bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticholinergic Burden in Hospice Patients With Dementia
Authors: Williams Anne , Sera Leah , McPherson Mary Lynn 
Published: September 2018

Background: End-of-life (EOL) patients with dementia have an increased risk for anticholinergic toxicities due to age-related pharmacokinetic and physiologic changes in conjunction with an increased susceptibility to drug-induced cognitive impairments. Despite this well-documented risk, the use of drugs with anticholinergic properties (DAPs) remains prevalent in EOL patients with dementia. Objective: The aims of this study were to describe prescribing patterns and characterize anticholinergic burden among hospice patients with dementia, as measured by the Anticholinergic Cognitive Burden (ACB) scale. Methods: This was a retrospective review of a national hospice patient information database. Patients included were admitted on January 1, 2016, discharged by death by December 31, 2016, and had a primary diagnosis of dementia. Patients’ anticholinergic burden was calculated using ACB scores. Results: A total of 1283 patients met the inclusion criteria. Of those, 37.1% (n = 476) were prescribed at least 1 DAP. Specifically, 28.9% (n = 371) were prescribed 1 DAP, 6.6% (n = 84) were prescribed 2 DAPs, 1.6% (n = 20) were prescribed 3 DAPs, and 0.08% (n = 1) were prescribed 4 DAPs. The majority of patients prescribed a DAP had an ACB score of 3 (n = 359, 75.4%) and an average ACB score of 3.8. The most common DAPs prescribed in patients with an ACB score of 2 or higher were quetiapine (n = 202, 42.4%), atropine (n = 155, 32.6%), hyoscyamine (n = 61, 12.8%), olanzapine (n = 46, 9.6%), and scopolamine (n = 35, 7.4%). Conclusion: Due to the limited benefit and increased harms with the use of DAPs, providers should aim to maximize nonpharmacologic options. By reducing the use of the top 5 DAPs identified in this study, the quality of life and care for EOL patients with dementia can potentially be improved.
Tricyclic Antidepressants Modulate Stressed Mitochondria in Glioblastoma Multiforme Cells
Authors: Bielecka-Wajdman Anna M. , Ludyga Tomasz , Machnik Grzegorz , Gołyszny Miłosz , Obuchowicz Ewa 
Published: September 2018

A common feature of solid tumors, including glioblastoma multiforme (GBM), is mitochondrial dysfunction. However, it is reported that the current standard of anti-GBM therapies may potentiate mitochondrial damage and, in effect, support the aggressive character of cancer. As mitochondria are implicated in the modulation of cellular drug sensitivity and chemoresistance mechanisms, activation-stressed mitochondria in GBM cells may represent a new target for anti-GBM therapy that is nontoxic for normal cells. Methods: As mitochondria are possible targets for antidepressant drugs used as adjuvant therapy in patients with GBM, we examined their influence on mitochondrial volume and activity, reactive oxygen species level, extracellular lactate concentration, and p65 NF-κB gene expression in GBM cells. Results: Our investigation showed, for the first time, that tricyclic antidepressants, imipramine and amitriptyline, partially reverse GBM abnormalities. Conclusion: In the light of reported studies, the mitochondrial disturbance observed in glioma cells is a dynamic process that can be reversed or silenced. Moreover, imipramine and amitriptyline are attractive cellular metabolic modulators and can potentially be used to restoring a proper function of mitochondria in GBM cells.
Fluticasone furoate/vilanterol 92/22 µg once a day: a 12-month study on outcomes in mild to moderate asthma
Authors: Dal Negro Roberto W. , Bonadiman Luca , Turco Paola 
Published: September 2018

