Characteristics of frequent emergency department users in Korea: a 4-year retrospective analysis using Korea Health Panel Study data.

OBJECTIVE: We aimed to investigate the characteristics of frequent emergency department (ED) users in Korea. METHODS: We analyzed the Korea Health Panel Study data of a sampled population from the 2005 Population Census of Korea data, and adults (age ≥18 years) who visited the ED at least once a year between 2014 and 2017 were included in the study. People who visited three or more times a year were classified as frequent users. We compared demographic, socioeconomic, and health-related factors between nonfrequent and frequent users. We used a multivariable logistic regression analysis to determine factors related to frequent ED visits. We also compared the characteristics of ED use in both nonfrequent and frequent users. RESULTS: A total of 5,090 panels were included, comprising 6,853 visits. Frequent users were 333 (6.5% of all panels), and their ED visits were 1,364 (19.9% of all ED visits). In the multivariable regression analysis, medical aid coverage (adjusted odds ratio [aOR] of the National Health Service coverage, 0.55; 95% confidence interval [CI], 0.40-0.75), unemployment (aOR of employment, 0.72; 95% CI, 0.56-0.91), prior ward admission in a year (aOR, 2.14; 95% CI, 1.67-2.75), and frequent outpatient department use (aOR, 1.72; 95% CI, 1.35-2.20) were associated with frequent use. Moreover, frequent users visited the ED of public hospitals more often than than nonfrequent users (19.2% vs. 9.8%). Medical problems rather than injury/poisoning were the more common reasons for visiting the ED (84.5% vs. 71.2%). CONCLUSION: We found that frequent ED users were likely to be those with socioeconomic disadvantage or with high demand for medical service. Based on this study, further studies on interventions to reduce frequent ED use are required for better ED services.

Real-time display of laboratory testing status improves satisfaction levels in an emergency department: A pilot study.

BACKGROUND: Clinicians need to know timelines of requested laboratory tests to provide effective patient management. We developed a real-time laboratory progress checking system and measured its effectiveness using appropriate indicators in an emergency room setting. METHODS: In our original in-house health information system display, blank spaces, which were generated for test results when tests were ordered, remained empty until the final results reported. We upgraded the laboratory reporting system to show real-time testing information. The stages included requests for test, label printing, sampling, laboratory receipts, performance of tests, verification of results, and interpretation of results and final report by laboratory physician. To assess the usefulness of the function, we measured the emergency department healthcare workers' satisfaction and compared the number of phone calls about test status before and after implementation. RESULTS: After the system upgrade, the healthcare workers' understanding of the testing process increased significantly as follows. More clinicians could estimate the time of final test results through the real-time testing status information (61.9% and 85.7%, P = .002), and respondents reported that the upgraded system was more convenient than the original system (41.3% and 22.2%, respectively, P = .022). The number of phone calls about the test status decreased after implementation of the upgrade; however, the difference was not statistically significant (before, 0.13% [63 calls/48 637 tests] and after, 0.09% [42/46 666]; P = .066). CONCLUSIONS: The real-time display of laboratory testing status increased understanding of testing process among healthcare workers in emergency room, which ultimately may increase the usefulness and efficiency of the laboratory service use.

International Rotational Program of Emergency Medicine Residents to Mozambique: Introducing a Medical Education Program to a Single Hospital.

INTRODUCTION: There are several medical elective programs for low-income countries especially in medically vulnerable places. The Hospital Central de Quelimane (HCQ) is a regional hospital in Quelimane, capital city of the province of Zambezia in Mozambique. The HCQ serves as a regional base hospital for urgent and severe patients. METHODS: Four emergency medicine (EM) residents participated in our 2017-2018 rotational program for HCQ, to share medical knowledge with the local medical doctors and support the demands of medical equipment skills and educational programs. We determined the current capabilities of HCQ and designed a rotational program in accordance with the demands in the following areas: resuscitation, trauma, critical care, and radiology. We also introduced continuous education programs and administrative methods for future development of education. RESULTS: Throughout the four rotations of our EM residents, we conducted daily education and several practical lessons based on the demands of the local doctors and equipment operation. The educational program was administered by an educational administrator who was responsible for updating the medical and technical knowledge of doctors. With our programs, the doctors of HCQ were able to perform resuscitation and critical protocols, including manipulating equipment such as mechanical ventilator and defibrillator. CONCLUSION: The rotation program by the four residents was successful, in terms of sharing medical knowledge and equipment management, and filling gaps identified in the operation of a modern hospital.

