compared with that in concurrent controls (mean, 12.8%; range, 1.9-45.4%). Prior smears from HSIL patients, although without morphologic abnormalities, had abnormally high proliferation fractions (mean, 59.1%; range, 1.0-94.7%), significantly raised over those from concurrent controls (mean, 9.4%; range In population-based cervical smear screening, HSIL patients already have abnormally raised proliferation fractions of reserve cells, even without morphologic changes in squamous cells, 1-5 (mean, 3.6) years prior to diagnosis.

CXCR5-Dependent Entry of CD8 T Cells into Rhesus Macaque B-Cell Follicles Achieved through T-Cell Engineering.

PubMed

Ayala, Victor I; Deleage, Claire; Trivett, Matthew T; Jain, Sumiti; Coren, Lori V; Breed, Matthew W; Kramer, Joshua A; Thomas, James A; Estes, Jacob D; Lifson, Jeffrey D; Ott, David E

2017-06-01

Follicular helper CD4 T cells, T FH , residing in B-cell follicles within secondary lymphoid tissues, are readily infected by AIDS viruses and are a major source of persistent virus despite relative control of viral replication. This persistence is due at least in part to a relative exclusion of effective antiviral CD8 T cells from B-cell follicles. To determine whether CD8 T cells could be engineered to enter B-cell follicles, we genetically modified unselected CD8 T cells to express CXC chemokine receptor 5 (CXCR5), the chemokine receptor implicated in cellular entry into B-cell follicles. Engineered CD8 T cells expressing human CXCR5 (CD8 hCXCR5 ) exhibited ligand-specific signaling and chemotaxis in vitro Six infected rhesus macaques were infused with differentially fluorescent dye-labeled autologous CD8 hCXCR5 and untransduced CD8 T cells and necropsied 48 h later. Flow cytometry of both spleen and lymph node samples revealed higher frequencies of CD8 hCXCR5 than untransduced cells, consistent with preferential trafficking to B-cell follicle-containing tissues. Confocal fluorescence microscopy of thin-sectioned lymphoid tissues demonstrated strong preferential localization of CD8 hCXCR5 T cells within B-cell follicles with only rare cells in extrafollicular locations. CD8 hCXCR5 T cells were present throughout the follicles with some observed near infected T FH In contrast, untransduced CD8 T cells were found in the extrafollicular T-cell zone. Our ability to direct localization of unselected CD8 T cells into B-cell follicles using CXCR5 expression provides a strategy to place highly effective virus-specific CD8 T cells into these AIDS virus sanctuaries and potentially suppress residual viral replication. IMPORTANCE AIDS virus persistence in individuals under effective drug therapy or those who spontaneously control viremia remains an obstacle to definitive treatment. Infected follicular helper CD4 T cells, T FH , present inside B-cell follicles represent a major source of this residual virus. While effective CD8 T-cell responses can control viral replication in conjunction with drug therapy or in rare cases spontaneously, most antiviral CD8 T cells do not enter B-cell follicles, and those that do fail to robustly control viral replication in the T FH population. Thus, these sites are a sanctuary and a reservoir for replicating AIDS viruses. Here, we demonstrate that engineering unselected CD8 T cells to express CXCR5, a chemokine receptor on T FH associated with B-cell follicle localization, redirects them into B-cell follicles. These proof of principle results open a pathway for directing engineered antiviral T cells into these viral sanctuaries to help eliminate this source of persistent virus. Copyright © 2017 American Society for Microbiology.

Fluoroscopically Guided Transcervical Fallopian Tube Recanalization of Post-Sterilization Reversal Mid-Tubal Obstructions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houston, J. Graeme; Anderson, David; Mills, John

2000-03-15

Purpose: To assess the technical success and early outcome of fluoroscopically guided transcervical fallopian tube recanalization (FTR) in mid-tubal occlusion following sterilization reversal surgery.Methods: From July 1995 to January 1998, patients with greater than 12 months secondary infertility underwent hysterosalpingography (HSG). FTR was performed in proximal or mid-tubal occlusion. Cases of FTR in mid-tubal occlusion were included in this study. Technical success (defined as complete tubal patency) using a standard guidewire and hydrophilic glidewire, the number of patients with at least one patent tube, and the intrauterine and ectopic pregnancy rates were determined.Results: Twenty-six infertile patients with previous sterilization reversalmore » underwent HSG. Eight of 26 (31%) patients (mean age 32 years, range 23-37 years), had attempted FTR for mid-tubal occlusion at the site of surgical anastomosis. Fourteen tubes were attempted as there were two previous salpingectomies. Technical success was achieved in eight of 14 (57%) tubes attempted, resulting in five of eight (62%) patients having at least one patent tube. At follow-up (mean 18 months, range 12-28 months) in these five patients there was one intrauterine pregnancy. There were no ectopic pregnancies.Conclusions: FTR in mid-tubal obstruction in infertile patients following sterilization reversal surgery is technically feasible and may result in intrauterine pregnancy. In this small group there was a lower technical success rate and lower pregnancy rate than in unselected proximal tubal occlusion.« less

Clinical and financial burden of active lupus in Greece: a nationwide study.

PubMed

Bertsias, G; Karampli, E; Sidiropoulos, P; Gergianaki, I; Drosos, A; Sakkas, L; Garyfallos, A; Tzioufas, A; Vassilopoulos, D; Tsalapaki, C; Sfikakis, P; Panopoulos, S; Athanasakis, K; Perna, A; Psomali, D; Kyriopoulos, J; Boumpas, D

2016-10-01

Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was €3741 for severe vs €1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need. © The Author(s) 2016.

Higher serum chloride concentrations are associated with acute kidney injury in unselected critically ill patients.

PubMed

Zhang, Zhongheng; Xu, Xiao; Fan, Haozhe; Li, Danyu; Deng, Hongsheng

2013-10-28

Chloride administration has been found to be harmful to the kidney in critically ill patients. However the association between plasma chloride concentration and renal function has never been investigated. This was a retrospective study conducted in a tertiary 24-bed intensive care unit from September 2010 to November 2012. Data on serum chloride for each patient during their ICU stay were abstracted from electronic database. Cl0 referred to the initial chloride on ICU entry, Cl(max), Cl(min) and Cl(mean) referred to the maximum, minimum and mean chloride values before the onset of AKI, respectively. AKI was defined according to the conventional AKIN criteria. Univariate and multivariable analysis were performed to examine the association of chloride and AKI development. A total of 1221 patients were included into analysis during study period. Three hundred and fifty-seven patients (29.2%) developed AKI. Cl(max) was significantly higher in AKI than in non-AKI group (111.8 ± 8.1 vs 107.9 ± 5.4 mmol/l; p < 0.001); Cl0 was not significantly different between AKI and non-AKI patients; Cl(mean) was significantly higher in AKI than non-AKI (104.3 ± 5.8 vs 103.4 ± 4.5;  = 0.0047) patients. Cl(max) remained to be associated with AKI in multivariable analysis (OR: 1.10, 95% CI: 1.08-1.13). Chloride overload as represented by Cl(mean) and Cl(max) is significantly associated with the development of AKI.

TEL/AML1 positivity in childhood ALL: average or better prognosis? Czech Paediatric Haematology Working Group.

PubMed

Zuna, J; Hrusák, O; Kalinová, M; Muzíková, K; Starý, J; Trka, J

1999-01-01

The presence of TEL/AML1 fusion gene in childhood acute lymphoblastic leukaemia (ALL) defines a subgroup of patients with better than average outcome. However, the prognostic significance of this aberration has recently been disputed by the Berlin-Frankfurt-Münster (BFM) study group due to its relatively high incidence found in relapsed patients (19.6% and 21.9%, in two cohorts). In contrast, only four out of 45 (8.9%) unselected relapsed patients (all of whom had been treated according to BFM protocols) in the Czech Republic carry this fusion. From March 1995 to June 1998, 41 out of 190 (21.6%) newly diagnosed children with ALL were TEL/AML1-positive. There is a statistically significant difference between the incidence of TEL/AML1 fusion at diagnosis and at relapse within our group (P = 0.035). Interim analysis of the minimal residual disease (MRD) detection shows heterogeneity within the group of newly diagnosed TEL/AML1-positive leukaemias--10 out of 24 patients tested at the end of induction therapy had detectable levels of MRD. However, only one of these patients reached relapse-predictive level (10(-3)) of MRD. In conclusion, we corroborate low frequency of TEL/AML1 positivity among relapsed patients with ALL among Czech children who are treated by the BFM protocols. Moreover, we demonstrate different patterns of bone marrow clean-up in TEL/AML1-positive patients.

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

PubMed

Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

2015-11-01

On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis.

PubMed

Takeda, Takashi; Banno, Kouji; Yanokura, Megumi; Adachi, Masataka; Iijima, Moito; Kunitomi, Haruko; Nakamura, Kanako; Iida, Miho; Nogami, Yuya; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke

2016-10-14

Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 ( MLH1 ) and MutS homolog 2 ( MSH2 ) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1 , MSH2 , and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6 . The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.

[Sequelae of severe craniocerebral injuries. An epidemiological study in the Canton of St. Gallen].

PubMed

Annoni, J M; Beer, S; Kesselring, J

1991-02-16

Severe head injuries often lead to serious medical and socioeconomic sequelae. The incidence rate indicated in other studies shows a wide variation due to differences in selection criteria. Based upon an unselected population, the incidence of severe head injury was calculated and the surviving patients were interviewed and clinically examined 3 years after the accident in order to describe the course, rehabilitation and psychosocial sequelae after severe head injury. Retrospectively we collected 80 patients living in the canton of St. Gallen who had a severe head injury requiring hospitalization in 1987, indicating an incidence of 20 per 100,000 inhabitants. 22 (28%) of these patients died as a consequence of the head trauma. The best predictor was the Glasgow coma score at admission, which showed a highly significant direct correlation with survival rate. Regarding the degree of impairment of survivors the duration of posttraumatic amnesia was the best predictive parameter. Of the 45 patients controlled 3 years after the head trauma only 11% were severely impaired in daily activities. 79% of the patients who were gainfully employed before the accident were working full- or at least part-time. However, only 3 patients (7%) were absolutely free of symptoms. Most patients suffered from cognitive and emotional deficits. Based on an estimated incidence for minor head trauma of 174 per 100,000 inhabitants, a total annual incidence for all head traumas of 194 per 100,000 inhabitants is calculated, with severe head injury representing about 1/9 of all head injuries.

Early and simple detection of diastolic dysfunction during weaning from mechanical ventilation

PubMed Central

2012-01-01

Weaning from mechanical ventilation imposes additional work on the cardiovascular system and can provoke or unmask left ventricular diastolic dysfunction with consecutive pulmonary edema or systolic dysfunction with inadequate increase of cardiac output and unsuccessful weaning. Echocardiography, which is increasingly used for hemodynamic assessment of critically ill patients, allows differentiation between systolic and diastolic failure. For various reasons, transthoracic echocardiographic assessment was limited to patients with good echo visibility and to those with sinus rhythm without excessive tachycardia. In these patients, often selected after unsuccessful weaning, echocardiographic findings were predictive for weaning failure of cardiac origin. In some studies, patients with various degrees of systolic dysfunction were included, making evaluation of the diastolic dysfunction to the weaning failure even more difficult. The recent study by Moschietto and coworkers included unselected patients and used very simple diastolic variables for assessment of diastolic function. They also included patients with atrial fibrillation and repeated echocardiographic examination only 10 minutes after starting a spontaneous breathing trial. The main finding was that weaning failure was not associated with systolic dysfunction but with diastolic dysfunction. By measuring simple and robust parameters for detection of diastolic dysfunction, the study was able to predict weaning failure in patients with sinus rhythm and atrial fibrillation as early as 10 minutes after beginning a spontaneous breathing trial. Further studies are necessary to determine whether appropriate treatment tailored according to the echocardiographic findings will result in successful weaning. PMID:22770365

Early and simple detection of diastolic dysfunction during weaning from mechanical ventilation.

PubMed

Voga, Gorazd

2012-07-06

Weaning from mechanical ventilation imposes additional work on the cardiovascular system and can provoke or unmask left ventricular diastolic dysfunction with consecutive pulmonary edema or systolic dysfunction with inadequate increase of cardiac output and unsuccessful weaning. Echocardiography, which is increasingly used for hemodynamic assessment of critically ill patients, allows differentiation between systolic and diastolic failure. For various reasons, transthoracic echocardiographic assessment was limited to patients with good echo visibility and to those with sinus rhythm without excessive tachycardia. In these patients, often selected after unsuccessful weaning, echocardiographic findings were predictive for weaning failure of cardiac origin. In some studies, patients with various degrees of systolic dysfunction were included, making evaluation of the diastolic dysfunction to the weaning failure even more difficult. The recent study by Moschietto and coworkers included unselected patients and used very simple diastolic variables for assessment of diastolic function. They also included patients with atrial fibrillation and repeated echocardiographic examination only 10 minutes after starting a spontaneous breathing trial. The main finding was that weaning failure was not associated with systolic dysfunction but with diastolic dysfunction. By measuring simple and robust parameters for detection of diastolic dysfunction, the study was able to predict weaning failure in patients with sinus rhythm and atrial fibrillation as early as 10 minutes after beginning a spontaneous breathing trial. Further studies are necessary to determine whether appropriate treatment tailored according to the echocardiographic findings will result in successful weaning.

The influence of animal fear on attentional capture by fear-relevant animal stimuli in children.

PubMed

Waters, Allison M; Lipp, Ottmar V

2008-01-01

The present study demonstrated that pictures of fear-relevant animals, snakes and spiders, presented among backgrounds of other animal stimuli captured attention and interfered in the detection of a neutral target to the same extent in a large sample of unselected children (N=81). Moreover, detection of a neutral target animal was slowed more in the presence of a feared fear-relevant distracter, e.g., a snake for snake fearful children, than in the presence of a not feared fear-relevant distracter, e.g., a spider for snake fearful children. These results indicate attentional capture by phylogenetically fear-relevant animal stimuli in children and the selective enhancement of this effect by fear of these animals. These findings are consistent with current models of preferential processing of phylogenetically prepared threat stimuli and with cognitive models of anxiety that propose an enhancing effect of fear in the processing of fear-related stimuli.

Health Care Utilization and Expenditures Associated With Remote Monitoring in Patients With Implantable Cardiac Devices.

PubMed

Ladapo, Joseph A; Turakhia, Mintu P; Ryan, Michael P; Mollenkopf, Sarah A; Reynolds, Matthew R

2016-05-01

Several randomized trials and decision analysis models have found that remote monitoring may reduce health care utilization and expenditures in patients with cardiac implantable electronic devices (CIEDs), compared with in-office monitoring. However, little is known about the generalizability of these findings to unselected populations in clinical practice. To compare health care utilization and expenditures associated with remote monitoring and in-office monitoring in patients with CIEDs, we used Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases. We selected patients newly implanted with an implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy defibrillator (CRT-D), or permanent pacemaker (PPM), in 2009, who had continuous health plan enrollment 2 years after implantation. Generalized linear models and propensity score matching were used to adjust for confounders and estimate differences in health care utilization and expenditures in patients with remote or in-office monitoring. We identified 1,127; 427; and 1,295 pairs of patients with a similar propensity for receiving an ICD, CRT-D, or PPM, respectively. Remotely monitored patients with ICDs experienced fewer emergency department visits resulting in discharge (p = 0.050). Remote monitoring was associated with lower health care expenditures in office visits among patients with PPMs (p = 0.025) and CRT-Ds (p = 0.006) and lower total inpatient and outpatient expenditures in patients with ICDs (p <0.0001). In conclusion, remote monitoring of patients with CIEDs may be associated with reductions in health care utilization and expenditures compared with exclusive in-office care. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic counseling for beta-thalassemia trait following health screening in a health maintenance organization: comparison of programmed and conventional counseling.

PubMed Central

Fisher, L; Rowley, P T; Lipkin, M

1981-01-01

Providing adequate counseling of patients identified in genetic screening programs is a major responsibility and expense. Adults in a health maintenance organization, unselected for interest, were screened for beta-thalassemia trait as part of preventive health care. Counseling was provided by either a trained physician (conventional counseling) or by a videotape containing the same information followed by an opportunity to question a trained physician (programmed counseling). Immediately before and after counseling, knowledge of thalassemia, knowledge of genetics, and mood change were assessed by questionnaire. Comparable mood changes and similar learning about thalassemia and genetics occurred with both counseling methods. Thus, as judged by immediate effects on knowledge and mood, videotaped instruction can greatly reduce professional time required for genetic counseling and facilitate the incorporation of genetic screening into primary health care. PMID:7325162

Clinical outcomes in real-world patients with small vessel disease treated with XIENCE V® everolimus-eluting stents: one year results from the XIENCE V® USA condition of approval post-market study.

