bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis
Authors: Bowen Randy C , Zhou Andrew Xingyu , Bondalapati Sailaja , Lawyer Thomas W , Snow Karisa B , Evans Patrick R , Bardsley Tyler , McFarland Mary , Kliethermes Matthew , Shi Dallas , Mamalis Christina A , Greene Tom , Rudnisky Christopher J , Ambati Balamurali Krishna 
Published: January 2018

BackgroundCurrent practice methods are unclear as to the most safe and effective prophylactic pharmacotherapy and method of delivery to reduce postoperative endophthalmitis occurrence.MethodsA systematic review and meta-analysis using Meta-analysis of Observational Studies in Epidemiology guidelines was performed to compare the efficacy of intracameral cefuroxime, moxifloxacin and vancomycin in preventing postphacoemulsification cataract surgery endophthalmitis. A safety analysis of intracameral antibiotics was concurrently performed.Data sourcesBIOSIS Previews, CINAHL, ClinicalTrials.gov, Cochrane Library, Dissertations & Theses, EMBASE, PubMed, ScienceDirect and Scopus were searched from inception to January 2017. Data were pooled using a random effects model. All articles were individually reviewed and data were extracted by two independent reviewers. Funnel plot, risk of bias and quality of evidence analyses were performed.ResultsSeventeen studies with over 900 000 eyes were included, which favoured the use of intracameral antibiotics at the end of cataract surgery (OR 0.20; 95% CI 0.13 to 0.32; P<0.00001). The average weighted postoperative endophthalmitis incidence rates with intracameral cefuroxime, moxifloxacin and vancomycin were 0.0332%, 0.0153% and 0.0106%, respectively. Secondary analyses showed no difference in efficacy between intracameral plus topical antibiotics versus intracameral alone (P>0.3). Most studies had low to moderate risk of bias. The safety analysis showed minimal toxicity for moxifloxacin. Dosing errors led to the majority of toxicities with cefuroxime. Although rare, vancomycin was associated with toxic retinal events.ConclusionIntracameral cefuroxime and moxifloxacin reduced endophthalmitis rates compared with controls with minimal or no toxicity events at standard doses. Additionally, intracameral antibiotics alone may be as effective as intracameral plus topical antibiotics.
Functional lesional neurosurgery for tremor: a systematic review and meta-analysis
Authors: Schreglmann Sebastian R , Krauss Joachim K , Chang Jin Woo , Bhatia Kailash P , Kägi Georg 
Published: January 2018

BackgroundThis work evaluates the consistency, effect size and incidence of persistent side effects of lesional neurosurgical interventions in the treatment of tremor due to Parkinson’s disease (PD), essential tremor (ET), multiple sclerosis (MS) and midbrain lesions.MethodsSystematic review and meta-analysis according to PRISMA-P guidelines. Random effects meta-analysis of standardised mean difference based on a peer-reviewed protocol (PROSPERO no. CRD42016048049).ResultsFrom 1249 abstracts screened, 86 peer-reviewed studies reporting 102 cohorts homogeneous for tremor aetiology, surgical target and technique were included.Effect on PD tremor was better when targeted at the ventral intermediate nucleus (V.im.) by radiofrequency ablation (RF) (Hedge’s g: −4.15;) over V.im. by Gamma Knife (GK) (−2.2), subthalamic nucleus (STN) by RF (−1.12) and globus pallidus internus (GPi) by RF (−0.89). For ET MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract (CTT) (−2.35) and V.im. (−2.08) showed similar mean tremor reductions to V.im. ablation by RF (−2.42) or GK (−2.13). In MS V.im. ablation by GK (−1.96) and RF (−1.63) were similarly effective.Mean rates of persistent side effects after unilateral lesions in PD were 12.8% (RF V.im.), 13.6% (RF STN), 9.2% (RF GPi), 0.7% (GK V.im.) and 7.0% (MRIgFUS V.im.). For ET, rates were 9.3% (RF V.im.), 1.8% (GK V.im.), 18.7% (MRIgFUS V.im.) and 0.0% (MRIgFUS CTT), for MS 37.7% (RF V.im.) and for rubral tremor 30.3% (RF V.im.).ConclusionThis meta-analysis quantifies safety, consistency and efficacy of lesional neurosurgical interventions for tremor by target, technique and aetiology.
Prevalence of hippocampal enlarged perivascular spaces in a sample of patients with hypertension and their relation with vascular risk factors and cognitive function
Authors: Jiménez-Balado Joan , Riba-Llena Iolanda , Garde Edurne , Valor Marta , Gutiérrez Belen , Pujadas Francesc , Delgado Pilar 
Published: January 2018