The importance of preliminary evaluation in developing ambulance staff training curriculum for developing countries: A survey in Uzbekistan.

BACKGROUND: The Tashkent city, the capital of the republic of Uzbekistan, started joint project with Korean emergency physicians to improve the quality of their ambulance services in 2016. Ambulance service in Tashkent city has been facing challenges in processing a large number of calls, and low competency of their staff in providing advanced prehospital emergency care. To design an appropriate capacity building training program for ambulance staff, we analyzed the current ambulance service in Tashkent concerning resources and competency of the staff. METHODS: In this study, ambulance staff participated in the constructed survey and pre-validated written test. Statistics and other information were provided by the Ministry of Health of Uzbekistan. RESULTS: Ninety-eight ambulance staff were participated in this study, and more than half (53.1%) of the participants were physicians. The average years of service in the ambulance were 8.71±6.9 years. In the ambulance, drugs were stocked in enough quantity include injections for critical care, except large volume fluids for resuscitation. Only 19 to 52 percent of the ambulances were equipped with essential monitoring devices. Competency for the basic procedure was surveyed higher than 60%, but critical care skills, such as defibrillation, were as low as 18%. The written test resulted in only 41.1% correct answer rate, though it was higher than 60% in the validation test for Korean ambulance staff. Conventional prehospital knowledge and skillset deemed to be essential for ambulance staff were found to be marginal in the test. CONCLUSION: The ambulance staff in Tashkent, Uzbekistan found to have insufficient medical knowledge and clinical decision-making abilities. Training program for ambulance staff in Tashkent should be developed on the basis of the findings in this study.

Enrichment of Exosome-Like Extracellular Vesicles from Plasma Suitable for Clinical Vesicular miRNA Biomarker Research.

Exosome-like extracellular vesicles (ELVs) contain biomolecules that have potential as diagnostic biomarkers, such as proteins, micro-RNAs (miRNAs), and lipids. However, it is difficult to enrich ELVs consistently with high yield and purity from clinical samples, which hampers the development of ELV biomarkers. This is particularly true for miRNAs in protein-rich plasma. Hence, we modified ELV isolation protocols of three commercially available polymer-precipitation-based kits using proteinase K (PK) treatment to quantify ELV-associated miRNAs in human plasma. We compared the yield, purity, and characteristics of enriched plasma ELVs, and measured the relative quantity of three selected miRNAs (miR-30c, miR-126, and miR-192) in ELVs using six human plasma samples. Compared with the original protocols, we demonstrated that ELVs can be isolated with PK treatment with high purity (i.e., lack of non-exosomal proteins and homogeneous size of vesicles) and yield (i.e., abundancy of exosomal markers), which were dependent on kits. Using the kit with the highest purity and yield with PK treatment, we successfully quantified ELV miRNAs (levels of 45%-65% in total plasma) with acceptable variability. Collectively, ELV enrichment using the modified easy-to-use method appears suitable for the analysis of miRNAs, although its clinical applicability needs to be confirmed in larger clinical studies.

Status of Emergency Signal Functions in Myanmar Hospitals: A Cross-Sectional Survey.

