bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing Opioid Use for Patients With Chronic Pain: An Evidence-Based Perspective
Authors: Wenger Sarah , Drott Jason , Fillipo Rebecca , Findlay Alyssa , Genung Amanda , Heiden Jessica , Bradt Joke 
Published: February 2018

Abstract
The implementation of recent Centers for Disease Control and Prevention recommendations to move away from opioids and toward nonpharmacological therapies for the treatment of chronic pain could involve a difficult transition period for patients and practitioners. The focus of treatment should shift from eliminating pain completely to minimizing the impact of pain on quality of life. Many patients with chronic pain take opioids either because opioids were previously prescribed as a first-line treatment for chronic pain, on the basis of old standards of care, or because opioids were initially prescribed for acute pain. Patients currently taking opioids will need a tapering period during which they transition their pain management to interdisciplinary care and nonpharmacological treatments. To provide useful treatment options, physical therapists need to have a good understanding of the neuroscientific mechanisms of chronic pain, biopsychosocial components of chronic pain management, issues related to opioid use, and pain management strategies used by other health care professionals. Armed with knowledge and good communication skills, physical therapists can work within an interdisciplinary team to adapt care to each patient's needs and abilities. This perspective article provides guidance for physical therapists to effectively treat patients with chronic pain during the opioid tapering process. A framework has been created to help health care providers structure their reasoning as they collaborate to develop a unique approach for each patient.
A Systematic Review and Meta-analysis of Free-style Flaps: Risk Analysis of Complications
Authors: Qian Youlei , Li Guangxue , Zang Huiran , Cao Saisai , Liu Yan , Yang Kai , Mu Lan 
Published: February 2018

Background:
Free-style flaps allow surgeons to overcome anatomical variations and raise perforator flaps wherever a pulsatile signal can be detected. We performed a systematic review and meta-analysis to identify the risk factors for complications and indications for free-style flaps in soft-tissue defect reconstructions.

Methods:
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The databases of MEDLINE, PubMed, ScienceDirect, and Cochrane Library were searched from January 1991 to January 2017 for original articles describing free-style flaps in soft-tissue defect reconstruction.

Results:
A total of 17 articles met the inclusion criteria, representing 453 free-style flaps. The percentage of free-style flaps conducted after primary oncologic resection was 54.4% (246/453). Free-style flaps were mostly used in the head and neck region (35.5%), and most of them were designed as pedicled perforator flaps (96.7%). Complete flap survival was accomplished in 91.8% of the free-style flaps. Complications were found in 13.5% of cases, and 2 risk factors were identified: extremity defects (risk ratio, 2.39; P = 0.006) and single perforator flaps (risk ratio, 4.93; P = 0.002). No significant differences were found among the criteria including patients aged greater than 60 years, female gender, chronic etiology, flap size over 100 cm2, flap rotation, or perforator skeletonization.

Conclusions:
Free-style flaps are both reliable and advanced forms of perforator flaps for use in soft-tissue defect reconstructions. Defects located on the extremities and flaps with single perforators are risk factors for flap failure and complications.
Personalized 3D Printed Surgical Tool for Guiding the Chisel during Hump Reduction in Rhinoplasty
Authors: Herrero Antón de Vez Hugo , Herrero Jover Javier , Silva-Vergara Claudio 
Published: February 2018

