tbuckley/cabot-search huggingface dataset:
Can we proceed with physical activity recommendations if (almost) no clinical trial data exist on mortality?
Authors: Eric J Shiroma, I-Min Lee
Journal: British Journal of Sports Medicine (2018)

Observational studies consistently show reduced mortality rates among participants with higher physical activity levels compared with participants with less activity.1 2 However, as Kujala eloquently points out,3 there are sparse data from randomised trials leading some argue that a causal relationship of physical activity with mortality cannot be confirmed. As current physical activity guidelines were developed primarily based on observational studies of physical activity and clinical outcomes,4 one might question how despite the lack of trial data—the gold standard for causality inference—policy and medical advice for physical activity can be made. This opinion piece aims to highlight some of the challenges and implications of examining physical activity and mortality solely through a lens which sees causality only when randomised trial data are available.

To our knowledge, there are currently no completed randomised trials of physical activity where mortality is a prespecified primary outcome, and where analyses are adequately powered to examine the effects of physical activity on mortality. While several large trials, such as LIFE5 and Look AHEAD,6 were able to provide a secondary look at mortality, they were not designed with mortality as a primary outcome. (And, further, Look AHEAD was not designed to exclusively target physical activity, but rather both diet and physical activity in order to achieve and maintain weight loss.) Thus, null findings for mortality or other clinical outcomes should be interpreted cautiously due to a lack of statistical power. For example, the LIFE study comprised 1635 adults between the ages of 70 and 89 years who were followed for an average duration of 2.6 years.5 Using the average probability of death, and the estimated reduction in mortality from a large observational study2 comparing those who participated in at least 150 min of moderate-to-vigorous activity with those who did no …
PREDICTION OF MODE OF DEATH BY MODEL OF END-STAGE LIVER DISEASE EXCLUDING INR (MELD-XI) SCORING SYSTEM IN PATIENTS ADMITTED FOR ACUTE DECOMPENSATED HEART FAILURE WITH PRESERVED AND REDUCED EJECTION FRACTION: A COMPARISON WITH NON-INVASIVE LIVER FIBROSIS MARKERS
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Jun Nakamura, Makoto Abe, Kazuya Tanabe, Kiyomi Kayama, Masatsugu Kawahira, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2018)
Renal Fanconi syndrome with meropenem-containing regimen in drug-resistant tuberculosis
Authors: Simon Tiberi, Marie-Christine Payen, Giovanni Sotgiu, Lia D'Ambrosio, Rosella Centis, Jan-Willem Alffenaar, Giovanni Battista Migliori
Journal: European Respiratory Journal (2018)

We read with great interest the correspondence by Abadie et al . [1] describing the case of extensively drug-resistant tuberculosis patient developing renal Fanconi syndrome while receiving a meropenem/amoxicillin–clavulanate-containing regimen. Renal Fanconi syndrome reported as rare adverse event during treatment of XDR-TB with meropenem <http://ow.ly/3RHG30hVsef>
Tumor-infiltrating lymphocytes to predict survival to anthracycline/taxane-based neoadjuvant chemotherapy in breast cancer.
Authors: Qiyun Ou, Yunfang Yu, Xiaoyun Xiao, Baoming Luo
Journal: Journal of Clinical Oncology (2018)