INTRODUCTION: Low- and middle-income countries (LMICs) have a large percentage of global mortality and morbidity rates from non-communicable diseases, including trauma. The establishment and development of emergency care systems is crucial for addressing this problem. Defining gaps in the resources and capacity to provide emergency healthcare in LMICs is essential for proper design and operation of ECS (emergency care services) reinforcement programs. Myanmar has particular challenges with road access for providing timely emergency medical care, and a shortage of trained health workers. To examine the ECS capacity in Myanmar, we used the Emergency Care Assessment Tool (ECAT), which features newly developed tools for assessing sentinel conditions and signal functions (key interventions to address morbidity and mortality) in emergency care facilities. METHODS: ECAT is composed of six emergent sentinel conditions and corresponding signal functions. We surveyed a total of nine hospitals in five states in Myanmar. A constructed survey sheet was delivered by e-mail, and follow-up interviews were conducted via messenger to clarify ambiguous answers. RESULTS: We categorized the nine participating institutions according to predefined criteria: four basic-level hospitals; four intermediate-level; and one advanced-level hospital. All basic hospitals were weak in trauma care, and two of 12 signal functions were unavailable. Half of the intermediate hospitals showed weakness in trauma care, as well as critical care such as shock management. Only half had a separate triage area for patients. In contrast, all signal functions and resources listed in ECAT were available in the advanced-level hospital. CONCLUSION: Basic-level facilities in Myanmar were shown to be suboptimal in trauma management, with critical care also inadequate in intermediate facilities. To reinforce signal functions in Myanmar health facilities, stakeholders should consider expanding critical functions in selected lower-level health facilities. A larger scale survey would provide more comprehensive data to improve emergency care in Myanmar.

Association of Circulating Irisin Concentrations with Weight Loss after Roux-en-Y Gastric Bypass Surgery.

Irisin is a myokine with potential anti-obesity properties that has been suggested to increase energy expenditure in obese patients. However, there is limited clinical information on the biology of irisin in humans, especially in morbidly obese patients undergoing bariatric surgery. We aimed to assess the association of circulating irisin concentrations with weight loss in obese patients undergoing bariatric surgery. This was a pilot, single-centre, longitudinal observational study. We recruited 25 morbidly obese subjects who underwent Roux-en-Y gastric bypass surgery (RYGBP), and blood samples from 12 patients were taken to measure serum irisin concentrations before, and one and nine months after surgery. Their clinical characteristics were measured for one year. The preoperative serum irisin concentration (mean 1.01 ± 0.23 µg/mL, range 0.73⁻1.49) changed bidirectionally one month after RYGBP. The mean concentration at nine months was 1.11 ± 0.15 µg/mL (range 0.92⁻1.35). Eight patients had elevated irisin levels compared with their preoperative values, but four did not. Elevations of irisin levels nine months, but not one month, after surgery, were associated with lower preoperative levels (p = 0.016) and worse weight reduction rates (p = 0.006 for the percentage excess weight loss and p = 0.032 for changes in body mass index). The preoperative serum irisin concentrations were significantly correlated with the percentage of excess weight loss for one year (R² = 0.612; p = 0.04) in our study. Our results suggest that preoperative circulating irisin concentrations may be at least in part associated with a weight loss effect of bariatric surgery in morbidly obese patients. Further large-scale clinical studies are needed to ratify these findings.

Use of smart glasses for ultrasound-guided peripheral venous access: a randomized controlled pilot study.

OBJECTIVE: Smart glasses can provide sonographers with real-time ultrasound images. In the present study, we aimed to evaluate the utility of smart-glasses for ultrasound-guided peripheral venous access. METHODS: In this randomized, crossover-design, simulation study, 12 participants were recruited from the emergency department residents at a university hospital. Each participant attempted ultrasound-guided peripheral venous access on a pediatric phantom at intervals of 5 days with (glasses group) or without (non-glasses group) the use of smart glasses. In the glasses group, participants confirmed the ultrasound image through the lens of the smart glasses. In the non-glasses group, participants confirmed the ultrasound image through the display viewer located next to the phantom. Procedure time was regarded as the primary outcome, while secondary outcomes included the number of head movements for the participant, number of skin punctures, number of needle redirections, and subjective difficulty. RESULTS: No significant differences in procedural time were observed between the groups (non-glasses group: median time, 15.5 seconds; interquartile range [IQR], 10.3 to 27.3 seconds; glasses group: median time, 19.0 seconds; IQR, 14.3 to 39.3 seconds; P=0.58). The number of head movements was lower in the glasses group than in the non-glasses group (glasses group: median, 0; IQR, 0 to 0; non-glasses group: median, 4; IQR, 3 to 5; P<0.01). No significant differences in the number of skin punctures or needle restrictions were observed between the groups. CONCLUSION: Our results indicate that smart-glasses may aid in ensuring ultrasound-guided peripheral venous access by reducing head movements.