Background: Fluticasone furoate/vilanterol (FF/V) is an effective long-acting β2 agonist/inhaled corticosteroid combination for managing persistent bronchial asthma. The aim of the study was to assess the outcomes achievable in patients with mild to moderate asthma receiving FF/V 92/22 µg once daily for 12 months. Methods: Data were automatically and anonymously obtained from the institutional database: forced expiratory volume in 1 s predicted values; the exacerbation and hospitalization rates; days of hospitalization; general practitioner (GP) or specialist visits; days of inactivity; courses of systemic steroids or antibiotics were recorded at baseline and after 3, 6 and 12 months of treatment. The overall adherence to treatment was also calculated. Analysis of variance was used for checking the trends of variables. The improvement in lung function was significant ( p < 0.001) and time dependent. The mean (±standard error) exacerbation rate per patient changed from 1.05 (±0.16) at baseline to 0.28 (±0.07) after 3 months, 0.33 (±0.08) after 6 months and 0.18 (±0.08) after 12 months ( p < 0.001). The mean hospitalization rate per patient changed from 0.30 (±0.07) at baseline to 0.08 (±0.04) after 3 months, 0.10 (±0.05) after 6 months and 0.03 (±0.03) after 12 months ( p < 0.001). Also mean duration of hospitalization and days of inactivity were reduced over time ( p < 0.001). GP visits were also reduced, together with specialist visits (both p < 0.001). Steroid and antibiotic courses dropped significantly ( p < 0.001 and p < 0.001, respectively). Moreover, changes in all outcomes considered proved time dependent, particularly over the second semester. Finally, over time, adherence to treatment was high. Conclusions: The once-daily inhalation of combined FF/V 92/22 µg optimized systematically the exacerbation and hospitalization rates in mild to moderate asthma, together with all other outcomes over time. The effectiveness of FF/V 92/22 µg once daily proved to be time dependent over the period of the study.
Predictors of Prolonged Length of Stay After Lumbar Interbody Fusion: A Multicenter Study
Authors: Kobayashi Kazuyoshi , Ando Kei , Kato Fumihiko , Kanemura Tokumi , Sato Koji , Hachiya Yudo , Matsubara Yuji , Kamiya Mitsuhiro , Sakai Yoshihito , Yagi Hideki , Shinjo Ryuichi , Ishiguro Naoki , Imagama Shiro 
Published: September 2018

Study Design: Retrospective analysis of a prospectively database. Objectives: To identify factors associated with prolonged length of stay (LOS) in posterior /transforaminal lumbar interbody fusion (PLIF/TLIF). Methods: The subjects were patients who underwent PLIF/TLIF at 10 facilities from 2012 to 2014. A total of 1168 such patients with a mean age of 65.9 ± 12.5 years (range 18-87 years) were identified in the database. Operations were PLIF (n = 675), TLIF (n = 443), minimally invasive surgery (MIS)-PLIF (n = 22), and MIS-TLIF (n = 32). Age, gender, body mass index, ambulatory status, comorbidities, perioperative American Society of Anesthesiologists (ASA) grade, operative factors, and complications were examined. LOS was defined as the number of calendar days from the operation to hospital discharge. LOS was categorized as normal (<75th percentile) or prolonged (≥75th percentile). Results: The average LOS was 20.8 ± 9.8 days (range 7-77 days). There was a significant correlation between LOS and age ( P < .05). Reoperation during hospitalization was performed in 20 cases for surgical site infection (n = 12), epidural hematoma (n = 5), and screw misplacement (n = 3). In multivariate analysis, prolonged LOS was associated with preoperative variables of age ≥70 years (odds ratio [OR] 1.87, 95% CI 1.38-2.54), and ASA class ≥III (OR 1.52, 95% CI 1.04-2.25); surgical variables of open procedures (OR 5.84, 95% CI 1.74-19.63), fused levels ≥3 (OR 5.17, 95% CI 3.17-8.43), operative time ≥300 minutes (OR 1.88, 95% CI 1.15-3.07), and estimated blood loss ≥500 mL (OR 1.71, 95% 1.07-2.75). Conclusions: The factors identified in this study should help with obtaining informed consent, surgical planning and complication prevention to reduce health care costs associated with prolonged LOS.
Sports Hernia/Athletic Pubalgia Among Women
Authors: Zoland Mark P. , Iraci Joseph C. , Bharam Srino , Waldman Leah E. , Koulotouros John P. , Klein Devon 
Published: September 2018

Background: “Athletic pubalgia,” a term that has gained acceptance over “sports hernia,” is more common in men than women; however, it represents a significant source of morbidity for patients of both sexes. Inconsistent terminology surrounding this entity poses a diagnostic challenge and makes studying the populations at risk difficult. Purpose: To review a case series of women with athletic pubalgia by analyzing their presentations, concomitant pathologies, and surgical outcomes. Study Design: Case series; Level of evidence, 4. Methods: Between 2013 and 2016, 197 patients were seen and evaluated for the diagnosis of athletic pubalgia. Eighteen patients seen during this time were women. All patients received “pubalgia protocol” magnetic resonance imaging and subsequent surgical intervention for their pathologies. Outcomes among 17 women were assessed with a patient questionnaire >1 year after surgery. Results: Of the 17 women, 9 had rectus aponeurotic plate injury only, or pure athletic pubalgia; the remaining 8 had athletic pubalgia in combination with ≥1 inguinal, obturator, and femoral hernias. Regarding female patients in both groups, 88.2% reported that the surgery was a success at follow-up. Conclusion: Surgical repair of athletic pubalgia among women is successful in dramatically reducing pain levels in this important subset of patients.
General Practitioners’ Barriers Toward Medication Reviews in Polymedicated Multimorbid Patients
Authors: Laursen Jannie , Kornholt Jonatan , Betzer Cecilie , Petersen Tonny S. , Christensen Mikkel B. 
Published: September 2018

