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Chien-Tzu Lee,1 Ping-Lun Hsieh,1,2 Meng-Yueh Chien,1 Jung-Yien Chien,3 Huey-Dong Wu,4 Jia-Shin Lin,1 Hsiao-Chen Lin,1 Pei-Yu Yang,2 Li-Ying Wang1,21School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, Taipei, Taiwan; 2Physical Therapy Center, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 4Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, TaiwanBackground: Pulmonary rehabilitation (PR) is now considered fundamental when managing patients with chronic respiratory disease. The individual variation in functional exercise capacity (FEC) response to PR within the cohort is unknown. The purpose of this study was to identify FEC patterns in response to PR in patients with chronic respiratory disease using the trajectory modeling method.Methods: The data of 67 patients with the chronic respiratory disease were retrospectively reviewed and analyzed in this study. All patients received once-weekly supervised training for 8 weeks. Six-minute walk distance (6MWD) was used to measure FEC. Muscle strength and 6MWD were assessed at baseline, Week 4, Week 8 and monthly for two months after PR completion. Group-based trajectory modeling (GBTM) was used to identify patterns in 6MWD in response to PR. The generalized estimating equation method was then used to detect the differences within and between the trajectories of identified groups across time.Results: Patients were grouped into low- (n=13), moderate- (n=34) and high- (n=20) FEC group based on GBTM analysis. All groups demonstrated significant improvements in 6MWD and leg muscle strength after 8-week PR. Compared to the high-FEC group, a greater proportion of the patients in the low-FEC group required oxygen supplementation during training and had worse baseline leg muscle strength.Conclusions: Patients showed distinct patterns of 6MWD changes in response to 8-week PR. Distinct characteristics for the low-FEC group included poor lower extremity strength and a greater proportion of required oxygen use at home and during training.Keywords: chronic respiratory disease, exercise training, functional exercise capacity, trajectory

Jing-Jhao Ye, Kuan-Ting Lee, Jing-Siang Lin, Chiung-Cheng Chuang Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li, Taiwan Abstract: Continuously monitoring and efficiently managing pain has become an important issue. However, no study has investigated a change in physiological parameters during the process of pain production/relief. This study modeled the process of pain production/relief using ramped thermal stimulation (no pain: 37°C water, process of pain production: a heating rate of 1°C/min, and subject feels pain: water kept at the painful temperature for each subject, with each segment lasting 10 min). In this duration, the variation of the heat rate variability and photoplethysmography-derived parameters was observed. A total of 40 healthy individuals participated: 30 in the trial group (14 males and 16 females with a mean age of 22.5±1.9 years) and 10 in the control group (7 males and 3 females with a mean age of 22.5±1.3 years). The results showed that the numeric rating scale value was 5.03±1.99 when the subjects felt pain, with a temperature of 43.54±1.70°C. Heart rate, R-R interval, low frequency, high frequency, photoplethysmography amplitude, baseline, and autonomic nervous system state showed significant changes during the pain production process, but these changes differed during the period Segment D (painful temperature 10: min). In summary, the study observed that physiological parameters changed qualitatively during the process of pain production and relief and found that the high frequency, low frequency, and photoplethysmography parameters seemed to have different responses in four situations (no pain, pain production, pain experienced, and pain relief). The trends of these variations may be used as references in the clinical setting for continuously observing pain intensity. Keywords: pain production, heart rate variability, photoplethysmography, thermal stimuli

Zhao Ma, Yong Yang,* JiSheng Lin, XiaoDong Zhang, Qian Meng, BingQiang Wang, Qi Fei* Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Purpose: To develop a simple new clinical screening tool to identify primary osteoporosis by dual-energy X-ray absorptiometry (DXA) in postmenopausal women and to compare its validity with the Osteoporosis Self-Assessment Tool for Asians (OSTA) in a Han Chinese population.Methods: A cross-sectional study was conducted, enrolling 1,721 community-dwelling postmenopausal Han Chinese women. All the subjects completed a structured questionnaire and had their bone mineral density measured using DXA. Using logistic regression analysis, we assessed the ability of numerous potential risk factors examined in the questionnaire to identify women with osteoporosis. Based on this analysis, we build a new predictive model, the Beijing Friendship Hospital Osteoporosis Self-Assessment Tool (BFH-OST). Receiver operating characteristic curves were generated to compare the validity of the new model and OSTA in identifying postmenopausal women at increased risk of primary osteoporosis as defined according to the World Health Organization criteria.Results: At screening, it was found that of the 1,721 subjects with DXA, 22.66% had osteoporosis and a further 47.36% had osteopenia. Of the items screened in the questionnaire, it was found that age, weight, height, body mass index, personal history of fracture after the age of 45 years, history of fragility fracture in either parent, current