PubMed

Hermiller, James B; Rutledge, David R; Mao, Vivian W; Zhao, Weiying; Wang, Jin; Gruberg, Luis; Lombardi, William; Sharma, Samin K; Krucoff, Mitchell W

2014-07-01

The purpose of this study was to evaluate the 1-year clinical outcomes of more complex XIENCE V USA real-world patients with small versus nonsmall vessel lesions. Patients with small vessel lesions undergoing coronary stent placement are at higher risk of major adverse cardiac events. Improved safety and efficacy of XIENCE V everolimus eluting stents (EES) have been previously demonstrated in selected low-risk small vessel populations in randomized clinical trials. The XIENCE V USA study was a condition of approval, single-arm study in unselected real-world patients. Baseline and 1-year clinical outcomes were compared between XIENCE V USA patients who received a single 2.5 mm stent (small vessel group, N = 838) and patients implanted with a single >2.5 mm stent (non-small vessel group, N = 2,015). Mean reference vessel diameter was 2.55 ± 0.36 and 3.25 ± 0.46 mm in the small and non-small vessel groups, respectively (P < 0.001). Small vessel group had more females, presented with a higher rate of diabetes, and had more complex lesion characteristics. The definite or probable ST rates analyzed using Kaplan-Meier method were low and not significantly different between the groups at 0.37 and 0.40% for the small and nonsmall vessel group (P = 0.88), respectively. The composite rate of cardiac death or MI was comparable at 4.5% for the small and 5.1% for the non-small vessel 1 groups (P = 0.57). The 1-year target lesion revascularization rate was also comparable in the small vessel group (3.8% vs. 3.0%, P = 0.35). Despite gender difference, higher prevalence of diabetes and more complex lesions in the small vessel groups, the 1-year clinical outcomes were similar in both small and nonsmall vessel groups. These results demonstrate the therapeutic benefit of XIENCE V EES in a real-world all inclusive patient population with small vessel disease. © 2013 Wiley Periodicals, Inc.

G1738R is a BRCA1 founder mutation in Greek breast/ovarian cancer patients: evaluation of its pathogenicity and inferences on its genealogical history.

PubMed

Anagnostopoulos, Theodore; Pertesi, Maroulio; Konstantopoulou, Irene; Armaou, Sofia; Kamakari, Smaragda; Nasioulas, George; Athanasiou, Athanassios; Dobrovic, Alex; Young, Mary-Anne; Goldgar, David; Fountzilas, George; Yannoukakos, Drakoulis

2008-07-01

We have performed screening in 287 breast/ovarian cancer families in Greece which has revealed that approximately 12% (8/65) of all index patients-carriers of a deleterious mutation in BRCA1 and BRCA2 genes, contain the base substitution G to A at position 5331 of BRCA1 gene. This generates the amino acid change G1738R for which based on a combination of genetic, in silico and histopathological analysis there are strong suggestions that it is a causative mutation. In this paper, we present further evidence suggesting the pathogenicity of this variant. Forty breast/ovarian cancer patients were reported in 11 Greek families: the above eight living in Greece, two living in Australia and one in USA, all containing G1738R. Twenty of these patients were screened and were all found to be carriers of the same base substitution. In addition, we have detected the same base change in five breast/ovarian cancer patients after screening 475 unselected patient samples with no apparent family history. The mean age of onset for all the above patients was 39.4 and 53.6 years for breast and ovarian cancer cases, respectively. A multi-factorial likelihood model for classification of unclassified variants in BRCA1 and BRCA2 developed previously was applied on G1738R and the odds of it being a deleterious mutation was estimated to be 11470:1. In order to explain the prevalence of this mutation mainly in the Greek population, its genealogical history was examined. DNA samples were collected from 11 carrier families living in Greece, Australia and USA. Screening of eight intragenic SNPs, three intragenic and seven extragenic microsatellite markers and comparison with control individuals, suggested a common origin for the mutation while the time to its most recent common ancestor was estimated to be 11 generations (about 275 years assuming a generational interval of 25 years) with a 1-lod support interval of 4-24 generations (100-600 years). Considering the large degree of genetic heterogeneity in the Greek population, the identification of a frequent founder mutation greatly facilitates genetic screening.

Clinical Significance of Epsilon Waves in Arrhythmogenic Cardiomyopathy.

PubMed

Protonotarios, Alexandros; Anastasakis, Aris; Tsatsopoulou, Adalena; Antoniades, Loizos; Prappa, Efstathia; Syrris, Petros; Tousoulis, Dimitrios; McKENNA, William J; Protonotarios, Nikos

2015-07-16

Epsilon waves are hallmark features of arrhythmogenic cardiomyopathy (ACM) but information about their clinical significance is variable. We evaluated epsilon wave prevalence, characteristics, and their clinical significance in an ACM population. Eighty-six unselected patients fulfilling the 2010 Task Force criteria were enrolled. Seventy-six of them were carriers of desmosomal mutations. All subjects were serially evaluated with standard 12-lead ECG and 2-dimensional echocardiography. Epsilon waves were evaluated in all precordial and inferior leads. Novel parameters assessed included their duration and precordial/inferior lead extension. Twenty-five subjects (29%) had epsilon waves that were present in lead V3 and beyond in 9, and in the inferior leads in 7. Epsilon waves were associated with right ventricular outflow tract (RVOT) (P = 0.001) but not RV posterior wall (P = 0.21), RV apex (P = 0.30), or left ventricular (P = 0.94) wall motion abnormalities. Patients with epsilon waves had increased RVOT diameter (P < 0.0001). Extension of epsilon waves in lead V3 and beyond was associated with increased epsilon wave duration (P = 0.002) and RVOT diameter (P = 0.04). The duration of epsilon waves was positively correlated with RVOT diameter (r = 0.70, P = 0.0001). Epsilon waves were also associated with episodes of sustained ventricular tachycardia (P = 0.004) but not with heart failure (P = 0.41) or sudden cardiac death (P = 0.31). Detection of epsilon waves on 12-lead ECG reflects significant RVOT involvement, which was associated with episodes of sustained ventricular tachycardia but not sudden cardiac death. © 2015 Wiley Periodicals, Inc.

Evaluation of an internet-based e-learning module to introduce nuclear medicine to medical students: a feasibility study.

PubMed

Diessl, Stefanie; Verburg, Frederik A; Hoernlein, Alexander; Schumann, Martin; Luster, Markus; Reiners, Christoph

2010-12-01

The advent of electronic learning, the so-called e-learning, offers new possibilities for instruction in addition to the traditional face-to-face teaching in the education of medical students. To evaluate the additional educational value of a voluntary e-learning module in a nuclear medicine course for third-year medical students. Twenty exemplary nuclear medicine patient cases from our department were developed for e-learning purposes and presented on the internet using the web-based training program ‘CaseTrain’. Subsequently, three selected test cases were handled and evaluated by an unselected population of third-year medical students. One hundred and twenty-eight students studied the three patient cases and filled out the evaluation questionnaire completely. The most important result is that both the interest in and the subjective feeling of the knowledge level regarding the specialized field of nuclear medicine had increased significantly after working through the three e-learning cases. Ninety-seven percent of the evaluating students considered the use of computer-based learning useful. The subjective grading of the content of the cases and the handling of the software were graded with high marks by the participants, 1.9 and 2.0, respectively, on a linear scale with 1 being the best and 6 being the worst. The addition of e-learning to face-to-face teaching as a form of ‘blended learning’ is highly appreciated by medical students, and will provide an effective medium for bringing better understanding of nuclear medicine to future colleagues.

Near and far space neglect: task sensitivity and anatomical substrates.

PubMed

Aimola, Lina; Schindler, Igor; Simone, Anna Maria; Venneri, Annalena

2012-05-01

Most group studies which have investigated neglect for near and far space have found an increased severity of symptoms in far space compared to near space. However, the majority of these studies used relatively small samples and based their findings almost exclusively on line bisection performance. The aim of the present study was, therefore, to explore the occurrence of neglect for near and far space in a larger group of unselected right brain damaged patients and to evaluate whether neglect specific to near and far space is a task-related deficit or generalises across distance irrespective of task. In addition, a lesion overlap analysis was carried out to identify critical lesion sites associated with distance specific neglect deficits. Thirty-eight right hemisphere damaged patients carried out a line bisection and a cancellation task by using a pen in near space (40 cm) and a laser pointer in far space (320 cm). The results showed that both the number of left-sided omissions and rightward bisection errors were significantly increased in near compared to far space. Distance specific dissociations, albeit less common, were more frequently observed for cancellation than line bisection. These results suggest that space representation in neglect is more severely impaired in near than in far space. In addition, distance related dissociations in neglect may depend on task demands. Although the anatomical findings were broadly consistent with a dorsal and ventral stream dichotomy for near and far space processing, they also suggest the involvement of intermediate structures in distance related neglect phenomena. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Comparative follow-up study of unselected male population with congenital defective color vision from inland and Mediterranean areas of Croatia].

PubMed

Rogosić, Veljko; Bojić, Lovro; Karaman, Ksenija; Rogosić, Lucija Vanjaka; Titlić, Marina; Poljak, Nikola Kolja; Plestina-Borjan, Ivna; Smerdelj, Andro; Duplancić, Darko; Alpeza-Dunato, Zvjezdana

2011-03-01

The aim of this ten-year study (from the end of 1998 to the end of 2008) was to assess the prevalence of congenital dyschromatopsia in unselected healthy male population aged 15-45 from two Croatian regions, i.e. inland and Mediterranean parts of Croatia. Results collected in these two regions were compared and respective conclusions drawn. The results primarily referred to the prevalence of color vision disturbances and their differences according to the main color groups (dichromacy and anomalous trichromacy) and subgroups (protanopia, deuteranopia, protanomaly, deuteranomaly, and others). To our knowledge, no such a long-term study in a large population sample has been carried out in southeast Europe to date. Color vision was examined after complete ophthalmologic examination in all subjects presenting for examination required for amateur driver license. Color vision examination was performed by use of pseudoisochromatic Ishihara tables, Nagel II anomaloscope and Panel D-15 color test at industrial medicine offices and ophthalmology departments in the two regions. There were 12,974 and 9,974 subjects in inland and Mediterranean Croatia, respectively. The results confirmed the hypothesis and clinical perception of a lower prevalence of color vision disturbances in southern parts, i.e. in Mediterranean Croatia (8.50%) as compared with inland Croatia (8.90%). The rate of dichromacy was higher in Mediterranean Croatia (2.40%), while the rate of anomalous trichromacy was greater in inland Croatia (6.93%). The results of this study provide better insight in the status of color vision disturbances and possible differences between the relatively close areas of north (inland) and south (Mediterranean) Croatia.

Comprehensive malnutrition inflammation score as a marker of nutritional status in Chinese peritoneal dialysis patients.

PubMed

Chan, Jessie Ying Wing; Che, Kit I; Lam, Karry Mau Chu; Chow, Kai-Ming; Chung, Kwok-Yi; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

2007-04-01

Malnutrition is common among peritoneal dialysis (PD) patients. However, the ideal marker of nutritional status in PD patients remained controversial. We studied 165 unselected adult PD patients. We compared the comprehensive Malnutrition-Inflammation Score (MIS) and the 7-point Subjective Global Assessment (SGA) score. The mean age was 59.2 +/- 11.5 years. Seventy patients were male. MIS significantly correlated with the SGA score (r =-0.667, P < 0.001). Of the 165 patients, 132 (80.0%) had similar classification of nutritional status by SGA and MIS (Group I); 17 (10.3%) were classified as normal by SGA but moderately malnourished by MIS (Group II), while 16 (9.7%) were classified as normal by MIS but moderately malnourished by SGA (Group III). Group II had been dialysed longer than Group I (71.7 +/- 50.3 vs 40.7 +/- 37.5 months, P = 0.011). As compared with Group I, Group III was more likely to require helper for PD exchange (37.5%vs 9.7%, P = 0.004), marginally more likely to be diabetic (62.5%vs 35.6%, P = 0.085) and had a slightly higher Charlson's comorbidity score (6.13 +/- 1.78 vs 4.98 +/- 2.1, P = 0.085), although the latter two were not statistically significant. MIS has a reasonable correlation with the conventional SGA score in PD patients. Patients with limited self-care capability, diabetes and multiple comorbidities probably had worse score (i.e. worse nutrition) revealed by SGA than by MIS, while patients who had been dialysed longer had worse score revealed by MIS than by SGA.

Pacemaker diagnostics in atrial fibrillation: limited usefulness for therapy initiation in a pacemaker practice.

PubMed

Yedlapati, Neeraja; Fisher, John D

2014-09-01

We aimed to determine the practical value of pacemaker diagnostics for atrial fibrillation (AF) in an unselected general pacemaker practice, specifically workflow and initiation of anticoagulation or antiarrhythmic drug (AAD) therapy. We prospectively followed consecutive pacemaker interrogations over a period of 1 year to identify patients with AF (burden from 1% to 99%). We contacted referring physicians with AF details, and then determined whether the information resulted in therapeutic changes. Of the 1,100 pacemakers interrogated, 728 were dual chamber (DDDs) with AF diagnostic capability. AF was recorded in 73 (10%) but seven had limited information, leaving 66 patients; of these, 42 (63%) patients were already anticoagulated and in five (7%) patients, anticoagulation had been stopped because of complications. Initial diagnosis of AF was made by the pacemaker in 17 patients (26% of 66; 2% of 728); four (6% of 66) patients were newly initiated on anticoagulation. Of the 66 patients, 17 patients were already on AADs; 49 (74%) had satisfactory rate control or had other issues; only two (3% of 66; 0.3% of 728) received new AADs. Of 728 patients with DDD pacemakers, only 17 were newly discovered to have AF, and six (0.8%) had changes in medications based on the pacemaker data. Adding pacemaker-derived data to existing clinical information had little therapeutic impact, due to a combination of cumbersome workflow, and because AF was usually known to practitioners. Developments in automated monitoring systems may provide more accessible and therapeutically useful information. ©2014 Wiley Periodicals, Inc.

Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms

PubMed Central

Marsh, Judith C. W.; Gutierrez-Rodrigues, Fernanda; Cooper, James; Jiang, Jie; Gandhi, Shreyans; Kajigaya, Sachiko; Feng, Xingmin; Ibanez, Maria del Pilar F.; Donaires, Flávia S.; Lopes da Silva, João P.; Li, Zejuan; Das, Soma; Ibanez, Maria; Smith, Alexander E.; Lea, Nicholas; Best, Steven; Ireland, Robin; Kulasekararaj, Austin G.; McLornan, Donal P.; Pagliuca, Anthony; Callebaut, Isabelle; Young, Neal S.; Calado, Rodrigo T.; Townsley, Danielle M.

2018-01-01

Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase 1) result in pathologic telomere erosion and cause dyskeratosis congenita. However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to disease development are not well defined. We screened 516 patients for germline mutations in telomere-associated genes by next-generation sequencing in 2 independent cohorts; one constituting unselected patients with idiopathic BMF, unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort comprising selected patients on the basis of the suspicion of constitutional/familial BMF (n = 59). Twenty-three RTEL1 variants were identified in 27 unrelated patients from both cohorts: 7 variants were likely pathogenic, 13 were of uncertain significance, and 3 were likely benign. Likely pathogenic RTEL1 variants were identified in 9 unrelated patients (7 heterozygous and 2 biallelic). Most patients were suspected to have constitutional BMF, which included aplastic anemia (AA), unexplained cytopenia, hypoplastic myelodysplastic syndrome, and macrocytosis with hypocellular bone marrow. In the other 18 patients, RTEL1 variants were likely benign or of uncertain significance. Telomeres were short in 21 patients (78%), and 3′ telomeric overhangs were significantly eroded in 4. In summary, heterozygous RTEL1 variants were associated with marrow failure, and telomere length measurement alone may not identify patients with telomere dysfunction carrying RTEL1 variants. Pathogenicity assessment of heterozygous RTEL1 variants relied on a combination of clinical, computational, and functional data required to avoid misinterpretation of common variants. PMID:29344583

Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms.

