tbuckley/cabot-search huggingface dataset:
Expectant management for men with early stage prostate cancer
Authors: Christopher P. Filson, Leonard S. Marks, Mark S. Litwin
Journal: CA A Cancer Journal for Clinicians (2015)

Since the dissemination of prostate-specific antigen screening, most men with prostate cancer are now diagnosed with localized, low-risk prostate cancer that is unlikely to be lethal. Nevertheless, nearly all of these men undergo primary treatment with surgery or radiation, placing them at risk for longstanding side effects, including erectile dysfunction and impaired urinary function. Active surveillance and other observational strategies (ie, expectant management) have produced excellent long-term disease-specific survival and minimal morbidity for men with prostate cancer. Despite this, expectant management remains underused for men with localized prostate cancer. In this review, various approaches to the expectant management of men with prostate cancer are summarized, including watchful waiting and active surveillance strategies. Contemporary cancer-specific and health care quality-of-life outcomes are described for each of these approaches. Finally, contemporary patterns of use, potential disparities in care, and ongoing research and controversies surrounding expectant management of men with localized prostate cancer are discussed.
Abstract P142: Smokers Can Lose Weight When They Quit Smoking
Authors: Charlotta H Pisinger, Ulla Toft, Torben Jørgensen
Journal: Circulation (2012)

Background: Smoking is one of the major risk factors of CVD. It is well-known that smokers increase weight when they quit smoking, and concomitant weight increase after smoking cessation may blunt beneficial effects of smoking cessation on e.g. glucose metabolism. However, not all smokers gain weight. To our knowledge, predictors of weight-loss after smoking cessation have not previously been investigated. Methods: in a large population-based study, the Inter99 study, 2,408 daily smokers were included at baseline. Out of these, 262 attended the five year follow-up and reported that they had not smoked for at least 12 months. Participants completed self-report questionnaires at baseline and follow-up. In multivariable logistic regression analyses we investigated predictors of weight-loss. Results: A total of 17.6% of the quitters had lost weight from baseline to 5 years follow-up. Neither sex, age, number of daily meals, energy intake, dietary quality, physical activity, alcohol consumption, nor change in physical activity or alcohol consumption from baseline to five year follow-up was associated with weight-loss at five year follow-up. Quitters with high education had significantly higher probability of weight-loss compared to quitters with low education (OR=3.88(1.04–14.50), p=0.044). Increasing BMI at baseline increased (OR=1.20(1.06–1.36), p=0.004) and increasing tobacco consumption decreased (OR=0.93(0.87–0.99), p=0.038) the probability of weight-loss. Furthermore, quitters who reported a healthier diet at five-year follow-up than at baseline had increased probability of weight-loss (OR=3.23(1.07–9.82), p=0.038). The mean weight-gain in quitters with normal baseline BMI was 5.66kg (±4.8), quitters who were overweight at baseline gained 5.32kg (±7.0) and quitters who were obese gained 1.98kg (±8.3), p=0.038. Conclusion: Weight-loss after quitting smoking is feasible and was achieved by about two out of ten quitters. High BMI, high education and low tobacco consumption at baseline and change to a healthier diet predicted weight loss in daily smokers who had quit for at least 12 months. Discussion: Obese smokers who had quit had the lowest weight-gain. A reason could be that normal-weight smokers are used to eat whatever they want, whereas obese smokers are used to focus on what and how much they eat. Obese smokers should definitely not be advised against quitting smoking in fear of further weight-gain. The large positive cardiovascular health effects of quitting overshadow the negative health effects of a small weight gain, and this study shows that weight-loss after smoking cessation is feasible, especially in obese smokers.
Prodromes and precursors: epidemiologic data for primary prevention of disorders with slow onset
Authors: William W. Eaton, Mohamed Badawi, Beth Melton
Journal: American Journal of Psychiatry (1995)