ObjectivesThe clinical importance of hippocampal enlarged perivascular spaces (H-EPVS) remains uncertain. We aimed to study their association with vascular risk factors, cognitive function and mild cognitive impairment (MCI).MethodsData were obtained from the ISSYS (Investigating Silent Strokes in hYpertensives, a magnetic resonance imaging Study) cohort, which is a prospective study of patients with hypertension aged 50–70 with no prior stroke or dementia. Participants were clinically evaluated and underwent a cognitive screening test, Dementia Rating Scale-2, which includes five cognitive subscales (attention, initiation/perseveration, conceptualisation, construction and memory). Besides, they were diagnosed with MCI or normal ageing following standard criteria. H-EPVS were manually counted on brain MRI according to a previous scale and defined as extensive when H-EPVS count was ≥7 (upper quartile). Multivariate models were created to study the relationship between H-EPVS, vascular risk factors and cognitive function.Results723 patients were included; the median age was 64 (59–67) and 51% were male. Seventy-two patients (10%) were diagnosed with MCI and 612 (84.6%) had at least 1 H-EPVS. Older age (OR per year=1.04, 95% CI 1.01 to 1.08) and poor blood pressure treatment compliance (OR=1.50, 95% CI 1.07 to 2.11) were independently associated with extensive H-EPVS. Regarding cognitive function, H-EPVS were independently and inversely correlated with verbal reasoning (β=−0.021, 95% CI −0.038 to −0.003). No association was found between H-EPVS and MCI.ConclusionsH-EPVS are a frequent finding in patients with hypertension and are associated with ageing and poor hypertension treatment compliance. Besides, H-EPVS are associated with worse verbal reasoning function.
Mixed-methods evaluation of a novel online STI results service
Authors: Gibbs Jo , Aicken Catherine R H , Sutcliffe Lorna J , Gkatzidou Voula , Tickle Laura J , Hone Kate , Sadiq S Tariq , Sonnenberg Pam , Estcourt Claudia S 
Published: January 2018

ObjectivesEvidence on optimal methods for providing STI test results is lacking. We evaluated an online results service, developed as part of an eSexual Health Clinic (eSHC).MethodsWe evaluated the online results service using a mixed-methods approach within large exploratory studies of the eSHC. Participants were chlamydia- positive and negative users of online postal self-sampling services in six National Chlamydia Screening Programme (NCSP) areas and chlamydia-positive patients from two genitourinary medicine (GUM) clinics between 21 July 2014 and 13 March 2015. Participants received a discreetly worded National Health Service ’NHS no-reply’ text message (SMS) informing them that their test results were ready and providing a weblink to a secure website. Participants logged in with their date of birth and mobile telephone or clinic number. Chlamydia-positive patients were offered online management. All interactions with the eSHC system were automatically logged and their timing recorded. Post-treatment, a service evaluation survey (n=152) and qualitative interviews (n=36) were conducted by telephone. Chlamydia-negative patients were offered a short online survey (n=274). Data were integrated.Results92% (134/146) of NCSP chlamydia-positive patients, 82% (161/197) of GUM chlamydia-positive patients and 89% (1776/1997) of NCSP chlamydia-negative participants accessed test results within 7 days. 91% of chlamydia-positive patients were happy with the results service; 64% of those who had tested previously found the results service better or much better than previous experiences. 90% of chlamydia-negative survey participants agreed they would be happy to receive results this way in the future. Interviewees described accessing results with ease and appreciated the privacy and control the two-step process gave them.ConclusionA discreet SMS to alert users/patients that results are available, followed by provision of results via a secure website, was highly acceptable, irrespective of test result and testing history. The eSHC results service afforded users privacy and control over when they viewed results without compromising access.
Maxillary nerve block as part of a multimodal anaesthesia in a lactating red‐necked wallaby (Macropus rufogriseus) undergoing partial maxillectomy
Authors: Rodrigo‐Mocholi Diego , Vlaminck Lieven , Gasthuys Frank , Schauvliege Stijn 
Published: January 2018

