bluuebunny/crossref_metadata_2025_split huggingface dataset:
De-escalation of Empiric Antibiotics Following Negative Cultures in Hospitalized Patients With Pneumonia: Rates and Outcomes
Authors: Deshpande Abhishek , Richter Sandra S , Haessler Sarah , Lindenauer Peter K , Yu Pei-Chun , Zilberberg Marya D , Imrey Peter B , Higgins Thomas , Rothberg Michael B 
Published: February 2020

AbstractBackgroundFor patients at risk for multidrug-resistant organisms, IDSA/ATS guidelines recommend empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. Following negative cultures, the guidelines recommend antimicrobial de-escalation. We assessed antibiotic de-escalation practices across hospitals and their associations with outcomes in hospitalized patients with pneumonia with negative cultures.MethodsWe included adults admitted with pneumonia in 2010–2015 to 164 US hospitals if they had negative blood and/or respiratory cultures and received both anti-MRSA and antipseudomonal agents other than quinolones. De-escalation was defined as stopping both empiric drugs on day 4 while continuing another antibiotic. Patients were propensity adjusted for de-escalation and compared on in-hospital 14-day mortality, late deterioration (ICU transfer), length-of-stay (LOS), and costs. We also compared adjusted outcomes across hospital de-escalation rate quartiles.ResultsOf 14 170 patients, 1924 (13%) had both initial empiric drugs stopped by hospital day 4. Hospital de-escalation rates ranged from 2–35% and hospital de-escalation rate quartile was not significantly associated with outcomes. At hospitals in the top quartile of de-escalation, even among patients at lowest risk for mortality, the de-escalation rates were &lt;50%. In propensity-adjusted analysis, patients with de-escalation had lower odds of subsequent transfer to ICU (adjusted odds ratio, .38; 95% CI, .18–.79), LOS (adjusted ratio of means, .76; .75–.78), and costs (.74; .72–.76).ConclusionsA minority of eligible patients with pneumonia had antibiotics de-escalated by hospital day 4 following negative cultures and de-escalation rates varied widely between hospitals. To adhere to recent guidelines will require substantial changes in practice.
Heparin ‘flush’ induced thrombocytopenia triggered by total hip replacement: a case report
Authors: Yoshida Ruka , Tanaka Akihito , Yoshioka Naoki , Yokote Jun 
Published: February 2020

Abstract

Background
Heparin-induced thrombocytopenia (HIT) typically responds to heparin termination. Some types of HIT can persist after heparin discontinuation.

Case summary
A 95-year-old woman was referred to the cardiology from orthopaedics because of acute limb ischaemia (ALI) 1 day after surgery of a femoral neck fracture. Despite thrombectomy, ALI relapsed the next day. She had been treated with intravenous antibiotics with a diagnosis of aspiration pneumonia for 1 week until 3 days before surgery, together with heparin flush twice a day. Of note, no intra-/post-operative heparin was administered, no cell salvage device, central venous, nor arterial catheters were used before development of ALI. The patient and her family refused reattempting invasive therapies; consequently, the patient continued to worsen and died on post-operative day 3. Diagnosis of autoimmune HIT, which was prompted by surgery without re-exposure to heparin, was confirmed posthumously.

Discussion
This case emphasizes the significance of suspecting autoimmune HIT in any patient presenting with thrombosis, even if the heparin exposure dates back more than a few days or even without heparin exposure.
Concept for a Multinational Patent Search using Elements of Blockchain Technology
Authors: Marschall Stefan 
Published: February 2020

Abstract
Blockchain Elements Integrated Multinational Search (BEIMS) is a response to an ongoing discussion about the search and examination procedures employed in patent offices, relaunched in 2018 when German law firms sent an open letter to the President of the European Patent Office.
The BEIMS concept turns away from patent examiners working by themselves in isolation, and instead involves experts from different offices working in close co-operation.
BEIMS integrates elements of Blockchain Technology – such as decentralized network, competition and consensus building – with the participation of several national and/or regional patent offices, and involves financial incentives. The co-operating patent offices are coequal and, as a consequence, a multinational search report is generated with cited prior art determined and evaluated by patent examiners of different patent offices in due time.
Does lobar or size-reduced lung transplantation offer satisfactory early and late outcomes?
Authors: Santos Silva João , Olland Anne , Massard Gilbert , Falcoz Pierre-Emmanuel 
Published: February 2020