smoking, and consumption of three of more alcoholic drinks per day were all predictive of osteoporosis. However, age at menarche and menopause, years since menopause, and number of pregnancies and live births were irrelevant in this study. The logistic regression analysis and item reduction yielded a final tool (BFH-OST) based on age, body weight, height, and history of fracture after the age of 45 years. The BFH-OST index (cutoff =9.1), which performed better than OSTA, had a sensitivity of 73.6% and a specificity of 72.7% for identifying osteoporosis, with an area under the receiver operating characteristic curve of 0.797.Conclusion: BFH-OST may be a powerful and cost-effective new clinical risk assessment tool for prescreening postmenopausal women at increased risk for osteoporosis by DXA, especially for Han Chinese women. Keywords: women, osteoporosis, osteoporosis screening tool, validation

JiSheng Lin,* Yong Yang,* Qi Fei, XiaoDong Zhang, Zhao Ma, Qi Wang, JinJun Li, Dong Li, Qian Meng, BingQiang Wang Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Objective: This cross-sectional study compared three tools for predicting painful new osteoporotic vertebral fractures (PNOVFs) in older Chinese men: bone mineral density (BMD), the Osteoporosis Self-Assessment Tool for Asians (OSTA), and the World Health Organization fracture risk assessment tool (FRAX) (without BMD). Methods: Men aged ≥50 years were apportioned to a group for men with fractures who had undergone percutaneous vertebroplasty (n=111), or a control group of healthy men (n=385). Fractures were verified on X-ray and magnetic resonance imaging. BMD T-scores were determined by dual energy X-ray absorptiometry. Diagnosis of osteoporosis was determined by a BMD T-score of ≤2.5 standard deviations below the average for a young adult at peak bone density at the femoral neck, total hip, or L1–L4. Demographic and clinical risk factor data were self-reported through a questionnaire. BMD, OSTA, and FRAX scores were assessed for identifying PNOVFs via receiver-operating characteristic (ROC) curves. Optimal cutoff points, sensitivity, specificity, and areas under the ROC curves (AUCs) were determined. Results: Between the men with fractures and the control group, there were significant differences in BMD T-scores (at femoral neck, total hip, and L1–L4), and OSTA and FRAX scores. In those with fractures, only 53.15% satisfied the criteria for osteoporosis. Compared to BMD or OSTA, the FRAX score had the best predictive value for PNOVFs: the AUC of the FRAX score (cutoff =2.9%) was 0.738, and the sensitivity and specificity were 82% and 62%, respectively. Conclusion: FRAX may be a valuable tool for identifying PNOVFs in older Chinese men. Keywords: osteoporosis, male, vertebral fracture, FRAX, OSTA, bone mineral density

Geologic reservoirs containing gas hydrate occur beneath permafrost environments and within marine continental slope sediments, representing a potentially vast natural gas source. Numerical simulators provide scientists and engineers with tools for understanding how production efficiency depends on the numerous, interdependent (coupled) processes associated with potential production strategies for these gas hydrate reservoirs. Confidence in the modeling and forecasting abilities of these gas hydrate reservoir simulators (GHRSs) grows with successful comparisons against laboratory and field test results, but such results are rare, particularly in natural settings. The hydrate community recognized another approach to building confidence in the GHRS: comparing simulation results between independently developed and executed computer codes on structured problems specifically tailored to the interdependent processes relevant for gas hydrate-bearing systems. The United States Department of Energy, National Energy Technology Laboratory, (DOE/NETL), sponsored the first international gas hydrate code comparison study, IGHCCS1, in the early 2000s. IGHCCS1 focused on coupled thermal and hydrologic processes associated with producing gas hydrates from geologic reservoirs via depressurization and thermal stimulation. Subsequently, GHRSs have advanced to model more complex production technologies and incorporate geomechanical processes into the existing framework of coupled thermal and hydrologic modeling. This paper contributes to the validation of these recent GHRS developments by providing results from a second GHRS code comparison study, IGHCCS2, also sponsored by DOE/NETL. IGHCCS2 includes participants from an international collection of universities, research institutes, industry, national laboratories, and national geologic surveys. Study participants developed a series of five benchmark problems principally involving gas hydrate processes with geomechanical components. The five problems range from simple geometries with analytical solutions to a representation of the world's first offshore production test of methane hydrates, which was conducted with the depressurization method off the coast of Japan. To identify strengths and limitations in the various GHRSs, study participants submitted solutions for the benchmark problems and discussed differing results via teleconferences. The GHRSs evolved over the course of IGHCCS2 as researchers modified their simulators to reflect new insights, lessons learned, and suggested performance enhancements. The five benchmark problems, final sample solutions, and lessons learned that are presented here document the study outcomes and serve as a reference guide for developing and testing gas hydrate reservoir simulators.

