tbuckley/cabot-search huggingface dataset:
Comparative effectiveness and safety of the implementation of universal public funding of FOLFIRINOX (FFX) and gemcitabine (G) + nab-paclitaxel (GnP) in advanced pancreatic cancer (APC): A population-based study.
Authors: Helen Guo, Jaclyn Marie Beca, Ruby Redmond-Misner, Wanrudee Isaranuwatchai, Lucy Qiao, Craig Earle, Scott R. Berry, James Joseph Biagi, Stephen Welch, Brandon Matthew Meyers, Nicole Mittmann, Natalie G. Coburn, Aliya Pardhan, Jessica Arias, Deborah Schwartz, Scott Gavura, Leta Marie Forbes, Robin McLeod, Erin Diane Kennedy, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2018)

375 Background: FFX has been universally publicly funded in Ontario, Canada, for metastatic pancreatic cancer (mPC) and unresectable locally advanced pancreatic cancer (uLAPC) since 11/2011 and 04/2015, respectively. GnP has been publicly funded for uLAPC and mPC (APC) since 04/2015. We examined the real world comparative effectiveness and safety of implementing funding of FFX and GnP for patients with APC. Methods: Patients with APC who received first-line FFX, GnP, or G from 01/2008-03/2016 were identified in CCO’s New Drug Funding Program database and divided into 3 periods: 01/2008-10/2011 (P1), 11/2011-03/2015 (P2), and 04/2015-03/2016 (P3). Data were linked with the Ontario Cancer Registry and others to ascertain demographics, comorbidities, and outcomes. Matching weights of propensity score to simultaneously compare three periods were generated using multinomial logistic regression. Crude and adjusted survival analyses were conducted to assess overall survival (OS) using Kaplan-Meier and weighted Cox regression methods.Weighted negative binomial models were used to estimate rate ratios (RR) for all-cause hospitalization (H) and ED visits. Results: We identified 3696 patients (1250 in P1, 1891 in P2, 555 in P3) (overall mean age 65, female 46%). In P2, 49% received FFX. In P3, 53% received FFX and 35% received GnP. Median OS was 5.7, 7.0, and 7.5 months for P1, P2, and P3, respectively. Median OS for FFX and GnP in mPC were 8.8 and 5.5 months, respectively. OS was improved in P2 vs. P1 (HR = 0.84, 0.78-0.90) and in P3 vs. P2 (HR = 0.82, 0.73-0.92). ED visits were similar compared P2 vs. P1 (RR=1.02, p = 0.75) and P3 vs. P2 (RR=1.04, p = 0.48), and H was reduced in P2 vs. P1 (RR = 0.86, p = 0.01), but similar in P3 vs. P2 (RR = 0.98, p = 0.78). H for febrile neutropenia (FN) was increased in P2 vs. P1 (RR = 2.18, p = 0.04) but not in P3 vs. P2 (RR = 1.32, p = 0.45). Conclusions: Implementation of universal public funding of FFX for mPC improved OS and reduced the rates H overall, but increased FN-related H. Funding of FFX for uLAPC and GnP for APC improved OS without increased in ER and H.
No Obesity Paradox in Pediatric Patients With Dilated Cardiomyopathy
Authors: Chesney D. Castleberry, John L. Jefferies, Ling Shi, James D. Wilkinson, Jeffrey A. Towbin, Ryan W. Harrison, Joseph W. Rossano, Elfriede Pahl, Teresa M. Lee, Linda J. Addonizio, Melanie D. Everitt, Justin Godown, Joseph Mahgerefteh, Paolo Rusconi, Charles E. Canter, Steven D. Colan, Paul F. Kantor, Hiedy Razoky, Steven E. Lipshultz, Tracie L. Miller
Journal: JACC Heart Failure (2018)
Pensions bill to hit NHS workers hardest, says BMA
Authors: Caroline White
Journal: BMJ (2012)

The public sector pensions bill currently before parliament is inherently unfair and would hit NHS workers harder than any other group of public sector workers, the BMA has argued in an analysis of the financial implications of the current proposals.

The legislation, which has its second parliamentary reading on 22 October, would embed disparities across and within public sector pension schemes and would give the government sweeping powers to make further, possibly retrospective, changes, the association said.

“There is no justification for the scale of the planned changes or the speed at which they are to be implemented,” it claimed.

