tbuckley/cabot-search huggingface dataset:
The Danish OPUS Early Intervention Services for First-Episode Psychosis: A Phase 4 Prospective Cohort Study With Comparison of Randomized Trial and Real-World Data
Authors: Christine Merrild Posselt, Nikolai Albert, Merete Nordentoft, Carsten Hjorthøj
Journal: American Journal of Psychiatry (2021)

The Danish OPUS trial showed significant efficacy of early intervention services for first-episode schizophrenia spectrum disorders compared with standard treatment, leading to implementation of the OPUS intervention in clinical practice. The authors sought to determine whether the effectiveness of OPUS treatment in real-world clinical practice is comparable to the efficacy seen in the trial.The study compared patients who received OPUS treatment as part of the original randomized trial to those who received standard treatment in the trial (the control group) and those who received OPUS treatment after it was implemented in Denmark. The authors investigated whether the three groups differed on register-based outcomes, such as use of secondary health care, functional outcomes, and death. Analyses were adjusted for relevant confounders.Compared with trial study participants, patients who received OPUS treatment after implementation (N=3,328) had a tendency toward lower mortality (hazard ratio=0.60, 95% CI=0.33, 1.09), fewer and shorter psychiatric admissions, and possibly fewer filled prescriptions of antipsychotics and other psycholeptics after 4 or 5 years. While at first less likely to be working or studying, patients who received postimplementation OPUS treatment eventually had higher odds of working than did those in the OPUS trial (after 5 years, odds ratio=1.49, 95% CI=1.07, 2.09). The odds of being in a couple relationship were also higher among patients in the postimplementation group than those in the trial. Other outcomes showed less clear associations with treatment group. Generally, the control group in the trial fared worse than both of the OPUS treatment groups.Not only did OPUS treatment maintain its efficacy after it was implemented as a standard treatment, it paralleled or surpassed many of the effects observed when the OPUS intervention was delivered in a randomized trial. The study results provide further evidence in support of implementation and funding of early intervention services worldwide.
<i>Candida auris</i> : CDC warns of risk of new, drug resistant strain in US
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

Outbreaks have been reported in the US of transmissible Candida auris fungal infections that have been found to be resistant to drugs and difficult to treat. In a report published on 22 July the Centers for Disease Control and Prevention said that two clusters of cases had been reported in Washington, DC, and in Texas.1

C auris is a different organism from the “black fungus” reported among covid-19 patients in India.

“These two simultaneous, independent clusters of pan- or echinocandin resistant C auris cases in patients with overlapping inpatient health care exposures and without previous echinocandin use provide the first evidence suggesting that pan- or echinocandin-resistant C auris strains might have been transmitted in US health care settings . …
Autologous Transplantation Improves Survival Rates for Follicular Lymphoma Patients Who Relapse within 2-Years of Chemoimmunotherapy: A Multi-Centre Retrospective Analysis of Consecutively Treated Patients in the Real World
Authors: Mita Manna, Richard Lee-Ying, Gwynivere Davies, Anthea Peters, Danielle Oh, Colin Stewart, Douglas A. Stewart
Journal: Blood (2017)
Search for effective treatments in patients with advanced refractory melanoma continues: can novel intratumoral therapies deliver?
Authors: Yana G Najjar
Journal: Journal for ImmunoTherapy of Cancer (2021)

Most patients with advanced melanoma ultimately fail immune checkpoint inhibitor (ICI) therapy because of primary or acquired resistance. There remains a critical unmet need for new therapies that function via alternative immune activation mechanisms to safely trigger an antitumor immune response in patients with ICI-refractory disease. This commentary discusses the recent failures and hope for novel intratumoral therapies under development in the advanced refractory melanoma setting, outlining key mechanistic differences that may be critical to yielding success in this difficult-to-treat population.
Paul Patrick Coffey
Authors: Duncan Coffey
Journal: BMJ (2021)

Paul Patrick Coffey was born in Sutterton, Lincolnshire, to Patrick and Mary (“Kit”) Coffey, both general practitioners. He was the youngest of four children. He attended Ratcliffe College, where he developed his keen interest in sports and the arts, which he kept up throughout his life.

