tbuckley/cabot-search huggingface dataset:
Cellulitis and Soft Tissue Infections
Authors: Rachel Bystritsky, Henry Chambers
Journal: Annals of Internal Medicine (2018)

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Cellulitis and soft tissue infections are a diverse group of diseases that range from uncomplicated cellulitis to necrotizing fasciitis. Management of predisposing conditions is the primary means of prevention. Cellulitis is a clinical diagnosis and thus is made on the basis of history and physical examination. Imaging may be helpful for characterizing purulent soft tissue infections and associated osteomyelitis. Treatment varies according to the type of infection. The foundations of treatment are drainage of purulence and antibiotics, the latter targeted at the infection's most likely cause.
A phase I study of afatinib combined with carboplatin or carboplatin plus paclitaxel in patients (pts) with advanced solid tumors.
Authors: Fangfei Gao, Mary O'Brien, Debashis Sarker, Jaishree Bhosle, Timothy Anthony Yap, Martina Maria Uttenreuther-Fischer, Karine Pemberton, Rainer-Georg Goeldner, Sabrina Wiebe, Johann S. De Bono, James F. Spicer
Journal: Journal of Clinical Oncology (2016)

2571 Background: The irreversible ErbB family blocker, afatinib, has demonstrated acceptable tolerability and promising efficacy when combined with cytotoxic agents. Methods: In an open-label, 3+3 dose escalation study, we evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics (PK) and antitumor activity of afatinib in combination with carboplatin (regimen A) or carboplatin + paclitaxel (regimen B). The starting dose was afatinib 20 mg/day + carboplatin AUC6 (Day 1 of a 3-weekly cycle) in both regimens. Paclitaxel 175 mg/m2 was given on Day 1 of each cycle in regimen B. Carboplatin was reduced to AUC5 in case of toxicity. Afatinib was to be escalated from 20 to 40 mg then 50 mg; if ≥2/6 pts experienced dose-limiting toxicity (DLT) at 40 mg, an intermediate dose of 30 mg was assessed. Results: 12 pts were treated in regimen A (8 male; median age 58 years) and 26 in regimen B (13 male; median age 61 years). The table shows dose cohorts and DLTs in both regimens. Although MTD was not reached for regimen A, it was decided not to escalate the dose further. Overall, the most frequent (any grade) drug-related adverse events (AEs) were rash/acne (75%), fatigue (67%) and diarrhea (58%) in regimen A and diarrhea (88%), rash/acne (73%) and fatigue (69%) in regimen B. Afatinib did not appear to alter carboplatin or paclitaxel PK. Partial response was reported in 3 pts (25%) in regimen A and 5 (19%) in regimen B. Conclusions: MTD was not reached for regimen A but the recommended phase 2 dose (RP2D) was afatinib 40 mg + carboplatin AUC6. MTD/RP2D for regimen B was afatinib 20 mg + carboplatin AUC5 + paclitaxel 175 mg/m2. At RP2D, AEs were manageable with antitumor activity observed. Clinical trial information: NCT00809133.Afatinib (mg/day) Paclitaxel (mg/m2)/ carboplatin (AUC) All pts/ evaluable pts/ pts with DLT DLT (all G3) Regimen A 20 -/6 3/3/0 40 -/6 9/6/1 Dermatitis acneiform Regimen B 20 175/6 7/6/2 Fatigue/C. difficile infection/diarrhea/ small intestinal hemorrhage/ dehydration/renal impairment/neutropenic sepsis; Mucosal inflammation 20 175/5 6/6/0* 40 175/5 5/5/2 Febrile neutropenia; Fatigue/mucosal inflammation 30 175/5 8/6/2 Stomatitis; Mucosal inflammation * No DLT in first 3 pts; cohort expanded to 6 pts after 40 and 30 mg dose exceeded MTD.
Abstract 20720: H2O2 from Mitochondrial Sources Increases PDE5 Activity in Pulmonary Artery Smooth Muscle Cells (PASMC) from Persistent Pulmonary Hypertension (PPHN) Lambs
Authors: Kathryn N Farrow, Stephen Wedgwood, Keng Jin Lee, Lyubov Czech, Sylvia F Gugino, Satyan Lakshminrusimha, Paul T Schumacker, Robin H Steinhorn
Journal: Circulation (2010)

