tbuckley/cabot-search huggingface dataset:
Activity of the combination of bevacizumab (Bev) with capecitabine/irinotecan (CapIri/Bev) or capecitabine/oxaliplatin (CapOx/Bev) in advanced colorectal cancer (ACRC): A randomized phase II study of the AIO Colorectal Study Group (AIO trial 0604)
Authors: A. C. Reinacher-Schick, S. Kubicka, W. Freier, D. Arnold, G. Dietrich, M. Geissler, S. Hegewisch-Becker, U. Graeven, H. Schmoll, W. Schmiegel
Journal: Journal of Clinical Oncology (2008)

4030 Background: The combination of Bev with 5-FU/FA and irinotecan or oxaliplatin is highly active in ACRC. A recent phase III trial demonstrated that infusional 5-FU and capecitabine (cape) have comparable efficacy when combined with oxaliplatin and Bev (Cassidy et al. 2007). In contrast, data are heterogeneous for cape/irinotecan combinations. This randomized phase II trial compared safety and efficacy of Bev with either CapOx or CapIri as first line therapy in ACRC. Methods: Prerequisites were: untreated ACRC, ECOG PS≤2, measurable lesion(s), adequate hematologic and organ functions. Primary endpoint in this non- comparative design was progression-free survival (PFS) rate after 6 months (mos). Regimen: Bev 7.5 mg/kg day (d)1 with either oxaliplatin (130 mg/m2 d1)/cape (1,000 mg/m2 bid d1–14; CapOx/Bev, arm A) or irinotecan (200 mg/m2 d1)/cape (800 mg/m2 bid d 1–14; CapIri/Bev, arm B), all q d22. Arm B doses were reduced by 20% for both, cape and irinotecan, compared to previous trials reporting unacceptable GI toxicity (Köhne et al., Ann Oncol 2007; Fuchs et al., J Clin Oncol 2007). Results: From July 2005 to Oct 2006, 255 patients (pts) were randomised. Patient characteristics (arm A/B): Median age 64/65 yrs, male 67%/68%, ECOG 0/1/2 52/45/3% and 52/45/2%, colon 60%/64%, rectum 40%/36%, respectively. Data are available for 244 (124/120) pts. Treatment characteristics (arm A/B): A total of 965/1069 cycles (median 8/9 cycles) have been administered. For 198 pts the end of treatment has been documented: 34% (30%/38%) due to progression, 29% (41%/18%) due to toxicity, 20% (16%/24%) because of pts´ decision. Most common CTC gr. 3/4 toxicities of pts, arm A/B: Diarrhea 19%/15%, hand-foot-syndrome 10%/7%, peripheral neuropathy 23%/0% Tumor response rates (CR+PR) were 54%/55%, tumor control rates (incl. SD) were 79%/80%. PFS rate at 6 mos were 78%/84%, median PFS 9.9/12.5 mos. Conclusions: Both regimen are highly active and safe. The absense of neuropathy favours the CapIri/Bev combination. Interestingly, the dose reduction of CapIri seemingly improves tolerability without compromising efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Pharma, sanofi-aventis Merck, Roche Pharma, sanofi-aventis GmbH Merck, Roche Pharma, sanofi-aventis GmbH Roche Pharma GmbH, sanofi-aventis GmbH
Thioacetamide-induced liver regeneration involves the expression of cyclooxygenase 2 and nitric oxide synthase 2 in hepatocytes
Authors: Amalia Fernández-Martı́nez, Nuria A Callejas, Marta Casado, Lisardo Boscá, Paloma Martı́n-Sanz
Journal: Journal of Hepatology (2004)
Evaluation of co-trimoxazole in the treatment of multidrug-resistant tuberculosis
Authors: Noor Alsaad, Richard van Altena, Arianna D. Pranger, Dick van Soolingen, Wiel C.M. de Lange, Tjip S. van der Werf, Jos G.W. Kosterink, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2012)