PubMed

Marsh, Judith C W; Gutierrez-Rodrigues, Fernanda; Cooper, James; Jiang, Jie; Gandhi, Shreyans; Kajigaya, Sachiko; Feng, Xingmin; Ibanez, Maria Del Pilar F; Donaires, Flávia S; Lopes da Silva, João P; Li, Zejuan; Das, Soma; Ibanez, Maria; Smith, Alexander E; Lea, Nicholas; Best, Steven; Ireland, Robin; Kulasekararaj, Austin G; McLornan, Donal P; Pagliuca, Anthony; Callebaut, Isabelle; Young, Neal S; Calado, Rodrigo T; Townsley, Danielle M; Mufti, Ghulam J

2018-01-09

Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase 1) result in pathologic telomere erosion and cause dyskeratosis congenita. However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to disease development are not well defined. We screened 516 patients for germline mutations in telomere-associated genes by next-generation sequencing in 2 independent cohorts; one constituting unselected patients with idiopathic BMF, unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort comprising selected patients on the basis of the suspicion of constitutional/familial BMF (n = 59). Twenty-three RTEL1 variants were identified in 27 unrelated patients from both cohorts: 7 variants were likely pathogenic, 13 were of uncertain significance, and 3 were likely benign. Likely pathogenic RTEL1 variants were identified in 9 unrelated patients (7 heterozygous and 2 biallelic). Most patients were suspected to have constitutional BMF, which included aplastic anemia (AA), unexplained cytopenia, hypoplastic myelodysplastic syndrome, and macrocytosis with hypocellular bone marrow. In the other 18 patients, RTEL1 variants were likely benign or of uncertain significance. Telomeres were short in 21 patients (78%), and 3' telomeric overhangs were significantly eroded in 4. In summary, heterozygous RTEL1 variants were associated with marrow failure, and telomere length measurement alone may not identify patients with telomere dysfunction carrying RTEL1 variants. Pathogenicity assessment of heterozygous RTEL1 variants relied on a combination of clinical, computational, and functional data required to avoid misinterpretation of common variants.

MLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features

PubMed Central

Li, Xia; Yao, Xiaoping; Wang, Yibaina; Hu, Fulan; Wang, Fan; Jiang, Liying; Liu, Yupeng; Wang, Da; Sun, Guizhi; Zhao, Yashuang

2013-01-01

Purpose To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis. Methods A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated. Results The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8–24.1%). They were 18.7% (95% CI: 14.7–23.6%) and 16.4% (95% CI: 11.9–22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215–2.215; P = 0.001), tumor location (pooled OR = 3.804, 95% CI: 2.715–5.329; P<0.001), tumor differentiation (pooled OR = 2.131, 95% CI: 1.464–3.102; P<0.001), MSI (OR: 27.096, 95% CI: 13.717–53.526; P<0.001). Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427–34.631; P<0.001) and 9.419 (95% CI: 2.613–33.953; P = 0.001), respectively). Conclusion The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation. PMID:23555617

Sex-Ratio and Gender Differences in Depression in an Unselected Adult Population.

ERIC Educational Resources Information Center

Baumgart, E. P.; Oliver, J. M.

1981-01-01

Neither sex-ratio nor gender differences in depression were found in adult sample, similar to pattern found among university students. No demographic variable was correlated significantly with depression. Suggests results may be due to the elimination of face-to-face interviews, which expose males to greater negative repercussions for exhibiting…

Autism Spectrum Disorders (ASD) in Blind Children: Very High Prevalence, Potentially Better Outlook

ERIC Educational Resources Information Center

Jure, Rubin; Pogonza, Ramón; Rapin, Isabelle

2016-01-01

Autism spectrum disorders affected 19 of 38 unselected children at a school for the blind in Cordoba, Argentina. Autism was linked to total congenital blindness, not blindness' etiology, acquired or incomplete blindness, sex, overt brain damage, or socioeconomic status. Autism "recovery," had occurred in 4 verbal children. Congenital…

Comparing Two Methods for Reducing Variability in Voice Quality Measurements

ERIC Educational Resources Information Center

Kreiman, Jody; Gerratt, Bruce R.

2011-01-01

Purpose: Interrater disagreements in ratings of quality plague the study of voice. This study compared 2 methods for handling this variability. Method: Listeners provided multiple breathiness ratings for 2 sets of pathological voices, one including 20 male and 20 female voices unselected for quality and one including 20 breathy female voices.…

Genome changes due to forty years of artificial selection associated with divergent dairy production and reproduction

USDA-ARS?s Scientific Manuscript database

Artificial selection in dairy cattle since 1964 has achieved steady increase in milk production that was accompanied by unintended declines in fertility. Direct comparison of 45,878 SNPs between a group of Holstein cattle unselected since 1964 and the contemporary Holsteins was conducted to identify...

Intensive Training in Youth Sport: An Example of Unequal Opportunity.

ERIC Educational Resources Information Center

Rowley, Stephen R. W.; Graham, Philip J.

1999-01-01

Examined the social composition of an unselected sample of 282 English 8- to 16-year olds involved in intensive training in football, swimming, tennis, and gymnastics. Found that working-class children and those from single-parent families were underrepresented in all sports. Concluded that financial considerations and difficulties in accessing…

Evaluation of Coronary Artery Stenosis by Quantitative Flow Ratio During Invasive Coronary Angiography: The WIFI II Study (Wire-Free Functional Imaging II).

PubMed

Westra, Jelmer; Tu, Shengxian; Winther, Simon; Nissen, Louise; Vestergaard, Mai-Britt; Andersen, Birgitte Krogsgaard; Holck, Emil Nielsen; Fox Maule, Camilla; Johansen, Jane Kirk; Andreasen, Lene Nyhus; Simonsen, Jo Krogsgaard; Zhang, Yimin; Kristensen, Steen Dalby; Maeng, Michael; Kaltoft, Anne; Terkelsen, Christian Juhl; Krusell, Lars Romer; Jakobsen, Lars; Reiber, Johan H C; Lassen, Jens Flensted; Bøttcher, Morten; Bøtker, Hans Erik; Christiansen, Evald Høj; Holm, Niels Ramsing

2018-03-01

Quantitative flow ratio (QFR) is a novel diagnostic modality for functional testing of coronary artery stenosis without the use of pressure wires and induction of hyperemia. QFR is based on computation of standard invasive coronary angiographic imaging. The purpose of WIFI II (Wire-Free Functional Imaging II) was to evaluate the feasibility and diagnostic performance of QFR in unselected consecutive patients. WIFI II was a predefined substudy to the Dan-NICAD study (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease), referring 362 consecutive patients with suspected coronary artery disease on coronary computed tomographic angiography for diagnostic invasive coronary angiography. Fractional flow reserve (FFR) was measured in all segments with 30% to 90% diameter stenosis. Blinded observers calculated QFR (Medis Medical Imaging bv, The Netherlands) for comparison with FFR. FFR was measured in 292 lesions from 191 patients. Ten (5%) and 9 patients (5%) were excluded because of FFR and angiographic core laboratory criteria, respectively. QFR was successfully computed in 240 out of 255 lesions (94%) with a mean diameter stenosis of 50±12%. Mean difference between FFR and QFR was 0.01±0.08. QFR correctly classified 83% of the lesions using FFR with cutoff at 0.80 as reference standard. The area under the receiver operating characteristic curve was 0.86 (95% confidence interval, 0.81-0.91) with a sensitivity, specificity, negative predictive value, and positive predictive value of 77%, 86%, 75%, and 87%, respectively. A QFR-FFR hybrid approach based on the present results enables wire-free and adenosine-free procedures in 68% of cases. Functional lesion evaluation by QFR assessment showed good agreement and diagnostic accuracy compared with FFR. Studies comparing clinical outcome after QFR- and FFR-based diagnostic strategies are required. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717. © 2018 The Authors.

Young adulthood cognitive ability predicts statin adherence in middle-aged men after first myocardial infarction: A Swedish National Registry study

PubMed Central

Lissåker, Claudia; Madison, Guy; Held, Claes; Olsson, Erik

2017-01-01

Background Cognitive ability (CA) is positively related to later health, health literacy, health behaviours and longevity. Accordingly, a lower CA is expected to be associated with poorer adherence to medication. We investigated the long-term role of CA in adherence to prescribed statins in male patients after a first myocardial infarction (MI). Methods CA was estimated at 18–20 years of age from Military Conscript Register data for first MI male patients (≤60 years) and was related to the one- and two-year post-MI statin adherence on average 30 years later. Background and clinical data were retrieved through register linkage with the unselected national quality register SWEDEHEART for acute coronary events (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) and secondary prevention (Secondary Prevention after Heart Intensive Care Admission). Previous and present statin prescription data were obtained from the Prescribed Drug Register and adherence was calculated as ≥80% of prescribed dispensations assuming standard dosage. Logistic regression was used to estimate crude and adjusted associations. The primary analyses used 2613 complete cases and imputing incomplete cases rendered a sample of 4061 cases for use in secondary (replicated) analyses. Results One standard deviation increase in CA was positively associated with both one-year (OR 1.15 (CI 1.01–1.31), P < 0.05) and two-year (OR 1.14 (CI 1.02–1.27), P < 0.05) adherence to prescribed statins. Only smoking attenuated the CA–adherence association after adjustment for a range of > 20 covariates. Imputed and complete case analyses yielded very similar results. Conclusions CA estimated on average 30 years earlier in young adulthood is a risk indicator for statin adherence in first MI male patients aged ≤60 years. Future research should include older and female patients and more socioeconomic variables. PMID:28195516

Safety of Percutaneous Patent Ductus Arteriosus Closure: An Unselected Multicenter Population Experience

PubMed Central

El‐Said, Howaida G.; Bratincsak, Andras; Foerster, Susan R.; Murphy, Joshua J.; Vincent, Julie; Holzer, Ralf; Porras, Diego; Moore, John; Bergersen, Lisa

2013-01-01

Background The technique and safety of transcatheter patent ductus arteriosus (PDA) closure have evolved during the past 20 years. We sought to report a multicenter experience of PDA closure with a focus on the rate of adverse events (AE) and a review of institutional practice differences. Methods and Results Outcome data on transcatheter PDA closure were collected at 8 centers prospectively using a multicenter registry (Congenital Cardiac Catheterization Project on Outcome Registry). Between February 2007 and June 2010, 496 PDA closures were recorded using a device in 338 (68%) or coils in 158 (32%). Most patients had an isolated PDA (90%). Fifty percent of patients were between 6 months and 3 years old, with only 40 patients (8%) <6 months old. Median minimum PDA diameter was 2.5 mm (range 1 to 12 mm; IQR 2 to 3 mm) for device closure and 1 mm (range 0.5 to 6 mm; IQR 1 to 2 mm) for coil closure (P<0.001). A device rather than coil was used in patients <3 years, weight <11 kg, and with a PDA minimum diameter >2 mm (all P<0.001). Three of 8 centers exclusively used a device for PDAs with a diameter >1.5 mm. In 9% of cases (n=46), an AE occurred; however, only 11 (2%) were classified as high severity. Younger age was associated with a higher AE rate. Coil‐related AEs were more common than device‐related AEs (10% versus 2%, P<0.001). Conclusions PDA closure in the present era has a very low rate of complications, although these are higher in younger children. Technical intervention‐related events were more common in coil procedures compared with device procedures. For PDAs ≤2.5 mm in diameter, institutional differences in preference for device versus coil exist. PMID:24284214

Pharmacogenetic Selection of Volunteers Increases Stringency of Bioequivalence Studies; The Case of Clopidogrel

PubMed Central

Garcés-Eisele, J.; Ruiz-Argüelles, A.; Estrada-Marín, Larisa; Reyes-Núñez, Virginia; Vázquez-Pérez, R.; Guzmán-García, Olga; Coutiño-Medina, R.; Acosta-Sandria, Leticia; Cedillo-Carvallo, Beatriz

2014-01-01

Clinical response to clopidogrel varies widely due to under-dosing, drug interactions and intrinsic interindividual differences resulting from genetic polymorphisms. Cytochrome P450-2C19 is the principal enzyme involved in the activation of the prodrug and loss-of-function alleles have been described. Upon expiration of the pharmaceutical patent of clopidogrel, generic manufacturers have started to subject interchangeable formulations to bioequivalence studies. The purpose of the current investigation was to study the effect of selection of volunteers homozygous for the CYP2C19*1 haplotype on the bioavailability of clopidogrel. A regular 2×2 bioequivalence study between two formulations of clopidogrel was performed in volunteers selected and unselected for relevant CYP2C19 haplotypes for the Mexican population. It was found that selection of volunteers homozygous for the CYP2C19*1 haplotype, increased the stringency of bioequivalence statistics and resulted in bioinequivalence of a generic clopidogrel compound that otherwise proved equivalent when tested in an open unselected population. Augmentation of bioequivalence strictness is expected to result from pharmacogenetic selection of volunteers. PMID:25284925

Survival and immune response of drones of a Nosemosis tolerant honey bee strain towards N. ceranae infections.

PubMed

Huang, Qiang; Kryger, Per; Le Conte, Yves; Moritz, Robin F A

2012-03-01

Honey bee colonies (Apis mellifera) have been selected for low level of Nosema in Denmark over decades and Nosema is now rarely found in bee colonies from these breeding lines. We compared the immune response of a selected and an unselected honey bee lineage, taking advantage of the haploid males to study its potential impact on the tolerance toward Nosema ceranae, a novel introduced microsporidian pathogen. After artificial infections of the N. ceranae spores, the lineage selected for Nosema tolerance showed a higher N. ceranae spore load, a lower mortality and an up-regulated immune response. The differences in the response of the innate immune system between the selected and unselected lineage were strongest at day six post infection. In particular genes of the Toll pathway were up-regulated in the selected strain, probably is the main immune pathway involved in N. ceranae infection response. After decades of selective breeding for Nosema tolerance in the Danish strain, it appears these bees are tolerant to N. ceranae infections. Copyright © 2012 Elsevier Inc. All rights reserved.

Changes in the structures of motile sperm subpopulations in dog spermatozoa after both cryopreservation and centrifugation on PureSperm(®) gradient.

PubMed

Dorado, J; Alcaráz, L; Duarte, N; Portero, J M; Acha, D; Hidalgo, M

2011-05-01

The aims of the present study were to: (1) determine if discrete motile sperm subpopulations exist and their incidence in fresh dog ejaculates, (2) evaluate the effects of cryopreservation on the distribution of spermatozoa within the different subpopulations, and (3) determine the effect of the discontinuous PureSperm(®) gradient on the sperm subpopulation structure of frozen-thawed dog spermatozoa. Semen from 5 dogs were collected and cryopreserved following a standard protocol. After thawing, semen samples were selected by centrifugation on PureSperm(®). Sperm motility (assessed by computerized-assisted semen analysis, CASA) was assessed before freezing, just after thawing and after preparation on the PureSperm(®) gradients. Cryopreservation had a significant (P<0.001) effect on CASA-derived parameters. PureSperm(®) centrifugation yielded sperm suspensions with improved motility (P<0.01). A multivariate clustering procedure separated 19414 motile spermatozoa into four subpopulations: Subpopulation 1 consisting of poorly active and non-progressive spermatozoa (20.97%), Subpopulation 2 consisting of slow and low-linear spermatozoa (18.24%), Subpopulation 3 consisting of highly active but non-progressive spermatozoa (20.75%), and Subpopulation 4 consisting of high speed and progressive spermatozoa (40.03%). Although, cryopreservation had a significant (P<0.001) effect on both the frequency distribution of spermatozoa within subpopulations and the motion characteristics of each subpopulation, the sperm subpopulation structure was perfectly maintained after freezing and thawing. The selected sperm samples was enrich in Subpopulation 4, reaching a proportion of 31.9% of the present spermatozoa, in contrast with the unselected sperm samples, where this sperm subpopulation accounted for 24.9% of the total. From these results, we concluded that four well-defined motile sperm subpopulations were present either in fresh semen, in unselected sperm samples or in selected preparations from dogs. The discontinuous PureSperm(®) gradient is a simple method to improve the quality of canine frozen-thawed semen samples, since Subpopulation 4 (high-speed and progressive spermatozoa) was more frequently observed after preparation on the gradient. Finally, this study also demonstrated that the general motile sperm structure present in dog remains constant despite the effect caused by either cryopreservation or separation on PureSperm(®) gradient. Copyright © 2011 Elsevier B.V. All rights reserved.

Obstructive sleep apnea is an important predictor of hepatic fibrosis in patients with nonalcoholic fatty liver disease in a tertiary care center.

