Clinical Utility of Plantar Pressure Measurements as Screening in Patients With Parkinson Disease With and Without Freezing of Gait History.

OBJECTIVE: To test the feasibility of objective assessments using the TekScan MatScan pressure mat plantar pressure measurement as a time-effective screening service for Parkinson disease (PD) with and without freezing of gait (FOG) history. DESIGN: Prospective cross-sectional study. SETTING: Largest medical center in southern Taiwan. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Plantar pressure measurements including average peak pressure (PP), contact area (CA), and pressure-time integral (PTI) in static and dynamic conditions as well as clinical scores during off-medication states. PARTICIPANTS: A total of 103 patients with PD and 22 age- and sex-matched volunteers without PD (N=125). RESULTS: Plantar pressure assessment including PP, CA, and PTI on the total foot areas between participants with PD and controls without PD in the static conditions are similar. Patients with PD presented higher PTI on total foot areas as well as hallux, midfoot area, and medial and lateral heels during dynamic conditions than controls without PD. The PP, CA, and PTI during the static condition and CA during the dynamic condition on the hallux showed statistical significance between PD with and without FOG history. Stepwise logistic regression after controlling with age and body mass index showed only PTI on hallux (static conditions) was significantly associated with the presence of FOG. The receiver operating characteristic curve analysis in diagnostic accuracy for FOG in PTI was statistically significant (P=.002; area under the curve, 0.71). CONCLUSIONS: FOG screening using the TekScan MatScan pressure mat plantar pressure measurement could serve as a time-effective screening service at the outpatient clinic. Based on our study, PTI may be valuable in auxiliary diagnosis.

Factors associated with subclinical inflammation of wrist joints in rheumatoid arthritis patients with low or no disease activity- a RA ultrasound registry study.

BACKGROUND: To evaluate the factors to predict subclinical inflammation of wrist joints in patients with RA who are in clinical remission or low disease activity. METHODS: Gray scale and power Doppler ultrasound were performed on the dorsal radio-lunate of both wrists. The presence of synovitis, comorbidities, and use of disease modifying anti-rheumatic drugs were recorded. A Multivariable forward logistical regression model was used to identify factors associated with subclinical inflammation. RESULTS: There were 1248 patients (1010 females, 238 males; mean age: 60.0 ± 10.5 years ). 57.4% of patients in complete remission and low disease activity had sonographic inflammation. Multivariable forward logistic regression analysis indicated that male sex, smoking are positively associated with inflammation and that age, alcohol consumption, and use of methotrexate, glucocorticoid, or a biological therapy are negatively associated with inflammation. Use of biological agents decreased the risk of inflammation by 40.9%. CONCLUSIONS: There was evidence of subclinical inflammation in most patients who were in low or no disease activity, those with biological therapy had lower risk of subclinical inflammation.

Leptin mediate central obesity on the severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes.

BACKGROUND: Evidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes. METHODS: The complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value). RESULTS: A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P < 0.0001) and the CASS value (r = 0.36, P < 0.0001). Further mediation analysis shows that leptin level serves as mediators between higher WC and higher CASS. CONCLUSIONS: Our results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.

The impact of long-term biologics/target therapy on bone mineral density in rheumatoid arthritis: a propensity score-matched analysis.

OBJECTIVES: To investigate changes in BMD in RA patients receiving 3-year biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or conventional synthetic DMARD (csDMARD). METHODS: Patients with RA were recruited from September 2014 until March 2019. Clinical characteristics, BMD and evidence of fragility fractures at enrolment were documented. Participants were treated according to the National Institute for Health and Care Excellence (NICE) guidelines over a 3-year observation period. Repeated BMD was measured at the end of the study period. Participants were grouped into those receiving b/tsDMARD or csDMARD and by propensity score matching (1:2). RESULTS: A total of 388 participants completed the 3-year follow-up. After propensity score matching, 92 and 184 participants were allocated to the b/tsDMARD (Group I) and csDMARD (Group II), respectively. After 3 years, BMD remained stable at the femoral neck (FN), hip (total) (TH) and lumbar vertebra (L1-4) (P =0.09, 0.15, 0.87) in Group I. However, BMD decreased significantly in Group II (P=0.045, <0.001, 0.004) at corresponding sites. Participants receiving combined b/tsDMARD and anti-osteoporosis therapy experienced a greater BMD preserving effect than other subgroups. CONCLUSION: Long-term b/tsDMARDs therapy had protective effects on bone loss for patients with RA. Patients receiving concomitant anti-osteoporosis therapy and b/tsDMARDs therapy experienced the greatest BMD preserving effect.