Factors associated with satisfaction with pediatric emergency department services in Korea: analysis of Korea Health Panel Data 2010 to 2012.

OBJECTIVE: We aimed to investigate the factors related to satisfaction with the pediatric emergency department service in Korea. METHODS: This study examined data from the Korea Health Panel Data from 2010 to 2012. Pediatric patients who visited the emergency department at least once between 2010 and 2012 in Korea were included. Data were collected on patient satisfaction with the emergency department service, and factors related to the patient characteristics, emergency department service process, and medical institution. We compared the dissatisfied and satisfied groups, and calculated the odds ratios for satisfaction according to each variable. RESULTS: A total of 1,505 emergency department visits from 947 pediatric patients during the 3-year period were analyzed. We estimated that about 79.5% of patients in the population were satisfied. The odds of expressing satisfaction were higher among males than in females, and among patients who were hospitalized after emergency department treatment compared to those who were transferred to another hospital. Conversely, the odds of expressing satisfaction were lower among patients who had a chronic disease, a financial source other than National Health Insurance, experienced hospitalization within 1 year. CONCLUSION: Our study results might be helpful for establishing a satisfactory pediatric emergency medical service system. In the future, further prospective studies evaluating the causal relationships between the relevant factors and patient satisfaction are warranted.

Characteristics of burn injuries among children aged under six years in South Korea: Data from the Emergency Department-Based Injury In-Depth Surveillance, 2011-2016.

Studies show that young children are vulnerable to burn injuries. We aimed to investigate the characteristics of thermal injuries in this population. We included children below 6 years of age who visited the emergency department (ED) after thermal injuries who were registered in the Korean Emergency Department-based Injury In-Depth Surveillance (2011-2016) database. Demographic characteristics, injury-related factors, and factors associated with ED treatment were gathered from the data. Then, we divided all children into two groups according to the ED discharge status: discharge versus admission (including cases transferred to other hospitals). The characteristics of the two groups were compared, and factors associated with admission were investigated. During the study period, 11,667 children with thermal injuries visited the ED. The number of boys was higher than the number of girls, and children aged 1 year accounted for the largest proportion. Most cases occurred in spring and indoors; the home was found to be the most common place. The most common type of burn was scald burns (69%), followed by contact burns (25.9%), and the most commonly burnt body area was the upper limbs (43.7%), followed by the lower limbs (16.8%). Most children (95.8%) were discharged home. The odds for hospital admission were lower for 2-3 and 4-5 year olds than for 0-1 year olds. The odds for hospital admission for contact burns were lower and those for electrical burns were higher than odds for hospital admission for scald burns. In summary, those aged 0-1 showed the largest incidence of thermal injuries and the most common burn mechanism was scald burns. Upper limbs were the most commonly affected body area, but their odds for requiring admission was lowest. Our results could be used as baseline data for prospective interventional studies investigating ways to reduce the incidence of childhood thermal injuries.

The characteristics of pediatric emergency department visits in Korea: An observational study analyzing Korea Health Panel data.

OBJECTIVE: We investigated the characteristics of pediatric emergency department (ED) patients in Korea and determined factors associated with hospital admission after ED treatment. METHODS: Korea Health Panel data from 2008 through 2013 were analyzed retrospectively; we included patients under 18 years old who visited the ED at least once. We collected patient and household epidemiologic data such as sex, age group, region of residence, disability, chronic disease, household income quintile, national health insurance type, use of private insurance, and annual frequency of ED visits. We also examined data related to each ED visit, such as reason for visit, medical service provided, and hospital size/ownership. We then investigated which factors were correlated with case disposition (discharge home or hospital admission) after ED treatment. RESULTS: In total, 3,160 pediatric ED visits occurred during the six-year period. Males (57.5%) and children aged 0-5 years (47.7%) made more visits than females and older children, respectively. The proportion of ED visits for disease (67.7%) was much higher than for injury or poisoning (32.2%), and 452 cases (14.3%) required hospital admission. For hospital admission, the odds ratio (OR) of females was 0.73 compared to males, and the OR of children aged 6-11 was 0.68 compared to children aged 0-5. The OR of capital residents was 0.69 compared to province residents, and the OR of the highest income quintile was 0.51 compared to the lowest quintile. The OR of children with private insurance coverage was 0.49 compared to those lacking private insurance, and the OR of ED visits due to disease was 1.82 compared to visits due to injury/poisoning. CONCLUSION: This analysis of clinical and demographic characteristics of pediatric ED visits and hospital admissions can serve as the foundation of future prospective studies required for establishing appropriate policies for the Korean pediatric emergency medical system.