Summary
A best evidence topic was constructed according to a structured protocol. The question addressed was whether size-reduced or lobar lung transplantation (LLTx) offers the same benefit as classic lung transplantation (LTx). Of the 147 papers found using the reported search, 9 were selected to provide the best evidence. Details of the studies regarding authors, date, journal, country of publication, study type, group studied, relevant outcomes and results are given. All studies reported survival rates of LLTx and most compared it with classical LTx. No statistical differences were reported in medium term and long term. Two of the studies reported a higher incidence of postoperative complications, such as the need for cardiopulmonary bypass, reperfusion oedema or primary graft dysfunction, and longer intubation or intensive care unit stay times. Although the largest study showed a significantly worse 1-year survival in LLTx, a sub-analysis considering patients successfully discharged showed similar outcomes at 1, 3 and 5 years when compared with classic LTx patients. We conclude that LLTx is a valid therapeutic option for recipients with significant donor size mismatch, offering similar outcomes as classical LTx in the medium term and long term.
Calcaneal Quantitative Ultrasonography and Urinary Retinol-Binding Protein in Antiretroviral-Treated Patients With Human Immunodeficiency Virus in Uganda: A Pilot Study
Authors: Costa Cecilia , Scabini Silvia , Kaimal Arvind , Kasozi William , Cusato Jessica , Kafufu Bosco , Borderi Marco , Mwaka Erisa , Di Perri Giovanni , Lamorde Mohammed , Calcagno Andrea , Castelnuovo Barbara 
Published: February 2020

AbstractBackgroundData on bone health and renal impairment in people with human immunodeficiency virus (HIV) in resource-limited settings are limited. The primary aim of this study was to investigate the potential role of calcaneal quantitative ultrasonography (QUS) in predicting bone mineral density (BMD) reduction in a population of Ugandan HIV-infected  individuals receiving long-term antiretroviral therapy; the secondary end point was to assess the prevalence of proximal tubular dysfunction and the correlation between elevated urinary retinol-binding protein–urinary creatinine ratio (uRBP/uCr) and reduced BMD.MethodsWe conducted a cross-sectional study at the Infectious Diseases Institute, Kampala, Uganda. We included 101 HIV-infected adults who had been receiving continuous antiretroviral therapy for ≥10 years and had undergone dual-energy x-ray absorptiometry (DXA) during the previous 12 months. All patients underwent calcaneal QUS evaluation and urine sample collection.ResultsDXA BMD measurements were significantly associated (P &lt; .01) with calcaneal speed of sound, broadband ultrasound attenuation, and QUS index. Forty-seven individuals (47%) had abnormal uRBP/uCr values. A significant inverse correlation was observed between uRBP/uCr and DXA T scores (lumbar [P = .03], femoral neck [P &lt; .001], and total hip [P = .002]).ConclusionsCalcaneal QUS results showed a moderate correlation with DXA outputs. The identified high prevalence of subclinical tubular impairment also highlights the importance of expanding access to tenofovir disoproxil fumarate–sparing regimens in resource-limited settings.
Changing Contact Patterns Over Disease Progression: Nipah Virus as a Case Study
Authors: Lee Kyu Han , Nikolay Birgit , Sazzad Hossain M S , Hossain M Jahangir , Khan A K M Dawlat , Rahman Mahmudur , Satter Syed Moinuddin , Nichol Stuart T , Klena John D , Pulliam Juliet R C , Kilpatrick A Marm , Sultana Sharmin , Afroj Sayma , Daszak Peter , Luby Stephen , Cauchemez Simon , Salje Henrik , Gurley Emily S 
Published: February 2020

Abstract
Contact patterns play a key role in disease transmission, and variation in contacts during the course of illness can influence transmission, particularly when accompanied by changes in host infectiousness. We used surveys among 1642 contacts of 94 Nipah virus case patients in Bangladesh to determine how contact patterns (physical and with bodily fluids) changed as disease progressed in severity. The number of contacts increased with severity and, for case patients who died, peaked on the day of death. Given transmission has only been observed among fatal cases of Nipah virus infection, our findings suggest that changes in contact patterns during illness contribute to risk of infection.
Order polarities
Authors: Egrot Rob 
Published: February 2020

