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Summary: Background: The Lancet Commission on Global Surgery established the Three Delays framework, categorising delays in accessing timely surgical care into delays in seeking care (First Delay), reaching care (Second Delay), and receiving care (Third Delay). Globally, knowledge gaps regarding delays for fracture care, and the lack of large prospective studies informed the rationale for our international observational study. We investigated delays in hospital admission as a surrogate for accessing timely fracture care and explored factors associated with delayed hospital admission. Methods: In this prospective observational substudy of the ongoing International Orthopaedic Multicenter Study in Fracture Care (INORMUS), we enrolled patients with fracture across 49 hospitals in 18 low-income and middle-income countries, categorised into the regions of China, Africa, India, south and east Asia, and Latin America. Eligible patients were aged 18 years or older and had been admitted to a hospital within 3 months of sustaining an orthopaedic trauma. We collected demographic injury data and time to hospital admission. Our primary outcome was the number of patients with open and closed fractures who were delayed in their admission to a treating hospital. Delays for patients with open fractures were defined as being more than 2 h from the time of injury (in accordance with the Lancet Commission on Global Surgery) and for those with closed fractures as being a delay of more than 24 h. Secondary outcomes were reasons for delay for all patients with either open or closed fractures who were delayed for more than 24 h. We did logistic regression analyses to identify risk factors of delays of more than 2 h in patients with open fractures and delays of more than 24 h in patients with closed fractures. Logistic regressions were adjusted for region, age, employment, urban living, health insurance, interfacility referral, method of transportation, number of fractures, mechanism of injury, and fracture location. We further calculated adjusted relative risk (RR) from adjusted odds ratios, adjusted for the same variables. This study was registered with ClinicalTrials.gov, NCT02150980, and is ongoing. Findings: Between April 3, 2014, and May 10, 2019, we enrolled 31 255 patients with fractures, with a median age of 45 years (IQR 31–62), of whom 19 937 (63·8%) were men, and 14 524 (46·5%) had lower limb fractures, making them the most common fractures. Of 5256 patients with open fractures, 3778 (71·9%) were not admitted to hospital within 2 h. Of 25 999 patients with closed fractures, 7141 (27·5%) were delayed by more than 24 h. Of all regions, Latin America had the greatest proportions of patients with delays (173 [88·7%] of 195 patients with open fractures; 426 [44·7%] of 952 with closed fractures). Among patients delayed by more than 24 h, the most common reason for delays were interfacility referrals (3755 [47·7%] of 7875) and Third Delays (cumulatively interfacility referral and delay in emergency department: 3974 [50·5%]), while Second Delays (delays in reaching care) were the least common (423 [5·4%]). Compared with other methods of transportation (eg, walking, rickshaw), ambulances led to delay in transporting patients with open fractures to a treating hospital (adjusted RR 0·66, 99% CI 0·46–0·93). Compared with patients with closed lower limb fractures, patients with closed spine (adjusted RR 2·47, 99% CI 2·17–2·81) and pelvic (1·35, 1·10–1·66) fractures were most likely to have delays of more than 24 h before admission to hospital. Interpretation: In low-income and middle-income countries, timely hospital admission remains largely inaccessible, especially among patients with open fractures. Reducing hospital-based delays in receiving care, and, in particular, improving interfacility referral systems are the most substantial tools for reducing delays in admissions to hospital. Funding: National Health and Medical Research Council of Australia, Canadian Institutes of Health Research, McMaster Surgical Associates, and Hamilton Health Sciences.