In 1970 he was awarded a place at St George’s Medical School. While he was a medical student he met Jane (nee Taylor), a nurse at St George’s, whom he married in 1976. They had three children—Laura, Patrick, and Duncan. Duncan followed Paul into medicine and is an orthopaedic registrar.

Paul undertook his GP training in Boston, Lincolnshire, attaining MRCP 1979 and MRCGP 1985. He accepted …
BATF regulates progenitor to cytolytic effector CD8+ T cell transition during chronic viral infection
Authors: Yao Chen, Ryan A. Zander, Xiaopeng Wu, David M. Schauder, Moujtaba Y. Kasmani, Jian Shen, Shikan Zheng, Robert Burns, Elizabeth J. Taparowsky, Weiguo Cui
Journal: Nature Immunology (2021)
Does depression screening in primary care improve mental health outcomes?
Authors: Brett D Thombs, Sarah Markham, Danielle B Rice, Roy C Ziegelstein
Journal: BMJ (2021)

### What you need to know

Depression is usually identified when patients report symptoms or when clinicians recognise them through routine assessment of patient wellbeing. Screening can potentially increase rates of depression recognition. Depression screening involves administering a symptom questionnaire to all patients not known or not suspected of having depression. It is intended to identify symptomatic people who may not otherwise be recognised or seek treatment.12 A cut-off is used to classify positive and negative results, with further assessment of those with positive results, and, as appropriate, management. The Patient Health Questionnaire-9 (PHQ-9) is among the most used depression screening tools in primary care.3

In the UK, the National Institute for Health and Care Excellence (NICE) encourages general practitioners to be alert to possible depression, but not to screen routinely.4 The National Screening Committee recommends against screening.5 Depression screening in general practice was financially incentivised by the UK Quality and Outcomes Framework from 2006 to 2013 but was subsequently removed owing to disappointing results; almost 1000 patients had to be screened for each new depression diagnosis and almost 700 for each new antidepressant prescription.6 In North America, the Canadian Task Force on Preventive Health Care (CTFPHC) recommends against screening,7 whereas the US Preventive Services Task Force (USPSTF) recommends screening all primary care patients “with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up.”8 …
Id1 Ablation Protects Hematopoietic Stem Cells from Stress-Induced Exhaustion and Aging
Authors: Shweta Singh, Satyendra Singh, Stephen Gadomski, Lei Sun, Serguei Kozlov, Alex Pfaennenstein, Lino Tessarollo, Kimberly Klarmann, Jonathan Keller
Journal: Blood (2017)
Correction
Journal: BMJ (2021)

In the article 'Interpreting a lateral flow SARS-CoV-2 antigen test' (BMJ 2021;373:n1411 doi:) the authors state that "Evidence shows a strong correlation between Ct values and in vitro infectiousness and some evidence for increased risk of transmission from patients with higher Ct values."The last part of that sentence should have referred to lower values (not higher) so that the corrected sentence reads "Evidence shows a strong correlation between Ct values and in vitro infectiousness and some evidence for increased risk of transmission from patients with lower Ct values."
MO36-4 A multi-institutional, single-arm phase II study of pembrolizumab plus amrubicin in relapsed small cell lung cancer
Authors: Koji Haratani, Hiroaki Akamatsu, Shunsuke Teraoka, Hidetoshi Hayashi, Atsushi Hayata, Takeshi Yoshida, Yuichi Ozawa, Tsutomu Iwasa, Daichi Fujimoto, Toshio Shimokawa, Keisuke Tomii, Kazuhiko Nakagawa, Nobuyuki Yamamoto
Journal: Annals of Oncology (2021)
Surface-based hippocampal subfield segmentation
Authors: Jordan DeKraker, Stefan Köhler, Ali R. Khan
Journal: Trends in Neurosciences (2021)

