tbuckley/cabot-search huggingface dataset:
Abstract 11803: Factors Associated With Delayed Diagnosis of Critical Congenital Heart Defects in Texas
Authors: Unnati Doshi, Syed S Hashmi, Lisa Marengo, Surabhi Kaul, Mousumi Moulik
Journal: Circulation (2014)

Purpose: Critical congenital heart defects (CCHD) require surgical and/or transcatheter intervention in infancy. They may or may not have ductal dependent circulation. Timely diagnosis before ductal closure is important to reduce morbidity and mortality. Our goal was to identify factors associated with delayed diagnosis of CCHD. Methods: This is a retrospective, population-based, observational study of liveborn infants in Texas born from 2000 - 2009 identified using the Texas Birth Defects Registry (TBDR). Inclusion required a definitive diagnosis of one of 13 selected CCHDs identified by diagnostic code and information on one of three “diagnostic” procedures: prenatal or postnatal echocardiogram or autopsy. Cases with aortic or pulmonary stenosis, coarctation of aorta, tricuspid stenosis or Ebsteins anomaly were included only if they underwent a cardiac surgical or catheterization procedure within 6 weeks of life. Stillborn infants or that died within three days of life (DOL) without evidence of an echocardiogram procedure were excluded. Date of diagnosis was defined as date of first echocardiogram. “Delayed diagnosis” was defined as any date of diagnosis after DOL3. Eligible infants with autopsy as the only “diagnostic” procedure were also classified as “delayed diagnosis”. Logistic regression models were created to identify factors that influence diagnosis delay. Results: A total of 5895 CCHD cases were identified. Diagnosis was delayed in 25% of cases. The CCHDs with highest rates of delayed diagnosis were critical coarctation (34%) and TAPVR (32%). In multivariate analysis, delayed diagnosis was more likely to be associated with single CCHD [adjusted odds ratio (aOR) 1.9; 95% CI 1.5-2.4], low maternal education [aOR1.7; 95% CI 1.2-2.3], prematurity &lt;32wks [aOR 1.6; 95% CI 1.21-2.26], and rural maternal residence [aOR 1.5; 95% CI 1.22-1.94]. Presence of noncardiac defects decreased delayed diagnosis only for a few CCHD phenotypes. Conclusions: A quarter of all births with CCHD have a delayed diagnosis in Texas. Maternal education and residence are associated with the delay. Future studies will have to investigate each CCHD phenotype for specific risk factors.
Messages for Clinicians: Moderators and Mediators of Treatment Outcome in Randomized Clinical Trials
Authors: Helena Chmura Kraemer
Journal: American Journal of Psychiatry (2016)

Many problems in randomized clinical trial design, execution, analysis, presentation and interpretation stem in part from an inadequate understanding of the roles of moderators and mediators of treatment outcome. As a result, 1) the results of clinical research are slow to have an impact on clinical decision making and thus to benefit patients; 2) it is difficult for clinicians or patients to apply randomized clinical trial results comparing two treatments (treatment versus control); 3) when such trials are conducted at various sites, the results often do not replicate; 4) when the results influence clinical decision making, the results clinicians obtain do not match what researchers report; and 5) the treatment effects comparing treatment and control conditions, particularly for psychiatric treatments, often seem trivial. In this review article, the author reviews and integrates the methodological literature concerning dealing with covariates in trials to emphasize their impact on clinical decision making. The goal of trials should ultimately be to establish who should get the treatment condition rather than the control condition (moderators) and to determine how to obtain the best outcomes with whatever is the preferred treatment (mediators). The author makes recommendations to clinicians as to which trials might best be ignored and which carefully considered, and urges clinical researchers to focus on studies best designed to reduce the burden of mental illness on patients.
Rape and rape-murder: one offender and twelve victims
Authors: R K Ressler, A W Burgess, J E Douglas
Journal: American Journal of Psychiatry (1983)