Objective: The main objective of this study was to analyze the ability of local anesthetic instillation into the retropharyngeal space to reduce dysphagia symptoms and occurrence rates in patients undergoing anterior cervical discectomy and fusion (ACDF) procedures., Methods: A single-center, prospective, randomized, double-blinded, and placebo-controlled clinical study was performed. We enrolled patients undergoing one- or two-level ACDF procedures for cervical degenerative disc disease with disc herniation, radiculopathy and/or myelopathy symptoms. The patients were randomly assigned (1:1 ratio) to receive either 0.5% bupivacaine hydrochloride or 0.9% NaCl solution., Results: Forty-three (74%) and 41 (77%) of patients reported dysphagia symptoms at the time of discharge in the investigational and control groups, respectively. There were no statistically significant differences in duration of dysphagia symptoms, Swallowing-Quality of Life (SWAL-QOL) survey or pain scores between the investigational and control patient groups at any of the follow-up time points. Controlling for independent variables, only younger age significantly predicted dysphagia symptoms at discharge, 2-week, and 3-month follow-ups (P ≤ 0.03; R ≥ -0.038; OR 0.96, 95% CI 0.93-0.99. Female sex was associated with lower SWAL-QOL scores at discharge (P = 0.046; R = 0.87; OR 2.38, 95% CI 1.02-5.56). A total of 8 (13.8%) and 6 (11.3%) patients in the investigational and control groups, respectively, were referred to a specialist or underwent speech therapy for their dysphagia symptoms. There were no adverse reactions to the study drug observed., Conclusions: Local retropharyngeal space anesthetic instillation did not reduce dysphagia symptoms or occurrence rates in patients undergoing anterior discectomy and fusion surgeries., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Children in rural areas are disproportionately affected by pediatric obesity. Poor access to healthcare providers, lack of nutrition education, lower socioeconomic status, and fewer opportunities to be physically active are all unique barriers that contribute to this growing health concern. There are very few pediatric obesity interventions that have been developed that target this unique population. iAmHealthy is a family-based behavioral, nutrition and physical activity intervention developed with input from rural children and families that capitalizes on the innovative use of mobile health applications (mHealth). iAmHealthy is a 25-contact hour multicomponent intervention delivered over an 8-month period targeting 2nd-4th grade school children and their families. This paper describes the rationale, design, participant/school enrollment, and planned implementation of a randomized controlled trial of the iAmHealthy intervention in comparison to a monthly newsletter delivered through rural elementary schools. Child Body Mass Index z-score (BMIz) is the primary outcome, along with child 24-hour dietary recall, and child accelerometer-determined physical activity and sedentary behavior as secondary outcomes. The study will include 18 schools (with 8 children each) resulting in a final planned sample size of 144 children. This project also has a strong focus on dissemination and implementation science, and thus includes many measures related to the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance). Data collection is completed at baseline, end of intervention (8 months), and follow-up (20 months). This study is the first randomized controlled trial to deliver a rurally tailored, empirically supported, family-based behavioral intervention for pediatric obesity solely over mHealth. Registered with ClinicalTrials.gov NCT ID 03304249., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hand preference is a sensorimotor skill whose development both reflects and promotes the development of hemispheric lateralization for manual and cognitive functions. Extensive comparative, crosscultural, and paleoanthropological evidence demonstrates the prevalence of limb lateralized preferences across vertebrate species and the prevalence of right-handedness within hominid evolution. Many reviews of the evolution and development of human handedness have proposed adaptive explanations for its evolution. However, during the last 3 decades a new approach to understanding evolution (the Extended Evolutionary Synthesis-EES) provided a persuasive alternative to the conventional (Neo-Darwinian Synthetic Theory-ST) evolutionary and developmental accounts. EES combines modern evolutionary and developmental research (Evo-Devo) in ways that alter understanding of natural selection, adaptation, and the role of genes in development and evolution. These changes make obsolete all past accounts of the evolution and development of lateralization and handedness because EES/Evo-Devo requires new study designs. The developmental trajectories of any structural or functional trait must be specified so that it may be related to variations in the developmental trajectories of other traits. First, we describe how the EES/Evo-Devo differs from the conventional ST, particularly for understanding of how traits develop. Then, we apply Evo-Devo to the study of handedness development in infancy and its relation to the development of other cognitive functions. Finally, we argue that identifying the development of atypical traits would benefit from knowledge of the range of individual differences in typical developmental trajectories of hand-use preference and their relation to variations in the developmental trajectories of cognitive functions., (© 2018 Elsevier B.V. All rights reserved.)

