tbuckley/cabot-search huggingface dataset:
Cost-effectiveness of capecitabine in combination with oxaliplatin (XELOX) compared with FOLFOX for the treatment of metastatic colorectal cancer: A Canadian evaluation
Authors: D. Belovich, M. Hux, P. Douglas, J. A. Maroun, N. Sommer
Journal: Journal of Clinical Oncology (2009)

e17502 Background: Capecitabine is an oral fluoropyrimidine used to treat patients with metastatic colorectal cancer (mCRC). Recent trials in 1 st - and 2 nd -line treatment have shown that capecitabine in combination with oxaliplatin (XELOX) is non-inferior to FOLFOX4 in terms of progression-free survival, overall survival and response rates. XELOX offers patients the advantage of treatment every 3 weeks rather than every 2 weeks without the need for lengthy infusions. This analysis evaluated the cost- effectiveness of replacing FOLFOX4 with XELOX for 1 st - and 2 nd -line treatment of mCRC from both Canadian healthcare system payor and societal perspectives. Methods: Based on evidence of non-inferiority of XELOX vs. FOLFOX4, cost-minimization analyses (CMA) were conducted using phase III clinical trial data. The CMA compared total cost associated with chemotherapy medications, administration of chemotherapy, and treatment related toxicities. For the societal perspective, patients’ costs and time were also included. The costs (or savings) were compared for 1 st -line XELOX vs. FOLFOX4 and 2 nd -line XELOX vs. FOLFOX4. Due to variation in Canadian clinical practice, sensitivity analyses using the FOLFOX6 regimen as a comparator were performed. Results: Cost savings per patient for XELOX vs. FOLFOX4 from a healthcare system payor perspective and a societal perspective are shown in the Table . XELOX was also associated with cost savings when compared with the simplified administration regimen of FOLFOX6. Reduced costs for chemotherapy administration and costs for patients’ time and travel primarily related to fewer clinic visits offset the increased drug acquisition cost of the XELOX regimen. Conclusions: Replacing FOLFOX with XELOX is associated with cost savings from the healthcare system payor and societal perspectives while preserving clinical efficacy. [Table: see text] [Table: see text]
Predictive value of PSA halving index (PSAHI) in patients (pts) with hormone refractory prostate cancer (HPRC): Results from a randomized phase II trial with docetaxel (D) ± estramustine phopshate (E)
Authors: T. Sava, E. Comploj, G. Fariello, F. Zustovich, R. Segati, C. Sacco, A. Perin, M. Mandarà, G. Cetto, O. Caffo
Journal: Journal of Clinical Oncology (2007)

15548 Background: D-based chemotherapy represents the standard treatment for HRPC pts. For several years PSA has been considered as a surrogate endpoint for studies involving pts with HRPC. The possibility of predicting a clinical advantage through the biochemical response rate is controversial. The PSAHI may represent a predictive parameter more than the simple PSA trend. We retrospectively evaluated the role of PSAHI in a consecutive series of patients affected by HRPC and treated in a randomized phase II trial with D±E. Methods: 95 pts affected by HRPC were randomized to D 70 mg/m 2 IV d1 q3w (arm A: 49 pts) or D 70 mg/m 2 IV d1 q3w + E 280 mg/TID PO starting 1 day prior to D, for 5 consecutive days (arm B: 46 pts). The treatment continued until best PSA response achievement or PSA progression. PSAHI was calculated comparing basal value (the day before first D administration) with those reached after every cycle at 21, 42, 63 and 84 days: each median value was then correlated across all pts. Correlations were made with response, time to progression (TTP) and overall survival (OS). Results: Responses, in terms of PSA? &gt;50% were: 40% in arm A and 75%in arm B with PSA normalization in 5% and 32% respectively. After a median follow-up of 17 months, 65 patients are died (31 in Arm A and 34 in Arm B). Progression free survival (biochemical) was 20 weeks in arm A and 30 in B. Median PSAHI was 2.1 (0.8–8.8) and resulted significantly related to response and TTP: pts with PSAHI less than 1 and more than 1 had a median TTP of 14 and 34 weeks respectively. Between the 4 PSAHI analyzed (after 21, 42, 63 and 84 day), those at 42 and, particularly, 63 day resulted statistically related to response, TTP and OS. After 3 cycles, the PSA decline (63-PSAHI) was highly predicyive of OS which was 63, 72 and 90 weeks respectively (p=0.03), for pts with PSAHI of less than 1, between 1 and 3 and more than 3. Conclusions: PSAHI seems to be highly predictive of TTP and OS. 63-PSAHI seems to be a good surrogate marker of D response and may help in discriminating pts who need to be further treated with D and those who do not. No significant financial relationships to disclose.
Effects of aclidinium on respiratory function in guinea pigs chronically exposed to cigarette smoke
Authors: Elisabet Ferrer, David Domínguez-Fandos, Raquel Puig-Pey, Cristina Carreño, Mònica Aparici, Jorge Beleta, Neus Prats, Amadeu Gavaldà, Montserrat Miralpeix, Victor I. Peinado, Joan Albert Barberà
Journal: European Respiratory Journal (2011)

