tbuckley/cabot-search huggingface dataset:
Excess mortality in a population with diabetes and the impact of material deprivation: longitudinal, population based study
Authors: N. A Roper
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To establish the age and sex specific mortality for people with diabetes in comparison with local and national background populations; to investigate the relationship between mortality and material deprivation in an unselected population with diabetes. <b>Design:</b> Longitudinal study, using a population based district diabetes register. <b>Setting:</b> South Tees, United Kingdom. <b>Participants:</b> All people known to have diabetes living in Middlesbrough and Redcar and Cleveland local authorities on 1 January 1994. <b>Main outcome measure:</b> Death, from any cause, between 1 January 1994 and 31 December 1999. <b>Results:</b> Over the six years of the study 1205 (24.9%) of 4842 participants died. All cause standardised mortality ratios for type 1 diabetes were 641 (95% confidence interval 406 to 962) in women and 294 (200 to 418) in men, and those for type 2 diabetes were 160 (147 to 174) in women and 141 (130 to 152) in men. Cause specific standardised mortality ratios were increased for ischaemic heart disease, cerebrovascular disease, and renal disease; no reductions in mortality from other causes were seen. The risk of premature death increased significantly with increasing material deprivation (P&lt;0.001). <b>Conclusions:</b> Diabetes is associated with excess mortality, even in an area with high background death rates from cardiovascular disease. This excess mortality is evident in all age groups, most pronounced in young people with type 1 diabetes, and exacerbated by material deprivation. Aggressive approaches to the management of cardiovascular risk factors could reduce the excess mortality in people with diabetes. <h3>What is already known on this topic</h3> Mortality, mainly from cardiovascular disease, is increased in people with diabetes, but this excess varies considerably by country and ethnic group Previous British studies have reported no excess mortality in old age, a reduction in deaths from non-cardiovascular causes, and that mortality may be adversely affected by deprivation <h3>What this study adds</h3> Mortality is increased, across all ages, in an unselected population with diabetes compared with the local population without diabetes, which itself has high mortality Most of the excess is from cardiovascular causes, but there are no reductions in other causes of death Mortality among people with diabetes is increased even in the most affluent group, and this excess increases with worsening material deprivation
Salvage Therapy of Progressive and Recurrent Hodgkin’s Disease: Results From a Multicenter Study of the Pediatric DAL/GPOH-HD Study Group
Authors: Günther Schellong, Wolfgang Dörffel, Alexander Claviez, Dieter Körholz, Georg Mann, Hans-G. Scheel-Walter, Jos P.M. Bökkerink, Marianne Riepenhausen, Heike Lüders, Richard Pötter, Ursula Rühl
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin’s disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Methods One hundred seventy-six patients with progression (n = 51) or first relapse (n = 125) were enrolled by 67 centers. The median time from initial diagnosis to progression/relapse was 1.1 year (range, 0.1 to 15.3 years), and the patients’ median age was 14.7 years (range, 4.3 to 24.5 years). Salvage chemotherapy consisted of two to three cycles of IEP alternating with one to two cycles of ABVD supplemented in part by one to two cycles of cyclophosphamide, vincristine, procarbazine, and prednisone or lomustine (CCNU), etoposide, and prednimustine. Radiotherapy was given to involved areas using individualized doses. In the 1990s, additional high-dose chemotherapy with autologous stem-cell transplantation (SCT) was introduced for patients with unfavorable prognosis. Results Disease-free survival (DFS) and overall survival (OS) after 10 years are 62% and 75%, respectively (SE, 4% each). Of 176 patients, 73 suffered second events. The risk-factor analysis revealed the time to progression/relapse as the strongest prognostic factor (P = .0001). Patients with progression have an inferior outcome (DFS, 41%; OS, 51%), whereas patients with late relapse (&gt; 12 months after end of therapy) do well (DFS, 86%; OS, 90%), although none of them received SCT in second remission. Conclusion The result can be considered favorable. Whereas the salvage strategy for progressive disease has to be optimized further, it is possible to reduce intensity and avoid SCT in late relapses after Hodgkin’s disease in childhood/adolescence.