Summary:
The authors aimed to present an introduction of patient-specific model in rhinoplasty by introducing a 3D printed surgical guide designed and adapted in an individualized manner for guiding dorsal hump reduction. To introduce the tool, we have designed a six step workflow. First, we obtain a digital 3D model of patient anatomy using computed tomography (CT) images. Second, we conduct a surgical preoperative planning of the rhinoplasty on the mentioned model. Third step consists of designing the guide, while taking into account nasal anthropometries and resection objectives. Fourth step is printing the guide and sterilizing it. Fifth step is performing the surgery. The last step is analyzing the main outcomes of the surgery. Our surgical guide allowed us to perform only 1 step osteotomy instead of the usual multistep osteotomy and remove exactly the amount of dorsum that we decided to remove during the preoperative planning. The duration of intervention was considerably shorter than conventional osteotomy. Using the guide was technically easier than the conventional method and reduced the learning curve from years to minutes (once the guide is printed). Moreover, the patient understanding of the procedure was significantly better after showing the 3D model of the surgery. The surgical guide allows a surgeon to transfer with extreme simplicity the presurgical planning to the surgical field. We have to point out that the design of the study does not allow us to quantify predictability, so future studies are needed to demonstrate an accuracy benefit over the former techniques.
Safety and Immunogenicity of the HPV-16/18 AS04-adjuvanted Vaccine in 4–6-year-old Girls
Authors: Lin Lan , Parra Mercedes Macias , Sierra Victor Y. , Cespedes Albino Salas , Granados Maria Angelica , Luque Adriana , Damaso Silvia , Castrejon Alba Maria Mercedes , Romano-Mazzotti Luis , Struyf Frank 
Published: February 2018

Background:
The burden of cervical cancer caused by human papillomavirus (HPV) is high in Latin America. The suboptimal HPV vaccination coverage in adolescents could be improved by pediatric immunization. HPV vaccination has not yet been reported in girls <9 years of age.

Methods:
This ongoing phase III, controlled, randomized, single-blind, multicenter study conducted in Colombia, Mexico and Panama (NCT01627561) evaluated the safety and immunogenicity of AS04-HPV-16/18 vaccine in 4–6-year-old girls. Healthy girls (randomized 1:1) received either 2 doses of AS04-HPV-16/18 vaccine (HPV group, N=74) or 1 dose of each measles-mumps-rubella and diphtheria-tetanus-acellular-pertussis vaccines (control group, N=74) 6 months apart. We report the safety and serum anti–HPV-16 and anti–HPV-18 antibodies (measured by enzyme-linked immunosorbent assay) up to 6 months postvaccination, that is, month (M) 12.

Results:
Injection site pain was the most frequently reported solicited local symptom in HPV vaccinees. The incidence of other solicited and unsolicited symptoms after each vaccination was similar between the HPV and control group. Until M12, 1 girl in the HPV group and 2 in the control group reported serious adverse events; all serious adverse events were assessed as unrelated to study vaccines. No potential immune-mediated diseases were identified. All girls seroconverted for both antigens after 2 doses of AS04-HPV-16/18. In initially seronegative girls, anti–HPV-16 geometric mean concentrations were 20080.0 enzyme-linked immunosorbent assay units (EU)/mL at M7 and 3246.5 EU/mL at M12; anti–HPV-18 geometric mean concentrations were 10621.8 EU/mL at M7 and 1216.6 EU/mL at M12.

Conclusions:
Two-dose vaccination with AS04-HPV-16/18 was well tolerated and induced adequate antibody responses in 4–6-year-old girls.
No Effect of Adjunctive Minocycline Treatment on Body Metabolism in Patients With Schizophrenia
Authors: Liu Fang , Xie Liqin , Zhang Bingkui , Ruan Ye , Zeng Yong , Xu XiuFeng , Zhao Jingping , Fan Xiaoduo 
Published: February 2018

Abstract

Purpose/Background
This study examined the effect of adjunctive minocycline on body metabolism in risperidone-treated patients with schizophrenia.

Methods/Procedures
Each subject had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia and had been on stable dose of risperidone for at least 4 weeks. In a 16-week randomized, double-blind, placebo-controlled study, subjects received either minocycline (200 mg/d) or placebo. Various metabolic parameters, including weight, waist circumference, fasting insulin, glucose, and lipids, were measured at baseline and week 16.

Findings/Results
A total of 63 subjects with schizophrenia were enrolled in the study. Fifty-five patients completed week-16 assessments (27 in the minocycline group, 28 in the placebo group). There were no significant differences between the 2 groups in week 16 changes for body weight, body mass index, waist circumference, fasting insulin, glucose, and lipids (P’s > 0.300).