The bill, which was published last month, would scrap final salary schemes for most public sector workers, …
The end of <i>Misplaced Trust</i>
Authors: Rhona MacDonald
Journal: BMJ (2004)

<i>After 84 episodes, we will no longer have a weekly instalment about the colourful characters and shenanigans going on in Murkton Moor in our soap opera</i> Misplaced Trust. <i>Its writer and creator, Nicola Sharp, shares her experiences with</i> Rhona MacDonald
Endogenous Replication Stress Marks Melanomas Sensitive to CHEK1 Inhibitors <i>In Vivo</i>
Authors: Zay Yar Oo, Alexander J. Stevenson, Martina Proctor, Sheena M. Daignault, Sebastian Walpole, Catherine Lanagan, James Chen, Dubravka Škalamera, Loredana Spoerri, Stephen A. Ainger, Richard A. Sturm, Nikolas K. Haass, Brian Gabrielli
Journal: Clinical Cancer Research (2018)

Purpose: Checkpoint kinase 1 inhibitors (CHEK1i) have single-agent activity in vitro and in vivo Here, we have investigated the molecular basis of this activity.Experimental Design: We have assessed a panel of melanoma cell lines for their sensitivity to the CHEK1i GNE-323 and GDC-0575 in vitro and in vivo The effects of these compounds on responses to DNA replication stress were analyzed in the hypersensitive cell lines.Results: A subset of melanoma cell lines is hypersensitive to CHEK1i-induced cell death in vitro, and the drug effectively inhibits tumor growth in vivo In the hypersensitive cell lines, GNE-323 triggers cell death without cells entering mitosis. CHEK1i treatment triggers strong RPA2 hyperphosphorylation and increased DNA damage in only hypersensitive cells. The increased replication stress was associated with a defective S-phase cell-cycle checkpoint. The number and intensity of pRPA2 Ser4/8 foci in untreated tumors appeared to be a marker of elevated replication stress correlated with sensitivity to CHEK1i.Conclusions: CHEK1i have single-agent activity in a subset of melanomas with elevated endogenous replication stress. CHEK1i treatment strongly increased this replication stress and DNA damage, and this correlated with increased cell death. The level of endogenous replication is marked by the pRPA2Ser4/8 foci in the untreated tumors, and may be a useful marker of replication stress in vivoClin Cancer Res; 24(12); 2901-12. ©2018 AACR.
How long does a visiting training number (VTN) last and what are the differences between a national training number (NTN) and a VTN?
Authors: Simon Eccles
Journal: BMJ (2005)

Have 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 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. <b>www.bmjcareers.com/advicezone</b>
2D Ultrathin MXene‐Based Drug‐Delivery Nanoplatform for Synergistic Photothermal Ablation and Chemotherapy of Cancer
Authors: Xiaoxia Han, Ju Huang, Han Lin, Zhigang Wang, Pan Li, Yu Chen
Journal: Advanced Healthcare Materials (2018)

Abstract Two‐dimensional (2D) MXenes, as a new 2D functional material nanosystem, have been extensively explored for broad applications. However, their specific performance and applications in theranostic nanomedicine have still rarely been explored. This work reports on the drug‐delivery performance and synergistic therapeutic efficiency of Ti 3 C 2 MXenes for highly efficient tumor eradication. These Ti 3 C 2 MXenes not only possess high drug‐loading capability of as high as 211.8%, but also exhibit both pH‐responsive and near infrared laser‐triggered on‐demand drug release. Especially, based on the high photothermal‐conversion capability of Ti 3 C 2 MXenes, they have been further explored for efficient tumor eradication by synergistic photothermal ablation and chemotherapy, which has been systematically demonstrated both in vitro and in vivo. These Ti 3 C 2 MXenes have also been demonstrated as the desirable contrast agents for photoacoustic imaging, showing the potential for diagnostic‐imaging guidance and monitoring during therapy. The high in vivo histocompatibility of Ti 3 C 2 and their easy excretion out of the body have been evaluated and demonstrated, showing the potential high biosafety for further clinical translation. This work paves a new way for broadening biomedical applications of MXenes in nanomedicine where they can exert the high performance and functionality for synergistic therapy, especially on combating cancer.
Do I have to be in a post for a certain period before I can claim for maternity benefit, or can I claim immediately I start my first senior house officer post?
Authors: Janet Thomas
Journal: BMJ (2004)

Got a career or related problem that needs answering? Can't 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.
S30 Nutrition and Exercise Rehabilitation in Obesity Hypoventilation Syndrome (NERO): A Pilot Randomised Controlled Trial
Authors: S Mandal, ES Suh, R Harding, A Vaughan-France, M Ramsay, B Connolly, D Bear, H McLaughlin, S Greenwood, M Polkey, M Elliott, A Douiri, J Moxham, N Hart
Journal: Thorax (2015)

