Viral Kinetics Model of SARS-CoV-2 Infection Informs Drug Discovery, Clinical Dose, and Regimen Selection.

Quantitative systems pharmacology (QSP) has been an important tool to project safety and efficacy of novel or repurposed therapies for the SARS-CoV-2 virus. Here, we present a QSP modeling framework to predict response to antiviral therapeutics with three mechanisms of action (MoA): cell entry inhibitors, anti-replicatives, and neutralizing biologics. We parameterized three distinct model structures describing virus-host interaction by fitting to published viral kinetics data of untreated COVID-19 patients. The models were used to test theoretical behaviors and map therapeutic design criteria of the different MoAs, identifying the most rapid and robust antiviral activity from neutralizing biologic and anti-replicative MoAs. We found good agreement between model predictions and clinical viral load reduction observed with anti-replicative nirmatrelvir/ritonavir (Paxlovid®) and neutralizing biologics bamlanivimab and casirivimab/imdevimab (REGEN-COV®), building confidence in the modeling framework to inform a dose selection. Finally, the model was applied to predict antiviral response with ensovibep, a novel DARPin therapeutic designed as a neutralizing biologic. We developed a new in silico measure of antiviral activity, area under the curve (AUC) of free spike protein concentration, as a metric with larger dynamic range than viral load reduction. By benchmarking to bamlanivimab predictions, we justified dose levels of 75, 225, and 600 mg ensovibep to be administered intravenously in a Phase 2 clinical investigation. Upon trial completion, we found model predictions to be in good agreement with the observed patient data. These results demonstrate the utility of this modeling framework to guide the development of novel antiviral therapeutics.

Osseointegration Potential Assessment of Bone Graft Materials Loaded with Mesenchymal Stem Cells in Peri-Implant Bone Defects.

Many studies have been exploring the use of bone graft materials (BGMs) and mesenchymal stem cells in bone defect reconstruction. However, the regeneration potential of Algipore (highly purified hydroxyapatite) and Biphasic (hydroxyapatite/beta-tricalcium phosphate) BGMs combined with bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we evaluated their osseointegration capacities in reconstructing peri-implant bone defects. The cellular characteristics of BMSCs and the material properties of Algipore and Biphasic were assessed in vitro. Four experimental groups-Algipore, Biphasic, Algipore+BMSCs, and Biphasic+BMSCs-were designed in a rabbit tibia peri-implant defect model. Implant stability parameters were measured. After 4 and 8 weeks of healing, all samples were evaluated using micro-CT, histological, and histomorphometric analysis. In the energy-dispersive X-ray spectroscopy experiment, the Ca/P ratio was higher for Algipore (1.67) than for Biphasic (1.44). The ISQ values continuously increased, and the PTV values gradually decreased for all groups during the healing period. Both Algipore and Biphasic BGM promoted new bone regeneration. Higher implant stability and bone volume density were observed when Algipore and Biphasic BGMs were combined with BMSCs. Biphasic BGM exhibited a faster degradation rate than Algipore BGM. Notably, after eight weeks of healing, Algipore with BSMCs showed more bone-implant contact than Biphasic alone (p < 0.05). Both Algipore and Biphasic are efficient in reconstructing peri-implant bone defects. In addition, Algipore BGM incorporation with BSMCs displayed the best performance in enhancing implant stability and osseointegration potential.

Are the sensorimotor control capabilities of the hands the factors influencing hand function in people with schizophrenia?