Co-trimoxazole (SXT), a combination of sulfamethoxazole and trimethoprim, has shown in vitro activity against Mycobacterium tuberculosis . However, the pharmacokinetic and pharmacodynamic parameters of SXT in multidrug-resistant (MDR) tuberculosis (TB) are, thus far, lacking. Therefore, we evaluated its pharmacokinetics and drug susceptibility, along with its tolerability during treatment. Based on drug susceptibility testing, MDR-TB patients received SXT as a part of their MDR treatment. The pharmacokinetic parameters of sulfamethoxazole, the effective component of SXT against M. tuberculosis , were evaluated. The ratio of the area under the curve from 0 to 24 h (AUC 0–24 ) to minimum inhibitory concentration (MIC) was used as the best pharmacokinetic/pharmacodynamic parameter to predict the efficacy of sulfamethoxazole. Adverse effects of SXT were also evaluated. 10 patients with MDR-TB (one of whom had extensively drug-resistant TB) received 480 mg of SXT with a median dosage of 6.5 mg·kg −1 of SXT (range 6.1–6.8 mg·kg −1 ) once daily for a median treatment period of 381 days (range 129–465 days). In two patients, the dose was escalated to 960 mg. The free AUC 0–24 /MIC of sulfamethoxazole exceeded 25 in only one patient. SXT was safe and well-tolerated, except for one patient who had gastrointestinal side-effects after receiving 960 mg of SXT. Additional studies are needed to find the pharmacokinetic and pharmacodynamic targets, and consequently to set the optimal dose, of SXT for MDR-TB treatment.
Cancer, Heart Disease, and Diabetes in Workers Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin
Authors: K. Steenland, L. Piacitelli, J. Deddens, M. Fingerhut, L. I. Chang
Journal: JNCI Journal of the National Cancer Institute (1999)

In 1997, the International Agency for Research on Cancer classified 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a group 1 human carcinogen, based largely on four highly exposed industrial cohorts that showed an excess of all cancers combined. In this study, we extended the follow-up period for the largest of these cohorts by 6 years and developed a job-exposure matrix.We did cohort mortality analyses involving 5132 chemical workers at 12 U.S. plants by use of life table techniques (U.S. population referent) and Cox regression (internal referent). We conducted exposure-response analyses for 69% of the cohort with adequate work history data and adequate plant data on TCDD contamination. All P values are two-sided.The standardized mortality ratio (SMR) for all cancers combined was 1.13 (95% confidence interval = 1.02-1.25). We found statistically significant positive linear trends in SMRs with increasing exposure for all cancers combined and for lung cancer. The SMR for all cancers combined for the highest exposure group was 1.60 (95% confidence interval = 1.15-1.82). SMRs for heart disease showed a weak increasing trend with higher exposure (P = .14). Diabetes (any mention on the death certificate) showed a negative exposure-response trend. Internal analyses with Cox regression found statistically significant trends for cancer (15-year lag time) and heart disease (no lag).Our analyses suggest that high TCDD exposure results in an excess of all cancers combined, without any marked specificity. However, excess cancer was limited to the highest exposed workers, with exposures that were likely to have been 100-1000 times higher than those experienced by the general population and similar to the TCDD levels used in animal studies.
High-dose therapy followed by autologous stem-cell transplantation with and without rituximab for primary treatment of high-risk diffuse large B-cell lymphoma
Authors: B. Glass, M. Ziepert, M. Reiser, M. Freund, L. Trümper, B. Metzner, A. Feller, M. Loeffler, M. Pfreundschuh, N. Schmitz
Journal: Annals of Oncology (2010)
Six year longitudinal study of respiratory function in dairy farmers in the Doubs province
Authors: JC Dalphin, MF Maheu, A Dussaucy, D Pernet, JC Polio, A Dubiez, JJ Laplante, A Depierre
Journal: European Respiratory Journal (1998)

A previous study, carried out in 1986 in France, showed the prevalence of respiratory symptoms and of respiratory function impairment to be higher in dairy farmers than in a control group of nonexposed subjects living in a rural zone. In order to confirm the harmful effect of dairy farming, the two groups were re-studied 6 yrs later at the same period of the year. One hundred and ninety-four (77.6%) farmers and 155 (62%) control subjects were available for re-examination. Non-re-evaluated subjects were comparable to re-evaluated subjects for age, sex, smoking and respiratory symptoms and function at initial evaluation. Dairy farmers consistently had more respiratory symptoms and lower levels of respiratory function than did control subjects. In the study populations as a whole, the mean annual decline in vital capacity (VC) and forced expiratory volume in one second (FEV1) was slightly, but nonsignificantly, higher in farmers than in control subjects: in mL x yr(-1) (SD), -43.1 (68.2) versus -37.9 (60.2) for VC and -32.8 (56.7) versus -30 (47.2) for FEV1. There was a positive interaction between farming and age (i.e. duration of exposure in this cohort) on respiratory function decline, and in male subjects aged &gt; or = 45 yrs, dairy farming was associated with an accelerated loss in VC (p&lt;0.05) and FEV1 (p&lt;0.05) after controlling for age, smoking, height and geographic location in a multiple linear regression model. Initial values of respiratory function, age and pack-years smoked (only for VC) were the other variables found to be significant determinants of decline in lung function. In conclusion, this study mainly suggests that dairy farming is associated to a very moderate accelerated loss in respiratory function that increases with duration of exposure and is significant in older male subjects.
Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Progressive or Recurrent Ovarian Cancer
Authors: Gabriella Ferrandina, Manuela Ludovisi, Domenica Lorusso, Sandro Pignata, Enrico Breda, Antonella Savarese, Pietro Del Medico, Laura Scaltriti, Dionyssios Katsaros, Domenico Priolo, Giovanni Scambia
Journal: Journal of Clinical Oncology (2008)