Establishing the geomechanical stability of marine sediments in the vicinity of a production well is one of the key design considerations in planning offshore gas production from marine hydrate reservoirs. This paper presents an assessment of the sediment stability at India's National Gas Hydrate Program, Expedition 2 (NGHP-02) Site 16 Area B offshore eastern India, for which gas production is to be carried out by depressurization. One important feature of the study is that extensive calibration of constitutive model parameters has been conducted based on laboratory test data from pressured core samples. From analysis perspective, the site is challenging because the hydrate reservoir consists of thin layers of hydrate-bearing sands interbedded with mud. Moreover, depressurization at the depth of a reservoir more than 2750 m below sea surface will lead to a pore pressure drop, and accordingly an effective confining stress increase as high as 25 MPa. In dealing with thin interbedded hydrate-bearing strata, meshing requirements for flow and geomechanical analysis are quite different from those for reservoirs with thicker massive layers, An axisymmetric model and one-way coupling simulations were thus adopted for this study, in which the geomechanical study utilizes pore pressure and hydrate saturation output from the flow study, but the flow study does not takes the porosity changes from the geomechanical analysis. Instead, the reduction of porosity due to sediment deformation in the flow study is based on a pressure-dependent pore compressibility relationship derived from geomechanical modeling. The rationality is validated through back computing the pore compressibility from the geomechanical deformation results. The study shows that large compression in the reservoir will result in movement of the sediments from above and below, as well as laterally in smaller magnitudes; and the sediment is deemed stable during the gas production period.

Background: Screening programs using conventional cytology have successfully reduced cervical cancer, but newer tests might enhance screening. Purpose: To systematically review the evidence on liquid-based cytology (LBC) and high-risk human papillomavirus (HPV) screening for U.S. Preventive Services Task Force use in updating its 2003 recommendation. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2000 through September 2010. Study Selection: Two independent reviewers selected fair- to good-quality English-language studies that compared LBC or HPV-enhanced primary screening with conventional cytology in countries with developed population-based screening for cervical cancer. Data Extraction: At least 2 independent reviewers critically appraised and rated the quality of studies and used standardized abstraction forms to extract data about test performance for detecting cervical intraepithelial neoplasia (CIN) and cancer and screening-related harms. Data Synthesis: On the basis of 4 fair- to good-quality studies (141 566 participants), LBC had equivalent sensitivity and specificity to conventional cytology. Six fair- to good-quality diagnostic accuracy studies showed that 1-time HPV screening was more sensitive than cytology for detecting CIN3+/CIN2+ but was less specific. On the basis of 2 fair- to good-quality randomized, controlled trials (RCTs) (120 533 participants), primary HPV screening detected more cases of CIN3 or cancer in women older than 30 years. Four fair- to good-quality diagnostic accuracy studies and 4 fair- to good-quality RCTs showed mixed results of cotesting (HPV plus cytology) in women aged 30 years or older compared with cytology alone, with no clear advantage over primary HPV screening. Incomplete reporting of results for all screening rounds, including detection of disease and colposcopies, limits our ability to determine the net benefit of HPV-enhanced testing strategies. Limitation: Resources were insufficient to gather unpublished data, short-term trial data showed possible ascertainment bias, and most RCTs used protocols that differed from current U.S. practice. Conclusion: Evidence supports the use of LBC or conventional cytology for cervical cancer screening, but more complete evidence is needed before HPV-enhanced primary screening is widely adopted for women aged 30 years or older. Primary Funding Source: Agency for Healthcare Research and Quality. [ABSTRACT FROM AUTHOR]