Regulated Overexpression of the A <sub>1</sub> -Adenosine Receptor in Mice Results in Adverse but Reversible Changes in Cardiac Morphology and Function
Authors: Hajime Funakoshi, Tung O. Chan, Julie C. Good, Joseph R. Libonati, Jarkko Piuhola, Xiongwen Chen, Scott M. MacDonnell, Ling L. Lee, David E. Herrmann, Jin Zhang, Jeffrey Martini, Timothy M. Palmer, Atsushi Sanbe, Jeffrey Robbins, Steven R. Houser, Walter J. Koch, Arthur M. Feldman
Journal: Circulation (2006)

Background— Both the A 1 - and A 3 -adenosine receptors (ARs) have been implicated in mediating the cardioprotective effects of adenosine. Paradoxically, overexpression of both A 1 -AR and A 3 -AR is associated with changes in the cardiac phenotype. To evaluate the temporal relationship between AR signaling and cardiac remodeling, we studied the effects of controlled overexpression of the A 1 -AR using a cardiac-specific and tetracycline-transactivating factor–regulated promoter. Methods and Results— Constitutive A 1 -AR overexpression caused the development of cardiac dilatation and death within 6 to 12 weeks. These mice developed diminished ventricular function and decreased heart rate. In contrast, when A 1 -AR expression was delayed until 3 weeks of age, mice remained phenotypically normal at 6 weeks, and &gt;90% of the mice survived at 30 weeks. However, late induction of A 1 -AR still caused mild cardiomyopathy at older ages (20 weeks) and accelerated cardiac hypertrophy and the development of dilatation after pressure overload. These changes were accompanied by gene expression changes associated with cardiomyopathy and fibrosis and by decreased Akt phosphorylation. Discontinuation of A 1 -AR induction mitigated cardiac dysfunction and significantly improved survival rate. Conclusions— These data suggest that robust constitutive myocardial A 1 -AR overexpression induces a dilated cardiomyopathy, whereas delaying A 1 -AR expression until adulthood ameliorated but did not eliminate the development of cardiac pathology. Thus, the inducible A 1 -AR transgenic mouse model provides novel insights into the role of adenosine signaling in heart failure and illustrates the potentially deleterious consequences of selective versus nonselective activation of adenosine-signaling pathways in the heart.
18F-Fluoro-2-Deoxy-Glucose Uptake Predicts Clinical Outcome in Patients with Gefitinib-Treated Non–Small Cell Lung Cancer
Authors: Im Il Na, Byung Hyun Byun, Hye Jin Kang, Gi Jeong Cheon, Jae Soo Koh, Cheol Hyeon Kim, Du Hwan Choe, Baek-Yeol Ryoo, Jae Cheol Lee, Sang Moo Lim, Sung Hyun Yang
Journal: Clinical Cancer Research (2008)

To evaluate response and survival according to (18)F-fluoro-2-deoxy-glucose uptake at presentation in patients with gefitinib-treated non-small cell lung cancer.We retrospectively analyzed 84 positron emission tomography/computed tomography findings. Patient characteristics, response rates, and survivals were evaluated according to the maximum standardized uptake value (SUV) of primary tumor. The cutoff value of SUVs was obtained from receiver operating characteristic analysis.The response rate (RR) was higher for never-smokers (41%) than ever-smokers (9%; P=0.001). Patients with adenocarcinoma showed higher RR than those with other tumor histopathology (35% versus 9%; P=0.009). The SUV was significantly lower in patients who were never-smokers (P=0.005), patients with adenocarcinoma (P<0.001), and female patients (P=0.017). Patients with a low SUV showed higher RR compared with those with a high SUV (53% versus 18%; P=0.003). Prolonged progression-free survival was observed in patients with low SUVs compared with those with high SUVs (median, 33.1 weeks versus 8.6 weeks; P=0.003). While controlling for performance status, smoking history, and pathology, the high SUV conferred unfavorable outcome (hazard ratio, 2.3; P=0.012). In terms of overall survival, a low SUV was associated with favorable outcome in univariate analysis (P=0.011). Patients with a low SUV showed prolonged survival in multivariate analysis (P=0.043).These results suggest that low SUVs at presentation can predict favorable response and survival in gefitinib-treated non-small cell lung cancer patients.