BACKGROUND: Previous works reported people with schizophrenia experienced inferior hand functions which influence their daily participation and work efficiency. Sensorimotor capability is one of indispensable elements acting in a well-executed feed-forward and feedback control loop to contribute to hand performances. However, rare studies investigated contribution of sensorimotor ability to hand functions for people with schizophrenia. This study aimed to explore hand function in people with schizophrenia based on the perspective of the sensorimotor control capabilities of the hands. METHODS: Twenty-seven people at the chronic stage of schizophrenia were enrolled. The following assessment tools were used: the Purdue Pegboard Test (PPT) and the VALPAR Component Work Sample-8 (VCWS 8) system for hand function; the Self-Reported Graphic version of the Personal and Social Performance (SRG-PSP) scale for functionality; and the Semmes-Weinstein Monofilaments (SWM), the pinch-holding-up-activity (PHUA) test and the Manual Tactile Test (MTT) for the sensory and sensorimotor parameters. The Clinical Global Impression-Severity (CGI-S) scale and the Extrapyramidal Symptom Rating Scale (ESRS) were used to grade the severity of the illness and the side-effects of the drugs. Spearman's rank correlation coefficient was used to analyze associations among hand function, functionality, and sensorimotor capabilities. A multiple linear regression analysis was used to identify the determinants of hand function. RESULTS: The results indicated that both hand function and sensorimotor capability were worse in people with schizophrenia than in healthy people, with the exception of the sensory threshold measured with the SWM. Moreover, the sensorimotor abilities of the hands were associated with hand function. The results of the regression analysis showed that the MTT measure of stereognosis was a determinant of the PPT measure of the dominant hand function and of the performance on the VCWS 8, and that the ESRS and the MTT measure of barognosis were determinants of the performance on the assembly task of the PPT. CONCLUSIONS: The findings suggested that sensorimotor capabilities, especially stereognosis and barognosis, are crucial determinants of hand function in people with schizophrenia. The results also revealed that the side effects of drugs and the duration of the illness directly affect hand function. CLINICAL TRAIL REGISTRATION: ClinicalTrials.gov , identifier NCT04941677, 28/06/2021.

Bridging the "Know-Do" Gaps in Five Non-Communicable Diseases Using a Common Framework Driven by Implementation Science.

According to the United Nations High-Level Meeting 2018, five non-communicable diseases (NCDs) including cardiovascular diseases, chronic respiratory diseases, diabetes mellitus, cancer, and mental health conditions accounted for two-thirds of global deaths. These five NCDs share five common risk factors including tobacco use, unhealthy diets, physical inactivity, alcohol use, and air pollution. Low- and middle-income countries (LMICs) face larger burden of NCDs than high-income countries (HICs), due to differences in ecological, technological, socioeconomic and health system development. Based on high-level evidence albeit mainly from HICs, the burden caused by NCDs can be reduced by affordable medicines and best practices. However, "know-do" gaps, ie, gaps between what we know in science and what we do in practice, has limited the impact of these strategies, especially in LMICs. Implementation science advocates the use of robust methodologies to evaluate sustainable solutions in health, education and social care aimed at informing practice and policies. In this article, physician researchers with expertise in NCDs reviewed the common challenges shared by these five NCDs with different clinical courses. They explained the principles of implementation science and advocated the use of an evidence-based framework to implement solutions focusing on early detection, prevention and empowerment, supplemented by best practices in HICs and LMICs. These successful stories can be used to motivate policymakers, payors, providers, patients and public to co-design frameworks and implement context-relevant, multi-component, evidence-based practices. In pursuit of this goal, we propose partnership, leadership, and access to continuing care as the three pillars in developing roadmaps for addressing the multiple needs during the journey of a person with or at risk of these five NCDs. By transforming the ecosystem, raising awareness and aligning context-relevant practices and policies with ongoing evaluation, it is possible to make healthcare accessible, affordable and sustainable to reduce the burden of these five NCDs.

Perception of the Use of the Direct Observation of Procedural Skills in Occupational Therapy Postgraduate Year Training in Taiwan: Survey of the Perspectives of Trainees and Supervisors.

Introduction: Assessment of clinical competence is a significant part of the training for young occupational therapists (OTs). Objective and systematic assessment allows both supervisors and trainees to be aware of the training objectives and monitor the progress. The direct observation of procedural skills (DOPS) is a work-based assessment to evaluate professional knowledge, skills, and attitude in clinical training. This study investigated the perspectives of OT educators and trainees on using DOPS and their discrepancy for OT postgraduate year (PGY) training. Methods: This study used a quantitative online survey. Eighty-six supervisors and 41 trainees of OT PGY training programs from 95 hospitals returned the questionnaire (a 90.5% return rate), and 64 supervisors and 30 trainees who used DOPS were analyzed. Outcomes included the practicality in using the DOPS in clinical settings, the ease of rating the DOPS, and advantages and the disadvantages of the DOPS. Results: Most respondents reported that completing one DOPS required at least 11 minutes for direct observation (11-40 minutes: teacher 92.2%; trainee 80.6%). Most respondents (teacher 96.9%, trainee 96.8%) had feedback after direct observation of DOPS, and about half of the feedback assessments took 5 to 10 minutes (teacher 53.1%, trainee 48.4%). Most OT educators and trainees agreed that clinical resources were sufficient and that DOPS matched with OT training goals, benefited OT competence training, and had a fair, objective, and consistent scoring system. Significantly higher percentages of OT trainees felt stressed in and satisfied with the DOPS assessment than trainers. Differences between teachers and trainees regarding easiness of rating DOPS items were not significant. Conclusion: Most OT educators and trainees agreed that DOPS was a practical and appropriate assessment for OT PGY training.