A review of outcomes in 13 patients with talar dome osteochondral or chondral lesions treated with a bone graft substitute plug was undertaken in an effort to evaluate its effectiveness in comparison with other reported surgical techniques. Mean patient age was 36.4 (range 16 to 57) years. Mean follow-up was 30.1 (range 7 to 43) months. Medial malleolar osteotomy was performed in 9 (69.23%) cases. Average defect diameter was 9.8 (range 5 to 20) mm. Pain decreased significantly from 6.2 (range 3 to 9) to 4.0 (range 0 to 9) (P = .009). Postoperative American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scores averaged 67.3 (range 26 to 100). Younger age, smaller defect size, and avoidance of medial malleolar osteotomy resulted in better outcomes. Mean Short Form-36 scores for the study group fell below US norms in all categories, and 12 (92.31%) ankles demonstrated persistent lesions radiographically. Postoperative magnetic resonance imaging in 2 (15.39%) patients demonstrated enlarged lesions, and 4 (30.77%) patients underwent revision surgery that revealed abnormal cartilage around the implant site. Complications included 1 (7.69%) deep venous thrombosis, 1 (7.69%) arthrofibrosis, and 1 (7.69%) superficial neuritis. Despite some improvement in pain, comparison of functional outcome showed bone graft substitute plug implantation to be less effective overall than other operative interventions. Future investigations with more specific selection criteria are warranted to gain further insight into the efficacy of these bone graft substitute plugs. [ABSTRACT FROM AUTHOR]

Previous work from our laboratory has demonstrated that the percentage differences of 2nd (C2) and 3rd (C3) pulse harmonics related to Kidney and Spleen were both increased toward another steady state in rats after acute hemorrhage. Therefore, it is suggested that changes in pulse spectra might represent the ability of animals to survive a model of progressive hemorrhage. In this study, the difference of the pulse spectra patterns between survivors and non-survivors after progressive hemorrhage (by loss of 5%, 10% or 20% of the estimated blood volume) in anesthetized rats is determined. Seven rats, dead within 2 hours after a loss of 20% of the estimated blood volume hemorrhage, were defined as 'non-survivors'. The other eleven rats, more than 2 hours after hemorrhage, were defined as 'survivors'. Pulse waves of arterial blood pressure before and after the hemorrhage were measured in parallel to the pulse spectrum analysis. Data among different phases were analyzed using one-way analysis of variance (ANOVA) with Duncan's test for pairwise comparisons. Differences between survivor and non-survivor groups at each phase were analyzed using Student's t-test. A mixed-effects linear regression model was applied to evaluate the relationship in harmonics, which significantly differed between the two groups. The study results showed that in rats, during progressive hemorrhage, the percentage differences of 2nd harmonic proportion increased significantly; however, the result failed to show any significant difference between survivors and non-survivors. After the third blood withdrawal process, the percentage differences of 3rd harmonic proportion increased more significantly in the survivors. In addition, the percentage differences of 1st harmonic proportion related to the Liver for the survivor group was significantly lower than that of the non-survivors. After analysis with the mixed linear regression model, C3 and C1 demonstrated a linear regression relationship, and there existed significant differences between survivors and non-survivors. These results suggest that C3 might play an important role in physiology regarding surviving capability after progressive hemorrhage. [ABSTRACT FROM AUTHOR]

A novel and facile method for the synthesis of Ga and GaN quantum dots in the channelsof mesoporous silicon materials, designated as an in situ and low-temperature nitrificationmethod, is described. In this method, the Si–H functional groups were directly introducedinto the channels of SBA-15 mesoporous materials resulting in highly dispersed Gananoparticles on the pore walls of the matrix, which can be nitrified easily under relativelylower temperature. [ABSTRACT FROM AUTHOR]

