tbuckley/cabot-search huggingface dataset:
David Oliver: The TaxPayers’ Alliance, Hancock, and health technology
Authors: David Oliver
Journal: BMJ (2019)

On 24 April the TaxPayers’ Alliance published a report on the potential benefits of automation for the NHS, social care, and wider local government services.1 The previous day the organisation, which describes itself as a think tank and “non-partisan grassroots campaign for lower taxes,” which “speaks up for taxpayers,”2 announced that it was launching the report “with” Matt Hancock, secretary of state for health and social care in England.3 I can’t see any evidence in the report of his involvement, beyond an enthusiastic foreword.

The report states, “There are barriers to entry into the NHS for companies offering innovative healthcare solutions. Many are being addressed and in the long term it’s crucial that the NHS remains open to new ideas and innovation.” …
Selection of rapid responses
Authors: Diane-Marie Campbell, Colin Mackenzie, Zarrin S Siddiqui, Shashi Kiran, Rob J Henderson
Journal: BMJ (2002)

When Kallur Sureshs viewpoint was originally published in the BMJ , it sparked off a virtual debate between doctors all over the world via the website (bmj.com). Here is a selection.

Editor—When I trained, the detailed neuroanatomy we studied seemed largely irrelevant to any but neurosurgeons. Now we have computed tomography scans in most hospitals—and those of us in the front line are expected to be able to see at least important abnormalities.

Budding surgeons who struggled with biochemistry and immunology may have wondered about their necessity, but now they work in concert with molecular oncologists and manage their own transplant patients.

How can a psychiatrist refer patients for ECT needing an anaesthetic if they dont know if they are fit for that procedure? And how can they safely prescribe if they have no understanding of drug interactions and physiology?

Possibly the move towards holistic care has gone too far, but I expect any clinician to be able to manage his own complications, and to assess sensibly, and if necessary refer appropriately, serious incidental conditions in his patients.

Editor—There is a lot of merit in this suggestion, and it was recognised many years ago by practitioners working on teeth. Now …
Surgical emergencies: acute abdominal pain (Part 2)
Authors: Kevin Turner, Adam Jones, Ashok Handa
Journal: BMJ (2000)

Adam Jones, Kevin Turner, and Ashok Handa continue to explain the treatment of patients in acute pain In last month's article we explained how to deal with a call from an accident and emergency department to see a patient with severe undiagnosed acute abdominal pain. This month we consider three specific surgical abdominal emergencies: ruptured abdominal aortic aneurysm, perforated viscus, and pancreatitis. Abdominal aortic aneurysms are important because they are common. About 1% of all men over 65 years have an abdominal aortic aneurysm, and if this ruptures mortality is over 50% - and that is only in the people who survive long enough to reach hospital.1 This diagnosis must not be missed because minutes matter. So when you see a patient in accident and emergency with abdominal pain who looks terrible, specifically try to exclude this diagnosis. Is the patient elderly? Is s/he known to have an abdominal aortic aneurysm? Is the pain radiating to the back and of sudden onset? The diagnosis is confirmed if you can feel a pulsatile mass in the abdomen. Here, the secret is to place both hands gently, side by side, in the epigastrium and wait for a few seconds. The pulsation is not always obvious because the patient is likely to be hypotensive. If you cannot feel a pulsatile mass consider other causes of collapse and shock - for example, myocardial infarction, pancreatitis, perforation, or renal calculi. Even so the presence of back pain and collapse still makes a ruptured aneurysm the likely diagnosis (see box 1). ### Box 1-Top tipsRETURN TO TEXT
Do we need the Hippocratic oath?
Authors: Kate Rampe
Journal: BMJ (2009)

