bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children
Authors: Nichols Kristen , Chung Eun Kyoung , Knoderer Chad A. , Buenger Lauren E. , Healy Daniel P. , Dees Jennifer , Crumby Ashley S. , Kays Michael B. 
Published: November 2015

ABSTRACT

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (
T
MIC
) of ≥50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 41 ml/min/1.73 m
2
, respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of >90% at MICs of ≤16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of >90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of ≥80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.
Efficacy of Extended-Interval Dosing of Micafungin Evaluated Using a Pharmacokinetic/Pharmacodynamic Study with Humanized Doses in Mice
Authors: Lepak A. , Marchillo K. , VanHecker J. , Azie N. , Andes D. 
Published: November 2015

ABSTRACT

The pharmacokinetic/pharmacodynamic (PK/PD) characteristics of the echinocandins favor infrequent administration of large doses. The
in vivo
investigation reported here tested the utility of a range of humanized dose levels of micafungin using a variety of prolonged dosing intervals for the prevention and therapy of established disseminated candidiasis. Humanized doses of 600 mg administered every 6 days prevented fungal growth in prophylaxis. Humanized doses of 300 to 1,000 mg administered every 6 days demonstrated efficacy for established infections.
Dose–response association of screen time-based sedentary behaviour in children and adolescents and depression: a meta-analysis of observational studies
Authors: Liu Mingli , Wu Lang , Yao Shuqiao 
Published: November 2015

BackgroundDepression represents a growing public health burden. Understanding how screen time (ST) in juveniles may be associated with risk of depression is critical for the development of prevention and intervention strategies. Findings from studies addressing this question thus far have been inconsistent. Therefore, we conducted a comprehensive systematic review and meta-analysis of data related to this question.MethodsThe meta-analysis was conducted in accordance with the PRISMA guideline. We searched the electronic databases of PubMed, Web of Science and EBSCO systematically (up to 6 May 2015). OR was adopted as the pooled measurement of association between ST and depression risk. Dose–response was estimated by a generalised least squares trend estimation.ResultsTwelve cross-sectional studies and four longitudinal studies (including 1 cohort study) involving a total of 127 714 participants were included. Overall, higher ST in preadolescent children and adolescents was significantly associated with a higher risk of depression (OR=1.12; 95% CI 1.03 to 1.22). Screen type, age, population and reference category acted as significant moderators. Compared with the reference group who had no ST, there was a non-linear dose–response association of ST with a decreasing risk of depression at ST<2 h/day, with the lowest risk being observed for 1 h/day (OR=0.88; 95% CI 0.84 to 0.93).ConclusionsOur meta-analysis suggests that ST in children and adolescents is associated with depression risk in a non-linear dose–response manner.
Community preparedness for emergency: a cross-sectional survey of residents in Heilongjiang of China
Authors: Xu Weilan , Hao Yanhua , Wu Qunhong , Ning Ning , You Jia , Liu Chaojie , Jiao Mingli , Gao Lijun , Kang Zheng , Liang Libo , Sun Hong , Cui Yu , Li Ye , Han Xiaonan , Fang Xin , Zhao Xiyan , Hu Man , Ding Ding , Gao Hao , Lu Jun 
Published: November 2015

ObjectiveThis article aims to identify factors that shape the knowledge, attitudes and behaviours of community residents in China's Heilongjiang province towards emergency preparedness. Findings of such a study may provide evidence to support the development of effective public risk communication strategies and education campaigns.DesignA cross-sectional household questionnaire survey was conducted in Heilongjiang province in 2014. A stratified cluster sampling strategy was employed to select study participants. The questionnaires were administered using face-to-face interviews. 2800 questionnaires were completed, among which 2686 (95.9%) were considered valid for data analyses. A multivariate logistic regression model was adopted to identify the extent to which the independent variables were associated with emergency preparedness.ResultsFewer than 5% respondents were well prepared for emergency. Over half (52%) of poorly prepared respondents did not know what to do in emergency; women (OR=1.691), higher household income (OR ranging from 1.666 to 2.117), previous experience with emergency (OR=1.552), higher levels of knowledge about emergency (OR=2.192), risk awareness (OR=1.531), self-efficacy (OR=1.796), as well as positive attitudes towards emergency preparedness (OR=2.265) were significant predictors for emergency preparedness. Neither educational attainment nor exposure to awareness-raising entered into the logic regression model as a significant predictor for emergency preparedness.ConclusionsThe level of emergency preparedness in Heilongjiang residents is very low, which is linked with poor knowledge and attitudes of the residents towards emergency preparedness. Future emergency awareness campaigns should be more focused and tailored to the needs of intended audience, taking into consideration of their usual source of information and knowledge in relation to emergency.
Patterns of platelet-rich plasma use among Australasian sports physicians
Authors: Samra David J , Orchard John W 
Published: November 2015