The effect of distraction by dual work on a CPR practitioner's efficiency in chest compression: A randomized controlled simulation study.

BACKGROUND: In the clinical setting, the dispersed practitioners' attention often leads to decreased competence in their performance. We aimed to investigate the effect of distracted practitioners on the quality of chest compression during cardiopulmonary resuscitation. METHODS: A randomized controlled crossover simulation study was conducted. Participants were recruited from among doctors, nurses, and paramedics working in a university tertiary hospital. The paced auditory serial addition test (PASAT) was used as a tool for distracting participants. In the crossover design, each participant played 2 scenarios with a 20-minute time gap, by a random order; 2-minute continuous chest compressions with and without PASAT being conducted. The primary outcome was the percentage of compression with an adequate compression rate. Secondary outcomes were the percentage of compression with adequate depth, the percentage of compression with full chest wall recoil, mean compression rate (per minute), mean compression depth, and subjective difficulty of chest compression. RESULTS: Forty-four participants were enrolled, and all of them completed the study. It was found that the percentage of compression with an adequate compression rate was lower when the PASAT was conducted. Although there was no difference in the percentage of compression with adequate depth (P = .88), the percentage of compression with complete chest recoil was lower when PASAT was conducted. In addition, while the mean compression rate was higher when PASAT was conducted, the mean compression depth was not significantly different (P = .65). The subjective difficulty was not different (P = .69). CONCLUSIONS: Health care providers who are distracted have a negative effect on the quality of chest compression, in terms of its rate and chest wall recoil. TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT03124290.

Systematic review and meta-analysis of initial management of pneumothorax in adults: Intercostal tube drainage versus other invasive methods.

OBJECTIVES: The ideal invasive management as initial approach for pneumothorax (PTX) is still under debate. The purpose of this systematic review and meta-analysis was to examine the evidence for the effectiveness of intercostal tube drainage and other various invasive methods as the initial approach to all subtypes of PTX in adults. METHODS: Three databases were searched from inception to May 29, 2016: MEDLINE, EMBASE, and the Cochrane CENTRAL. Randomised controlled trials that evaluated intercostal tube drainage as the control and various invasive methods as the intervention for the initial approach to PTX in adults were included. The primary outcome was the early success rate of each method, and the risk ratios (RRs) were used for an effect size measure. The secondary outcomes were recurrence rate, hospitalization rate, hospital stay, and complications. RESULTS: Seven studies met our inclusion criteria. Interventions were aspiration in six studies and catheterization connected to a one-way valve in one study. Meta-analyses were conducted for early success rate, recurrence rate, hospitalization rate, and hospital stay. Aspiration was inferior to intercostal tube drainage in terms of early success rate (RR = 0.82, confidence interval [CI] = 0.72 to 0.95, I2 = 0%). While aspiration and intercostal tube drainage showed no significant difference in the recurrence rate (RR = 0.84, CI = 0.57 to 1.23, I2 = 0%), aspiration had shorter hospital stay than intercostal tube drainage (mean difference = -1.73, CI = -2.33 to -1.13, I2 = 0%). Aspiration had lower hospitalization rate than intercostal tube drainage, but marked heterogeneity was present (RR = 0.38, CI = 0.19 to 0.76, I2 = 85%). CONCLUSION: Aspiration was inferior to intercostal tube drainage in terms of early resolution, but it had shorter hospital stay. The recurrence rate of aspiration and intercostal tube drainage did not differ significantly. The efficacy of catheterization connected to a one-way valve was inconclusive because of the small number of relevant studies. (Registration of study protocol: PROSPERO, CRD42016037866).

Effects of task-specific rehabilitation training on tau modification in rat with photothrombotic cortical ischemic damage.