PubMed

Agrawal, Swastik; Duseja, Ajay; Aggarwal, Ashutosh; Das, Ashim; Mehta, Manu; Dhiman, Radha K; Chawla, Yogesh

2015-04-01

The association of obstructive sleep apnea (OSA) with nonalcoholic fatty liver disease (NAFLD) has only been studied in selected subgroups such as the morbidly obese. We aimed to determine the prevalence and effect of OSA on NAFLD and vice versa in unselected patients attending the outpatient department. OSA was diagnosed by polysomnography, done in patients having symptoms of OSA, in patients with NAFLD attending the liver clinic. Polysomnography-proven patients with OSA attending the chest clinic were evaluated for NAFLD by ultrasonography. Anthropometry, liver function tests, metabolic syndrome evaluation and transient elastography were performed in all patients. Three (3%; 95% CI 1.03-8.45%) out of 100 patients with NAFLD (mean age 41 ± 11 years) had symptomatic OSA. Of 23 patients with OSA (mean age 46 ± 12 years,), 3 (13%) had mild, 5 (22%) moderate and 15 (65%) severe OSA. Twenty-one (91.3%; 95% CI 73.2-97.6%) patients with OSA had NAFLD, while raised hepatic transaminase levels were seen in seven (30.4%; 95% CI 15.6-50.9%). Body mass index (OR 1.21, 95% CI 1.02-1.44) and male gender (OR 4.79, 95% CI 1.12-20.48) were significant independent predictors of OSA in NAFLD. The apnea-hypopnea index (OR 1.084, 95% CI 1.002-1.172), a marker of OSA severity, was the only significant independent predictor of significant fibrosis in patients with NAFLD. Prevalence of symptomatic OSA in patients with NAFLD is low and is predicted by male gender and obesity. Prevalence of NAFLD in patients with OSA is very high. Significant hepatic fibrosis in patients with NAFLD is predicted by OSA independent of obesity and metabolic syndrome.

Use and impact of thrombectomy in primary percutaneous coronary intervention for acute myocardial infarction with persistent ST-segment elevation: results of the prospective ALKK PCI-registry.

PubMed

Härle, Tobias; Zeymer, Uwe; Hochadel, Matthias; Schmidt, Karin; Zahn, Ralf; Darius, Harald; Behrens, Steffen; Lauer, Bernward; Mudra, Harald; Schächinger, Volker; Elsässer, Albrecht

2015-10-01

Data about the impact of thrombectomy in primary percutaneous coronary intervention (PCI) are inconsistent. The aim of our study was an evaluation of both the real-world use of thrombectomy and the impact of thrombectomy on outcome in unselected patients treated with primary PCI for ST-elevation myocardial infarction (STEMI). We used the data of the prospective ALKK PCI-registry of 35 hospitals from January 2010 to December 2013. A total of 10,755 patients receiving single-vessel primary PCI for acute STEMI were included. In 2176 patients (20.2 %) thrombectomy was performed. There was a wide range of use of thrombectomy in the different ALKK hospitals from 1.1 to 61.7 % (median 18.6 %, quartiles 6.0 and 40.3 %) with a general increase of use over the first years of the study period. In patients with and without thrombectomy there was TIMI 0 flow present before PCI in 6010 patients, TIMI 1 in 1338, TIMI 2 in 2002, and TIMI 3 in 1405. Patients with acute heart failure or cardiogenic shock received significantly more often thrombectomy. Fluoroscopy time (8.1 vs. 7.3 min, p < 0.0001) and dose area product (5373 cGy × cm(2) vs. 4802 cGy × cm(2), p < 0.0001) were significantly higher in patients treated with thrombectomy. The subgroup of patients with TIMI 0 flow before PCI had significantly higher rates of TIMI 3 flow after PCI when treated with thrombectomy (87.1 vs. 84.1 %, p < 0.01), while there was no difference in post-PCI TIMI 3 flow in patients with TIMI 1, 2 or 3 flow before PCI. Rates of major adverse cardiac and cerebrovascular events were similar in both groups in general and in all subgroups of TIMI flow. The use of thrombectomy in patients with STEMI is heterogenous between hospitals. Overall, there was no impact of thrombectomy on TIMI 3 patency or mortality after PCI. In the subgroup of STEMI patients with TIMI 0 flow before PCI individualized thrombectomy had a positive impact on restoration of normal blood flow.

Enhanced care for primary hip arthroplasty: factors affecting length of hospital stay.

PubMed

Panteli, Michalis; Habeeb, Shayma'u; McRoberts, John; Porteous, Matthew J

2014-04-01

Enhanced care in joint replacement requires identification and correction of the causes of delay in discharge while ensuring practice remains safe. We conducted prospective studies of factors delaying discharge following hip replacement in 2006 and 2010. Daily data were twice collected prospectively in 100 consecutive unselected primary cemented THR, by an independent observer. Reasons for delays in discharge and variation from the patient pathway were identified and addressed. The mean length of stay (LOS) in 2006 was 4.3 days and in 2010, 3.56 days (target for discharge 4 days). In 2006, 31 patients had a stay of more than 4 days, 17 due to inadequate physiotherapy provision, 10 for medical and 4 for other reasons. In 2010, 15 patients had a stay of more than 4 days, 1 patient had inadequate physiotherapy provision, in 7 cases discharge was delayed because of need for blood transfusion and 7 because of need for catheterisation. Women aged more than 70 with preoperative haemoglobin of <12 g/dL were at particularly high risk of requiring transfusion. Catheterisation was also identified as a factor causing significant increase in LOS. Patients going home in less than 4 days were more likely to have had their operation in the morning. Patient LOS is multifactorial and can be reduced by regular review of the care pathway to effect incremental changes that have a significant impact on reducing stay.

From Clinical Trials to the Front Line: Vinflunine for Treatment of Urothelial Cell Carcinoma at the National Cancer Institute of Naples.

PubMed

Facchini, Gaetano; Della Pepa, Chiara; Cavaliere, Carla; Cecere, Sabrina C; Di Napoli, Marilena; D'Aniello, Carmine; Crispo, Anna; Iovane, Gelsomina; Maiolino, Piera; Tramontano, Teresa; Piscitelli, Raffaele; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Sorrentino, Domenico; Perdonà, Sisto; Pignata, Sandro

2016-01-01

The efficacy of Vinflunine, after failure of platinum-based chemotherapy in patients with metastatic or recurrent Transitional Cell Cancer of the Urothelial Tract, TCCU, has been demonstrated in an international, randomized, phase III trial comparing Vinflunine plus Best Supportive Care, BSC, with BSC alone. On the basis of that study vinflunine has been approved by the European Medicine Association, EMA, for treatment of TCCU patients after failure of a platinum treatment. However, since data in clinical trials often differ from routine clinical practice due to unselected population and less strict monitoring, "real life" experiences are very helpful to verify the efficacy of a new therapy. This was a spontaneous, observational, retrospective study involving 43 patients with metastatic TCCU treated with vinflunine at our cancer center, data about demographics, disease characteristics, and previous treatments were collected and outcome and toxicities of vinflunine were analyzed. 41 of 43 patients were eligible for RR analysis, the Overall RR was 12%, the Disease Control Rate was 29%; when including only patients treated in II line the DCR rose to 33%; the median PFS and the median OS were 2.2 and 6.9 months, respectively. Our findings were consistent with the outcome data emerged in the phase III randomized trial and in the other observational studies conducted all around Europe in the last 2-3 years. This experience supports the use of vinflunine in patients with advanced TTCU as effective and manageable antineoplastic drug.

The feasibility and perioperative complications of outpatient knee arthroplasty.

PubMed

Berger, Richard A; Kusuma, Sharat K; Sanders, Sheila A; Thill, Elizabeth S; Sporer, Scott M

2009-06-01

The duration of hospitalization and subsequent length of recovery after elective knee arthroplasty have decreased. We hypothesized same-day discharge following either a unicompartmental (UKA) or total knee arthroplasty (TKA) in an unselected group of patients would not result in a higher perioperative complication rate than standard-length hospitalization when following a comprehensive perioperative clinical pathway, including preoperative teaching, regional anesthesia, preemptive oral analgesia, preemptive antiemetics, and a rapid rehabilitation protocol. We prospectively followed 111 of all 121 patients who had primary knee arthroplasty completed by noon and who agreed to be followed prospectively; 25 had UKA and 86 TKA. Of the 111 patients, 104 (94%, 24 with UKA and 80 with TKA) met discharge criteria and were discharged directly to home the day of surgery. Nausea requiring additional treatment before discharge was the most common reason for a delay in discharge. There were four (3.6%) readmissions (all with TKA) and one emergency room visit without readmission (in a patient with a TKA) within the first week after surgery, while there were four subsequent readmissions (3.6%) and one additional emergency room visit without readmission within three months of surgery, all among patients undergoing TKA. There were no deaths, cardiac events, or pulmonary complications during this study. Outpatient knee arthroplasty surgery is feasible in a large percentage of patients yet early readmissions may be decreased with a prolonged hospitalization. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

ACE genotype, phenotype and all-cause mortality in different cohorts of patients with type 1 diabetes.

PubMed

Færch, Louise H; Sejling, Anne-Sophie; Lajer, Maria; Tarnow, Lise; Thorsteinsson, Birger; Pedersen-Bjergaard, Ulrik

2015-06-01

Carrying the D-allele of the angiotensin-converting enzyme (ACE) I/D polymorphism and high ACE activity are prognostic factors in diabetic nephropathy, which predicts mortality in type 1 diabetes. We studied the association between the ACE D-allele and ACE phenotype and long-term all-cause mortality in three single-institution outpatient cohorts. Genotype-based analyses were performed in 269 patients from Hillerød Hospital (HIH) (follow-up: 12 years) and in 439 patients with diabetic nephropathy and 437 patients with persistent normoalbuminuria from the Steno Diabetes Center (SDC) (follow-up: 9.5 years). Patients not on renin-angiotensin system (RAS)-blocking treatment were included in analyses of serum ACE activity (HIH: n = 208) and plasma ACE concentration (SDC: n=269). In the HIH cohort, carrying a D-allele was associated with excess mortality (hazard ratio (HR) = 4.0 (95% confidence interval (CI) 1.0-16)), but not in the SDC cohorts. At HIH, serum ACE activity was associated with excess mortality (HR=1.04 (95% CI 1.0-1.1 per unit increase)), but in the SDC cohort plasma ACE concentration was not. In unselected patients with type 1 diabetes, carrying the ACE D-allele and high spontaneous serum ACE activity were associated with 12-year excess mortality. These findings could not be reproduced in two other cohorts with persistent normoalbuminuria or diabetic nephropathy. © The Author(s) 2013.

Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.

PubMed

Burrage, Lindsay C; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H; Nagamani, Sandesh C S

2014-01-01

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Sodium Phenylbutyrate Decreases Plasma Branched-Chain Amino Acids in Patients with Urea Cycle Disorders

PubMed Central

Burrage, Lindsay C.; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H.; Nagamani, Sandesh CS.

2014-01-01

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, they could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. PMID:25042691

A retrospective analysis of cross-reacting cetuximab IgE antibody and its association with severe infusion reactions.

PubMed

Maier, Sabine; Chung, Christine H; Morse, Michael; Platts-Mills, Thomas; Townes, Leigh; Mukhopadhyay, Pralay; Bhagavatheeswaran, Prabhu; Racenberg, Jan; Trifan, Ovidiu C

2015-01-01

Severe infusion reactions (SIRs) at rates of 5% or less are known side effects of biological agents, including mAbs such as cetuximab. There are currently no prospectively validated risk factors to aid physicians in identifying patients who may be at risk of experiencing an SIR following administration of any of these drugs. A retrospective analysis of 545 banked serum or plasma samples from cancer patients participating in clinical trials of cetuximab was designed to evaluate whether the presence of pretreatment IgE antibodies against cetuximab, as determined by a commercially available assay system, is associated with SIRs during the initial cetuximab infusion. Patients with a positive test indicating the presence of pretreatment antibodies had a higher risk of experiencing an SIR; however, at the prespecified cutoff utilized in this analysis, the test has a relatively low-positive predictive value (0.577 [0.369-0.766]) and a negative predictive value of 0.961 (0.912-0.987) in an unselected patient population. Data collected in this large retrospective validation study support prior observations of an association between the presence of pretreatment IgE antibodies cross-reactive with cetuximab and SIRs. Further analysis of the test's ability to predict patients at risk of an SIR would be required before this assay could be used reliably in this patient population. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Genomic Footprints in Selected and Unselected Beef Cattle Breeds in Korea.

PubMed

Lim, Dajeong; Strucken, Eva M; Choi, Bong Hwan; Chai, Han Ha; Cho, Yong Min; Jang, Gul Won; Kim, Tae-Hun; Gondro, Cedric; Lee, Seung Hwan

2016-01-01

Korean Hanwoo cattle have been subjected to intensive artificial selection over the past four decades to improve meat production traits. Another three cattle varieties very closely related to Hanwoo reside in Korea (Jeju Black and Brindle) and in China (Yanbian). These breeds have not been part of a breeding scheme to improve production traits. Here, we compare the selected Hanwoo against these similar but presumed to be unselected populations to identify genomic regions that have been under recent selection pressure due to the breeding program. Rsb statistics were used to contrast the genomes of Hanwoo versus a pooled sample of the three unselected population (UN). We identified 37 significant SNPs (FDR corrected) in the HW/UN comparison and 21 known protein coding genes were within 1 MB to the identified SNPs. These genes were previously reported to affect traits important for meat production (14 genes), reproduction including mammary gland development (3 genes), coat color (2 genes), and genes affecting behavioral traits in a broader sense (2 genes). We subsequently sequenced (Illumina HiSeq 2000 platform) 10 individuals of the brown Hanwoo and the Chinese Yanbian to identify SNPs within the candidate genomic regions. Based on allele frequency differences, haplotype structures, and literature research, we singled out one non-synonymous SNP in the APP gene (APP: c.569C>T, Ala199Val) and predicted the mutational effect on the protein structure. We found that protein-protein interactions might be impaired due to increased exposed hydrophobic surfaces of the mutated protein. The APP gene has also been reported to affect meat tenderness in pigs and obesity in humans. Meat tenderness has been linked to intramuscular fat content, which is one of the main breeding goals for brown Hanwoo, potentially supporting a causal influence of the herein described nsSNP in the APP gene.

Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart.

PubMed

Liu, G S; Richards, S C; Olsson, R A; Mullane, K; Walsh, R S; Downey, J M

1994-07-01

Agonists selective for the A1 adenosine receptor mimic the protective effect of ischaemic preconditioning against infarction in the rabbit heart. Unselective adenosine antagonists block this protection but, paradoxically, the A1 adenosine receptor selective antagonist 8-cyclopentyl- 1,3-dipropylxanthine (DPCPX) does not. The aim of this study was to test the hypothesis that the newly described A3 adenosine receptor, which has an agonist profile similar to the A1 receptor but is insensitive to DPCPX, might mediate preconditioning. Isolated rabbit hearts perfused with Krebs buffer experienced 30 min of regional ischaemia followed by 120 min of reperfusion. Infarct size was measured by tetrazolium staining. In control hearts infarction was 32.2(SEM 1.5)% of the risk zone. Preconditioning by 5 min ischaemia and 10 min reperfusion reduced infarct size to 8.8(2.3)%. Replacing the regional ischaemia with 5 min perfusion with 10 microM adenosine or 65 nM N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA), an adenosine A3 receptor agonist, was equally protective. The unselective antagonist 8-p-sulphophenyl theophylline at 100 microM abolished protection by preconditioning, adenosine, and APNEA, but 200 nM DPCPX did not block protection by any of the interventions. Likewise the potent but unselective A3 receptor antagonist 8-(4-carboxyethenylphenyl)-1,3-dipropylxanthine (BW A1433) completely blocked protection from ischaemic preconditioning. Because protection against infarction afforded by ischaemic preconditioning, adenosine, or the A3 receptor agonist APNEA could not be blocked by DPCPX and because the potent A3 receptor antagonist BW A1433 blocked protection from ischaemic preconditioning, these data indicate that the protection of preconditioning is not exclusively mediated by the adenosine A1 receptor in rabbit heart and could involve the A3 receptor.

[Migraine in SLE: role of antiphospholipid antibodies and Raynaud's phenomenon].

PubMed

Annese, Virginia; Tomietto, Paola; Venturini, Paolo; D'Agostini, Serena; Ferraccioli, Gianfranco

2006-01-01

To determine the role of antiphospholipid antibodies (aPL) and of Raynaud's phenomenon (RP) in the development of migraine in patients with systemic lupus erythematosus (SLE). 50 unselected SLE patients and 20 rheumatoid arthritis (RA) controls underwent an interview to define the presence of migraine according to the guidelines of the International Headache Society (1988). Serological tests for aPL were performed in all patients. SLE patients were divided according to positivity for RP and/or aPL into 4 subsets: R-/aPL-, R-/aPL+, R+/aPL- and R+/aPL+. Data were analysed using Fisher's exact test, Chi-square test and U Mann-Whitney test. SLE and RA patients were similar for demographic and clinical features; aPL positivity was found in a greater proportion of SLE patients versus RA controls (68% vs 25%, p=0.0036). 31 of the 50 lupic patients (62%) and 7 of the 20 RA controls (35%) suffered from migraine (OR=3, CI:1-8.9). Among SLE and RA patients, migraine was associated with aPL positivity (p=0.027 and p=0.019). Analysing the combined effect of aPL and RP on migraine, in R+/aPL+ patients we detected an higher frequency of migraine (85.7%) with respect to the patients negative for these two features (27%, p=0.0051, OR=16, CI:2.2-118) and to the patients positive only for aPL (65%, p=0.0031, OR=6.2, CI:1.2-32). Migraine in SLE and RA associates with aPL positivity. The simultaneous presence of RP increases by 2,5 times the probability of having migraine, suggesting that cerebral vasospasm might be more common in patients with peripheral vasospasm, given the presence of aPL.