Background: Emergency physicians can utilize point-of-care thoracic ultrasound to aid in the diagnosis of a variety of cardiovascular and respiratory complaints., Case Report: An emergency physician utilized point-of-care cardiac ultrasound to identify catheter-associated atrial thrombi in a hemodialysis patient presenting with dyspnea. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Based on this case, point-of-care ultrasound can be utilized in patients with central venous catheters, to identify intracardiac thrombi as the cause of dyspnea, thereby facilitating appropriate consultation and treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: According to the published reports, revision surgery is sometimes recommended even in patients with asymptomatic anterior lumbar intervertebral graft migrations. The main purpose of this chart review study was to report on the clinical course and outcomes of patients who had anterior intervertebral graft extrusions after transforaminal lumbar interbody fusion (TLIF)., Methods: From July 2002 to July 2014, 1259 consecutive TLIF surgeries were performed. These were reviewed, and patients who had anterior intervertebral graft extrusions were identified., Results: The incidence of graft extrusion was 0.6% (7 of 1259 patients). There were 6 female patients and 1 male patient with an average age of 65.7 years (range, 44-80 years). All patients underwent TLIF with bilateral pedicle screw fixation, and 6 received recombinant human bone morphogenetic protein-2. Graft migrations were diagnosed between 5 days and 8 months postoperatively except for 2 cases in which migration occurred intraoperatively. The patients were closely followed for an average of 27.4 months (range, 12-43 months). All patients remained asymptomatic during the follow-up period and had solid fusion despite extrusions with an average time to fusion of 13 months (range, 10-18 months). No other adverse events occurred during the follow-up period., Conclusions: The risks of additional and highly invasive revision surgery should be weighed against the potential short-term and long-term complications associated with graft extrusions or migrations. It was demonstrated that fusion may take longer but can be achieved, and close observation may be adequate for asymptomatic patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Transforaminal lumbar interbody fusion with bilateral segmental pedicle screw (PS) fixation is a widely used and well-recognized technique that provides fixation and load-bearing capacity, while restoring morphometric spine parameters and relieving symptoms in patients with degenerative disc disease. A supplemental interspinous process fixation plate (ISFP) as an adjunct to unilateral PS fixation allows for reduced invasiveness of this technique compared with bilateral PS placement. The biomechanical comparison results have been previously reported, but the significance of these findings has not been studied in clinical settings., Methods: A prospective cohort study with a supplemental retrospective chart review and radiographic analysis was performed. Patients were divided into 2 groups: bilateral PS fixation (n = 75) or unilateral PS fixation + ISFP (n = 96). Lateral lumbar standing radiographs were obtained for preoperative and postoperative foraminal height (FH), disc height, segmental sagittal alignment, and lumbar sagittal alignment measurements. Standardized questionnaires were used to compare postoperative clinical outcomes., Results: The estimated blood loss, duration of procedure, and length of hospital stay were significantly lower for 1-level and 2-level procedures in the unilateral PS + ISFP group. A statistically significant mean disc height increase was observed in both groups. Regardless of the disc height increase, a statistically significant FH loss was detected in the bilateral PS group (from 17.1 mm to 16.3 mm; 4.7% loss; P = 0.04) compared with FH height loss in the unilateral PS + ISFP group that was not statistically significant (from 19.0 mm to 18.4 mm; 3.2% loss; P = 0.1). The analysis of segmental sagittal alignment, lumbar sagittal alignment, clinical outcomes, and fusion rates did not demonstrate any statistically significant differences., Conclusions: Significantly reduced surgical invasiveness was associated with unilateral PS + ISFP fixation, which represents the major advantage of this technique. Unilateral fixation was also associated with a slightly lower reduction in FH and was equally effective as bilateral PS fixation in regard to fusion rates, clinical outcomes, and other radiographic outcomes studied., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013., Methods: We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs)., Findings: Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down., Interpretation: Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene., Funding: Bill & Melinda Gates Foundation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Cancer risk-related stressors are prominent among BRCA mutation carriers. Loss of one's mother to a BRCA-associated cancer is an additional stressor, which may be related to an enhanced inflammatory response. This study examined the effect of mother's vital status on psychological factors and stress-associated biomarkers among BRCA mutation carriers. The role of bereavement on biopsychological variables was also