tbuckley/cabot-search huggingface dataset:
The use of complementary and alternative medicine in patients with terminal cancer in Korea: Nationwide cross-sectional study
Authors: J. Park, Y. Chang, K. Kang, H. Jeong, D. Moon, S. Kim, Y. Yun
Journal: Journal of Clinical Oncology (2007)

19534 Background: Although the use of complementary and alternative medicine(CAM) is widespread among patients with chronic diseases including cancer, little is known about CAM use in terminal cancer patients. Methods: This study included 4,042 families of cancer patients who died at 17 hospitals in Korea between January and December 2004. We conducted with telephone survey to decedents’ families. The response rate was 41.1%. The questionnaire included whether cancer patients had used CAM during last one year before death, type of modality, motivation for use, attitudes to CAM, and consultation with doctors. Results: CAM use of cancer patients was reported by 36.3% (604 of 1,662) and the average rate of CAM cost was 32% of total medical costs during one year before patient’s death. CAM use was more likely to death at hospitals (adjusted Odds Ratio: 1.35, 95% Confidential Interval: 1.15–1.58), residence in rural (aOR:1.26, 95%CI:1.08–1.47), need consultations about care (aOR:1.65, 95%CI:1.30–2.09) and religious support (aOR:1.3, 95% CI:1.11–1.53), diagnosis except liver/gallbladder cancer (aOR:0.67, 95%CI:0.55–0.81), and longer disease period (aOR:1.85, 95% CI:1.5–2.2). Use was greatest for mushrooms (41.6%), vegetable juice (25.6%), ginseng (21.8%) and Chinese medicine (16.4%). The motivation for CAM use was the recommendations from family members or friends (83.5%) and internet or advertisement (16.1%) but physicians’ recommendation or education (1.4%) was rare. The 37.4% of families of CAM-used patients were satisfied with CAM because of but feeling better or comfortable (79.3%), not cure (5.4%). And otherwise, the 62.1% of them were unsatisfied with CAM because of no effect (87.3%). Only 41.7% CAM users consulted with their physician. Conclusions: This study revealed a high prevalence of CAM use among terminal cancer patients without recommendation from doctors. Medical staffs should evaluate patients’ CAM use and inform accurately about CAM to terminal cancer patients and family for quality of care improvement. No significant financial relationships to disclose.
ME guideline is unworkable
Authors: Charles B Shepherd
Journal: BMJ (2007)

The National Institute for Health and Clinical Excellence (NICE) recommends that everyone with mild or moderate myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) should be offered a course of either cognitive behaviour therapy (CBT) or graded exercise therapy (GET).1

This is despite published evidence remaining weak (especially for group CBT) and inconsistent 2. Patient evidence …
The Paris terror attacks, mental health and the spectre of fear
Authors: Robert E Bartholomew
Journal: Journal of the Royal Society of Medicine (2016)

The year 2015 saw an upsurge in terrorist attacks on Western countries that were reportedly inspired by Islamic State in Iraq and Syria (ISIS). The two most significant incidents occurred in Europe and North America. In Paris on the night of 13 November, a series of coordinated shootings and bombings left 130 dead and 367 wounded. On the morning of 2 December, 14 more were killed and 21 injured in a shooting in San Bernardino, California. A number of less serious incidents have also occurred including the stabbing of three passengers on the London Underground rail network on 5 December. Yet the physical casualties are only part of the story. The less obvious social and psychological after-effects on individuals, groups and society pose a formidable long-term threat that will continue to impact the affected individuals and communities for years to come. For every physical casualty of a terror attack, it is estimated that there are between four and fifty times the number of victims of acute stress and psychological trauma. 1 Historically, attacks have also led
Retinoic acid has the possibility of the treatment for endometrial carcinoma
Authors: H. Utsunomiya, K. Tanabe, N. Takahashi, H. Niikura, T. Takano, K. Yoshinaga, S. Nagase, K. Ito, N. Yaegashi
Journal: Journal of Clinical Oncology (2008)

