bluuebunny/crossref_metadata_2025_split huggingface dataset:
An 8-Week, Randomized, Phase 2, Double-Blind, Sequential Parallel-Group Comparison Study of Two Dose Levels of the GABAA Positive Allosteric Modulator PF-06372865 Compared With Placebo as an Adjunctive Treatment in Outpatients With Inadequate Response to Standard of Care for Generalized Anxiety Disorder
Authors: Simen Arthur , Whitlock Mark , Qiu Ruolun , Miceli Jeff , Zumpano Laura , Du Metz Michaele , Dua Pinky , Binneman Brendon 
Published: December 2018

Abstract

Background
Generalized anxiety disorder (GAD) is a common psychiatric disorder, but many patients experience only partial relief of symptoms with existing therapies. Benzodiazepines are effective in many cases but are limited by a number of significant adverse effects. PF-06372865 is a subtype-selective gamma-aminobutyric acid A (GABAA)–positive allosteric modulator lacking in functional activity at alpha 1–containing receptors that are believed to mediate many of these adverse effects.

Methods
PF-06372865 was evaluated as an adjunct to current GAD treatment in a double-blind, placebo-controlled, sequential parallel comparison study in patients with GAD who showed an incomplete response to current standard-of-care pharmacotherapy. A total of 90 subjects (of the planned 384) were randomized into the study before the decision to terminate the study. Two doses of PF-06372865 (2.5 mg twice daily and 7.5 mg twice daily) were compared with placebo.

Results
Neither dose of PF-06372865 differentiated from placebo on week 4 Hamilton Anxiety Inventory total (primary end point) or on the Sheehan Disability Scale total score (secondary end point). Adverse events including dizziness, headache, and somnolence were observed, and the 7.5 mg dose demonstrated some impairment on the Digit Symbol Substitution test and the Epworth Sleepiness Scale relative to placebo and the 2.5 mg dose.

Conclusions
Factors contributing to the negative results include the limited sample size and failure to explore a broader range of doses.
Five-year-term results in cirrhotics without varices, either affected or not by portal hypertensive gastropathy
Authors: Zardi Enrico M. , Pipita Maria E. , Lichinchi Domenico , Dobrina Aldo 
Published: December 2018

Objectives
Information is lacking on the appearance of varices in cirrhotics, either affected or not by portal hypertensive gastropathy (PHG). We assessed whether the absence or presence and the grade of PHG influenced the development of varices in cirrhotics without varices over time.

Patients and methods
Forty cirrhotics without varices affected or not by PHG at baseline underwent follow-up endoscopy after 5 years. One-tailed t-test and the χ
2-test were used to evaluate variable comparison and the presence of associations. Multivariate logistic regression analysis and the analysis of variance test were carried out to compare the variables and identify predictors of varices.

Results
The Child–Pugh score at baseline and after 5 years was significantly different (5.72±0.98 vs. 6.25±1.67, P<0.001). After 5 years, 10 (25%) cirrhotics were affected by varices, whereas 30 (75%) patients remained without varices. PHG was associated significantly with varices (P=0.001), proving to be a significant predictive independent factor for their development over time (F=4.765, significant=0.004; analysis of variance test, P<0.001).

Conclusion
A link between the duration of PHG and the development of varices is likely. An early therapeutic management of PHG might delay the development of varices in cirrhotics.
Spondylolysis 2019 update
Authors: Berger Rachel G. , Doyle Shevaun M. 
Published: December 2018

Purpose of review
Provide a comprehensive overview of lumbar spondylolysis, a frequent cause of lower back pain in children and adolescents, from evaluation to management.

Recent findings
With the surge of structured sports participation in the pediatric population, spondylolysis is a common ailment that afflicts many young athletes due to rigorous competition that taxes the growing spine with repetitive extension and rotation.

