tbuckley/cabot-search huggingface dataset:
Effect of Evidence-Based Supported Employment vs Transitional Work on Achieving Steady Work Among Veterans With Posttraumatic Stress Disorder
Authors: Lori L. Davis, Tassos C. Kyriakides, Alina M. Suris, Lisa A. Ottomanelli, Lisa Mueller, Pamela E. Parker, Sandra G. Resnick, Richard Toscano, Alexandra A. Scrymgeour, Robert E. Drake
Journal: JAMA Psychiatry (2018)

Posttraumatic stress disorder (PTSD) often interferes with a person's ability to obtain or sustain employment, which leads to premature exit from the labor force and reduced income.To determine whether individual placement and support (IPS)-supported employment is more effective than stepwise vocational rehabilitation involving transitional work assignments at helping veterans with PTSD attain steady, competitive employment.The Veterans Individual Placement and Support Toward Advancing Recovery (VIP-STAR) study was a prospective, multisite, randomized clinical trial that included 541 unemployed veterans with PTSD at 12 Veterans Affairs medical centers. Data were collected from December 23, 2013, to May 3, 2017. Intent-to-treat analysis was performed.Individual placement and support is a supported employment intervention that rapidly engages people with disabilities in community job development to obtain work based on their individual job preferences. Transitional work is a stepwise vocational rehabilitation intervention that assigns people temporarily to noncompetitive jobs as preparation for competitive employment in the community.A priori hypotheses were that, compared with those in transitional work, more participants in the IPS group would become steady workers (primary) and earn more income from competitive jobs (secondary) over 18 months. Steady worker was defined as holding a competitive job for at least 50% of the 18-month follow-up period.A total of 541 participants (n = 271 IPS; n = 270 transitional work) were randomized. Mean (SD) age was 42.2 (11) years; 99 (18.3%) were women, 274 (50.6%) were white, 225 (41.6%) were African American, and 90 (16.6%) were of Hispanic, Spanish, or Latino ethnicity. More participants in the IPS group achieved steady employment than in the transitional work group (105 [38.7%] vs 63 [23.3%]; odds ratio, 2.14; 95% CI, 1.46-3.14). A higher proportion of IPS participants attained any competitive job (186 [68.6%] vs 154 [57.0%]; P = .005) and had higher cumulative earnings from competitive jobs (median [interquartile range] $7290 [$23 174] in IPS vs $1886 [$17 167] in transitional work; P = .004).This multisite trial demonstrated significantly greater effectiveness of IPS-supported employment over stepwise transitional work vocational rehabilitation for veterans living with chronic PTSD. The results provide supporting evidence for increasing access to IPS for veterans living with PTSD.clinicaltrials.gov Identifier: NCT01817712.
Major arterial resection for stage 3 adenocarcinoma of the pancreas.
Authors: Benjamin Loveday, Koji Tomiyama, Nathan Zilbert, Amélie Tremblay St-Germain, Pablo Emilio Serrano Aybar, Adrian Fox, Maja Segedi, Paul Scholtz, Martin O'Malley, Ayelet Borgida, Teresa Bianco, Anna Dodd, Monika K. Krzyzanowska, Malcolm J. Moore, Joon-Hyung J. Kim, Alice Chia-chi Wei, Steven Gallinger, Neesha C. Dhani, Ian M McGilvray
Journal: Journal of Clinical Oncology (2018)