16594 Background: The retinoids, vitamin A and its biologically active derivatives, are essential for the health and survival of the individual. Several studies have reported a strong rationale for the use of retinoids in cancer treatment and chemoprevention. It has been discovered that expression of retinoic acid receptor (RAR) β is frequently silenced in epithelial carcinogenesis, which has led to the hypothesis that RARβ could act as a tumor suppressor. However, the status of RARβ in human endometrial carcinoma has not been examined. Methods: In this study, we initially studied the effects of retinoic acid on the cell proliferation and the expression of RARα, RARβ, and RARγ using AM580 (a RAR-specific agonist) in the Ishikawa endometrial cancer cell line. We also examined the expression of RARs in human eutopic endometrium (30 cases), endometrial hyperplasia (28 cases), and endometrial carcinoma (103 cases) using immunohistochemistry. Finally we correlated these findings with the clinicopathological parameters. Results: In vitro, the cell growth was inhibited and RARβ and RARγ mRNAs were significantly induced by AM580, compared with vehicle controls, whereas RARα mRNA was significantly attenuated by AM580, compared with vehicle. RARβ was predominantly detected in endometrial hyperplasia, compared with endometrial carcinoma. No statistically significant correlation was obtained between the expression of any other RAR subtypes and clinicopathological parameters in human endometrial carcinoma. Conclusions: The results of our study demonstrated that the expression level of RARβ, which was induced by AM580, had no relation to clinical prognosis in human endometrial carcinoma although AM580 inhibited the cell growth and induced RARβ mRNA expression in Ishikawa cell. Differential expression of different RARβ isoforms, at least in part, might underlie the contradictory associations of RARβ expression. No significant financial relationships to disclose.
Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age-Related Macular Degeneration, by Multimodal Imaging
Authors: Anna V. Zarubina, David C. Neely, Mark E. Clark, Carrie E. Huisingh, Brian C. Samuels, Yuhua Zhang, Gerald McGwin, Cynthia Owsley, Christine A. Curcio
Journal: Ophthalmology (2016)
Demonstrating junior doctors ask Jeremy Hunt to stop misusing statistics
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Credit: Sophie Bergbern

A group of junior doctors and senior academics has delivered a letter of protest to the Department of Health for England to demand that the government stop using statistics that mislead the public over the so called “weekend effect” in hospitals.

The group also delivered a giant cover of Trisha Greenhalgh’s acclaimed textbook on medical statistics, How to Read a Paper , before demonstrating outside parliament on Thursday 21 January. Greenhalgh herself sent the health secretary, Jeremy Hunt, a copy of the book in October 2015.

The campaigners said that they had organised the protest as they were angry …
Involving Patients and the Public–is it Worth the Effort?
Authors: Ruth Chambers
Journal: Journal of the Royal Society of Medicine (2001)

Should patients and the public be involved in planning and delivery of healthcare and services; is it worth the effort? Faced with this question, most professionals feel frustrated that they cannot meet current demands and wary of asking patients what else they want. They do not appreciate the potential advantages of responsible involvement. The question cannot properly be answered without some clarifications.
Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques
Authors: Philip G Conaghan, Mikkel Østergaard, Michael A Bowes, Chunying Wu, Thomas Fuerst, Désirée van der Heijde, Fedra Irazoque-Palazuelos, Oscar Soto-Raices, Pawel Hrycaj, Zhiyong Xie, Richard Zhang, Bradley T Wyman, John D Bradley, Koshika Soma, Bethanie Wilkinson
Journal: Annals of the Rheumatic Diseases (2016)