Summary
Spondylolysis is a fracture through the pars interarticularis. When a child presents with lower back pain, spondylolysis should be at the top of the differential. A thorough history and physical examination are essential. In addition, radiographs of the lumbar spine, anterior posterior and lateral views, MRI and, selectively, computed tomography are useful adjuncts to uncover a pars injury. Timely diagnosis facilitates early treatment which includes rest, optimizing bone health, brace treatment, and physical therapy. If delayed or untreated, spondylolysis may result in nonunion or pars defect. If symptomatic, patients may need surgery to fuse the lumbar facet joints or repair the par interarticularis.
Pediatric and adolescent ankle instability: diagnosis and treatment options
Authors: Gruskay Jordan A. , Brusalis Christopher M. , Heath Madison R. , Fabricant Peter D. 
Published: December 2018

Purpose of review
The purpose of this review is to discuss the epidemiology, pathoanatomy, diagnosis, and treatment for lateral ankle instability in pediatric patients.

Recent findings
Chronic ankle instability is a common sequela of lateral ankle sprain in young athletes. Incidence is increasing, possibly due in part to inadequate treatment of first-time ankle sprains, as well as increased youth participation in organized and competitive sports. The anterior talofibular ligament (ATFL) is injured in every case, whereas the calcaneofibular ligament (CFL) and syndesmosis may be involved in severe cases. A clinical history, focused physical exam, and appropriate radiographic studies aid in diagnosis, and predisposing factors must be identified. Early treatment of ankle sprains involves bracing or immobilization, followed by a course of physical therapy. Surgery involves anatomic repair of the torn ligaments, and may be required in cases of severe functional and mechanical instability with recurrent sprains refractory to nonsurgical management. Intraarticular disorders should be identified and may be addressed with ankle arthroscopy.

Summary
Prompt treatment of lateral ankle instability in young athletes is important to prevent chronic ankle instability. Many patients are successfully treated without surgery, and those requiring operative intervention improve function postoperatively.
Cardioprotective Effects of Spirulina Therapy in Children With Beta-Thalassemia Major
Authors: El-Shanshory Mohammed , Tolba Osama , El-Shafiey Rasha , Mawlana Wegdan , Ibrahim Magda , El-Gamasy Mohamed 
Published: December 2018

Introduction:
Cardiac failure in children with Thalassemia major (TM) is the major cause of death due to iron overload. Spirulina is a micro alga with proven anti-inflammatory, antioxidant and may have a cardioprotective effect.

Aim of the Work:
The aim of this study was to evaluate the possible beneficial effect of spirulina supplement in TM children.

Subject and Methods:
It is an interventional study carried out in 60 children with TM and 30 healthy children matched for age and sex as control. Both groups received spirulina supplement at a dose of 250 mg/kg/d for 3 months. 2D Echo, Tissue Doppler, and speckle tracking imaging (STI) were done for all the studied cohort before and after the 3-month duration of spirulina supplement.

Results:
There was significant improvement in hemoglobin level at the end of 3-month period (8.27±1.3 vs. 9.023±1.7; P <0.033) with decrease the frequency of blood transfusion in TM patients (66.6% vs. 40% required transfusion at interval less than 2 wk). Left ventricle global longitudinal strain (LVGLS) significantly improved after 3-month period (−21.7±4.64 vs. −24.67±4.478; P <0.002).

Conclusions:
Spirulina supplement has possible beneficial effect in minimizing the frequency of blood transfusion as well as cardioprotective effect against cardiac damage in TM patients.
Exercise and Parkinson Disease: Comparing Tango, Treadmill, and Stretching
Authors: Rawson Kerri S. , McNeely Marie E. , Duncan Ryan P. , Pickett Kristen A. , Perlmutter Joel S. , Earhart Gammon M. 
Published: December 2018

Background and Purpose:
Impaired gait, balance, and motor function are common in Parkinson disease (PD) and may lead to falls and injuries. Different forms of exercise improve motor function in persons with PD, but determining which form of exercise is most effective requires a direct comparison of various approaches. In this prospective, controlled trial, we evaluated the impact of tango, treadmill walking, and stretching on gait, balance, motor function, and quality of life. We hypothesized tango and treadmill would improve forward walking and motor symptom severity, and tango would also improve backward walking, balance, and quality of life.