Randomized Controlled Trial of Chlorhexidine Dressing and Highly Adhesive Dressing for Preventing Catheter-related Infections in Critically Ill Adults
Authors: Jean-François Timsit, Olivier Mimoz, Bruno Mourvillier, Bertrand Souweine, Maïté Garrouste-Orgeas, Serge Alfandari, Gaétan Plantefeve, Régis Bronchard, Gilles Troche, Remy Gauzit, Marion Antona, Emmanuel Canet, Julien Bohe, Alain Lepape, Aurélien Vesin, Xavier Arrault, Carole Schwebel, Christophe Adrie, Jean-Ralph Zahar, Stéphane Ruckly, Caroline Tournegros, Jean-Christophe Lucet
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Most vascular catheter-related infections (CRIs) occur extraluminally in patients in the intensive care unit (ICU). Chlorhexidine-impregnated and strongly adherent dressings may decrease catheter colonization and CRI rates.Objectives: To determine if chlorhexidine-impregnated and strongly adherent dressings decrease catheter colonization and CRI rates.Methods: In a 2:1:1 assessor-masked randomized trial in patients with vascular catheters inserted for an expected duration of 48 hours or more in 12 French ICUs, we compared chlorhexidine dressings, highly adhesive dressings, and standard dressings from May 2010 to July 2011. Coprimary endpoints were major CRI with or without catheter-related bloodstream infection (CR-BSI) with chlorhexidine versus nonchlorhexidine dressings and catheter colonization rate with highly adhesive nonchlorhexidine versus standard nonchlorhexidine dressings. Catheter-colonization, CR-BSIs, and skin reactions were secondary endpoints.Measurements and Main Results: A total of 1,879 patients (4,163 catheters and 34,339 catheter-days) were evaluated. With chlorhexidine dressings, the major-CRI rate was 67% lower (0.7 per 1,000 vs. 2.1 per 1,000 catheter-days; hazard ratio [HR], 0.328; 95% confidence interval [CI], 0.174–0.619; P = 0.0006) and the CR-BSI rate 60% lower (0.5 per 1,000 vs. 1.3 per 1,000 catheter-days; HR, 0.402; 95% CI, 0.186–0.868; P = 0.02) than with nonchlorhexidine dressings; decreases were noted in catheter colonization and skin colonization rates at catheter removal. The contact dermatitis rate was 1.1% with and 0.29% without chlorhexidine. Highly adhesive dressings decreased the detachment rate to 64.3% versus 71.9% (P < 0.0001) and the number of dressings per catheter to two (one to four) versus three (one to five) (P < 0.0001) but increased skin colonization (P < 0.0001) and catheter colonization (HR, 1.650; 95% CI, 1.21–2.26; P = 0.0016) without influencing CRI or CR-BSI rates.Conclusions: A large randomized trial demonstrated that chlorhexidine-gel–impregnated dressings decreased the CRI rate in patients in the ICU with intravascular catheters. Highly adhesive dressings decreased dressing detachment but increased skin and catheter colonization.Clinical trial registered with www.clinicaltrials.gov (NCT 01189682).
Recognizing Increased Risk of Depressive Comorbidity after Myocardial Infarction: Looking for 4 Symptoms of Anxiety-Depression
Authors: Johan Denollet, Jacqueline J. Strik, Richel Lousberg, Adriaan Honig
Journal: Psychotherapy and Psychosomatics (2006)

&lt;i&gt;Background:&lt;/i&gt; Screening for depression in myocardial infarction (MI) patients must be improved: (1) depression often goes unrecognized and (2) anxiety has been largely overlooked as an essential feature of depression in these patients. We therefore examined the co-occurrence of anxiety and depression after MI, and the validity of a brief mixed anxiety-depression index as a simple way to identify post-MI patients at increased risk of comorbid depression. &lt;i&gt;Methods:&lt;/i&gt; One month after MI, 176 patients underwent a psychiatric interview and completed the Beck Depression Inventory (BDI) and the Symptoms of Anxiety-Depression index (SAD&lt;sub&gt;4&lt;/sub&gt;) containing four symptoms of anxiety (tension, restlessness) and depression (feeling blue, hopelessness). &lt;i&gt;Results:&lt;/i&gt; Thirty-one MI patients (18%) had comorbid depression and 37 (21%) depressive or anxiety disorder. High factor loadings and item-total correlations (SAD&lt;sub&gt;4&lt;/sub&gt;, α = 0.86) confirmed that symptoms of anxiety and depression co-occurred after MI. Mixed anxiety-depression (SAD&lt;sub&gt;4&lt;/sub&gt;≧3) was present in 90% of depressed MI patients and in 100% of severely depressed patients. After adjustment for standard depression symptoms (BDI; OR = 4.4, 95% CI 1.6–12.1, p = 0.004), left ventricular ejection fraction, age and sex, mixed anxiety-depression symptomatology was associated with an increased risk of depressive comorbidity (OR = 11.2, 95% CI 3.0–42.5, p &lt; 0.0001). Mixed anxiety-depression was also independently associated with depressive or anxiety disorder (OR = 9.2, 95% CI 3.0–27.6, p &lt; 0.0001). &lt;i&gt;Conclusions:&lt;/i&gt; Anxiety is underrecognized in post-MI patients; however, the present findings suggest that anxiety symptomatology should not be overlooked in these patients. Depressive comorbidity after MI is characterized by symptoms of mixed anxiety-depression, after controlling for standard depression symptoms. The SAD&lt;sub&gt;4&lt;/sub&gt; represents an easy way to recognize the increased risk of post-MI depression.