The classic version is outdated, but we still need an ethical declaration on graduation rampe.k@gmail.com The tradition of making an ethical and professional declaration on graduation from medical school is currently a popular one. Through a formal statement, the newly qualified doctor makes a commitment to behave in a professional and ethical manner, to consider the wellbeing of their patients, and above all, to work to improve their patients’ health. Oath taking now takes place in half of UK medical schools, in nearly all US schools, and in about half of schools in Australia.12 The custom of physicians taking an oath to uphold an ethical code is old and widespread: the oath of the Hindu physician (1400s BC); “Advice to a physician” (Persia, 900s); and the 17 rules of Enjuin (Japan, 1500s) are just three examples.3 In the West the best known is the Hippocratic oath (box 1), composed around 410 BC and the inspiration or foundation for most of the oaths used today, including the World Medical Association’s Geneva Declaration, originally formulated by the association in 1948 for the specific purpose of setting ethical guidelines for newly qualified doctors (box 2).34 There are a wide variety of oaths used within and between countries, and many faculties or graduating classes choose to compose their own, generally based on one of the older oaths but uniquely tailored to their ideals.56 #### Box 1: The Hippocratic oath I swear by Apollo the physician, and Asclepius, and Hygieia and Panacea and all the gods and goddesses as my witnesses, that, according to my ability and judgement, I will keep this Oath and this contract:
Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents
Authors: Chen Lossos, Yunpeng Liu, Kellie E. Kolb, Amanda L. Christie, Alexandria Van Scoyk, Sanjay M. Prakadan, Kay Shigemori, Kristen E. Stevenson, Sara Morrow, Olivia D. Plana, Cameron Fraser, Kristen L. Jones, Huiyun Liu, Christian P. Pallasch, Rebecca Modiste, Quang-De Nguyen, Jeffrey W. Craig, Elizabeth A. Morgan, Francisco Vega, Jon C. Aster, Kristopher A. Sarosiek, Alex K. Shalek, Michael T. Hemann, David M. Weinstock
Journal: Cancer Discovery (2019)

The extraordinary activity of high-dose cyclophosphamide against some high-grade lymphomas was described nearly 60 years ago. Here we address mechanisms that mediate cyclophosphamide activity in bona fide human double-hit lymphoma. We show that antibody resistance within the bone marrow (BM) is not present upon early engraftment but develops during lymphoma progression. This resistance required a high tumor:macrophage ratio, was recapitulated in spleen by partial macrophage depletion, and was overcome by multiple, high-dose alkylating agents. Cyclophosphamide induced endoplasmic reticulum (ER) stress in BM-resident lymphoma cells in vivo that resulted in ATF4-mediated paracrine secretion of VEGFA, massive macrophage infiltration, and clearance of alemtuzumab-opsonized cells. BM macrophages isolated after cyclophosphamide treatment had increased phagocytic capacity that was reversed by VEGFA blockade or SYK inhibition. Single-cell RNA sequencing of these macrophages identified a "super-phagocytic" subset that expressed CD36/FCGR4. Together, these findings define a novel mechanism through which high-dose alkylating agents promote macrophage-dependent lymphoma clearance. SIGNIFICANCE: mAbs are effective against only a small subset of cancers. Herein, we recapitulate compartment-specific antibody resistance and define an ER stress-dependent mechanism induced by high-dose alkylating agents that promotes phagocytosis of opsonized tumor cells. This approach induces synergistic effects with mAbs and merits testing across additional tumor types.See related commentary by Duval and De Palma, p. 834.This article is highlighted in the In This Issue feature, p. 813.
Abstract A53: Akt inhibitior MK2206 combination to neoadjuvant radiotherapy: Improving the rectal cancer treatment
Authors: Fernanda C. Koyama, Camila M. Lopes Ramos, Jennifer M. Fernandes, Fernanda C. Ledesma, Venancio A F Alves, Fernanda C. Vailati, Angelita Habr-Gama, Rodrigo O. Perez, Anamaria A. Camargo
Journal: Clinical Cancer Research (2018)