Background: In the pulmonary vasculature, phosphodiesterase 5 (PDE5) degrades cGMP and inhibits NO-mediated vasorelaxation. We previously reported that 24 h of 100% O2 ventilation increases PDE5 ac...
Is it time to give population health surveillance a late fitness test?
Authors: Gavin Sandercock, Ben Jones
Journal: British Journal of Sports Medicine (2018)

Tomkinson et al 1 report temporal trends in aerobic fitness of 1 142 026 children aged 7–19 years old using estimates from the 20 m shuttle run. The data show continued declines in fitness described as ‘ indicative of declines in population health ’. The authors propose that surveillance of children’s fitness should be undertaken within ‘ harmonised national health surveys ’. The authors’ convictions in the potential value of extending paediatric health surveillance to include fitness measures will be shared by readers who recognise the utility of fitness testing performed routinely for diagnostic screening and athlete monitoring.2

Aerobic fitness is a stronger predictor of mortality than established cardiovascular disease risk factors.3 Medicine acknowledges the diagnostic utility of exercise tests, but their tendency to ‘ focus on the ischemic ST-segment ’3 may explain why aerobic fitness is so rarely reported as an outcome in the medical literature (figure 1). The American Heart Association’s call for a US national fitness registry4 echoed recently the authors’5 proposal for a repository of children’s shuttle-run data to ‘enable temporal tracking and improve health surveillance’.



Figure 1 
Health outcomes reported in the leading …
Ascertainment of asthma prognosis using natural language processing from electronic medical records
Authors: Sunghwan Sohn, Chung-Il Wi, Stephen T. Wu, Hongfang Liu, Euijung Ryu, Elizabeth Krusemark, Alicia Seabright, Gretchen A. Voge, Young J. Juhn
Journal: Journal of Allergy and Clinical Immunology (2018)
Quality-of-Life After Everolimus-Eluting Stents or Bypass Surgery for Left-Main Disease
Authors: Suzanne J. Baron, Khaja Chinnakondepalli, Elizabeth A. Magnuson, David E. Kandzari, John D. Puskas, Ori Ben-Yehuda, Gerrit-Anne van Es, David P. Taggart, Marie-Claude Morice, Nicholas J. Lembo, W. Morris Brown, Adrian Banning, Charles A. Simonton, A. Pieter Kappetein, Joseph F. Sabik, Patrick W. Serruys, Gregg W. Stone, David J. Cohen
Journal: Journal of the American College of Cardiology (2017)
Abstract 16873: Safety and Efficacy of Alirocumab in Patients With Atherosclerotic Cardiovascular Disease, Based on Statin Intensity: Pooled Analyses of 5 Placebo-controlled Phase 3 Trials
Authors: Christie M Ballantyne, Peter A McCullough, Santosh K Sanganalmath, Andrew Koren, Alexia Letierce, Michael H Davidson
Journal: Circulation (2016)

Introduction:  Atherosclerotic cardiovascular disease (ASCVD) patients are at high risk for recurrent CV events and the 2013 ACC/AHA guidelines recommend at least moderate intensity statin therapy. We examined efficacy and safety of alirocumab (ALI), a PCSK9 inhibitor, in 2100 ASCVD patients on moderate or high intensity concomitant statins.   Methods:  ASCVD was defined as coronary heart disease, stroke, and peripheral arterial disease. Enrolled patients pooled from 5 Phase 3 placebo (PL)-controlled studies (≥52 Weeks [W]) were on stable maximally tolerated statin ± other lipid-lowering therapies. Mean % LDL-C reduction from baseline to W12 and W24 was analyzed by statin intensity and initial ALI dose.   Results:  Baseline characteristics were comparable between treatment groups with mean age ~61 years, ~67% male and mean BMI of ~30 kg/m 2 . In a subset of 1431 patients (ALI 150 mg Q2W), baseline mean ± SD free PCSK9 was 322.9 ± 134.2 and 293.5 ± 106.3 ng/ml in high and moderate intensity statin-treated patients, respectively ( P  P  values between subgroups were not significant, indicating no effect modification between statin intensity and LDL-C reduction (Fig. 1). Common treatment emergent adverse events with ALI were nasopharyngitis, upper respiratory tract infections and injection site reactions (Table 1).   Conclusions:  Despite slightly increased PCSK9 levels in subset of high vs. moderate intensity statin patients, ALI was comparably efficacious and well-tolerated in ASCVD patients on high or moderate intensity statins.
New cancer drugs fund keeps within £340m a year budget
Authors: Nigel Hawkes
Journal: BMJ (2018)

The new Cancer Drugs Fund has treated 15 700 patients since it began operating in July 2016, NHS England has reported.1 Just under a third of them benefited from earlier access to treatment than they would have had if the fund had not existed.