Introduction: Chronic obstructive pulmonary disease is characterised functionally by decreased respiratory function due to airflow obstruction.

Aims: To evaluate the effects of aclidinium bromide, a novel muscarinic antagonist, on respiratory function and signs of bronchial irritation in guinea pigs chronically exposed to cigarette smoke (CS).

Methods: Male guinea pigs (n=46) were divided into 2 groups: control (n=22) and CS-exposed (n=24, 6 cigarettes/day, 5 days/week for 24 weeks). Animals received vehicle, aclidinium 10μg/mL or aclidinium 30μg/mL for 6 months. Respiratory function was evaluated twice-weekly using the enhanced pause (Penh) parameter, before CS exposure (24 h after last exposure; baseline) and 10 min after CS exposure. Changes in Penh were assessed as the area under the curve. The number of cough episodes in the first minute post CS exposure and the number of respiratory crises were monitored throughout the study period.

Results: Exposure to CS increased Penh at baseline and 10 min after CS exposure. Compared with CS-exposed non-treated animals, treatment with aclidinium 30μg/mL resulted in a lower increase in Penh after CS exposure (vehicle vs aclidinium 30μg/mL: 110.6±26.7 vs 71.4±32.4; p=0.016). CS exposure resulted in cough episodes and respiratory crises which were attenuated by aclidinium 30μg/mL.

Conclusions: In guinea pigs chronically exposed to CS, aclidinium 30μg/mL improved respiratory function by significantly reducing the increase in Penh after CS exposure and reducing the development of cough and respiratory crises.

This study was supported by Almirall S.A., Barcelona, Spain, and Consorcios Estrategicos Nacionales en Investigaciόn Tecnica (CENIT).
Tobacco and marijuana co-use among high school students in the US using the YRBSS (2009 & 2011)
Authors: Mayowa Olusunmade, Itegbemie Obaitan, Filippos Filippidis, Israel Agaku, Constantine Vardavas
Journal: European Respiratory Journal (2014)

Introduction: The most widely used drugs among adolescents in the US are tobacco and marijuana. The purpose of the present study was to determine the predictors of their co-use as no recent studies have been done to demonstrate this. Our aim was to test the hypothesis that there is no differences in pattern of co-use of tobacco and marijuana across levels of age, sex and race/ethnicity.  Methods: Data from the 2009 and 2011 waves of the Youth Risk Behavior Survey (n=31,385) were analyzed through STATA 11.0. Indexes were self reported and anonymous. The secondary analysis was IRB exempt: IRB14-0346.  Results: Among participants, 18% had smoked tobacco in the past one month while 22% had used marijuana, with 11% of smokers reporting co-use of tobacco and marijuana in the past month. A chi-square test for trend showed increasing co-use with increasing age of adolescents (P 15yrs (OR= 1.64 P  Conclusion: This study demonstrates that current co-use of tobacco and marijuana is significantly predicted by race/ethnicity. Co-use among adolescents also increased with age and was more common among males. These preliminary findings identify the need to assess through further research the impact of concurrent tobacco and marijuana use on addiction and health outcomes among adolescents.
사례보고 : 칡즙 복용 후 발생한 독성간염 2예
Authors: 김승영 ( Seung Young Kim ), 임형준 ( Hyung Joon Yim ), 안재홍 ( Jae Hong Ahn ), 김정한 ( Jeong Han Kim ), 김진남 ( Jin Nam Kim ), 윤익 ( Ik Yoon ), 김동일 ( Dong Il Kim ), 이홍식 ( Hong Sik Lee ), 이상우 ( Sang Woo Lee ), 최재현 ( Jai Hyun Choi )
Journal: Clinical and Molecular Hepatology (2009)

