tbuckley/cabot-search huggingface dataset:
Age trends in 30 day hospital readmissions: US national retrospective analysis
Authors: Jay G Berry, James C Gay, Karen Joynt Maddox, Eric A Coleman, Emily M Bucholz, Margaret R O’Neill, Kevin Blaine, Matthew Hall
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To assess trends in and risk factors for readmission to hospital across the age continuum. <h3>Design</h3> Retrospective analysis. <h3>Setting and participants</h3> 31 729 762 index hospital admissions for all conditions in 2013 from the US Agency for Healthcare Research and Quality Nationwide Readmissions Database. <h3>Main outcome measure</h3> 30 day, all cause, unplanned hospital readmissions. Odds of readmission were compared by patients’ age in one year epochs with logistic regression, accounting for sex, payer, length of stay, discharge disposition, number of chronic conditions, reason for and severity of admission, and data clustering by hospital. The middle (45 years) of the age range (0-90+ years) was selected as the age reference group. <h3>Results</h3> The 30 day unplanned readmission rate following all US index admissions was 11.6% (n=3 678 018). Referenced by patients aged 45 years, the adjusted odds ratio for readmission increased between ages 16 and 20 years (from 0.70 (95% confidence interval 0.68 to 0.71) to 1.04 (1.02 to 1.06)), remained elevated between ages 21 and 44 years (range 1.02 (1.00 to 1.03) to 1.12 (1.10 to 1.14)), steadily decreased between ages 46 and 64 years (range 1.02 (1.00 to 1.04) to 0.91 (0.90 to 0.93)), and decreased abruptly at age 65 years (0.78 (0.77 to 0.79)), after which the odds remained relatively constant with advancing age. Across all ages, multiple chronic conditions were associated with the highest adjusted odds of readmission (for example, 3.67 (3.64 to 3.69) for six or more versus no chronic conditions). Among children, young adults, and middle aged adults, mental health was one of the most common reasons for index admissions that had high adjusted readmission rates (≥75th centile). <h3>Conclusions</h3> The likelihood of readmission was elevated for children transitioning to adulthood, children and younger adults with mental health disorders, and patients of all ages with multiple chronic conditions. Further attention to the measurement and causes of readmission and opportunities for its reduction in these groups is warranted.
The prognostic significance of CD45 expression by clonal bone marrow plasma cells in multiple myeloma.
Authors: Wilson I. Gonsalves, Vincent Rajkumar, William Morice, Michael Timm, Angela Dispenzieri, Francis Buadi, Martha Lacy, Yi Lin, David Dingli, Suzanne R. Hayman, Steven R. Zeldenrust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Morie A. Gertz, Shaji Kumar
Journal: Journal of Clinical Oncology (2015)

8577 Background: Evaluation of clonal plasma cells (cPCs) in the bone marrow (BM) of multiple myeloma (MM) patients (pts) reveals two distinct cPC populations based on CD45 expression, i.e. CD45- and CD45+. We explored the prognostic significance of CD45 expression by cPCs in the BM of MM pts using flow cytometry. Methods: All MM pts seen at the Mayo Clinic, Rochester from 2009 to 2011 who had BM PCs evaluated by flow cytometry were included. For flow cytometry, a 6-color method was used with each sample stained with antibodies to CD45, CD19, CD38, CD138 and cytoplasmic Kappa and Lambda Ig light chains. Samples where > 20% of the cPCs detected expressed CD45 were classified as CD45+ and the rest were CD45-. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. Results: There were 604 consecutive MM pts who had their BM PCs evaluated by flow cytometry. Of these pts, 156 were newly diagnosed and 448 were previously treated with systemic therapy. Among newly diagnosed pts, the median follow up was 42 mos and 41 pts (27%) had high risk disease by FISH. The median time to next therapy (TTNT) for pts in the CD45+ group was 12 mos (n = 26, 17%) versus 29 mos for pts in the CD45- group (n = 130, 83%) (P = 0.002). The median overall survival (OS) for pts in the CD45+ group was 23 mos versus not reached for the CD45- group (P < 0.001). Among previously treated pts, the median follow up was 44 mos and 45% had a prior ASCT. There were 240 previously treated pts that were actively relapsing at the time of their bone marrow analysis. The median OS for actively relapsing pts classified as CD45+ was 11 mos (n = 61, 14%) versus 29 mos (n = 386, 86%) for CD45- (P < 0.001). In a multivariable analysis, CD45+ status and PCLI > 3 were independent predictors of worse OS among the newly diagnosed and actively relapsing pts. Increasing age and elevated LDH were independent predictors of worse OS in newly diagnosed and actively relapsing pts, respectively. Conclusions: The presence of > 20% cPCs in the BM expressing CD45 appears to bear negative prognostic value in newly diagnosed and actively relapsing MM pts. This may be a surrogate for a more aggressive phenotype of MM.
Hammersmith interview course
Authors: Yisu Gu
Journal: BMJ (2011)

