bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54
Authors: Dellborg Mikael , Bonaca Marc P , Storey Robert F , Steg P Gabriel , Im Kyung A , Cohen Marc , Bhatt Deepak L , Oude Ophuis Ton , Budaj Andrezej , Hamm Christian , Spinar Jindrich , Kiss Robert G , Lopez-Sendon José , Kamensky Gabriel , Van de Werf Frans , Ardissino Diego , Kontny Frederic , Montalescot Gilles , Johanson Per , Bengtsson Olof , Himmelmann Anders , Braunwald Eugene , Sabatine Marc S 
Published: June 2019

Abstract

Aims
In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15–16% in stable patients with a prior myocardial infarction (MI) 1–3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.

Methods and results
Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan–Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70–0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67–0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65–3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68–2.01; P = 0.58).

Conclusion
In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population.

Clinical trial registration
http://www.clinicaltrials.gov NCT01225562
The impact factor: implications for research policy, editorial rules and scholarly reputation
Authors: Argüelles Juan Carlos , Argüelles-Prieto Raquel 
Published: June 2019

ABSTRACT
The assessment of scientific research is essentially based on several metric parameters, the so-termed Impact Factor perhaps being the predominant one. Despite well-founded criticisms and the wide opposition of reputed scientists, this procedure has become a tool of scientific policy, and is applied in editorial procedures for scientific publication, the evaluation of research groups, the concession of grants, fellowships or even academic positions. Indeed, cutting-edge research is today a competitive and exigent task, where the legitimacy and restrictions of such metric factors remain a preoccupation. However, whatever the policy of evaluation implemented, most breakthroughs are revolutionary, and involve a change in a given paradigm, usually being made by unorthodox scientists, whose scholarly reputation may be questioned by the establishment, and who may often be excluded as a result of the current system of highly productive research.
Do phenothiazines possess antimicrobial and efflux inhibitory properties?
Authors: Grimsey Elizabeth M , Piddock Laura J V 
Published: June 2019

ABSTRACT
Antibiotic resistance is a global health concern; the rise of drug-resistant bacterial infections is compromising the medical advances that resulted from the introduction of antibiotics at the beginning of the 20th century. Considering that the presence of mutations within individuals in a bacterial population may allow a subsection to survive and propagate in response to selective pressure, as long as antibiotics are used in the treatment of bacterial infections, development of resistance is an inevitable evolutionary outcome. This, combined with the lack of novel antibiotics being released to the clinical market, means the need to develop alternative strategies to treat these resistant infections is critical. We discuss how the use of antibiotic adjuvants can minimise the appearance and impact of resistance. To this effect, several phenothiazine-derived drugs have been shown to potentiate the activities of antibiotics used to treat infections caused by Gram-positive and Gram-negative bacteria. Outside of their role as antipsychotic medications, we review the evidence to suggest that phenothiazines possess inherent antibacterial and efflux inhibitory properties enabling them to potentially combat drug resistance. We also discuss that understanding their mode of action is essential to facilitate the design of new phenothiazine derivatives or novel agents for use as antibiotic adjuvants.
Empty Institutions in Global Environmental Politics
Authors: Dimitrov Radoslav S 
Published: June 2019

AbstractWhy are some institutions without any policy powers or output? This study documents the efforts by governments to create empty international institutions whose mandates deprive them of any capacity for policy formulation or implementation. Examples include the United Nations Forum on Forests, the Copenhagen Accord on Climate Change, and the UN Commission on Sustainable Development. Research is based on participation in twenty-one rounds of negotiations over ten years and interviews with diplomats, policymakers, and observers. The article introduces the concept of empty institutions, provides evidence from three empirical cases, theorizes their political functions, and discusses theoretical implications and policy ramifications. Empty institutions are deliberately designed not to deliver and serve two purposes. First, they are political tools for hiding failure at negotiations, by creating a public impression of policy progress. Second, empty institutions are “decoys” that distract public scrutiny and legitimize collective inaction, by filling the institutional space in a given issue area and by neutralizing pressures for genuine policy. Contrary to conventional academic wisdom, institutions can be raised as obstacles that preempt governance rather than facilitate it.
Effectiveness of an intervention to improve antibiotic-prescribing behaviour in primary care: a controlled, interrupted time-series study
Authors: Teixeira Rodrigues António , Roque Fátima , Piñeiro-Lamas Maria , Falcão Amílcar , Figueiras Adolfo , Herdeiro Maria Teresa 
Published: June 2019

Abstract

Background
High rates of antibiotic misprescribing in primary care, with alarming clinical and economic consequences, highlight the urgent need for interventions to improve antibiotic prescribing in this setting.

