tbuckley/cabot-search huggingface dataset:
How to read a funnel plot in a meta-analysis
Authors: Philip Sedgwick, Louise Marston
Journal: BMJ (2015)

Researchers undertook a meta-analysis of the effects of home blood pressure monitoring on blood pressure levels. Randomised controlled trials were included if home or “self” monitoring was compared with standard monitoring in the healthcare system. Participants were patients with essential hypertension, followed for two to 36 months. The main outcomes included measurements of systolic and diastolic blood pressure and the achievement of hypertension targets.1 Eighteen trials were eligible for inclusion. When the results of the trials were combined, home monitoring resulted in significantly lower systolic blood pressure than standard monitoring (mean difference 4.2 mm Hg, 95% confidence interval 1.5 to 6.9) and significantly lower diastolic blood pressure (2.4 mm Hg, 1.2 to 3.5). Home monitoring patients were more likely to achieve predetermined targets (relative risk 1.11, 1.00 to 1.11). The researchers presented funnel plots for the outcomes of systolic and diastolic blood pressure (figure⇓). Egger’s test gave P=0.038 for systolic blood pressure and P=0.095 for diastolic blood pressure. Funnel plots for the meta-analysis of the effects on blood pressure of home monitoring compared with standard monitoring in the healthcare system It was concluded that home monitoring results in lower blood pressure than standard monitoring. Although the difference in blood pressure between the two methods was small it may contribute to an important reduction in vascular complications in the hypertensive population. Which of the following statements, if any, are true?
Brainstem evoked response abnormalities in late-life depression with vascular disease
Authors: B Kalayam, G S Alexopoulos, F E Musiek, T Kakuma, A Toro, D Silbersweig, R C Young
Journal: American Journal of Psychiatry (1997)

The purpose of this study was to examine whether the brainstem evoked responses of geriatric depressed patients with vascular disease show greater changes in wave V latency after increased stimulation than do responses of geriatric depressed patients without vascular disease and elderly comparison subjects with and without vascular disease.Geriatric patients with unipolar depression (N = 53) were recruited from a university psychiatric hospital. Elderly comparison subjects (N = 23) were recruited through advertisements. All subjects were assessed for depressive symptoms, cognitive performance, overall medical burden, vascular disease, and disability. Brainstem evoked response was elicited at stimulation rates of 11.4 and 80.0 clicks/sec.The interaction between depression and vascular disease had a significant effect on change in wave V latency. This effect was synergistic, more than an additive effect. Post hoc comparisons showed that the depressed patients with vascular disease had greater changes in wave V latency that did the depressed patients without vascular disease, comparison subjects with vascular disease, and comparison subjects without vascular disease. Linear discriminant function analysis showed that 82% of the subjects with abnormal changes in wave V latency (sensitivity: 75%, specificity: 81%) could be identified on the basis of ratings for depression and vascular disease.Demyelination afflicting the pons and mesencephalon may explain the greater change in wave V latency for the brainstem evoked response in depressed patients with vascular disease. Further studies combining brainstem evoked response with brain imaging may determine whether depression develops only after vascular disease leads to demyelination.
Interim analysis of hepatocellular carcinoma (HCC) screening and survival in 4,087 veterans diagnosed with HCC from 2008 to 2010.
Authors: David Edward Kaplan, Tamar H. Taddei, Ayse Aytaman, Kristel Hunt, Astrid Knott, Eric Dieperink, Michelle Baytarian, Rena Fox, Marcos Pedrosa, Kathryn D'Addeo, Feng Dai, Rajni Mehta, Mona Duggal, Christine Pocha, Melissa Skanderson, Adriana Valderrama
Journal: Journal of Clinical Oncology (2015)