2 Background: Current guidelines have limited information regarding tumour-infiltrating lymphocytes (TILs) were predictive in breast cancer survival treated with neoadjuvant chemotherapy, although some studies suggest a benefit. We quantify the prognostic value of this biomarker for neoadjuvant chemotherapy in patients with breast cancer. Methods: PubMed and EMBASE were searched until March 2017 for studies that investigated the association of TILs with survival for anthracycline/taxane-based neoadjuvant chemotherapy in breast cancer. Overall survival (OS) and disease-free survival (DFS) were combined using random-effects meta-analysis calculated as combined hazard ratio (HR) with 95% credible intervals (CIs). The interaction test was adopted in order to determine the differential effect according to the histology subtypes and TILs subsets. The PROSPERO registry number is CRD42017072133. Results: We identified 16 studies comprising 2,523 patients were entitled. According to histology subtypes analysis indicated that TILs were not prognostic markers for DFS and OS in overall population, but high TILs were related to improved DFS (HR = 0.73, 95% CI, 0.63 – 0.86) and OS (HR = 0.65, 95% CI, 0.51 – 0.83) in triple negative breast cancer (TNBC) patients, and high TILs were also related to better DFS (HR = 0.62, 95% CI, 0.40 – 0.96) in HER2–positive patients. For TILs subsets, our results indicated that high TILs were prognostic markers for DFS (HR = 0.94, 95% CI, 0.89 – 0.98) and OS (HR = 0.74, 95% CI, 0.58 – 0.94). In an ad-hoc analysis, increasing CD8+ lymphocytes were associated with improved DFS (HR = 0.46, 95% CI, 0.33 – 0.65) and OS (HR = 0.41, 95% CI, 0.24 – 0.71), high CD8/FOXP3 ratio was correlated with prolonged DFS (HR = 0.43, 95% CI, 0.29 – 0.63) and OS (HR = 0.45, 95% CI, 0.26 – 0.76), while rich FOXP3+ lymphocytes were associated with reduced DFS (HR = 1.47, 95% CI, 1.01 – 2.15) in overall population. Conclusions: The present results reveal TILs as a predictor of survival to anthracycline/taxane-based neoadjuvant chemotherapy in breast cancer patients. Furthermore, predictive benefit appears to be influenced by breast cancer subtypes and TILs subsets as well.
Will the introduction of the MMC foundation programme mean that there will be a significant reduction in the number of stand alone training posts in different specialties in the future?
Authors: Trevor Pickersgill
Journal: BMJ (2006)

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>
OUTCOMES AND SOCIETY OF THORACIC SURGEONS RISK SCORE: A SUBANALYSIS OF THE REPRISE III RANDOMIZED CLINICAL TRIAL
Authors: Michael Reardon, Christopher Meduri, Raj Makkar, Tanvir Bajwa, Axel Linke, Dean Kereiakes, Ron Waksman, Vinod H. Thourani, Steven J. Yakubov, Wesley Pederson, Bruce Rutkin, John Wang, Dominic Allocco, Ian Meredith, Ted Feldman, Neil Kleiman
Journal: Journal of the American College of Cardiology (2018)
Find and treat or find and lose? Tuberculosis treatment outcomes among screened newly arrived asylum seekers in Germany 2002 to 2014
Authors: Anna Kuehne, Barbara Hauer, Bonita Brodhun, Walter Haas, Lena Fiebig
Journal: Eurosurveillance (2018)

Background Germany has a low tuberculosis (TB) incidence. A relevant and increasing proportion of TB cases is diagnosed among asylum seekers upon screening. Aim: We aimed to assess whether cases identified by screening asylum seekers had equally successful and completely reported treatment outcomes as cases diagnosed by passive case finding and contact tracing in the general population. Methods: We analysed characteristics and treatment outcomes of pulmonary TB cases notified in Germany between 2002 and 2014, stratified by mode of case finding. We performed three multivariable analyses with different dependent variables: Model A: successful vs all other outcomes, Model B: successful vs documented non-successful clinical outcome and Model C: known outcome vs lost to follow-up. Results: TB treatment success was highest among cases identified by contact tracing (87%; 3,139/3,591), followed by passive case finding (74%; 28,804/39,019) and by screening asylum seekers (60%; 884/1,474). Cases identified by screening asylum seekers had 2.4 times higher odds of not having a successful treatment outcome as opposed to all other outcomes (A), 1.4 times higher odds of not having a successful treatment outcome as opposed to known non-successful outcomes (B) and 2.3 times higher odds of loss to follow-up (C) than cases identified by passive case finding. Conclusion: Screened asylum seekers had poorer treatment outcomes and were more often lost to follow-up. Linking patients to treatment facilities and investigating potential barriers to treatment completion are needed to secure screening benefits for asylum seekers and communities.
Sexual Dimorphism in Eosinophilic Esophagitis: Roles of Differential Chemokine and Profibrogenic Expression
Authors: Quan M. Nhu, Loan D. Duong, Renee Rawson, Ranjan Dohil, Richard C. Kurten, Fouad J. Moawad, Seema S. Aceves
Journal: Journal of Allergy and Clinical Immunology (2018)
CCGs seeking authorisation without full member practice sign up, warns BMA
Authors: Caroline White
Journal: BMJ (2012)