We aimed at investigating the efficacy, tolerability, and quality of life (QOL) of gemcitabine (GEM) compared with pegylated liposomal doxorubicin (PLD) in the salvage treatment of recurrent ovarian cancer.A phase III randomized multicenter trial was planned to compare GEM (1,000 mg/m(2) on days 1, 8, and 15 every 28 days) with PLD (40 mg/m(2) every 28 days) in ovarian cancer patients who experienced treatment failure with only one platinum/paclitaxel regimen and who experienced recurrence or progression within 12 months after completion of primary treatment.One hundred fifty-three patients were randomly assigned to PLD (n = 76) or GEM (n = 77). Treatment arms were well balanced for clinicopathologic characteristics. Grade 3 or 4 neutropenia was more frequent in GEM-treated patients versus PLD-treated patients (P = .007). Grade 3 or 4 palmar-plantar erythrodysesthesia was documented in a higher proportion of PLD patients (6%) versus GEM patients (0%; P = .061). The overall response rate was 16% in the PLD arm compared with 29% in the GEM arm (P = .056). No statistically significant difference in time to progression (TTP) curves according to treatment allocation was documented (P = .411). However, a trend for more favorable overall survival was documented in the PLD arm compared with the GEM arm, although the P value was of borderline statistical significance (P = .048). Statistically significantly higher global QOL scores were found in PLD-treated patients at the first and second postbaseline QOL assessments.GEM does not provide an advantage compared with PLD in terms of TTP in ovarian cancer patients who experience recurrence within 12 months after primary treatment but should be considered in the spectrum of drugs to be possibly used in the salvage setting.
GUESSTIMATING BODY MASS INDEX (BMI): HOW GOOD ARE WE, REALLY?
Authors: O Jagun, G Chan, W J Tee, Z Ahmed, S Brady, Z Elsafty, H Martin, M Buckley, S Sarwar, C Smyth, R Farrell
Journal: Gut (2013)

<h3>Introduction</h3> According to the World Health Organisation definition, the body mass index (BMI) is a simple index of weight-for-height that is commonly used to classify overweight and obesity in adults. Although it has it9s limitations it provides the most useful population-level measure of overweight and obesity as it is the same for both sexes and for all ages of adults. Visual estimation of BMI is routinely used in the clinic setting to direct lifestyle advice. Identifying the correct BMI is particularly important in gastroenterology as we frequently manage patients with malabsorption, chronic inflammatory diseases and liver disease. <h3>Aims/Background</h3> To evaluate and compare the positive predictive value (PPV), negative predictive value (NPV) sensitivity and specificity of prediction of overweight/obese in gastroenterology patients among doctors and nurses. Also, to assess for individual bias in the physicians making the judgements based on their own BMI calculations. <h3>Method</h3> For the purposes of our study, BMI was defined as &lt;18=underweight, 18–24.9=normal, 25–29.9=overweight and &gt;30=obese. All consecutive patients attending the gastroenterology clinic in the month of December 2012 were recruited prospectively. The patients9 BMI were measured using Seca weight and height measuring devices in clinic. BMI estimation sheets were distributed to the four junior doctors and the clinic nurse at each clinic over a one-month period. The estimations between the two groups were blinded as to prevent any bias. <h3>Results</h3> In total, 80 patients were recruited of which there were 48(60%) males and 32(40%) female patients, mean age 46.4±14.6 years. The mean weight was 77.3±17.0kg and the mean height was 163.9±9.4 cm. The mean BMI was 29.3±4.3 kg/m2 in males and 28.4±6.7 kg/m2 in females, p=0.500. There were 2 (2.5%) patients who were underweight, 19 (23.8%) who had a normal BMI, 24 (30.0%) who were overweight and 35 (43.8%) who were obese. The PPV, NPV, sensitivity and specificity for the prediction of overweight/obese patients were 90.0%, 73.7%, 91.5% and 70.0% respectively for nurses compared to 94.0%, 60.0%, 79.7% and 85.7% for doctors. It was also found that if doctors were of a normal BMI, they were less likely to predict the correct patients9 BMI compared to those who were overweight, 44.7% vs 100%, p=0.31. <h3>Conclusion</h3> Healthcare professionals were poor at predicting patients9 BMI in the setting of gastroenterology outpatients. There was a trend, particularly among doctors to underestimate patients9 weight. This trend was more common among doctors who were of a normal BMI. Worryingly, approximately three quarter of our patients are overweight or obese, higher than previously reported prevalence by the department of health. To allow for accurate lifestyle and dietary advice, it is important that all patients have their weight and height measured in clinic.
Reassurance: Medically Unexplained Physical Symptoms
Authors: Bill Anderson
Journal: PLoS Medicine (2006)