In order to assess the prevalence of erectile dysfunction (ED), and its association with chronic diseases and impact upon sexual activity and satisfaction during sexual intercourse, a reproductive survey was conducted among 1002 Taiwanese men aged over 40?y. The information collected comprised age, gender, level of education, history of chronic diseases, and self-reported data pertaining to erectile function, sexual activity, and sexual satisfaction during sexual intercourse. The prevalence of ED amongst study subjects was 17.7%, and the frequency increased with age. A history of chronic diseases were significantly associated with ED (P<0.05). A reduced incidence of sexual activity and a decreased level of satisfaction during sexual intercourse were observed among subjects suffering from ED as compared to those not suffering such a condition. In conclusion, based upon the results of a community-based survey the prevalence of ED among Taiwanese men aged 40?y or more was 17.7% and it increased with age. It was also found that ED was associated with various chronic diseases and that it exerted a negative impact upon sexual activity and the level of satisfaction associated with its conduct.International Journal of Impotence Research (2004) 16, 249-255. doi:10.1038/sj.ijir.3901218 Published online 25 March 2004 [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Case study. OBJECTIVE: We present an unusual case of cauda equina syndrome due to a penetrating injury in which the brake caliper of a motorcycle lodged in the lumbar canal of the operator of the vehicle after a road accident and provide a review of the literature on penetrating injury to the spine. SUMMARY OF BACKGROUND DATA: While the large majority of penetrating spinal injuries are due to gunshot wounds, penetrating injury to the spine causing cauda equina syndrome is rare. METHODS: We report the case of a 42-year-old man involved in a motorcycle accident in which the brake caliper penetrated the lumbar region and entered the lumbar canal through the interlaminar space between L2 and L3. He had a complete motor and sensory deficit in the lower extremities with absent rectal tone. The patient was taken urgently to the operating room and underwent removal of the foreign object and repair of a dural laceration. He was treated with a course of intravenous antibiotics. RESULTS: The wound healed without evidence for cerebrospinal fluid leakage or infection. The patient made a good neurologic recovery, becoming ambulatory with bowel and bladder continence at 5 months following the injury. CONCLUSIONS: Surgical removal of foreign object resulted in resolution of cauda equina syndrome injury. [ABSTRACT FROM AUTHOR]

Background: One key population related to achieving the global goal of hepatitis C virus (HCV) elimination is people who inject drugs (PWID). By surveying opioid agonist treatment (OAT) programs nationwide in Taiwan, this study aimed to examine (1) the current status of HCV care cascade provision by OAT programs and (2) the opinions of the programs' directors on integrating the HCV care cascade into OAT programs., Methods: From September to November 2022, questionnaires were sent via administrative networks to case managers for information on daily operation and routine booking and to directors for information on the HCV care cascade of 185 OAT programs. The responses of the 125 OAT programs that provided information from both case managers and directors were included for subsequent analyses., Results: Among the 125 OAT programs, 91 (73 %) offered HCV antibody testing, and 69 (55 %) offered HCV treatment services. The provision of HCV antibody testing was associated with being general hospital- or psychiatric hospital-based and having more care team personnel, whereas the provision of HCV treatment was associated with being general hospital-based. However, on-site HCV treatment was found to be rarely offered, and the future willingness to do so remained low., Conclusion: Our survey revealed that the provision of HCV screening and treatment in OAT programs in Taiwan has substantial room for improvement. Increasing the number of care personnel for satellite-dispensing OAT programs is key to expanding the service for HCV screening, as more issues related to multidisciplinary medical resources are involved in the provision of HCV treatment. Our results point to some options that might help accomplish these goals., Competing Interests: Declaration of competing interest We declare that we have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study explores the impact of SYNLAC Prime probiotics on the growth performance, health status, and metabolic profile of white shrimp, Penaeus vannamei. Shrimp fed with the experimental diets, including the control diet without probiotic supplementation, and the diets supplemented with SYNLAC Prime probiotics at concentrations of 10 5  CFU (g diet) -1 (P5) and 10 6  CFU (g diet) -1 (P6) for 56 days. Results indicated a significant enhancement in growth performance in probiotic-treated shrimp relative to the control group, attributed to structural improvements in the digestive tract, particularly the increased abundances of B cells in the hepatopancreas. The administration of dietary probiotics markedly reduced the severity of Enterocytozoon hepatopenaei (EHP) infection and decreased cumulative mortalities following