With core medical interviews coming up, I decided to invest in an interview skills course to boost my chances of success. One course that is often talked about is the Hammersmith interview course in London. The testimonials of previous attendants posted on its website, along with the claim that “we are the most experienced interview trainers in the UK,” were enough to persuade me to sign up and pay up.

The Hammersmith interview course runs two sessions side by side on the day, one for candidates preparing for consultant interviews and the other for more junior doctors hoping for success at core trainee, specialty trainee, or specialty registrar interviews.

The course is held in a …
Abstract 16083: Urinary Proteome and its Application to Predict Cardiovascular Risk in Patients With Stable Coronary Heart Disease
Authors: Thomas Hraha, Kirk DeLisle, Rachel Ostroff, Stephen Williams, Peter Ganz
Journal: Circulation (2016)

Introduction: Factors that lead to atherosclerosis can cause systemic effects, including impaired kidney function, potentially creating distinct urine protein signatures prognostic of cardiovascula...
Complaints against doctors rose 24% in 2012
Authors: Caroline White
Journal: BMJ (2013)

The number of complaints made about doctors to the UK regulator was 24% higher in 2012 than in 2011, show final figures published in the General Medical Council’s third annual state of medical education and practice report.1

The report, which looks at trends and challenges in the profession, shows that the GMC received 8109 complaints in 2012. The number of complaints made against doctors has more than doubled since 2005.

But the report emphasises that the figures do not necessarily mean that standards of medical practice are falling. Rather, it argues that higher patient expectations and greater willingness of other doctors to raise concerns may have driven the rise. 

“Relative to the number of interactions between doctors and patients, the number …
SURVIVAL BENEFIT OF SURGERY IN PATIENTS WITH PRIMARY SEVERE MITRAL REGURGITATION AND SEVERE LEFT VENTRICULAR DYSFUNCTION
Authors: Seung-Ah Lee, Ran Heo, Sahmin Lee, Dae-Hee Kim, Jong-Min Song, Jae-Kwan Song, Jae-Won Lee, Duk-Hyun Kang
Journal: Journal of the American College of Cardiology (2018)
Long working hours linked to higher alcohol consumption
Authors: Marika Davies
Journal: BMJ (2015)

Working more than 48 hours a week is associated with an increased risk of harmful alcohol consumption, researchers have found.

In a study published in The BMJ researchers found that people who worked more than 48 hours a week were 11% more likely than people who worked 35-40 hours a week to drink more than their recommended weekly allowance of alcohol (14 units for women and 21 units for men).1

The researchers carried out a systematic review and …
Real world patterns of treatment sequencing in Canada for metastatic castrate-resistant prostate cancer.
Authors: Sebastien J. Hotte, Antonio Finelli, Shawn Malone, Bobby Shayegan, Alan I. So, Christina M. Canil, Huong Hew, Laura Park-Wyllie, Fred Saad, Kim N. Chi
Journal: Journal of Clinical Oncology (2018)

320 Background: The Canadian GU Research Consortium (GURC) was recently established to bring advanced prostate cancer centres together to collaborate on research, education, and adoption of best practices. As an initial step to inform the work of the GURC, an electronic questionnaire was designed to assess management of advanced prostate cancer care in Canada and how prostate cancer treatments are sequenced in a real-world setting. Methods: A 59-item online questionnaire was developed by a multidisciplinary scientific committee to measure physician practices, patterns of care, treatment sequencing, and management of mCRPC. After pre-testing, the online questionnaire was sent to 93 urologists, uro-oncologists, medical oncologists, radiation oncologists, and general practitioner oncologists who are actively involved in the treatment of prostate cancer. Results: A total of 49 (53%) respondents completed the questionnaire between April 17, 2017 to May 17, 2017. Based on physician reports, the most frequently used treatment for first-line mCRPC was AR-targeted therapy (94%, n = 46 physicians) such as abiraterone acetate plus prednisone and enzalutamide. Among those 46 physicians, AR-targeted therapy was usually followed by docetaxel second-line therapy (57%, 31 physicians). The most common line 1 to line 3 treatment sequence for mCRPC was: AR-targeted therapy--Docetaxel--AR-targeted therapy (35%, 17 physicians), followed by AR-targeted therapy--Docetaxel--Radium 223 (14%, n = 7), Provincial differences were observed in the line 1 to line 3 treatment sequences, which aligned to variation in provincial policies for access to the treatments. In patients previously treated with docetaxel in the hormone sensitive setting, the most frequently used treatment for first-line mCRPC was AR-targeted therapy (76%, 37 physicians). Conclusions: AR targeted therapy followed by docetaxel is the predominant pattern of practice for management of mCRPC, with variability beyond these lines of therapy. Prospective ongoing work through the GURC in research, education and best practices will aim to understand these practice patterns.
When sorry seems to be the hardest word
Authors: Peter M English
Journal: BMJ (2007)