examined., Methods: BRCA-carriers with known maternal transmission enrolled in the Gilda Radner Hereditary Cancer Program were invited to participate. Focus group composition was predetermined based on participants' personal cancer history and mother's vital status. Prior to the focus group, participants completed a Quality of Life (QOL) survey and collected a first morning saliva sample. Inflammatory biomarkers were analyzed from proximal archived serum. One day post focus group, a process survey, and morning saliva were collected., Results: QOL was significantly lower for those whose mothers are deceased (n = 17) compared to those whose mothers are alive (n = 15) (P = 0.003) after adjusting for age, personal cancer history and prophylactic surgery. Similarly, those whose mothers are deceased reported significantly more perceived stress (P = 0.015), more intrusive thoughts related to cancer risk (P = 0.049), and more anxiety (P = 0.003). Higher bereavement scores were significantly associated with QOL and psychological measures. Biomarker correlates were consistent with and significantly correlated to the patient-reported psychological outcomes for those whose mothers were deceased., Conclusions: BRCA mutation carriers with a known maternal transmission whose mother is deceased report higher perceived stress and anxiety, lower QOL, and a stress-associated biomarker profile that is potentially globally immune suppressive., (Copyright © 2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Here, we analyze for the first time the immunological and therapeutic efficacy of a dendritic cell (DC) vaccine based on a cancer-testis antigen, Brother of regulator of imprinted sites (BORIS), an epigenetically acting tumor-promoting transcription factor. Vaccination of mice with DC loaded with truncated form of BORIS (DC/mBORIS) after 4T1 mammary tumor implantation induced strong anti-cancer immunity, inhibited tumor growth (18.75% of mice remained tumor-free), and dramatically lowered the number of spontaneous clonogenic metastases (50% of mice remained metastases-free). Higher numbers of immune effector CD4 and CD8 T cells infiltrated the tumors of vaccinated mice vs. control animals. Vaccination significantly decreased the number of myeloid-derived suppressor cells (MDSCs) infiltrating the tumor sites, but not MDSCs in the spleens of vaccinated animals. These data suggest that DC-based mBORIS vaccination strategies have significant anti-tumor activity in a therapeutic setting and will be more effective when combined with agents to attenuate tumor-associated immune suppression., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: This study's purpose was to adapt the Roter Interaction Analysis System (RIAS) for telemedicine clinics and to investigate the adapted measure's reliability. The study also sought to better understand the volume of technology-related utterance in established telemedicine clinics and the feasibility of using the measure within the telemedicine setting. This initial evaluation is a first step before broadly using the adapted measure across technologies and raters., Methods: An expert panel adapted the RIAS for the telemedicine context. This involved accounting for all consultation participants (patient, provider, presenter, family) and adding technology-specific subcategories. Ten new and 36 follow-up telemedicine encounters were videotaped and double coded using the adapted RIAS. These consisted primarily of follow-up visits (78.0%) involving patients, providers, presenters, and other parties. Reliability was calculated for those categories with 15 or more utterances., Results: Traditional RIAS categories related to socioemotional and task-focused clusters had fair to excellent levels of reliability in the telemedicine setting. Although there were too few utterances to calculate the reliability of the specific technology-related subcategories, the summary technology-related category proved reliable for patients, providers, and presenters. Overall patterns seen in traditional patient-provider interactions were observed, with the number of provider utterances far exceeding patient, presenter, and family utterances, and few technology-specific utterances., Conclusion: The traditional RIAS is reliable when applied across multiple participants in the telemedicine context. Reliability of technology-related subcategories could not be evaluated; however, the aggregate technology-related cluster was found to be reliable and may be especially relevant in understanding communication patterns with patients new to the telemedicine setting. Use of the RIAS instrument is encouraged to facilitate comparison between traditional, face-to-face clinics and telemedicine; among diverse consultation mediums and technologies; and across different specialties. Future research is necessary to further investigate the reliability and validity of adding technology-related subcategories to the RIAS. The limited number of technology-related utterances, however, implies a certain degree of comfort with two-way interactive video consultation among study participants., Practice Implications: Telemedicine continues to increase access to healthcare. The technology-related categories of the adapted RIAS were reliable when aggregated, thereby providing a tool to better understand how telemedicine affects provider-patient communication and outcomes.