The concepts of prodrome and precursor are used to show how epidemiologic data on age at onset can be used in timing preventive interventions and selecting target populations.Data concerning onset of DSM-III major depression and panic disorder were taken from the Epidemiologic Catchment Area Program. Cumulative distributions of ages at onset of diagnosis and onset of precursors are presented, and the concept of attributable risk is introduced. Attributable risk is the maximum proportion of cases that would be prevented if an intervention were 100% effective in eliminating a specific precursor.Illustrative results for depression and panic are presented. Precursors vary in the degree to which they predict onset of the full disorder; 2 or more weeks of sad mood in the year before full-blown depression is a better predictor (relative odds, 7.0) than weight loss or gain (relative odds, 3.0). The formula for population attributable risk was applied to the precursor relative risks and prevalences to estimate the potential success of interventions for specific precursors in preventing the disorder. The precursor attributable risks indicate that sleep problems would identify 47% of the new cases of major depression occurring in the following year, and the question "Are you a nervous person?" would identify 60% of persons with onset of panic disorder in the following year.This conceptual framework links the early natural history of disorders with the search for syndromes. Knowledge of precursor prevalence and attributable risk, combined with other host characteristics and environmental risk factors, can be used in screening and prevention.
The Hajj: updated health hazards and current recommendations for 2012
Authors: J A Al-Tawfiq, Z A Memish
Journal: Eurosurveillance (2012)

This year the Hajj will take place during 24-29 October. Recent outbreaks of Ebola haemorrhagic fever in Uganda and the Democratic Republic of the Congo, cholera in Sierra Leone, and infections associated with a novel coronavirus in Saudi Arabia and Qatar required review of the health recommendations of the 2012 Hajj. Current guidelines foresee mandatory vaccination with quadrivalent meningococcal vaccine for all pilgrims, and yellow fever and poliomyelitis vaccine for pilgrims from high-risk countries. Influenza vaccine is strongly recommended.
Low discharge weight and outcome in anorexia nervosa
Authors: S A Baran, T E Weltzin, W H Kaye
Journal: American Journal of Psychiatry (1995)

Because recent limitations in health care coverage have resulted in shorter lengths of inpatient stay, many patients with anorexia nervosa are discharged while still underweight. The authors' goal was to determine whether anorectic patients who were underweight when they were discharged had a worse outcome and a higher rate of rehospitalization than those who had achieved normal weight at discharge.They assessed weight and height, eating disorder symptoms, and severity of depressive and anxiety symptoms in 22 women with anorexia nervosa at hospital admission and at follow-up a mean of 29 months after discharge.Anorectic patients who were discharged while severely underweight reported significantly higher rates of rehospitalization and endorsed more symptoms than those who had achieved normal weight before discharge.These data suggest that brief hospitalization for severely underweight women with anorexia may not be cost effective because the majority are rehospitalized.
Uncoupling of myofilament Ca<sup>2+</sup>sensitivity from troponin I phosphorylation by mutations can be reversed by epigallocatechin-3-gallate
Authors: Maria Papadaki, Petr G. Vikhorev, Steven B. Marston, Andrew E. Messer
Journal: Cardiovascular Research (2015)

Heart muscle contraction is regulated via the β-adrenergic response that leads to phosphorylation of Troponin I (TnI) at Ser22/23, which changes the Ca2+ sensitivity of the cardiac myofilament. Mutations in thin filament proteins that cause dilated cardiomyopathy (DCM) and some mutations that cause hypertrophic cardiomyopathy (HCM) abolish the relationship between TnI phosphorylation and Ca2+ sensitivity (uncoupling). Small molecule Ca2+ sensitizers and Ca2+ desensitizers that act upon troponin alter the Ca2+ sensitivity of the thin filament, but their relationship with TnI phosphorylation has never been studied before. Quantitative in vitro motility assay showed that 30 µM EMD57033 and 100 µM Bepridil increase Ca2+ sensitivity of phosphorylated cardiac thin filaments by 3.1- and 2.8-fold, respectively. Additionally they uncoupled Ca2+ sensitivity from TnI phosphorylation, mimicking the effect of HCM mutations. Epigallocatechin-3-gallate (EGCG) decreased Ca2+ sensitivity of phosphorylated and unphosphorylated wild-type thin filaments equally (by 2.15 ± 0.45- and 2.80 ± 0.48-fold, respectively), retaining the coupling. Moreover, EGCG also reduced Ca2+ sensitivity of phosphorylated but not unphosphorylated thin filaments containing DCM and HCM-causing mutations; thus, the dependence of Ca2+ sensitivity upon TnI phosphorylation of uncoupled mutant thin filaments was restored in every case. In single mouse heart myofibrils, EGCG reduced Ca2+ sensitivity of force and kACT and also preserved coupling. Myofibrils from the ACTC E361G (DCM) mouse were uncoupled; EGCG reduced Ca2+ sensitivity more for phosphorylated than for unphosphorylated myofibrils, thus restoring coupling. We conclude that it is possible to both mimic and reverse the pathological defects in troponin caused by cardiomyopathy mutations pharmacologically. Re-coupling by EGCG may be of potential therapeutic significance for treating cardiomyopathies.
Chemotherapy administration sequences -Review of the literature &amp; administration recommendations
Authors: B. L. Stanford, S. D. Zondor, C. A. Jumper
Journal: Journal of Clinical Oncology (2005)