Proband-only medical exome sequencing as a cost-effective first-tier genetic diagnostic test for patients without prior molecular tests and clinical diagnosis in a developing country: the China experience.

PubMed

Hu, Xuyun; Li, Niu; Xu, Yufei; Li, Guoqiang; Yu, Tingting; Yao, Ru-En; Fu, Lijun; Wang, Jiwen; Yin, Lei; Yin, Yong; Wang, Ying; Jin, Xingming; Wang, Xiumin; Wang, Jian; Shen, Yiping

2017-11-02

PurposeTo evaluate the performance of proband-only medical exome sequencing (POMES) as a cost-effective first-tier diagnostic test for pediatric patients with unselected conditions.MethodsA total of 1,323 patients were tested by POMES, which targeted 2,742 known disease-causing genes. Clinical relevant variants were Sanger-confirmed in probands and parents. We assessed the diagnostic validity and clinical utility of POMES by means of a survey questionnaire.ResultsPOMES, ordered by 136 physicians, identified 512 pathogenic or likely pathogenic variants associated with over 200 conditions. The overall diagnostic rate was 28.8%, ranging from 10% in neonatal intensive care unit patients to over 35% in pediatric intensive care unit patients. The test results had an impact on the management of the 45.1% of patients for whom there were positive findings. The average turnaround time was 57 days; the cost was $360/case.ConclusionWe adopted a relatively efficient and cost-effective approach in China for the molecular diagnosis of pediatric patients with suspected genetic conditions. While training for clinical geneticists and other specialists is lagging behind in China POMES is serving as a diagnostic equalizer for patients who do not normally receive extensive clinical evaluation and clinical diagnosis prior to testing. This Chinese experience should be applicable to other developing countries that are lacking clinical, financial, and personnel resources.GENETICS in MEDICINE advance online publication, 2 November 2017; doi:10.1038/gim.2017.195.

Efficacy and safety of certolizumab pegol induction therapy in an unselected Crohn's disease population: results of the FACTS survey.

PubMed

Schoepfer, Alain M; Vavricka, Stephan R; Binek, Janek; Felley, Christian; Geyer, Martin; Manz, Michael; Rogler, Gerhard; de Saussure, Philippe; Sauter, Bernhard; Seibold, Frank; Straumann, Alex; Michetti, Pierre

2010-06-01

Switzerland was the first country to approve certolizumab pegol (Cimzia, CZP) for the treatment of patients with moderate to severe Crohn's disease (CD) in September 2007. This phase IV study aimed to evaluate the efficacy and safety of CZP in a Swiss multicenter cohort of practice-based patients. Baseline and Week 6 evaluation questionnaires were sent to all Swiss gastroenterologists in hospitals and private practices. Disease activity was assessed with the Harvey-Bradshaw Index (HBI) and adverse events were evaluated according to WHO guidelines. Fifty patients (31 women, 19 men) were included; 56% had complicated disease (stricture or fistula) and 52% had undergone prior CD-related surgery. All patients had prior exposure to systemic steroids, 96% to immunomodulators, 78% to infliximab, and 50% to adalimumab. A significant decrease in HBI was observed at Week 6 (versus Week 0) following induction therapy with CZP 400 mg subcutaneously at Weeks 0, 2, and 4 (12.6 +/- 4.7 Week 0 versus 6.2 +/- 4.4 Week 6, P < 0.001). Response and remission rates at Week 6 were 54% and 40%, respectively. We identified 8/11 CD patients undergoing a 50% fistula response (P = 0.021). The frequency of adverse drug reactions attributed to CZP was 6%. CZP was continued in 80% of patients beyond Week 6. In a population of CD patients with complicated disease behavior, CZP induced a response and remission in 54% and 40% of patients, respectively. This series provides the first evidence of the effectiveness of CZP in perianal fistulizing CD.

Short-term clinical outcomes after off-pump coronary artery bypass grafting at a single Veterans Affairs Medical Center.

PubMed

Lushaj, Entela B; Schreiner, Athanasia; Jonuzi, Besa; Badami, Abbasali; DeOliveira, Nilto; Lozonschi, Lucian

2016-05-17

We retrospectively assessed the outcomes after coronary revascularization at a single Veterans Affairs Medical Center when a strategy of assigning higher risk patients to off-pump coronary artery bypass grafting (CABG) was employed. Over a 5 year period all consecutive patients that underwent CABG at our VA Medical Center were assigned to a surgeon who either performs the CABG exclusively off-pump or to one who performed the CABG on-pump. The higher risk patients were assigned preferentially for off-pump revascularization. VASQIP (VA Hospitals Surgical Quality Improvement Program) data between 10/2007 and 12/2012 were retrospectively reviewed at our VA Medical Center and the short term outcomes were assessed. A total of 252 consecutive patients underwent off-pump CABG (n = 170) and on-pump CABG (n = 82). There were significantly more patients with low LVEF (<45 %; p = 0.008) and cerebrovascular disease in the off-pump group (p = 0.024). The number of patients smoking at the time of surgery was significantly higher in the off-pump group (p = 0.002) as well. The 30-day composite morbidity and mortality was 6 % for all CABG patients and significantly lower with off-pump vs. on-pump CABG (3.5 % vs. 11 %; p = 0.019). There were no conversions from off-pump to on-pump surgery. A selective strategy to direct higher risk patients towards an off-pump revascularization yielded favorable outcomes in an unselected veteran population treated at a single VA Medical Center over a 5 year period.

The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study

PubMed Central

Boch, Christian; Kollmeier, Jens; Roth, Andreas; Stephan-Falkenau, Susann; Misch, Daniel; Grüning, Wolfram; Bauer, Torsten Thomas; Mairinger, Thomas

2013-01-01

Objectives Owing to novel therapy strategies in epidermal growth factor receptor (EGFR)-mutated patients, molecular analysis of the EGFR and KRAS genome has become crucial for routine diagnostics. Till date these data have been derived mostly from clinical trials, and thus collected in pre-selected populations. We therefore screened ‘allcomers’ with a newly diagnosed non-small cell lung carcinoma (NSCLC) for the frequencies of these mutations. Design A cohort study. Setting Lung cancer centre in a tertiary care hospital. Participants Within 15 months, a total of 552 cases with NSCLC were eligible for analysis. Primary and secondary outcome measures Frequency of scrutinising exons 18, 19 and 21 for the presence of activating EGFR mutation and secondary codon 12 and 13 for activating KRAS mutations. Results Of the 552 patients, 27 (4.9%) showed a mutation of EGFR. 19 of these patients (70%) had deletion E746-A750 in codon 19 or deletion L858R in codon 21. Adenocarcinoma (ACA) was the most frequent histology among patients with EGFR mutations (ACA, 22/254 (8.7%) vs non-ACA, 5/298 (1.7%); p<0.001). Regarding only ACA, the percentage of EGFR mutations was higher in women (16/116 (14%) women vs 6/138 (4.3%) men; p=0.008). Tumours with an activating EGFR mutation were more likely to be from non-smokers (18/27; 67%) rather than smoker (9/27; 33%). KRAS mutation was present in 85 (15%) of all cases. In 73 patients (86%), the mutation was found in exon 12 and in 12 cases (14%) in exon 13. Similarly, ACA had a higher frequency of KRAS mutations than non-ACA (67/254 (26%) vs 18/298 (6.0%); p<0.001). Conclusions We found a lower frequency for EGFR and KRAS mutations in an unselected Caucasian patient cohort as previously published. Taking our results into account, clinical trials may overestimate the mutation frequency for EGFR and KRAS in NSCLC due to important selection biases. PMID:23558737

Screening the nutritional status in oncology: a preliminary report on 1,000 outpatients.

PubMed

Bozzetti, Federico

2009-03-01

This study presents the preliminary data of a prospective multi-centre investigation on the screening of the nutritional status of cancer outpatients with the purpose to define: (1) prevalence and rate of weight loss and nutritional risk in this patient population, and (2) to assess the association among some patient-dependent, tumour-dependent and therapy-dependent variables with the nutritional status and the nutritional risk. Seventeen centres were involved to collect demographic data (age and sex), oncologic data (site of primary tumour, stage, Eastern Cooperative Oncology Group Performance State, oncologic therapy) and presence and severity of systemic and digestive/nutritional symptoms (fatigue, anorexia, nausea/vomiting, early satiety, dysgeusia/dysosmia, dysphagia/odynophagia, diarrhoea/constipation). Furthermore, the percentage of the weight loss on the usual body weight and the body mass index were computed. The nutritional risk was assessed according to the Nutrition Risk Screening 2002 questionnaire which scores the risk from 0 to 7. On the first 1,000 screened patients, a significant weight loss (>or=10%) and a nutritional risk score >or=3 were observed in 39.7% and 33.8% of patients, respectively. Weight loss was higher in upper gastrointestinal tumours, in advanced stages of disease and in patients with a poor performance status. Similarly, the nutritional risk was higher in esophageal and pancreatic cancer and in those with a worse performance status. There was a good correlation between the severity of anorexia and the rate of the weight loss The majority of patients with no weight loss or a weight loss <10% were not anorectic; on the contrary, the majority of those with more severe weight loss had some degree of anorexia. Weight loss and nutritional risk are frequent in an unselected series of cancer outpatients. Site of primary tumour, stage and performance state appear to be associated, at a preliminary analysis, with significant weight loss and nutritional risk. Anorexia and weight loss are closely related, and this supports the concept that nutritional depletion can play a major role in the onset of malnutrition-cachexia.

[Prevalence of renal involvement in a population of type Ii diabetics followed up in primary care].

PubMed

Marín, R; Coca, A; Tranche, S; Rodríguez Mañas, L; Abellán, J; Moyá, A

2002-01-01

Patients with type 2 diabetes use to be managed in their primary care settings during the early stages of the disease. The main objective of the study was to determine renal impairment prevalence, and to assess its significance, within type 2 diabetics controlled by their family physicians. Transverse observation of patients with type 2 diabetes who were the first 20 unselected cases seen by 183 family physicians from 16 of the 17 Autonomic Communities of our country. The following variables were determined: serum creatinine, glucose, and HbA1c concentrations, proteinuria (dipstick test in a first-voided morning urine sample), blood pressure levels, and associated cardiovascular disease. Data from 3,583 type 2 diabetic subjects were evaluated. Mean age was 64 +/- 10 years and 45% were male. A serum creatinine > or = 1.2 mg/dl was observed in 523 (15.5%) patients. Proteinuria was present in 794 (23.5%) cases, being > or = 2 + in 215 (6.5%) subjects. Patients with a serum creatinine > or = 1.2 mg/dl were older, shower higher blood pressure levels, and suffered from more cardiovascular disease (32.0 vs 19.5%) than those with a serum creatinine < 1.2 mg/dl. In a multivariate analysis, this difference continued to be significant (OR 1.47; 95% CI 1.14 to 1.90; p = 0.002. Patients with proteinuria showed a higher prevalence of cardiovascular disease (OR 1.83; 95% CI 1.47 to 2.27; p < 0.0001) than those without proteinuria. This association was continuous through no proteinuria to the > or = 2 + proteinuria (p < 0.001). Blood pressure level was > or = 140/90 mmHg in 69% of the cases, being < 130/85 mmHg in only 8% of the subjects. There is a high prevalence of renal impairment, approximately of 25% within type 2 diabetic patients seen at the primary care level. Optimal blood pressure level seems to be extremely infrequent bearing in mind the diagnosis of diabetes and the associated cardiovascular disease.

Recovery after uncomplicated laparoscopic cholecystectomy.

PubMed

Bisgaard, Thue; Klarskov, Birthe; Kehlet, Henrik; Rosenberg, Jacob

2002-11-01

After laparoscopic cholecystectomy, the duration of convalescence is 2 to 3 weeks with an unclear pathogenesis. This study was undertaken to analyze postoperative recovery after uncomplicated elective laparoscopic cholecystectomy. Twenty-four consecutive unselected employed patients were followed up prospectively from 1 week before to 1 week after outpatient laparoscopic cholecystectomy. Daily computerized monitoring of physical motor activity and sleep duration and night sleep fragmentation (actigraphy), subjective sleep quality, pulmonary function, pain, and fatigue were registered. Treadmill exercise performance (preoperatively and at postoperative days 2 and 8) and nocturnal pulse oximetry at the patients' homes (preoperatively and postoperative nights 1-3) were completed. Median age was 41 years (range, 21-56). Compared with preoperatively, levels of physical motor activity, fatigue, and pain scores were normalized 2 days after operation. Subjective sleep quality was significantly worsened on the first postoperative night, and sleep duration was significantly increased on the first 2 postoperative nights. There were no significant perioperative changes in actigraphy night sleep fragmentation, incidence of self-reported awakenings or nightmares/distressing dreams, exercise performance, or nocturnal oxygenation. Pulmonary peak flow measurements were normalized the day after operation. After uncomplicated outpatient laparoscopic cholecystectomy, there is no pathophysiologic basis for recommending a postoperative convalescence of more than 2 to 3 days in otherwise healthy younger patients.

At-risk gambling in patients with severe mental illness: Prevalence and associated features.

PubMed

Bergamini, Annalisa; Turrina, Cesare; Bettini, Francesca; Toccagni, Anna; Valsecchi, Paolo; Sacchetti, Emilio; Vita, Antonio

2018-06-05

Background and aims The primary objective of this study was to investigate the prevalence of at-risk gambling in a large, unselected sample of outpatients attending two community mental health centers, to estimate rates according to the main diagnosis, and to evaluate risk factors for gambling. Methods All patients attending the centers were evaluated with the Canadian Problem Gambling Index and the Mini International Neuropsychiatric Interview. Diagnoses were checked with the treating psychiatrists and after a chart review of the university hospital discharge diagnoses. Results The rate of at-risk gambling in 900 patients was 5.3%. In those who gambled over the last year, 10.1% were at-risk gamblers. The rates in the main diagnostic groups were: 4.7% schizophrenia and related disorders, 4.9% bipolar disorder, 5.6% unipolar depression, and 6.6% cluster B personality disorder. In 52.1% of the cases, at-risk gambling preceded the onset of a major psychiatric disorder. In a linear regression analysis, a family history of gambling disorder, psychiatric comorbidities, drug abuse/dependence, and tobacco smoking were significantly associated with at-risk gambling. Discussion and conclusion The results of this study evidenced a higher rate of at-risk gambling compared to community estimates and call for a careful screening for gambling in the general psychiatric population.

Clinical impact of tumour biology in the management of gastroesophageal cancer.

PubMed

Lordick, Florian; Janjigian, Yelena Y

2016-06-01

The characterization of oesophageal and gastric cancer into subtypes based on genotype has evolved in the past decade. Insights into the molecular landscapes of gastroesophageal cancer provide a roadmap to assist the development of new drugs and their use in combinations, for patient stratification, and for trials of targeted therapies. Trastuzumab is the only approved treatment for gastroesophageal cancers that overexpress HER2. Acquired resistance usually limits the duration of response to this treatment, although a number of new agents directed against HER2 have the potential to overcome or prolong the time until resistance occurs. Beyond that, anti-VEGFR2 therapy with ramucirumab was the first biological treatment strategy to produce a survival benefit in an unselected population of patients with chemotherapy-refractory gastroesophageal cancer. Large initiatives are starting to address the role of biomarker-driven targeted therapy in the metastatic and in the perioperative setting for patients with this disease. Immunotherapy also holds promise, and our understanding of subsets of gastroesophageal cancer based on patterns of immune response continues to evolve. Efforts are underway to identify more relevant genomic subsets through genomic screening, functional studies, and molecular characterization. Herein, we provide an overview of the key developments in the treatment of gastroesophageal cancer, and discuss potential strategies to further optimize therapy by targeting disease subtypes.

Prevalence of Obstructive Sleep Apnea in Patients with Chronic Wounds

PubMed Central

Patt, Brian T.; Jarjoura, David; Lambert, Lynn; Roy, Sashwati; Gordillo, Gayle; Schlanger, Richard; Sen, Chandan K.; Khayat, Rami N.