Objectives
To assess the effectiveness on antibiotic prescribing quality indicators of a multifaceted intervention targeting health professionals’ and patients’ behaviour regarding antibiotic use.

Methods
We conducted a pragmatic cluster-randomized controlled trial in the catchment area covered by Portugal’s Central Regional Health Administration. The intervention consisted of a multidisciplinary, multifaceted programme involving physicians, pharmacists and patients, and comprising outreach visits for physicians and pharmacists, and educational materials for health professionals and patients. The following were assessed: relative ratios of prescription of penicillins sensitive to β-lactamase, penicillin combinations including β-lactamase inhibitors, third- and fourth-generation cephalosporins and fluoroquinolones; and the ratio of broad- to narrow-spectrum antibiotics. An interrupted time-series analysis for multiple-group comparisons was performed. The study protocol was registered on Clinical.trials.gov (NCT02173509).

Results
The participation rate in the educational intervention was 64% (197/309 GPs) in a total of 25 counties. Statistically significant improvements were obtained, not only in the relative prescription of penicillins sensitive to β-lactamase (overall relative change of +896%) and penicillin combinations including β-lactamase inhibitors (−161%), but also in the ratio of broad- to narrow-spectrum antibiotics (−200%). Statistically significant results were also obtained for third- and fourth-generation cephalosporins, though only in the immediate term.

Conclusions
This study showed that quality indicators of antibiotic prescribing can be improved by tackling influences on behaviour including knowledge and attitudes surrounding physicians’ clinical practice. Accordingly, these determinants must be considered when implementing interventions aimed at improving antibiotic prescribing.
Thrombolytic Salvage of Threatened Frostbitten Extremities and Digits: A Systematic Review
Authors: Drinane James , Kotamarti Vasanth S , O’Connor Casey , Nair Lakshmi , Divanyan Alex , Roth Malcolm Z , Patel Ashit , Ricci Joseph A 
Published: June 2019

Abstract
Frostbite is a cold injury that results in soft tissue loss and can lead to amputation. Vascular thrombosis following injury causes ischemic tissue damage. Despite understanding the pathology, its treatment has remained largely unchanged for over 30 years. Threatened extremities may be salvaged with thrombolytics to restore perfusion. The authors performed a systematic review to determine whether thrombolytic therapy is effective and to identify patients who may benefit from this treatment. The Pubmed, EBSCO, and Google Scholar databases were queried using the key words “thrombolytics,” “frostbite,” “fibrinolytics,” and “tPA.” Studies written after 1990 in English met inclusion criteria. Exclusion criteria were failure to delineate anatomic parts injured, failure to report number of limbs salvaged, animal studies, and non-English language publications. Thrombolytic therapy was defined as administration of tPA, alteplase, urokinase, or streptokinase. Forty-two studies were identified and 17 included. Included were 1 randomized trial, 10 retrospective studies, 2 case series, and 4 case reports. One thousand eight hundred and forty-four limbs and digits in 325 patients were studied and 216 patients treated with thrombolytics and 346 amputations performed. The most common means of thrombolysis was intra-arterial tPA. The most common duration of therapy was 48 hours. Limb salvage rates ranged from 0% to 100% with a weighted average of 78.7%. Thrombolytics are a safe and effective treatment of severe frostbite. They represent the first significant advancement in frostbite treatment by preventing otherwise inevitable amputations warranting both greater utilization and further research to clarify the ideal thrombolytic protocol.
Serum Level of Musclin Is Elevated Following Severe Burn
Authors: Clark Audra , Huebinger Ryan M , Carlson Deborah L , Wolf Steven E , Song Juquan 
Published: June 2019