Methods:
Ninety-six participants (age: 67.2 ± 8.9 years, 42% female) with mild to moderate idiopathic PD were serially assigned to tango, treadmill walking, or stretching (active control group) and attended 1-hour classes twice weekly for 12 weeks. Assessments occurred OFF anti-PD medication before and after the intervention and at follow-up 12 weeks after the intervention.

Results:
Forward velocity and backward velocity improved for the treadmill group from baseline to posttest and improvements persisted at follow-up. Backward velocity and motor functioning improved for the stretching group from baseline to posttest, but results did not persist at follow-up. There were no significant changes in the tango group across time points.

Discussion and Conclusions:
Contrary to our hypotheses, only treadmill improved forward walking, while backward walking improved with treadmill and stretching. Future research should examine combinations of exercises with a focus on optimizing dosing and examining whether specific characteristics of people with PD correlate with different types of exercise.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A237).
Effectiveness of Two Targeted Temperature Management Methods After Pediatric Postcardiac Arrest: A Multicenter International Study*
Authors: Yunge Mauricio , Cordero Jaime , Martinez Daniela , Bustos Raul , Wegner Adriana , Castro Magdalena , Arrau Lorena , Diaz Betsy , Dalmazzo Roberto , Hickmann Lilian , Lapadula Michelangelo , Yañez Leticia , Roque Jorge , Cecchetti Corrado , Bravo Pablo , Cruces Pablo , Acuña Carlos , Oyaguez Pablo , Miras Alicia , Morales Antonio , Nieto Manuel , Lopez Yolanda , Morales Gonzalo , Drago Michele , Nalegach Maria Elisa , Sepulveda German , Menchaca Amanda , Jerez Florencia , Glasinovic Maritza , Mallea Fernando , Lopez-Herce Jesus 
Published: December 2018

Objectives:
It is currently recommended that after return of spontaneous circulation following cardiac arrest, fever should be prevented using TTM through a servo-controlled system. This technology is not yet available in many global settings, where manual physical measures without servo-control is the only option. Our aim was to compare feasibility, safety and quality assurance of servo-controlled system versus no servo-controlled system cooling, TTM protocols for cooling, maintenance and rewarming following return of spontaneous circulation after cardiac arrest in children.

Design:
Prospective, multicenter, nonrandomized, study.

Setting:
PICUs of 20 hospitals in South America, Spain, and Italy, 2012–2014.

Patients:
Under 18 years old with a cardiac arrest longer than 2 minutes, in coma and surviving to PICU admission requiring mechanical ventilation were included.

Methods:
TTM to 32–34°C was performed by prospectively designed protocol across 20 centers, with either servo-controlled system or no servo-controlled system methods, depending on servo-controlled system availability. We analyzed clinical data, cardiac arrest, temperature, mechanical ventilation duration, length of hospitalization, complications, survival, and neurologic outcomes at 6 months. Primary outcome: feasibility, safety and quality assurance of the cooling technique and secondary outcome: survival and Pediatric Cerebral Performance Category at 6 months.

Measurements and Main Results:
Seventy patients were recruited, 51 of 70 TTM (72.8%) with servo-controlled system. TTM induction, maintenance, and rewarming were feasible in both groups. Servo-controlled system was more effective than no servo-controlled system in maintaining TTM (69 vs 60%; p = 0.004). Servo-controlled system had fewer temperatures above 38.1°C during the 5 days of TTM (0.1% vs 2.9%; p < 0.001). No differences in mortality, complications, length of mechanical ventilation and of stay, or neurologic sequelae were found between the two groups.

Conclusions:
TTM protocol (for cooling, maintenance and rewarming) following return of spontaneous circulation after cardiac arrest in children was feasible and safe with both servo-controlled system and no servo-controlled system techniques. Achieving, maintaining, and rewarming within protocol targets were more effective with servo-controlled system versus no servo-controlled system techniques.
Impact of Economic Downturn on the Surgical Volumes of Common Hand Procedures
Authors: Fujihara Nasa , Fujihara Yuki , Sterbenz Jennifer M. , Shauver Melissa J. , Chung Ting-Ting , Chung Kevin C. 
Published: December 2018

Background:
Economic conditions affect surgical volumes, particularly for elective procedures. In this study, the authors aimed to identify the effects of the 2008 U.S. economic downturn on hand surgery volumes to guide surgeons and managers when facing future economic crises.

