tbuckley/cabot-search huggingface dataset:
Now is the time to retire the term "organic mental disorders"
Authors: R L Spitzer, M B First, J B Williams, K Kendler, H A Pincus, G Tucker
Journal: American Journal of Psychiatry (1992)

The organic/nonorganic distinction in contemporary classifications of mental disorders such as DSM-III and DSM-III-R has important prognostic and treatment implications, because it directs the clinician to pay special attention to the possibility of an underlying "physical" disorder as the cause of the mental disturbance. However, the term "organic" raises serious and intractable problems, since the connotative meaning of the term always returns to its historical roots, which imply an outmoded functional/structural, psychological/biological, and mind/body dualism. The authors present a proposal being considered for DSM-IV that would eliminate the term "organic" and reorganize the classification of organic mental disorders. Disorders previously referred to as "organic mental disorders" would be renamed as either "secondary disorders" (if they are due to "physical" disorders) or "substance-induced disorders." The entire classification of mental disorders would be reorganized to distribute the secondary and substance-induced disorders into the major groups with which they share phenomenology. The traditional organic mental disorders--delirium, dementia, and amnestic disorder--would be grouped together under the rubric of "cognitive impairment disorders." While acknowledging problems with the suggested new terminology and reorganization of the classification, the authors argue that the potential benefits of the proposal for clarity and for facilitating differential diagnosis justify putting to rest the familiar but now anachronistic term "organic mental disorders."
Abstract 14362: Eligibility for Ivabradine in Heart Failure: Representativeness of SHIFT in a Broad Population
Authors: Debraj Das, Gianluigi Savarese, Ulf Dahlström, Michael Fu, Jonathan G Howlett, Justin A Ezekowitz, Lars H Lund
Journal: Circulation (2016)

Background:  Elevated resting heart rate is a risk factor for adverse outcomes in patients with chronic heart failure (HF). The sinus node inhibitor ivabradine was EMA and FDA approved in 2005 and 2015 respectively, with the SHIFT trial confirming its efficacy and safety. Our objective was to characterize proportions of patients eligible for ivabradine, and the representativeness of the SHIFT clinical trial enrolees as compared to those in the Swedish Heart Failure Registry (SwedeHF).   Methods:  We examined 26,404 patients with an EF   70 bpm and baseline sinus rhythm. Baseline characteristics and medication use were compared between both groups and change in eligibility over time was reported at 6-months and 1-year in a subset of patients with follow-up registrations of eligibility variables.   Results:  Overall, 14.2% (n=3741) of patients were SHIFT-type. These patients were more likely to be younger, male, have diabetes, ischemic heart disease, lower EF and more recent onset of HF ( 50% of the target dose compared to 67.3% in non-SHIFT-type patients (p   Conclusion:  From SwedeHF, ~1 in 10 patients with chronic HF are eligible for ivabradine. These patients have a distinct clinical profile with a large percentage not meeting target beta-blocker dose. SHIFT-type patients who became ineligible over time did so due to lower subsequent heart rates.
Regional Differences in Efficacy, Safety, and Biomarkers for Second-Line Axitinib in Patients with Advanced Hepatocellular Carcinoma: From a Randomized Phase II Study
Authors: Masatoshi Kudo, Yoon-Koo Kang, Joong-Won Park, Shukui Qin, Yoshitaka Inaba, Eric Assenat, Yoshiko Umeyama, Maria José Lechuga, Olga Valota, Yosuke Fujii, Jean-Francois Martini, J. Andrew Williams, Shuntaro Obi
Journal: Liver Cancer (2017)