Vibrio alginolyticus challenge. Shrimp in the P6 group exhibited significant elevations in phenoloxidase activity, respiratory burst, lysozyme activity and phagocytic activity compared to control group. Furthermore, there was an upregulation of several immune-related genes in hepatopancreas, including serine protease (SP), prophenoloxidase (proPO) I, proPO II, and penaeidin 3a. Additionally, the expression of β-1, 3-glucan binding protein and SP mRNA was significantly increased in hemocytes. Untargeted metabolomics analysis using LC-MS/MS revealed significant changes in the hepatopancreas metabolic profile, highlighting alterations in energy metabolisms pathways, such as citrate cycle and nicotinate and nicotinamide metabolism, as well as amino acid metabolisms pathways including arginine and proline metabolism, taurine and hypotaurine metabolism, and histidine metabolism. These findings underscore the potential of SYNLAC Prime probiotics in enhancing shrimp growth, immune function, and metabolic pathways, offering valuable insights for advancing health management strategies in shrimp aquaculture., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Recovery from SARS CoV-2 infection is expected within 3 months. Long COVID occurs after SARS-CoV-2 when symptoms are present for more than 3 months that are continuous, relapsing and remitting, or progressive. Better understanding of Long COVID illness trajectories could strengthen patient care and support., Methods: We characterized functional impairments, quality of life (QoL), and cognition among patients who recovered from SARS-CoV-2 infection within 3 months (without Long COVID), after 3 months (Recovered Long COVID), or remained symptomatic (Long COVID). Among 7305 patients identified with previous SARS-CoV-2 infection between March 2020 and December 2021, confirmed in the medical record with laboratory test or physician diagnosis, 435 (6%) completed a single self-administered survey between March 2022 and September 2022. Multi-domain QoL and cognitive concerns were evaluated using PROMIS-29 and the Cognitive Change Index-12., Results: Nearly half the participants (47.7%) were surveyed more than 2 years from initial infection (median = 23.3 months; IQR = 18.6, 26.7) and 86.7% were surveyed more than 1 year from infection. A significantly greater proportion of the Long COVID (n = 215) group, (Current and Recovered combined), had moderate-to-severe impairment in all health domains assessed compared to those Without Long COVID (n = 220; all p < 0.05). The Recovered Long COVID group (n = 34) had significantly lower prevalence of fatigue, pain, depression, and physical and social function impairment compared to those with Current Long COVID (n = 181; all p < 0.05). However, compared to patients Without Long COVID, the Recovered Long COVID group had greater prevalences of fatigue, pain (p ≤ 0.06) and subjective cognitive decline (61.8% vs 29.1%; p < 0.01). Multivariate relative risk (RR) regression indicated Long COVID risk was greater for older age groups (RR range 1.46-1.52; all p ≤ 0.05), those without a bachelor's degree (RR = 1.33; 95% CI = 1.03-1.71; p = 0.03), and those with 3 or more comorbidities prior to SARS-CoV-2 infection (RR = 1.45; 95% CI = 1.11-1.90; p < 0.01)., Conclusions: Long COVID is associated with long-term subjective cognitive decline and diminished quality of life. Clinically significant cognitive complaints, fatigue, and pain were present even in those who reported they had recovered from Long COVID. These findings have implications for the sustainability of participation in work, education, and social activities., (© 2024. The Author(s).)

Importance: Oral anticoagulation for adults with atrial fibrillation or atrial flutter (AFF) who are at elevated stroke risk reduces the incidence of ischemic stroke but remains underused. Efforts to increase anticoagulation initiation on emergency department (ED) discharge have yielded conflicting results., Objective: To evaluate the effectiveness of a multipronged intervention supporting anticoagulation initiation for eligible adult ED patients., Design, Setting, and Participants: The Clinical Decision Support to Optimize Care of Patients With Atrial Fibrillation or Flutter in the Emergency Department (O'CAFÉ) pragmatic, stepped-wedge cluster randomized clinical trial was conducted from July 1, 2021, through April 30, 2023, at 13 community medical centers (in 9 clusters) of an integrated health system in Northern California. The study included adult ED patients with primary AFF eligible for anticoagulation initiation when discharged home. Clusters were randomly assigned to staggered dates for 1-way crossover from the