Although stroke elicits progressive cognitive decline and is a leading cause of dementia, molecular interplay between stroke and Alzheimer's disease (AD) pathology has not been fully elucidated. Furthermore, studies on the effects of post-stroke rehabilitation on AD pathology are limited. We evaluated the acute effect of stroke on tau modification, and the molecular effects of task-specific training (TST) on tau modification using a model of photochemically-induced thrombosis (PIT)-induced cortical infarction. Following PIT in the dominant side of sensorimotor cortex, the rehabilitation group received 4-weeks of TST rehabilitation once daily by single pellet reaching training, whereas the sedentary control group did not received any type of training. Cortical expression levels of proteins related to tau modification were evaluated on post-stroke day 1 (PSD1) and 28; functional tests were also evaluated performed every week. The expression levels of acetyl-tau, phosphorylated-tau (p-tau), cyclooxygenase-2 and Akt-mTORC1-p70S6K pathway in infarcted cortices on PSD1 were significantly greater, whereas the expression levels of p-AMPK were significantly lower than in the paired contralateral sides. TST rehabilitation for 4 weeks greatly improved functional motor performance but not memory, which concurred with the down-regulations of ipsilateral p-AMPK, cyclooxygenase-2, Akt-mTORC1-p70S6K pathway, and p-tau in rehabilitation group. PIT-induced cortical infarction was found to induce cortical tau modification through the Akt-mTORC1-p70S6K activation, and to suppress the expression of AMPK-related proteins. TST rehabilitation greatly improved motor function, but not memory, and suppressed p-tau expression and neuroinflammation. Nevertheless, the role of TST-mediated regulation of tau hyperphosphorylation required further clarification.

Chronological changes in the expression of phosphorylated tau and 5­AMP­activated protein kinase in the brain of senescence­accelerated P8 mice.

Senescence-accelerated mouse prone 8 (SAMP8), a non­transgenic animal model used for researching sporadic Alzheimer's disease (AD), presents AD pathologies and overall dysregulation in brain energy metabolism, which is one of the early pathogenic characteristics of AD. In the present study, the authors examined chronological changes in the expression patterns of phosphorylated tau and of proteins related to energy metabolism to evaluate the association of tau phosphorylation and metabolism, using young­ (2­months­old), middle­ (5­months­old) and old­aged (10­months­old) SAMP8. The levels of phosphorylated 5'­AMP activated protein kinase at Thr172 (p­AMPK) and phosphorylated glycogen synthase kinase 3ß (p­GSK3ßS9) in the cortex of SAMP8 at 2 months were significantly higher than those in senescence­accelerated mouse resistant 1 (SAMR1). The differences were not detected at 5 and 10 months of age, which were concurrent with the changes in levels of phosphorylated tau at Ser396 (p­tauS396), but not with p­tauS262. The level of p­tauS262 was considerably higher in the cortex of middle­aged SAMP8 when compared with that of SAMR1 and sustained in old­aged SAMP8, but not in the young cortex. The levels of cortical sirtuin1 (Sirt1) and insulin receptor substrate 1 (IRS­1) expression of young SAMP8 were significantly lower, when compared with those in SAMR1. However, in the hippocampus of SAMP8, the patterns of chronological changes and levels of p­tau, p­AMPK, Sirt1 and IRS­1 relative to SAMR1 were different from those in the cortex. Taken together, the results suggested that regulation of tau phosphorylation via the AMPK­GSK3ß pathway concurrent with dysregulation of energy metabolism may precede the pathological tau hyperphosphorylation in the cortex of SAMP8, and that the regulation of AMPK­GSK3ß­mediated tau phosphorylation may be dependent on phosphor­epitope in tau or the region of brain.

Playground Equipment Related Injuries in Preschool-Aged Children: Emergency Department-based Injury In-depth Surveillance.