The original and now discredited Cancer Drugs Fund treated some 74 000 patients in its first four and a half years, so the annual treatment rate has not changed much. What sunk the old fund was its cost, which grew rapidly and exceeded the allotted budget. Set up in 2010, the fund had spent £1.27bn (€1.51bn; $1.64bn) by the time it closed in 2016.2

The new fund, which started in July 2016,3 is integrated into the National Institute …
Lung clearance index to monitor treatment response in pulmonary exacerbations in preschool children with cystic fibrosis
Authors: Jonathan H Rayment, Sanja Stanojevic, Stephanie D Davis, George Retsch-Bogart, Felix Ratjen
Journal: Thorax (2018)

Background Antibiotic treatment for pulmonary symptoms in preschool children with cystic fibrosis (CF) varies among clinicians. The lung clearance index (LCI) is sensitive to early CF lung disease, but its utility to monitor pulmonary exacerbations in young children has not been assessed. Objective We aim to (1) understand how LCI changes during lower respiratory tract symptoms relative to a recent clinically stable measurement, (2) determine whether LCI can identify antibiotic treatment response and (3) compare LCI changes to changes in spirometric indices. Methods LCI and spirometry were measured at quarterly clinic visits over a 12-month period in preschool children with CF. Symptomatic visits were identified and classified as treated or untreated. Treatment response was estimated using propensity score matching methods. Results 104 symptomatic visits were identified in 78 participants. LCI increased from baseline in both treated (mean relative change +23.8% (95% CI 16.2 to 31.4)) and untreated symptomatic visits (mean relative change +11.2% (95% CI 2.4 to 19.9)). A significant antibiotic treatment effect was observed when LCI was used as the outcome measure (average treatment effect −15.5% (95% CI −25.4 to −5.6)) but not for z-score FEV 1 . Conclusion LCI significantly deteriorated with pulmonary symptoms relative to baseline and improved with antibiotic treatment. These data suggest that LCI may have a role in the routine clinical care of preschool children with CF.
NHS must stop sharing confidential patient data with Home Office, say MPs
Authors: Gareth Iacobucci
Journal: BMJ (2018)

NHS officials must stop sharing confidential patient data with the Home Office for immigration tracing purposes, an influential group of MPs has said.

The House of Commons Health Committee has asked NHS Digital to immediately withdraw from a memorandum of understanding with the Home Office that allows personal details, including patients’ address and date of birth, to be shared to help trace potential immigration offenders.

In a letter to Sarah Wilkinson, chief executive of NHS Digital, the committee’s chair, Sarah Wollaston, said that NHS Digital had failed to give due consideration to patient confidentiality and …
Encouraging Self-Reflection by Veterinary Clinicians: Ethics on the Clinic Floor
Authors: Sandra A. Corr, Clare Palmer, Peter Sandøe
Journal: The American Journal of Bioethics (2018)

Rosoff et al. (2017) describe some difficult ethical decisions facing veterinarians in clinics treating dogs, cats and other companion animals.They propose adapting the human clinical consultation committee model, and establishing clinical ethics committees (CECs) to assist in resolving such ethical challenges in the more advanced of these clinics, the so-called tertiary care veterinary specialty hospitals.In this commentary, we agree that veterinarians often face troubling ethical decisions involving potential over-or under-treatment of their animal patients, the financial constraints of their clients, and, sometimes, the goals of the institutions that employ them.While we accept that a CEC may, in some contexts, be an appropriate structure in which to deal with such difficult decisions, we argue that this is not the only, or necessarily the best, approach.We suggest that the ethical problems facing veterinarians differ significantly in different countries; that many acute ethical issues typically arise before animals even arrive at the veterinary specialty hospital; and that even within such hospitals, approaches other than CECs might be more effective, especially at gaining acceptance by the veterinarians themselves.The context of Rosoff et al (2017)'s account is rather US-centered.Cultural norms and legal requirements around animal treatments, and especially euthanasia, vary significantly by country.In many European countries, for example, veterinary decisions about the life and death of companion animal patients are much more constrained by legal frameworks.While in the US and Canada euthanasia of healthy animals for owner convenience is legally permitted, in countries such as Austria and Germany, it is not allowed.Conversely, in these and many other European countries, including Scandinavia and the UK, veterinarians are obliged by law to euthanase a severely ill animal if continuing treatment will not cure
Two‐Photon‐Excited Silica and Organosilica Nanoparticles for Spatiotemporal Cancer Treatment
Authors: Jonas G. Croissant, Jeffrey I. Zink, Laurence Raehm, Jean‐Olivier Durand
Journal: Advanced Healthcare Materials (2018)