건강에 대한 관심 증가와 함께 대체요법의 사용이 늘어나면서 각종 식물제제를 포함한 건강보조식품으로 인한 부작용들이 나타나고 있다. 저자들은 칡즙을 복용한 후 발생한 독성간염 두 예를 경험하여 보고한다. 환자들은 구역, 구토 등으로 내원하였으며, 입원 후 혈액생화학검사, 혈청검사 및 간조직검사를 시행받았고 RUCAM 점수체계를 기준으로 독성간염으로 진단되었다. 이들은 보존적 치료 후 검사실 소견 및 순간탄성도검사 등에서 빠른 호전을 보였다. 칡즙의 복용으로도 독성간염이 생길 수 있다는 점을 염두에 두고, 건강보조식품에 대한 경각심을 가져야겠다.
Thyroid Cancer: Cohort Analysis of Increasing Incidence in New York State, 1941–1962&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Robert E. Carroll, M.D., William Haddon, Jr., M.D., Vincent H. Handy, M.D., Edward E. Wieben, Sr.
Journal: JNCI Journal of the National Cancer Institute (1964)

Thyroid cancer incidence rates based on cases reported to the New York State Cancer Registry have more than doubled from 1941–62. The increase has occurred only in persons under age 55. Cohorts born prior to 1900 have about the same incidence at each age. After 1910 the rate at each age approximately doubles for each successive decade of birth. Changes in reporting and diagnosis cannot account for the increase, which seems to reflect a true increase in the disease. The change in the cohort pattern about 1910 coincides with the onset of X-ray therapy for thymic enlargement and strongly supports the hypothesis that irradiation in infancy and childhood is a significant causal factor in thyroid cancer. A method of cohort analysis allowing more precise determination of the year of change in cohort rates is described in the Appendix.
Cycle of abuse goes on : Remember referral for imaging is referral for an opinion
Authors: Derrick Martin
Journal: BMJ (2003)

Editor—Your author, anonymous to us and his radiologist, demanded magnetic resonance imaging and got short shrift.1 The radiologist was probably reporting magnetic resonance—numerous images, taking concentration and time to influence treatment. Because disturbance breaks concentration, increasing error, she was probably as irritated as he would be if disturbed during a ward round. Would he expect to make a surgical referral by a personal appearance in theatre?

We have half the number of radiologists we need. The need for diagnosis and staging demanded by the Cancer Plan is increasing: surgeons wish to image before operating; we need to police the use of radiation and manage the demands of training if more national training numbers are to allow us to dig ourselves out of the manpower hole. Is it surprising that radiologists feel tetchy?

The Royal College of Radiologists asserts that we are clinical radiologists—referral for imaging is a referral for an opinion, clinical information allowing the radiologist to select the method of imaging. Would he or she refer his patient for surgery by demanding hypophysectomy or by asking the surgeon's advice? The appropriate use of limited resources in imaging is where radiologists can help. We want to provide clinically based services but demands for imaging based on ill conceived clinical strategies only frustrate us. The constant flow of juniors sent to demand imaging and intervention but unable to provide clinical information tests our patience.

Your author needs some humility. He should find his colleague and apologise for his arrogance in disturbing her while she was busy, not introducing himself, treating her as a technician rather than a fellow clinician, and making the assumption that his own view of this encounter is the only tenable view. He will find that she is only too willing to provide his patients with the imaging service they need.
Metabolic Impact of Nonalcoholic Steatohepatitis in Obese Patients With Type 2 Diabetes
Authors: Romina Lomonaco, Fernando Bril, Paola Portillo-Sanchez, Carolina Ortiz-Lopez, Beverly Orsak, Diane Biernacki, Margaret Lo, Amitabh Suman, Michelle H. Weber, Kenneth Cusi
Journal: Diabetes Care (2016)