Escobar et al.'s discussion of medically unexplained physical symptoms is useful, and could trigger a renewal of how the medical profession works [1]. We are in transition at the present, and what we have been trained for is less and less relevant. This disjunction between our training and practise has given rise to a generation of unhappy doctors.

The traditional “doctor” dealt with symptoms and illnesses for which there was no useful explanation and became expert in managing these. We have completed a century or more of science and pathology and have trained doctors to derive their interventions from an (often cursory) consideration of the patient's illness and the application of reason within this scientific framework, in the unshakable belief that this strategy gave the best and at times the only possibility of assisting the patient in a meaningful way. The practical effects of such practices were rarely if ever examined. This approach had many successes but lots of failures, and we have moved on. We now have built upon the science a growing evidence base which to date principally addresses disease states (pathological processes) rather than illnesses (patients' experiences).

There is however no reason why evidence-based approaches cannot be applied to the management of symptoms and illness as well as disease states. As we develop that evidence base, the nature of clinicians can change. We will not require all “doctors,” for want of a better word, to be comprehensively trained in bioscience. There will be more need for them to deploy skills in implementing well-developed, evidence-based interventions and fitting them to the illness the patient is experiencing. Such “doctors” will deliver most care and pay better attention to the patient's symptoms and illness than we do today. We will of course require another different sort of “doctor” who will do the research and the sifting to develop the evidence base upon which therapies will become universally dependent.
A randomized, double-blind comparison of the total dose of 1.0% lidocaine with 1:100,000 epinephrine versus 0.5% lidocaine with 1:200,000 epinephrine required for effective local anesthesia during Mohs micrographic surgery for skin cancers
Authors: Pamela A. Morganroth, Joel M. Gelfand, Anokhi Jambusaria, David J. Margolis, Christopher J. Miller
Journal: Journal of the American Academy of Dermatology (2009)
Hypoxia-Inducible Factor-1 Inhibition in Combination with Temozolomide Treatment Exhibits Robust Antitumor Efficacy <i>In vivo</i>
Authors: Leiming Li, Xiaoyu Lin, Alex R. Shoemaker, Daniel H. Albert, Stephen W. Fesik, Yu Shen
Journal: Clinical Cancer Research (2006)

Inhibiting hypoxia-inducible factor-1 (HIF-1) represents a unique mechanism for cancer therapy. It is conceived that HIF-1 inhibitors may synergize with many classes of cancer therapeutic agents, such as angiogenesis inhibitors and cytotoxic drugs, to achieve a more robust tumor response. However, these hypotheses have not been rigorously tested in tumor models in vivo. The present study was carried out to evaluate the antitumor efficacy of combining HIF-1 inhibition with angiogenesis inhibitors or cytotoxic agents.Using a D54MG-derived tumor model that allows knockdown of HIF-1alpha on doxycycline treatment, we examined the tumor responses to chemotherapeutic agents, including the angiogenesis inhibitor ABT-869 and cytotoxic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and temozolomide, in the presence or absence of an intact HIF-1 pathway.Surprisingly, inhibiting HIF-1 in tumors treated with the angiogenesis inhibitor ABT-869 did not produce much added benefit compared with ABT-869 treatment alone, suggesting that the combination of an angiogenesis inhibitor with a HIF-1 inhibitor may not be a robust therapeutic regimen. In contrast, the cytotoxic drug temozolomide, when used in combination with HIF-1alpha knockdown, exhibited a superadditive and likely synergistic therapeutic effect compared with the monotherapy of either treatment alone in the D54MG glioma model.Our results show that the DNA alkylating agent temozolomide exhibits robust antitumor efficacy when used in combination with HIF-1 inhibition in D54MG-derived tumors, suggesting that the combination of temozolomide with HIF-1 inhibitors might be an effective regimen for cancer therapy. In addition, our results also show that the RNA interference-based inducible knockdown model can be a valuable platform for further evaluation of the combination treatment of other cancer therapeutics with HIF-1 inhibition.
Time to Coronary Angiography and Outcomes Among Patients With High-Risk Non–ST-Segment–Elevation Acute Coronary Syndromes
Authors: Pierluigi Tricoci, Yuliya Lokhnygina, Lisa G. Berdan, Steven R. Steinhubl, Dietrich C. Gulba, Harvey D. White, Neal S. Kleiman, Philip E. Aylward, Anatoly Langer, Robert M. Califf, James J. Ferguson, Elliott M. Antman, L. Kristin Newby, Robert A. Harrington, Shaun G. Goodman, Kenneth W. Mahaffey
Journal: Circulation (2007)