BackgroundWe hypothesised that the application, production and administration of platelet-rich plasma (PRP) varies widely among sports physicians, bringing into question the validity and consistency of PRP described in research and clinical use. We also assessed congruence between the reported clinical indications for PRP, and the available research evidence for these indications.MethodsWe conducted an anonymous 23 question online survey of 153 current Fellows of the Australasian College of Sports Physicians (ACSP), using an emailed link. It was opened from April 2014 until August 2014.ResultsThe survey confirmed that there is wide variation in the application, production and administration of PRP. Over one-third (38%) of sports physicians performed PRP injections themselves. Almost half of clinicians (49%) did not provide the service themselves, and only referred for PRP injections. The remaining clinicians did not inject PRP or refer for PRP injections at all. Clinicians who provided PRP injections varied from an average of 0–500 injections per month, with a median of 12 times per month. Australian sports physicians were far more likely to use PRP than their New Zealand counterparts. For sports physicians who provided or referred for PRP injections, tendinopathy was overwhelmingly cited (n=63) as the condition for which clinicians thought PRP was most effective. 30 respondents cited effectiveness for osteoarthritis.ConclusionsThis study confirms that there is no clear consensus among sports physicians on the preparation, administration or best clinical indications for PRP.
Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection
Authors: Langenmair Elia R. , Kubosch Eva J. , Salzmann Gian M. , Beck Samuel , Schmal Hagen 
Published: November 2015

Objective. Osteoarthritis is a long‐term complication of acute articular infections. However, the roles of cartilage and synovia in this process are not yet fully understood. Methods. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions compared in patients with arthroplasty (n = 8) or with intact joints (n = 67). Cytokines and cell function were also analyzed using a human in vitro model of joint infection. Results.	Synovial IL‐1β levels were significantly higher in patients with arthroplasty (p = 0.004). Higher IL‐1β concentrations were also found in the in vitro model without chondrocytes (p < 0.05). The anti‐inflammatory cytokines IL‐4 and IL‐10 were consistently expressed in vivo and in vitro, showing no association with the presence of cartilage or chondrocytes. In contrast, FasL levels increased steadily in vitro, reaching higher levels without chondrocytes (p < 0.05). Likewise, the viability of synovial fibroblasts (SFB) during infection was higher in the presence of chondrocytes. The cartilage‐metabolism markers aggrecan and bFGF were at higher concentrations in intact joints, but also synthesized by SFB. Conclusions. Our data suggest an anti‐inflammatory effect of cartilage associated with the SFBs’ increased resistance to infections, which displayed the ability to effectively synthesize cartilage metabolites.The trial is registered with DRKS 00003536, MISSinG.
Calcium Signaling Pathway Genes
RUNX2
and
CACNA1C
Are Associated With Calcific Aortic Valve Disease
Authors: Guauque-Olarte Sandra , Messika-Zeitoun David , Droit Arnaud , Lamontagne Maxime , Tremblay-Marchand Joël , Lavoie-Charland Emilie , Gaudreault Nathalie , Arsenault Benoit J. , Dubé Marie-Pierre , Tardif Jean-Claude , Body Simon C. , Seidman Jonathan G. , Boileau Catherine , Mathieu Patrick , Pibarot Philippe , Bossé Yohan 
Published: November 2015

Background—
Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS.

Methods and Results—

A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. mRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had
P
<5×10
−6
in the genome-wide association studies meta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in
RUNX2
(runt-related transcription factor 2), encoding an osteogenic transcription factor, demonstrated some association with AS (genome-wide association studies
P
=5.33×10
−5
). The mRNA expression levels of
RUNX2
were upregulated in calcified valves and associated with eQTL-SNPs.
CACNA1C
encoding a subunit of a voltage-dependent calcium channel was upregulated in calcified valves. The eQTL-SNP with the most significant association with AS located in
CACNA1C
was associated with higher expression of the gene.

Conclusions—

This integrative genomic study confirmed the role of RUNX2 as a potential driver of AS and identified a new AS susceptibility gene,
CACNA1C
, belonging to the calcium signaling pathway.
Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension
Authors: Rothman Alexander M.K. , Arnold Nadine D. , Chang William , Watson Oliver , Swift Andrew J. , Condliffe Robin , Elliot Charlie A. , Kiely David G. , Suvarna S. Kim , Gunn Julian , Lawrie Allan 
Published: November 2015

Background—
Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level.