362 Background: Stage 3 pancreas ductal adenocarcinoma (PDAC) is defined by arterial involvement, and its resection remains controversial. The objective of this study was to evaluate clinical and oncologic outcomes for patients with stage 3 PDAC who entered a treatment program of neoadjuvant therapy (NAT) and pancreatic resection, with comparison between those who underwent arterial (AR) vs. standard resection (SR). Methods: This cohort study included patients from 2009-2016 in a single academic institution, with biopsy-proven potentially resectable stage 3 PDAC who entered a treatment program of NAT followed by surgical exploration if non-progressive disease on imaging. AR was performed if required to achieve R0 resection. Oncological outcomes were analyzed as intention to treat from diagnosis date. Results: Eighty-nine patients met inclusion criteria, of whom 87 (97.8%) received chemotherapy and 50 (56.2%) received radiotherapy. 46/89 (51.7%) underwent surgical exploration; 31 underwent pancreas resection (AR n = 20, SR n = 11), and 15 were found to have metastatic or unresectable disease. The AR group had a longer operative time (681 vs. 563 minutes, p = 0.0059) and more blood loss (1600 vs. 575 mL, p = 0.0004) compared with SR, with no difference between groups for blood transfusion, overall complications, pancreatic fistula, length of stay, reoperation, readmission or mortality. R0 rate was 100% for resected patients. Post-operative 90-day mortality was 1.1%. Median overall survival of resected patients was longer than in non-resected patients (25.9 vs. 14.8 months, p = 0.01), while AR had comparable overall survival to SR (19.7 vs. 28.4 months, p = 0.41). Conclusions: Patients with non-progressive stage 3 PDAC after NAT should be considered for pancreas resection. AR had comparable clinical and oncologic outcomes to SR. Resection may offer a survival advantage over non-surgical therapy alone, and AR should be considered if required to obtain a negative resection margin.
Public health doctors must feel free to speak out about concerns, says BMA
Authors: Abi Rimmer
Journal: BMJ (2015)

Employers of UK public health doctors should tell them that they should never hesitate to raise concerns, the BMA has said.

Delegates at the BMA’s annual conference of public health medicine in London on 27 April voted unanimously in favour of a motion saying that public health doctors should be encouraged to speak out if they …
Well‐Controlled Cell‐Trapping Systems for Investigating Heterogeneous Cell–Cell Interactions
Authors: Koki Kamiya, Yuta Abe, Kosuke Inoue, Toshihisa Osaki, Ryuji Kawano, Norihisa Miki, Shoji Takeuchi
Journal: Advanced Healthcare Materials (2018)

Abstract Microfluidic systems have been developed for patterning single cells to study cell–cell interactions. However, patterning multiple types of cells to understand heterogeneous cell–cell interactions remains difficult. Here, it is aimed to develop a cell‐trapping device to assemble multiple types of cells in the well‐controlled order and morphology. This device mainly comprises a parylene sheet for assembling cells and a microcomb for controlling the cell‐trapping area. The cell‐trapping area is controlled by moving the parylene sheet on an SU‐8 microcomb using tweezers. Gentle downward flow is used as a driving force for the cell‐trapping. The assembly of cells on a parylene sheet with round and line‐shaped apertures is demonstrated. The cell–cell contacts of the trapped cells are then investigated by direct cell–cell transfer of calcein via connexin nanopores. Finally, using the device with a system for controlling the cell‐trapping area, three different types of cells in the well‐controlled order are assembled. The correct cell order rate obtained using the device is 27.9%, which is higher than that obtained without the sliding parylene system (0.74%). Furthermore, the occurrence of cell–cell contact between the three cell types assembled is verified. This cell‐patterning device will be a useful tool for investigating heterogeneous cell–cell interactions.
Independent assessment of <i>TP53</i> and <i>PTEN</i> as predictors of response to enzalutamide (ENZ) or abiraterone acetate (AA) in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Andrew W Hahn, Nityam Rathi, David Michael Gill, Sidney VanAlstine, Austin Poole, Neeraj Agarwal, Benjamin Louis Maughan
Journal: Journal of Clinical Oncology (2018)