243 Background: The Veterans Health Administration (VHA) is the largest provider of liver disease care in the US. From 2000-2007, there was a 5-fold increase in the incidence of hepatocellular carcinoma (HCC) among Veterans. The aim of the VOCAL group is to study outcomes and cost of Veterans diagnosed with cirrhosis and HCC from 2008-2010. Methods: The VA Corporate Data Warehouse was queried to identify all patients with ICD9 codes for HCC (155.0, 155.2) and cirrhosis (571.2, 571.5, 571.6). Chart abstraction was performed for each HCC patient to determine tumor characteristics, BCLC stage, and eligibility for transplantation. Results: This is an interim analysis of the first 4087 of 7,111 patients with HCC. HCC was confirmed in 3,207/4,087 (78%). Of these 3,207 patients, 778 (24%) were managed outside the VHA and 156 (6%) were diagnosed prior to 2008. Thus, 2,323 patients were analyzed. Median age was 60y (38-91). Males comprised 99% of the cohort; 61% were white, 24% were black, and 0.5% were Asian. Etiologies of cirrhosis were hepatitis C (HCV) (27%), alcohol-related (11%), HCV+alcohol (49%), hepatitis B (HBV) (9%), and other (metabolic, NASH) (2%). 63 (3%) were HIV-infected. Cirrhosis was coded in 83% (1918) prior to HCC diagnosis. Of cirrhotics, 11% (248) were optimally screened and 14% (335) were near-optimally screened; 75% of HCC were diagnosed incidentally or due to symptoms. AJCC stage was I/II/IIIA/IIIB/IIIC/IVA/IVB in 42/23/10/13/1/4/7%, respectively. 963 (41%) of patients were within Milan Criteria. BCLC staging was 0/A/B/C/D in 8/39/27/13/13%, respectively. Median OS was 400d and 1214/857/404/163/107d in BCLC 0/A/B/C/D, respectively. In multivariate survival model, age, the presence of ascites, serum albumin, serum bilirubin, serum sodium, CirCom score, Charlson-Deyo index, number of tumors, largest tumor size, and total tumor size were all statistically significantly predictive of survival. Conclusions: ICD9 codes for HCC have a PPV of ~80% for identifying true HCC cases in the CDW. Approximately 1/4 of patients received screening within AASLD 2010 guidelines. The majority of Veterans diagnosed with HCC present with intermediate to advanced disease with median survival 4.5-9.2 months.
A metanalysis of the efficacy and safety of pegylated liposomal doxorubicin.
Authors: A. Castellanos-Toledo
Journal: Journal of Clinical Oncology (2010)

e13040 Background: Doxorubicin has an excellent activity profile to use it as a standard component to treat several malignancies with improved survival, mainly in pediatric cancer. Dose intensity seems to be related to outcome; however, its continued use is limited by doxorubicin-induced cardiotoxicity (DIC). One strategy to decrease conventional DIC involves use of pegylated liposomal doxorubicin (PLD). Several clinical studies have appointed that PLD decrease DIC risk with superior antineoplastic (AN) activity; however, its conclusions have widespread differences due to heterogeneity clinical of patients included. This study is intended unify outcomes of these trials. Methods: With a predetermined grade system and the Cochrane Handbook criterions only randomized clinical studies (RCS) were selected. RCS with incomplete outcomes were excluded. The Collaborative Review Group search general strategy was accomplished including MEDLINE, EMBASE, CINAHL, Current Contents, and Cochrane Register of Controlled Trials. Individual and merged statistics were estimated by the fixed effects method and were informed as OR with 95% CI, heterogeneity among equivalent trials was proved by Chi2 and p<0.05. Results: Six individuals RCS made in hospital centers was identified published from Jan 96-Aug 04 (JCO 2001,19:3312-22; AnnOncol 2004,15:440-49; JCO 1998,16:2445-51; EurJCancer 2001,37:870-77; JCO 2004,22:3893-3901; JCO 1998,16: 683-91). 947 patients exposed to PLD (cases) and 928 exposed to others AN drugs including free doxorubicin (controls) were included. Median age was 56 years (25-85). There were not pediatrics RCS. PLD dose was 20-50mg/m2 IV in 30-60 min, by 21.2-60 weeks. Trials showed a significant lower risk to develop DIC in PLD group (OR 0.62, 95% CI 0.40-0.95), p0.03. There was not significant differences in the efficacy antitumor (OR 1.08, 95% CI 0.87–1.35), p0.47. The main toxicity was PPE (OR 11.7, 95% CI 9.15–14.96), p< 0.00001 in PLD group. Grade 4 neutropenia was significant lower in PLD group (OR 0.49, 95% CI 0.4–0.61) p< 0.00001. Conclusions: PLD is an effective and safe drug to treat several cancers. More trials that include more homogeneous patients group are necessary. It is a priority to have RCS about use of PLD in pediatric cancer. No significant financial relationships to disclose.
TWiST analysis to estimate overall benefit for metastatic renal cell carcinoma (mRCC) patients (pts) treated in a phase III trial of sunitinib versus interferon-alfa (IFN-α).
Authors: S. Patil, R. A. Figlin, T. E. Hutson, D. Michaelson, S. Negrier, S. T. Kim, X. Huang, R. J. Motzer
Journal: Journal of Clinical Oncology (2010)