control phase (usual care) to the intervention phase., Intervention: Physician education, facility-specific audit and feedback, and access to decision support, which identified eligible patients and recommended shared decision-making, anticoagulation initiation (if suitable), and timely follow-up., Main Outcomes and Measures: The main outcome was a composite of anticoagulation on discharge or within 30 days. A primary intention-to-treat analysis (decision support access regardless of use) and a secondary per-protocol analysis (decision support use) were performed. Multivariable analyses adjusted for intervention and exposure months with random effects, accounting for clustering by facility and patient., Results: A total of 3388 eligible patients with atrial fibrillation were discharged home: 2185 (64.5%) were receiving pre-ED arrival anticoagulation and 1203 (35.5%) were eligible for anticoagulation. Among the 1203 patients with an initiation-eligible encounter, the median age was 74.0 (IQR, 68.0-82.0) years and approximately half (618 [51.4%]) were men. Among the 387 patients with an initiation-eligible control encounter, 244 (63.0%) received anticoagulation (190 [49.0%] at discharge and 54 [14.0%] within 30 days). Among the 816 patients with an initiation-eligible intervention encounter, 558 (68.4%) received anticoagulation (428 [52.5%] on discharge and 130 [15.9%] within 30 days). There was no statistically significant change in initiation of anticoagulation associated with the intervention (adjusted odds ratio, 1.33 [95% CI, 0.75-2.35]; P = .13). Decision support was used for 217 eligible case patients (26.6%) (per protocol) and was associated with a statistically significant change in anticoagulation initiation when compared with 599 patients for whom decision support was not used (164 [75.6%] vs 394 [65.8%]; P = .008)., Conclusions and Relevance: In this trial, a multipronged intervention to facilitate thromboprophylaxis among eligible ED patients with AFF did not significantly increase anticoagulation initiation. Opportunities exist to further improve stroke prevention among ED patients with primary AFF., Trial Registration: ClinicalTrials.gov Identifier: NCT05009225.

Introduction: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) experience cognitive problems with attention, information processing speed, working memory, learning efficiency, and executive function. Commonly, patients report worsening of cognitive symptoms over time after physical and/or cognitive challenges. To determine, monitor, and manage longitudinal decrements in cognitive function after such exposures, it is important to be able to screen for cognitive dysfunction and changes over time in clinic and also remotely at home. The primary objectives of this paper were: (1) to determine whether a brief computerized cognitive screening battery will detect differences in cognitive function between ME/CFS and Healthy Controls (HC), (2) to monitor the impact of a full-day study visit on cognitive function over time, and (3) to evaluate the impact of exercise testing on cognitive dysfunction., Methods: This cognitive sub-study was conducted between 2013 and 2019 across seven U.S. ME/CFS clinics as part of the Multi-Site Clinical Assessment of ME/CFS (MCAM) study. The analysis included 426 participants (261 ME/CFS and 165 HC), who completed cognitive assessments including a computerized CogState Brief Screening Battery (CBSB) administered across five timepoints (T0-T4) at the start of and following a full day in-clinic visit that included exercise testing for a subset of participants (182 ME/CFS and 160 HC). Exercise testing consisted of ramped cycle ergometry to volitional exhaustion. The primary outcomes are performance accuracy and latency (performance speed) on the computerized CBSB administered online in clinic (T0 and T1) and at home (T2-T4)., Results: No difference was found in performance accuracy between ME/CFS and HCs whereas information processing speed was significantly slower for ME/CFS at most timepoints with Cohen's d effect sizes ranging from 0.3-0.5 ( p < 0.01). The cognitive decline over time on all CBSB tasks was similar for patients with ME/CFS independent of whether exercise testing was included in the clinic visit., Conclusion: The challenges of a clinic visit (including cognitive testing) can lead to further cognitive deficits. A single short session of intense exercise does not further reduce speed of performance on any CBSB tasks., Competing Interests: AK was employed by Basis Diagnostics, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lange, Lin, Chen, Fall, Peterson, Bateman, Lapp, Podell, Natelson, Kogelnik, Klimas and Unger.)