Abstract
Muscle wasting induced by severe burn worsens clinical outcomes is associated with hyperglycemia. A novel muscle-specific secretory factor, musclin, was reported to regulate glucose metabolism with a homologous sequence of natriuretic peptides. The purpose of the study was to investigate musclin expression in response to burn injury in both human and animal models. Serum was collected from 13 adult burn patients and circulating levels of musclin protein were measured via elisa. The cytokine profile was measured by Bio-Plex multiple immunoassay. Following the clinical study, we used a burn rat model with 40% TBSA to study the time course of musclin expression till day 14. Rat serum and muscle tissue sample were harvested. Finally, an in vitro study was applied to investigate whether the muscle cell C2C12 myoblast expressed musclin under 10% burn serum stimulation. Pearson analysis showed that there was a significant positive correlation of musclin expression to total body surface area of burn in patients (P &= .038). Musclin expression was significantly positively correlated with IL-4, IL-7, IL-12, and IL-13 in burn patients’ serum (P < .05). In the animal study, we found that the musclin level evaluated at 6 hours and 1 day in burn rat serum (P < .05). In vitro, musclin mRNA expression significantly increased with burn serum stimulation at 24 hours (P < .05). In conclusion, serum level of musclin elevated both in human patients and burn animals; musclin was correlated with the severity of burn injury as well as with an elevated cytokine profile in patients; burn serum-stimulated musclin expression in vitro further identified the resource of musclin expression after burn.
Interim results of a real-world observational study of eribulin in soft tissue sarcoma including rare subtypes
Authors: Kobayashi Eisuke , Naito Yoichi , Asano Naofumi , Maejima Aiko , Endo Makoto , Takahashi Shunji , Megumi Yasunori , Kawai Akira 
Published: June 2019

AbstractBackgroundAlthough eribulin is used to treat soft tissue sarcomas (STSs), treatment data for rare subtypes are limited. We conducted a post-marketing surveillance study to assess safety and efficacy of eribulin in STS patients stratified by subtype.MethodsJapanese patients (n = 256) with advanced or metastatic STS receiving eribulin treatment were monitored for treatment status, adverse events, diagnostic imaging, and clinical outcomes at 3 months and 1 year. Interim analysis was performed. Patients will be monitored up to 2 years.ResultsInterim analysis included 3-month (n = 255), imaging (n = 226), and 1-year (n = 105) data. STS subtype distribution was normal. Median number of eribulin cycles was 3.0 (range: 1–17 cycles). Among patients with imaging data, best overall tumor response (12 weeks) was partial response, 7.5% (n = 17); stable disease, 34.5% (n = 78); and stable disease ≥11 weeks, 10.2% (n = 23). Overall response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) for all patients were 7.5%, 42.0% and 17.7%, respectively. ORR, DCR, and CBR were 10.3%, 32.0% and 16.5%, respectively, for patients with STS subtypes other than liposarcoma and leiomyosarcoma and included responses from patients with rare STS subtypes. Adverse drug reactions (ADRs) occurred in 211 (82.7%) patients (42 [16.5%] patients had serious ADRs), and none led to death. ADRs leading to drug withdrawal and dose reduction occurred in 27 (10.6%) and 55 (21.6%) patients, respectively.ConclusionEribulin was generally well tolerated and showed antitumor activity against STSs, including rare subtypes that currently have few treatment options.Clinical trial numberNCT03058406 (ClinicalTrials.gov)
Post transplant cyclophosphamide based haplo-identical transplant versus umbilical cord blood transplant; a meta-analysis
Authors: Poonsombudlert Kittika , Kewcharoen Jakrin , Prueksapraopong Chattip , Limpruttidham Nath 
Published: June 2019

Abstract

Objectives
Both haplo-identical transplant (haplo) and umbilical cord transplant (UC) are valuable graft options for patients without available matched relative. Previous studies showed inconsistent outcomes comparing Post transplant Cyclophosphamide based haplo (PTCy-haplo) and UC; therefore, we attempt to compare the studies by mean of meta-analysis.