Methods:
The authors used the California State Ambulatory Surgery and Services Database from January of 2005 to December of 2011, which includes the entire period of the Great Recession (December of 2007 to June of 2009). The authors abstracted the monthly volume of five common hand procedures using International Classification of Diseases, Ninth Revision, and Current Procedural Terminology codes. Pearson statistics were used to identify the correlation between unemployment rate and surgical volume for each procedure.

Results:
The total number of operative cases was 345,583 during the 7-year study period. Most common elective hand procedures, such as carpal tunnel release and trigger finger release, had a negative correlation with unemployment rate, but the volume of distal radius fracture surgery did not show any correlation. Compared with carpal tunnel release (r = −0.88) or trigger finger release volumes (r = −0.85), thumb arthroplasty/arthrodesis volumes (r = −0.45) showed only a moderate correlation.

Conclusions:
The economic downturn decreased elective hand procedure surgical volumes. This may be detrimental to small surgical practices that rely on revenue from elective procedures. Taking advantage of the principle that increased volume reduces unit cost may mitigate the lost revenue from these elective procedures. In addition, consolidating hand surgery services at larger, regional centers may reduce the effect of the economic environment on individual hand surgeons.
A Novel Model for Cutaneous Wound Healing and Scarring in the Rat
Authors: Zhou Sizheng , Wang Wenjin , Zhou Shuangbai , Zhang Guoyou , He Jizhou , Li Qingfeng 
Published: December 2018

Background:
Current rodent models of wound healing and scarring are flawed because of rapid wound contraction and inconspicuous scarring after healing, which is not closely parallel to the physiologic process in humans. This study aimed to establish a novel model of wound healing and scarring in rats.

Methods:
Excisional wounds were generated in rat tail or dorsal skin and histologic changes and wound contraction were assessed 2, 10, and 16 days after injury. After healing, rat tail scar was investigated for 24 consecutive weeks by histologic and immunohistochemical staining. Finally, a stretched scar model was generated in rat tail with high or low strain after reepithelialization to mimic human hypertrophic scars. The tail hypertrophic scars were analyzed by histology, immunohistochemical staining, and mRNA quantification 0, 2, 6, 12, and 24 weeks after stretching.

Results:
Compared with the dorsal wounds, a larger dermal gap percentage (p < 0.05) and more pronounced granulation were found in rat tail wounds. Tail scars remained conspicuous and underwent maturation over 24 weeks after wound healing. In addition, high mechanical strain induced significantly increased scar area (p < 0.01), scar height (p < 0.05), vessel density (p < 0.01) and hypertrophic scar–related molecule expression, and distorted collagen arrangement in rat tail scars.

Conclusions:
The rat tail model exhibits minor wound contraction and biological features analogous to both normotrophic and hypertrophic scar in humans when generated with or without stretching, respectively. It is a promising new model for studies of both cutaneous wound healing and scarring.
Retrospective Review of the Complication Profile Associated with 71 Subcranial and Transcranial Midface Distraction Procedures at a Single Institution
Authors: Zhang Rosaline S. , Lin Lawrence O. , Hoppe Ian C. , Swanson Jordan W. , Bartlett Scott P. , Taylor Jesse A. 
Published: December 2018

Background:
This study characterizes the perioperative morbidity of a large cohort of subjects with syndromic craniosynostosis who underwent transcranial or subcranial midface distraction.

Methods:
Demographic and perioperative data were compared between those who underwent transcranial or subcranial midface distraction osteogenesis between July of 1999 and December of 2017. Univariate analysis was conducted using chi-square and Fisher’s exact tests for categorical variables and the Mann-Whitney U test for continuous variables. Multivariate analysis was conducted using logistic regression modeling. Complications were graded using the Clavien-Dindo classification.