IgE‐mediated anaphylaxis to Thiomucase®, a mucopolyssacharidase: allergens and cross‐reactivity
Authors: T. Caballero, A. Alonso, S. De Miguel, M. Martín‐Esteban, B. Varga, C. Y. Pascual, M. C. López‐Serrano
Journal: Allergy (2002)

Thiomucase is a mucopolysaccharidase obtained from ovine tissues mainly used to facilitate the diffusion of local anaesthetics and in the treatment of cellulitis. A patient with an anaphylaxis in relation to the intramuscular administration of Thiomucase is reported.To investigate Thiomucase allergens and their possible relationship with dander allergens and animal albumins.Skin prick tests (SPT) and serum-specific IgE were performed with Thiomucase and danders. Thiomucase SDS-PAGE immunoblotting was performed in order to study allergens. RAST/CAP inhibition and SDS-PAGE immunoblotting inhibition were carried out to study the cross-reactivity.Skin prick tests (SPT) were positive to Thiomucase, animal dander (cat, dog, sheep, other), bovine serum albumin (BSA), and echinococcus. Specific IgE was also positive to Thiomucase, animal dander (cat, dog, sheep, other), BSA and echinococcus. In the RAST-CAP inhibition assays BSA was nearly completely inhibited by Thiomucase, Thiomucase was partially inhibited by BSA and cat and Echinococcus granulosus was partially inhibited by sheep and Thiomucase. In the Thiomucase SDS-PAGE immunoblotting several proteins fixed IgE, ranging from 20 kDa to > 94 kDa, the strongest with 43 kDa. The IgE fixation to BSA, cat and sheep in the SDS-PAGE immunoblotting was completely inhibited by the preincubation of the serum with Thiomucase.An IgE-mediated anaphylaxis to Thiomucase is documented. Multiple allergens are recognized in Thiomucase by the patient serum, the main with 43 kDa. Partial cross-reactivity with BSA, cat dander and sheep dander is documented.
A Novel Mechanism of Chemoprotection by Sulforaphane
Authors: Melinda C. Myzak, P. Andrew Karplus, Fung-Lung Chung, Roderick H. Dashwood
Journal: Cancer Research (2004)

Abstract Sulforaphane (SFN), a compound found at high levels in broccoli and broccoli sprouts, is a potent inducer of phase 2 detoxification enzymes and inhibits tumorigenesis in animal models. SFN also has a marked effect on cell cycle checkpoint controls and cell survival and/or apoptosis in various cancer cells, through mechanisms that are poorly understood. We tested the hypothesis that SFN acts as an inhibitor of histone deacetylase (HDAC). In human embryonic kidney 293 cells, SFN dose-dependently increased the activity of a β-catenin-responsive reporter (TOPflash), without altering β-catenin or HDAC protein levels. Cytoplasmic and nuclear extracts from these cells had diminished HDAC activity, and both global and localized histone acetylation was increased, compared with untreated controls. Studies with SFN and with media from SFN-treated cells indicated that the parent compound was not responsible for the inhibition of HDAC, and this was confirmed using an inhibitor of glutathione S-transferase, which blocked the first step in the metabolism of SFN, via the mercapturic acid pathway. Whereas SFN and its glutathione conjugate (SFN-GSH) had little or no effect, the two major metabolites SFN-cysteine and SFN-N-acetylcysteine were effective HDAC inhibitors in vitro. Finally, several of these findings were recapitulated in HCT116 human colorectal cancer cells: SFN dose-dependently increased TOPflash reporter activity and inhibited HDAC activity, there was an increase in acetylated histones and in p21Cip1/Waf1, and chromatin immunoprecipitation assays revealed an increase in acetylated histones bound to the P21 promoter. Collectively, these findings suggest that SFN may be effective as a tumor-suppressing agent and as a chemotherapeutic agent, alone or in combination with other HDAC inhibitors currently undergoing clinical trials.