Methods
We searched for titles of articles in MEDLINE (PubMed), Cochrane library, EMBASE database and Google scholar that compared transplantation with PTCy-haplo versus UC. We conducted a random-effect meta-analysis of seven studies involving a total of 3434 participants and reported the pooled odd ratios (OR) of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), relapse and overall survival (OS) between PTCy-haplo and UC groups.

Results
We found a significantly decreased risk of aGVHD and relapse in the PTCy-haplo group compared to the UC group with a pooled OR of 0.78, 95% Confidence Interval (CI) 0.67-0.92, I2=0%, and 0.74, 95% CI 0.57–0.97, I2=23.9% respectively. We also found a significantly increased rate of cGVHD and OS with a pooled OR of 1.41, 95% CI 1.02–1.95, I2=56.8%, and 1.77, 95% CI 1.1–2.87, I2=82.5%, respectively.

Conclusion
Our meta-analysis of clinical trials demonstrated superior outcome from PTCy-haplo group compared to the UC group in terms of decreased rate of aGVHD and relapse as well as the increased rate of OS but inferior in terms of increased cGVHD risk compared to UC transplant.
Germline Pathogenic Variants in 7636 Japanese Patients With Prostate Cancer and 12 366 Controls
Authors: Momozawa Yukihide , Iwasaki Yusuke , Hirata Makoto , Liu Xiaoxi , Kamatani Yoichiro , Takahashi Atsushi , Sugano Kokichi , Yoshida Teruhiko , Murakami Yoshinori , Matsuda Koichi , Nakagawa Hidewaki , Spurdle Amanda B , Kubo Michiaki 
Published: June 2019

AbstractBackgroundGenetic testing has been conducted in patients with prostate cancer (PCa) using multigene panels, but no centralized guidelines for genetic testing exist. To overcome this limitation, we investigated the demographic and clinical characteristics of patients with pathogenic variants.MethodsWe sequenced eight genes associated with hereditary PCa in 7636 unselected Japanese patients with PCa and 12 366 male, cancer-free control individuals. We assigned clinical significance for all 1456 variants using the American College of Medical Genetics and Genomics guidelines and ClinVar. We compared the frequency of carriers bearing pathogenic variants between cases and control participants with calculated PCa risk in each gene and documented the demographic and clinical characteristics of patients bearing pathogenic variants. All statistical tests were two-sided.ResultsWe identified 136 pathogenic variants, and 2.9% of patients and 0.8% of control individuals had a pathogenic variant. Association with PCa risk was statistically significant for variants in BRCA2 (P &lt; .001, odds ratio [OR] = 5.65, 95% confidence interval [CI] = 3.55 to 9.32), HOXB13 (P &lt; .001, OR = 4.73, 95% CI = 2.84 to 8.19), and ATM (P &lt; .001, OR = 2.86, 95% CI = 1.63 to 5.15). We detected recurrent new pathogenic variants such as p.Gly132Glu of HOXB13. Patients with pathogenic variants were 2.0 years younger at diagnosis and more often had smoking and alcohol drinking histories as well as family histories of breast, pancreatic, lung, and liver cancers.ConclusionsThis largest sequencing study of PCa heredity provides additional evidence supporting the latest consensus among clinicians for developing genetic testing guidelines for PCa.
Stereotactic body radiotherapy for primary non-small cell lung cancer patients with clinical T3-4N0M0 (UICC 8th edition): outcomes and patterns of failure
Authors: Narita Atsuya , Takeda Atsuya , Eriguchi Takahisa , Saigusa Yusuke , Sanuki Naoko , Tsurugai Yuichiro , Enomoto Tatsuji , Kuribayashi Hidehiko , Mizuno Tomikazu , Yashiro Kae , Hara Yu , Kaneko Takeshi 
Published: June 2019