Abstract
We define an order polarity to be a polarity $(X,Y,{\operatorname{R}})$ where $X$ and $Y$ are partially ordered, and we define an extension polarity to be a triple $(e_X,e_Y,{\operatorname{R}})$ such that $e_X:P\to X$ and $e_Y:P\to Y$ are poset extensions and $(X,Y,{\operatorname{R}})$ is an order polarity. We define a hierarchy of increasingly strong coherence conditions for extension polarities, each equivalent to the existence of a preorder structure on $X\cup Y$ such that the natural embeddings, $\iota _X$ and $\iota _Y$, of $X$ and $Y$, respectively, into $X\cup Y$ preserve the order structures of $X$ and $Y$ in increasingly strict ways. We define a Galois polarity to be an extension polarity satisfying the strongest of these coherence conditions and where $e_X$ and $e_Y$ are meet- and join-extensions, respectively. We show that for such polarities the corresponding preorder on $X\cup Y$ is unique. We define morphisms for polarities, providing the class of Galois polarities with the structure of a category, and we define an adjunction between this category and the category of $\varDelta _1$-completions and appropriate homomorphisms.
Ectopic RNF168 expression promotes break-induced replication-like DNA synthesis at stalled replication forks
Authors: Krais John J , Johnson Neil 
Published: February 2020

Abstract
The RNF168 E3 ubiquitin ligase is activated in response to double stranded DNA breaks (DSBs) where it mono-ubiquitinates γH2AX (ub-H2AX). RNF168 protein expression and ubiquitin signaling are finely regulated during the sensing, repair and resolution of DNA damage in order to avoid excessive spreading of ubiquitinated chromatin. Supra-physiological RNF168 protein expression levels have been shown to block DNA end resection at DSBs and increase PARP inhibitor (PARPi) sensitivity. In this study, we examined the impact of ectopic RNF168 overexpression on hydroxyurea (HU)-induced stalled replication forks in the setting of BRCA1 deficiency. Surprisingly, RNF168 overexpression resulted in the extension of DNA fibers, despite the presence of HU, in BRCA1 deficient cells. Mechanistically, RNF168 overexpression recruited RAD18 to ub-H2AX at HU-induced DNA breaks. Subsequently, a RAD18-SLF1 axis was responsible for initiating DNA synthesis in a manner that also required the break-induced replication (BIR) factors RAD52 and POLD3. Strikingly, the presence of wild-type BRCA1 blocked RNF168-induced DNA synthesis. Notably, BIR-like repair has previously been linked with tandem duplication events found in BRCA1-mutated genomes. Thus, in the absence of BRCA1, excessive RNF168 expression may drive BIR, and contribute to the mutational signatures observed in BRCA1-mutated cancers.
Impact of acute kidney injury on anticancer treatment dosage and long-term outcomes: a pooled analysis of European Organisation for Research and Treatment of Cancer trials
Authors: Péron Julien , Neven Anouk , Collette Laurence , Launay-Vacher Vincent , Sprangers Ben , Marreaud Sandrine 
Published: February 2020

Abstract

Background
The impact of kidney dysfunction on long-term outcomes of patients with advanced cancer remains unclear.

Methods
Patients with advanced cancer included in trials conducted by the European Organisation for Research and Treatment of Cancer were eligible for this retrospective analysis. Acute kidney injury (AKI) was identified using serum creatinine levels and using adverse events reported by investigators. The impact of baseline estimated glomerular filtration rates (eGFRs) on progression-free survival (PFS) and overall survival (OS) was investigated. Pooled estimates of the impact of AKI on dose intensity, treatment duration, PFS and OS were obtained following a meta-analytic process.

Results
Nine trials were included in this study, totalling 2872 metastatic patients with various tumour types and various systemic treatment types. Baseline eGFR had homogeneously no impact on PFS or OS. Most Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (RIFLE) events occurred early during the course of the treatment. AKI was not associated with an increased rate of treatment discontinuation, while it decreased the study treatment dose intensity. Occurrence of a first RIFLE event significantly and homogeneously reduced PFS (pooled hazard ratio = 1.18, 95% confidence interval 1.07–1.30; P = 0.0012), while its impact on OS was more heterogeneous across trials.