Implications/Conclusions
In the present study, adjunctive treatment of minocycline did not seem to improve body metabolism in patients with schizophrenia receiving risperidone. The implications for future studies were discussed.
Effects of Alcohol on the Pharmacokinetics of Blonanserin and N-Deethylated Blonanserin in Healthy Chinese Subjects
Authors: Deng Shuhua , Ni Xiaojia , Shang Dewei , Wang Zhanzhang , Zhang Ming , Hu Jinqing , Zhu Xiuqing , Lu Haoyang , Chen Yuqing , Zhang Yuefeng , Peng Huan , Wen Yuguan 
Published: February 2018

Abstract

Purpose/Background
Blonanserin is a novel antipsychotic drug approved for the treatment of schizophrenia in East Asia. The main objective of the present study was to investigate the effect of alcohol on the pharmacokinetic properties of blonanserin and its metabolite N-deethyl blonanserin in healthy Chinese male subjects under fasting conditions.

Methods/Procedures
The study was designed as a randomized, open-label, crossover clinical investigation in 10 male volunteers, each of whom received 2 treatments under fasted conditions: treatment A, blonanserin (8 mg) with water, and treatment B, blonanserin (8 mg) with alcohol (1 mL/kg).

Findings/Results
The average values of areas under the curve (AUCs) and mean peak plasma concentrations (C
max) were noticeably increased by alcohol consumption. In treatment A, average values of AUC0–24h, AUC0–∞, and C
max were 3178 ng/h/L, 3879 ng/h/L, and 492 ng/L for blonanserin, and 1932 ng/h/L, 4208 ng/h/L, and 137 ng/L for N-deethylated blonanserin, respectively. In treatment B, AUC0–∞ and C
max were both increased 2.4-fold for blonanserin and 1.4-fold and 1.7-fold, respectively, for N-deethylated blonanserin (P < 0.05). Compared with treatment A, clearance (Clz/F) of blonanserin and N-deethylated blonanserin decreased significantly (2.4-fold and 1.7-fold, respectively) in treatment B (P < 0.05). Alcohol delayed the absorption and reduced the clearance of blonanserin, leading to a 1.8-fold increase in the time to reach C
max (T
max) and half life time (t
1/2) (P < 0.05).

Implications/Conclusions
Alcohol increased the bioavailability of blonanserin and N-deethyl blonanserin in healthy subjects and the marked effect of alcohol on blonanserin bioavailability should be taken into consideration in deciding dosing schedules in clinical therapy.
The Antioxidant Effect of Rosmarinic Acid by Different Delivery Routes in the Animal Model of Noise-Induced Hearing Loss
Authors: Fetoni Anna R. , Eramo Sara Letizia Maria , Di Pino Antonella , Rolesi Rolando , Paciello Fabiola , Grassi Claudio , Troiani Diana , Paludetti Gaetano 
Published: February 2018

Hypothesis:
Trans-tympanic Rosmarinic Acid (RA), as compared with the systemic administration, protects against noise-induced auditory hair cell and hearing losses in rats in vivo.

Background:
ROS production, lipoperoxidative damage, and an imbalance of antioxidant defences play a significant role in noise-induced hearing loss. Several molecules with antioxidant properties have been tested to restore redox homeostasis; however, drug delivery system represents a challenge for their effectiveness. In our model, acute and intense noise exposure induces hearing loss, hair cell death, and oxidative stress, with an increase in superoxide production and over-expression of lipid peroxidation in cochlear structures.

Methods:
RA was administrated in male Wistar rats by trans-tympanic (20 μl) and systemic (10 mg/kg) modality. In systemic administration, RA was injected 1 hour before noise exposure and once daily for the following 3 days. ABRs were measured before and at days 1, 3, 7, and 30 after noise exposure. Rhodamine-phalloidin staining, dihydroethidium and 8-isoprostane immunostainings were performed to assess and quantify outer hair cells loss, superoxide production, and lipid peroxidation in the different experimental groups.

Results:
Systemic RA administration significantly decreased noise-induced hearing loss and the improvement of auditory function was paralleled by a significant reduction in cochlear oxidative stress. The trans-tympanic modality of drug administration showed a similar degree of protection both at the functional and morphological levels.