This study analyzes data pertaining to 12 rapes and rape-murders committed by one male adolescent offender over a 4-year period. All offenses except the first were committed while the offender was under psychiatric and probationary supervision. The use or relinquishment of violence by the offender was found to be dependent on subtle interpersonal factors. The authors stress the importance of the use of crime scene data and interviews of patients who have committed sex crimes, the role of psychological profiles in apprehension of suspects, and the contribution of law enforcement as a data resource.
Dependence on Barbiturates and Other Sedative Drugs
Authors: I ALTMAN, H H KROEGER, D A CLARK, A C JOHNSON, C G SHEPS
Journal: JAMA (1965)

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Reduction therapy of ALT levels and prevention of HCC development in patients with HCV-associated cirrhosis
Authors: Y. Rino, N. Yukawa, T. Yamada, T. Imada, S. Morinaga, S. Ohkawa, K. Miyakawa, M. Ueno, K. Tarao
Journal: Journal of Clinical Oncology (2007)

1529 Background: Approximately 30 million people worldwide are estimated to have liver cirrhosis (LC) associated with hepatitis C virus (HCV). In addition, patients with HCV-associated liver cirrhosis (HCV-LC) have a high risk of developing hepatocellular carcinoma (HCC). Namely, 60–80% of the patients may develop HCC in 10 years. So, preventing these patients from developing HCC is an urgent problem to be solved. To find a way to prevent the development of hepatocellular carcinoma (HCC) from hepatitis C-virus associated liver cirrhosis (HCV-LC), an analysis of the HCV-LC patients who had reduction therapy of ALT levels was performed. Patients and Methods: Seventy-four consecutive HCV-LC patients of Child Stage A were followed for &gt; 10 years for the development of HCC. They were divided into two groups: In group A, the reduction therapy for ALT levels is aggressively performed and in group B, the reduction therapy was not performed aggressively. Results: Initial ALT was higher in group A than in group B, but there was no significance. After reduction therapy, ALT level was significantly high in group A in the first year. However, there were no significant differences between ALT levels in groups A and B of after the second year. In total, 39 patients out of 74 (52.7%) developed HCC within 13 years from the beginning of the study and 35 patients did not developed HCC in the same observation period. The incidence of HCC development in group B [65.7% (23/35)] was significantly higher than in group A [41.0% (16/39)] (p=0.039). The median HCC developing time in group A (12.8 years) was significantly longer than in group B (3.8 years) (p=0.0013). Multivariate analysis demonstrated that reduction therapy and ALT levels were the significant factors affecting HCC development. The incidence of HCC development in group B was 5.8 times higher than in group A. The high and unclassified ALT groups were 4.6 times and 2.2 times higher than in the low ALT group. Conclusion: The chances of surviving for more than 10 years without developing HCC in the HCV-LC patients of Child Stage A were far more favorable in group A than in group B. These results suggest that aggressive reduction therapy for ALT levels in HCV-LC patients could significantly prevent HCC development. No significant financial relationships to disclose.
Idiopathic multicentric Castleman's disease: a systematic literature review
Authors: Amy Y Liu, Christopher S Nabel, Brian S Finkelman, Jason R Ruth, Razelle Kurzrock, Frits van Rhee, Vera P Krymskaya, Dermot Kelleher, Arthur H Rubenstein, David C Fajgenbaum
Journal: The Lancet Haematology (2016)
Cetuximab, docetaxel, and cisplatin (TPEx) as first-line treatment in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Final results of phase II trial GORTEC 2008-03.
Authors: Joel Guigay, Jerome Fayette, Anne-Francoise Dillies, Christian Sire, Joseph N. Kerger, Isabelle Tennevet, Jean-Pascal H. Machiels, Sylvie Zanetta, Yoann Pointreau, Laurence Bozec Le Moal, Lydia Brugel Ribere, Stefanie Henry, Stéphane Temam
Journal: Journal of Clinical Oncology (2012)