6121 Background: Combination chemotherapy is the mainstay of treatment for a variety of malignancies. The sequence of chemotherapy administration can be important due to the effect of interactions on efficacy, toxicity, pharmacokinetics, or any combination of these. Although many reports have been published on this subject, there is, to our knowledge, no single source that describes the best sequence of administration for various chemotherapy regimens. Therefore, we conducted a review of the literature to identify sequence-dependent interactions to develop administration recommendations. Methods: A comprehensive literature search was conducted through November 2004 in Medline, PubMed, Embase, Cochrane Databases, CINAHL, & International Pharmaceutical Abstracts (IPA) as well as ASCO abstracts from 1995 through 2004. The bibliographies of identified articles were also reviewed for relevant citations. Only in vivo human studies that specifically compared various sequences of a chemotherapy regimen were included. Studies were assessed for sequence-dependent differences in toxicity, efficacy, & pharmacokinetics. All authors reviewed all studies in order to reach a consensus for development of specific administration recommendations. Results: A total of 50 studies evaluating 32 different regimens were identified in the literature search. Sequence-dependent interactions were categorized as follows: 18 toxicity, 9 pharmacokinetic and 3 efficacy. Nine studies reported combinations of sequence-dependent interactions, all of which included both pharmacokinetic & toxicity. Of the identified studies, no differences due to sequence were found in 11 regimens. Conclusions: Improper sequence of administration of certain chemotherapeutic agents may result in increased toxicity, decreased efficacy, as well as pharmacokinetic differences. Specific recommendations for administration sequences, and their related interactions, will be presented. No significant financial relationships to disclose.
Submitting articles to the BMJ via the web
Authors: J. Smith
Journal: BMJ (2002)

From this week we are inviting all authors who want to submit a paper to the BMJ to do so via the web (http://submit.bmj.com).

We have introduced Benchpress, our new web based manuscript tracking system, with the aim of streamlining our processes and providing better, quicker information for authors, reviewers, and editors. Although using Benchpress demands new ways of working from all these groups, our experience in piloting the system suggests it will succeed in these aims.

Benchpress is a website where authors deposit their manuscripts and editors go to read them and record their decisions. When editors decide to send a paper for peer review they use the system to select a reviewer; an email then goes to the …
The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease
Authors: Agha W Haider, Peter W.F Wilson, Martin G Larson, Jane C Evans, Eric L Michelson, Philip A Wolf, Christopher J O’Donnell, Daniel Levy
Journal: Journal of the American College of Cardiology (2002)
Abstract 3104: Heart Failure: Is there an Epidemic? A 17-Year Longitudinal Study on the Incidence, Prevalence and Survival Outcomes
Authors: Tiew-Hwa K Teng, Judith Finn, Michael Hobbs, Elizabeth Geelhoed, Joseph Hung
Journal: Circulation (2008)

