bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inter-Rater Reliability of the Modified Radiographic Union Score for Diaphyseal Tibial Fractures With Bone Defects
Authors: Mitchell Stuart L. , Obremskey William T. , Luly Jason , Bosse Michael J. , Frey Katherine P. , Hsu Joseph R. , MacKenzie Ellen J. , Morshed Saam , O'Toole Robert V. , Scharfstein Daniel O. , Tornetta Paul ,   the Major Extremity Trauma Rehabilitation Consortium (METRC)
Published: February 2019

Objectives:
To evaluate inter-rater reliability of the modified Radiographic Union Score for Tibial (mRUST) fractures among patients with open, diaphyseal tibia fractures with a bone defect treated with intramedullary nails (IMNs), plates, or definitive external fixation (ex-fix).

Design:
Retrospective cohort study.

Setting:
Fifteen-level one civilian trauma centers; 2 military treatment facilities.

Patients/Participants:
Patients ≥18 years old with open, diaphyseal tibia fractures with a bone defect ≥1 cm surgically treated between 2007 and 2012.

Intervention:
Three of 6 orthopedic traumatologists reviewed and applied mRUST scoring criteria to radiographs from the last clinical visit within 13 months of injury.

Main Outcome Measurements:
Inter-rater reliability was assessed using Krippendorff's alpha (KA) statistic; intraclass correlation coefficient (ICC) is presented for comparison with previous publications.

Results:
Two hundred thirteen patients met inclusion criteria including 115 IMNs, 24 plates, 29 ex-fixes, and 45 cases that no longer had instrumentation at evaluation. All reviewers agreed on the pattern of scoreable cortices for 90.4% of IMNs, 88.9% of those without instrumentation, 44.8% of rings, and 20.8% of plates. Thirty-one (15%) cases, primarily plates and ex-fixes, did not contribute to KA and ICC estimates because <2 raters scored all cortices. The overall KA for the 85% that could be analyzed was 0.64 (ICC 0.71). For IMNs, plates, ex-fixes, and no instrumentation, KA (ICC) was 0.65 (0.75), 0.88 (0.90), 0.47 (0.62), and 0.48 (0.57), respectively.

Conclusions:
In tibia fractures with bone defects, the mRUST seems similarly reliable to previous work in patients treated with IMN but is less reliable in those with plates or ex-fixes, or after removal of instrumentation.
Declining Mortality in Patients With Acute Respiratory Distress Syndrome: An Analysis of the Acute Respiratory Distress Syndrome Network Trials
Authors: Zhang Zhongheng , Spieth Peter Markus , Chiumello Davide , Goyal Hemant , Torres ; Antoni , Laffey John G. , Hong Yucai 
Published: February 2019

Objectives:
There has been multiple advances in the management of acute respiratory distress syndrome, but the temporal trends in acute respiratory distress syndrome–related mortality are not well known. This study aimed to investigate the trends in mortality in acute respiratory distress syndrome patients over time and to explore the roles of daily fluid balance and ventilation variables in those patients.

Design:
Secondary analysis of randomized controlled trials conducted by the Acute Respiratory Distress Syndrome Network from 1996 to 2013.

Setting:
Multicenter study involving Acute Respiratory Distress Syndrome Network trials.

Patients:
Patients with acute respiratory distress syndrome.

Interventions:
None.

Measures and Main Results:
Individual patient data from 5,159 acute respiratory distress syndrome patients (excluding the Late Steroid Rescue Study trial) were enrolled in this study. The crude mortality rate decreased from 35.4% (95% CI, 29.9–40.8%) in 1996 to 28.3% (95% CI, 22.0–34.7%) in 2013. By adjusting for the baseline Acute Physiology and Chronic Health Evaluation III, age, ICU type, and admission resource, patients enrolled from 2005 to 2010 (odds ratio, 0.61; 95% CI, 0.50–0.74) and those enrolled after 2010 (odds ratio, 0.73; 95% CI, 0.58–0.92) were associated with lower risk of death as compared to those enrolled before 2000. The effect of year on mortality decline disappeared after adjustment for daily fluid balance, positive end-expiratory pressure, tidal volume, and plateau pressure. There were significant trends of declines in daily fluid balance, tidal volume, and plateau pressure and an increase in positive end-expiratory pressure over the 17 years.