Early changes of fecal short-chain fatty acid levels in patients with mild cognitive impairments.

AIMS: To compare the fecal levels of short-chain fatty acids (SCFAs) in patients with mild cognitive impairment (MCI) and normal controls (NCs) and to examine whether fecal SCFAs could be used as the biomarker for the identification of patients with MCI. To examine the relationship between fecal SCFAs and amyloid-ß (Aß) deposition in the brain. METHODS: A cohort of 32 MCI patients, 23 Parkinson's disease (PD) patients, and 27 NC were recruited in our study. Fecal levels of SCFAs were measured using chromatography and mass spectrometry. Disease duration, ApoE genotype, body mass index, constipation, and diabetes were evaluated. To assess cognitive impairment, we used the Mini-Mental Status Examination (MMSE). To assess brain atrophy, the degree of medial temporal atrophy (MTA score, Grade 0-4) was measured by structural MRI. Aß positron emission tomography with 18 F-florbetapir (FBP) was performed in seven MCI patients at the time of stool sampling and in 28 MCI patients at an average of 12.3 ± 0.4 months from the time of stool sampling to detect and quantify Aß deposition in the brain. RESULTS: Compared with NC, MCI patients had significantly lower fecal levels of acetic acid, butyric acid, and caproic acid. Among fecal SCFAs, acetic acid performed the best in discriminating MCI from NC, achieved an AUC of 0.752 (p = 0.001, 95% CI: 0.628-0.876), specificity of 66.7%, and sensitivity of 75%. By combining fecal levels of acetic acid, butyric acid, and caproic acid, the diagnostic specificity was significantly improved, reaching 88.9%. To better verify the diagnostic performance of SCFAs, we randomly assigned 60% of participants into training dataset and 40% into testing dataset. Only acetic acid showed significantly difference between these two groups in the training dataset. Based on the fecal levels of acetic acid, we achieved the ROC curve. Next, the ROC curve was evaluated in the independent test data and 61.5% (8 in 13) of patients with MCI, and 72.7% (8 in 11) of NC could be identified correctly. Subgroup analysis showed that reduced fecal SCFAs in MCI group were negatively associated with Aß deposition in cognition-related brain regions. CONCLUSION: Reductions in fecal SCFAs were observed in patients with MCI compared with NC. Reduced fecal SCFAs were negatively associated with Aß deposition in cognition-related brain regions in MCI group. Our findings suggest that gut metabolite SCFAs have the potential to serve as early diagnostic biomarkers for distinguishing patients with MCI from NC and could serve as potential targets for preventing AD.

The investigation of composition and thermal behavior of two types of backfilling gutta-percha.

Background/purpose: In the warm gutta-percha technique, soft-type and regular-type gutta-percha are using for backfilling thermoplasticized injection system. However, there are limited reports about the properties of these backfilling gutta-percha. This study aimed to analyze and compare the composition, thermal behavior and compact force of two types of backfilling gutta-percha. Materials and methods: Soft-type and regular-type backfilling gutta-percha (B&L BioTech, Fairfax, VA, USA) were investigated. The inorganic and organic fractions of these gutta-perchas were separated by quantitative chemical analysis (n = 6). Their composition was analyzed using energy dispersive spectroscopy. Thermal behavior in response to temperature variations was analyzed using differential scanning calorimetry. Additionally, a compaction model was used to investigate the relation between compaction force and temperature (n = 10). Results: The soft-type contained more gutta-percha (3.69-5.85%), carbon ratio (38.96-48.52%) and less inorganic substance (86.51-90.45%), zinc ratio (29.36-35.67%). The composition ratio of two types gutta-percha were statistically significant different (P < 0.05). There were three phase transitions of the soft-type gutta-percha which started at 39.84 °C, 49.32 °C and 54.15 °C while the two phase transitions of the regular-type gutta-percha started at 40.48 °C and 53.45 °C. The glass transition temperature of the regular-type gutta-percha (44.24 °C) was higher than that of the soft-type gutta-percha (40.66 °C). Under various setting temperature, the higher compaction force in the regular-type gutta-percha was required (P < 0.05). Conclusion: The different components in gutta-percha contribute to its differences in thermal behavior. The soft-type had a higher proportion of gutta-percha and lower ZnO which makes the fluidity better than the regular-type.