2010-01-01

Study Objectives: Chronic non-healing wounds are a major human and economic burden. Obstructive sleep apnea (OSA) is prevalent in patients with obesity, diabetes, aging, and cardiovascular disease, all of which are risk factors for chronic wounds. We hypothesized that OSA would have more prevalence in patients of a wound center than the general middle-aged population. Methods: Consecutive patients of the Ohio State University Comprehensive Wound Center (CWC) were surveyed with the Berlin and Epworth questionnaires. In the second stage of the protocol, 50 consecutive unselected CWC patients with lower extremity wounds underwent home sleep studies. Results: In 249 patients of the CWC who underwent the survey study, OSA had been previously diagnosed in only 22%. The prevalence of high-risk status based on questionnaires for OSA was 46% (95% CI 40%, 52%). In the 50 patients who underwent home sleep studies, and using an apnea hypopnea index of 15 events per hour, the prevalence of OSA was 57% (95% CI 42%, 71%). There was no difference between the Berlin questionnaire score and weight between patients with OSA and those without. Conclusions: The prevalence of OSA in patients with chronic wounds exceeds the estimated prevalence of OSA in the general middle aged population. This study identifies a previously unrecognized population with high risk for OSA. Commonly used questionnaires were not sufficiently sensitive for the detection of high risk status for OSA in this patient population. Citation: Patt BT; Jarjoura D; Lambert L; Roy S; Gordillo G; Schlanger R; Sen CK; Khayat RN. Prevalence of obstructive sleep apnea in patients with chronic wounds. J Clin Sleep Med 2010;6(6):541-544. PMID:21206743

Psychiatric comorbidity and psychosocial impairment among patients with vertigo and dizziness.

PubMed

Lahmann, Claas; Henningsen, Peter; Brandt, Thomas; Strupp, Michael; Jahn, Klaus; Dieterich, Marianne; Eckhardt-Henn, Annegret; Feuerecker, Regina; Dinkel, Andreas; Schmid, Gabriele

2015-03-01

Vertigo and dizziness are often not fully explained by an organic illness, but instead are related to psychiatric disorders. This study aimed to evaluate psychiatric comorbidity and assess psychosocial impairment in a large sample of patients with a wide range of unselected organic and non-organic (ie, medically unexplained) vertigo/dizziness syndromes. This cross-sectional study involved a sample of 547 patients recruited from a specialised interdisciplinary treatment centre for vertigo/dizziness. Diagnostic evaluation included standardised neurological examinations, structured clinical interview for major mental disorders (SCID-I) and self-report questionnaires regarding dizziness, depression, anxiety, somatisation and quality of life. Neurological diagnostic workup revealed organic and non-organic vertigo/dizziness in 80.8% and 19.2% of patients, respectively. In 48.8% of patients, SCID-I led to the diagnosis of a current psychiatric disorder, most frequently anxiety/phobic, somatoform and affective disorders. In the organic vertigo/dizziness group, 42.5% of patients, particularly those with vestibular paroxysmia or vestibular migraine, had a current psychiatric comorbidity. Patients with psychiatric comorbidity reported more vertigo-related handicaps, more depressive, anxiety and somatisation symptoms, and lower psychological quality of life compared with patients without psychiatric comorbidity. Almost half of patients with vertigo/dizziness suffer from a psychiatric comorbidity. These patients show more severe psychosocial impairment compared with patients without psychiatric disorders. The worst combination, in terms of vertigo-related handicaps, is having non-organic vertigo/dizziness and psychiatric comorbidity. This phenomenon should be considered when diagnosing and treating vertigo/dizziness in the early stages of the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Long-term therapeutic efficacy of photo-selective vaporization of prostate

NASA Astrophysics Data System (ADS)

Arum, Carl-Jørgen; Muller, Camilla; Romundstad, Pal; Stokkan, Inger; Mjønes, Jan

2010-02-01

OBJECTIVES: We evaluated the long term therapeutic efficacy of 80 watt photo-selective vaporization of the prostate (PVP) in patients suffering from lower urinary tract symptoms (LUTS) secondary to prostatic obstruction. MATERIAL & METHODS: 150 unselected patients at the average age 73 (range 51-92) and a mean American Society of Anesthesiologists score of 2.4 (median 2.0), of whom 33% were medicated with acetylsalicylic acid and 5% were anticoagulated with warfarin. Inclusion/exclusion criteria were the same as for TUR-P at our institution. First patient was operated March 2004 and yearly follow-up of all patients has been attempted for 5 years. Follow-up variables have included yearly creatinine, PSA, IPSS, ØOL, post-void residual urin and maximum/average urine flow rate. RESULTS: At 12 and 24 months postoperatively, the following parameters were significantly (p<0.001) improved: trans-rectal ultrasound, international prostate symptom score, quality of life score, post-void residual urine volume, flow max/average, opening pressure, pressure @ flow-max, and micturition resistance. At 48 and 60 months creatinine, PSA, IPSS, ØOL, post-void residual urin and maximum/average urine flow rates were still significantly (p<0.001) improved compared to pre-operative values. CONCLUSION: Up to 5 year follow-up reveals that 80 watt PVP provides significant and stable symptom relief as well as objective improvement in residual urine and flowmetric outcomes.

Do different fairness contexts and facial emotions motivate 'irrational' social decision-making in major depression? An exploratory patient study.

PubMed

Radke, Sina; Schäfer, Ina C; Müller, Bernhard W; de Bruijn, Ellen R A

2013-12-15

Although 'irrational' decision-making has been linked to depression, the contribution of biases in information processing to these findings remains unknown. To investigate the impact of cognitive biases and aberrant processing of facial emotions on social decision-making, we manipulated both context-related and emotion-related information in a modified Ultimatum Game. Unfair offers were (1) paired with different unselected alternatives, establishing the context in which an offer was made, and (2) accompanied by emotional facial expressions of proposers. Responder behavior was assessed in patients with major depressive disorder and healthy controls. In both groups alike, rejection rates were highest following unambiguous signals of unfairness, i.e. an angry proposer face or when an unfair distribution had deliberately been chosen over an equal split. However, depressed patients showed overall higher rejection rates than healthy volunteers, without exhibiting differential processing biases. This suggests that depressed patients were, as healthy individuals, basing their decisions on informative, salient features and differentiating between (i) fair and unfair offers, (ii) alternatives to unfair offers and (iii) proposers' facial emotions. Although more fundamental processes, e.g. reduced reward sensitivity, might underlie increased rejection in depression, the current study provides insight into mechanisms that shape fairness considerations in both depressed and healthy individuals. © 2013 Elsevier Ireland Ltd. All rights reserved.

Pyroglutamate (5-oxoproline) measured with hydrophilic interaction chromatography (HILIC) tandem mass spectrometry in acutely ill patients.

PubMed

Pretorius, Carel J; Reade, Michael C; Warnholtz, Chris; McWhinney, Brett; Phua, Meng Mei; Lipman, Jeffrey; Ungerer, Jacobus P J

2017-03-01

Pyroglutamic acid (PGA) is challenging to quantify in plasma and is a rare cause of metabolic acidosis that is associated with inherited disorders or acquired after exposure to drugs. We developed a hydrophilic interaction liquid chromatography tandem mass spectrometry method with a short analysis time. We established a reference interval and then measured PGA in acutely ill patients to investigate associations with clinical, pharmaceutical and laboratory parameters. The assay limit of the blank was 0.14μmol/L and was linear to 5000μmol/L with good precision. In-source formation of PGA from glutamate and glutamine was avoided by chromatographic separation. The PGA in controls had a reference interval of 22.6 to 47.8μmol/L. The median PGA concentration in acutely ill patients was similar (P=0.21), but 18 individuals were above the reference interval with concentrations up to 250μmol/L. We detected an association between PGA concentration and antibiotic and acetaminophen administration as well as renal impairment and severity of illness. Elevations of PGA in this unselected cohort were small compared to those reported in patients with pyroglutamic acidosis. The method is suitable for routine clinical use. We confirmed several expected associations with PGA in an acutely ill population. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Stable Genetic Influence on Anxiety-Related Behaviours across Middle Childhood

ERIC Educational Resources Information Center

Trzaskowski, Maciej; Zavos, Helena M. S.; Haworth, Claire M. A.; Plomin, Robert; Eley, Thalia C.

2012-01-01

We examined the aetiology of anxiety symptoms in an unselected population at ages 7 and 9, a period during which anxiety disorders first begin to develop (mean age at onset is 11 years). Specifically, the aim of the study was to investigate genetic and environmental continuity and change in components of anxiety in middle childhood. Parents of…

Scan for allele frequency differences from pooled samples in lines of pigs selected for components of litter size

USDA-ARS?s Scientific Manuscript database

Direct single trait selection within two seasonal replicates for 11 generations resulted in a 1.6 pig advantage for uterine capacity (UC) and a 3.0 advantage for ovulation rate (OR) compared to an unselected control (CO) population. Our objective was to gain insight and identify genetic loci impacte...

Unselective Overimitators: The Evolutionary Implications of Children's Indiscriminate Copying of Successful and Prestigious Models

ERIC Educational Resources Information Center

Chudek, Maciej; Baron, Andrew S.; Birch, Susan

2016-01-01

Children are both shrewd about whom to copy--they selectively learn from certain adults--and overimitators--they copy adults' obviously superfluous actions. Is overimitation also selective? Does selectivity change with age? In two experiments, 161 two- to seven-year-old children saw videos of one adult receiving better payoffs or more bystander…

The Place of Drugs in the Religion of the Counter Culture.

ERIC Educational Resources Information Center

Clark, Walter Houston

The thesis of this paper is that the main catalyst of religious interest of the counter culture has been the use of psychedelic drugs along with marijuana. The author determined, through investigating subjective experiences of an unselected population of 100 users of LSD type drugs and 20 users of cannabis drugs, that psychedelic drugs are…

WISC-R Verbal and Performance IQ Discrepancy in an Unselected Cohort: Clinical Significance and Longitudinal Stability.

ERIC Educational Resources Information Center

Moffitt, Terrie E.; Silva, P. A.

1987-01-01

Examined children whose Wechsler Intelligence Scale for Children-Revised (WISC-R) verbal and performance Intelligence Quotient discrepancies placed them beyond the 90th percentile. Longitudinal study showed 23 percent of the discrepant cases to be discrepant at two or more ages. Studied frequency of perinatal difficulties, early childhood…

Parents' Views on Changing Communication after Cochlear Implantation

ERIC Educational Resources Information Center

Watson, Linda M.; Hardie, Tim; Archbold, Sue M.; Wheeler, Alexandra

2008-01-01

We sent questionnaires to families of all 288 children who had received cochlear implants at one center in the United Kingdom at least 5 years previously. Thus, it was a large, unselected group. We received 142 replies and 119 indicated that the child and family had changed their communication approach following cochlear implantation. In 113 cases…

Children's Subjective Emotional Reactivity to Affective Pictures: Gender Differences and Their Antisocial Correlates in an Unselected Sample of 7-11-Year-Olds

ERIC Educational Resources Information Center

Sharp, Carla; Van Goozen, Stephanie; Goodyer, Ian

2006-01-01

Background: Differential responses in terms of gender and antisocial behaviour in emotional reactivity to affective pictures using the International Affective Picture System (IAPS) have been demonstrated in adult and adolescent samples. Moreover, a quadratic relationship between the arousal (intensity) and valence (degree of unpleasantness) has…

The Hierarchical Factor Model of ADHD: Invariant across Age and National Groupings?

ERIC Educational Resources Information Center

Toplak, Maggie E.; Sorge, Geoff B.; Flora, David B.; Chen, Wai; Banaschewski, Tobias; Buitelaar, Jan; Ebstein, Richard; Eisenberg, Jacques; Franke, Barbara; Gill, Michael; Miranda, Ana; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; Thompson, Margaret; Tannock, Rosemary; Asherson, Philip; Faraone, Stephen V.

2012-01-01

Objective: To examine the factor structure of attention-deficit/hyperactivity disorder (ADHD) in a clinical sample of 1,373 children and adolescents with ADHD and their 1,772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and…

Genetic Variance for Autism Screening Items in an Unselected Sample of Toddler-Age Twins

ERIC Educational Resources Information Center

Stilp, Rebecca L. H.; Gernsbacher, Morton Ann; Schweigert, Emily K.; Arneson, Carrie L.; Goldsmith, H. Hill

2010-01-01

Objective: Twin and family studies of autistic traits and of cases diagnosed with autism suggest high heritability; however, the heritability of autistic traits in toddlers has not been investigated. Therefore, this study's goals were (1) to screen a statewide twin population using items similar to the six critical social and communication items…

Extreme antagonistic pleiotropy effects of DGAT1 on fat, milk and protein yields

USDA-ARS?s Scientific Manuscript database

A large-scale analysis using 294,079 first lactation Holstein cows, as well as a group of contemporary Holsteins and a Holstein line unselected since 1964, were used to study the genetic architecture associated with a mutation in the DGAT1 gene that has large effects on milk production. The ‘G’ alle...

Review: The Development of Coping across Childhood and Adolescence--An Integrative Review and Critique of Research

ERIC Educational Resources Information Center

Zimmer-Gembeck, Melanie J.; Skinner, Ellen A.

2011-01-01

Despite consensus that development shapes every aspect of coping, studies of age differences in coping have proven difficult to integrate, primarily because they examine largely unselected age groups, and utilize overlapping coping categories. A developmental framework was used to organize 58 studies of coping involving over 250 age comparisons or…

A network view on psychiatric disorders: network clusters of symptoms as elementary syndromes of psychopathology.

PubMed

Goekoop, Rutger; Goekoop, Jaap G

2014-01-01

The vast number of psychopathological syndromes that can be observed in clinical practice can be described in terms of a limited number of elementary syndromes that are differentially expressed. Previous attempts to identify elementary syndromes have shown limitations that have slowed progress in the taxonomy of psychiatric disorders. To examine the ability of network community detection (NCD) to identify elementary syndromes of psychopathology and move beyond the limitations of current classification methods in psychiatry. 192 patients with unselected mental disorders were tested on the Comprehensive Psychopathological Rating Scale (CPRS). Principal component analysis (PCA) was performed on the bootstrapped correlation matrix of symptom scores to extract the principal component structure (PCS). An undirected and weighted network graph was constructed from the same matrix. Network community structure (NCS) was optimized using a previously published technique. In the optimal network structure, network clusters showed a 89% match with principal components of psychopathology. Some 6 network clusters were found, including "Depression", "Mania", "Anxiety", "Psychosis", "Retardation", and "Behavioral Disorganization". Network metrics were used to quantify the continuities between the elementary syndromes. We present the first comprehensive network graph of psychopathology that is free from the biases of previous classifications: a 'Psychopathology Web'. Clusters within this network represent elementary syndromes that are connected via a limited number of bridge symptoms. Many problems of previous classifications can be overcome by using a network approach to psychopathology.

Occurrence and species distribution of pathogenic Mucorales in unselected soil samples from France.

PubMed

Mousavi, B; Costa, J M; Arné, P; Guillot, J; Chermette, R; Botterel, F; Dannaoui, E

2018-04-01

Mucormycosis is a life-threatening invasive fungal disease that affects a variety of patient groups. Although Mucorales are mostly opportunistic pathogens originating from soil or decaying vegetation, there are currently few data on prevalence of this group of fungi in the environment. The aim of the present study was to assess the prevalence and diversity of species of Mucorales from soil samples collected in France. Two grams of soil were homogenized in sterile saline and plated on Sabouraud dextrose agar and RPMI agar supplemented with itraconazole or voriconazole. Both media contained chloramphenicol and gentamicin. The plates were incubated at 35 ± 2 °C and checked daily for fungal growth for a maximum of 7 d. Mucorales were subcultured for purity. Each isolate was identified phenotypically and molecular identification was performed by ITS sequencing. A total of 170 soil samples were analyzed. Forty-one isolates of Mucorales were retrieved from 38 culture-positive samples. Among the recovered isolates, 27 Rhizopus arrhizus, 11 Mucor circinelloides, one Lichtheimia corymbifera, one Rhizopus microsporus and one Cunninghamella bertholletiae were found. Positive soil samples came from cultivated fields but also from other types of soil such as flower beds. Mucorales were retrieved from samples obtained in different geographical regions of France. Voriconazole-containing medium improved the recovery of Mucorales compared with other media. The present study showed that pathogenic Mucorales are frequently recovered from soil samples in France. Species diversity should be further analyzed on a larger number of soil samples from different geographic areas in France and in other countries.

An acute stroke evaluation app: a practice improvement project.