Conclusion:
The effectiveness of RA given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.
Immunotherapy for recurrent/metastatic head and neck cancer
Authors: Alfieri Salvatore , Cavalieri Stefano , Licitra Lisa 
Published: February 2018

Purpose of review
In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less ‘immunogenic’ than other malignancies (e.g. melanoma), was field of application of several new immune agents. To date, the most important data regard drugs acting on PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) axis that is a crucial checkpoint used by tumor for immune escape. Our purpose is to summarize the results of these PD-1/PD-L1 inhibitors, outlining some critical points and few practical suggestions.

Recent findings
Nivolumab was recently approved by main regulatory agencies as second-line treatment for platinum-refractory R/M HNSCC. In the same setting, pembrolizumab was approved by FDA. Atezolizumab and durvalumab have already showed similar benefit in phase Ia and II studies, respectively.

Summary
Anti-PD1/PD-L1 agents are new effective therapies in R/M HNSCC. Their combination with conventional/novel compounds, as well as a better selection of responding patients, could lead to improve current results.
Leukocyte Telomere Length and Pancreatic Cancer Risk
Authors: Antwi Samuel O. , Petersen Gloria M. 
Published: February 2018

Abstract
Many risk factors have been firmly established for pancreatic cancer (PC), but the molecular processes by which known risk factors influence susceptibility to PC are not clear. There has been a recent upsurge of interest in the role of telomere length (TL), the protective DNA sequence repeats at chromosome ends, in pancreatic carcinogenesis. Given this heightened interest, we performed an in-depth, focused, and up-to-date review of the epidemiological evidence linking leukocyte TL (LTL) with PC risk. We searched MEDLINE, Embase, and the Cochrane Library databases for all published studies on LTL and PC risk, up to May 2017. Five studies were identified for review: 4 nested case-control studies and 1 retrospective case-control study. Two studies found opposite associations between LTL and PC risk: 1 found a dose-response positive association and the other found a dose-response inverse association. Two studies also found a “U-shaped” association, whereas another reported a weak nonlinear relationship. We offer potential reasons for the conflicting findings including variation in study design, biospecimen characteristics, and differences in interlaboratory measurements of TL. Future studies should carefully control for risk factors of PC that are associated also with telomere attrition and investigate the role of genetic variation in TL maintenance.
Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Fonseca Annabelle L. , Kirkwood Kimberly , Kim Michael P. , Maitra Anirban , Koay Eugene J. 
Published: February 2018

Abstract
The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the past decade, mainly owing to increased awareness and the increased use of cross-sectional imaging. The Sendai and Fukuoka consensus guidelines provide us with clinical management guidelines and algorithms; however, the clinical management of IPMNs continues to be challenging. Our incomplete understanding of the natural history of the disease, and the events and pathways that permit progression to adenocarcinoma, result in difficulties predicting which tumors are high risk and will progress to invasive disease. In this review, we summarize the current management guidelines and describe ongoing efforts to more clearly stratify IPMNs by risk of malignancy and identify IPMNs with malignant potential or ongoing malignant transformation.
Anemia in Adolescents and Young Adult Patients With Congenital Heart Disease
Authors: Rodríguez-Hernández Juan L. , Rodríguez-González Fayna , Martínez-Quintana Efrén 
Published: February 2018

Introduction:
Despite anemia in acquired heart disease being a common problem, little is known in patients with congenital heart disease (CHD).

Methods:
In total, 544 consecutive stable noncyanotic CHD patients were studied to determine demographic, clinical, and analytic parameters. Anemia was defined as a condition in which hemoglobin concentration was <13 g/dL in male individuals and <12 g/dL in female individuals.

Results:
In total, 49 (9%) CHD patients had anemia. Patients with complex anatomy had the highest prevalence of anemia (33%). The median hemoglobin concentration was 14.4 (13.5 to 15.6) mg/dL. Of the total anemic CHD patients, 21 of 49 (43%) were microcytic (mean corpuscular volume <84 fL) and 46 of 49 (94%) had a mean corpuscular volume under 95 fL. Oral anticoagulation, oral antiaggregation, diuretic treatment, and having valve prostheses or cardiovascular risk factors, such as arterial hypertension or diabetes mellitus, did not reach statistical significance between anemic and nonanemic CHD patients. Multivariate analyses determined as risk factors for anemia a worse New York Heart Association functional class (patients in class >II/IV) (odds ratio [OR], 8.37; 95% confidence interval [CI], 1.69-41.35), N-terminal proB-type natriuretic peptide levels >125 pg/mL (OR, 7.90; 95% CI, 2.88-21.69), and apoferritn levels below 15 ng/mL (OR, 0.21; 95% CI, 0.09-0.50). The Kaplan-Meier survival analysis showed no significant differences in mortality between anemic and nonanemic CHD patients (P=0.143).