Dr Sellar's article is very helpful, but I am not sure I would be content with statements in the Compensation Act or from royal colleges stating that an apology “shall not . . . amount to an admission of negligence . . . .”1 The first definition of “apologise” given by Chambers UK is “to acknowledge a mistake or offence and express …
New GMS contract could cost general practices £31 000 a year on average
Authors: Helen Jaques
Journal: BMJ (2012)

Proposed changes to the general medical services (GMS) contract for 2013-14 could cost the average practice £31 000 a year, the BMA has warned.

On the basis of an average practice list of 6651 patients, the BMA has calculated that the proposed increases in Quality and Outcomes Framework (QOF) thresholds to the upper quartile of current achievement could cost practices £11 000 and that removal of the organisational domain could mean practices losing another £20 000. The total sum of £31 000 that practices stand to lose could pay for at least one member of clinical staff, the …
The president of Médecins Sans Frontières
Authors: Rowan Gillies
Journal: BMJ (2004)

T hirty three year old Rowan Gillies, from Sydney, Australia, completed his basic surgical training in 1999 and is currently in his third year of advanced surgical training. He worked as a field doctor for Medecins Sans Frontieres (MSF) in Afghanistan and Sierra Leone before becoming MSF medical coordinator in south Sudan and then Liberia. He became president of MSF Australia in January 2002 and was elected international president of MSF later the same year.

My getting the job is a reflection of the strength of MSF Australia. We sent 120 doctors away last year and they have got a very good reputation in our organisation, so my appointment was recognition of that in some ways. I became a field worker and then became a board member of MSF Australia. I became president of the Australian group after my predecessor became pregnant. International president is chosen from the various group presidents—and so I decided to do this for about two years.

To a degree, I always wanted to do it. As a student in 1994, I went to the border of Burundi and Tanzania and saw …
Abstract P5-04-04: Eribulin differentially disrupts TGF-β signaling pathway in BT-549 and HCC1937 breast cancer cell lines
Authors: R Kaul, AL Risinger, SL Mooberry
Journal: Cancer Research (2018)

Abstract Microtubule targeting agents (MTAs) continue to be valuable in treating breast cancer. While these drugs were classically identified as only antimitotic agents, recent evidence demonstrates that the ability of MTAs to disrupt key signaling components in interphase cells likely contributes to their anticancer actions. Yoshida and colleagues demonstrated that eribulin reverses TGF-β-induced epithelial-to-mesenchymal transition (EMT) in preclinical models of triple negative breast cancer (TNBC) within 7days. To gain a deeper understanding of the interphase effects of eribulin in comparison with other MTAs on the TGF-β signaling pathway, we tested the hypothesis that a short-term, 2 h treatment of TNBC cells with MTAs would disrupt TGF- β signaling. The effects of the microtubule destabilizers eribulin and vinorelbine and the microtubule stabilizers paclitaxel and ixabepilone on downstream targets of the TGF-β pathway were evaluated in two TNBC cell lines. In the mesenchymal type BT-549 cells, eribulin and vinorelbine significantly inhibited TGF-β induced expression of Snail and Slug, while the microtubule stabilizers had no effect on their expression. In the basal-like 1 type HCC1937 cells, the microtubule destabilizers inhibited the expression of Snail when compared to vehicle and stabilizer-treated cells, but caused increased expression of Slug. These data suggest that MTAs have different effects on the TGF-β signaling pathway in distinct molecular contexts. Our efforts are directed towards deciphering the effects of eribulin and other MTAs on the TGF- β pathway and how this contributes to differential sensitivity. Preliminary data suggest that eribulin initiated inhibition of Snail and Slug in BT-549 cells is mediated by the scaffold protein NEDD9 and we are testing whether the differential levels of expression of NEDD9 help explain the differences in the effects of eribulin in BT-549 and HCC1937 cells. These results will begin to decipher differences among MTAs in different molecular contexts and might help identify biomarkers for optimal therapies. Funding for this work was provided by Eisai Inc. Citation Format: Kaul R, Risinger AL, Mooberry SL. Eribulin differentially disrupts TGF-β signaling pathway in BT-549 and HCC1937 breast cancer cell lines [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-04-04.
Anti-CD137 Cancer Immunotherapy Suppresses Tumor Growth—Letter
Authors: Bhushan Dharmadhikari, Qun Zeng, Meihui Wu, Herbert Schwarz
Journal: Cancer Research (2018)