Background— Optimal timing for an early invasive strategy in patients with non–ST-segment–elevation acute coronary syndrome remains unclear. We evaluated the relationship between time from hospital admission to coronary angiography and outcomes in high-risk patients with non–ST-segment–elevation acute coronary syndrome who underwent angiography within 48 hours of admission. Methods and Results— Data from 10 027 patients enrolled in the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial were analyzed. Patients were grouped by 6-hour intervals of time from hospital admission to coronary angiography. Primary outcomes were 30-day death or myocardial infarction, in-hospital Thrombolysis In Myocardial Infarction (TIMI) and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) major bleeding, and blood transfusion. Adjusted estimates of event rates were obtained by use of a multivariable methodology that included possible confounders through baseline and accounted for propensity of time to angiography. The landmark method was used to calculate odds ratios and 95% confidence intervals of outcomes for each time period adjusted for baseline and postbaseline clinical events. Overall, 9216 patients (92%) underwent angiography, 6352 (63%) within 48 hours. Unadjusted and adjusted rates of death/myocardial infarction increased with increasing time to angiography. The adjusted odds ratio for death/myocardial infarction in patients receiving angiography in &lt;6 hours was 0.56 (95% confidence interval 0.41 to 0.74), whereas after 30 hours, there was no significant benefit compared with further delayed angiography. Major bleeding and transfusion did not vary significantly across time-to-angiography intervals. Conclusions— A decrease in the time to coronary angiography was associated with fewer ischemic outcomes and no increase in bleeding. Randomized clinical trials are needed to provide definitive evidence on optimal timing of coronary angiography but are difficult to design and conduct. Ongoing trials should instead clarify whether delaying angiography to administer aggressive upstream antithrombotic therapies is effective in the current setting of non–ST-segment–elevation acute coronary syndrome management.
Use of percutaneous coronary intervention to treat heart attack continues to rise in UK, audit shows
Authors: S. Mayor
Journal: BMJ (2013)

Primary percutaneous coronary intervention (PCI) is now used as the reperfusion strategy in the acute treatment of most patients who have had a heart attack, but large regional variations in its use remain, show the latest results from a UK audit.1

The 2011 annual report from the national audit of percutaneous coronary intervention shows that primary PCI accounted for more than 95% of reperfusion treatment for patients with an ST segment elevation myocardial infarction (STEMI), replacing thrombolysis as the preferred option.

The proportion of patients with STEMI treated with primary PCI, which improves blood flow to the heart by inflating a small balloon that widens narrowed arteries identified by coronary angiography, has more than doubled since 2006, from 11% to 25.1%.

The time to treatment has also improved, …
Microvascular studies in human radiation bowel disease.
Authors: N D Carr, B R Pullen, P S Hasleton, P F Schofield
Journal: Gut (1984)

The microvasculature was investigated in the normal bowel (n = 43 patients) and in radiation bowel disease (n = 18 patients). Tissue samples obtained from postoperative colectomy specimens in which the intramural vessels had been perfused with barium sulphate suspension were examined. Microradiography was used to study vascular pattern which was abnormal in radiation bowel disease. A recently described radiograph fluorescence system was used to estimate barium concentration, and hence microvascular volume. The radiation group showed a highly significant reduction in barium concentration (p less than 0.001), when compared with the normal group. This reduction was diffuse in samples from 15 patients who had received combined intracavity and external radiotherapy, but localised in two patients who had received intracavity treatment only. It is concluded that microvascular compromise is an important factor in the natural history of radiation bowel disease.