<h3>Introduction</h3> We have previously shown that treatment of obesity hypoventilation syndrome (OHS) with non-invasive ventilation (NIV) results in weight reduction and an increase in physical activity (Murphy <i>et al</i>., 2012). We therefore hypothesised that a multi-modal rehabilitation programme, in addition to NIV, would lead to enhanced weight loss. <h3>Method</h3> We conducted a randomised controlled trial of NIV alone vs. NIV and a personalised rehabilitation programme in patients with OHS. Subjects in the intervention group received a bespoke diet and exercise regime, from a dietician and physiotherapist. All patients, in both groups, were reviewed monthly for 3 months. Anthropometrics, exercise capacity and health related quality of life (HQRL) were measured at baseline and at 3 months. The primary outcome measure at 3 months was weight loss. Secondary outcomes included: body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC) blood pressure (BP), rectus femoris cross-sectional area (RF<sub>CSA</sub>) and quadriceps maximal voluntary contraction (QMVC), 6 min walk distance (6MWD) and HRQL measures. <h3>Results</h3> 37 subjects were randomised with data from 30 patients analysed at 3 months (15 in each group). There were no differences between the groups in all parameters measured at baseline. The intervention group showed greater weight loss than the control group (-11.9 ± 6.7 <i>vs. -</i>2.4 ± 6.2 kg; p &lt; 0.0001). There were also differences in NC, WC and HC (all p &lt; 0.001, Table 1) with an improvement in BP observed in the intervention group (Table 1). In addition, there was an increase in weight corrected RF<sub>CSA</sub> and muscle strength (p &lt; 0.0001, Table 1) with an increase in 6MWD in the intervention group (122 ± 161 <i>vs.</i> 46 ± 60 m; p = 0.005; Table 1). Finally, HRQL improved in the intervention group as evidenced by a greater reduction in Epworth sleepiness score, an increase in severe respiratory insufficiency questionnaire sum score and a greater decrease in the hospital and anxiety depression score (Table 1, all p &lt; 0.0001). <h3>Conclusion</h3> In patients with OHS, the addition of a hospital-home hybrid personalised diet and exercise programme to standard NIV was shown to enhance weight loss as well as, skeletal muscle area and strength, exercise capacity and HRQL. <h3>Reference</h3> 1 Murphy PB, Davidson C, Hind MD, <i>et al.</i> Volume targeted versus pressure support non-invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised controlled trial. <i>Thorax</i>. 2012;<b>67</b>:727–34
Testosterone (T) suppression by weight and age groups in four pivotal trials of in-situ forming polymer-delivered, subcutaneously administered leuprolide acetate in men with prostate cancer (PCa).
Authors: Scott T. Tagawa, John A. McLane, Stuart Atkinson, Debbie Boldt-Houle, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2018)

172 Background: In-situ forming polymer-delivered, subcutaneous leuprolide acetate (SC-LA) has previously been shown to suppress serum T levels to ≤20ng/dL in advanced PCa patients. Currently, luteinizing hormone releasing hormone agonists are dosed independently of body weight (BW) or age. Reaching nadir T&lt;20ng/dL within the first year of androgen deprivation therapy (ADT) is associated with improved clinical outcomes such as time to progression and disease specific survival (Klotz 2015). As maintaining castrate T levels during ADT is important, it is of interest to understand if factors such as BW or age should be considered when selecting a therapy. This study aims to determine if patient BW and age correlate with the pharmacodynamic profile of all SC-LA formulations. Methods: In 4 open-label, prospective single-arm, fixed dose, pivotal studies, 438 PCa patients were treated with either 7.5, 22.5, 30, or 45mg SC-LA lasting 1, 3, 4, or 6 months. Blood was sampled at screening, baseline, 2, 4, 8 hours post dosing, day 1, 2, 3, 7, and every other week until end of study and assayed for total T by radioimmunoassay. Results: Mean BW of 86 kg (range 49-146) and age of 73 years (range 40-86) was similar across the 4 studies. &gt;90% of patients in all age groups (including 100% of those &lt;60 years) and ≥92% of patients in all BW groups (including 97% of those ≥90 kg) achieved T≤50ng/dL by week 4. When pooled, all age and BW groups achieved median T≤20ng/dL by week 4 and maintained until the end of the study (Table). Conclusions: The results demonstrate that all SC-LA dose formulations consistently achieve and maintain T≤20ng/dL across all BW and age subgroups, including those with the highest BW (&gt;90 kg) and youngest age (&lt;70 years). BW and age do not appear to have an impact on consistent drug delivery and T suppression by SC-LA. Consistent achievement of T ≤20ng/dL may have implications for improved clinical outcomes and progression free survival in PCa patients. [Table: see text]
Abstract P3-14-09: Low rates of chronic breast cancer related lymphedema (BCRL) in a cohort of high-Risk patients undergoing prospective surveillance with bioimpedance spectroscopy (BIS)
Authors: D Kaufman, C Shah, F Vicini
Journal: Cancer Research (2018)