Abstract Resistance to therapy is the major obstacle to a favorable outcome in cancer treatment. Neoadjuvant chemoradiotherapy (nCRT) can lead to complete tumor regression in a significant proportion of patients with rectal cancer (up to 40%). The possibility of avoiding radical surgery and its associated functional consequences for those who present complete response has become increasingly attractive, but approximately 60% of patients have only partial or no tumor remission after nCRT. In order to identify molecular mechanisms determining poor response to nCRT and to uncover optimized treatment strategies, we have conducted global gene expression analysis followed by pathway enrichment analysis in pretreatment biopsies from patients showing complete or poor clinical response to nCRT. We show that mitochondrial oxidative phosphorylation and phosphatidylinositol signaling pathways are consistently altered in rectal tumors comparatively. Both pathways have already been associated with resistance to radiation and chemotherapy in solid tumors and appear to converge on the activation of the Akt pathway in nonresponding tumors. To further address the role of Akt activation in response to nCRT, we evaluated by immunohistochemistry, Akt activation in an independent set of pretreatment biopsies from rectal cancer patients and observed not only high pAkt levels in those presenting poor response to nCRT but also that nuclear pAkt can also discriminate resistant tumors. We also evaluated the combination of an allosteric Akt-inhibitor MK2206 to chemoradiation in a radioresistant colorectal cancer cell line SW480 either in vitro and in vivo and observed an improvement of 50% of tumoricidal effect. Altogether, our results indicate that activation of the Akt pathway is a key event affecting response to nCRT and that combining chemoradiotherapy and Akt inhibitors such as MK2206 may significantly improve response rates to neoadjuvant therapy in rectal cancer. Citation Format: Fernanda C. Koyama, Camila M. Lopes Ramos, Jennifer M. Fernandes, Fernanda C. Ledesma, Venancio A F Alves, Fernanda C. Vailati, Angelita Habr-Gama, Rodrigo O. Perez, Anamaria A. Camargo. Akt inhibitior MK2206 combination to neoadjuvant radiotherapy: Improving the rectal cancer treatment [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A53.
A handlebar injury to the abdomen
Authors: Adam M Sierakowski, Alex Self, Maria Memtsa, Sadasivam Selvakumar, Fida Alaeddin
Journal: BMJ (2008)

A 14 year old boy presented at the emergency department with severe abdominal pain in the right upper quadrant. Two hours before he had lost control of his bicycle and landed heavily on the handlebar. He had vomited once since. On examination there was bruising to the right upper quadrant. The abdomen was soft but diffusely tender throughout the right side. There were no signs of haemodynamic instability. His white cell count was raised at 19×109/l (normal range 4-11×109/l), but all other results of blood tests were normal. Figure 1 shows the patient's initial plain abdominal radiograph and figure 2 the computerised tomogram that followed. Fig 1 Plain abdominal radiograph Fig 2 Axial contrast computed tomogram of the abdomen
Risk of dying unnaturally among people aged 15–35 years who have harmed themselves and inflicted violence on others: a national nested case-control study
Authors: Sarah Steeg, Roger T Webb, Pearl L H Mok, Carsten Bøcker Pedersen, Sussie Antonsen, Nav Kapur, Matthew J Carr
Journal: The Lancet Public Health (2019)

BackgroundSelf-harm and violent criminality have overlapping causes, but people who engage in these behaviours are typically studied as two discrete populations. In this study, we aimed to examine the risk of unnatural death (ie, death from external causes such as accidents, suicide, and undetermined causes) among people with a history of self-harm and violent crime, focusing specifically on those with co-occurring behaviours.MethodsFor this population-based nested case-control study, we used national interlinked Danish registers. Individuals aged 35 years or younger, who were alive and residing in the country on their 15th birthday, and who died from external causes (cases) were matched by age and gender to living people (controls). We compared risks of suicide, accidental death, and any death by external causes among those with a history of hospital-treated self-harm, violent criminality, or both behaviours with those in individuals without histories of either behaviour. We estimated incidence rate ratios (IRRs), adjusted for age and gender, to compare risks.FindingsWe identified 2246 individuals who died from external causes, whom we matched to 44 920 living controls. 1499 (66·7%) of 2246 individuals died from accidental causes and 604 (26·9%) died by suicide. The risk of unnatural death was elevated for individuals with a history of violence (IRR 5·19, 95% CI 4·45–6·06) or self-harm (12·65, 10·84–14·77), but the greatest risk increase was among those with histories of both behaviours (29·37, 23·08–37·38). Substance misuse disorders, particularly multiple drug use, was more prevalent among individuals with co-occurring self-harm and violence than among those engaging in just one of these behaviours. Psychiatric disorders seemed to account for some of the excess risk of unnatural death among people with dual-harm histories, but excess risk, particularly of accidental death, persisted in the multivariable models.InterpretationAmong individuals with co-occurring self-harm and violence, the risk of accidental death, particularly accidental self-poisoning, should be considered to be as important as the risk of suicide. People with a history of both behaviours who also have a substance misuse disorder are at particularly high risk of dying from external causes. Strategies should be designed to be accessible for people facing turbulent lives with multiple problems. Individuals in this group with both behaviours are likely to be treated by health-care services for self-harm and have contact with criminal justice services, providing multiple opportunities for proactive intervention.FundingEuropean Research Council.
Measuring chances: Wai-Ching Leung explains odds and probabilities
Authors: Wai-Ching Leung
Journal: BMJ (2002)