Conclusions:
Our study shows an improvement in the acute respiratory distress syndrome-related mortality rate in the critically ill patients enrolled in the Acute Respiratory Distress Syndrome Network trials. The effect was probably mediated via decreased tidal volume, plateau pressure, and daily fluid balance and increased positive end-expiratory pressure.
Prevalence of Axonal Sensory Neuropathy With IgM Binding to Trisulfated Heparin Disaccharide in Patients With Fibromyalgia
Authors: Malik Asma , Lopate Glenn , Hayat Ghazala , Jones Jacqueline , Atluri Rama , Malo Bassam , Pestronk Alan 
Published: February 2019

Objective:
To assess the intraepidermal nerve fiber density in patients diagnosed with fibromyalgia (FM) and to evaluate the role of IgM binding to trisulfated heparin disaccharide (TS-HDS) in these patients.

Methods:
FM is a poorly understood pain disorder with several proposed pathophysiologic mechanisms. It is characterized by widespread pain, fatigue, and sleep abnormalities. Small fiber neuropathy (SFN) has been proposed as an underlying mechanism, and patients with FM have been shown to have a reduction in the intraepidermal nerve fiber density. An underlying inflammatory process that could be a result of autoimmune phenomena has also been suggested. Non–length-dependent SFN (NLDSFN) has been shown to have a higher incidence of autoimmune disease. Twenty-two patients with established diagnosis of FM underwent skin biopsy at 2 sites; 10 cm above the lateral malleolus and 10 cm above the patella. Serum IgM binding to TS-HDS was assayed using an ELISA method.

Results:
A total of 5/22 patients had positive TS-HDS antibodies; of these, 4 had NLDSFN (P = 0.0393). Comparison with a control group at Washington University showed no significant difference in percentage with TS-HDS antibodies (P = 0.41). When compared with Washington University database of skin biopsy, there was a trend for an increased percentage of NLDSFN in patients with FM (P = 0.06).

Conclusions:
This study further supports the hypothesis that a subgroup of patients with FM has SFN. We suggest a correlation between the presence of NLDSFN and TS-HDS antibodies.
Amifampridine Phosphate (Firdapse) Is Effective in a Confirmatory Phase 3 Clinical Trial in LEMS
Authors: Shieh Perry , Sharma Khema , Kohrman Bruce , Oh Shin J. 
Published: February 2019

Objective:
To assess tolerability and efficacy of amifampridine phosphate versus placebo for symptomatic treatment of Lambert–Eaton Myasthenic Syndrome (LEMS).

Methods:
This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in 26 adults with LEMS compared efficacy of amifampridine phosphate versus placebo over a 4-day period. The primary endpoints were quantitative myasthenia gravis score (QMG) and subject global impression, and the secondary endpoint was Clinical Global Impression–Improvement. The exploratory endpoints were 3TUG (timed up and go) test and QMG limb domain score. All participants had been receiving amifampridine phosphate (30–80 mg/d divided into 3 or 4 doses daily) in an expanded access protocol and had been titrated to the optimal dose and frequency for at least 1 week before randomization into the current study. After completion of assessments after 4 days of double-blind treatment, patients had the option to return to open-label amifampridine phosphate. The efficacy endpoints were mean changes from baseline in the various evaluation parameters.

Results:
Amifampridine phosphate (n = 13) demonstrated significant benefit in QMG and subject global impression compared with placebo (n = 13) at 4 days. Other measures of efficacy, including Clinical Global Impression–Improvement, 3TUG, and QMG limb domain score were also improved. The most common “adverse events” in the placebo group were muscle weakness (n = 5) and fatigue (n = 4), as expected from withdrawal of amifampridine phosphate, whereas only back pain (n = 1), pain in extremity (n = 1), and headache (n = 1) were reported in amifampridine phosphate group.

Conclusions:
This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in adults with LEMS provided class I evidence of efficacy of amifampridine phosphate as symptomatic treatment in LEMS.
Retrospective Balance Study for Individuals With Chronic Obstructive Pulmonary Disease: Evaluating the Effect of a 1-Month Physical Therapy Program
Authors: Champion Tiffany , Sanford Kathleen , Byrd Rebecca 
Published: February 2019

Purpose:
To determine whether a 1-month physical therapy (PT) program that includes a balance component improves balance impairments and fear of falling in individuals with chronic obstructive pulmonary disease (COPD), and to evaluate the utility of the Four Square Step Test (FSST) and Functional Reach Test (FRT) in this population.

Methods:
A retrospective analysis of participants with COPD in a PT program between May 2015 and December 2015. Assessments performed before and after therapy were the Berg Balance Scale (BBS), FRT, FSST, and Activities Balance Confidence Scale (ABC) questionnaire. Statistical analysis used Pearson product–moment coefficient of correlation, 1-tailed T test, and Independent T test.