The authorisation of clinical commissioning groups (CCGs) is in danger of going ahead without full member practice sign up—a key requirement of the process—GP leaders have warned.

Chaand Nagpaul, negotiator for the BMA’s General Practitioners Committee (GPC), said that some CCGs were pressing ahead with authorisation without all practices having signed the constitution. This was despite the fact that one of the key requirements of authorisation, as specified by the NHS Commissioning Board, is that there should be “demonstrable sign up by member practices.” 

“What we are seeing is …
Patients are more important than protocols, says CQC adviser
Authors: Abi Rimmer
Journal: BMJ (2014)

Evidence of effective patient care is more important than protocols or how often stethoscopes are cleaned, the Care Quality Commission (CQC) has said. 

Nigel Sparrow, senior national GP adviser at the CQC, commented on the issue at a Medical Protection Society conference in London. He explained that, since April, the regulator had adopted a new approach to inspections of GP practices. He said that one GP, whose practice had been recently inspected, had advised other practices to ensure that their protocols were up to date in anticipation of a …
Heart Block After Discharge in Patients Undergoing TAVR With Latest-Generation Valves
Authors: Amneet Sandhu, Wendy Tzou, Karen Ream, Javier Valle, Christine Tompkins, Duy T. Nguyen, William H. Sauer, John D. Carroll, John Messenger, Ryan G. Aleong
Journal: Journal of the American College of Cardiology (2018)
A NEW STANDARD FOR ULTRA-LOW DOSE OF CONTRAST WITH THE USE OF AUTOMATIC INJECTOR SPECIALIZED ALGORITHM IN CORONARY PROCEDURES
Authors: Maheedhar Gedela, Filip Oleszak, Udit Bhatnagar, Shenjing Li, Chirag Desai, Jeffrey Wilson, Tomasz Stys, Adam Stys
Journal: Journal of the American College of Cardiology (2018)
COMPARISON OF PULMONARY ARTERY CATHETER USE IN CARDIOGENIC SHOCK VERSUS SEPTIC SHOCK
Authors: Gbolahan Ogunbayo, Patricia Santos, Naoki Misumida, Le Dung Ha, Suartcha Prueksaritanond, Karam Ayoub, Meera Marji, Andrew Kolodziej, Ahmed Abdel-Latif, Maya Guglin
Journal: Journal of the American College of Cardiology (2018)
I have just started a three year rotation and my first job is banded 2A. Is this pay protected for the rest of the contract?
Authors: Simon Eccles
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>
Genetic profiling using plasma-derived cell-free DNA in therapy-naïve hepatocellular carcinoma patients: a pilot study
Authors: C.K.Y. Ng, G.G. Di Costanzo, N. Tosti, V. Paradiso, M. Coto-Llerena, G. Roscigno, V. Perrina, C. Quintavalle, T. Boldanova, S. Wieland, G. Marino-Marsilia, M. Lanzafame, L. Quagliata, G. Condorelli, M.S. Matter, R. Tortora, M.H. Heim, L.M. Terracciano, S. Piscuoglio
Journal: Annals of Oncology (2018)
What Is an Addictive Disorder?
Authors: Carlos Blanco, Wilson M. Compton, Marsha F. Lopez
Journal: JAMA Psychiatry (2018)