Objective: Systematic reviews hold immense promise as tools to highlight evidence-based practices that can reduce or aim to eliminate racial health disparities. Currently, consensus on centering racial health equity, in systematic reviews and other evidence synthesis products is lacking. Centering racial health equity implies concentrating or focusing attention on health equity in ways that bring attention to the perspectives or needs of groups that are typically marginalized., Study Design and Setting: This Cochrane US Network team and colleagues, with the guidance of a steering committee, sought to understand the views of varied interest holders through semi-structured interviews, and conducted evidence syntheses addressing (1) definitions of racial health equity, (2) logic models and frameworks to center racial health equity, (3) interventions to reduce racial health inequities, and (4) interest holder engagement in evidence syntheses. Our methods and teams include a primarily American and Canadian lens; however, findings and insights derived from this work are applicable to any region in which racial or ethnic discrimination and disparities in care due to structural causes exist., Results: In this series, we explain why centering racial health equity matters, what gaps exist and may need to be prioritized. The interviews and systematic reviews identified numerous gaps to address racial health equity that require changes not merely to evidence synthesis practices but also to the underlying evidence ecosystem. These changes include increasing representation, establishing foundational guidance (on definitions and causal mechanisms and models, building a substantive evidence base on racial health equity, strengthening methods guidance, disseminating and implementing results, and sustaining new practices)., Conclusion: Centering racial health equity requires consensus on the part of key interest holders. As part of the next steps in building consensus, the manifold gaps identified by this series of papers need to be prioritized. Given resource constraints, changes in norms around systematic reviews are most likely to occur when evidence-based standards for success are clearly established and the benefits of centering racial health equity are apparent., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Chronic overlapping pain conditions (COPCs), pain-related conditions that frequently occur together, may occur in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and could impact illness severity. This study aimed to identify comorbid COPCs in patients with ME/CFS and evaluate their impact on illness severity., Methods: We used data from 923 participants in the Multi-Site Clinical Assessment of ME/CFS study, conducted in seven U.S. specialty clinics between 2012 and 2020, who completed the baseline assessment (595 ME/CFS and 328 healthy controls (HC)). COPCs included chronic low back pain (cLBP), chronic migraine/headache (cMHA), fibromyalgia (FM), interstitial cystitis/irritable bladder (IC/IB), irritable bowel syndrome (IBS), temporomandibular disorder (TMD). Illness severity was assessed through questionnaires measuring symptoms and functioning. Multivariate analysis of variance and analysis of covariance models were used for analyses. Log-binomial regression analyses were used to compute prevalence of COPCs and prevalence ratios (PR) between groups with 95% confidence intervals. Both unadjusted and adjusted results with age and sex are presented., Results: 76% of participants with ME/CFS had at least one COPCs compared to 17.4% of HC. Among ME/CFS participants, cMHA was most prevalent (48.1%), followed by FM (45.0%), cLBP (33.1%), and IBS (31.6%). All individual COPCs, except TMD, were significantly more frequent in females than males. The unadjusted PR (ME/CFS compared to HC) was highest for FM [147.74 (95% confidence interval (CI) = 20.83-1047.75], followed by cLBP [39.45 (12.73-122.27)], and IC/IB [13.78 (1.88-101.24)]. The significance and order did not change after age and sex adjustment. The COPC comorbidities of cLBP and FM each had a significant impact on most health measures, particularly in pain attributes (Cohen's d effect size 0.8 or larger). While the impact of COPC comorbidities on non-pain attributes and quality of life measures was less pronounced than that on pain, statistically significant differences between ME/CFS participants with and without COPCs were still evident., Conclusions: More than 75% of ME/CFS participants had one or more COPCs. Multiple COPCs further exacerbated illness severity, especially among females with ME/CFS. Assessment and management of COPCs may help improve the health and quality of life for patients with ME/CFS., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Efforts to develop disease-modifying treatments for Parkinson's disease (PD) have been hindered by the lack of animal models replicating all hallmarks of PD and the insufficient attention to extra-nigrostriatal regions pathologically critical for the prodromal appearance of non-motor symptoms. Among PD models, 6-hydroxydopamine (6-OHDA) infusion in mice has gained prominence since 2012, primarily focusing on the nigrostriatal region. This study characterized widespread tyrosine hydroxylase-positive neuron and fiber loss across the brain following a unilateral 6-OHDA (20 μg) infusion into the dorsal striatum. Our analysis integrates immunolabeling, brain clearing (iDISCO+), light sheet microscopy, and computational methods, including fMRI and machine learning tools. We also examined sex differences, disease progression, neuroinflammatory responses, and pro-apoptotic signaling in nigrostriatal regions of C57BL/6 mice exposed to varying 6-OHDA dosages (5, 10, or 20 μg). This comprehensive, spatiotemporal analysis of 6-OHDA-induced pathology may guide the future design of experimental PD studies and neurotherapeutic development., Competing Interests: Declarations Competing interests BH is a member of the Scientific Advisory Boards of Osmind and Journey Clinical, and is a paid consultant to Arcadia Medicine, Inc.