Methods and Results—

Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A
2
analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters.

Conclusions—
Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety.
mActive: A Randomized Clinical Trial of an Automated mHealth Intervention for Physical Activity Promotion
Authors: Martin Seth S. , Feldman David I. , Blumenthal Roger S. , Jones Steven R. , Post Wendy S. , McKibben Rebeccah A. , Michos Erin D. , Ndumele Chiadi E. , Ratchford Elizabeth V. , Coresh Josef , Blaha Michael J. 
Published: November 2015

Background

We hypothesized that a fully automated mobile health (
mH
ealth) intervention with tracking and texting components would increase physical activity.

Methods and Results

mA
ctive enrolled smartphone users aged 18 to 69 years at an ambulatory cardiology center in Baltimore, Maryland. We used sequential randomization to evaluate the intervention's 2 core components. After establishing baseline activity during a blinded run‐in (week 1), in phase I (weeks 2 to 3), we randomized 2:1 to unblinded versus blinded tracking. Unblinding allowed continuous access to activity data through a smartphone interface. In phase
II
(weeks 4 to 5), we randomized unblinded participants 1:1 to smart texts versus no texts. Smart texts provided smartphone‐delivered coaching 3 times/day aimed at individual encouragement and fostering feedback loops by a fully automated, physician‐written, theory‐based algorithm using real‐time activity data and 16 personal factors with a 10 000 steps/day goal. Forty‐eight outpatients (46% women, 21% nonwhite) enrolled with a mean±
SD
age of 58±8 years, body mass index of 31±6 kg/m
2
, and baseline activity of 9670±4350 steps/day. Daily activity data capture was 97.4%. The phase I change in activity was nonsignificantly higher in unblinded participants versus blinded controls by 1024 daily steps (95% confidence interval [
CI
], −580 to 2628;
P
=0.21). In phase
II
, participants receiving texts increased their daily steps over those not receiving texts by 2534 (95%
CI
, 1318 to 3750;
P
<0.001) and over blinded controls by 3376 (95%
CI
, 1951 to 4801;
P
<0.001).

Conclusions

An automated tracking‐texting intervention increased physical activity with, but not without, the texting component. These results support new
mH
ealth tracking technologies as facilitators in need of behavior change drivers.

Clinical Trial Registration

URL
:
http://ClinicalTrials.gov/
. Unique identifier:
NCT01917812
.
Impact of Alcohol Consumption on Substrate Remodeling and Ablation Outcome of Paroxysmal Atrial Fibrillation
Authors: Qiao Yu , Shi Rui , Hou Bingbo , Wu Lingmin , Zheng Lihui , Ding Ligang , Chen Gang , Zhang Shu , Yao Yan 
Published: November 2015

Background

The effect of alcohol consumption on substrate remodeling and ablation outcome of paroxysmal atrial fibrillation (
PAF
) remains unknown.

Methods and Results

We performed circumferential pulmonary vein isolation (
CPVI
) and voltage mapping of left atrium (
LA
) during sinus rhythm in 122 consecutive patients with symptomatic
PAF
(age, 55.4±9.4 years; 73.8% men). Low‐voltage zones (
LVZ
s) were semiquantitatively estimated and presented as low‐voltage index (
LVI
). Each patient's daily alcohol consumption history was recorded at baseline and classified into alcohol abstainers, moderate drinkers, and heavy drinkers based on the National Institute on Alcohol Abuse and Alcoholism definition. Follow‐up was ≥12 months for
AF
recurrence. Alcohol abstainers and moderate and heavy drinkers were 70 (57.4%), 13 (10.6%), and 39 (32.0%), respectively. In total,
LVZ
s were observed in 44 patients (36.1%). Daily alcohol consumption independently predicted presence of
LVZ
s (odds ratio [
OR
], 1.097; 95% confidence interval [
CI
], 1.001–1.203;
P
=0.047). During mean follow‐up of 20.9±5.9 months, 40 patients (35.1%) experienced
AF
recurrence. Success rate was 81.3%, 69.2%, and 35.1% in alcohol abstainers, moderate drinkers, and heavy drinkers, respectively (overall log rank,
P
<0.001). Multivariate analysis showed that both alcohol consumption and
LVI
were independent predictors of
AF
recurrence (hazard ratio [
HR
], 1.579; 95%
CI
, 1.085–2.298;
P
=0.017;
HR
, 2.188; 95%
CI
, 1.582–3.026;
P
<0.001, respectively). Furthermore, mediation analysis revealed that
LVZ
s acted as a partial mediator in effect of alcohol consumption on
AF
ablation outcomes.