Background: An unmet need exists for treatment of patients with advanced hepatocellular carcinoma (HCC) who progress on or are intolerant to sorafenib. A global randomized phase II trial (ClinicalTrial.gov No. NCT01210495) of axitinib, a vascular endothelial growth factor receptor 1-3 inhibitor, in combination with best supportive care (BSC) did not prolong overall survival (OS) over placebo/BSC, but showed improved progression-free survival in some patients. Subgroup analyses were conducted to identify potential predictive/prognostic factors. Methods: The data from this phase II study were analyzed for the efficacy and safety of axitinib/BSC in patients from Asia versus non-Asia versus Asian subgroups (Japan, Korea, or mainland China/Hong Kong/Taiwan) and predictive/prognostic values of baseline microRNAs and serum soluble proteins, using the Cox proportional hazards model. Results: Of 202 patients, 78 were from non-Asia and 124 from Asia (37 Japanese, 36 Korean, and 51 Chinese). No significant differences in OS were found between axitinib/BSC and placebo/BSC in non-Asians, Asians, or Asian subgroups. However, in an exploratory analysis, axitinib/BSC showed favorable OS in Asians, especially Japanese, when patients intolerant to prior antiangiogenic therapy were excluded from the data set. Axitinib/BSC was well tolerated by non-Asians and Asians alike. The presence of 4 circulating microRNAs, including miR-5684 and miR-1224-5p, or a level lower than or equal to the median protein level of stromal cell-derived factor 1 at baseline was significantly associated with longer OS in axitinib/BSC-treated Asians or non-Asians. Conclusions: Axitinib/BSC did not prolong survival over placebo/BSC in non-Asians, Asians, or Asian subgroups, but favorable OS with axitinib/BSC was observed in a subset of Japanese patients. A patient population that excludes sorafenib-intolerant patients might potentially be more suitable for clinical trials of new agents in advanced HCC. Since these results are very preliminary, further investigation is warranted. The potential predictive/prognostic value of several baseline microRNAs and soluble proteins identified in this study would require validation in prospective studies on a large cohort of patients.
Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration
Authors: Ariadna Tibau, Consolación Molto, Alberto Ocana, Arnoud J Templeton, Luis P Del Carpio, Joseph C Del Paggio, Agustí Barnadas, Christopher M Booth, Eitan Amir
Journal: JNCI Journal of the National Cancer Institute (2017)

It is uncertain whether drugs approved by the US Food and Drug Administration (FDA) have clinically meaningful benefit as determined by validated scales such as the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).We searched the Drugs@FDA website for applications of anticancer drugs from January 2006 to December 2016. Study characteristics, outcomes, and regulatory pathways were collected from drug labels and reports of registration trials. For randomized controlled trials (RCTs), ESMO-MCBS grades were applied. Meaningful benefit was defined as a grade of A or B for (neo)adjuvant intent and 4 or 5 for palliative intent. All statistical tests were two-sided.We identified 63 individual drugs for 118 indications. These were supported by 135 studies, among which were 105 RCTs for which ESMO-MCBS could be applied. Only 46 (43.8%) met the ESMO-MCBS meaningful benefit threshold (100% of (neo)adjuvant trials and 38.8% of palliative trials). In palliative therapy trials, meaningful ESMO-MCBS grades were associated with phase III trials (compared with phase II; odds ratio [OR] = 38.45, 95% confidence interval [CI] = 3.27 to 452.00, P = .004), those with overall survival as their primary end point (compared with intermediate end points; OR = 8.28, 95% CI = 2.49 to 27.50, P = .001) and trials of targeted drugs with companion diagnostics (OR = 11.62, 95% CI = 2.95 to 45.78, P < .001). Over time, there has been an increase in the number of trials meeting the ESMO-MCBS threshold (Ptrend = .04). There were insufficient (neo)adjuvant studies to perform statistical analysis.The number of trials meeting the ESMO-MCBS threshold for clinical benefit has improved over time. However, fewer than half of RCTs supporting FDA approval meet the threshold for clinically meaningful benefit.
Population measurement for health systems
Authors: Bruce R. Schatz
Journal: npj Digital Medicine (2017)

Abstract How can health systems make good use of digital medicine? For healthcare infrastructure, the answer is population measurement, monitoring people to compute status for clustering cohorts. In chronic care, most effective is measuring all the time, to track health status as it gradually changes. Passive monitors run in the background, without additional tasks to activate monitors, especially on mobile phones. At its core, a health system is a “sorting problem”. Each patient entering the system must be effectively sorted into treatment cohorts. Health systems have three primary problems: Case Finding (which persons have which diagnoses), Risk Stratification (which persons are which status), and Care Routing (which persons need which treatments). The issue is then which measures can be continuously monitored at appropriate periodicity. The solutions of population measurement measure vital signs with passive monitors. These are input to predictive analytics to detect clinical values for providing care within health systems. For chronic care, complex vitals must be measured for overall status, such as oxygen saturation or gait speed. This enables healthcare infrastructure to support stratification, with persons placed into current levels of health status. Practical considerations for health systems influence implementation of new infrastructure. Case finding is more likely to be useful in urban settings, with barriers to entry based upon lower incomes. Care routing is more likely to be useful in rural settings, with barriers to entry based upon isolated geographies. Viable healthcare at acceptable quality and affordable cost is now possible for the range of geographies and incomes.
Acquired triggering of the fingers and thumb in adults
Authors: Michael David, Madhav Rangaraju, Andrew Raine
Journal: BMJ (2017)