Purpose: The aim of this study was to explore whether general practitioners (GPs) experienced barriers toward medication reviews in polymedicated, multimorbid patients, and how a clinical pharmacologist with a focus on pharmacotherapy can support the GPs in an outpatient clinic. Design: The study was descriptive and exploratory and had a qualitative design with a phenomenological/hermeneutic orientation for the interviews. Participants: The study comprised 14 interviews with 14 different GPs from the Capital Region of Denmark. Results: Three themes emerged from the interviews: (1) The care of patients With polypharmacy is challenged by the lack of professional dialogue and collaboration between GPs and hospital-based clinical pharmacologists, (2) the relationship between the patients with polypharmacy and the GP is characterized by care and individual considerations, and (3) the culture encourages adding medication and inhibits dialogue about medication withdrawal even for patients with polypharmacy. Conclusion and implications for practice: This study found that the primary barriers toward multimorbid patients with polypharmacy were the need for communication and teamwork with specialists (cardiologists, neurologists, endocrinologists, etc). Often, GPs felt that the specialists at the hospitals were more concerned about following standards and guidelines regarding specific diseases instead of a more holistic patient approach. To improve management of polypharmacy patients, the GPs suggest that a joint force is necessary, a partner-like relationship with greater transparency regarding information transfer, feedback, and shared decision-making, but also more education in the pharmacological field is essential.
Comparison of reversal activity and mechanism of action of UHRA, andexanet, and PER977 on heparin and oral FXa inhibitors
Authors: Kalathottukaren Manu T. , Creagh A. Louise , Abbina Srinivas , Lu Genmin , Karbarz Mark J. , Pandey Anjali , Conley Pamela B. , Kizhakkedathu Jayachandran N. , Haynes Charles 
Published: September 2018

Key PointsAnticoagulant therapy–associated bleeding is a concern; a specific antidote is needed for emergency reversal of anticoagulant activity. Thermodynamic, electron microscopic, and clotting studies reveal distinct mechanisms of action for 3 different antidotes in development.
TREM-like transcript 1: a more sensitive marker of platelet activation than P-selectin in humans and mice
Authors: Smith Christopher W. , Raslan Zaher , Parfitt Lola , Khan Abdullah O. , Patel Pushpa , Senis Yotis A. , Mazharian Alexandra 
Published: September 2018

Key Points
Platelet activation in vitro results in a more rapid and greater upregulation of TLT-1 surface expression compared with P-selectin. TLT-1 is more rapidly translocated to the surface of activated platelets than P-selectin during thrombus formation in vivo.
Characterization of Tfrc-mutant mice with microcytic phenotypes
Authors: Conway Ashlee J. , Brown Fiona C. , Rank Gerhard , Kile Benjamin T. , Morton Craig J. , Jane Stephen M. , Curtis David J. 
Published: September 2018

Key Points
Novel Tfrc-mutant mouse identified in ENU mutagenesis screen with stable receptor expression. Flow imaging cytometry demonstrates microcytosis in mutants derives from dysfunctional receptor-mediated endocytosis of Tf-TfR complex.
Inter-α inhibitor proteins maintain neutrophils in a resting state by regulating shape and reducing ROS production
Authors: Htwe Soe Soe , Wake Hidenori , Liu Keyue , Teshigawara Kiyoshi , Stonestreet Barbara S. , Lim Yow-Pin , Nishibori Masahiro 
Published: September 2018

Key PointsIAIP, but not bikunin, maintains spherical shape, small size, and smooth surface of human neutrophils and supports capillary passage. IAIP reduced ROS production from neutrophils in a concentration-dependent manner probably through the p47phox phosphorylation on Ser328.
Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment
Authors: Georges George E. , Doney Kris , Storb Rainer 
Published: September 2018

AbstractTreatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive therapy (IST) for the treatment of aplastic anemia and then summarize the recommendations for first-line treatment. Based on recent data, we argue that guidelines for the initial treatment of patients with newly diagnosed severe aplastic anemia require revision. At the time of diagnosis, before beginning treatment, HLA typing should be done to identify a marrow donor among family members or in the unrelated donor registries, and a marrow transplant should be considered first-line therapy. The priority order of donor source for bone marrow transplantation is: (1) HLA-identical sibling, (2) HLA-matched unrelated donor, and (3) HLA-haploidentical donor if an HLA-matched unrelated donor is not rapidly available. Each of these donor marrow sources may be preferable to nontransplant IST. We make this recommendation because of the long-term persistent risk for disease relapse and secondary myelodysplastic syndrome or acute myeloid leukemia with the use of nontransplant IST for patients with aplastic anemia. In contrast, marrow transplantation is associated with high cure rates of aplastic anemia and a relatively low risk for graft-versus-host disease, with many patients now living for decades without the risk for disease recurrence or the development of clonal disorders. Implementation of this first-line treatment strategy will provide patients with severe aplastic anemia the best chance of long-term disease-free survival.
Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI: a pilot study
Authors: Ai Leo , Bansal Priya , Mueller Jerel K. , Legon Wynn 
Published: September 2018

Abstract
Background
Transcranial focused ultrasound (tFUS) is a new non-invasive neuromodulation technique that uses mechanical energy to modulate neuronal excitability with high spatial precision. tFUS has been shown to be capable of modulating EEG brain activity in humans that is spatially restricted, and here, we use 7T MRI to extend these findings. We test the effect of tFUS on 7T BOLD fMRI signals from individual finger representations in the human primary motor cortex (M1) and connected cortical motor regions. Participants (N = 5) performed a cued finger tapping task in a 7T MRI scanner with their thumb, index, and middle fingers to produce a BOLD signal for individual M1 finger representations during either tFUS or sham neuromodulation to the thumb representation.

Results
Results demonstrated a statistically significant increase in activation volume of the M1 thumb representation for the tFUS condition as compared to sham. No differences in percent BOLD changes were found. This effect was spatially confined as the index and middle finger M1 finger representations did not show similar significant changes in either percent change or activation volume. No effects were seen during tFUS to M1 in the supplementary motor area or the dorsal premotor cortex.

Conclusions
Single element tFUS can be paired with high field MRI that does not induce significant artifact. tFUS increases activation volumes of the targeted finger representation that is spatially restricted within M1 but does not extend to functionally connected motor regions.
Trial registration ClinicalTrials.gov NCT03634631 08/14/18
Predictive factors for multidrug-resistant gram-negative bacteria among hospitalised patients with complicated urinary tract infections
Authors: Gomila Aina , Shaw Evelyn , Carratalà Jordi , Leibovici Leonard , Tebé Cristian , Wiegand Irith , Vallejo-Torres Laura , Vigo Joan M. , Morris Stephen , Stoddart Margaret , Grier Sally , Vank Christiane , Cuperus Nienke , Van den Heuvel Leonard , Eliakim-Raz Noa , Vuong Cuong , MacGowan Alasdair , Addy Ibironke , Pujol Miquel ,   on behalf of COMBACTE-MAGNET WP5- RESCUING Study
Published: September 2018

Abstract
Background
Patients with complicated urinary tract infections (cUTIs) frequently receive broad-spectrum antibiotics. We aimed to determine the prevalence and predictive factors of multidrug-resistant gram-negative bacteria in patients with cUTI.

Methods
This is a multicenter, retrospective cohort study in south and eastern Europe, Turkey and Israel including consecutive patients with cUTIs hospitalised between January 2013 and December 2014. Multidrug-resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. A mixed-effects logistic regression model was used to determine predictive factors of multidrug-resistant gram-negative bacteria cUTI.

Results
From 948 patients and 1074 microbiological isolates, Escherichia coli was the most frequent microorganism (559/1074), showing a 14.5% multidrug-resistance rate. Klebsiella pneumoniae was second (168/1074) and exhibited the highest multidrug-resistance rate (54.2%), followed by Pseudomonas aeruginosa (97/1074) with a 38.1% multidrug-resistance rate. Predictors of multidrug-resistant gram-negative bacteria were male gender (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.20–2.29), acquisition of cUTI in a medical care facility (OR, 2.59; 95%CI, 1.80–3.71), presence of indwelling urinary catheter (OR, 1.44; 95%CI, 0.99–2.10), having had urinary tract infection within the previous year (OR, 1.89; 95%CI, 1.28–2.79) and antibiotic treatment within the previous 30 days (OR, 1.68; 95%CI, 1.13–2.50).