Conclusions

Daily alcohol consumption was associated with atrial remodelling, and heavy drinkers have substantial risk for
AF
recurrence after
CPVI
.
Systematic review of the diagnostic category muscle dysmorphia
Authors: dos Santos Filho Celso Alves , Tirico Patrícia Passarelli , Stefano Sergio Carlos , Touyz Stephen W , Claudino Angélica Medeiros 
Published: November 2015

Objectives: (1) To collect, analyze and synthetize the evidence on muscle dysmorphia diagnosis as defined by Pope et al. and (2) To discuss its appropriate nosology and inclusion as a specific category in psychiatric classificatory systems. Method: A systematic search in the MEDLINE, the PsycNET, the LILACS and SciELO databases and in the International Journal of Eating Disorders was conducted looking for articles published between January 1997 and October 2014 and in EMBASE database between January 1997 and August 2013. Only epidemiological and analytical studies were considered for selection. The methodological quality of included studies was assessed according to the Evidence-Based Mental Health and the National Health and Medical Research Council’s guidelines. The support for inclusion of muscle dysmorphia in psychiatric classificatory systems was examined against Blashfield et al.’s criteria. Results: Thirty-four articles were considered eligible out of 5136. Most of the studies were cross-sectional and enrolled small, non-clinical samples. The methodological quality of all selected papers was graded at the lowest hierarchical level due to studies’ designs. Forty-one percent of the publications considered the available evidence insufficient to support the inclusion of muscle dysmorphia in any existing category of psychiatric disorders. The current literature does not fulfill Blashfield et al.’s criteria for the inclusion of muscle dysmorphia as a specific entity in psychiatric diagnostic manuals. Conclusion: The current evidence does not ensure the validity, clinical utility, nosological classification and inclusion of muscle dysmorphia as a new disorder in classificatory systems of mental disorders.
Hemoglobin A1c and Self-Monitored Average Glucose
Authors: Kovatchev Boris P. , Breton Marc D. 
Published: November 2015

Background: Previously we have introduced the eA1c—a new approach to real-time tracking of average glycemia and estimation of HbA1c from infrequent self-monitoring (SMBG) data, which was developed and tested in type 2 diabetes. We now test eA1c in type 1 diabetes and assess its relationship to the hemoglobin glycation index (HGI)—an established predictor of complications and treatment effect. Methods: Reanalysis of previously published 12-month data from 120 patients with type 1 diabetes, age 39.15 (14.35) years, 51/69 males/females, baseline HbA1c = 7.99% (1.48), duration of diabetes 20.28 (12.92) years, number SMBG/day = 4.69 (1.84). Surrogate fasting BG and 7-point daily profiles were derived from these unstructured SMBG data and the previously reported eA1c method was applied without any changes. Following the literature, we calculated HGI = HbA1c – (0.009 × Fasting BG + 6.8). Results: The correlation of eA1c with reference HbA1c was r = .75, and its deviation from reference was MARD = 7.98%; 95% of all eA1c values fell within ±20% from reference. The HGI was well approximated by a linear combination of the eA1c calibration factors: HGI = 0.007552* θ1 + 0.007645* θ2 – 3.154 ( P < .0001); 73% of low versus moderate-high HGIs were correctly classified by the same factors as well. Conclusions: The eA1c procedure developed in type 2 diabetes to track in real-time changes in average glycemia and present the results in HbA1c-equivalent units has shown similar performance in type 1 diabetes. The eA1c calibration factors are highly predictive of the HGI, thereby explaining partially the biological variation causing discrepancies between HbA1c and its linear estimates from SMBG data.
Quality of HbA1c Measurement in Trinidad and Tobago
Authors: Rastogi Maynika V. , Ladenson Paul , Goldstein David E. , Little Randie R. 
Published: November 2015

Background: Monitoring of HbA1c is the standard of care to assess diabetes control. In Trinidad & Tobago (T&T) there are no existing data on the quality of HbA1c measurement. Our study examined the precision and accuracy of HbA1c testing in T&T. Methods: Sets of 10 samples containing blinded duplicates were shipped to laboratories in T&T. This exercise was repeated 6 months later. Precision and accuracy were estimated for each laboratory/method. Results: T&T methods included immunoassay, capillary electrophoresis, and boronate affinity binding. Most, but not all, laboratories demonstrated acceptable precision and accuracy. Conclusions: Continuous oversight of HbA1c testing (eg, through proficiency testing) in T&T is recommended. These results highlight the lack of oversight of HbA1c testing in some developing countries.