#### What you need to know

#### Search and selection criteria

Articles and published textbooks were used based on the recommended reading list for the UK Diploma in Hand Surgery, which is run by the University of Manchester and the British Society of Surgery of the Hand. An additional PubMed search was performed to identify relevant articles based around the keywords “trigger finger,” “trigger thumb,” and “stenosing tenovaginitis,” filtering articles based on full text availability and English language. Search date 21 Dec 2016.

Trigger finger and trigger thumb are common conditions presenting to primary care and specialist hand surgery clinics. This article seeks to explain the causes and clinical features of acquired triggering of the digit, and to describe the options and techniques for its management while discussing the evidence base behind them.

The acquired trigger digit has a lifetime prevalence of 2%,1 requiring approximately 13 533 day case admissions for surgical release over a 12 month period in England.2 Primary care attendances are common, and incidence is estimated at 28 per 100 000 in the adult population.3 Trigger finger is synonymous with “tenosynovitis” and “tenovaginitis” in medical texts.

Patients present with jerky movements, or visible “triggering” or “catching” of the digit. There might be painful crepitus over the flexor tendons in the distal palm, which is worse during movement. Early disease can present with a painful nodule at the base of the finger (Notta’s nodule)4 or isolated morning stiffness of an individual digit, while a locked digit …
Corrections to "Audit-based education lowers systolic blood pressure in chronic kidney disease: the Quality Improvement in CKD (QICKD) trial results"
Authors: Simon de Lusignana, Hugh Gallagher, Simon Jones, Tom Chan, Jeremy van Vlymen, Aumran Tahir, Nicola Thomas, Neerja Jain, Olga Dmitrieva, Imran Rafi, Andrew McGovern, Kevin Harris
Journal: Kidney International (2013)
Benzyl Isothiocyanate, a constituent of cruciferous vegetables, retards the growth of BxPC-3 human pancreatic cancer xenografts in vivo.
Authors: Jeffrey Richards, Ruifen Zhang, Sanjay K. Srivastava
Journal: Cancer Research (2006)

5594   We have shown previously that benzyl isothiocyanate (BITC), a constituent of cruciferous vegetables, inhibits the growth of BxPC-3 human pancreatic cancer cells in culture by inducing apoptosis. Present studies were undertaken to determine the efficacy of BITC in vivo in athymic nude mice. The experimental group of animals received 6 or 12 μmol BITC by oral gavage 5 days a week, beginning the day of tumor cell implantation. Mice in control group received normal saline only. The tumors were measured with vernier calipers 3 times a week (Monday, Wednesday and Friday) and each animal was weighed twice a week (Monday and Friday). Feeding mice with 12 μmol BITC significantly retarded the growth of BxPC-3 xenograft (P
Abstract 14685: The Antiplatelet Activity of Direct Oral Anticoagulants in Acute Ischemic Stroke Patients
Authors: Taizen Nakase, Akifumi Suzuki
Journal: Circulation (2016)