In my latest article in the Student BMJ , I noted that statistics are useful when events are not entirely predictable.1 An important use of medical statistics is to measure this level of certainty and estimate how likely certain events are to happen. One clinical example is our attempt to estimate from our clinical assessment how likely it is that a patient is suffering from a given disease. If a 70 year old woman is admitted to an emergency department with central chest pain but with a normal electrocardiogram, how likely is it that has she had a heart attack? Another example relates to hypothesis testing. Suppose we wish to find out whether brain tumours are associated with use of mobile phones. But no matter how many people we get data on, we can never be absolutely certain. Instead we measure the level of certainty by estimating how likely the data we obtain would have occurred if brain tumours were not associated with mobile phone use.

I will discuss these two specific examples in more detail in future articles. In this article, I will look at how chance can be measured, some examples and one pitfall in interpretation that should be avoided.

Chance can be measured in two ways. Probability is the more commonly used measure, and almost all medical students should have come across it. We can think of it as the number of ways an event can occur compared with the total number of possible outcomes. Suppose we throw a dice, we expect the probability that it will land on a “1” is 1/6, that it is an even number is 3/6=1/2, and that it is greater than 2 is 4/6=2/3. Sometimes, we may estimate probability by observations-the number of events to the total number of possible …
Should medical students be introduced to patients as “student doctors”?
Authors: Daniel K Sokol
Journal: BMJ (2005)

In the first article of a new section on medical controversies, Daniel Sokol discusses the implications of introducinging medical students as student doctors

Medical ethicists are notorious for their interest in rare and far-fetched cases. “Vive la difference!” could be an ethicist's motto. But this is one of the most ordinary ethical issues in clinical medicine. So ordinary is it that many do not consider it an ethical issue at all. What is undeniable is that the issue—ethical or not—affects many patients, doctors, and medical students across the country.

Most medical students, at one time in their training, have been called “student doctors” by their seniors. Registrars and consultants regularly boost the egos of their eager students with a taster of that delectable title—Doctor. Many patients are led to believe that “student doctors” are genuine doctors and go on to address them as such for the rest of the consultation. More than encouraging the students, the title also serves to reassure the patient that the nervous looking youth before them is not feebly attempting to assault them but is examining them. The title acts as a verbal tranquilizer, putting anxious patients and students at ease and “getting the best” out of both parties.

Throughout their hospital stay, however brief, patients are asked many questions by healthcare staff. It can be an exasperating experience. A weary or irate patient is more likely to answer questions if asked by a doctor. Introducing students as “student doctors” thus increases the compliance rate and provides opportunities for students to practise their history taking. So what is the fuss about if no one is harmed by the benevolent subterfuge? Is this another case of an ethicist creating an ethical issue out of nothing?

Arguably, patients have a duty to allow medical students to train on …
Picture quiz An evolutionary relic?
Authors: Victoria J Doyle, Adrian C Bateman
Journal: BMJ (2007)

An 89 year old woman was admitted to hospital with central abdominal pain and vomiting. Examination showed a tense distended abdomen with right iliac fossa tenderness but no scars, masses, or organomegaly. There was tenderness on digital rectal examination but no blood or mucus. An abdominal radiograph showed features suggestive of distal small bowel obstruction. No free subdiaphragmatic gas was identified on chest radiograph. Initial estimates of full blood count and serum electrolytes were normal. She was kept nil by mouth, rehydrated with intravenous fluids, and given analgesia.

Computed tomography of the abdomen was carried out (fig 1). Subsequent laparotomy revealed a mass in the region of the appendix with adhesions to the terminal ileum, right ovary and uterus. A limited right hemicolectomy and hysterectomy was performed.



Fig 1 
Computed tomogram of the abdomen



The surgical resection specimen contained a mass associated with the appendix (fig 2), and sectioning indicated a tumour centred on the appendix.