4594 Background: Sunitinib has shown significant improvement in progression-free survival (PFS) compared with IFN-α (11 vs. 5 months; p<0.001) and longer overall survival (26.4 vs. 21.8 months; p=0.051) in a randomized phase III trial of treatment-naive mRCC pts. The proportion of grade 3/4 toxicities was relatively low in both groups. An analysis of toxicity- adjusted time without disease progression or toxicity (TWiST; Am Stat 49:1995) was performed to estimate overall benefit for pts. Methods: The highest frequency grade 3/4 treatment-related toxicities were included in the analysis. Any toxicity with onset after the progression date was excluded. Toxicities unresolved by the progression date were censored. The number of days a pt was progression free was calculated (PFS time). Pts without progression were censored at their last follow-up date. Overall benefit was defined as PFS time adjusted for the number of days spent without treatment-related toxicity. Results: Grade 3/4fatigue/asthenia was reported for a median of 17 and 13 days for sunitinib (n=57) and IFN-α (n=44) pts, respectively, but median time without progression was substantially longer for sunitinib pts (480 and 156 days). Sunitinib pts had hypertension (n=41) or diarrhea (n=31) for a median of 22 and 12 days, respectively, with median time to progression of 435 and 441 days. Similar trends were seen for dermatitis/hand-foot syndrome (HFS) and nausea/vomiting. More IFN-α pts had depression (n=5) with median time to progression of 71 days. Conclusions: Certain toxicities have been shown to occur with greater frequency in the sunitinib arm, but the number of days a pt experiences these toxicities is very small compared to the time a pt remains progression free. These results suggest that pts taking sunitinib not only have greater PFS, but also greater toxicity-adjusted PFS than IFN-α pts. Grade 3/4 treatment-related toxicity n Sunitinib Median days without progression n IFN- α Median days without progression Fatigue/asthenia (n=101) 57 480 44 156 Hypertension (n=41) 41 435 - - Diarrhea (n=33) 31 441 2 - Dermatitis/HFS (n=32) 31 408 1 - Nausea/vomiting (n=21) 18 290 3 33 Depression (n=6) 1 - 5 71 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Bayer, Pfizer, Roche Pfizer
Meta-analysis of RNA-seq expression data across species, tissues and studies
Authors: Peter H. Sudmant, Maria S. Alexis, Christopher B. Burge
Journal: Genome biology (2015)

Differences in gene expression drive phenotypic differences between species, yet major organs and tissues generally have conserved gene expression programs. Several comparative transcriptomic studies have observed greater similarity in gene expression between homologous tissues from different vertebrate species than between diverse tissues of the same species. However, a recent study by Lin and colleagues reached the opposite conclusion. These studies differed in the species and tissues analyzed, and in technical details of library preparation, sequencing, read mapping, normalization, gene sets, and clustering methods.To better understand gene expression evolution we reanalyzed data from four studies, including that of Lin, encompassing 6-13 tissues each from 11 vertebrate species using standardized mapping, normalization, and clustering methods. An analysis of independent data showed that the set of tissues chosen by Lin et al. were more similar to each other than those analyzed by previous studies. Comparing expression in five common tissues from the four studies, we observed that samples clustered exclusively by tissue rather than by species or study, supporting conservation of organ physiology in mammals. Furthermore, inter-study distances between homologous tissues were generally less than intra-study distances among different tissues, enabling informative meta-analyses. Notably, when comparing expression divergence of tissues over time to expression variation across 51 human GTEx tissues, we could accurately predict the clustering of expression for arbitrary pairs of tissues and species.These results provide a framework for the design of future evolutionary studies of gene expression and demonstrate the utility of comparing RNA-seq data across studies.
Associations of Fc gamma receptor (FcgR2a, FcgR3a and FcgR2c) genotype with outcome in metastatic renal cell carcinoma (mRCC) patients receiving high dose interleukin 2 (HD-IL2)
Authors: Amy K Erbe, Wei Wang, Kyung Mann Kim, Laskeesha Carmichael, MIkayla Gallendberger, Dustin Hess, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Su-Chun Chen, Sabina Signoretti, Michael B Atkins, Alexander Carlson, James Mier, David Panka, David F McDermott, Paul M Sondel
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts HD-IL2 was given to patients with mRCC in a prospective trial (ClinicalTrials.gov ID: [NCT00554515][1]) that demonstrated an overall response rate of 25%. To identify predictors of response, we genotyped patients for single nucleotide polymorphisms (SNPs) in FcgR genes: FcgR2a,
Abstract 2945: Normalization of Beta Adrenergic Receptor Signaling Improves Left Ventricular Myocyte Function with Urotensin II Receptor Blockade in Murine Heart Failure
Authors: Heng-Jie Cheng, Peng Zhou, Michael Cross, Michael F Callahan, William C Little, Che-Ping Cheng
Journal: Circulation (2008)