Results:
Twenty-five individuals with COPD completed the PT program. Individuals at high risk of falls experienced significant improvements on the BBS (6.6 points, P = .0097), FSST (6.75 seconds, P = .001), and FRT (5.63 cm, P = .01333). The BBS and FSST were correlated with each other (r = 0.70) at baseline. Improvements in the ABC were not statistically significant (P = .071). Use of supplemental oxygen was not correlated with any assessment tool.

Conclusions:
People with greater balance deficits had significant improvements in balance after a 1-month PT program. The FSST should be investigated further in patients with COPD.
ALDH2 Activation Inhibited Cardiac Fibroblast-to-Myofibroblast Transformation Via the TGF-β1/Smad Signaling Pathway
Authors: Yuan Qiuhuan , Cao Shengchuan , Dong Qianqian , Wang Zheng , Xu Youshun , Han Qi , Ma Jingjing , Wei Shujian , Pang Jiaojiao , Yang Feihong , Zhang Rui , Liu Baoshan , Dai Shuai , Xue Li , Wang Jiali , Xue Mengyang , Xu Tonghui , Zheng Wen , Xu Feng , Chen Yuguo , Guo Ping 
Published: February 2019

Abstract:
Pathological stimulus–triggered differentiation of cardiac fibroblasts plays a major role in the development of myocardial fibrosis. Aldehyde dehydrogenase 2 (ALDH2) was reported to exert a protective role in cardiovascular disease, and whether ALDH2 is involved in cardiac fibroblast differentiation remains unclear. In this study, we used transforming growth factor-β1 (TGF-β1) to induce the differentiation of human cardiac fibroblasts (HCFs) and adopted ALDH2 activator Alda-1 to verify the influence of ALDH2 on HCF differentiation. Results showed that ALDH2 activity was obviously impaired when treating HCFs with TGF-β1. Activation of ALDH2 with Alda-1 inhibited the transformation of HCFs into myofibroblasts, demonstrated by the decreased smooth muscle actin (α-actin) and periostin expression, reduced HCF-derived myofibroblast proliferation, collagen production, and contractility. Moreover, application of Smad2/3 inhibitor alleviated TGF-β1–induced HCF differentiation and improved ALDH2 activity, which was reversed by the application of ALDH2 inhibitor daidzin. Finally, Alda-1–induced HCF alterations alleviated neonatal rat cardiomyocyte hypertrophy, supported by the immunostaining of α-actin. To summarize, activation of ALDH2 enzymatic activity inhibited the differentiation of cardiac fibroblasts via the TGF-β1/Smad signaling pathway, which might be a promising strategy to relieve myocardial fibrosis of various causes.
Validity of a Submaximal 6-min Recumbent Stepper Test for Cardiac Rehabilitation
Authors: Donaldson Seth , Wright Lanecia , Day Amanda , Weiford Brian 
Published: February 2019

Purpose:
Submaximal exercise tests, such as the 6-min walk test (6MWT), are used to assess and determine changes in cardiorespiratory fitness in cardiopulmonary rehabilitation (CR) programs. However, other modalities such as recumbent steppers are frequently utilized in rehabilitation settings and suit individuals of all ability levels; yet, no self-paced submaximal test has been developed for this exercise modality. The aim of this study was to produce a self-paced, submaximal 6-min recumbent stepper test (6MRST) that is comparable with the 6MWT and can be used as pre- and post-CR assessments.

Methods:
Seventy subjects participating in CR performed a 6WMT and a 6MRST at the beginning and end of their CR program. Distance exercised, blood pressure, heart rate, and perceived exertion were measured to determine whether the 6MRST was comparable with the 6MWT.

Results:
Significant correlations were found between the distance exercised in the 6MWT and the 6MRST during both pre- and post-CR testing (r = 0.540 and r = 0.700, respectively; P < .001). The distance for the 6MRST increased from 1599 to 2101 ft after CR. Heart rate and rating of perceived exertion showed strong correlations between the 6MWT and the 6MRST at both testing time points.

Conclusions:
The 6MRST was found to produce similar results to that of the 6MWT in a CR setting. The 6MRST could therefore serve as an alternative to the 6MWT in those patients who cannot adequately perform a 6MWT, in a facility where space may be too limited, and a walking track is not available or simply due to patient or staff preference.
An Examination of the Frequency of Paravascular Defects and Epiretinal Membranes in Eyes With Early Glaucoma Using En-face Slab OCT Images
Authors: Mavrommatis Maria A. , De Cuir Nicole , Reynaud Juan , De Moraes Carlos G. , Xin Daiyan , Rajshekhar Rashmi , Liebmann Jeffrey M. , Ritch Robert , Fortune Brad , Hood Donald C. 
Published: February 2019

Purpose:
To examine the frequency of paravascular defects (PDs) and macular epiretinal membranes (ERMs) in eyes categorized as having mild glaucoma or glaucoma suspect using en-face slab analysis of optical coherence tomography (OCT) scans.