Fig 2 
Intact surgical resection specimen



Histological examination showed a primary adenocarcinoma of the appendix, predominantly moderately differentiated and partly mucinous in nature, which extended through the wall of the appendix to ulcerate the peritoneal surface (fig 3).



Fig 3 
Histological section of the tumour showing malignant epithelial cells (arrowed) with pools of mucin, characteristic of mucinous adenocarcinoma. These cells …
Exosomal let-7d-3p and miR-30d-5p as diagnostic biomarkers for non-invasive screening of cervical cancer and its precursors
Authors: Mengyue Zheng, Ling Hou, Yu Ma, Lanyun Zhou, Fenfen Wang, Bei Cheng, Wei Wang, Bingjian Lu, Pengyuan Liu, Weiguo Lu, Yan Lu
Journal: Molecular Cancer (2019)

Cervical cancer screening through detection and treatment of high-grade cervical intraepithelial neoplasia (CIN) is most successful in cancer prevention. However, the accuracy of the current cervical cancer screening tests is still low. The aim of this study was to develop a more accurate method based on circulating exosomal miRNAs. The miRNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 121 plasma samples from healthy volunteers, cervical carcinoma patients, and CIN patients. A panel with eight differentially expressed exosomal miRNAs was identified to distinguish patients in the CIN II+ group (including advanced CIN II patients) from those in the CIN I− group (including CIN I patients and healthy volunteers). Let-7d-3p and miR-30d-5p showed significant difference between cervical tumors and adjacent normal tissues (P < 0.005), exhibited a consistent trend in plasma samples, and were further validated in 203 independent plasma samples. Integrating these two miRNAs yielded an AUC value of 0.828 to distinguish patients in CIN II+ group from those in CIN I− group. Further integrating them into a cytological test-based model resulted in a higher AUC of 0.887, while the AUC value based on the cytological test alone was 0.766. In summary, plasma exosomal miR-30d-5p and let-7d-3p are valuable diagnostic biomarkers for non-invasive screening of cervical cancer and its precursors. Further validation using large sample sizes is required for clinical diagnosis.
Regional Variations in Quality of Survival Among Men with Prostate Cancer Across the United Kingdom
Authors: David W. Donnelly, Anna Gavin, Amy Downing, Luke Hounsome, Therese Kearney, Emma McNair, Dawn Allan, Dyfed W. Huws, Penny Wright, Peter J. Selby, Paul Kind, Eila Watson, Richard Wagland, Sarah Wilding, Hugh Butcher, Rebecca Mottram, Majorie Allen, Oonagh McSorley, Linda Sharp, Malcolm D. Mason, William R. Cross, James W.F. Catto, Adam W. Glaser
Journal: European Urology (2019)

Prostate cancer incidence, treatment, and survival rates vary throughout the UK, but little is known about regional differences in quality of survival.To investigate variations in patient-reported outcomes between UK countries and English Cancer Alliances.A cross-sectional postal survey of prostate cancer survivors diagnosed 18-42mo previously.Urinary, bowel, and sexual problems and vitality were patient reported using the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. General health was also self-assessed. Regional variations were identified using multivariable log-linear regression.A total of 35823 men responded, 60.8% of those invited. Self-assessed health was significantly lower than the UK average in Wales and Scotland. Respondents reported more urinary incontinence in Scotland, more urinary irritation/obstruction in Scotland and Northern Ireland (NI), poorer bowel function in Scotland and NI, worse sexual function in Scotland, and reduced vitality/hormonal function in Scotland, Wales, and NI. Self-assessed health was poorer than the English average in South Yorkshire and North-East and Cumbria, with more urinary incontinence in North-East and Cumbria and Peninsula, greater sexual problems in West Midlands, and poorer vitality in North-East and Cumbria and West Midlands. Limitations include difficulty identifying clinically significant differences and limited information on pretreatment conditions.Despite adjustment for treatment, and clinical and sociodemographic factors, quality of survival among prostate cancer survivors varied by area of residence. Adoption of best practice from areas performing well could support enhanced survival quality in poorer performing areas, particularly with regard to bowel problems and vitality, where clinically relevant differences were reported.We conducted a UK-wide survey of patient's quality of life after treatment for prostate cancer. Outcomes were found to vary depending upon where patients live. Different service providers need to ensure that all prostate cancer patients receive the same follow-up care.