A partial maxillectomy was performed in a four‐year‐old, 12‐kg lactating female red‐necked wallaby or Bennett’s wallaby (Macropus rufogriseus) with a diagnosis of oral necrobacillosis or ‘lumpy jaw disease’. After intramuscular administration of dexmedetomidine and ketamine, anaesthesia was maintained with isoflurane in a mixture of oxygen and medical air. A maxillary nerve block was performed through the infraorbital canal with bupivacaine 0.5 per cent (0.2 ml/kg) to provide perioperative analgesia. Inhalant anaesthesia requirements gradually decreased during maintenance of anaesthesia. Oral tramadol was administered for postoperative pain management. During the following days, no behavioural or other signs of pain or discomfort were recorded. Physiological parameters stayed within reference values.
Vagally mediated gastric effects of brain stem α2-adrenoceptor activation in stressed rats
Authors: Jiang Yanyan , Browning Kirsteen N. , Toti Luca , Travagli R. Alberto 
Published: January 2018

Chronic stress exerts vagally dependent effects to disrupt gastric motility; previous studies have shown that, among other nuclei, A2 neurons are involved in mediating these effects. Several studies have also shown robust in vitro and in vivo effects of α2-adrenoceptor agonists on vagal motoneurons. We have demonstrated previously that brainstem vagal neurocircuits undergo remodeling following acute stress; however, the effects following brief periods of chronic stress have not been investigated. Our aim, therefore, was to test the hypothesis that different types of chronic stress influence gastric tone and motility by inducing plasticity in the response of vagal neurocircuits to α2-adrenoreceptor agonists. In rats that underwent 5 days of either homotypic or heterotypic stress loading, we applied the α2-adrenoceptor agonist, UK14304, either by in vitro brainstem perfusion to examine its ability to modulate GABAergic synaptic inputs to vagal motoneurons or in vivo brainstem microinjection to observe actions to modulate antral tone and motility. In neurons from naïve rats, GABAergic currents were unresponsive to exogenous application of UK14304. In contrast, GABAergic currents were inhibited by UK14304 in all neurons from homotypic and, in a subpopulation of neurons, heterotypic stressed rats. In control rats, UK14304 microinjection inhibited gastric tone and motility via withdrawal of vagal cholinergic tone; in heterotypic stressed rats, the larger inhibition of antrum tone was due to a concomitant activation of peripheral nonadrenergic, noncholinergic pathways. These data suggest that stress induces plasticity in brainstem vagal neurocircuits, leading to an upregulation of α2-mediated responses. NEW & NOTEWORTHY Catecholaminergic neurons of the A2 area play a relevant role in stress-related dysfunction of the gastric antrum. Brief periods of chronic stress load induce plastic changes in the actions of adrenoceptors on vagal brainstem neurocircuits.
Successive contractile periods activate mitochondria at the onset of contractions in intact rat cardiac trabeculae
Authors: Wüst Rob C. I. , Stienen Ger J. M. 
Published: January 2018

The rate of oxidative phosphorylation depends on the contractile activity of the heart. Cardiac mitochondrial oxidative phosphorylation is determined by free ADP concentration, mitochondrial Ca2+accumulation, mitochondrial enzyme activities, and Krebs cycle intermediates. The purpose of the present study was to examine the factors that limit oxidative phosphorylation upon rapid changes in contractile activity in cardiac muscle. We tested the hypotheses that prior contractile performance enhances the changes in NAD(P)H and FAD concentration upon an increase in contractile activity and that this mitochondrial “priming” depends on pyruvate dehydrogenase activity. Intact rat cardiac trabeculae were electrically stimulated at 0.5 Hz for at least 30 min. Thereafter, two equal bouts at elevated stimulation frequency of 1, 2, or 3 Hz were applied for 3 min with 3 min of 0.5-Hz stimulation in between. No discernible time delay was observed in the changes in NAD(P)H and FAD fluorescence upon rapid changes in contractile activity. The amplitudes of the rapid changes in fluorescence upon an increase in stimulation frequency (the on-transients) were smaller than upon a decrease in stimulation frequency (the off-transients). A first bout in glucose-containing superfusion solution resulted, during the second bout, in an increase in the amplitudes of the on-transients, but the off-transients remained the same. No such priming effect was observed after addition of 10 mM pyruvate. These results indicate that mitochondrial priming can be observed in cardiac muscle in situ and that pyruvate dehydrogenase activity is critically involved in the mitochondrial adaptation to increases in contractile performance.NEW & NOTEWORTHY Mitochondrial respiration increases with increased cardiac contractile activity. Similar to mitochondrial “priming” in skeletal muscle, we hypothesized that cardiac mitochondrial activity is altered upon successive bouts of contractions and depends on pyruvate dehydrogenase activity. We found altered bioenergetics upon repeated contractile periods, indicative of mitochondrial priming in rat myocardium. No effect was seen when pyruvate was added to the perfusate. As such, pyruvate dehydrogenase activity is involved in the mitochondrial adaptation to increased contractile performance.
Evaluation of Overall Response Rate and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Immunotherapy Trials
Authors: Mushti Sirisha L. , Mulkey Flora , Sridhara Rajeshwari 
Published: January 2018