5505 Background: Cetuximab in combination with platinum and 5FU (PFEx) has become a standard in first-line treatment of patients (pts) with R/M SCCHN. Cetuximab and taxane combinations have shown promising activity. This multicenter phase II study evaluates the efficacy and safety of cetuximab, docetaxel and cisplatin combination (TPEx) as first-line treatment in pts with R/M SCCHN. Methods: Pts were required to have WHO PS 0-1, no prior systemic therapy for R/M SCCHN, cumulative dose of cisplatin less than 300 mg/m² and no prior anti-EGFR therapy. Pts received docetaxel 75 mg/m² day 1, cisplatin 75 mg/m² day 1 and cetuximab (400 mg/m² on day 1 of cycle 1 then 250 mg/m² weekly), repeated every 21 days x 4 cycles then followed by cetuximab 500 mg/m² every 2 weeks (wks) as maintenance therapy until disease progression or unacceptable toxicity. G-CSF support with lenograstim 150 µg/m²/day was delivered after each cycle of chemotherapy. Response was assessed every 6 wks, according to RECIST. The primary endpoint was objective response rate (ORR) at 12 wks. Secondary endpoints were safety, best overall response, progression-free survival (PFS), overall survival (OS) and biomarkers. Results: 54 pts have been enrolled: 52 males, median age 57.8years (28-69), 12 (22.2%) oropharynx, 55% metastatic.48 pts could be evaluated for ORR at 12 wks: partial response, stable disease and progression were respectively found in 23 pts (PR 47.9%), 21 pts (SD 43.7%) and 4 pts (PD 8.3%). Best overall ORR was 54% (1 CR, 27 PR). The median PFS and OS were 7.1 and 15.3 months, respectively. The 1-year OS was 58.6%. Median PFS after start of maintenance therapy was 4.2 months. Toxicity was manageable with G-CSF support. Treatment related toxicities included G4 neutropenia (n=3). Grade 3 events were skin rash (n=5), hypersensitivity reaction (n=3), mucositis (n=1), fatigue (n=1) and febrile neutropenia (n=1). Alopecia was common. 1 toxic death was related to sepsis on feeding tube. Conclusions: Efficacy analysis demonstrates that TPEx regimen is effective and might be a relevant substitute for PFEx as first-line treatment in fit pts with R/M SCCHN.
Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia
Authors: Joseph A. Fraietta, Kyle A. Beckwith, Prachi R. Patel, Marco Ruella, Zhaohui Zheng, David M. Barrett, Simon F. Lacey, Jan Joseph Melenhorst, Shannon E. McGettigan, Danielle R. Cook, Changfeng Zhang, Jun Xu, Priscilla Do, Jessica Hulitt, Sagar B. Kudchodkar, Alexandria P. Cogdill, Saar Gill, David L. Porter, Jennifer A. Woyach, Meixiao Long, Amy J. Johnson, Kami Maddocks, Natarajan Muthusamy, Bruce L. Levine, Carl H. June, John C. Byrd, Marcela V. Maus
Journal: Blood (2016)
The Burden of Hypertension and Associated Risk for Cardiovascular Mortality in China
Authors: Sarah Lewington, Ben Lacey, Robert Clarke, Yu Guo, Xiang Ling Kong, Ling Yang, Yiping Chen, Zheng Bian, Junshi Chen, Jinhuai Meng, Youping Xiong, Tianyou He, Zengchang Pang, Shuo Zhang, Rory Collins, Richard Peto, Liming Li, Zhengming Chen
Journal: JAMA Internal Medicine (2016)