Abstract Coherent two‐photon‐excited (TPE) therapy in the near‐infrared (NIR) provides safer cancer treatments than current therapies lacking spatial and temporal selectivities because it is characterized by a 3D spatial resolution of 1 µm 3 and very low scattering. In this review, the principle of TPE and its significance in combination with organosilica nanoparticles (NPs) are introduced and then studies involving the design of pioneering TPE‐NIR organosilica nanomaterials are discussed for bioimaging, drug delivery, and photodynamic therapy. Organosilica nanoparticles and their rich and well‐established chemistry, tunable composition, porosity, size, and morphology provide ideal platforms for minimal side‐effect therapies via TPE‐NIR. Mesoporous silica and organosilica nanoparticles endowed with high surface areas can be functionalized to carry hydrophobic and biologically unstable two‐photon absorbers for drug delivery and diagnosis. Currently, most light‐actuated clinical therapeutic applications with NPs involve photodynamic therapy by singlet oxygen generation, but low photosensitizing efficiencies, tumor resistance, and lack of spatial resolution limit their applicability. On the contrary, higher photosensitizing yields, versatile therapies, and a unique spatial resolution are available with engineered two‐photon‐sensitive organosilica particles that selectively impact tumors while healthy tissues remain untouched. Patients suffering pathologies such as retinoblastoma, breast, and skin cancers will greatly benefit from TPE‐NIR ultrasensitive diagnosis and therapy.
Modified surveillance of influenza A(H1N1)v virus infections in France
Authors: None Influenza A(H1N1)v investigation teams
Journal: Eurosurveillance (2009)

Up to early July 2009, surveillance of H1N1 cases in France was based on the identification of all possible cases in order to implement, around each of them, control measures aimed at delaying the spread of the virus. The global dissemination of the virus and the starting community transmission in France led us to shift to a population-based surveillance relying mainly on the identification and investigation of clusters of influenza-like illness, on the identification and individual follow-up of confirmed hospitalised cases as well as on the monitoring, through various sentinel systems, of the use of ambulatory and hospital care for influenza-like symptoms.
Overview of Current Drugs and Molecules in Development for Spinal Muscular Atrophy Therapy
Authors: Hannah K. Shorrock, Thomas H. Gillingwater, Ewout J. N. Groen
Journal: Drugs (2018)

Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily characterized by a loss of spinal motor neurons, leading to progressive paralysis and premature death in the most severe cases. SMA is caused by homozygous deletion of the survival motor neuron 1 (SMN1) gene, leading to low levels of SMN protein. However, a second SMN gene (SMN2) exists, which can be therapeutically targeted to increase SMN levels. This has recently led to the first disease-modifying therapy for SMA gaining formal approval from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Spinraza (nusinersen) is a modified antisense oligonucleotide that targets the splicing of SMN2, leading to increased SMN protein levels, capable of improving clinical phenotypes in many patients. In addition to Spinraza, several other therapeutic approaches are currently in various stages of clinical development. These include SMN-dependent small molecule and gene therapy approaches along with SMN-independent strategies, such as general neuroprotective factors and muscle strength-enhancing compounds. For each therapy, we provide detailed information on clinical trial design and pharmacological/safety data where available. Previous clinical studies are also discussed to provide context on SMA clinical trial development and the insights these provided for the design of current studies.
Positive End-Expiratory Pressure Lower Than the ARDS Network Protocol Is Associated with Higher Pediatric Acute Respiratory Distress Syndrome Mortality
Authors: Robinder G. Khemani, Kaushik Parvathaneni, Nadir Yehya, Anoopindar K. Bhalla, Neal J. Thomas, Christopher J. L. Newth
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The ARDS Network (ARDSNet) used a positive end-expiratory pressure (PEEP)/FiO2 model in many studies. In general, pediatric intensivists use less PEEP and higher FiO2 than this model.To evaluate whether children managed with PEEP lower than recommended by the ARDSNet PEEP/FiO2 model had higher mortality.This was a multicenter, retrospective analysis of patients with pediatric acute respiratory distress syndrome (PARDS) managed without a formal PEEP/FiO2 protocol. Four distinct datasets were combined for analysis. We extracted time-matched PEEP/FiO2 values, calculating the difference between PEEP level and the ARDSNet-recommended PEEP level for a given FiO2. We analyzed the median difference over the first 24 hours of PARDS diagnosis against ICU mortality and adjusted for confounding variables, effect modifiers, or factors that may have affected the propensity to use lower PEEP.Of the 1,134 patients with PARDS, 26.6% were managed with lower PEEP relative to the amount of FiO2 recommended by the ARDSNet protocol. Patients managed with lower PEEP experienced higher mortality than those who were managed with PEEP levels in line with or higher than recommended by the protocol (P < 0.001). After adjustment for hypoxemia, inotropes, comorbidities, severity of illness, ventilator settings, nitric oxide, and dataset, PEEP lower than recommended by the protocol remained independently associated with higher mortality (odds ratio, 2.05; 95% confidence interval, 1.32-3.17). Findings were similar after propensity-based covariate adjustment (odds ratio, 2.00; 95% confidence interval, 1.24-3.22).Patients with PARDS managed with lower PEEP relative to FiO2 than recommended by the ARDSNet model had higher mortality. Clinical trials targeting PEEP management in PARDS are needed.
Controversies in Management: Alternatives are still unproved
Authors: M C Bishop
Journal: BMJ (1994)

For many years transurethral resection of prostate has been established as the optimum treatment for benign prostatic hyperplasia. This viewpoint is now being challenged because of criticism of the operation itself and by the availability of a bewildering variety of alternative treatments (box). Most are recent innovations, and results of long term follow up studies are not yet available. Unfortunately, claims for their superiority have sometimes been exaggerated by their enthusiastic proponents.

Treatments for benign prostatic hyperplasia

Physical

Balloon dilatation

Intraurethral implants - Spirals, stents

Microwave thermotherapy - Transrectal, transurethral

Laser - “Side fire” ablation, contact incision, transurethral needle ablation

Ultrasonic tissue - External source

Disintegration - Transurethral probe

Cryosurgery Transurethral resection or incision of prostate

Pharmacotherapy

(alpha) Adrenergic antagonists - for example, prazosin, indoramin, terazosin, doxazosin

Antiandrogen treatment - Surgical castration, medical castration (luteinising hormone releasing hormone analogues, cyproterone, flutamide

Specific prostatic androgen inhibitor - 5(alpha) reductase inhibitor (finasteride)

Recent reports of an unexpectedly high incidence of complications after transurethral resection of prostate need to be taken seriously, but few would agree that the early and late mortality figures published by Roos et al are typical of modern practice.1 Mortality is influenced by many factors that have not necessarily been evaluated or reported but could bias results. More obviously these include the skill and continuing experience of the surgeon, the size of the prostate resected (which in turn influences duration of resection and hence blood loss and irrigant absorption), and cardiovascular …
Comprehensive review of autoantibodies in patients with hyper-IgM syndrome
Authors: Mohamed-Ridha Barbouche, Qubo Chen, Marco Carbone, Imen Ben-Mustapha, Zakera Shums, Mehdi Trifa, Federica Malinverno, Francesca Bernuzzi, Haiyan Zhang, Nourhen Agrebi, Gary L Norman, Christopher Chang, M Eric Gershwin, Pietro Invernizzi
Journal: Cellular and Molecular Immunology (2018)
Telemonitoring and/or self-monitoring of blood pressure in hypertension (TASMINH4): A Randomised Controlled Trial
Authors: R J Mcmanus, Hobbs Fdr., L Tarassenko, L Yu, A Farmer, C Heneghan, R parera, A nickless, C schwartz, S mort, E ogburn, M franssen
Journal: The Lancet (2018)