The publication of the DSM-5 and the evolution of the Research Domain Criteria have rekindled interest in defining what an addictive disorder truly is. The study of Lee et al,1 by postulating the existence of betel use disorder, offers an opportunity to examine this important question.
Elevated Serum Xanthine Oxidase Activity Is Associated With the Development of Type 2 Diabetes: A Prospective Cohort Study
Authors: Xue Li, Xing Meng, Xiangchun Gao, Xiuyu Pang, Yanjiao Wang, Xiaoyan Wu, Xinrui Deng, Qiao Zhang, Changhao Sun, Ying Li
Journal: Diabetes Care (2018)

OBJECTIVE We aimed to evaluate whether xanthine oxidase (XO), a key enzyme in uric acid (UA) metabolism and a major source of reactive oxygen species, plays a causal and important role in the development of type 2 diabetes mellitus (T2DM) in a large prospective cohort study. RESEARCH DESIGN AND METHODS A total of 4,412 diabetes-free adults (2,071 women and 2,341 men) aged 30–65 years at baseline in 2008 were involved. Participants were followed for incident change of glucose metabolism during an average of 4.7 years. At baseline, serum XO and UA, serum lipids, and glucose homeostasis indexes including fasting blood glucose (FBG), 2-h blood glucose (PBG), glycosylated hemoglobin A1c (HbA1c), and fasting insulin were tested for analysis. RESULTS During an average follow-up period of 4.7 years, 249 women and 360 men developed new-onset T2DM. Serum XO activity was positively associated with UA concentration (all P values &amp;lt;0.001). When XO activity and UA concentration were considered in the same model of the sex-specific analysis, only XO activity was significantly associated with the incidence of T2DM, with the hazard ratios from the bottom to the top quartile of XO activity being 1.00, 1.67 (95% CI 1.00–2.79), 1.86 (1.11–3.13), and 2.36 (1.43–3.90) in women and 1.00, 1.01 (0.68–1.52), 1.41 (0.98–2.03), and 1.90 (1.30–2.78) in men. CONCLUSIONS Elevated serum XO activity, but not UA concentration, was associated with an increased risk of developing T2DM in women and men with mutual adjustment for XO and UA. Further studies are needed to examine the underlying mechanisms.
EARLY READMISSIONS AFTER REVASCULARIZATION IN PATIENTS PRESENTING WITH NON-ST ELEVATION MYOCARDIAL INFARCTION
Authors: Robin Jacob, Pimprapa Vejpongsa, Kassra Poosti, Viraj Bhise, Yelin Zhao, Salman Arain, Prakash Balan, Konstantinos Charitakis, Mohammad Madjid, Nils Johnson, H. Vernon Anderson, Richard Smalling, Abhijeet Dhoble
Journal: Journal of the American College of Cardiology (2018)
DIAGNOSIS AND DIFFERENTIATION OF ACUTE MASSIVE AND SUBMASSIVE FROM SUBSEGMENTAL PULMONARY EMBOLISM USING NOVEL ECHOCARDIOGRAPHIC METHODS
Authors: Aditya Sood, Mobeen Rehman, Arshad Ali Javed, Emmanuel Akintoye, Kartik Kumar, Manmohan Singh, Luis Afonso
Journal: Journal of the American College of Cardiology (2018)
Phase II randomized study of abiraterone acetate plus ADT versus apalutamide versus abiraterone and apalutamide in patients with advanced prostate cancer with non-castrate testosterone levels. (LACOG 0415).
Authors: Fernando C. Maluf, Oren Smaletz, Fabio A. B. Schutz, Vinicius Carrera Souza, Andre Poisl Fay, Daniel Herchenhorn, Gustavo Werutsky, Telma Murias Santos
Journal: Journal of Clinical Oncology (2018)