Nonalcoholic steatohepatitis (NASH) is increasingly common in obese patients. However, its metabolic consequences in patients with type 2 diabetes mellitus (T2DM) are unknown.We studied 154 obese patients divided in four groups: 1) control (no T2DM or NAFLD), 2) T2DM without NAFLD, 3) T2DM with isolated steatosis, and 4) T2DM with NASH. We evaluated intrahepatic triglycerides by proton MRS ((1)H-MRS) and assessed insulin secretion/resistance during an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp with glucose turnover measurements.No significant differences among groups were observed in sex, BMI, or total body fat. Metabolic parameters worsened progressively with the presence of T2DM and the development of hepatic steatosis, with worse hyperinsulinemia, insulin resistance, and dyslipidemia (hypertriglyceridemia and low HDL cholesterol) in those with NASH (P < 0.001). Compared with isolated steatosis, NASH was associated with more dysfunctional and insulin-resistant adipose tissue (either as insulin suppression of plasma FFA [33 ± 3 vs. 48 ± 6%] or adipose tissue insulin resistance index [9.8 ± 1.0 vs. 5.9 ± 0.8 mmol/L ⋅ µIU/mL]; both P < 0.03). Furthermore, insulin suppression of plasma FFA correlated well with hepatic steatosis (r = -0.62; P < 0.001) and severity of steatohepatitis (rs = -0.52; P < 0.001). Hepatic insulin sensitivity was also more significantly impaired among patients with T2DM and NASH, both fasting and with increasing insulin levels within the physiological range (10 to 140 µIU/mL), compared with other groups.In obese patients with T2DM, the presence of NAFLD is associated with more severe hyperinsulinemia, dyslipidemia, and adipose tissue/hepatic insulin resistance compared with patients without NAFLD. The unfavorable metabolic profile linked to NAFLD should prompt strategies to identify and treat this population early on.
Similarity of reverse transcriptase-like sequences of viruses, transposable elements, and mitochondrial introns.
Authors: Y Xiong, T H Eickbush
Journal: Molecular Biology and Evolution (1988)

Sequences similar to reverse transcriptase (RT) of retroviruses have been found in certain DNA viruses, mitochondrial intron sequences, and a wide variety of transposable elements. While total amino acid similarity between these diverse elements is quite low, we have identified seven regions, consisting of 182 amino acids, that are common to all elements. Highly conserved residues identified in each of these regions are diagnostic for the identification and alignment of these and for future RT-like sequences. Using both the neighbor-joining and the unweighted-pair-group methods, we have derived a probable phylogenetic tree for all RT-containing elements. These elements can be divided into two major groups. Retroviruses and DNA viruses whose propagation involves an RNA intermediate are grouped with a series of transposable elements containing long terminal repeats (LTRs). The second group is made up of RT-containing sequences of fungal mitochondrial introns and a series of transposable elements that lack LTRs. The transposable elements, copia and Ty, were found to be the most difficult to position on the phylogenetic tree, as a result of their higher rate of sequence divergence. The data are most consistent with their being distant members of the LTR group (retroviruses/LTR retrotransposons).
A patient-based utility measure of health for clinical trials of cancer therapy
Authors: A. S. Pickard, J. W. Shaw, H. Lin, P. C. Trask, N. K. Aaronson, T. A. Lee, D. Cella
Journal: Journal of Clinical Oncology (2008)

6529 Background: The EORTC QLQ-C30 is a widely used measure of quality of life in oncology clinical trials. The ability to generate utility scores and calculate quality-adjusted life years would further expand its use. The aim of this study was to develop utility mapping algorithms for the QLQ-C30 using utilities for own health elicited from cancer patients. Methods: Using data from 1,432 patients, two distinct approaches were applied. A conventional multi-attribute health state (MAHS) approach employed psychometric analysis and expert input to identify items from the functioning and symptom scales for model development. Second, using a conceptual model of health preference formation, models were developed using global health and quality-of-life (QoL) items. All models were fit using quantile regression and robust bootstrap variance estimators. Criteria for model selection included parsimony, statistical significance and logical consistency of parameter estimates, number of unique states, and range of scale. Predictive accuracy was evaluated using a 10-fold cross- validation approach. Results: The best-fitting MAHS model included one or more items from each scale except Emotional Functioning. The model included 14 parameters, described 2,304 unique states, and predicted values ranging from 0.61 to 1.00. However, it had poor predictive accuracy (cross-validation pseudo-R2=0.073), and most parameter estimates were insignificant. The best-fitting QoL approach-based model described 24 unique states using 9 parameters (all of which were significantly significant), predicted values ranging from 0.17 to 1.00, and exhibited better fit statistics than the MAHS model (e.g., cross-validation pseudo-R2=0.127). Conclusions: Using conventional and novel methodologies, utility-mapping algorithms were developed for the QLQ-C30. Each approach yielded algorithms with different strengths and weaknesses. Notably, the QoL-based model has more desirable statistical properties and a wider range of scale, while the MAHS-based model produces a far greater number of unique predicted values. Both algorithms may be used to predict patient preferences for own health to inform economic evaluations of cancer therapeutics. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology
Elevation of serum napsin A levels in patients with hypersensitive pneumonia
Authors: Tomohiro Kumamoto, Asami Harumatsu, Kouta Sakaue, Tsutomu Hamada, Masuki Yamamoto, Tetsurou Hamasaki, Keiko Mizuno, Ikkou Higashimoto, Takuya Samukawa, Hiromasa Inoue
Journal: European Respiratory Journal (2013)

Background: Napsin A, an aspartic protease, is mainly expressed in alveolar type II cells and renal proximal tubules. We previously reported increased napsin A levels in patients with IPF, compared with healthy controls. However, serum napsin A levels in patients with hypersensitive pneumonia (HP) have never been evaluated.