Conclusion
AKI is associated with reduced treatment dose intensity and reduced PFS. Therefore, close monitoring of the kidney function during the first months of treatment should be included in clinical trial protocols and probably also in daily practice to enable early AKI diagnosis and management. Collaboration between oncologists and nephrologists is needed to reduce the risk of undertreatment of patients experiencing AKI.
Imaging and histopathologic correlates of plasma cell-free DNA concentration and circulating tumor DNA in adult patients with newly diagnosed glioblastoma
Authors: Nabavizadeh Seyed Ali , Ware Jeffrey B , Guiry Samantha , Nasrallah MacLean P , Mays Jazmine J , Till Jacob E , Hussain Jasmin , Abdalla Aseel , Yee Stephanie S , Binder Zev A , O’Rourke Donald M , Brem Steven , Desai Arati S , Wolf Ronald , Carpenter Erica L , Bagley Stephen J 
Published: February 2020

Abstract

Background
Plasma cell-free DNA (cfDNA) concentration is lower in glioblastoma (GBM) compared to other solid tumors, which can lead to low circulating tumor DNA (ctDNA) detection. In this study, we investigated the relationship between multimodality magnetic resonance imaging (MRI) and histopathologic features with plasma cfDNA concentration and ctDNA detection in patients with treatment-naive GBM.

Methods
We analyzed plasma cfDNA concentration, MRI scans, and tumor histopathology from 42 adult patients with newly diagnosed GBM. Linear regression analysis was used to examine the relationship of plasma cfDNA concentration before surgery to imaging and histopathologic characteristics. In a subset of patients, imaging and histopathologic metrics were also compared between patients with and without a detected tumor somatic mutation.

Results
Tumor volume with elevated (&gt;1.5 times contralateral white matter) rate transfer constant (Kep, a surrogate of blood–brain barrier [BBB] permeability) was independently associated with plasma cfDNA concentration (P = .001). Histopathologic characteristics independently associated with plasma cfDNA concentration included CD68+ macrophage density (P = .01) and size of tumor vessels (P = .01). Patients with higher (grade ≥3) perivascular CD68+ macrophage density had lower volume transfer constant (Ktrans, P = .01) compared to those with lower perivascular CD68+ macrophage density. Detection of at least 1 somatic mutation in plasma cfDNA was associated with significantly lower perivascular CD68+ macrophages (P = .01).

Conclusions
Metrics of BBB disruption and quantity and distribution of tumor-associated macrophages are associated with plasma cfDNA concentration and ctDNA detection in GBM patients. These findings represent an important step in understanding the factors that determine plasma cfDNA concentration and ctDNA detection.
Navigating the Intersection Between Persistent Pain and the Opioid Crisis: Population Health Perspectives for Physical Therapy
Authors: Davenport Todd E , DeVoght Andra C , Sisneros Holly , Bezruchka Stephen 
Published: February 2020

Abstract
The physical therapy profession has recently begun to address its role in preventing and managing opioid use disorder (OUD). This topic calls for discussion of the scope of physical therapist practice, and the profession’s role, in the prevention and treatment of complex chronic illnesses, such as OUD. OUD is not just an individual-level problem. Abundant scientific literature indicates OUD is a problem that warrants interventions at the societal level. This upstream orientation is supported in the American Physical Therapy Association’s vision statement compelling societal transformation and its mission of building communities. Applying a population health framework to these efforts could provide physical therapists with a useful viewpoint that can inform clinical practice and research, as well as develop new cross-disciplinary partnerships. This Perspective discusses the intersection of OUD and persistent pain using the disease prevention model. Primordial, primary, secondary, and tertiary preventive strategies are defined and discussed. This Perspective then explains the potential contributions of this model to current practices in physical therapy, as well as providing actionable suggestions for physical therapists to help develop and implement upstream interventions that could reduce the impact of OUD in their communities.
Anti-IL1 treatment in colchicine-resistant paediatric FMF patients: real life data from the HELIOS registry
Authors: Sag Erdal , Akal Fuat , Atalay Erdal , Akca Ummusen Kaya , Demir Selcan , Demirel Dilara , Batu Ezgi Deniz , Bilginer Yelda , Ozen Seza 
Published: February 2020

Abstract

Objectives
FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine-resistant/intolerant FMF patients. We aimed to investigate the efficacy and safety of anti-IL1 treatment in paediatric FMF patients in our local [Hacettepe univErsity eLectronIc research fOrmS (HELIOS)] registry.