Objectives To explore the effects of tofacitinib—an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)—with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand. Methods In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p&lt;0.05 (vs MTX monotherapy) were considered significant. Results In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were −1.55 (90% CI −2.52 to −0.58) for tofacitinib + MTX and −1.74 (−2.72 to −0.76) for tofacitinib monotherapy (both p&lt;0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were −0.63 (−1.58 to 0.31) for tofacitinib + MTX and −0.52 (−1.46 to 0.41) for tofacitinib monotherapy (both p&gt;0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy. Conclusions These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage. Trial registration number NCT01164579.
Evaluation of state-of-the-art segmentation algorithms for left ventricle infarct from late Gadolinium enhancement MR images
Authors: Rashed Karim, Pranav Bhagirath, Piet Claus, R. James Housden, Zhong Chen, Zahra Karimaghaloo, Hyon-Mok Sohn, Laura Lara Rodríguez, Sergio Vera, Xènia Albà, Anja Hennemuth, Heinz-Otto Peitgen, Tal Arbel, Miguel A. Gonzàlez Ballester, Alejandro F. Frangi, Marco Götte, Reza Razavi, Tobias Schaeffter, Kawal Rhode
Journal: Medical Image Analysis (2016)

Studies have demonstrated the feasibility of late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging for guiding the management of patients with sequelae to myocardial infarction, such as ventricular tachycardia and heart failure. Clinical implementation of these developments necessitates a reproducible and reliable segmentation of the infarcted regions. It is challenging to compare new algorithms for infarct segmentation in the left ventricle (LV) with existing algorithms. Benchmarking datasets with evaluation strategies are much needed to facilitate comparison. This manuscript presents a benchmarking evaluation framework for future algorithms that segment infarct from LGE CMR of the LV. The image database consists of 30 LGE CMR images of both humans and pigs that were acquired from two separate imaging centres. A consensus ground truth was obtained for all data using maximum likelihood estimation. Six widely-used fixed-thresholding methods and five recently developed algorithms are tested on the benchmarking framework. Results demonstrate that the algorithms have better overlap with the consensus ground truth than most of the n-SD fixed-thresholding methods, with the exception of the Full-Width-at-Half-Maximum (FWHM) fixed-thresholding method. Some of the pitfalls of fixed thresholding methods are demonstrated in this work. The benchmarking evaluation framework, which is a contribution of this work, can be used to test and benchmark future algorithms that detect and quantify infarct in LGE CMR images of the LV. The datasets, ground truth and evaluation code have been made publicly available through the website: https://www.cardiacatlas.org/web/guest/challenges.
A phase I study of cetuximab (cet) in combination with S-1 and irinotecan (iri) (SIRC) in first-line treatment for metastatic colorectal cancer (mCRC) (JACCRO CC-10).
Authors: Akihito Tsuji, Masato Nakamura, Toshiki Masuishi, Masahito Kotaka, Ken Shimada, Mitsugu Kochi, Masahiro Takeuchi, Wataru Ichikawa, Masashi Fujii, Toshifusa Nakajima
Journal: Journal of Clinical Oncology (2015)

735 Background: S-1 combined with iri and cet are also effective treatments in patients (pts) with mCRC. However, diarrhea is one of the concerned toxicities overlapping of each 3 drugs. To evaluate the safety of this combination, we conducted a multi-center phase I study. Methods: The phase I trial was designed to determine the maximum tolerated dose (MTD) and recommended dose (RD) based on a 3+3 cohort expansion design. The cohort at the level of speculated RD was expanded to 10 pts. The main criteria for eligibility was as follows; histologically confirmed mCRC, ECOG PS 0-1, KRAS wild type. The dose adaptation schedule of iri was 125 mg/m2 for level 1 and 150 mg/m2 for level 2. Patients received cet (initial dose 400, and 250 mg/m2 weekly) followed by SIR (iri on day 1 and S-1 40 mg/m2 twice daily on days 1-14). The treatment was repeated every 3 weeks. Dose-limiting toxicity (DLT) was defined as any of the following findings during cycle 1:1) neutrophil count less than 500/mm 3 for 4 days or more; 2) febrile neutropenia; 3) platelet count less than 50,000/mm 3 ; 4) grade 3 or 4 diarrhea; 5) grade 3 or 4 of nonhematologic toxicity, excluding nausea, vomiting, diarrhea, anorexia, and skin toxicities; 5) the number of S-1 administration less than two-third; 6) the delayed start of the second course greater than 1-week as the drug-related toxicity. Results: The MTD was not determined, because DLT was not observed in level 1 (n=3) and level 2 (n=6). Level 2 was speculated to be the RD. Because 4 pts in the expansion cohort experienced no DLT, level 2 was determined as the RD. The completion rate of cycle 4 was 76.9%. Median dose intensities at the level 2 were 97%, 89%, and 91% for iri, S-1, and cet, respectively. During cycle 4 at level 2, grade 3 or worse adverse events were anorexia (20%) and dry skin (10%). The response rate according to RECIST criteria was 62.7% (95% CI, 50.4 to 75.1). Conclusions: We determined 150 mg/m 2 of irinotecan as the RD for SIRC. This combination is tolerable at full doses of cet and SIR, with manageable toxicities. We are now planning the further phase II/III trial including SIRC as an experimental arm. Clinical trial information: UMIN000010639.
Factors associated with tumor recurrence and 5-year postoperative survival in ampullary carcinoma: Cleveland Clinic Experience
Authors: A. Lazaryan, K. Almhanna, P. Elson, S. Kalmadi, D. Vogt, M. Walsh, M. Henderson, R. Pelley, R. D. Kim
Journal: Journal of Clinical Oncology (2008)