Sural nerve sensory response in diabetic distal symmetrical polyneuropathy.

INTRODUCTION: The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS: Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS: Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P < .0001), and changes in sural SNAP amplitudes were negatively correlated with those of CAS after controlling for follow-up duration (r = -.531, P = .028). DISCUSSION: When a patient's baseline sural SNAP amplitude is above zero, it can be used as one measure of DSPN in screening, severity evaluation, and follow-up. However, if the patient's sural SNAP value is zero, CAS can be used as a follow-up measure.

Novel algorithm generating strategy to identify high fracture risk population using a hybrid intervention threshold.

INTRODUCTION: The aim of this study was to develop an algorithm to identify high-risk populations of fragility fractures in Taiwan. MATERIALS AND METHODS: A total of 16,539 postmenopausal women and men (age ≥ 50 years) were identified from the Taiwan Osteoporosis Survey database. Using the Taiwan FRAX® tool, the 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) and the individual intervention threshold (IIT) of each participant were calculated. Subjects with either a probability above the IIT or those with MOF ≥ 20% or HF ≥ 9% were included as group A. Subjects with a bone mineral density (BMD) T-score at femoral neck based on healthy subjects of ≤ - 2.5 were included in group B. We tested several cutoff points for MOF and HF so that the number of patients in group A and group B were similar. A novel country-specific hybrid intervention threshold along with an algorithm was generated to identify high fracture risk individuals. RESULTS: 3173 (19.2%) and 3129 (18.9%) participants were categorized to groups A and B, respectively. Participants in group B had a significantly lower BMD (p < 0.001), but clinical characteristics, especially the 10-year probability of MOF (p < 0.001) or HF (p < 0.001), were significantly worse in group A. We found the algorithm generated from the hybrid intervention threshold is practical. CONCLUSION: The strategy of generating an algorithm for fracture prevention by novel hybrid intervention threshold is more efficient as it identifies patients with a higher risk of fragility fracture and could be a template for other country-specific policies.

Adherence to anti-osteoporosis medication associated with lower mortality following hip fracture in older adults: a nationwide propensity score-matched cohort study.

BACKGROUND: We investigated the association of anti-osteoporosis medication with mortality risk in older adults with hip fractures and evaluated the influence of medication adherence on mortality. METHODS: We conducted a population-based cohort study and identified a total of 13,123 patients aged 65 years or older with hip fracture from the Taiwan National Health Insurance Database during the period 2001-2010. Individuals with (n = 2092) and without (n = 2092) receiving anti-osteoporosis medication were matched using propensity score matching (1:1 ratio). The 1-, 3- and 5-year survival rates after the index fracture were compared between patients with and without treatment. In the treated group, survival rate was compared between those with good and non-adherence. Good adherence was defined as the medication possession ratio of ≥80% and non-adherence as a ratio < 80%. RESULTS: The 1-, 3- and 5-year mortality rates were significantly lower in the treated vs. the non-treated group (all p < 0.0001). In the treated group, the estimated 1-, 3- and 5-year survival rates were higher in those with good adherence than in those with non-adherence (all p < 0.0001). Regarding all-cause mortality, the adjusted hazard ratio in the treated vs. the non-treated group was 0.63 (95% confidence interval 0.58-0.68, p < 0.0001). The good adherence subgroup showed a significantly lower mortality risk than that in the non-adherence subgroup (hazard ratio 0.41, 95% confidence interval 0.32-0.51, p < 0.0001). CONCLUSIONS: The 1-, 3- and 5-year survival rates were significantly higher in patients receiving anti-osteoporosis medication than in the untreated group. All-cause mortality rates were lower in patients with good adherence to anti-osteoporosis medication.

Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus: a nested case-control study.