Though it is often termed 'subcortical,' the hippocampus is composed of a folded 'archicortical' sheet contiguous with the neocortex. The human hippocampus varies considerably in its internal folding configuration, creating major challenges in interindividual alignment and parcellation into subfields. In this opinion article, we discuss surface-based methods that aim to explicitly model hippocampal folding, similar to methods used in the neocortex, allowing interindividual alignment in an unfolded or flat-mapped 2D space. Such an approach enables detailed morphological characterization, constrains the problem of subfield segmentation, and provides a way to visualize data without occlusions. We argue that, when applied to magnetic resonance imaging (MRI) data, such methods overcome pitfalls of more conventional manual or registration-based subfield segmentation approaches.
Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study
Authors: Marja K. Puurunen, Jerry Vockley, Shawn L. Searle, Stephanie J. Sacharow, John A. Phillips, William S. Denney, Benjamin D. Goodlett, David A. Wagner, Larry Blankstein, Mary J. Castillo, Mark R. Charbonneau, Vincent M. Isabella, Vasu V. Sethuraman, Richard J. Riese, Caroline B. Kurtz, Aoife M. Brennan
Journal: Nature Metabolism (2021)
Identification and characterization of relapse-initiating cells in MLL-rearranged infant ALL by single-cell transcriptomics
Authors: Tito Candelli, Pauline Schneider, Patricia Garrido Castro, Luke A. Jones, Eduard Bodewes, Dedeke Rockx-Brouwer, Rob Pieters, Frank C. P. Holstege, Thanasis Margaritis, Ronald W. Stam
Journal: Leukemia (2021)

Infants with MLL-rearranged infant acute lymphoblastic leukemia (MLL-r iALL) undergo intense therapy to counter a highly aggressive malignancy with survival rates of only 30-40%. The majority of patients initially show therapy response, but in two-thirds of cases the leukemia returns, typically during treatment. The glucocorticoid drug prednisone is established as a major player in the treatment of leukemia and the in vivo response to prednisone monotreatment is currently the best indicator of risk for MLL-r iALL. We used two different single-cell RNA sequencing technologies to analyze the expression of a prednisone-dependent signature, derived from an independent study, in diagnostic bone marrow and peripheral blood biopsies. This allowed us to classify individual leukemic cells as either resistant or sensitive to treatment and show that quantification of these two groups can be used to better predict the occurrence of future relapse in individual patients. This work also sheds light on the nature of the therapy-resistant subpopulation of relapse-initiating cells. Leukemic cells associated with high relapse risk are characterized by basal activation of glucocorticoid response, smaller size, and a quiescent gene expression program with cell stemness properties. These results improve current risk stratification and elucidate leukemic therapy-resistant subpopulations at diagnosis.
Twist1 contributes to developing and sustaining corticosteroid resistance in ulcerative colitis
Authors: Changqin Liu, Li-Hua Mo, Bai-Sui Feng, Qiao-Ruo Jin, Yan Li, Jianli Lin, Qing Shu, Zhi-Gang Liu, Zhanju Liu, Xiaomin Sun, Ping-Chang Yang
Journal: Theranostics (2021)

Rationale: Corticosteroid resistance (CR) is a serious drawback to steroid therapy in patients with ulcerative colitis (UC); the underlying mechanism is incompletely understood. Twist1 protein (TW1) is an apoptosis inhibitor and has immune regulatory functions. This study aims to elucidate the roles of TW1 in inducing and sustaining the CR status in UC. Methods: Surgically removed colon tissues of patients with ulcerative colitis (UC) were collected, from which neutrophils were isolated by flow cytometry. The inflammation-related gene activities in neutrophils were analyzed by RNA sequencing. A CR colitis mouse model was developed with the dextran sulfate sodium approach in a hypoxia environment. Results: Higher TW1 gene expression was detected in neutrophils isolated from the colon tissues of UC patients with CR and the CR mouse colon tissues. TW1 physically interacted with glucocorticoid receptor (GR)α in CR neutrophils that prevented GRα from interacting with steroids; which consequently abrogated the effects of steroids on regulating the cellular activities of neutrophils. STAT3 (Signal Transducer and Activator of Transcription-3) interacted with Ras protein activator like 1 to sustain the high TW1 expression in colon mucosal neutrophils of CR patients and CR mice. Inhibition of TW1 restored the sensitivity to corticosteroid of neutrophils in the colon tissues of a CR murine model. Conclusions: UC patients at CR status showed high TW1 expression in neutrophils. TW1 prevented steroids from regulating neutrophil activities. Inhibition of TW1 restored the sensitivity to corticosteroids in the colon tissues at the CR status.
Home Diagnosis of Wide Complex Tachycardia—The Value for Remote Monitoring
Authors: Shawn Lee, Gregory P. Siroky, Ranjit Suri
Journal: JAMA Internal Medicine (2021)