PubMed

Rubin, Mark N; Fugate, Jennifer E; Barrett, Kevin M; Rabinstein, Alejandro A; Flemming, Kelly D

2015-04-01

A point-of-care workflow checklist in the form of an iOS (iPhone Operating System) app for use by stroke providers was introduced with the objective of standardizing acute stroke evaluation and documentation at 2 affiliated academic medical centers. Providers used the app in unselected, consecutive patients undergoing acute stroke evaluation in an emergency department or hospital setting between August 2012 and January 2013 and August 2013 and February 2014. Satisfaction surveys were prospectively collected pre- and postintervention from residents, staff neurologists, and clinical data specialists. Residents (20 preintervention and 16 postintervention), staff neurologists (6 pre and 5 post), and clinical data specialists (4 pre and 4 post) participated in this study. All 16 (100%) residents had increased satisfaction with their ability to perform an acute stroke evaluation postintervention but only 9 (56%) of 16 felt the app was more help than hindrance. Historical controls aligned with preintervention results. Staff neurologists conveyed increased satisfaction with resident presentations and decision making when compared to preintervention surveys. Stroke clinical data specialists estimated a 50% decrease in data abstraction when the app data were used in the clinical note. Concomitant effect on door-to-needle (DTN) time at 1 site, although not a primary study measure, was also evaluated. At that 1 center, the mean DTN time decreased by 16 minutes when compared to the corresponding months from the year prior. The point-of-care acute stroke workflow checklist app may assist trainees in presenting findings in a standardized manner and reduce data abstraction time. The app may help reduce DTN time, but this requires further study.

Initiation and adherence to secondary prevention pharmacotherapy after myocardial infarction in patients with rheumatoid arthritis: a nationwide cohort study.

PubMed

Lindhardsen, Jesper; Ahlehoff, Ole; Gislason, Gunnar Hilmar; Madsen, Ole Rintek; Olesen, Jonas Bjerring; Torp-Pedersen, Christian; Hansen, Peter Riis

2012-09-01

To examine whether rheumatoid arthritis (RA) is associated with less optimal secondary prevention pharmacotherapy after first-time myocardial infarction (MI). The authors identified all patients with first-time MI in the Danish National Patient Register from 2002 to 2009 and gathered individual level information including pharmacy records from nationwide registers. Initiation of standard care post-MI secondary prevention drugs, that is, aspirin, β-blockers, clopidogrel, renin angiotensin system (RAS) blockers and statins, was determined after discharge. In addition, adherence to each drug was evaluated as the proportion of patients on treatment during follow-up and time to first treatment gap. A total of 66 107 MI patients (37% women) were discharged alive; 877 were identified as RA patients (59% women). Thirty days after discharge, RA was associated with significantly lower initiation of aspirin (OR 0.80 (0.67-0.96)), β-blockers (0.77 (0.65-0.92)) and statins (0.69 (0.58-0.82)), while initiation of RAS blockers (0.80 (0.57-1.11)) and clopidogrel (0.88 (0.75-1.02)) was non-significantly reduced. These estimates were virtually unchanged at day 180 and the results were corroborated by Cox regression analyses. Adherence to statins was lower in RA patients relative to non-RA patients (HR for treatment gap of 90 days: 1.26 (1.07-1.48)), while no significant differences were found in adherence to the other drugs. In this nationwide study of unselected patients with first-time MI, a reduced initiation of secondary prevention pharmacotherapy was observed in RA patients. This undertreatment may contribute to the increased cardiovascular disease burden in RA and the underlying mechanisms warrant further study.

Sleep apnea-related risk of motor vehicle accidents is reduced by continuous positive airway pressure: Swedish Traffic Accident Registry data.

PubMed

Karimi, Mahssa; Hedner, Jan; Häbel, Henrike; Nerman, Olle; Grote, Ludger

2015-03-01

Obstructive sleep apnea (OSA) is associated with an increased risk of motor vehicle accidents (MVAs). The rate of MVAs in patients suspected of having OSA was determined and the effect of continuous positive airway pressure (CPAP) was investigated. MVA rate in patients referred for OSA was compared to the rate in the general population using data from the Swedish Traffic Accident Registry (STRADA), stratified for age and calendar year. The risk factors for MVAs, using demographic and polygraphy data, and MVA rate before and after CPAP were evaluated in the patient group. Clinical sleep laboratory and population based control (n = 635,786). There were 1,478 patients, male sex 70.4%, mean age 53.6 (12.8) y. CPAP. The number of accidents (n = 74) among patients was compared with the expected number (n = 30) from a control population (STRADA). An increased MVA risk ratio of 2.45 was found among patients compared with controls (P < 0.001). Estimated excess accident risk was most prominent in the elderly patients (65-80 y, seven versus two MVAs). In patients, driving distance (km/y), EDS (Epworth Sleepiness score ≥ 16), short habitual sleep time (≤5 h/night), and use of hypnotics were associated with increased MVA risk (odds ratios 1.2, 2.1, 2.7 and 2.1, all P ≤ 0.03). CPAP use ≥ 4 h/night was associated with a reduction of MVA incidence (7.6 to 2.5 accidents/1,000 drivers/y). The MVA risk in this large cohort of unselected patients with OSA suggests a need for accurate tools to identify individuals at risk. Sleep apnea severity (e.g., apnea-hypopnea index) failed to identify patients at risk. © 2015 Associated Professional Sleep Societies, LLC.

Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North American Brain Tumor Consortium Study

PubMed Central

de Groot, John F.; Lamborn, Kathleen R.; Chang, Susan M.; Gilbert, Mark R.; Cloughesy, Timothy F.; Aldape, Kenneth; Yao, Jun; Jackson, Edward F.; Lieberman, Frank; Robins, H. Ian; Mehta, Minesh P.; Lassman, Andrew B.; DeAngelis, Lisa M.; Yung, W.K. Alfred; Chen, Alice; Prados, Michael D.; Wen, Patrick Y.

2011-01-01

Purpose Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma. Patients and Methods Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle. Results The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance. Conclusion Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma. PMID:21606416

Prospective analysis of safety and efficacy of medical cannabis in large unselected population of patients with cancer.

PubMed

Bar-Lev Schleider, Lihi; Mechoulam, Raphael; Lederman, Violeta; Hilou, Mario; Lencovsky, Ori; Betzalel, Oded; Shbiro, Liat; Novack, Victor

2018-03-01

Cancer is a major public health problem as the leading cause of death. Palliative treatment aimed to alleviate pain and nausea in patients with advanced disease is a cornerstone of oncology. In 2007, the Israeli Ministry of Health began providing approvals for medical cannabis for the palliation of cancer symptoms. The aim of this study is to characterize the epidemiology of cancer patients receiving medical cannabis treatment and describe the safety and efficacy of this therapy. We analyzed the data routinely collected as part of the treatment program of 2970 cancer patients treated with medical cannabis between 2015 and 2017. The average age was 59.5 ± 16.3 years, 54.6% women and 26.7% of the patients reported previous experience with cannabis. The most frequent types of cancer were: breast (20.7%), lung (13.6%), pancreatic (8.1%) and colorectal (7.9%) with 51.2% being at stage 4. The main symptoms requiring therapy were: sleep problems (78.4%), pain (77.7%, median intensity 8/10), weakness (72.7%), nausea (64.6%) and lack of appetite (48.9%). After six months of follow up, 902 patients (24.9%) died and 682 (18.8%) stopped the treatment. Of the remaining, 1211 (60.6%) responded; 95.9% reported an improvement in their condition, 45 patients (3.7%) reported no change and four patients (0.3%) reported deterioration in their medical condition. Cannabis as a palliative treatment for cancer patients seems to be well tolerated, effective and safe option to help patients cope with the malignancy related symptoms. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Feasibility and efficacy of the 2.5 L and 3.8 L impella percutaneous left ventricular support device during high-risk, percutaneous coronary intervention in patients with severe aortic stenosis.

PubMed

Spiro, Jon; Venugopal, Vinod; Raja, Yogesh; Ludman, Peter F; Townend, Jonathan N; Doshi, Sagar N

2015-05-01

Assessment of the feasibility and outcomes of the 2.5 L and 3.8 L Impella cardiac pump in patients with severe aortic stenosis (AS) and left ventricular impairment undergoing percutaneous revascularization (PCI) with or without balloon aortic valvuloplasty (BAV). We reviewed the clinical and procedural findings from a consecutive series of unselected patients with severe AS who underwent PCI during Impella support. In addition, we describe novel "balloon-assist" techniques that allowed implantation of Impella into the left ventricle (LV) when initial unassisted attempts failed. Five patients with severe AS were identified (four males, age 78.2 years, aortic valve area (AVA) 0.6 cm(2) , left ventricular ejection fraction (LVEF) 24 ± 5%, mean Society of Thoracic Surgeons (STS) mortality 11% (range 3-17%)). The Impella catheter traversed the aortic valve (AV) unassisted in only one patient, with four cases requiring balloon-assist techniques. All patients underwent planned revascularisation; mean procedure time 177 min (range 135-252 min), mean number of stents 3.4 (range 1-8), with three patients requiring rotational atherectomy. All procedures were well tolerated, with absence of arrhythmia, hypotension, pulmonary edema, stroke, or myocardial infarction. One patient died 48 hr post-PCI of multi-organ failure. The four remaining patients were well at 30 days. Implantation of the 2.5 and 3.8 L Impella appears feasible in patients with severe AS and left ventricle (LV) impairment. A balloon-assist technique may be used to facilitate device implantation when initial unassisted attempts fail. Improved hemodynamic stability may enhance the tolerability of lengthy and complex procedures. © 2014 Wiley Periodicals, Inc.

Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program.

PubMed

Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I

2018-01-01

Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods: Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results: Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions: Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable.

Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program

PubMed Central

Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I.

2018-01-01

Purpose:Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods:Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results:Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions:Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable. PMID:29344270

The perspective of celiac disease patients on emerging treatment options and non-celiac gluten sensitivity.

PubMed

Greuter, Thomas; Schmidlin, Sandra; Lattmann, Jaqueline; Stotz, Matthias; Lehmann, Romina; Zeitz, Jonas; Scharl, Michael; Misselwitz, Benjamin; Pohl, Daniel; Fried, Michael; Tutuian, Radu; Fasano, Alessio; Schoepfer, Alain M; Rogler, Gerhard; Biedermann, Luc; Vavricka, Stephan R

2017-03-01

Non-celiac gluten sensitivity (NCGS) and emerging treatment options are hot topics in the celiac disease (CeD) scientific literature. However, very little is known about the perspective on these issues of CeD patients. We performed a large patient survey among unselected CeD patients in Switzerland. A total of 1689 patients were analyzed. 57.5% have previously heard of NCGS. 64.5% believe in the existence of this entity. Regarding a potential influence of NCGS on CeD awareness, 31.7% show a positive and 27.5% a negative perception. Patients with prior use of alternative medicine and women more often have heard of and believe in the existence of NCGS vs. those never having used alternative methods and men, respectively (66.9 vs. 56.9%, p=0.001 and 78.5 vs. 69.0%, p=0.001; 60.7 vs. 44.2%, p<0.001 and 71.0 vs. 60.8%, p=0.002). Women and patients ≥30 years more often show a negative attitude towards NCGS (32.2% vs. 24.8%, p=0.024 and 32.2% vs. 24.2%, p=0.018). With regard to emerging treatment options for CeD, 43.3% have previously heard of novel agents, more women than men (46.0 vs. 38.0%, p=0.019). Perception of and attitude towards NCGS differ depending on sex, age and prior use of alternative medicine. Knowledge of the progress towards emerging treatment options is currently limited. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Reprint of "Decline in platelet count and long-term post-PCI ischemic events: implication of the intra-aortic balloon pump".

PubMed

Schiariti, Michele; Saladini, Patrizia; Cuturello, Domenico; Iannetta, Loredana; Torromeo, Concetta; Puddu, Paolo Emilio

2014-04-01

Thrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations. We studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count ≥25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan-Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p=0.05) and the use of IABP (p=0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p=0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p=0.0042) between the delta platelet count and ischemic events. In this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Decline in platelet count and long-term post-PCI ischemic events: implication of the intra-aortic balloon pump.

PubMed

Schiariti, Michele; Saladini, Patrizia; Cuturello, Domenico; Iannetta, Loredana; Torromeo, Concetta; Puddu, Paolo Emilio

2014-01-01

Thrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations. We studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count ≥25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan-Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p=0.05) and the use of IABP (p=0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p=0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p=0.0042) between the delta platelet count and ischemic events. In this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.

PubMed

Cetica, Valentina; Sieni, Elena; Pende, Daniela; Danesino, Cesare; De Fusco, Carmen; Locatelli, Franco; Micalizzi, Concetta; Putti, Maria Caterina; Biondi, Andrea; Fagioli, Franca; Moretta, Lorenzo; Griffiths, Gillian M; Luzzatto, Lucio; Aricò, Maurizio

2016-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. From our registry, we have analyzed a total of 500 unselected patients with HLH. Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

High prevalence of Anisakis simplex hypersensitivity and allergy in Sicily, Italy.

PubMed

Heffler, Enrico; Sberna, Maria Eva; Sichili, Stefania; Intravaia, Rossella; Nicolosi, Giuliana; Porto, Morena; Liuzzo, Maria Teresa; Picardi, Giuseppe; Fichera, Silvia; Crimi, Nunzio

2016-02-01

Anisakis simplex can elicit allergic reactions when ingested in raw or marinated fish. The prevalence of A simplex hypersensitivity and allergy in Sicily (Italy), an area where the consumption of raw or marinated fish is very common, has not been investigated thus far. To investigate the prevalence of A simplex sensitization and its clinical relevance in a large group of unselected patients. All consecutive patients referred to the authors' allergy clinic during a 22 month-period were included in the study, evaluated for sensitization to A simplex and other allergens depending on their clinical history, and investigated for allergic symptoms after the ingestion of raw or marinated fish. Of 3,419 patients screened, 527 (15.4%) were sensitized to A simplex and 29 of these (5.5% of sensitized patients) had a history of A simplex allergy. Approximately 30% of patients had mono-sensitization to A simplex. Co-sensitization to house dust mites or molds yielded an odds ratio of 1.98 or 3.18, respectively, for allergy to A simplex. A high prevalence of A simplex sensitization in a large proportion of patients with mono-sensitization was found, confirming that eating habits influence sensitization to this nematode. Allergic symptoms from A simplex ingestion in raw or marinated fish were quite frequent, with symptoms ranging from oral allergy syndrome to anaphylaxis. Patients sensitized to A simplex were more prone to have allergic symptoms when they had co-sensitization to house dust mites or molds, suggesting possible cross-reactive but clinically relevant allergens between these allergenic sources. Copyright © 2016. Published by Elsevier Inc.

PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status

PubMed Central

Edqvist, Per-Henrik D.; Hägerstrand, Daniel; Carlson, Joseph; Lysiak, Malgorzata; Henriksson, Roger; Pontén, Fredrik; Rosell, Johan; Söderkvist, Peter; Stupp, Roger; Tchougounova, Elena; Nistér, Monica; Malmström, Annika; Smits, Anja

2016-01-01

PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma. Representing the younger population of glioblastomas, we studied 80 IDH-wildtype glioblastomas from patients aged 18-60 years. There was no correlation between PROX1 protein and survival for patients with primary glioblastomas included in these cohorts. In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas. The prognostic impact of PROX1 in IDH-mutant 1p19q non-codeleted high-grade astrocytomas, as well as the negative findings in primary glioblastomas, was corroborated by gene expression data extracted from the Cancer Genome Atlas. We conclude that PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing low-grade tumors and harbor IDH mutations. PMID:27626492

Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study.

PubMed

Xu, Yan; Schulman, Sam; Dowlatshahi, Dar; Holbrook, Anne M; Simpson, Christopher S; Shepherd, Lois E; Wells, Philip S; Giulivi, Antonio; Gomes, Tara; Mamdani, Muhammad; Khuu, Wayne; Frymire, Eliot; Johnson, Ana P

2017-07-01

Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in < 40% of cases, raising concerns about the generalizability of this finding. Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases. Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Characteristics of compensated hypogonadism in patients with sexual dysfunction.