Materials and Methods:
Fifty-seven glaucomatous eyes, 44 low-risk suspect eyes, and 101 healthy control eyes were included in the study. The 101 glaucomatous and suspect eyes had a mean deviation better than −6 dB on the 24-2 visual field, and a spherical refractive error between±6 D or axial length <26.5 mm. Two OCT-graders masked to eye classification identified ERMs and PDs on en-face slab images of the macula and peripapillary retina using horizontal B-scans and derived vertical B-scans.

Results:
Glaucomatous eyes had a significantly higher number of PDs and ERMs than healthy controls (PD, P<0.001; ERM, P=0.046) and low-risk glaucoma suspects (PD, P=0.004; ERM, P=0.043). PDs and/or ERMs were present in 16 of 57 (28.1%) glaucomatous eyes, 2 of 44 (4.5%) suspect eyes, and 3 of 101 (3.0%) control eyes. Further, PDs were present in 11 of the 57 (19.3%) glaucomatous eyes, 1 of the 44 (2.3%) suspect eyes and 0 of the 101 (0%) control eyes, ERMs were seen in 7 of the 57 (12.3%) glaucomatous eyes, 1 of the 44 (2.3%) suspects, and 3 of the 101 (3.0%) control eyes.

Conclusions:
Eyes with early glaucoma have a higher frequency of PDs and ERMs than suspects or controls and exhibit PDs even in the absence of ERMs or high myopia.
Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain
Authors: Barkai Omer , Puig Stephanie , Lev Shaya , Title Ben , Katz Ben , Eli-Berchoer Luba , Gutstein Howard B. , Binshtok Alexander M. 
Published: February 2019

Abstract
Endogenous inflammatory mediators contribute to the pathogenesis of pain by acting on nociceptors, specialized sensory neurons that detect noxious stimuli. Here, we describe a new factor mediating inflammatory pain. We show that platelet-derived growth factor (PDGF)-BB applied in vitro causes repetitive firing of dissociated nociceptor-like rat dorsal root ganglion neurons and decreased their threshold for action potential generation. Injection of PDGF-BB into the paw produced nocifensive behavior in rats and led to thermal and mechanical pain hypersensitivity. We further detailed the biophysical mechanisms of these PDGF-BB effects and show that PDGF receptor–induced inhibition of nociceptive M-current underlies PDGF-BB–mediated nociceptive hyperexcitability. Moreover, in vivo sequestration of PDGF or inhibition of the PDGF receptor attenuates acute formalin-induced inflammatory pain. Our discovery of a new pain-facilitating proinflammatory mediator, which by inhibiting M-current activates nociceptive neurons and thus contributes to inflammatory pain, improves our understanding of inflammatory pain pathophysiology and may have important clinical implications for pain treatment.
A National Survey of Quality Improvement Education in Physician Assistant Programs
Authors: Berkowitz Oren , Goldgar Constance , White Susan E. , Warner Mary L. 
Published: February 2019

Purpose
Quality improvement (QI) is emerging as a leadership and career track for physician assistants (PAs). Information on how PA programs teach QI is sparse. This study aimed to define how PA programs are providing education in QI through a national program survey.

Methods
Curriculum survey questions were deployed as a part of the 2014–2015 Physician Assistant Education Association program survey. Questions were grouped into 4 categories: QI champion, pedagogy, integration strategy, and curriculum content. Differences between groups were analyzed, and logistic regression models were built to explore associations.

Results
All 194 (100%) PA programs responded to the survey. There were 137 (70.6%) programs that were teaching QI. The median number of total instructional hours was 12 (interquartile range = 16, overall range = 109). There were 37 (27%) programs that were categorized as having a “mature curriculum.” Mature curricula were significantly associated with a QI champion who is an expert from an outside department/institution (odds ratio [OR], 5.05; 95% confidence interval [CI], 1.14–22.33) and with programs that have a QI capstone or thesis project (OR, 3.66; 95% CI, 1.14–11.72) whose educational hours correlated more with experiential learning (r = 0.51, P < .01), small group sessions (r = 0.42, P = .01), and web-based modules (r = 0.36, P = .03).