In this study, we investigated playground equipment related injuries in preschool-aged children. This was a retrospective observational study using Emergency Department based Injury In-depth Surveillance, (2011-2014). We included the preschool-aged children with playground equipment related injuries. We surveyed the mechanism and incidence of injuries, and estimated the odds ratio (OR) of traumatic brain injury (TBI) and upper/lower extremities fracture. There were 6,110 patients, mean age was 4.14 ± 1.95 years old. Slide and swing related injuries were 2,475 (40.5%) and 1,102 (18.0%). Fall down (48.5%) was the most common mechanism. The OR of TBI in children 0-2 years old was 1.88 times higher than children 3-7 years old, and in swing was 4.72 (OR, 4.72; 95% confidence interval [CI], 2.37-9.40) times higher than seesaw. The OR of upper extremity fracture in children 3-7 years old was 3.07 times higher than children 0-2 years old, and in climbing was 2.03 (OR, 2.03; 95% CI, 1.63-2.52) times higher than swing. The OR of lower extremity fractures in horizontal bars, tightropes, and trampolines was 2.95 (OR, 2.95; 95% CI, 1.55-5.61) times higher than swing. The most common mechanism and playground equipment were fall down and slide. TBI was associated to younger children (0-2 years old) and swing. Fracture of upper extremities was associated to older children (3-7 years old) and climbing. Fracture of lower extremities was associated to others such as horizontal bars, tightropes, and trampolines.

Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges.

No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

Radiographic basal ganglia abnormalities secondary to nonketotic hyperglycemia with unusual clinical features.

A 77-year-old woman was admitted to a local clinic for altered consciousness and presented with a suspected basal ganglion hemorrhage detected on brain computed tomography. The patient was stuporous, but her vital signs were stable. Her initial blood glucose was 607 mg/dL, and a hyperdense lesion was found in the right basal ganglion on brain computed tomography. T1-weighted magnetic resonance imaging revealed high signal intensity in the right basal ganglion. Electroencephalography showed no seizure activity. The patient was treated with a fluid infusion, and serum glucose level was controlled with insulin. The patient gradually recovered consciousness and was alert within 24 hours as serum glucose level normalized. The basal ganglion lesion caused by hyperglycemia was not accompanied by involuntary limb movement. This is the first report of a patient presenting with decreased consciousness and typical neural radiographic changes associated with nonketotic hyperglycemia but without movement abnormalities.

Activation of the 5'-AMP-Activated Protein Kinase in the Cerebral Cortex of Young Senescence-Accelerated P8 Mice and Association with GSK3ß- and PP2A-Dependent Inhibition of p-tau396 Expression.

The 5'-AMP-activated protein kinase (AMPK), which is a sensor of cellular energy, regulates neuronal survival and energy homeostasis. However, the roles of AMPK in the pathogenesis of Alzheimer's disease (AD) are unclear. The senescence-accelerated mouse prone 8 (SAMP8) strain is characterized by deficits in learning and memory, exhibits pathological characteristics of AD as early as 5 months of age, and is being increasingly recognized as a model of AD. Here, we investigated the relationship between AMPK activation and phosphorylation of the tau protein in the brain of young (2-month-old) SAMP8 animals and in differentiated SH-SY5Y cells. Upregulation of p-AMPK, p-ACC, and p-GSK3ßS9 and downregulation of p-tau396 and sirtuin 1 (Sirt1) were observed in the cerebral cortex of young SAMP8 mice compared with that of age-matched SAMR1 animals. The hippocampal levels of p-AMPK and p-tau396 in SAMP8 animals were not significantly different from those of SAMR1, whereas upregulation of p-GSK3ßS9 and downregulation of sirt1 was observed in the hippocampus of SAMP8 mice. Consistent with in vivo findings in the cortex, AMPK activation in SH-SY5Y cells upregulated p-GSK3ßS9 but downregulated p-tau396, whereas it had no significant effect on p-tau262 expression. In addition, the AMPK-mediated inhibition of p-tau396 expression was attenuated by okadaic acid, a protein phosphatase 2A (PP2A) inhibitor. Taken together, our data showed that AMPK activation inhibits p-tau396 expression in a GSK3ß- and PP2A-dependent manner, and suggest that differential regulation of tau phosphorylation in young SAMP8 mice by AMPK plays a compensatory role against accelerated senescence in this AD animal model.

Role of cerebrospinal fluid biomarkers in clinical trials for Alzheimer's disease modifying therapies.

Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) Aß1-42, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the.