Abstract
Purpose: With the approval of immunotherapies for a variety of indications, methods to assess treatment benefit addressing the response patterns observed are important. We evaluated RECIST criteria–based overall response rate (ORR) and progression-free survival (PFS) as potential surrogate endpoints of overall survival (OS), and explored a modified definition of PFS by altering the threshold percentage determining disease progression to assess the association with survival benefit in immunotherapy trials.
Experimental Design: Thirteen randomized, multicenter, active-control trials containing immunotherapeutic agents submitted to the FDA were analyzed. Associations between treatment effects of ORR, PFS, modified PFS, and OS were evaluated at individual and trial levels. Patient-level responder analysis was performed for PFS and OS.
Results: The coefficient of determination (R²) measured the strength of associations, where values near 1 imply surrogacy and values close to 0 suggest no association. At the trial level, the association between hazard ratios (HR) of PFS and OS was R2 = 0.1303, and between the odds ratio (OR) of ORR and HR of OS was R2 = 0.1277. At the individual level, the Spearman rank correlation coefficient between PFS and OS was 0.61. Trial-level associations between modified PFS and OS ranged between 0.07 and 0.1, and individual-level correlations were approximately 0.6. HRs of PFS and OS for responders versus nonresponders were 0.129 [95% confidence interval (CI), 0.11–0.15] and 0.118 (95% CI, 0.11–0.13), respectively.
Conclusions: Although responders exhibited longer survival and PFS than nonresponders, the trial-level and individual-level associations were weak between PFS/ORR and OS. Modifications to PFS did not improve associations. Clin Cancer Res; 24(10); 2268–75. ©2018 AACR.
See related commentary by Korn and Freidlin, p. 2239
Plasma n-3 and n-6 Fatty Acids Are Differentially Related to Carotid Plaque and Its Progression
Authors: Steffen Brian T. , Guan Weihua , Stein James H. , Tattersall Mathew C. , Kaufman Joel D. , Sandfort Veit , Szklo Moyses , Tsai Michael Y. 
Published: January 2018

Objective—
ω-3 (n-3) fatty acids (FAs) have long been considered healthful dietary components, yet recent clinical trials have questioned their cardiovascular benefits. By contrast, the ω-6 (n-6) FAs have been considered harmful, proatherogenic macronutrients, despite an absence of empirical evidence supporting this hypothesis. We aimed to determine whether plasma n-3 and n-6 FAs are related to risk of carotid plaque and its progression in 3327 participants of MESA (Multi-Ethnic Study of Atherosclerosis).

Approach and Results—

Carotid plaque was assessed using ultrasonography at baseline and after a median period of 9.5 years. Plasma phospholipid n-3 and n-6 FAs were determined using gas chromatography-flame ionization detection. Relative risk regression analyses assessed the relations of FAs with the presence or progression of carotid plaque adjusted for typical cardiovascular disease risk factors. At baseline, it was found that participants in the fourth quartile of n-3 docosahexaenoic acid showed a 9% lower risk of carotid plaque (
P
=0.05), whereas those in the second quartile of n-3 α-linolenic acid showed an 11% greater risk compared with respective referent quartiles (
P
=0.02). In prospective analyses, individuals in the top quartile of docosahexaenoic acid showed a 12% lower risk of carotid plaque progression during 9.5 years compared with those in the referent quartile (
P
=0.002). No significant relations were observed among n-6 FAs and plaque outcomes. No significant race/ethnicity interactions were found.