Aims: To evaluate the level of napsin A in patients with HP and correlation between napsin A and other parameters.

Methods: Ten patients with HP, and nineteen patients with idiopathic interstitial pneumonia (IIP) who had been admitted to our institution and thirty-three healthy controls were enrolled. Serum napsin A levels were measured by ELISA. Serum SP-A, SP-D, and KL-6 levels, pulmonary function, and immunohistochemistry for napsin A were also evaluated in patients with HP.

Results: Serum napsin A levels were significantly increased in patients with HP, compared with healthy controls and IIP (331.4±198.6 ng/mL, 26.9±28.9 ng/mL, 167.1±180.7 ng/mL, respectively, p <0.05). In patients with HP, serum napsin A levels had negative correlation with DLco (r=-0.736, p <0.01). Immunohistochemistry for napsin A in patients with HP revealed high expression in alveolar epithelium cells. In the case of HP, serum napsin A levels were decreased by antigen avoidance.

Conclusion: Serum napsin A might be useful as a biomarker for HP.
Combined loss of M2 and M3 muscarinic acetylcholine receptor (mAChR) function in mutant mice increases serotonin airway responsiveness (AR)
Authors: John Fisher, Sandra Vincent, Paul Wannas, Jurgen Wess
Journal: European Respiratory Journal (2014)

The lack of mAChR-subtype selective antagonists has made it difficult to define mAChR airway biology. Mutant murine models lacking specific mAChR subtypes are an important experimental tool to define the  in vivo  role of M2 and M3 mAChRs in AR. Since lack of M3 function results in loss of  in vivo  ACh AR ( FASEB J  18:711,2004), 5-hydroxytryptamine (5-HT) can be used to assess changes in respiratory system resistance (Rrs) to an  i.v.  dose-response challenge (5-100 μg/kg). We investigated the impact of combined loss of M2 and M3 function on the 5HT AR phenotype in M2  -/-  /M3  -/-   double mutant mice. AR to 5HT was assessed in 8 wildtype (WT) and 6 mutant mice that received Alum adjuvant exposure. The Rrs response to 5HT was significantly greater in the M2  -/-  /M3  -/-   than in the WT mice (max increase 301%+28 vs 102%+ 28.4; p  -/-  /M3  -/-   mice (100% inhibition). We conclude that loss of M2/M3 function causes an upregulation of 5HT airway responsiveness, which may reflect a change in 5HT receptor expression. Although the molecular mechanisms responsible for the altered phenotype are unclear, our results are an important consideration for the use of mutant mAChR murine models to explore the mechanisms responsible for the development of allergic airway hyperresponsiveness and remodeling.  Supported by the Canadian Institutes of Health Research & Ontario Thoracic Society (JF - MOP81211) and the Intramural Research Program of the NIDDKD (JW).
Gastroenterology training in Europe-unmet educational needs beyond the machines: response from the European Section and Board of Gastroenterology
Authors: Ian G Barrison, Jean-Paul Jacques
Journal: Gut (2015)

Ianiro and Gasbarrini suggest that the role of the European Section and Board of Gastroenterology (ESBGH) has been 'lost in translation'. 1ata on the timeline and distribution of our recognised training centres are used to suggest that there has been a decline in training centre applications which may be a marker for problems in specialist gastroenterology training across Europe.The initial preponderance of numbers of training centres in the UK was due to the enthusiastic recruitment of UK centres by the UK National delegate in the late 1990s, and does not reflect in any way on the quality of training across Europe.This does however account for the apparent relative decline in the numbers of training centres applying for and obtaining ESBGH approval, which has been steady year on year for the last 10 years.The ESBGH has provided a curriculum (the Blue Book) in 2012, 2 and introduced a high-quality knowledge-based examination in 2014 in collaboration with the British Society of Gastroenterology and the Royal College of Physicians, with the aim of setting standards for the training of specialists throughout Europe. 3 These measures, in conjunction with our responsibility for assessing all Gastroenterology and Hepatology CME approval applications to UEMS, and our commitment to workforce development, underpin our determination to support our colleagues to deliver the highest standards of care to patients in all parts of Europe.