Background Despite concerns of a heart failure ‘epidemic’, long term population trends on the incidence, prevalence and survival outcomes of heart failure (HF) are not well characterized. Methods The Western Australian Hospital Morbidity Database was used to identify index patients with first-time admissions for HF from 1990 to 2006, with no prior admission for HF since 1 January 1980. Age and gender adjusted temporal trends in HF incidence were examined and Cox-proportional hazards model used to analyse 5-year survival following index admissions, adjusted for significant covariates. Prevalence was calculated at end of each calendar year. Base period used was 1990–1993. Results There were 70,967 index heart failure (HF) patients identified during 1990–2006, with almost equal distribution between genders. There was a significant downward trend for age and gender-adjusted incidence of HF with average decline of 1.73% (95% CI 1.5%, 1.9%, p=0.001) per year over the 17-year period. Incidence rate reached a peak in 1993 and thereafter there was a steady decline. Compared to the base period, age and gender-adjusted survival at 5-year after index HF admission improved with an absolute survival gain of 6.9% (95% CI 4.3%, 9.4% p=0.001) for 1994–97 period, 9.3% (95% CI 6.7%, 11.9%, p=0.001) for 1998–2001 period and 7.0% (95% CI 4.1%, 9.8%, p=0.001) for 2002– 05 period respectively. Prevalence of HF increased significantly over the different time periods, with a 2.26 fold higher prevalence in 2002–2006 compared to base period. The increase in prevalence was greatest in the 70–79 year age group, with an increase from 200.3 per 10,000 in the base period to 606.0 per 10,000 in 2002–2006. Conclusions In the last 17 years, incidence of hospitalized HF patients has declined steadily in both genders. However, there has been a marked increase in prevalence of HF due in part to an ageing population and improved HF survival. Management of these chronic elderly HF patients remains a major public health problem.
Nation-wide prospective surveillance of Clostridium difficile infections in hospitals in Belgium, July 2007-June 2008
Authors: M L Lambert, K Mertens, I Ramboer, M Delmée, C Suetens
Journal: Eurosurveillance (2009)

We report here baseline data from the first year of compulsory surveillance of Clostridium difficile infections (CDI) in hospitals in Belgium. Between 1 July 2007 and 30 June 2008, 2,704 CDI were reported: 12% were recurrent and 66% were hospital-associated (half of which occurred 15 days or more after admission). CDI was considered the cause of death (direct or indirect) for 10% of the episodes. The median incidence of CDI was 1.5 per 1,000 admissions and 1.9 per 10,000 hospital-days for all cases, and 0.9 per 1,000 admissions, and 1.1 per 10,000 hospital-days for hospital-associated cases. Further investigation of risk stratification by average length of stay in the reporting hospitals is warranted as a way to improve the comparability of indicators across hospitals and surveillance systems. In spite of methodological issues, the surveillance of CDI in Belgian hospitals has been able to produce robust baseline data that should allow monitoring of trends at hospital and national level, and provide a basis for international comparisons. Remaining challenges are to define and monitor targets for the control of CDI, and to improve the individual feed-back of data at hospital level.
Soluble E-Selectin Levels in Sepsis and Critical Illness
Authors: C. JAMES CUMMINGS, CURTIS N. SESSLER, L. DAWSON BEALL, BERNARD J. FISHER, AL M. BEST, ALPHA A. FOWLER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

E-selectin, an early mediator of leukocyte-endothelial adhesion, is expressed on activated endothelium. Soluble E-selectin is present in the supernatant of cytokine-activated endothelial cells and elevated serum levels are found in a variety of inflammatory conditions. We documented elevated E-selectin serum levels in 119 critically ill medical ICU patients (log transformed mean E-selectin level, measured by ELISA, was 5.28 ng/ml) compared to normal volunteers (1 ng/ml). Forty-three patients with culture-positive sepsis had higher (p < 0.05) E-selectin levels (15.39 ng/ml) than 24 patients with culture-negative sepsis (4.87 ng/ml), 44 with noninfectious SIRS (2.33 ng/ml), and eight without SIRS (1.97 ng/ml). E-selectin levels related strongly to the degree of hemodynamic compromise (p < 0.0001). Further analysis demonstrated microbiological status and hemodynamic status to be independent variables related to E-selectin level. Day 1 E-selectin levels correlated positively with peak organ failure score over the course of ICU hospitalization (r = 0.30, p = 0.001) and were higher (p < 0.05) for nonsurvivor (10.61 ng/ml, n = 26) than survivors (4.35 ng/ml, n = 93). We conclude that soluble E-selectin levels are higher in serum of patients with microbiologically documented sepsis than in other critically ill medical ICU patients. Day 1 E-selectin levels correlate highly with hemodynamic compromise and modestly with subsequent organ dysfunction and survival.
Guanethidine and related agents
Authors: Jerry R. Mitchell, John H. Cavanaugh, Luis Arias, John A. Oates
Journal: Journal of Clinical Investigation (1970)