Background. Urotensin II (UII), the most potent vasoconstrictor and its receptors (UT) are upregulated in heart failure (HF). Although the role of UII in cardiac regulation is not fully understood, increasing evidence suggests that in the failing myocardium, UII may exert an enhanced negative modulation on cardiac contractile performance and cardiac β-AR regulation, thus providing a potential mechanism for progressive deterioration in cardiac function in HF. We assessed the hypothesis that blocking UII may prevent HF-induced alterations in cardiac β-adrenergic receptor (AR) expression, restore normal β-adrenergic regulation, and improve left ventricular (LV) myocyte functional performance. Methods. We compared β 1 - and β 3 -AR expression and responses to β- and β 3 -AR stimulation in freshly isolated LV myocytes obtained from 3 groups of mice (6/group): 1) HF-2 months after receiving isoproterenol (ISO, 170 mg/kg, sq, for 2 days); 2) HF/UIIBK-one month after receiving ISO, then urantide, a potent UIIBK (10 −5 M/kg/day via sq implanted osmotic minipump) initiated after the onset of HF and given for 1 month; and 3) Controls. Results. Compared with controls, ISO-treated mice had established HF. Isolated cardiomyocyte studies showed about 42% reductions in cell contraction (dL/dt max , 78 vs 134 μm/s) and relaxation (dR/dt max , 69 vs 120 μm/s) with a much less increase in dL/dt max (29 vs 68%) and dR/dt max (31 vs 62%) in response to superfusion of ISO (10 −8 M). These changes were associated with significantly decreased β 1 -AR mRNA (40%, 0.57 vs 0.95), but increased β 3 -AR mRNA (54%, 0.43 vs 0.28) expression. Treatment with UII BK prevented HF-induced contrast changes of β 1 - and β 3 -AR mRNA expression. The signal ratios of β 1 -AR mRNA (0.85) and β 3 -AR mRNA (0.34) remained close to control levels. Basal and ISO-stimulated adenylate cyclase activity were normal, and ISO-induced increase in dL/dt max (61%) and dR/dt max (58%) were significantly augmented. Conclusion. In a murine model of progressive HF, chronic UIIBK prevents HF-induced contrast alterations of LV β 1 - and β 3 -AR expression, restores normal responsiveness of myocyte to β-AR stimulation, and improves LV myocyte function. Thus, UIIBK may provide a new therapeutic strategy for the treatment of HF.
Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial
Authors: Gordon S Doig, Fiona Simpson, Philippa T Heighes, Rinaldo Bellomo, Douglas Chesher, Ian D Caterson, Michael C Reade, Peter W J Harrigan
Journal: The Lancet Respiratory Medicine (2015)
An Exposome Perspective on Environmental Enteric Dysfunction
Authors: Job O. Mapesa, Amy L. Maxwell, Elizabeth P. Ryan
Journal: Environmental Health Perspectives (2015)

Environmental exposures to chemicals have been shown to influence gastrointestinal function, yet little is known regarding whether chemical mixtures may be involved in the development of a subclinical enteric dysfunction found in infants and children born into poor hygiene and sanitation. Advances in gastrointestinal and immunotoxicology fields merit inclusion in complex discussions of environmental enteric dysfunction (EED) that severely affects children in developing countries.We aimed to highlight exposome approaches for investigating the potential influence of environmental chemical exposures on EED development, including a role for toxicant modulation of gut immune system and microbiome function.A major focus on fecal-oral contamination in impoverished living conditions already exists for EED, and should now expand to include environmental chemicals such as pesticides and heavy metals that may be anthropogenic or dietary or from microbial sources. A comprehensive characterization of environmental chemical exposures prenatally and occurring in infants and young children will enhance our knowledge of any associated risks for EED and stunting.Integrating EED, chemical exposure, and stunting at various ages during childhood will enhance our apparent limited view when evaluating EED. Etiology and intervention studies should evaluate the suite of environmental chemical exposures as candidates in the composite of EED biomarkers.Mapesa JO, Maxwell AL, Ryan EP. 2016. An exposome perspective on environmental enteric dysfunction. Environ Health Perspect 124:1121-1126; http://dx.doi.org/10.1289/ehp.1510459.
Osteoblast integration of dental implant materials after challenge by sub-gingival pathogens: a co-culture study in vitro
Authors: Bingran Zhao, Henny C van der Mei, Minie Rustema-Abbing, Henk J Busscher, Yijin Ren
Journal: International Journal of Oral Science (2015)