351 Background: Alterations in androgen receptor signaling are well-established mechanisms of resistance to medical castration. Pre-clinical studies suggest that alterations to key tumor suppressor genes, such as TP53 or PTEN, may also be associated with development of androgen independence as an alternate mechanism of castration-resistance. Previous studies have shown that TP53 inactivation and PTEN loss are predictive of response to novel androgen axis inhibitors. Here, we independently assess whether TP53 and PTEN genomic alterations are predictive of response to ENZ and AA in men with mCRPC. Methods: Clinical data and samples were analyzed from a prospective prostate cancer registry at the University of Utah (Salt Lake City, UT). Next-generation sequencing (NGS) was performed on predominantly primary tumor tissue for 343 somatic and germline genetic alterations using FoundationOne. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Patients with mCRPC who were treated with any line AA or enzalutamide were included. We performed a univariate analysis to assess the predictive value of TP53 and PTEN. Only patients treated with single-agent therapy were included. Results: Of 141 men with prostate cancer and NGS available, 56 were included. Most patients were treated with abiraterone (n = 50), and only 6 with enzalutamide. 28.6% had PTEN loss and 35.7% had a TP53 mutation. OS and PFS did not differ significantly according to PTEN or TP53 status. Median OS was 40.9 months and not reached for men with and without TP53 mutation (HR 1.85, p = 0.31). Median PFS was 7.5 months and 9.5 months for men with and without TP53 mutation (HR 1.18, p = 0.60). Median PFS was 7.2 months and 9.5 months for men with and without PTEN loss (HR 1.15, p = 0.66). Median OS for PTEN was not mature enough to analyze. Conclusions: In our independent cohort, neither TP53 mutation nor PTEN loss is predictive of response to androgen-directed therapy in men with mCRPC patients. However, this is a relatively small retrospective sample with few events. These results should be considered exploratory only.
Update on improving working lives for doctors
Authors: Rhona MacDonald
Journal: BMJ (2004)

In October last year, 300 or so doctors attended the third Improving Working Lives for Doctors conference organised by the Department of Health.

The programme included equality and diversity, modernising medical careers, and doctors' health. Journalist and television presenter Nick Ross chaired the event, which included having interactive keypad votes on various topics. The results highlight what doctors think are the important issues in improving their working lives (see box).

Although the feedback from delegates in the official evaluation forms was mostly positive, we are now a few months on. So has all the energy and enthusiasm of the conference dissipated or is the Department of Health still on the case? I asked David Amos, deputy director of human resources from the Department of Health, to share his views.

He explains why the Department of Health felt another conference was needed: “The conference involved consulting and involving frontline doctors. All …
PREVALENCE, MECHANISMS AND RISK FACTORS OF LEAD MACRODISLODGEMENT AFTER IMPLANTATION OF CARDIAC IMPLANTABLE ELECTRONIC DEVICES
Authors: Andrew Tseng, Justin Shipman, Justin Lee, Lanyu Mi, Yong-Mei Cha, Komandoor Srivathsan, Win-Kuang Shen, Mustapha Amin, Michael Osborn, Samuel Asirvatham, Paul Friedman, Siva Mulpuru
Journal: Journal of the American College of Cardiology (2018)
Post-MMC doctors more certain of career choice than predecessors
Authors: Helen Jaques
Journal: BMJ (2013)

Doctors who graduated after the Modernising Medical Careers (MMC) overhaul of postgraduate medical training are more confident of their choice of specialty than those who graduated pre-MMC, research has found.1

Researchers surveyed 39 115 doctors who graduated in 1974, 1977, 1983, 1993, 1996, 1999, 2000, 2002, 2005, 2008, and 2009. Doctors were asked at one, three, or five years after graduating about their choice …
The realities of career breaks and working part time in medicine
Authors: Naureen Bhatti, Rebecca Viney
Journal: BMJ (2013)

Health minister Anna Soubry’s comments on the “unintended consequences” for the NHS of women doctors working part time after starting families drew criticism from doctors. <b>Naureen Bhatti</b> and <b>Rebecca Viney</b> look at the reality of how men and women can take career breaks and work part time in medicine
Abstract P5-08-01: Reconstructing the evolutionary paths of BIG 1-98
Authors: LL Lara-Gonzalez, S Loi, D Ferrari, A Papenfuss, DL Goode
Journal: Cancer Research (2018)