Hypertension is a leading cause of premature death in China, but limited evidence is available on the prevalence and management of hypertension and its effect on mortality from cardiovascular disease (CVD).To examine the prevalence, diagnosis, treatment, and control of hypertension and to assess the CVD mortality attributable to hypertension in China.This prospective cohort study (China Kadoorie Biobank Study) recruited 500 223 adults, aged 35 to 74 years, from the general population in China. Blood pressure (BP) measurements were recorded as part of the baseline survey from June 25, 2004, to August 5, 2009, and 7028 deaths due to CVD were recorded before January 1, 2014 (mean duration of follow-up: 7.2 years). Data were analyzed from June 9, 2014, to July 17, 2015.Prevalence and diagnosis of hypertension (systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or receiving treatment for hypertension) and treatment and control rates overall and in various population subgroups.Cox regression analysis yielded age- and sex-specific rate ratios for deaths due to CVD comparing participants with and without uncontrolled hypertension, which were used to estimate the number of CVD deaths attributable to hypertension.The cohort included 205 167 men (41.0%) and 295 056 women (59.0%) with a mean (SD) age of 52 (10) years for both sexes. Overall, 32.5% of participants had hypertension; the prevalence increased with age (from 12.6% at 35-39 years of age to 58.4% at 70-74 years of age) and varied substantially by region (range, 22.7%-40.7%). Of those with hypertension, 30.5% had received a diagnosis from a physician; of those with a diagnosis of hypertension, 46.4% were being treated; and of those treated, 29.6% had their hypertension controlled (ie, systolic BP <140 mm Hg; diastolic BP <90 mm Hg), resulting in an overall control rate of 4.2%. Even among patients with hypertension and prior CVD, only 13.0% had their hypertension controlled. Uncontrolled hypertension was associated with relative risks for CVD mortality of 4.1 (95% CI, 3.7-4.6), 2.6 (95% CI, 2.4-2.9) and 1.9 (95% CI, 1.8-2.0) at ages 35 to 59, 60 to 69, and 70 to 79 years, respectively, and accounted for about one-third of deaths due to CVD (approximately 750 000) at 35 to 79 years of age in 2010.About one-third of Chinese adults in this national cohort population had hypertension. The levels of diagnosis, treatment, and control were much lower than in Western populations, and were associated with significant excess mortality.
Use of anti-neuropilin 1, 2 antibodies to predict colorectal cancer prognosis
Authors: A. Takeda
Journal: Journal of Clinical Oncology (2009)

e15111 Background: Neuropilin (NRP) was initially described as non-tyrosine kinase receptors for neuron guidance factor belonging to the Semaphorin family. Two subtypes, NRP-1 and NRP-2 have been isolated. Neuropilins are widely expressed not only normal developing tissues but also several types of tumor cells. It was reported that the expression of NRP-1 is increased by VEGF, mediated through VEGFR-2, which correlates with tumor growth and invasiveness in colorectal cancer. NRP-2 knockout mice studies showed marked deficits in the development of small lymphatic vessels and its function was associated with the formation of lymphatic network, but the role of NRP-2 in colorectal cancer remains unknown. Methods: We have newly established two useful anti- Neuropilin antibodies against CUB domains of NRP-1 and cytoplasmic domains of NRP-2. In recent study, we have analyzed the expression of NRP-1 and NRP-2 in some cultured cell lines by western blot and the clinicopathological significance in colorectal cancer. Tissues samples were obtained from 72 primary colorectal adenocarcinomas (colon:39 cases, rectum:33 cases). The pathologic stage were as follows; stageI:10 patients, II:25 patients, III:26 patients and IV:11 patients. NRP-1 and NRP-2 gene expression was evaluated by RT- PCR, which was compared with immunohistochemical examination of colorectal cancer tissues. Constitutive expression of NRP-1 was detected in PC3, HT29, PC9 and PC13 cell lines and NRP-2 in HT29, PC3 and PC9. Results: There was significant correlation between NRP-1 and -2 protein expression and both of mRNA expression. The expression of NRP-1 showed apparent correlation with liver metastasis (p=0.027) and venous invasion (p=0.0025), while NRP-2 expression was correlated with lymph node metastasis (0.001) and lymphatic invasion (0.039) by immunohistochemical analysis. The post-surgical treatment observation revealed that patients with co- expression of NRP-1 and NRP-2 were significantly correlated with poorer prognosis than both NRP-1 and NRP-2 negative patients (p=0.035). Conclusions: These results suggest that NRP-1 acts as angiogenesis factor and NRP-2 acts lymphangiogenesis factor, both of them are useful predictive marker in colorectal cancer. No significant financial relationships to disclose.
Overexpression of cell cycle inhibitors (p16INK4 and p21Cip1) and cyclin D1 using adenovirus vectors regulates proliferation of rat mesangial cells.
Authors: Y Terada, T Yamada, O Nakashima, M Tamamori, H Ito, S Sasaki, F Marumo
Journal: Journal of the American Society of Nephrology (1997)