This case report presents the electrocardiographic findings of a patient in their 60s with a history of myocardial infarction, coronary artery bypass surgery, reduced left ventricular ejection fraction, and a single-chamber implantable cardioverter-defibrillator who experienced palpitations at home.
Increase in serum levels of phosphatidylserine-specific phospholipase A1 in COVID-19 patients
Authors: Takuya Shimura, Makoto Kurano, Koh Okamoto, Daisuke Jubishi, Kuniyuki Kano, Koji Igarashi, Satoshi Shimamoto, Junken Aoki, Kyoji Moriya, Yutaka Yatomi
Journal: Cellular and Molecular Immunology (2021)
Glucose Regulation Beyond HbA1c in Type 2 Diabetes Treated With Insulin: Real-World Evidence From the DIALECT-2 Cohort
Authors: Niala den Braber, Miriam M.R. Vollenbroek-Hutten, Kathryn M. Westerik, Stephan J.L. Bakker, Gerjan Navis, Bert-Jan F. van Beijnum, Gozewijn D. Laverman
Journal: Diabetes Care (2021)

OBJECTIVE To investigate glucose variations associated with glycated hemoglobin (HbA1c) in insulin-treated patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients included in Diabetes and Lifestyle Cohort Twente (DIALECT)-2 (n = 79) were grouped into three HbA1c categories: low, intermediate, and high (≤53, 54–62, and ≥63 mmol/mol or ≤7, 7.1–7.8, and ≥7.9%, respectively). Blood glucose time in range (TIR), time below range (TBR), time above range (TAR), glucose variability parameters, day and night duration, and frequency of TBR and TAR episodes were determined by continuous glucose monitoring (CGM) using the FreeStyle Libre sensor and compared between HbA1c categories. RESULTS CGM was performed for a median (interquartile range) of 10 (7–12) days/patient. TIR was not different for low and intermediate HbA1c categories (76.8% [68.3–88.2] vs. 76.0% [72.5.0–80.1]), whereas in the low category, TBR was higher and TAR lower (7.7% [2.4–19.1] vs. 0.7% [0.3–6.1] and 8.2% [5.7–17.6] vs. 20.4% [11.6–27.0], respectively; P &amp;lt; 0.05). Patients in the highest HbA1c category had lower TIR (52.7% [40.9–67.3]) and higher TAR (44.1% [27.8–57.0]) than the other HbA1c categories (P &amp;lt; 0.05), but did not have less TBR during the night. All patients had more (0.06 ± 0.06/h vs. 0.03 ± 0.03/h; P = 0.002) and longer (88.0 [45.0–195.5] vs. 53.4 [34.4–82.8] minutes; P &amp;lt; 0.001) TBR episodes during the night than during the day. CONCLUSIONS In this study, a high HbA1c did not reduce the occurrence of nocturnal hypoglycemia, and low HbA1c was not associated with the highest TIR. Optimal personalization of glycemic control requires the use of newer tools, including CGM-derived parameters.
Multimedia: Oxford Handbook of Patients’ Welfare: A Doctor’s Guide to Benefits and Services
Authors: Richard Neal
Journal: BMJ (1999)

Adam Sandell


Oxford University Press, £18.95, pp 283 




ISBN 0 19 262957 3

———————

Rating: ★★★

The welfare of patients is at centre of medical care, either at the level of delivering “technical” welfare (removing a gall bladder or prescribing antibiotics to an ill child with otitis media) or delivering “social” welfare (non-medical interventions to improve health). Such social interventions include pastoral and spiritual support and providing practical and financial advice to improve quality of life. The balance between the provision of these types of welfare varies enormously between specialties, between personalities and consulting styles, and between views of the role of doctors.