PubMed

Corona, Giovanni; Maseroli, Elisa; Rastrelli, Giulia; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2014-07-01

In the last few years, a view that subclinical endocrine disorders represent milder forms of the clinically overt disease has emerged. Accordingly, it has been proposed that compensated hypogonadism represents a genuine clinical subset of late-onset hypogonadism. The aim of the present study is to investigate the associations of compensated hypogonadism with particular clinical and psychological characteristics of male subjects complaining of sexual dysfunction. After excluding documented genetic causes of hypogonadism, an unselected consecutive series of 4,173 patients consulting our unit for sexual dysfunction was studied. Compensated hypogonadism was identified according to the European Male Ageing study criteria: total testosterone ≥10.5 nmol/L and luteinizing hormone >9.4 U/L. Several hormonal, biochemical, and instrumental (penile Doppler ultrasound) parameters were studied, along with results of the Structured Interview on Erectile Dysfunction (SIEDY) and ANDROTEST. One hundred seventy (4.1%) subjects had compensated hypogonadism, whereas 827 (19.8%) had overt hypogonadism. After adjustment for confounding factors, no specific sexual symptoms were associated with compensated hypogonadism. However, compensated hypogonadism individuals more often reported psychiatric symptoms, as detected by Middlesex Hospital Questionnaire score, when compared with both eugonadal and overt hypogonadal subjects (adjusted odds ratios = 1.018 [1.005;1.031] and 1.014 [1.001;1.028], respectively; both P < 0.005). In addition, subjects with compensated or overt hypogonadism had an increased predicted risk of cardiovascular events (as assessed by Progetto Cuore risk algorithm) when compared with eugonadal individuals. Accordingly, mortality related to major adverse cardiovascular events (MACEs), but not MACE incidence, was significantly higher in subjects with both compensated and overt hypogonadism when compared with eugonadal subjects. The present data do not support the concept that compensated (subclinical) hypogonadism represents a new clinical entity. The possibility that subclinical hypogonadism could be a normal response of the hypothalamus-pituitary-testis axis to somatic illness should be considered. Further studies are urgently needed to clarify this latter point. © 2014 International Society for Sexual Medicine.

How Long Should Routine EEG Be Recorded to Get Relevant Information?

PubMed

Doudoux, Hannah; Skaare, Kristina; Geay, Thomas; Kahane, Philippe; Bosson, Jean L; Sabourdy, Cécile; Vercueil, Laurent

2017-03-01

The optimal duration of routine EEG (rEEG) has not been determined on a clinical basis. This study aims to determine the time required to obtain relevant information during rEEG with respect to the clinical request. All rEEGs performed over 3 months in unselected patients older than 14 years in an academic hospital were analyzed retrospectively. The latency required to obtain relevant information was determined for each rEEG by 2 independent readers blinded to the clinical data. EEG final diagnoses and latencies were analyzed with respect to the main clinical requests: subacute cognitive impairment, spells, transient focal neurologic manifestation or patients referred by epileptologists. From 430 rEEGs performed in the targeted period, 364 were analyzed: 92% of the pathological rEEGs were provided within the first 10 minutes of recording. Slowing background activity was diagnosed from the beginning, whereas interictal epileptiform discharges were recorded over time. Moreover, the time elapsed to demonstrate a pattern differed significantly in the clinical groups: in patients with subacute cognitive impairment, EEG abnormalities appeared within the first 10 minutes, whereas in the other groups, data could be provided over time. Patients with subacute cognitive impairment differed from those in the other groups significantly in the elapsed time required to obtain relevant information during rEEG, suggesting that 10-minute EEG recordings could be sufficient, arguing in favor of individualized rEEG. However, this conclusion does not apply to intensive care unit patients.

Variability of Sorafenib Toxicity and Exposure over Time: A Pharmacokinetic/Pharmacodynamic Analysis

PubMed Central

Ropert, Stanislas; Mir, Olivier; Coriat, Romain; Billemont, Bertrand; Tod, Michel; Cabanes, Laure; Franck, Nathalie; Blanchet, Benoit; Goldwasser, François

2012-01-01

Background. Sorafenib displays major interpatient pharmacokinetic variability. It is unknown whether the pharmacokinetics of sorafenib influence its toxicity. Methods. We analyzed the severity and kinetics of sorafenib-induced toxicities in unselected consecutive patients with cancer, as well as their relationship with biological, clinical, and pharmacokinetic parameters. Toxicity was recorded bimonthly. Sorafenib plasma concentrations were assessed by liquid chromatography. Results. For 83 patients (median age, 62 years; range, 21–84 years), median sorafenib 12-hour area under the curve (AUC0–12) was 52.8 mg · h/L (range: 11.8–199.6). A total of 51 patients (61%) experienced grade 3–4 toxicities, including hand-foot skin reactions (23%), asthenia (18%), and diarrhea (11%). Sorafenib AUC0–12 preceding grade 3–4 toxicities was significantly higher than that observed in the remaining population (61.9 mg · h/L vs. 53 mg · h/L). In 25 patients treated with fixed doses of sorafenib for the first 4 months, median dose-normalized AUC0–12 on day 120 was significantly lower than on day 15 (63 vs. 102 mg · h/L). The incidence of hypertension and hand-foot skin reactions significantly decreased over time. Conclusion. Sorafenib AUC0–12 decreases over time, similarly to the incidence of hypertension and hand-foot skin reactions. Monitoring of sorafenib plasma concentrations may help to prevent acute severe toxicities and detect patients with suboptimal exposure at disease progression. PMID:22752067

Significance of off-hours in centralized primary percutaneous coronary intervention network.

PubMed

Becker, David; Soos, Pal; Berta, Balazs; Nagy, Andrea; Fulop, Gabor; Szabo, Gyorgy; Barczi, Gyorgy; Belicza, Eva; Martai, Istvan; Merkely, Béla

2009-10-01

To analyze the efficacy of a regionally organized primary percutaneous coronary intervention (PCI) network at the Heart Center, Semmelweis University Budapest, part of the "Budapest model," and the factors that influence it. In order to investigate the differences between regular and off-hours patient care in a 24-hour myocardial infarction primary care system, we included 1890 consecutive, unselected patients with ST-segment elevation myocardial infarction and followed them until at least one year. The follow-up was complete for all participants. The difference between regular hours and off-hours mortality was not significant either after 30 days (8.6% vs 8.8%, respectively) or after 1 year (15.3% vs 14.7%, respectively). The rate of patients with re-infarction, frequency of re-intervention, and major adverse cardiac events, including death, re-infarction, re-intervention, and coronary artery bypass graft surgery, were similar in both patient groups. The time delay between the onset of chest pain and arrival to the clinic was 5.9+/-5.8 hours (mean+/- standard deviation) during regular hours and 5.2+/-4.6 hours during off-hours (P=0.235). Direct transport caused significant decrease in the 30-day and 1-year mortality independent of duty time (7.2% vs 9.9%, P=0.027; 12.6% vs 16.7%, P=0.028; respectively). Centralized primary PCI network of the "Budapest model" achieved the same level of patient care during both off-hours and regular hours.

Suspected acute coronary syndrome in the emergency room: Limited added value of heart type fatty acid binding protein point of care or ELISA tests: The FAME-ER (Fatty Acid binding protein in Myocardial infarction Evaluation in the Emergency Room) study.

PubMed

Bank, Ingrid Em; Dekker, Marieke S; Hoes, Arno W; Zuithoff, Nicolaas Pa; Verheggen, Peter Whm; de Vrey, Evelyn A; Wildbergh, Thierry X; Timmers, Leo; de Kleijn, Dominique Pv; Glatz, Jan Fc; Mosterd, Arend

2016-08-01

Timely recognition of acute coronary syndrome remains a challenge as many biomarkers, including troponin, remain negative in the first hours following the onset of chest pain. We assessed the diagnostic accuracy of heart-type fatty acid binding protein (H-FABP), a cardiac biomarker with potential value immediately post symptom onset. Prospective monocentre diagnostic accuracy study of H-FABP bedside point of care (CardioDetect®) and ELISA tests in acute coronary syndrome suspected patients presenting within 24 hours of symptom onset to the emergency department, in addition to clinical findings, electrocardiography and the currently recommended biomarker high sensitivity troponin-T (hs-cTnT). The final diagnosis of acute coronary syndrome was adjudicated by two independent cardiologists, blinded to H-FABP results. Acute coronary syndrome was diagnosed in 149 (32.9%) of 453 unselected patients with suspected acute coronary syndrome (56% men, mean age 62.6 years). Negative predictive values were similar for H-FABP point of care and ELISA tests (79% vs. 78% respectively), but inferior to initial hs-cTnT (negative predictive value 86%). The addition of H-FABP point of care results to hs-cTnT increased the negative predictive value to 89%. In a multivariable logistic regression model, H-FABP point of care and ELISA tests yielded relevant diagnostic information in addition to clinical findings and ECG (likelihood ratio test p<0.001) and increased area under the receiver operating characteristics curve (AUC; 0.82 vs. 0.84 and 0.84). This added value attenuated, however, after inclusion of hs-cTnT in the diagnostic model (AUC 0.88). In patients suspected of acute coronary syndrome presenting to the emergency department, H-FABP testing improves diagnostic accuracy in addition to clinical findings and electrocardiography. H-FABP, however, has no additional diagnostic value when hs-cTnT measurements are also available. © The European Society of Cardiology 2015.

Individualization of radiotherapy in breast cancer patients: possible usefulness of a DNA damage assay to measure normal cell radiosensitivity.

PubMed

Ruiz de Almodóvar, José Mariano; Guirado, Damian; Isabel Núñez, María; López, Escarlata; Guerrero, Rosario; Valenzuela, María Teresa; Villalobos, Mercedes; del Moral, Rosario

2002-03-01

The purpose of this study was to determine whether the distribution of sensitivities in breast cancer patients, measured using a DNA damage assay on lymphocytes, is likely to provide sufficient discrimination to enable the reliable identification of patients with abnormal sensitivities. Radiosensitivity (x) was assessed in 226 samples of lymphocytes from unselected women with breast cancer and was quantified as the initial number of DNA double-strand breaks (dsb) induced per Gy and per DNA unit (200 Mbp). The existence of an inter-individual variation in the parameter (x) is described through the range (0.40-4.72 dsb/Gy/DNA unit) of values found, which have been fitted to the mathematical model defined by the log-normal distribution (mu = 0.42+/-0.03; sigma = 0.52+/-0.03; R(2)=0.9475). A total of 189 patients received radiotherapy after surgical treatment. Among them, we have detected 15 patients who developed severe skin reactions and we have compared their radiosensitivity values with the rest of patients treated. Our results suggest that DNA initial damage measured on lymphocytes offers an approach to predict the acute response of human normal tissues prior to radiotherapy. Values of x higher than 3.20 dsb/Gy/DNA unit theoretically should correspond to the highly radio-sensitive patients. Using the experimental results, we have calculated the strength of the test by means of the area under the receiver operator characteristic curves (A(Z)) to determine whether the radiosensitivity assay can discriminate between patients according to their radiation response. The value found (A(Z)=0.675+/-0.072) is indicative of a fair-poor discriminating capacity of the test to identify the patients with higher risk of developing a severe acute reaction during the radiotherapy treatment.

Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer.

PubMed

Martín, Miguel; González-Rivera, Milagros; Morales, Serafín; de la Haba-Rodriguez, Juan; González-Cortijo, Lucía; Manso, Luis; Albanell, Joan; González-Martín, Antonio; González, Sónia; Arcusa, Angels; de la Cruz-Merino, Luis; Rojo, Federico; Vidal, María; Galván, Patricia; Aguirre, Elena; Morales, Cristina; Ferree, Sean; Pompilio, Kristen; Casas, Maribel; Caballero, Rosalía; Goicoechea, Uxue; Carrasco, Eva; Michalopoulos, Steven; Hornberger, John; Prat, Aleix

2015-06-01

Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status. Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p < 0.05). Though this study does not include evaluation of the impact of GEP on long-term outcomes, it was found that GEP results influenced the treatment decisions of medical oncologists and their confidence in adjuvant therapy selection. Patients' anxiety about the selected adjuvant therapy decreased with use of the GEP.

Classification of non-demented patients attending a memory clinic using the new diagnostic criteria for Alzheimer's disease with disease-related biomarkers.

PubMed

Ivanoiu, Adrian; Dricot, Laurence; Gilis, Nathalie; Grandin, Cécile; Lhommel, Renaud; Quenon, Lisa; Hanseeuw, Bernard

2015-01-01

New diagnostic criteria for predemential Alzheimer's disease (AD) advocate the use of biomarkers. However, the benefit of using biomarkers has not been clearly demonstrated in clinical practice. To investigate whether a combination of biomarkers may be helpful in classifying a population of non-demented patients attending a Memory Clinic. Sixty non-demented patients were compared with 31 healthy elderly subjects. All subjects underwent a neuropsychological examination, brain 3T magnetic resonance imaging, [F18]-fluorodeoxyglucose and [F18]-flutemetamol positron emission tomography. According to their performance on memory, language, executive, and visuo-spatial domains, the patients were classified as mild cognitive impairment (amnestic, non-amnestic, single, or multiple domain) or subjective cognitive impairment. Patients were then classified according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, using the normalized mean hippocampal volume (Freesurfer), [F18]-FDG PALZAD, and [F18]-flutemetamol standard uptake value ratio (SUVr) (cut-off at the 10th percentile of controls). The standard of truth was the clinical status at study entry (patient versus control). The sensitivity/specificity of the clinical classification was 65/84%. The NIA-AA criteria were applicable in 85% of patients and 87% of controls. For biomarkers the best sensitivity (72%) at a fixed specificity of 84% was achieved by a combination of the three biomarkers. The clinical diagnosis was reconsidered in more than one third of the patients (42%) as a result of including the biomarker results. Application of the new NIA-AA AD diagnostic criteria based on biomarkers in an unselected sample of non-demented patients attending a Memory Clinic was useful in allowing for a better classification of the subjects.

Impact of exclusion criteria for the DASISION and ENESTnd trials in the front-line treatment of a 'real-life' patient population with chronic myeloid leukaemia.

PubMed

Latagliata, Roberto; Carmosino, Ida; Vozella, Federico; Volpicelli, Paola; De Angelis, Federico; Loglisci, Maria Giovanna; Salaroli, Adriano; De Luca, Maria Lucia; Montagna, Chiara; Serrao, Alessandra; Molica, Matteo; Diverio, Daniela; Nanni, Mauro; Mancini, Marco; Breccia, Massimo; Alimena, Giuliana

2017-06-01

Both Dasision and ENESTnd trials had many exclusion criteria, with a possible selection bias compared with the real-life. To address the impact of this bias on the first-line treatment in the current clinical practice, we revised 207 unselected newly diagnosed chronic phase chronic myeloid leukaemia (CML) patients [M/F 108/99, median age 58.8 years, interquartile range 42.3-70.2] treated with front-line imatinib from June 2002 to June 2013 at our Institution, and evaluated how many of them would have been excluded from enrolment in the two trials. Twenty-eight patients (13.5%) should have been excluded by both trials because of polycomorbidities (12), severe cardiomyopathy (five), age > 80 with frailty (three), drug abuse (two) or other severe concomitant diseases (six). In addition, eight patients should have been excluded by Dasision due to isolated chronic obstructive broncopulmonar disease, and 19 patients should have been excluded by ENESTnd due to isolated diabetes (10), arrhythmia (four), acute myocardial infarction > 6 months before CML diagnosis (two), chronic pancreatic disease (two) and peripheral arterial obstructive disease (one). On the whole, 36 patients (17.4%) would have been excluded by Dasision trial and 47 (22.7%) by ENESTnd trial. The patients potentially not eligible for both trials were significantly older and with imatinib had a worse outcome compared with patients potentially eligible. Our data highlight that an automatic transposition of results available in clinical controlled trials into the frontline real-life management of CML patients should be regarded with caution. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Serological markers are associated with disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years.

PubMed

Høie, Ole; Aamodt, Geir; Vermeire, Severine; Bernklev, Tomm; Odes, Selwyn; Wolters, Frank L; Riis, Lene; Politi, Patrizia; Tsianos, Epameinondas V; Butrón, Mercedes; Stockbrügger, Reinhold W; Munkholm, Pia; Vatn, Morten; Moum, Bjørn

2008-06-01

Perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) have been proposed as markers for diagnosis and for subtyping of inflammatory bowel disease (IBD). The aim of this study was to investigate the association of p-ANCA and ASCA with a 10-year disease outcome in terms of cumulative rate of colectomy and relapse in a population-based European inception cohort of ulcerative colitis (UC) patients. Serum samples from 432 consenting patients were analysed for p-ANCA and ASCA. The results were compared with the cumulative colectomy rate, relapsing disease and total number of relapses. We used multiple regression analyses adjusted for age, sex, residence, disease extent at diagnosis, smoking, familial IBD and drug treatment to study the relationship between serological values and disease course. The relapse rate was higher in the p-ANCA-positive patients: 82% (95% confidence interval [CI] 75-89%) compared with 67% (CI 62-72%, p=0.011) in the p-ANCA-negative patients. The risk of relapsing disease course was higher by a factor of 1.4 (CI 1.1-1.8, p=0.009) for p-ANCA-positive patients than for p-ANCA-negative patients, and the corresponding relative risk (RR) for the total number of relapses was 1.9 (CI 1.7-2.1, p<0.001). In ASCA-positive patients RR for the total number of relapses was 1.8 (CI 1.5-2.1, p<0.001). No significant association with colectomy rate was found for the presence of either p-ANCA or ASCA. UC patients positive for p-ANCA and possibly for ASCA may have a more unfavourable long-term disease outcome in terms of relapse than UC patients without these markers.