TPS404 Background: Androgen deprivation therapy (ADT) combined with abiraterone (AA) or docetaxel are considered the standard of care (SOC) for patients with hormone sensitive (HS) advanced/ metastatic prostate cancer (PC) (STAMPEDE, LATITUDE, CHAARTED). Treatment that could delay disease progression with less toxicities and better quality of life is warrant. Recently, enzalutamide monotherapy showed a 92% PSA response in patients with advanced/ mestatatic prostate cancer without previous hormone therapy. Our study aims to evaluate the efficacy of apalutamide, a second-generation AR inhibitor, monotherapy or in combination with AA vs. SOC in advanced/metastatic HSPC. Methods: This is a phase II, open label, randomized trial evaluating the efficacy of AA 1000mg po qd plus prednisone 5mg po bid and ADT vs. Apalutamide 240mg po alone vs. AA and Apalutamide in patients with advanced or metastatic PC with non-castrate testosterone levels. Main eligible criteria are: 1. Histologically confirmed prostate adenocarcinoma; 2. Hormone naïve patients with indication to ADT in the following settings: Advanced loco-regional disease not amenable to curative local therapy (T3/4 or node positive); Biochemical relapse after primary treatment (surgery or radiotherapy) with PSA &gt;= 4 ng/ml and rising with doubling time less than 10 months or PSA &gt;= 20 ng/ml or N+ or M+; 3. Newly diagnosed metastatic disease; 4. Patient is symptomatic or moderately symptomatic; 5. Non-castration level of testosterone &gt;= 230 ng/dL. The primary endpoint is undetectable PSA levels (below 0.2ng/mL) at week 25. The study aims for 65% of undetectable PSA at week 25 (power of 80% and alfa of 5%) and a total sample size of 126 patients. Secondary endpoints are PSA progression and PSA response (50% and 80%) at week 25, radiographic progression-free survival, safety, health quality of life (FACT-P) and correlation of serum androgen levels with response. As of October 17th, 2017 the study enrolled 1 patient and the recruitment is planned for 12 months in a total of 10 sites in Brazil. This trial is registered at Clinical trial information: NCT02867020.
BSREM Reconstruction for Improved Detection of In-Transit Metastases With Digital FDG-PET/CT in Patients With Malignant Melanoma
Authors: Arwa Aljared, Abdullah Awad Alharbi, Martin W. Huellner
Journal: Clinical Nuclear Medicine (2018)

Block sequential regularized expectation maximization (BSREM) is a Bayesian penalized-likelihood reconstruction algorithm for PET, which reaches full convergence without the detriment of deteriorating the image quality by noise. Therefore, BSREM might have implications particularly for the detection of small lesions, which may be beneficial in melanoma patients. Our case of a 70-year-old man with metastasized malignant melanoma illustrates the impact of such a novel iterative PET reconstruction algorithm. Whereas the lymph node metastases are seen with the latest generation ordered subset expectation maximization reconstruction, the in-transit metastases are identified straightforward only with BSREM reconstruction.
Editor’s Choice: The importance of being civil
Authors: Tom Moberly
Journal: BMJ (2015)

Doctors are often rude to one another. As with any other group of people, they are discourteous, they ignore unwanted advice, and they belittle others to make themselves seem superior. 

When doctors are uncivil to one another, they hamper their team’s ability to diagnose and treat patients appropriately, say researchers writing in the journal Paediatrics . In BMJ Careers Matthew …
All medical students to sit the same exam under GMC plans
Authors: Abi Rimmer
Journal: BMJ (2017)

The General Medical Council has launched a consultation on proposals for a single licensing exam for all doctors who wish to practise in the UK.1

If introduced, the national medical licensing assessment (MLA) will apply to all UK medical graduates. Currently, every one of the UK’s 32 medical schools has its own assessment system and there is no …
Removing GP training supplement would be disaster, says BMA
Authors: Abi Rimmer
Journal: BMJ (2015)

Plans to remove the GP trainee supplement would be a disaster at a time when the specialty is facing a retention and recruitment crisis, the BMA has warned.