Objectives: Immunosuppressive therapy is necessary to alter the natural course of SLE. However, immunosuppressant-related cancer risk is a major concern. The aim of this study was to determine whether immunosuppressant use is associated with cancer risk in SLE. Methods: We designed a retrospective nested case-control study within an SLE population based on the National Health Insurance Research Database in Taiwan. We screened 14 842 patients with SLE from 2001 to 2013 and compared patients with SLE complicated by later cancer with patients with SLE but without cancer. The cumulative dose of immunosuppressants was calculated from the SLE diagnosis date to the occurrence of cancer. The immunosuppressants of interest were AZA, CYC, MTX, HCQ and systemic glucocorticoids. Adjusted odds ratios (ORs) for cancer were calculated in conditional Cox regression models after propensity score matching. Results: The top five types of cancers were breast (16.9%), haematological (11.7%), colorectal (11.0%), lung (10.6%) and hepatobiliary (10.4%) cancers. After matching, this study included 330 cancer patients and 1320 matched cancer-free patients. The adjusted analyses showed an association of a higher cumulative CYC dose (OR = 1.09, 95% CI: 1.04, 1.13) and lower HCQ dose (OR = 0.93, 95% CI: 0.90, 0.97) with cancer risk in comparison with the controls. Conclusion: Diverse cancer risks are associated with different immunosuppressants in patients with SLE. CYC increases the risk of cancer, and HCQ decreases this risk in SLE patients, both in a dose-dependent manner.

Anti-TNF-Alpha-Adalimumab Therapy Had Time Lag of Improvement in Synovial Hypertrophy Compared to Rapid Response in Power Doppler Synovial Vascularity.

OBJECTIVES: The quantification of synovitis is of great significance for follow-up in patients with rheumatoid arthritis (RA). This study aimed to validate the use of power Doppler ultrasonography (PDUS) for evaluating synovial vascularity and synovial hypertrophy for synovitis in patients with rheumatoid arthritis treated with adalimumab. MATERIALS AND METHODS: The synovial disease activity and vascularity of RA on both wrists (radio-carpal joint) were assessed using GS and PDUS to derive the composite US scores based on abnormal counts and severity. The relationship between each measure was determined. RESULTS: The 71 patients who received adalimumab therapy had significantly decreased DAS28, ESR, and CRP. After one month, PD score decreased and then remained low for 12 months. Synovial hypertrophy did not change until 3-6 months after, when it started to improve (p = 0.017). By multivariate analysis, sex, age, BMI, and DAS28 did not lead to any difference between synovial hypertrophy and PDUS changes (p = 0.498). DISCUSSION: Composite US markers of synovial hypertrophy correlate significantly to the DAS28 score and ESR/CRP in adult RA. The time needed for synovial hypertrophy to decrease may be up to 3-6 months after adalimumab therapy. Switching to biological therapy before 3-6 months is inappropriate and ineffective.

Delayed anti-TNF therapy increases the risk of total knee replacement in patients with severe rheumatoid arthritis.

BACKGROUND: This study evaluated the effect of early anti-tumor necrosis factor (TNF) therapy in patients with severe rheumatoid arthritis (RA) on the subsequent risk of total knee replacement (TKR) surgery. METHODS: This retrospective observational study included a hospital-based cohort of 200 patients diagnosed with severe RA who received treatment with anti-TNF therapy between 2003 and 2014. Clinical parameters including age, sex, body mass index, and the time from the diagnosis of RA to the initiation of anti-TNF therapy were analyzed. RESULTS: Of the 200 enrolled patients, 84 underwent an early intervention (≤3 years from the diagnosis of RA to the initiation of anti-TNF therapy), and 116 underwent a late intervention(>3 years from the diagnosis of RA to the initiation of anti-TNF therapy). Five (6.0%) patients in the early intervention group underwent TKR compared to 31 (26.7%) in the late intervention group (p = 0.023). After adjusting for confounding factors, the late intervention group still had a significantly higher risk of TKR (p = 0.004; odds ratio, 5.572; 95% confidence interval, 1.933-16.062). Those receiving treatment including methotrexate had a lower risk of TKR (p = 0.004; odds ratio, 0.287; 95% confidence interval, 0.122-0.672). CONCLUSIONS: Delayed initiation of anti-TNF therapy in the treatment of severe RA was associated with an increased risk of TKR surgery. Adding methotrexate treatment decreased the risk of future TKR.