15575 Background: Ampullary carcinoma accounts for less than one percent of all GI malignancies. Despite the relatively favorable outcome of resection for ampullary carcinomas, up to one-half of patients recur and ultimately die of tumor recurrence. There are limited contemporary data on prognostic factors of resected ampullary adenocarcinoma. Methods: We performed a retrospective cohort study of 74 patients from 1995 to 2007 with carcinoma of the ampulla of Vater who underwent Whipple procedure at the Cleveland Clinic Foundation. Kaplan-Meier survival curves, log-rank tests, and Cox proportional hazard ratios (HR) were used to analyze the data. Results: Median age of the study population was 71 (60% males, 95% Caucasians). Median hospital stay following surgery was 10 days. R0 resection was successfully achieved in 96% of patients. Median study follow up was 3.2 years, and 5-year survival reached 60%. 19% of patients experienced a tumor relapse within 5 years. 36% of patients received some form of adjuvant therapy following resection. Factors associated with higher rates of tumor relapse included advanced tumor stage T3 or T4 (HR=3.8, p=0.04), African-American ethnicity (HR=4.4, p=0.03), and receiving adjuvant chemotherapy (HR=4.7, p=0.01). Patient age, tumor size, margins, degree of differentiation, number of affected lymph nodes, or elevated level of CA19–9 were not appreciably associated with tumor recurrence (all p>0.1). In the 5-year overall survival analysis, both the perineural invasion (HR=2.9, p=0.04) of adenocarcinoma and its dissemination to regional lymph nodes (HR=2.6, p=0.02) conferred significantly poorer prognosis. Conclusions: Ampullary adenocarcinoma continues to portend an overall better prognosis as compared to pancreatic cancer. Factors associated with poor outcomes in this contemporary single-institution study, included tumor stage, lymph node involvement, perineural tumor invasion, patient ethnicity, and receiving adjuvant therapy. Detrimental effect of adjuvant therapy can be attributed to the fact the patients with unfavorable prognostic factors received adjuvant treatment. No significant financial relationships to disclose.
Incidence and risk of central nervous system (CNS) metastases as a site of first recurrence in patients (pts) with HER2-positive (HER2+) breast cancer treated with adjuvant trastuzumab (T).
Authors: Erin Macrae Olson, Mahmoud Abdel-Rasoul, Christina Sing-Ying Wu, Joseph Maly, Xueliang Jeff Pan, Charles L. Shapiro
Journal: Journal of Clinical Oncology (2012)