Abstract Background: We report outcomes using prospective BIS surveillance in a high-risk cohort of patients who all underwent axillary lymph node dissection (ALND). Methods: From 8/2010 through 12/2016, 206 consecutive patients were evaluated with BIS as part of a prospective surveillance program. 30 underwent ALND and constitute the study population. The program included pre-operative BIS measurement as well as post-operative assessments at regular intervals. Patients with L-Dex readings increasing by more than 10 from baseline were considered to have subclinical BCRL and treated with an over-the-counter (OTC) compression sleeve for 4 weeks. For the purpose of this analysis, additional high-risk features were defined as receipt of axillary radiation, a high body mass index (BMI) or the use of taxane based chemotherapy. Chronic BCRL was defined as the need for complex decongestive physiotherapy (CDP). Results: Median follow-up was 36 months (range: 4.8-122.1 months). The median number of nodes removed was 18 (range: 5-32) and the median number of positive nodes was two. The median age for the cohort was 57.5 years old with 70% of patients undergoing mastectomy and the remainder breast conserving therapy. With respect to additional high-risk features, 77% also received taxane-based chemotherapy, 62% axillary irradiation, and 48% had an elevated BMI. Overall, 86% of patients had at least one additional high-risk feature, 70% at least two, and 23% had all three additional high-risk features. Seven patients (23%) had an elevated L-Dex score at some point during follow-up and underwent intervention with an OTC sleeve for 4 weeks. To date, no patients have required CDP at any time. Conclusions: Prospective surveillance with BIS in a high-risk cohort of patients all undergoing ALND (plus additional high-risk features) led to no patients requiring CDP. These excellent findings are consistent with growing data supporting the use of BIS in prospective BCRL surveillance programs. Citation Format: Kaufman D, Shah C, Vicini F. Low rates of chronic breast cancer related lymphedema (BCRL) in a cohort of high-Risk patients undergoing prospective surveillance with bioimpedance spectroscopy (BIS) [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 P3-14-09.
Physician associates must have statutory regulation, says GMC head
Authors: Abi Rimmer
Journal: BMJ (2015)

Physician associates must be subject to statutory regulation, the chief executive of the General Medical Council (GMC) has said.

Speaking at the Medical Women’s Federation autumn conference in London on Friday 6 November, Niall Dickson said that the GMC hadn’t ruled out acting as the regulator of physician associates. “One thing we are absolutely convinced [about is] that physician associates must be regulated, they must come …
Health and education needs in Kurdistan
Authors: Teshk Shawis
Journal: BMJ (2004)

Editor—We are writing on behalf of the medical schools in Iraqi Kurdistan to highlight several points.

Between 1991 and 2003, the Kurdistan region of Iraq suffered a state of double embargo: one imposed by the United Nations' sanctions, which affected the entire country, and another created by Saddam Hussein's central government.

One of the most negative impacts of this situation was on health and education. The Kurdistan regional government soon realised that the only existing university and …
Effect of Dermatology Consultation on Outcomes for Patients With Presumed Cellulitis
Authors: Lauren N. Ko, Anna C. Garza-Mayers, Jessica St John, Lauren Strazzula, Priyanka Vedak, Radhika Shah, Allison S. Dobry, Sowmya R. Rao, Leslie W. Milne, Blair Alden Parry, Daniela Kroshinsky
Journal: JAMA Dermatology (2018)