Shank Circumference Reduction by Sleep Compression Stockings in University Students and Convenience Store Cashiers.

Compression stockings (CSs) are a relatively simple and effective tool for alleviating varicose veins and are often used as a preventive measure among workers whose jobs require prolonged standing. Nevertheless, the efficacy of CSs that are advertised as sleepwear remains unverified. This study recruited 10 female university students and 10 cashiers as participants to test the effects of sleep CSs. During the experiment, the changes in shank circumference (SC) and the subjective discomfort rating upon getting up and going to bed were collected. Data were recorded immediately after getting up and SC measurement was repeated 10 min later. The results demonstrated that both CS condition and measurement time significantly affected SC reduction, whereas cashier or student status did not. The reported discomfort and tightness of the legs attributed to CSs were relatively high, and the benefit toward SC reduction was minimal. Cashiers exhibited slightly larger SC values and higher perceived discomfort levels, which may be attributed to their occupational characteristic of prolonged standing, and the cumulative effect of prolonged standing on muscle properties warrants further study. The study findings suggest that wearing CSs for sleep may not be effective for reducing OE.

Chronic Low-Level Cyanide Intoxication in an Electroplating Plant in Taiwan.

OBJECTIVE: This study aimed to investigate clinical symptoms among electroplating workers exposed to cyanide. METHODS: In this study, 26 silver-plating and 51 gold-plating workers completed questionnaires and were tested for urinary thiocyanates. Air cyanide, urinary thiocyanates, and clinical symptoms were compared between workers using Student t and χ 2 test and further analyzed by multivariate linear regression. RESULTS: Air cyanide and urinary thiocyanate were higher in the silver-plating plant than the gold-plating plant. In both plants, a dose-response relationship was observed between exposure status and thiocyanate levels. Silver-plating workers reported a higher frequency of almond odor detection, nasal bleeding, excessive salivation, skin scalding, and corrosion. Urinary thiocyanates were associated with the plant and exposure status, but not with smoking. CONCLUSIONS: Our study suggests that silver-plating workers had higher exposure and more symptoms. Urinary thiocyanate may be a useful biomarker for cyanide exposure.

Model-based dose selection to inform translational clinical oncology development of WNT974, a first-in-class Porcupine inhibitor.

WNT974 is a potent, selective, and orally bioavailable first-in-class inhibitor of Porcupine, a membrane-bound O-acyltransferase required for Wnt secretion, currently under clinical development in oncology. A phase I clinical trial is being conducted in patients with advanced solid tumors. During the dose-escalation part, various dosing regimens, including once or twice daily continuous and intermittent dosing at a dose range of 5-45 mg WNT974 were studied, however, the protocol-defined maximum tolerated dose (MTD) was not established based on dose-limiting toxicity. To assist in the selection of the recommended dose for expansion (RDE), a model-based approach was utilized. It integrated population pharmacokinetic (PK) modeling and exposure-response analyses of a target-inhibition biomarker, skin AXIN2 mRNA expression, and the occurrence of the adverse event, dysgeusia. The target exposure range of WNT974 that would provide a balance between target inhibition and tolerability was estimated based on exposure-response analyses. The dose that was predicted to yield an exposure within the target exposure range was selected as RDE. This model-based approach integrated PK, biomarker, and safety data to determine the RDE and represented an alternative as opposed to the conventional MTD approach for selecting an optimal biological dose. The strategy can be broadly applied to select doses in early oncology trials and inform translational clinical oncology drug development.

The Impact of COVID-19 on the Care of Patients With Noncommunicable Diseases in Low- and Middle-Income Countries: An Online Survey of Patient Perspectives.