Introduction:  Recently, in addition to warfarin, direct thrombin and direct factor Xa inhibitors have been used as oral anticoagulants for prevention of embolic stroke. While in Japan, argatroban, also a direct thrombin inhibitor, is available for the treatment of atherothrombotic stroke patients, supported by the evidence of decreasing micro thrombus from fragile atheromatous plaque.   Hypothesis:  We aimed to explore whether there is any differences between direct thrombin and direct factor Xa inhibitors regarding the inhibiting effect against thrombogenesis in acute ischemic stroke (AIS) patients.   Methods:  Between January 2015 and May 2016, AIS patients newly prescribed anti-thrombotic agents were consecutively screened, and 36 patients were enrolled (average age 74.0 yo). Patients who had multiple anti-thrombotic agents, consciousness disturbance, dysphagia and complications such as pneumonia and active malignancy were excluded. Blood sampling was performed at 1 and 2 weeks after the medication started. Evaluated factors were platelet aggregation with ADP, pentraxin-3 (PTX), IL-6, prothrombin time, activated partial thromboplastin time, prothrombin fragment (F1+2) and thrombin antithrombin III complex. Patients with antiplatelets were used as control.   Results:  Prescribed anti-thrombotics were dabigatran (group D: n=8), apixaban (group A: n=10) and antiplatelet agents (group P: n=18). Prevalence of stroke risks was not different between group D and A. Anticoagulation activity was equally observed in group D and A. PTX and IL-6 were declined during one week in both group D and A. However, the reduction of IL-6 was higher in group D compared with group A (p=0.295: 8.5 pg/ml and 2.2 pg/ml, respectively). While 88.9% of group P patients showed reduced platelet aggregation activity, 62.5% of group D and 40.0% of group A presented moderate reduction of platelet aggregation activity.   Conclusions:  This is the first report which investigated the antiplatelet activity of direct oral anticoagulants in AIS patients. Although the effect of anticoagulation was the same between dabigatran and apixaban, there is value in continuing to investigate the difference of antiplatelet effects.
Six Cycles of R-CHOP-21 Is Non-Inferior to 8 Cycles for Treatment of Diffuse Large B-Cell Lymphoma - a Nordic Lymphoma Group Population Based Study
Authors: Tove Wästerlid, Jorne Lionel Biccler, Peter de Nully Brown, Jacob Haaber Christensen, Gunilla Enblad, Judit Mészáros Jørgensen, Karin E Smedby, Tarec Christoffer El-Galaly, Mats Jerkeman
Journal: Blood (2017)
Standardised classification of the aetiology of bronchiectasis using an objective algorithm
Authors: David Araújo, Michal Shteinberg, Stefano Aliberti, Pieter C. Goeminne, Adam T. Hill, Tom Fardon, Dusanka Obradovic, Katerina Dimakou, Eva Polverino, Anthony De Soyza, Melissa J. McDonnell, James D. Chalmers
Journal: European Respiratory Journal (2017)

Bronchiectasis (BE) is a chronic and progressive respiratory disease with multiple possible causes [1, 2]. Many require a specific therapy and thus, a systematic aetiologic evaluation is recommended by guidelines [3]. Studies have shown wide heterogeneity in the proportion of different aetiologies identified among centres [4–8], which can be partially justified because of geographical risks factors, but may also reflect variations in testing practice or in the definitions of aetiology used [9]. The proportion of patients classified as idiopathic varies (26–74%) across the literature, and this variability is likely to be somewhat linked to a lack of use of a standard aetiological algorithm [4–8]. The use of a standardised aetiological algorithm in bronchiectasis can improve the diagnosis of underlying cause <http://ow.ly/5dga30gxrq3>
Always think of the right ventricle, even in “low-risk” pulmonary embolism
Authors: Mareike Lankeit
Journal: European Respiratory Journal (2017)

Patients with pulmonary embolism (PE) represent a prognostically heterogeneous patient population. Therefore, the current European Society of Cardiology (ESC) guidelines recommend risk stratification to guide risk-adjusted management [1]. Since no individual clinical, imaging or laboratory finding has been shown to predict risk of an adverse in-hospital outcome with adequate sensitivity and specificity to justify treatment decisions numerous studies have investigated combination models for an optimised risk classification [2, 3]. Despite considerable progress made in the identification of intermediate-high-risk patients who might benefit from reperfusion therapy, there is an ongoing discussion whether patients classified as low-risk based on clinical parameters (such as the simplified pulmonary embolism severity index (sPESI) or the Hestia criteria) should undergo imaging or laboratory testing for right ventricular (RV) function. The ESC guidelines do not provide a clear recommendation, but suggest that "patients with a sPESI of 0 points and elevated cardiac biomarkers or signs of RV dysfunction on imaging test should be classified into the intermediate-low-risk category" and thus are not candidates for home treatment [1]. There are strong arguments for and against routine imaging or laboratory testing for RV function in low-risk patients: opponents argue that routine testing has not been shown to have therapeutic implications, is time- and cost-intensive, and does not provide additive prognostic information since the risk of adverse events is low per se in patients identified by the sPESI or the Hestia criteria. The study by Côté et al. [4] published in this issue of the European Respiratory Journal appears to support, at least in part, this notion. This pooled analysis of three prospective cohorts, namely the Prognostic Factors for Pulmonary Embolism (PREP) study, the PROgnosTic valuE of Computed Tomography scan in haemodynamically stable patients with acute symptomatic pulmonary embolism (PROTECT) study and a French prospective single-centre registry, confirms that the risk of PE-related adverse events and all-cause mortality during the first 30 days was low (0.77% and 0.39%, respectively) in 779 PE patients without relevant comorbidities (no cancer, cardiopulmonary disease and age ≤80 years) and stable vital signs on admission (normal systolic blood pressure, heart rate and oxygen saturation) [4]. In this context, it should be remembered that the 30-day mortality rate was 1.0% in 305 "low-risk" patients of the sPESI derivation cohort and 1.1% in 2569 patients of the sPESI validation cohort [5]. RV dilation on MDCT is of prognostic relevance in apparently healthy and stable patients with pulmonary embolism <http://ow.ly/pqFV30gQahd>
Mitochondrial genetic variation and gout in Māori and Pacific people living in Aotearoa New Zealand
Authors: Anna L Gosling, James Boocock, Nicola Dalbeth, Jennie Harré Hindmarsh, Lisa K Stamp, Eli A Stahl, Hyon K Choi, Elizabeth A Matisoo-Smith, Tony R Merriman
Journal: Annals of the Rheumatic Diseases (2017)