Conclusions:
The incidence of anemia in CHD patients is similar to that of the normal population and iron deficiency anemia accounts for most of the cases. There were no significant differences in mortality between CHD patients with and without anemia.
How Do Patients Respond to Genetic Testing for Age-related Macular Degeneration?
Authors: McCarty Catherine A. , Fuchs Michael J. , Lamb Allan , Conway Pat 
Published: February 2018

SIGNIFICANCE
The American Academy of Ophthalmology currently recommends against routine genetic testing for complex diseases such as age-related macular degeneration (AMD). The results of this study demonstrate that patients are very interested in predictive genetic testing for AMD, find the information useful, and make behavioral changes as a result of the information.

PURPOSE
The goal of this project was to conduct a pilot AMD genomic medicine study.

METHODS
Eligible patients were aged 50 to 65 years with no personal history of AMD. DNA samples were genotyped for five single-nucleotide polymorphisms (SNPs) in the CFH gene, one SNP in the ARMS-2 gene, one SNP in the C3 gene, and one SNP in the mitochondrial ND2 gene. A risk score was calculated utilizing a model based on odds ratios, lifetime risk of advanced AMD and known population prevalence of genotype, haplotype, and smoking risk. The study optometrist provided the patient's risk score and counseling for personal protective behaviors. Telephone interviews were conducted 1 to 3 months after the counseling visit.

RESULTS
One hundred one subjects (85%) participated in the genetic testing; 78 (77.2%) were female. Follow-up interviews were conducted with 94 participants (93.1%). More than half (n = 48) of the participants said that they were motivated to participate in the study because they had a family member with AMD or another eye or genetic disorder. Despite low risk levels, many participants reported making changes as a result of the genetic testing. Twenty-seven people reported making specific changes, including wearing sunglasses and brimmed hat and taking vitamin supplements. Another 16 people said that they were already doing the recommended activities, including wearing glasses, quitting smoking, and/or taking vitamins.

CONCLUSIONS
Interest in genetic testing for future risk of AMD was high in this population and resulted in support to continue current health behaviors or incentive to improve behaviors related to eye health.
What Is the Nature of the Reach and Grasp Deficit in Wet Age-related Macular Degeneration?
Authors: Corveleyn Xavier , Lenoble Quentin , Szaffarczyk Sébastien , Tran Thi Ha Chau , Boucart Muriel 
Published: February 2018

SIGNIFICANCE
Vision is paramount for motor actions directed toward objects. Vision allows not only the identification of objects and their shape and spatial location, but also the adaptation of our movement when it arrives on the object. These findings show that vision deficits, as in age-related macular degeneration (AMD), can lead to reaching and grasping deficits.

PURPOSE
Few studies have investigated reaching and grasping in patients with AMD. They showed a deficit in the execution of motor actions in people with AMD, even though these people do not mention difficulties in their daily lives. The purpose of this study was to understand the nature of impairments in motor actions in patients.

METHODS
We compared performance in two reach-and-grasp tasks determined by whether the participants (16 people with wet AMD and 17 age-matched control subjects) had time to look at the object before reaching and grasping it.

RESULTS
The results show that the kinematic parameters of reach-and-grasp movements do not differ between groups when participants are provided time to look at the object before the movement. In contrast, performance in terms of movement duration, acceleration time, time to reach the maximum grip aperture, and the maximum velocity differ between patients and control subjects when the object is displayed immediately before the movement.

CONCLUSIONS
The motor perturbations observed in people with AMD in previous studies seem to result from difficulties in target identification rather than from visuomotor deficits.