Conclusions—
These findings support docosahexaenoic acid as an atheroprotective macronutrient, whereas null findings for n-6 FAs challenge the view that they promote atherosclerosis.
Efficacy of a Chronic Care–Based Intervention on Secondary Stroke Prevention Among Vulnerable Stroke Survivors
Authors: Cheng Eric M. , Cunningham William E. , Towfighi Amytis , Sanossian Nerses , Bryg Robert J. , Anderson Thomas L. , Barry Frances , Douglas Susan M. , Hudson Lillie , Ayala-Rivera Monica , Guterman Jeffrey J. , Gross-Schulman Sandra , Beanes Sylvia , Jones Andrea S. , Liu Honghu , Vickrey Barbara G. 
Published: January 2018

Background
Disparities of care among stroke survivors are well documented. Effective interventions to improve recurrent stroke preventative care in vulnerable populations are lacking.

Methods and Results
In a randomized controlled trial, we tested the efficacy of components of a chronic care model–based intervention versus usual care among 404 subjects having an ischemic stroke or transient ischemic attack within 90 days of enrollment and receiving care within the Los Angeles public healthcare system. Subjects had baseline systolic blood pressure (SBP) ≥120 mm Hg. The intervention included a nurse practitioner/physician assistant care manager, group clinics, self-management support, report cards, decision support, and ongoing care coordination. Outcomes were collected at 3, 8, and 12 months, analyzed as intention-to-treat, and used repeated-measures mixed-effects models. Change in SBP was the primary outcome. Low-density lipoprotein reduction, antithrombotic medication use, smoking cessation, and physical activity were secondary outcomes. Average age was 57 years; 18% were of black race; 69% were of Hispanic ethnicity. Mean baseline SBP was 150 mm Hg in both arms. SBP decreased to 17 mm Hg in the intervention arm and 14 mm Hg in the usual care arm; the between-arm difference was not significant (−3.6 mm Hg; 95% confidence interval, −9.2 to 2.2). Among secondary outcomes, the only significant difference was that persons in the intervention arm were more likely to lower their low-density lipoprotein <100 md/dL (2.0 odds ratio; 95% confidence interval, 1.1–3.5).

Conclusions
This intervention did not improve SBP control beyond that attained in usual care among vulnerable stroke survivors. A community-centered component could strengthen the intervention impact.

Clinical Trial Registration

URL:
https://clinicaltrials.gov
. Unique identifier: NCT00861081.
Acute Myocardial Infarction Readmission Risk Prediction Models
Authors: Smith Lauren N. , Makam Anil N. , Darden Douglas , Mayo Helen , Das Sandeep R. , Halm Ethan A. , Nguyen Oanh Kieu 
Published: January 2018

Background
Hospitals are subject to federal financial penalties for excessive 30-day hospital readmissions for acute myocardial infarction (AMI). Prospectively identifying patients hospitalized with AMI at high risk for readmission could help prevent 30-day readmissions by enabling targeted interventions. However, the performance of AMI-specific readmission risk prediction models is unknown.

Methods and Results
We systematically searched the published literature through March 2017 for studies of risk prediction models for 30-day hospital readmission among adults with AMI. We identified 11 studies of 18 unique risk prediction models across diverse settings primarily in the United States, of which 16 models were specific to AMI. The median overall observed all-cause 30-day readmission rate across studies was 16.3% (range, 10.6%–21.0%). Six models were based on administrative data; 4 on electronic health record data; 3 on clinical hospital data; and 5 on cardiac registry data. Models included 7 to 37 predictors, of which demographics, comorbidities, and utilization metrics were the most frequently included domains. Most models, including the Centers for Medicare and Medicaid Services AMI administrative model, had modest discrimination (median C statistic, 0.65; range, 0.53–0.79). Of the 16 reported AMI-specific models, only 8 models were assessed in a validation cohort, limiting generalizability. Observed risk-stratified readmission rates ranged from 3.0% among the lowest-risk individuals to 43.0% among the highest-risk individuals, suggesting good risk stratification across all models.

Conclusions
Current AMI-specific readmission risk prediction models have modest predictive ability and uncertain generalizability given methodological limitations. No existing models provide actionable information in real time to enable early identification and risk-stratification of patients with AMI before hospital discharge, a functionality needed to optimize the potential effectiveness of readmission reduction interventions.