Results:
Sixty-four subjects underwent a total of 71 midface distraction procedures. There was a total of 28 complications (39 percent). The trans cranial cohort had a significantly higher frequency of complications (58 percent) compared with the subcranial cohort (29 percent; p = 0.017), with a significantly greater proportion of infection-related complications in the transcranial cohort (80 percent versus 54 percent; p = 0.028). Transcranial complications included cranial contamination, whereas most subcranial cohort infections were superficial or limited facial abscesses. The only significant predictor variable for complications in a multivariate analysis was whether the osteotomy approach was transcranial as opposed to subcranial, with an odds ratio of 5.80 (p = 0.013).

Conclusions:
Complication rates in midface distraction remain high, with transcranial procedures having significantly higher complication rates, infection-related complications, and notably greater severity of complications. Although the goals of surgery often dictate choice of osteotomy, the risks associated with transcranial procedures must be thoroughly understood by surgeon and patient alike.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Buffering Internalization of HIV Stigma: Implications for Treatment Adherence and Depression
Authors: Turan Bulent , Crockett Kaylee B. , Buyukcan-Tetik Asuman , Kempf Mirjam-Colette , Konkle-Parker Deborah , Wilson Tracey E. , Tien Phyllis C. , Wingood Gina , Neilands Torsten B. , Johnson Mallory O. , Weiser Sheri D. , Turan Janet M. 
Published: December 2018

Background:
One mechanism through which social stigma of HIV affects health outcomes for people living with HIV (PLWH) is through internalization of stigma. However, this transformation of social stigma in the community into internalized stigma may not be of the same magnitude for all PLWH. We examined the moderating effects of 3 personality traits—fear of negative social evaluation, attachment-related anxiety, and dispositional resilience—in transforming perceived stigma in the community into internalized stigma. Furthermore, we investigated downstream effects of these moderated associations on depressive symptoms and antiretroviral treatment (ART) adherence.

Setting/Methods:
In study 1, data from 203 PLWH in the Southeast United States were analyzed controlling for age, sex, education, race, and time on ART. In study 2, data from 453 women in a multisite study were analyzed controlling for age, education, race, time on ART, and substance use.

Results:
In both studies, fear of negative evaluation and attachment-related anxiety moderated the effect of perceived HIV stigma in the community on internalized HIV stigma: People higher on those moderating variables had stronger associations between perceived stigma in the community and internalized stigma. In study 2, resilience was assessed and also moderated the effect of perceived HIV stigma in the community on internalized stigma. In moderated mediation models, fear of negative evaluation, attachment-related anxiety, and resilience moderated the indirect effect of perceived HIV stigma in the community on ART adherence and depression through internalized stigma.

Conclusions:
Interventions to assuage internalization of HIV stigma should focus on bolstering attachment-related security, social competence, and resilience.
The Evolving Role of Shear Wave Elastography in the Diagnosis and Treatment of Prostate Cancer
Authors: Gandhi Jason , Zaidi Saher , Shah Janki , Joshi Gunjan , Khan Sardar Ali 
Published: December 2018

Abstract
To forego misdiagnosis and biopsy-related complications, we explore a novel technique that embraces tissue elasticity to circumvent the current limitations in the accurate, non-invasive detection of prostate cancer. A MEDLINE® database search of literature pertinent to prostate elastography published in the last five years was guided using the following terms: tissue elasticity, ultrasound elastography, strain elastography, magnetic resonance elastography, and shear wave elastography. Ultrasound shear wave elastography (SWE) utilizes the propagation of induced shear waves to provide a quantitative measurement of elasticity of soft tissue. Studies attempting to prove SWE as a strong predictor of malignant prostatic tissue have validated its high specificity and sensitivity compared to the sub-50% range observed with magnetic resonance imaging or transrectal ultrasound. Because its median positive predictive value is also much higher than the sub-40% range attributed to more conventional techniques, SWE yields reduced false-negative biopsy rates. It furthermore exhibits higher intraobserver reproducibility compared to conventional ultrasound. Recent treatments have also utilized SWE for noninvasive prostate cancer tissue ablation. Future improvements include standardized cutoff ranges for quantifying elasticity of malignant tissue. The implementation of a scoring system to predict cancer aggressiveness and prognosis may eliminate the need for unwarranted repeat biopsies postdiagnosis.