Conclusion
Quality improvement is an important skill set for PAs, but nearly one-third of PA programs do not have a QI curriculum. Mature curricula were associated with more experiential learning and project-based learning (including capstone/thesis). This study captured many elements of QI education for PAs, which can be used by programs to develop and improve their curricula.
Physician factors in utilizing haemodynamic data in patient care
Authors: Boerma Evert Christiaan , Bootsma Inge Tjitske 
Published: February 2019

Purpose of review
To focus on the missing link between accuracy and precision of monitoring devices and effective implementation of therapeutic strategies.

Recent findings
Haemodynamic monitoring is generally considered to be an essential part of intensive care medicine. However, randomized controlled trials fail to demonstrate improved outcome unequivocally as a result of hemodynamic monitoring. This absence of solid proof renders doctors to hesitance to apply haemodynamic monitoring in clinical practise. Profound understanding of the underlying mechanisms, adequate patient selection and timing, meaningful representation and software-supported interpretation of data all play an important role. Furthermore, protocol adherence and human behaviour seem to form the often missing link between a solid physiologic principle and clinically relevant outcome. Introduction of haemodynamic monitoring should therefore not be limited to theoretical and practical issues, but also involve integration strategies. By learning from others, we might be able to implement haemodynamic monitoring in such a way that it has potential to modify the course of a disease.

Summary
The clinical success of haemodynamic monitoring goes far beyond accuracy and precision of monitoring devices. Understanding of the factors influencing the effective implementation of therapeutic strategies plays an important role in the meaningful introduction of haemodynamic monitoring.
Analysis of bone mass and its relationship with body composition in school-aged children and adolescents based on stage of puberty and site specificity
Authors: Song Cui , Zhu Min , Zheng Rongfei , Hu Yujuan , Li Rong , Zhu Gaohui , Chen Long , Xiong Feng 
Published: February 2019

Abstract
The aim of this study was to better understand the relationship of bone mass with body composition based on different stages of puberty and to illuminate the contribution of site-specific fat mass and lean mass (FM and LM) compared with bone mass in school-aged children and adolescents in Chongqing, China.
A total of 1179 healthy subjects of both sexes were recruited. Bone mineral content (BMC), bone mineral density (BMD), bone area, and both FM and LM were measured by dual-energy X-ray absorptiometry (DXA). The fat mass and lean mass indexes (FMI and LMI, respectively) were calculated as the FM (kg) and LM (kg) divided by the height in meters squared, respectively.
Most of the bone mass indicators were significantly higher for postpubertal boys than for girls at the same stage (P < .001). The proportion of subjects with normal bone mass increased, while the proportion of subjects with osteopenia and osteoporosis decreased with increased body weight regardless of gender and puberty stage (P < .01). FM and LM were significantly positively related to bone mass regardless of gender and puberty stage (P < .0001). FMI and LMI were significantly positively related to bone mass in most conditions (P < .05 and P < .0001, respectively). Four components of the FM and LM were linearly and significantly associated with BMD and BMC for TB and TBHL. Among them, the head fat mass and head lean mass showed the greatest statistical contribution.
In the process of assessing bone status, we recommend measuring fat and lean masses, including the fat and lean masses of the head.
Perineural cyst with intracystic hemorrhage following aneurysmal subarachnoid hemorrhage
Authors: Cho Keun-Tae , Nam Kiyeun 
Published: February 2019

Abstract

Rationale:
Most perineural cysts are asymptomatic and discovered incidentally at the time of imaging. Although enlargement of the perineural cyst (PC) through a ball-valve mechanism and resultant compression of the adjacent neural or bony structures are known to be a source of pain in PCs, the reason why asymptomatic PCs become symptomatic is unclear. The authors report a case of PC, which was presumed to become symptomatic after subarachnoid hemorrhage without enlargement of the pre-existing PC.

Patient concerns:
A 47-year-old woman complained of lumbosacral pain after neck clipping for a ruptured cerebral aneurysm.

Diagnoses:
Magnetic resonance imaging (MRI) revealed a PC with intracystic hemorrhage at the S2 level. In comparison with the size of the PC on computed tomography performed 3 years ago, there was no change in the size. Electrodiagnostic studies performed 6 weeks after the onset of the pain showed subacute right S2 radiculopathy.

Interventions:
With conservative treatment, her pain gradually diminished.

Outcomes:
When the lumbosacral pain improved, follow-up MRI showed that a fluid-fluid level within the PC disappeared.

Lessons:
Hemorrhage from the subarachnoid space, such as spontaneous aneurysmal SAH, into the pre-existing PC can cause an asymptomatic PC to become symptomatic without getting enlarged. Stretching of the nerve root due to hemorrhage or irritation of the nerve root due to an inflammatory reaction to blood products can make asymptomatic PCs symptomatic without enlargement of PCs.