Abstract We are reconstructing the dynamics of tumour growth, treatment response, and origins of resistance of the Breast International Group (BIG) 1-98 study to determine the evolutionary paths of non-responders. We established the somatic alteration landscape of primary tumours collected at surgery from BIG 1-98 patients using targeted DNA sequencing of 287 genes of FFPE samples from 538 patients. Combined analysis of genetic and clinical data indicates increased genomic instability; TP53 mutations and copy number variations of 11q13 and 8p11 are associated with poor prognosis. We developed an in silico simulation framework to investigate if the non-responder outcome is due to (over)-treatment or intrinsic to evolutionary selection prior to diagnosis. To reconstruct the evolutionary history of tumours, we created a computational multitype branching process that tracks the expansion of diverse clonal lineages as they acquire driver and passenger mutations that alter their proliferation and mutation rates. To account for the heterogeneity between patients, we created a fitting procedure based on the Cramer-von Misses statistic to find the likelihood of parameters of our computational model that recreate the mutational landscape and clinicopathological factors observed in each patient. Once the fitting procedure is done, we simulate the course of treatment following the study arm scheme accounting for the cell-cycle action mechanism of Tamoxifen and Letrozole. Using our tool, we are characterising the range of tumour development scenarios covering different degrees of aggressiveness and genomic instability. Our computational model allows simulation of diverse adjuvant-schemes to predict optimised treatment regimes for validation in patient-derived tumour xenograft mouse models. Citation Format: Lara-Gonzalez LL, Loi S, Ferrari D, Papenfuss A, Goode DL. Reconstructing the evolutionary paths of BIG 1-98 [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 P5-08-01.
NICE proposes targets for clinical commissioning groups
Authors: Adrian O’Dowd
Journal: BMJ (2012)

The National Institute for Health and Clinical Excellence (NICE) has published a proposed menu of commissioning outcomes framework (COF) indicators by which clinical commissioning groups (CCGs) will be held to account.

The 44 indicators recommended by the COF advisory committee include targets on cancer mortality, care after a stroke, emergency admissions, and patients’ quality of life. 1

Several doctors’ representatives and charities have raised doubts over the indicators, saying that there are too many and that they may be too rigid to allow doctors trying to commission the necessary freedom to succeed and be innovative.

The proposed indicators cover domains and topics such as preventing people from dying prematurely, enhancing …
I am interested in a career change from emergency medicine to toxicology. I have membership of the Royal College of Surgeons. Any advice?
Authors: Emma Baker
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
Impact of cabazitaxel on metastatic bone health in patients with castration resistant prostate cancer previously treated with docetaxel: CaBone Study.
Authors: Daniele Santini, Franco Morelli, Francesco Bertoldo, Gaetano Facchini, Daniele Rizzi, Davide Gatti, Evaristo Maiello
Journal: Journal of Clinical Oncology (2018)

TPS405 Background: The most significant morbidity of prostate cancer (PC) is bone metastasis (BM). More than 90% of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) have radiologic evidence of BM, which are a major cause of death, disability, decreased QoL, and increased treatment cost. Unlike deaths from many other types of cancer, deaths from PC are often due to bone disease and its complications. In vitro data demonstrate a role for taxanes in the regulation of osteoclast formation and function, with a decreased resorption activity. ÊSTAMPEDE study has shown a strong clinical benefit, in term of OS, PFS and skeletal related events (SREs) delay compared with ADT alone, in metastatic hormone-sensitive pts treated with docetaxel (DOC) and ADT. TROPIC Study has shown that cabazitaxel (CBZ) prolongs OS regardless of DOC response in responder, resistant and refractory pts. Some data are available on pain progression, pain response and ECOG PS deterioration but in a unselected ITT population with a low prevalence of only BM disease at baseline, 25% of men had visceral metastasis. No data are available on effects of CBZ on BM and his direct impact on quality of life, bone turnover markers and time to the first SRE events. The aim of CaBone phase II study is to investigate, specifically, the effects on bone disease, bone turnover and on the bone related quality of life of CBZ in mCRPC pts with skeletal involvement without visceral disease. Methods: CaBone is a single arm, prospective, open label, multi center, phase II - GOIM - cooperative study of CBZ 25 mg/m2 q21 plus daily PDN (10 mg) in mCRPC pts with bone mets without visceral disease progressed during or after DOC treatment. Primary endpoint is Bone PFS according to PCWG2 while the Secondary are related on Evaluation of bone disease: Time to SRE, Time to Bone Pain Progression, Bone Pain Response, Time to opiate use for cancer-related pain, Time to deterioration in ECOG PS, Evaluation of Quality of Life and Functional status, Safety and centralized bone turnover markers: ALP, Bone ALP , LDHÊ, Serum CTx, iPTH, 1.25 (OH)2ÊD3. 107 subjects will be enrolled in CaBone study. CaBone is partially supported by Sanofi Genzyme. Clinical trial information: 2016-001253-41.
First prospective study evaluating effect of metformin (M) on disease control (DC) and activation of AMP-activated protein kinase (AMPKα) in patients (pts) with GI malignancies.
Authors: Amandeep Godara, Nauman S Siddiqui, Hilal Hachem, Robert E. Martell, Wasif M. Saif
Journal: Journal of Clinical Oncology (2018)