Methods
HELIOS is a web-based biologic drug registry for paediatric rheumatology patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agents.

Results
Forty paediatric FMF patients (34 continuous and six on-demand use) were included. Among the continuously treated group (61.7% female), the mean age at the start of colchicine was 5.55 (3.87) years. Age at onset of the anti-IL1 treatment was 11.47 (5.41) years with a mean follow-up duration of 3.87 (1.96) years. Apart from two, all patients had biallelic exon-10 mutations. We also gave anti-IL1 treatment on an on-demand basis in six patients. Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients with canakinumab. Anti-IL1 treatment decreased the CRP levels and number and severity of the attacks. There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leucopenia with anakinra and one patient had thrombocytopenia with canakinumab. There was no malignancy or other severe adverse reactions.

Conclusion
Anakinra and canakinumab are efficient and safe alternatives in colchicine-resistant or -intolerant paediatric FMF patients. We also, for the first time, report on-demand use of anti-IL1 in paediatric FMF patients.
Gender Mainstreaming as a Universal Tool for Constitution Writing: The Case of Iraq
Authors: Forman-Rabinovici Aliza 
Published: February 2020

Abstract
In light of postcolonial feminist criticisms, this article asks how does gender mainstreaming function as a strategy for introducing a gender perspective into the constitution writing process and constitutional text? The 2005 Iraqi Constitution is used to explore the method outside of its usual Western-dominated intergovernmental organization (IGO) context. Three main questions guide the analysis: Did gender mainstreaming promote gender equality effectively? Were there any shortcomings that were a result of a failure to account for intersectionality? Was the association of gender mainstreaming with Western-dominated IGOs a hindrance to the advancement of gender equality?
Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives
Authors: Haas David W. , Cramer Yoninah S. , Godfrey Catherine , Rosenkranz Susan L. , Aweeka Francesca , Berzins Baiba , Coombs Robert , Coughlin Kristine , Moran Laura E. , Gingrich David , Zorrilla Carmen D. , Baker Paxton , Cohn Susan E. , Scarsi Kimberly K. 
Published: February 2020

Objective
In AIDS Clinical Trials Group study A5316, efavirenz lowered plasma concentrations of etonogestrel and ethinyl estradiol, given as a vaginal ring, while atazanavir/ritonavir increased etonogestrel and lowered ethinyl estradiol concentrations. We characterized the pharmacogenetics of these interactions.

Methods
In A5316, women with HIV enrolled into control (no antiretrovirals), efavirenz [600 mg daily with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)], and atazanavir/ritonavir (300/100 mg daily with NRTIs) groups. On day 0, a vaginal ring was inserted, releasing etonogestrel/ethinyl estradiol 120/15 μg/day. Intensive plasma sampling for antiretrovirals was obtained on days 0 and 21, and single samples for etonogestrel and ethinyl estradiol on days 7, 14, and 21. Seventeen genetic polymorphisms were analyzed.

Results
The 72 participants in this analysis included 25, 24 and 23 in the control, efavirenz, and atazanavir/ritonavir groups, respectively. At day 21 in the efavirenz group, CYP2B6 genotype was associated with increased plasma efavirenz exposure (P = 3.2 × 10−3), decreased plasma concentrations of etonogestrel (P = 1.7 × 10−3), and decreased ethinyl estradiol (P = 6.7 × 10−4). Compared to controls, efavirenz reduced median etonogestrel concentrations by at least 93% in CYP2B6 slow metabolizers versus approximately 75% in normal and intermediate metabolizers. Efavirenz reduced median ethinyl estradiol concentrations by 75% in CYP2B6 slow metabolizers versus approximately 41% in normal and intermediate metabolizers.

Conclusion

CYP2B6 slow metabolizer genotype worsens the pharmacokinetic interaction of efavirenz with hormonal contraceptives administered by vaginal ring. Efavirenz dose reduction in CYP2B6 slow metabolizers may reduce, but will likely not eliminate, this interaction.