Sub-gingival anaerobic pathogens can colonize an implant surface to compromise osseointegration of dental implants once the soft tissue seal around the neck of an implant is broken. In vitro evaluations of implant materials are usually done in monoculture studies involving either tissue integration or bacterial colonization. Co-culture models, in which tissue cells and bacteria battle simultaneously for estate on an implant surface, have been demonstrated to provide a better in vitro mimic of the clinical situation. Here we aim to compare the surface coverage by U2OS osteoblasts cells prior to and after challenge by two anaerobic sub-gingival pathogens in a co-culture model on differently modified titanium (Ti), titanium-zirconium (TiZr) alloys and zirconia surfaces. Monoculture studies with either U2OS osteoblasts or bacteria were also carried out and indicated significant differences in biofilm formation between the implant materials, but interactions with U2OS osteoblasts were favourable on all materials. Adhering U2OS osteoblasts cells, however, were significantly more displaced from differently modified Ti surfaces by challenging sub-gingival pathogens than from TiZr alloys and zirconia variants. Combined with previous work employing a co-culture model consisting of human gingival fibroblasts and supra-gingival oral bacteria, results point to a different material selection to stimulate the formation of a soft tissue seal as compared to preservation of osseointegration under the unsterile conditions of the oral cavity.
Sexual assault and psychiatric disorders among a community sample of women
Authors: I Winfield, L K George, M Swartz, D G Blazer
Journal: American Journal of Psychiatry (1990)

The authors examined the relationships between sexual assault and psychiatric disorders in a sample of 1,157 women 18-64 years old in the North Carolina site of the NIMH Epidemiologic Catchment Area Program. The results suggest that sexual assault is a risk factor for a number of psychiatric disorders. In addition, several characteristics of the assault among sexual assault victims were significantly related to one or more psychiatric disorders. However, there was no clear pattern relating characteristics of the assault to the risk of specific psychiatric disorders.This paper examines the relationships between sexual assault and psychiatric disorders, as well as the extent to which characteristics of the sexual assault affected these relationships. Data were collected from a sample of 1157 women 18-64 years old in the North Carolina site of the National Institute of Mental Health Epidemiologic Catchment Area Program. Findings revealed that sexual assault was a risk factor for a number of psychiatric disorders but more so for some than for others. Major depression, alcohol abuse or dependence, drug abuse or dependence, panic disorder, post-traumatic stress disorder, and obsessive-compulsive disorder were psychiatric disorders associated with sexual disorders. In addition, strong associations were seen in alcohol abuse or dependence, drug abuse or dependence, panic disorder, post-traumatic stress disorder, and obsessive-compulsive disorder. However, no clear pattern relating characteristics of the assault to the risk of specific psychiatric disorders was noted. Further study employing a very large sample is recommended.
A Phase I Study Of Myeloablative Radioimmunotherapy Using Iodine-131 Anti-CD45 Antibody Followed By Autologous Stem Cell Transplantation For High-Risk B-Cell and T-Cell Non-Hodgkin Lymphoma and Hodgkin Lymphoma
Authors: Ryan D. Cassaday, Oliver W. Press, John M. Pagel, Joseph G. Rajendran, Theodore A. Gooley, Darrell R. Fisher, Sally J. Lundberg, Lacey M. Hedin, Andrew T. Shields, Damian J. Green, Robert S. Miyaoka, Frederick R. Appelbaum, Ajay K. Gopal
Journal: Blood (2013)
Public Health and International Partnerships in the Democratic People’s Republic of Korea
Authors: John Grundy, Beverley-Ann Biggs, David B. Hipgrave
Journal: PLoS Medicine (2015)

Points• The health system in the Democratic People's Republic of Korea (DPRK) is suitable for high public health program coverage, with a wide facility network and high staffpopulation ratios.• Economic difficulties, natural disasters, and poor resourcing of the health sector in the 1990s had catastrophic impacts on public health and system functioning, leading to sharp declines in vaccination coverage.• With considerable international support, diphtheria, tetanus, and pertussis (DTP) vaccine coverage has risen from 37% in 1997 to 96% in 2013.Major challenges related to immunization services and the health sector more generally have been reduced.