Abstract
The evidence for stereotactic body radiotherapy (SBRT) is meagre for patients with clinical T3-4N0M0 non-small cell lung cancer (8th Edition of the Union for International Cancer Control (UICC)). This study retrospectively investigated clinical outcomes following SBRT for such patients. Among consecutive patients treated with SBRT, patients staged as cT3-4N0M0 by all criteria were examined, most of whom were unsuitable to chemoradiotherapy due to their fragile characters. Clinical outcomes were evaluated and factors associated with outcomes were investigated. Between 2005 and 2017, 70 eligible patients (T3: 58, T4: 12; median age 81 (63–93) years) were identified. Median follow-up duration was 28.6 (1.0–142.5) months. No adjuvant chemotherapy was administered. The 3-year local recurrence rates were 15.8% and 16.7% in T3 and T4 patients, respectively, and they were significantly lower in the high-dose group (3.1% vs 28.6%, P < 0.01). Multivariate analyses showed that the dose-volumetric factor was the significant factor for local recurrence. The 3-year regional and distant metastasis rates, cancer-specific mortality, and overall survival in T3 and T4 patients were 22.7% and 25.0%, 26.5% and 33.3%, 32.2% and 41.7%, and 39.5% and 41.7%, respectively. Only age was correlated with overall survival. Radiation pneumonitis ≥grade 3 and fatal hemoptysis occurred in 3 and 1 patients, respectively. SBRT for cT3-4N0M0 lung cancer patients achieved good local control. Survival was rather good considering that patients were usually frail, staged with clinical staging, and were not given adjuvant chemotherapy, and it may be comparable to surgery. To validate these outcomes following SBRT, a prospective study is warranted.
Radiotherapy for localized sebaceous carcinoma of the eyelid: a retrospective analysis of 83 patients
Authors: Takagawa Yoshiaki , Tamaki Wakana , Suzuki Shigenobu , Inaba Koji , Murakami Naoya , Takahashi Kana , Igaki Hiroshi , Nakayama Yuko , Shigematsu Naoyuki , Itami Jun 
Published: June 2019

Abstract
The current study retrospectively analyzed the results of radiotherapy for clinically localized sebaceous carcinoma of the eyelid.We reviewed records of 83 patients with histologically confirmed sebaceous carcinoma who were treated radiotherapeutically between 1983 and 2015. Sixty-five patients (78%) were initially treated with radiotherapy of curative intent, while the remaining 18 patients underwent postoperative radiotherapy due to tumor recurrence or positive surgical margins. Thirty-seven patients belonged to T1–2, while 46 belonged to T3–4. All 83 patients were treated with radiotherapy with a median radiation dose of 60 Gy. The median follow-up period was 92.1 months (range, 2.8–310.3 months).
At the time of analysis, 13 patients (15.1%) died, and 36 patients (43.3%) had local recurrence. The 7-year overall survival, freedom from neck lymph node recurrence, and local control (LC) rates for all patients were 83.5%, 75.5%, and 52.3%, respectively. Patients with a tumor size ≤10 mm had a higher 7-year LC rate than those with a tumor size >10 mm (58.8% vs 46.6%, P = 0.054). Neck lymph node recurrence was observed in 17 patients (20%) and significantly related to the tumor size. Late toxicity of an eyelid dysfunction of grade 3 was observed in 1 patient with T3 tumor.
Radiotherapy for sebaceous carcinoma of the eyelid is a reasonable alternative to surgical resection for tumors <10 mm in size with few severe complications, while larger tumors should be treated with surgery if feasible.
Surgical excision of a giant pedunculated hydatid cyst of the liver
Authors: Mohammed Ayad Ahmad , Arif Sardar Hassan 
Published: June 2019

Abstract
Hydatid disease is caused by a tape worm Echinococcus Granulosus that lives in the intestines of the definitive host which is the dog or other carnivore. Human is the accidental intermediate host and become infected by ingesting contaminated vegetables or water with the eggs of the parasite.
A-37-year old male presented with right side abdominal pain for 2 months. Abdominal examination showed a large right side abdominal mass extending from the right subcostal region to the right iliac fossa. CT-scan showed two cystic lesions in the right lobe of the and a third one extending to the pelvis. During surgery aspiration of 10 liters of bile stained fluid done. Excision of the cysts done. Tube drain put inside the cyst cavity with omentoplasty. There was bile leak to the drain which stopped over one month. The patient received anthelminthic medication for 3 months.