We read with great interest the publication by Kang and colleagues (1). The authors describe that agonistic anti-CD137 (TNFRSF9, 4-1BB) antibodies enhance antitumor T-cell responses in murine xenograft models that is consistent with the findings of many other groups and that corresponds to the consensus in the field. In the same publication, the authors report that in CD137-deficient mice, growth of CT26 colon carcinoma and Renca renal carcinoma was significantly inhibited.This is puzzling and in contrast to a multitude of findings that show the importance of CD137–CD137 ligand (CD137L) interactions for transplant rejection, pathogen clearance, and protection against malignant disease. In addition, the current report is also in contrast with an earlier one by some of the same authors who found an increased growth of B16F10 melanoma in CD137-deficient mice (2). The research community would benefit if the authors could provide an explanation for the contrasting growth patterns of different tumors in CD137-deficient mice.Furthermore, the authors propose that "blockade of the CD137L signaling pathway may be used to promote therapy-induced immunosurveillance." While CD137 forward signaling, that is, costimulation of T cells, is conserved between human and mouse, there is evidence that reverse CD137L signaling into monocytic cells differs between the two species. Reverse CD137L signaling in murine monocytes induces cell activation and IL10 secretion but does not lead to a proinflammatory phenotype (3). However, in human monocytes and dendritic cells (DC), reverse CD137L signaling causes a proinflammatory cell activation. In monocytes, it induces the release of proinflammatory cytokines, prolonged survival, endomitosis, and migration. Furthermore, reverse CD137L signaling induces maturation of human immature DCs and even differentiation of peripheral human monocytes to inflammatory DCs that resemble inflammatory DCs isolated from a tumor ascites or the synovial fluid of a rheumatoid arthritis patient and that have an enhanced capability to induce antiviral T-cell responses (4).This species difference may have its cause in the unusually low homology of 36% between human and murine CD137L, whereas for most other members of the TNF and TNF receptor families, the human–mouse homology is 60%–80% (5). We are therefore sceptical that data on reverse CD137L signaling obtained from murine cells or mice are translatable to the human system and would strongly caution against using CD137L blockade for human cancer immunotherapy.See the Response, p. 1572No potential conflicts of interest were disclosed.
Combination of carboplatin (AUC4) and cabazitaxel (25 mg/m2) in mCRPC patients not or no longer responding to cabazitaxel monotherapy.
Authors: Rebecca Louhanepessy, Margriet van Rijssen, Vincent van der Noort, Andre M. Bergman
Journal: Journal of Clinical Oncology (2018)