Objective: The objective of the study was to examine the association in humans between maternal psychosocial stress exposure during pregnancy and measures of glucose-insulin metabolism in the adult offspring., Study Design: Healthy young adults whose mothers experienced major stressful life events during their pregnancy (n = 36, prenatal stress, PS group, mean age 25 +/- 5.14 [SD] years) and a comparison group (n = 22, CG, mean age 24 +/- 3.7 [SD] years) underwent an oral glucose tolerance test., Results: Glucose levels were not significantly different across the groups; however, prenatally stressed subjects showed significantly elevated 2-hour insulin (P = .01) and C-peptide levels (P = .03). These differences were independent of other major risk factors for insulin resistance, including birth phenotype (birthweight, length of gestation), a family history of diabetes, gestational diabetes, body mass index, proinflammatory state, and smoking., Conclusion: Higher insulin responses reflect relative insulin resistance in these prenatally stressed young adults. This study is the first to provide evidence for a link in humans between prenatal psychosocial stress exposure and alterations in glucose-insulin metabolic function.

As the number of telemedicine programs continues to grow, the accuracy of diagnosis over interactive televideo is a central concern. Although investigators have begun to address diagnostic equivalency in telehealth clinics, few published studies reflect strong research design. The two presented telehealth programs completed randomized controlled trials in real-world clinical settings that addressed some of the methodologic shortcomings of prior studies. Diagnostic equivalency studies were completed across five telehealth specialty clinics: physical therapy, speech therapy, ambulatory pediatrics, child psychiatry, and developmental disabilities services. The two research teams encountered similar decision points in designing and implementing the equivalency protocols. This article addresses methodologic issues in choosing design, participants, technology, and evaluation measures. Although the paper focuses on interactive televideo, the issues raised are pertinent across telehealth technologies.

Recent studies suggest that large numbers of health-care consumers are turning to the Internet as a source of health information. This article considers the potential impact of on-line health information on women's health-care decisions, and the role of physicians relating to their patients' use of the Internet as an information source. In particular, the article examines the effect of on-line health information on the informed consent process. Physicians' disclosure obligations (their legal duty to provide information to patients) and the law of informed consent are briefly described. The article then considers the Internet as a source of health information, and instances and types of misinformation. Finally, the article suggests steps physicians may take to help their patients benefit from Internet health information and to become critical consumers who do not fall victim to inaccurate or misleading information. The article concludes by suggesting that physicians make a practice of asking their patients about alternate sources of information they may have accessed, in order to help ensure that patients' health-care decisions are based on current, accurate, and complete information.

Patients with non-Hodgkin's B-cell lymphoma who received an antitumor vaccine of idiotypic ig protein showed humoral and proliferative immune responses. Because immunity to some antigens, including tumor antigens and human pathogenic viruses, may be better correlated with the cytolytic cellular immune response, we evaluated 16 non-Hodgkin's lymphoma patients immunized with autologous idiotypic ig molecules for changes in tumor-specific cytotoxic T-lymphocyte precursor (CTLp) frequency using limiting dilution analysis. Eleven patients had a significant increase in tumor-specific CTLp. Eight of these 11 patients remain without evidence of disease or with stable minimal disease. In contrast, all five patients who did not have a significant change in tumor-specific CTLp have developed progressive disease. Patient vaccination with tumor associated protein antigens can increase tumor-specific CTLp frequencies. The correlation of increased tumor specific CTLp with freedom from progression is significant at P = .002. This study indicates that measurement of CTLp frequencies are relevant to the clinical evaluation of human tumor vaccines and suggests that cell-mediated cytolytic immune responses may be an important determinant of vaccine efficacy.

Juvenile aponeurotic fibromas, although locally recurrent, generally do not metastasize. This observation supports the practice of incomplete excision of the tumor to preserve the function of the involved extremity. We report on a patient with a juvenile aponeurotic fibroma of the palm, who returned 5 years after the second local surgical excision with metastatic fibrosarcoma of the lungs and bones.