609 Background: T is the mainstay of adjuvant therapy in pts with HER2+ breast cancer. CNS disease as the site of first relapse after exposure to adjuvant T has been reported, although the overall incidence and relative risk (RR) of this remains unclear. We performed an up-to-date meta-analysis to determine the risk of CNS metastases as the first site of recurrence in pts with HER2+ breast cancer who received adjuvant T. Methods: Pubmed databases were searched for articles from 1966 to 2011. Abstracts presented at the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium were also searched for relevant clinical trials. Eligible studies include randomized trials with adjuvant T administered for 1 year in pts with HER2+ breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the summary incidence, RR, and 95% CIs using fixed effects inverse variance models. Results: A total of 9,020 pts were included. The incidence of CNS metastases as first site of disease recurrence in HER2+ pts receiving adjuvant T was 2.56% (95% CI 2.07% to 3.01%) compared to 1.94% (95% CI: 1.54% to 2.38%) in HER2+ pts who did not receive adjuvant T. The RR of CNS as first site of relapse in T-treated pts was 1.35 (95% CI 1.02 to 1.78, p=0.038) compared with control arms without T therapy. In subgroup analyses, there was no significant difference in CNS incidence or risk between pts treated with concurrent versus sequential T (p=0.29), weekly versus every 3 week T (p=0.56), and no difference in the T groups between studies due to median follow up time in years (p=0.68). No evidence of publication bias was observed (Q=1.78; P=0.62; I 2 = 0.0%). Conclusions: This is the largest report to date demonstrating that adjuvant T is associated with an increased risk of CNS metastases as a site of first recurrence in HER2+ breast cancer pts.
Size homoplasy and mutational processes of interrupted microsatellites in two bee species, Apis mellifera and Bombus terrestris (Apidae).
Authors: Arnaud Estoup, C. Tailliez, J.M. Cornuet, M. Solignac
Journal: Molecular Biology and Evolution (1995)

Similar microsatellite electromorphs (PCR products of the same size) can arise from independent mutational events. Such alleles are not identical by descent. This phenomenon, termed size homoplasy, was studied by sequencing electromorphs of two microsatellite loci in which the stretch of basic repeats is interrupted by different short (1-2 bp) DNA motifs. The number and position of these interruptions were established for electromorphs from closely and distantly related populations of honeybees and bumblebees. No sequence difference was found when electromorphs came from the same subspecies or from closely related subspecies, suggesting that they were probably identical by descent. In contrast, sequence differences were often detected in distantly related subspecies, showing that size homoplasy frequently occurs at this level of population differentiation. Size homoplasy is increased by limits to free length variation of alleles, a phenomenon that seems to act on interrupted microsatellites when comparing distantly related taxa, that is, honeybee subspecies from different evolutionary lineages. Electromorph sequences suggest that, within the scope of these limits, large mutation events have occurred frequently at both interrupted loci studied. In good agreement with the molecular data, computations based on the observed heterozygosity and number of electromorphs and simulation studies showed that neither locus fits the one-step stepwise mutant model (SMM). We speculate that interrupted microsatellites in general could be characterized by a higher variance in repeat number and consequently a lower homoplasy rate than pure ones. Hence, interrupted microsatellites should be most appropriate for investigating population differentiation and evolutionary relationship between relatively distant populations.
A comparison of two methods for constructing evolutionary distances from a weighted contribution of transition and transversion differences.
Authors: D D Pollock, D B Goldstein
Journal: Molecular Biology and Evolution (1995)

Since the initial work of Jukes and Cantor (1969), a number of procedures have been developed to estimate the expected number of nucleotide substitutions corresponding to a given observed level of nucleotide differentiation assuming particular evolutionary models. Unlike the proportion of different sites, the expected number of substitutions that would have occurred grows linearly with time and therefore has had great appeal as an evolutionary distance. Recently, however, a number of authors have tried to develop improved statistical approaches for generating and evaluating evolutionary distances (Schöniger and von Haeseler 1993; Goldstein and Polock 1994; Tajima and Takezaki 1994). These studies clearly show that the estimated number of nucleotide substitutions is generally not the best estimator for use in reconstruction of phylogenetic relationships. The reason for this is that there is often a large error associated with the estimation of this number. Therefore, even though its expectation is correct (i.e., on average the expected number of substitutions is proportional to time--but see Tajima 1993), it is not expected to be as useful as estimators designed to have a lower variance.