Objective Mitochondria have an important role in the induction of the NLRP3 inflammasome response central in gout. The objective was to test whether mitochondrial genetic variation and copy number in New Zealand Māori and Pacific (Polynesian) people in Aotearoa New Zealand associate with susceptibility to gout. Methods 437 whole mitochondrial genomes from Māori and Pacific people (predominantly men) from Aotearoa New Zealand (327 people with gout, 110 without gout) were sequenced. Mitochondrial DNA copy number variation was determined by assessing relative read depth using data produced from whole genome sequencing (32 cases, 43 controls) and targeted resequencing of urate loci (151 cases, 222 controls). Quantitative PCR was undertaken for replication of copy number findings in an extended sample set of 1159 Māori and Pacific men and women (612 cases, 547 controls). Results There was relatively little mitochondrial genetic diversity, with around 96% of those sequenced in this study belonging to the B4a1a and derived sublineages. A B haplogroup heteroplasmy in hypervariable region I was found to associate with a higher risk of gout among the mitochondrial sequenced sample set (position 16181: OR=1.57, P = 0.001). Increased copies of mitochondrial DNA were found to protect against gout risk with the effect being consistent when using hyperuricaemic controls across each of the three independent sample sets (OR=0.89, P=0.007; OR=0.90, P=0.002; OR=0.76, P = 0.03). Paradoxically, an increase of mitochondrial DNA also associated with an increase in gout flare frequency in people with gout in the two larger sample sets used for the copy number analysis (β=0.003, P=7.1×10 –7 ; β=0.08, P=1.2×10 –4 ). Conclusion Association of reduced copy number with gout in hyperuricaemia was replicated over three Polynesian sample sets. Our data are consistent with emerging research showing that mitochondria are important for the colocalisation of the NLRP3 and ASC inflammasome subunits, a process essential for the generation of interleukin-1β in gout.
Acquired Resistance to Afatinib Due to T790M-Positive Squamous Progression in EGFR-Mutant Adenosquamous Lung Carcinoma
Authors: Biagio Ricciuti, Giulio Metro, Marta Brambilla, Vienna Ludovini, Sara Baglivo, Annamaria Siggillino, Enrico Prosperi, Rita Chiari
Journal: Journal of Thoracic Oncology (2017)
Hormone Therapy for Primary Prevention of Chronic Conditions in Postmenopausal Women
Authors: Jill Jin
Journal: JAMA (2017)

Gerald Gartlehner, MD, MPH; Sheila V. Patel, BSPH; Cynthia Feltner, MD, MPH; Rachel Palmieri Weber, PhD, MSPH; Rachel Long, PharmD, BCPS, CPP; Kelly Mullican, PharmD, CPP; Erin Boland, MSPH; Linda Lux, MPA; Meera Viswanathan, PhD
Diversification of human plasmacytoid predendritic cells in response to a single stimulus
Authors: Solana G. Alculumbre, Violaine Saint-André, Jeremy Di Domizio, Pablo Vargas, Philemon Sirven, Pierre Bost, Mathieu Maurin, Paolo Maiuri, Maxime Wery, Mabel San Roman, Léa Savey, Maxime Touzot, Benjamin Terrier, David Saadoun, Curdin Conrad, Michel Gilliet, Antonin Morillon, Vassili Soumelis
Journal: Nature Immunology (2017)