Each year, cellulitis leads to 650 000 hospital admissions and is estimated to cost $3.7 billion in the United States. Previous literature has demonstrated a high misdiagnosis rate for cellulitis, which results in unnecessary antibiotic use and health care cost.To determine whether dermatologic consultation decreases duration of hospital stay or intravenous antibiotic treatment duration in patients with cellulitis.This randomized clinical trial was conducted in a large urban tertiary care hospital between October 2012 and January 2017, with 1-month follow-up duration. Patients were randomized to the control group, which received the standard of care (ie, treatment by primary medicine team), or the intervention group, which received dermatology consultation. Medical chart review of demographic information and hospital courses was performed. Adult patients hospitalized with presumed diagnosis of cellulitis were eligible. A total of 1300 patients were screened, 1125 were excluded, and 175 were included. Statistical analysis was employed to identify significant outcome differences between the 2 groups.Dermatology consultation within 24 hours of hospitalization.Length of hospital stay and duration of intravenous antibiotic treatment.Of 175 participants, 70 (40%) were women and 105 (60%) were men. The mean age was 58.8 years. Length of hospital stay was not statistically different between the 2 groups. The duration of intravenous antibiotic treatment (<4 days: 86.4% vs 72.5%; absolute difference, 13.9%; 95% CI, 1.9%-25.9%; P = .04) and duration of total antibiotic treatment was significantly lower in patients who had early dermatology consultation (<10 days: 50.6% vs 32.5%; absolute difference, 18.1%; 95% CI, 3.7%-32.5%; P = .01). Clinical improvement at 2 weeks was significantly higher for those in the intervention group (79 [89.3%] vs 59 [68.3%]; absolute difference, 21.0%; 95% CI, 9.3%-32.7%; P < .001). There was no significant difference in 1-month readmission rate between the groups (4 [4.5%] vs 6 [6.9%]; absolute difference, -2.4%; 95% CI, -9.3% to 4.5%; P = .54). In the intervention group, the rate of cellulitis misdiagnosis was 30.7% (27 of 88 participants). Among the entire cohort, 101 (57.7%) patients were treated with courses of antibiotics longer than what is recommended by guidelines.Early dermatologic consultation can improve outcomes in patients with suspected cellulitis by identifying alternate diagnoses, treating modifiable risk factors, and decreasing length of antibiotic treatment.clinicaltrials.gov Identifier: NCT01706913.
CHEMICAL DENERVATION OF THE RENAL ARTERY BY VINCRISTINE IN SWINE. A NEW CATHETER BASED TECHNIQUE
Authors: Christodoulos Stefanadis, Konstantinos Toutouzas, Andreas Synetos, Costas Tsioufis, Antonios Karanasos, Georgios Agrogiannis, Leonidas Stefanis, Efstratios Patsouris, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2012)
Patient reported outcome measures(PROMs) in neuro-oncological surgery: questionnaire survey in brain tumour patients and the proposed framework of new neuro-oncological surgery PROM
Authors: Prajwal Ghimire, Keyoumars Ashkan, Victoria Hurwitz
Journal: Neuro-Oncology (2018)

Neuro-oncological surgery is a major field of neurosurgery with variety of surgical methods for diagnosis and treatment of different types of brain tumours. Patient reported outcome measures currently in use in neurosurgery do not address the specific needs of the patients with brain tumours. In this study, we identify the unmet needs of brain tumour patients and incorporate them into a framework of specific PROM. A questionnaire survey was conducted among diagnosed cases of brain tumour patients in different stages of treatment during a brain tumour support group meeting. The responses were recorded and analysed and the unmet need of the brain tumour patients were identified. 66.67% of patients mentioned that their physical symptoms were not adequately addressed. Similarly, 33.33% patients felt that their mental and emotional issues were not adequately dealt with during the diagnosis, treatment and follow up period of their brain tumor management. The target population for the PROM will be brain Tumor patients (adult and pediatric). The PROM would collect information from patients preoperatively and Post-operatively. The conceptual domains for neuro-oncology PROM will include health related quality of life (physical, mental, social and emotional), symptoms (specific to neuro-oncology) including weakness, memory, taste, seizure, incontinence, neuro-oncology specific disability and functional status. In conclusion, there is an emergent need to develop a neuro-oncological surgery PROM to address the specific unmet needs of the field of neuro-oncological surgery. The proposed framework would be beneficial in further study and development of the PROM.
Culture of fear in NHS is making doctors ill, says Gerada
Authors: Abi Rimmer
Journal: BMJ (2014)

A culture of fear in the NHS is one of the main causes of doctors’ illness, Clare Gerada, former chair of the Royal College of General Practitioners, has said.

Gerada is medical director of the Practitioner Health Programme (PHP), a confidential London based health service for doctors and dentists. Speaking at the Medical Women’s Federation autumn conference in London, Gerada said that one of the chief causes of illness among doctors treated by PHP was the environment they worked in.

“I think the NHS as a system is the cause of many of …