In its report on the junior doctor and consultant contracts published last month, the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) recommended that the GP trainee supplement be removed.1 It said that GP trainees …
A phase II randomized, placebo controlled study to evaluate the efficacy of the combination of gemcitabine, erlotinib, and metformin in patients with locally advanced or metastatic pancreatic cancer.
Authors: Johanna Wilmink, Sil Kordes, Koos Zwinderman, Ron Mathot, Cornelis J. A. Punt, Dirk Richel
Journal: Journal of Clinical Oncology (2014)

4021 Background: In addition to clinical data from retrospective observational studies, there is a strong preclinical rationale for a beneficial effect of metformin in cancer treatment. Therefore we conducted a randomized phase II, placebo controlled study to assess the clinical effects of metformin in pancreatic cancer. Methods: Patients with locally advanced or metastatic pancreatic cancer were randomly assigned to gemcitabine at 1000 mg/m2 on day 1, 8 and 15 q 4 weeks plus erlotinib 100 mg once daily in combination with metformin or placebo. Metformin was administered at a dose of 500 mg twice daily during the first week. If tolerated well, the dose was increased to 1000 mg twice daily. Patients were stratified according to stage of disease and the presence of diabetes. The primary endpoint was survival at 6 months. Secondary endpoints were overall survival (OS), progression free survival (PFS), objective response rate(ORR), toxicity profile, pharmacodynamics, and biomarker research. Results: A total of 121 patients were included. Baseline characteristics were well balanced. Median follow-up is 23.6 months (95%CI: 17.5-29.6). Survival at 6 months was 55% (95% CI: 42-68) for the metformin arm versus 66% (95% CI: 54-78) for the placebo arm (p=0.23). Median OS and PFS were 6.8 (95%CI: 5.3-8.3)and 4.4 (95%CI: 2.0-6.7) months for the metformin arm versus 7.6 (95%CI: 6.3-9.0) and 5.4 (95%CI: 4.7-6.1) months for the placebo arm (p=0. 62 and p=0.45), respectively. The objective response rate was 9% in both groups. The addition of metformin was well tolerated with no significant differences in grade ≥3 toxicity between treatment arms. Baseline insulin and glucose levels were not predictive for outcome. Conclusion: The addition of metformin to gemcitabine and erlotinib does not improve the outcome of patients with locally advanced or metastatic pancreatic cancer. Additional data on predictive biomarkers, including IGF1 and IGF binding protein-3 and pharmacodynamics will be presented at the meeting. Clinical trial information: NCTO1210911.
ATRIAL FIBRILLATION IS ASSOCIATED WITH HIGHER RATES OF DEATH AND HEART FAILURE HOSPITALIZATIONS IN PATIENTS UNDERGOING MITRACLIP: OUTCOMES FROM THE TVT REGISTRY
Authors: Sameer Arora, Sreekanth Vemulapalli, Amanda Stebbins, Cassandra Ramm, Andrzej Kosinski, Zehra Husain, Alice Wang, Thomas Caranasos, Matthew Cavender, John Vavalle
Journal: Journal of the American College of Cardiology (2018)
The health policy guru
Authors: Sabina Dosani
Journal: BMJ (2006)

Chris Ham is professor of health policy and management at the University of Birmingham. He has worked on NHS reforms, including foundation trusts, primary care trusts, payment by results, and independent inspection. He advised the World Bank, the World Health Organization, the Health Departments of New Zealand and Sweden, the Audit Commission, the British Dental Association, the British Medical Association, the NHS Confederation, and the House of Commons Health Committee. He is a fellow of the Royal Society of Medicine, a founding fellow of the Academy of Medical Sciences and an honorary fellow of the Royal College of Physicians. He was awarded a CBE in 2004 for services to the NHS