Endothelial activation and circulating vascular adhesion molecules in alcoholic liver disease
Authors: David H. Adams, Patrizia Burra, Stefan G. Hubscher, Elwyn Elias, Walter Newman
Journal: Hepatology (1994)

Alcoholic hepatitis is characterized by hepatocyte necrosis associated with infiltration of the liver parenchyma by neutrophils. The mechanisms responsible for recruiting neutrophils to the liver are unknown. We report high circulating levels and tissue expression of the endothelial adhesion molecule E-selectin in alcoholic hepatitis. Because expression of E-selectin is involved in neutrophil transmigration into inflamed tissue, it may play a crucial role in the recruitment of neutrophils to the liver in alcoholic hepatitis. By contrast, we detected high levels of vascular cell adhesion molecule-1, the endothelial counter-receptor for the lymphocyte adhesion molecule very late antigen-4, in alcoholic cirrhosis, which is associated with a predominantly mononuclear cell infiltrate. Both diseases were associated with high levels of circulating intercellular adhesion molecule-1, which is released by activated lymphocytes, providing further evidence of immune activation in alcoholic liver disease.
Outcomes One and Two Winters Following Cognitive-Behavioral Therapy or Light Therapy for Seasonal Affective Disorder
Authors: Kelly J. Rohan, Jonah Meyerhoff, Sheau-Yan Ho, Maggie Evans, Teodor T. Postolache, Pamela M. Vacek
Journal: American Journal of Psychiatry (2015)

Objective: The central public health challenge for winter seasonal affective disorder (SAD) is recurrence prevention. Preliminary studies suggest better long-term outcomes following cognitive-behavioral therapy tailored for SAD (CBT-SAD) than light therapy. The present study is a large, randomized head-to-head comparison of these treatments on outcomes one and two winters after acute treatment. Method: Community adults with major depression, recurrent with seasonal pattern (N=177) were followed one and two winters after a randomized trial of 6 weeks of CBT-SAD (N=88) or light therapy (N=89). Prospective follow-up visits occurred in January or February of each year, and major depression status was assessed by telephone in October and December of the first year. The primary outcome was winter depression recurrence status on the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD). Other outcomes were depression severity on the SIGH-SAD and the Beck Depression Inventory-Second Edition (BDI-II), remission status based on severity cutoff scores, and major depression status from tracking calls. Results: The treatments did not differ on any outcome during the first year of follow-up. At the second winter, CBT-SAD was associated with a smaller proportion of SIGH-SAD recurrences (27.3% compared with 45.6%), less severe symptoms on both measures, and a larger proportion of remissions defined as a BDI-II score ≤8 (68.3% compared with 44.5%) compared with light therapy. Nonrecurrence at the next winter was more highly associated with nonrecurrence at the second winter among CBT-SAD participants (relative risk=5.12) compared with light therapy participants (relative risk=1.92). Conclusions: CBT-SAD was superior to light therapy two winters following acute treatment, suggesting greater durability for CBT-SAD.
Cost-Effectiveness Analyses of Colorectal Cancer Screening
Authors: Michael Pignone, Somnath Saha, Tom Hoerger, Jeanne Mandelblatt
Journal: Annals of Internal Medicine (2002)

Purpose: To perform a systematic review of the cost-effectiveness of colorectal cancer screening for the U.S. Preventive Services Task Force. Data Sources: MEDLINE and the British National Health Service Economic Evaluation Database, January 1993 through September 2001. Study Selection: Original economic evaluations of colorectal cancer screening in average-risk patients were reviewed. The authors sought studies addressing the incremental cost-effectiveness of different screening strategies compared with no screening, of different screening strategies compared with one another, and of different ages of screening initiation and cessation. Two investigators independently reviewed each abstract, and potentially eligible articles were retrieved. A four-member working group reached consensus regarding final inclusion or exclusion of articles. Data Extraction: One reviewer extracted data into evidence tables. The results were checked by other members and discrepancies resolved by consensus. Data Synthesis: Among 180 potential articles identified, 7 were retained in the final analysis. Compared with no screening, cost-effectiveness ratios for screening with any of the commonly considered methods were generally between $10 000 and $25 000 per life-year saved. No one strategy was consistently found to be the most effective or to have the best incremental cost-effectiveness ratio. Currently available models provided insufficient evidence to determine optimal starting and stopping ages for screening. Conclusions: Screening for colorectal cancer appears cost-effective compared with no screening, but a single optimal strategy cannot be determined from the currently available data. Additional data regarding adherence with screening over time, complication rates in real-world settings, and colorectal cancer biology are needed. Additional analyses are necessary to determine optimal ages of initiation and cessation.