Conclusions
The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance.
CNS Metastases in Epidermal Growth Factor Receptor Mutation–Positive Non–Small-Cell Lung Cancer: Impact on Health Resource Utilization
Authors: Chooback Negar , Lefresne Shilo , Lau Sally C. , Ho Cheryl 
Published: September 2018

Purpose: Patients with epidermal growth factor receptor (EGFR) mutation–positive (EGFRm) non–small-cell lung cancer commonly experience disease progression in the CNS. Here, we assess the impact of CNS disease on resource utilization and outcomes in patients who are EGFRm. Methods: We completed a retrospective review of all advanced patients who were EGFRm, referred to BC Cancer, and treated with a first- and/or second-generation EGFR tyrosine kinase inhibitor from 2010 to 2015. Baseline characteristics, systemic treatment, and CNS management were collected. We compared health resource utilization (HRU) between patients with CNS-negative disease and those with CNS metastases from the median time of CNS metastases diagnosis to death or last follow-up (9.1 months) and at 9 months preceding death or last follow-up for the CNS-negative group. Results: Four hundred ninety-nine patients were referred, of which 68% were female; 51% were of Asian ethnicity; and 57%, 37%, and 6% were exon 19, 21, or other, respectively; with a median age of 66 years. Two hundred twenty-nine (46%) of 499 patients developed CNS metastases—39% at diagnosis and 61% over the course of disease. CNS metastases were managed with surgery with or without whole-brain radiotherapy (WBRT; 13%) WBRT alone (73%), stereotactic radiosurgery with or without WBRT (5%), or no CNS-directed therapy (9%). The median time from the development of CNS metastases diagnosis to death was 9.1 months. CNS-negative patients used less HRU versus patients that were CNS-positive in the 9 months preceding death or last follow-up—in the average number of clinic visits (8.53 v 12.71, respectively; P < .001), hospitalizations (0.43 v 0.76, respectively; P < .001), CNS imaging investigations (0.52 v 2.65, respectively; P < .001), emergency room visits (0.03 v 0.14, respectively; P = .001), palliative care unit admission (8% v 10%, respectively; P = .64), and hospice admission (3% v 19%, respectively; P < .001). Conclusion: The incidence of CNS metastases in patients with EGFRm is high and associated with increased HRU. Prevention or delay of CNS metastases with newer systemic therapy options may translate into lower resource utilization.
The feasibility of synthetic MRI in breast cancer patients: comparison of T
2 relaxation time with multiecho spin echo T
2 mapping method
Authors: Jung Yongsik , Gho Sung-Min , Back Seung Nam , Ha Taeyang , Kang Doo Kyoung , Kim Tae Hee 
Published: September 2018

Objective:
To compare the T 2 relaxation times acquired with synthetic MRI to those of multi-echo spin-echo sequences and to evaluate the usefulness of synthetic MRI in the clinical setting.

Methods:
From January 2017 to May 2017, we included 51 patients with newly diagnosed breast cancer, who underwent additional synthetic MRI and multiecho spin echo (MESE) T 2 mapping sequences. Synthetic MRI technique uses a multiecho and multidelay acquisition method for the simultaneous quantification of physical properties such as T 1 and T 2 relaxation times and proton density image map. A radiologist with 9 years of experience in breast imaging drew region of interests manually along the tumor margins on two consecutive axial sections including the center of tumor mass and in the fat tissue of contralateral breast on both synthetic T 2 map and MESE T 2 map images.

Results:
The mean T 2 relaxation time of the cancer was 84.75 ms (± 15.54) by synthetic MRI and 90.35 ms (± 19.22) by MESE T 2 mapping. The mean T 2 relaxation time of the fat was 129.22 ms (± 9.53) and 102.11 ms (± 13.9), respectively. Bland–Altman analysis showed mean difference of 8.4 ms for the breast cancer and a larger mean difference of 27.8 ms for the fat tissue. Spearman’s correlation test showed that there was significant positive correlation between synthetic MRI and MESE sequences for the cancer (r = 0.713, p &lt; 0.001) and for the fat (r = 0.551, p &lt; 0.001). The positive estrogen receptor and low histologic grade were associated with little differences between two methods (p = 0.02  and = 0.043, respectively).

Conclusion:
T 2 relaxation times of breast cancer acquired with synthetic MRI showed positive correlation with those of MESE T 2 mapping. Synthetic MRI could be useful for the evaluation of tissue characteristics by simultaneous acquisition of several quantitative physical properties.

Advances in knowledge:
Synthetic MRI is useful for the evaluation of T 2 relaxation times of the breast cancers.