We sought to gain insights into the impacts of COVID-19 and associated control measures on health and health care of patients from low- and middle-income countries with cardiovascular disease, diabetes, and mental health conditions, using an online survey during the COVID-19 pandemic. The most common concern for the 1487 patients who took part was contracting COVID-19 when they accessed health care. Of those infected with COVID-19, half said that their health had been worse since being infected. Collectively, most people reported an increase in feelings of stress and loneliness. The COVID-19 pandemic has led to a range of health care impacts on patients with noncommunicable diseases, including constraints on access to care and health effects, particularly mental well-being.

The impact of COVID-19 on the care of people living with noncommunicable diseases in low- and middle-income countries: an online survey of physicians and pharmacists in nine countries.

BACKGROUND: The global COVID-19 pandemic has disrupted healthcare worldwide. In low- and middle-income countries (LMICs), where people may have limited access to affordable quality care, the COVID-19 pandemic has the potential to have a particularly adverse impact on the health and healthcare of individuals with noncommunicable diseases (NCDs). A World Health Organization survey found that disruption of delivery of healthcare for NCDs was more significant in LMICs than in high-income countries. However, the study did not elicit insights into the day-to-day impacts of COVID-19 on healthcare by front-line healthcare workers (FLHCWs). AIM: To gain insights directly from FLHCWs working in countries with a high NCD burden, and thereby identify opportunities to improve the provision of healthcare during the current pandemic and in future healthcare emergencies. METHODS: We recruited selected frontline healthcare workers (general practitioners, pharmacists, and other medical specialists) from nine countries to complete an online survey (n = 1347). Survey questions focused on the impact of COVID-19 pandemic on clinical practice and NCDs; barriers to clinical care during the pandemic; and innovative responses to the many challenges presented by the pandemic. FINDINGS: The majority of FLHCWs responding to our survey reported that their care of patients had been impacted both adversely and positively by the public health measures imposed. Most FLHCs (95%) reported a deterioration in the mental health of their patients. CONCLUSIONS: Continuity of care for NCDs as part of pandemic preparedness is needed so that chronic conditions are not exacerbated by public health measures and the direct impacts of the pandemic.

Association of visual motor processing and social cognition in schizophrenia.

Patients with schizophrenia have difficulties in social cognitive domains including emotion recognition and mentalization, and in sensorimotor processing and learning. The relationship between social cognitive deficits and sensorimotor function in patients with schizophrenia remains largely unexplored. With the hypothesis that impaired visual motor processing may decelerate information processing and subsequently affects various domains of social cognition, we examined the association of nonverbal emotion recognition, mentalization, and visual motor processing in schizophrenia. The study examined mentalization using the verbal subset of the Chinese version of Theory of Mind (CToM) Task, an equivalent task of the Faux Pas Test; emotion recognition using the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and visual motor processing using a joystick tracking task controlled for basic motor function in 34 individuals with chronic schizophrenia in the community and 42 healthy controls. Patients with schizophrenia had significantly worse performance than healthy controls in social cognition, including facial, prosodic emotion recognition, and mentalization. Visual motor processing was also significantly worse in patients with schizophrenia. Only in patients with schizophrenia, both emotion recognition (mainly in prosodic modality, happy, and sad emotions) and mentalization were positively associated with their learning capacity of visual motor processing. These findings suggest a prospective role of sensorimotor function in their social cognitive deficits. Despite that the underlying neural mechanism needs further research, our findings may provide a new direction for restoration of social cognitive function in schizophrenia by enhancing visual motor processing ability.

A Methodology for Mapping the Patient Journey for Noncommunicable Diseases in Low- and Middle-Income Countries.

Noncommunicable diseases (NCDs) are responsible for 71% of all worldwide mortality each year, and have an exceptionally large impact in low- and middle-income countries (LMICs). However, there is often a lack of local data from these countries to inform practice and policy improvements. Generating locally contextualized evidence base for NCDs that can help identify gaps, aid decision-making and improve patient care in LMICs needs an innovative approach. The approach used in Mapping the Patient Journey Towards Actionable Beyond the Pill Solutions (MAPS) is designed to quantitatively map different stages of the patient journey in four critical NCDs, ie, hypertension, dyslipidemia, depression, and pain (chronic and neuropathic) across selected LMICs in Africa, the Middle East, South East Asia, and Latin America. The key touchpoints along the patient journey include awareness, screening, diagnosis, treatment, adherence, and control or remission. MAPS employs an evidence mapping methodology that follows a three-step semi-systematic review: 1) systematic peer-reviewed database search; 2) unstructured searches of local or real-world data; and 3) expert opinion. Evidence generation and visualization is based on locally validated and deduplicated data published over the last 10 years. This approach will be the first to provide quantitative mapping of the different stages of the patient journey for selected NCDs in LMICs. By focusing on local, patient-centric data, the goal of the MAPS initiative is to address and prioritize local research and knowledge gaps, then contribute to evidence-based, high-quality, and affordable advances in the management of NCDs in LMICs. This will ultimately improve patient outcomes and contribute towards the achievement of global NCD targets.