Antagonism of the antihypertensive action of guanethidine by the tricyclic antidepressants, desipramine and protriptyline, has been demonstrated in controlled studies. These antidepressants also prevent the effect of the related ring-substituted guanidinium adrenergic neuron blockers, bethanidine and debrisoquin. That the rise in blood pressure when desipramine is added to guanethidine therapy is not due simply to a pressor action of the two drugs in combination was demonstrated by the lack of an increase in blood pressure when guanethidine was added to desipramine therapy. Investigations were conducted to determine whether antagonism of guanethidine's clinical effect could result from blockade by the tricyclic antidepressants of the norepinephrine pump in the adrenergic neuron membrane, thereby preventing the uptake of guanethidine into the neuron by this pump. Like guanethidine, the indirectly acting pressor amine, tyramine, enters the neuron via the norepinephrine pump. Desipramine, protriptyline, and amitriptyline in clinical doses all were found to block the pressor action of tyramine while potentiating the pressor effect of norepinephrine. The amino acid, methyldopa, does not enter the neuron via the norepinephrine pump, and its antihypertensive action is not altered by concomitant administration of tricyclic antidepressants. It is concluded from the evidence in this investigation together with the results of previous studies in experimental animals that clinical doses of desipramine-like drugs inhibit the norepinephrine pump in the peripheral adrenergic neuron in man and thereby prevent uptake of guanethidine to its site of action.
SWOG S1115: Randomized phase II clinical trial of selumetinib (AZD6244; ARRY 142886) hydrogen sulfate (NSC-748727) and MK-2206 (NSC-749607) versus mFOLFOX in patients withmetastatic pancreatic cancer after prior chemotherapy.
Authors: Vincent M. Chung, Shannon McDonough, Philip Agop Philip, Dana Backlund Cardin, Andrew M. Lowy, Jacqueline K. Benedetti, Charles Davic Blanke
Journal: Journal of Clinical Oncology (2013)

TPS4145 Background: Pancreatic cancer remains a deadly disease and despite advances in chemotherapy treatment, survival for most patients is still less than one year. Over 80% of pancreatic cancers are KRAS mutant which activates the PI3K/AKT pathway and signals downstream to mTOR leading to cell growth, proliferation and survival. Recent data has shown that blocking both the PI3K/AKT and MEK pathways simultaneously is effective in KRASmutant tumors. Our trial is a novel, molecular targeted treatment approach for patients with metastatic pancreatic cancer that has the potential to establish a new treatment paradigm. Methods: S1115 was activated in SWOG in August 2012 and is currently IRB approved at 130 institutions within SWOG and the Clinical Trials Support Unit (CTSU). Patients (performance status 0 or 1) with metastatic pancreatic cancer failing standard gemcitabine chemotherapy are randomized to MK-2206 135 mg orally weekly plus selumetinib 100 mg orally daily or mFOLFOX IV every 2 weeks. Eligibility criteria allow metastatic patients who have progressed within 6 months of receiving adjuvant gemcitabine. Patients receiving prior 5-fluorouracil (excluding radiation-sensitizing doses), capecitabine, oxaliplatin, MEK or PI3K/AKT inhibitors are not eligible. Stratification factors include duration of prior systemic therapy and presence of liver metastases. The primary endpoint of this study is overall survival (OS) in patients treated with the combination of MK-2206 and selumetinib compared with those treated with mFOLFOX. Based on previous studies, median OS in the control group is approximately 6 months. Assuming a one-sided type 1 error of 10%, 80% power, approximately 2 years of accrual and 1.5 years of follow-up, 120 eligible patients will be accrued to detect an improvement in median survival from 6 to 9 months (corresponding to a 1.5 hazard ratio). Prospective tumoral tissue collection will be undertaken. ClinicalTrials.gov Identifier: NCT01658943. Support: NCI grants CA32102 & CA38926 Clinical trial information: NCT01658943.