264 Background: Observational studies have demonstrated association of M with reduced cancer incidence and mortality in multiple cancer types, including GI. Anti-neoplastic effects of M are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway. Methods: In a pilot, delayed-start randomized study, non-diabetic pts with GI cancers were randomized to 2 arms, Stage 1: concurrent M (500mg twice daily) plus chemotherapy (M+C) vs. Chemo alone (C) followed by cross over to M+C arm in Stage 2, while adverse events (DLT) were assessed by CTCAE v.3.0. As a translational correlate, we used phosphorylation of AMPKα at Thr172 to measure AMPK activation by western blot technique in PBMCs isolated from pts before and after receiving M. These levels were correlated with radiological (RECIST 1.1) and tumor marker outcomes by descriptive analysis. Results: 41 pts with GI cancers (CRC: 22, PC: 12, GE: 4, BD: 2, others: 1) were treated in this trial. Mean duration of M therapy was 85 days (range: 9-443). There was no significant difference in grade 3 or above DLT in M+C vs. C arm (14% vs. 12% respectively). Gel band density analysis on 19 pts showed that 63% pts had increased phosphorylation of AMPKα after M (ratio of phospho-AMPKα after M to before M &gt; 1) with mean = 1.227 (± 0.134). RECIST 1.1 restaging showed DC in 55% pts and 45% pts had decline in tumor markers. 8 of 12 pts with APC showed DC at the completion of study. Of note, 60% of pts with DC also showed increase in phosphorylation of AMKα. Conclusions: Our study is the first human study that prospectively demonstrates the impact of M on AMPKα phosphorylation, thus implying a potential role of M both as a chemopreventive and chemotherapeutic agent in GI cancers. Our study also shows the safety of M across various chemoregimens, providing a platform and justification for future studies. Potential benefits of M in preventive and treatment settings warrant further investigation in adequately powered prospective studies. We aim to perform a dose-escalation of M in our next study with additional metabolomics correlates. Clinical trial information: NCT01442870.
POOR GLYCEMIC CONTROL IS ASSOCIATED WITH INCREASED INTERSTITIAL FIBROSIS IN DIABETIC PATIENTS WITH AND WITHOUT HEART FAILURE WITH PRESERVED EJECTION FRACTION(HFPEF)
Authors: Julio A. Chirinos, Amer A. Syed, Anila Hussain, Zeba Hashmath, Maheswara Reddy Koppula, Ali Tariq, Swapna Varakantam, Bilal Ansari, Jonathan Lee, Scott Akers
Journal: Journal of the American College of Cardiology (2018)
Only one in 10 doctors is confident in effectiveness of whistleblowing procedures
Authors: Helen Jaques
Journal: BMJ (2012)

Only 11% of doctors have confidence in the process for whistleblowing, with almost half (47%) not confident and a similar proportion (42%) unsure, shows a survey of more than 1500 doctors by the Medical Protection Society (MPS).

“Fear of consequences” was the number one reason doctors gave for not having faith in the current process for raising concerns, with …
Pustular Eruption (Iododerma?) in a Patient With Cancer Treated With Complementary and Alternative Medicine
Authors: Lawrence Chukwudi Nwabudike
Journal: JAMA Dermatology (2018)

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LONG-TERM FOLLOW UP AFTER CORONARY ARTERY BYPASS GRAFT OPERATION WITH REFRACTORY CARDIOGENIC SHOCK AND EXTRACORPOREAL MEMBRANE OXYGENATION THERAPY
Authors: Sven Lehmann, Isabell Altmann, Alexandro Hoyer Sepulveda, Khalil Jawad, Piroze Davierwala, Thomas Schroeder, Jens Garbade, Michael Borger
Journal: Journal of the American College of Cardiology (2018)