Renal Function-Dependent Associations of Statins with Outcomes of Ischemic Stroke.

AIM: Chronic kidney disease (CKD) is associated with unfavorable outcomes in patients with ischemic stroke. One major metabolic derangement of CKD is dyslipidemia, which can be managed by statins. This study aimed to investigate whether the association of statins with post-stroke outcomes would be affected by renal function. METHODS: We evaluated the association of statin therapy at discharge with 3-month outcomes according to the estimated glomerular filtration rate (eGFR) of 50,092 patients with acute ischemic stroke from the Taiwan Stroke Registry from August 2006 to May 2016. The outcomes were mortality, functional outcome as modified Rankin Scale (mRS), and recurrent ischemic stroke at 3 months after index stroke. RESULTS: Statin therapy at discharge was associated with lower risks of mortality (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.34 to 0.50) and unfavorable functional outcomes (mRS 3-5; aHR, 0.80; 95% CI, 0.76 to 0.84) in ischemic stroke patients. After stratification by eGFR, the lower risk of mortality associated with statins was limited to patients with an eGFR above 15 mL/min/1.73 m2. Using statins at discharge was correlated with a lower risk of unfavorable functional outcomes in patients with an eGFR of 60-89 mL/min/1.73 m2. Statin therapy in patients with an eGFR of 60-89 mL/min/1.73 m2 may be associated with a higher risk of recurrent ischemic stroke compared with nonusers (aHR, 1.29; 95% CI, 1.07 to 1.57). CONCLUSIONS: In patients with acute ischemic stroke, the associations of statins with mortality and functional outcomes was dependent on eGFR.

Effects of adding a concurrent cognitive task on manual dexterity in people with schizophrenia: Implications for performance of daily life activities.

This study investigated the effect of dual task performance of hand dexterity tasks and the relationship to daily functioning in 40 people with chronic schizophrenia and 35 healthy participants. Participants performed the Purdue Pegboard Test, O'Connor Finger Dexterity Test, and the Serial Subtracting Seven Task as the secondary task under single- and dual-task conditions and completed the Activities of Daily Living Rating Scale-III (ADLRS-III). The hand dexterity of all participants declined from the single to the dual tasks, and the discrepancy between single- and dual-task performance was significantly greater in the schizophrenia group than in the control group. Significant condition and group effects were found for both hand dexterity tests. People with schizophrenia who took longer time in performing hand dexterity tasks had significantly worse daily life function. Negative correlations were noted between discrepancy of dual tasking and the ADLRS-III score in the schizophrenic group. Deficits in dual-task performance of hand dexterity is significant in people with schizophrenia and is related to daily life performance. Occupational therapy practitioners can consider using dual tasks as a therapeutic activity for people with schizophrenia to promote functional abilities in real-world environments.

[Using Healthcare Failure Mode and Effects Analysis to Reduce Intra-Arterial Thrombectomy Preoperative Preparation Error Rates in the Emergency Room].