Many doctors regard the provision of social welfare as somebody else’s job, whether that of a social worker, the patient’s family or advocate, or a nurse. This may be due to a high level of specialism in the doctor’s role, arrogance, time pressures, or simply that others are readily available to take on these roles. More importantly, from medical school onwards doctors are not taught or encouraged to think in such ways. Even the most patient centred general practitioners still effectively run “sickness shops” according to a strict medical model, and non-medical welfare is rarely high on the agenda.

The latest in the Oxford “fit in your pocket” series shows the enormous scope for influencing patient welfare. The breadth and the depth of the material contained is staggering, and it has been meticulously put together in a user friendly format. The goldmine of material includes contact details for all manner of potentially useful organisations. Where else could you find the contact details for HM Inspector of Anatomy (to be contacted in the event of the death of a person who has bequeathed his or her body to medical science) alongside those for the Disabled Living Foundation (to be contacted for advice and information about equipment for disabled people) and the Plain English Campaign (for advice on the language used in patient letters and leaflets)? It makes me glad I’m not a social worker.

However, changes in legislation and benefits will make it out of date very quickly. While free updates are available via email and the web, it is hard to envisage the dual use of paper and web versions. Surely this is the type of information that we should be accessing only via the web, and from every ward and every consulting room.
Abstract 14667: Vitamin C Deficiency, High-Sensitivity C-Reactive Protein, and Cardiac Event-Fee Survival in Patients with Heart Failure
Authors: Eun Kyeung Song, Debra K Moser, Heather Payne-Emerson, Sandra B Dunbar, Susan J Pressler, Terry A Lennie
Journal: Circulation (2011)

Background. Vitamin C is associated with lower levels of high-sensitivity C-reactive protein (hsCRP), an inflammatory biomarker that predicts cardiovascular disease. However, whether low vitamin C ...
In search of the golden ratio for cannabis allergy: Utility of specific allergen‐to‐total IgE ratios
Authors: Ine I. Decuyper, Hans‐Peter Rihs, Christel H. Mertens, Athina Ludovica Van Gasse, Jessy Elst, Margaretha A. Faber, Margo M. Hagendorens, Vito Sabato, Didier G. Ebo
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Alteration of Endothelial Cell Hemostatic Equilibrium By Cancer Cell-Derived Microparticles, a New Insight in Pathogenesis of Cancer Associated Thrombosis
Authors: Aurélie Rousseau, Rania Amrane, Patrick Van Dreden, Loula Papageorgiou, Annette Larsen, Amir Khaterchi, Ismail Elalamy, Grigorios T. Gerotziafas
Journal: Blood (2017)
Abstract 9955: Cooperative Operation of PGD2/FP and 15d-PGJ2/nrf2 Pathway in the L-PGDS-Mediated Cardioprotection
Authors: Yoshinori Katsumata, Motoaki Sano, Ken Shinmura, Tomohiro Matsuhashi, Shugo Tohyama, Jin Endo, Atsushi Anzai, Cardex Yan, Keiishi Fukuda
Journal: Circulation (2011)

Background Lipocalin-type prostaglandin D synthase (L-PGDS) is abundantly expressed in adult cardiomyocytes. We recently demonstrated that dexamethasone stimulates PGD2-dominated activation of pros...
Prophylactic vaccine delivery systems against epidemic infectious diseases
Authors: Chao Pan, Hua Yue, Li Zhu, Guang-hui Ma, Heng-liang Wang
Journal: Advanced Drug Delivery Reviews (2021)

Prophylactic vaccines have evolved from traditional whole-cell vaccines to safer subunit vaccines. However, subunit vaccines still face problems, such as poor immunogenicity and low efficiency, while traditional adjuvants are usually unable to meet specific response needs. Advanced delivery vectors are important to overcome these barriers; they have favorable safety and effectiveness, tunable properties, precise location, and immunomodulatory capabilities. Nevertheless, there has been no systematic summary of the delivery systems to cover a wide range of infectious pathogens. We herein summarized and compared the delivery systems for major or epidemic infectious diseases caused by bacteria, viruses, fungi, and parasites. We also included the newly licensed vaccines (e.g., COVID-19 vaccines) and those close to licensure. Furthermore, we highlighted advanced delivery systems with high efficiency, cross-protection, or long-term protection against epidemic pathogens, and we put forward prospects and thoughts on the development of future prophylactic vaccines.