To elucidate the mechanisms of the cell cycle of mesangial cells, adenovirus vectors containing coding sequences of cyclin D1 (AxCAD1), p16INK4 (AxCAp16) and p21Cip1 (AxCAp21) were produced and investigated to determine whether transfer of these genes changes serum- and PDGF-induced proliferation of rat mesangial cells. Efficiency of the transfer of the genes was examined by Northern and Western blot analyses. The cell cycle of mesangial cells was evaluated by measurement of [3H]-thymidine incorporation, flow cytometry, and cyclin-dependent kinase 4 kinase assay. Expression of cyclin D1, p16INK4 and p21Cip1 was observed from 24 h after the infection, and the expression increased up to 48 h. AxCAp16 and AxCAp21 caused a significant inhibition in the [3H]-thymidine incorporation to 47% and 76%, respectively. AxCAp16 and AxCAp21 also inhibited the mitogen-induced increase in cyclin-dependent kinase 4 kinase activity and reduced the percentage of cells in S phase. Coinfection of AxCAp16 with AxCAp21 showed no additive inhibition. Overexpression of cyclin D1 reduced cell size and increased the percentage of the cells in S and G2 phase. These findings suggest that p16INK4 and p21Cip1 function as inhibitors of the proliferation of mesangial cells induced by growth-promoting factors and that deregulated expression of cyclin D1 causes cell cycle disturbances. Adenovirus-mediated gene transfer of p16INK4 and p21Cip1 serves as a potential therapeutic approach to mesangial proliferative diseases.
Pharmacogenetic approach for capecitabine or 5-fluorouracil (5FU) selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer
Authors: E. Martinez-Balibrea, A. Abad, E. Aranda, J. Sastre, J. L. Manzano, J. Aparicio, T. García, I. Maestu, A. Martinez- Cardus, A. Ginés, E. Guinó
Journal: Journal of Clinical Oncology (2008)

4132 Background: The possible replacement of continuous infusion 5FU by the oral pro-drug capecitabine is controversial. The aim of this work was to study genetic polymorphisms and their role in tailoring fluroropyrimidine/oxaliplatin treatment in metastatic colorectal cancer (mCRC). Methods: A total of 110 patients participating in the clinical phase III trial done by the Spanish TTD group comparing the efficacy and safety of capecitabine plus oxaliplatin (XELOX) versus Spanish-based continuous-infusion high-dose 5FU plus oxaliplatin (FUOX) regimens as first-line therapy for mCRC, were selected prospectively for TS (5’VNTR, 5’SNP and 3’UTR), XRCC1–399, XPD-751, ERCC1–118 and XRCC3–241 genotyping. Genotypes were analyzed as codominant, dominant and recessive models. Contingency tables, Chi-square and Fisher’s exact test were used to evaluate the association of polymorphisms with categorical variables. The association of genetic variants and clinical parameters with progression free survival (PFS) was estimated by calculating HR and their 95% CI from univariate and multivariate Cox proportional hazards regression models. The differences were considered statistically significant when two- sided p-values were less than 0.05. Results: In the FUOX group, TS-3’UTR +6bp/+6bp and ERCC1–118 C/T or C/C genotypes correlated with a shorter PFS (HR = 2.62, 95% CI (1.3 - 5.3) p = 0.007 and, HR =1.96, 95% CI (0.99 - 3.92) p = 0.050). When analyzed jointly, the higher the number of favorable genotypes (FG) the longer the PFS (6.8 m for 0 FG (group 3), 9.6 m for 1 FG (group 2) and 25.8 m for 2 FG (group 1); p = 0.005, group 2 HR = 2.57, 95% CI 0.94–7; group 3 HR = 5.63, 95% CI 1.92–16.53). Disease-control rate was higher in group 1 (100% vs. 87% group 2 and 38.5% group 3; p = 0.001). In the multivariate analysis, ERCC1–118 C/T or C/C (p = 0.0037) and TS-3’UTR +6bp/+6bp (p = 0.006) were strong independent prognostic factors. No differences were found in the XELOX group in which median PFS for the equivalent group 3 was 10.2 months. Conclusions: According to this, mCRC patients harboring TS- 3’UTR +6bp/+6bp and ERCC1–118 C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first line treatment. No significant financial relationships to disclose.