BACKGROUND & PROBLEMS: Intra-arterial thrombectomy (IAT) is a novel surgery that may restore cerebral blood flow in patients with ischemic stroke and lower the risks of permanent brain damage and disability. Because the process of preoperative preparation for IAT is complicated, error rates for this process have been reported in previous studies to be as high as 100%. Although these errors did not result in serious damage to patients, the risk to patient safety remains. Therefore, reducing the error rate for IAT preoperative preparation is necessary to improve patient safety. PURPOSE: To reduce the rate of IAT preoperative preparation error in an emergency room. RESOLUTION: This project applied healthcare failure mode and effect analysis (HFMEA) to evaluate the potential risks of IAT preoperative preparation in an emergency room. Based on the resultant hazard score, critical preventive measures were adopted, including creating a quick response code consent form, designing order packages, developing a checklist form, modifying stroke operating procedures and policies, planning suitable education content for staffs, developing criteria for evaluating preoperative preparation procedures, and installing vital signs equipment. RESULTS: After implementation of these measures, the hazard scores of 13 out of the 16 potential failure causes decreased to < 8, and the progress rate was 81.3%. The follow-up error rate for preoperative preparation was 0% in October 2019, which fulfilled the goal of this project. CONCLUSIONS: Preoperative preparation for IAT is complicated and time-consuming. In this project, HFMEA was introduced to ensure that preoperative preparation was accomplished in a complete and timely manner. Based on the results, after implementation, preparation work was effectively completed and operations were performed on schedule. Other hospitals may consider using this tool to evaluate potential risks to patient safety and to develop solutions to improve the quality of healthcare processes.

Relationship Among Sensory Over-Responsivity, Problem Behaviors, and Anxiety in Emerging Adults with Autism Spectrum Disorder.

INTRODUCTION: Despite the highly prevailing rate of sensory over-responsivity, problem behaviors, and anxiety among emerging adults with autism spectrum disorder (ASD), little is known about the nature of their experiences. While previous studies have indicated potential relationships among these conditions, their connections still need to be clarified. This study aimed to examine the relationships between sensory over-responsivity, problem behaviors, and anxiety. METHODS: Fifty-seven emerging adults with ASD (Mage = 21.4, SD = 2.5; males = 80.7%) were recruited. The Adult Sensory Profile - Chinese version, Problem Behavior Scale of Scales of Independent Behavior - Revised, and Generalized Anxiety Disorder-7 - Chinese version (GAD-7) were used. RESULTS: The percentage of emerging adults with ASD who scored more than most people in the two quadrants were sensation sensitivity = 33.3% and sensation avoiding = 26.3%. Approximately 66.7%, 27.5%, and 50.9% of participants had internalizing behaviors, externalizing behaviors, and asocial behaviors, respectively. Approximately, 64.9% of the participants scored on or above the cut-off score of 6 on the GAD-7. Sensation sensitivity and sensation avoiding were significantly correlated to problem behaviors; and anxiety was a mediating variable that accounts for the relationships between sensory over-responsivity and problem behaviors. CONCLUSION: These results indicated that emerging adults with ASD showing problem behaviors might also report more exaggerated responses toward sensory inputs and experience more anxiety symptoms. The results indicate that sensory over-responsivity, problem behaviors, and anxiety may have common underlying mechanisms. Findings can be useful to understand the impacts of such difficulties for emerging adults with ASD.

Plasma Exosomal Brain-Derived Neurotrophic Factor Correlated with the Postural Instability and Gait Disturbance-Related Motor Symptoms in Patients with Parkinson's Disease.

Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin, responsible for neuronal development, function, and survival. Assessments of peripheral blood BDNF in patients with Parkinson's disease (PD) previously yielded inconsistent results. Plasma exosomes can carry BDNF, so this study investigated the role of plasma exosomal BDNF level as a biomarker of PD. A total of 114 patients with mild to moderate PD and 42 non-PD controls were recruited, and their clinical presentations were evaluated. Plasma exosomes were isolated with exoEasy Maxi Kits, and enzyme-linked immunosorbent assay was used to assess plasma exosomal BDNF levels. Statistical analysis was performed using SPSS version 19.0, and findings were considered significant at p < 0.05. The analysis revealed no significant differences in plasma exosomal BDNF levels between patients with PD and controls. Patients with PD with low plasma exosomal BDNF levels (in the lowest quartile) exhibited a significant association with daily activity dysfunction but not with cognition/mood or overall motor symptoms as assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Investigation of UPDRS part III subitems revealed that low plasma exosomal BDNF level was significantly associated with increased motor severity of postural instability and gait disturbance (PIGD)-associated symptoms (rising from a chair, gait, and postural stability) after adjustment for age and sex. In conclusion, although plasma exosomal BDNF level could not distinguish patients with PD from controls, the association with PIGD symptoms in patients with PD may indicate its potential role as a biomarker. Follow-up studies should investigate the association between plasma exosomal BDNF levels and changes in clinical symptoms.