371 Background: Cabazitaxel monotherapy is a second line treatment option for mCRPC patients. However, not all patients have a PSA response on this treatment, while a proportion of patients develop resistance during cabazitaxel treatment. Platinum drugs might be effective in poorly differentiated disease. Ongoing trials suggest effectivity of the combination in mCRPC, however, thus far clinical parameters cannot predict a response. Therefore, we investigated the addition of carboplatin to cabazitaxel in mCRPC patients who do not have a psa response on cabazitaxel monotherapy or have a PSA rise during treatment. Methods: 19 patients (WHO PS ≤2) who were not responding to ≥2 cycles cabazitaxel monotherapy (25 mg/m2) or two rises of PSA during cabazitaxel were included in this prospective cohort study. All patients received the combination of carboplatin (AUC 4) and cabazitaxel (25 mg/m2). Previous therapies, PSA response, WHO performance score, Progression Free Survival (PFS), Overall Survival (OS) and adverse events were monitored. Results: Median age was 66.7 years, 21% of patients had a WHO PS of 2, 68% had a Gleason score ≥8, 74% had bone metastases, 63% lymph node metastases and 26% visceral metastases. All patients received docetaxel prior to cabazitaxel, 6 patients (31,6%) received abiraterone and 15 patients (78,9%) enzalutamide. Combination therapy was initiated after a median of 4.1 cycles monotherapy [IQR 3.0-6.0]. Patients were treated with a median of 3.8 [IQR 2.8-6.3] cycles of combination therapy. Eight patients (42,2%) had a PSA decrease of &gt; 25% and 4 patients (21,1%) had a PSA decrease of ≥50%. One patient had a WHO PS improvement of 2. Median PFS was 8.1 [IQR 6.0-15.1] months and median OS 13.0 months. Anemia was the most common adverse event (≥ grade 2) during combination therapy (62%), while thrombopenia was only found in one patient (5%). Other common adverse events were fatigue (43%), nausea (24%), pain (33%) and constipation (10%). Conclusions: Our data suggests that combination treatment of cabazitaxel and carboplatin might be effective in heavily pretreated patients not, or no longer responding to cabazitaxel monotherapy.
Metformin and <i>Helicobacter pylori</i> Infection in Patients With Type 2 Diabetes
Authors: Chin-Hsiao Tseng
Journal: Diabetes Care (2018)

Patients with diabetes have an increased risk of gastric cancer (1,2), and metformin may protect against gastric cancer (3). This study investigated whether metformin might protect against Helicobacter pylori infection, an important risk factor of gastric cancer.

The reimbursement database of Taiwan’s National Health Insurance was used. Disease diagnoses were based on the ICD-9-CM. Diabetes was coded 250.XX, and H. pylori infection was defined by a diagnostic code of 041.86 plus receiving H. pylori eradication therapy (4). A propensity score (PS)-matched cohort (based on the Greedy 8→1 digit match algorithm) (3) comprised 16,060 metformin ever users and 16,060 metformin never users with new-onset diabetes, who were enrolled during 1999–2005 and followed up until the end of 2011. Patients with type 1 diabetes, cancer diagnoses, or H. pylori infections at …
Vaccination Patterns in Children After Autism Spectrum Disorder Diagnosis and in Their Younger Siblings
Authors: Ousseny Zerbo, Sharareh Modaressi, Kristin Goddard, Edwin Lewis, Bruce H. Fireman, Matthew F. Daley, Stephanie A. Irving, Lisa A. Jackson, James G. Donahue, Lei Qian, Darios Getahun, Frank DeStefano, Michael M. McNeil, Nicola P. Klein
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> In recent years, rates of vaccination have been declining. Whether this phenomenon disproportionately affects children with autism spectrum disorder (ASD) or their younger siblings is unknown. <h3>Objectives</h3> To investigate if children after receiving an ASD diagnosis obtain their remaining scheduled vaccines according to the Advisory Committee on Immunization Practices (ACIP) recommendations and to compare the vaccination patterns of younger siblings of children with ASD with the vaccination patterns of younger siblings of children without ASD. <h3>Design, Setting, and Participants</h3> This investigation was a retrospective matched cohort study. The setting was 6 integrated health care delivery systems across the United States within the Vaccine Safety Datalink. Participants were children born between January 1, 1995, and September 30, 2010, and their younger siblings born between January 1, 1997, and September 30, 2014. The end of follow-up was September 30, 2015. <h3>Exposures</h3> Recommended childhood vaccines between ages 1 month and 12 years. <h3>Main Outcome and Measure</h3> The proportion of children who received all of their vaccine doses according to ACIP recommendations. <h3>Results</h3> The study included 3729 children with ASD (676 [18.1%] female), 592 907 children without ASD, and their respective younger siblings. Among children without ASD, 250 193 (42.2%) were female. For vaccines recommended between ages 4 and 6 years, children with ASD were significantly less likely to be fully vaccinated compared with children without ASD (adjusted rate ratio, 0.87; 95% CI, 0.85-0.88). Within each age category, vaccination rates were significantly lower among younger siblings of children with ASD compared with younger siblings of children without ASD. The adjusted rate ratios varied from 0.86 for siblings younger than 1 year to 0.96 for those 11 to 12 years old. Parents who had a child with ASD were more likely to refuse at least 1 recommended vaccine for that child's younger sibling and to limit the number of vaccines administered during the younger sibling's first year of life. <h3>Conclusions and Relevance</h3> Children with ASD and their younger siblings were undervaccinated compared with the general population. The results of this study suggest that children with ASD and their younger siblings are at increased risk of vaccine-preventable diseases.