Predictor of Hand Radiological Progression in Patients With Rheumatoid Arthritis Receiving TNF Antagonist Therapy by Change in Grayscale Synovitis-A Preliminary Study.

OBJECTIVES: This prospective study aimed to compare synovial ultrasound scores to conventional measures (DAS28, CRP levels) in predicting radiographic progression in patients with rheumatoid arthritis under TNF antagonist therapy. METHODS: Patients with RA who received TNF antagonist therapy were enrolled, all of whom underwent clinical, laboratory, and ultrasonographic assessments with grayscale and power Doppler assessments of bilateral elbows (anterior and posterior recess), wrists (dorsal, palmar, and ulnar aspects), second and third MCP joints (dorsal and palmar recess), and PIP II and III (dorsal and palmar) at baseline and at 1, 3 months. Hand radiographic damage was evaluated using van der Heijde modified Total Sharp Score (TSS) at baseline and 12 months. RESULTS: Thirty-two patients (384 joints, 832 synovial sites) continued the same treatment regimen for 12 months and completed the study, 41.6% of whom showed radiographic progression during the study period. Baseline DAS28 (P = 0.123), CRP level (P = 0.177), grayscale synovitis (P = 0.092), and power Doppler synovitis (P = 0.120) could not predict radiological damage in the TNF antagonist therapy group. However, ΔTSS was significantly related to changes in grayscale synovitis between baseline and 1 month (P = 0.011), but not at 3 months (P = 0.591), and was not related to changes in the power Doppler score at 1 (P = 0.634) and 3 months (P = 0.298). CONCLUSIONS: Our data confirm that delayed improvement in grayscale synovitis between baseline and 1 month more accurately reflects 1-year radiological damage than conventional measures such as DAS28 score and CRP level. Therefore, we recommend serial ultrasound follow-up of patients with RA receiving TNF antagonist therapy.

Medical specialty-related adherence to anti-osteoporotic regimens in fragility hip fracture patients.

There is poor adherence in the management of osteoporotic fractures. We designed a study to investigate adherence to osteoporotic regimens among osteoporotic hip fracture patients and to analyze the risk factors associated with poor compliance. This retrospective chart-review study was carried out using a database of osteoporotic hip fracture patients at a medical center in Taiwan for the period 2001-2007. Adherence was assessed using compliance and persistence. Compliance was calculated by the medication possession ratio (MPR) and persistence by the time from treatment initiation to discontinuation. The MPR and corresponding risk factors for poor compliance (MPR < 80 %) were evaluated for year 1. The year 2 results were analyzed only for those subjects with good compliance (MPR ≥ 80 %) at the end of year 1. There were 366 osteoporotic hip fracture patients (323 women, 43 men) with a mean age of 73.9 ± 7.6 years. Of these, 53.8 % had good compliance for year 1 and 68.5 % for year 2. During 2 years of follow-up, the overall persistence ratio was 33.1 %. The risk factor associated with poor compliance in the first year was index prescription by orthopedists [odds ratio (OR) 1.69, 95 % confidence interval (CI) 1.10-2.59]. Subjects with hypertension (OR 0.69, 95 % CI 0.46-0.99) had good compliance. Index prescription by orthopedists (OR 2.44, 95 % CI 1.31-4.51) was the sole risk factor for poor compliance in year 2. In conclusion, although adherence to osteoporotic regimens was sub-optimal in hip fracture patients, the majority of patients' decreased adherence occurred within the first year. Medical specialties showed different adherences in both year 1 and year 2.

Predictive value of heart rate variability and electrochemical skin conductance measurements for cardiovascular autonomic neuropathy persistence in type 2 diabetes and prediabetes: A 3-year follow-up study.

OBJECTIVE: The study aimed to explore risk stratification approaches for cardiovascular autonomic neuropathy (CAN) in individuals with prediabetes and type 2 diabetes (T2DM) over a three-year follow-up period. METHODS: Participants underwent evaluations of autonomic function encompassing cardiovascular autonomic reflex tests (CARTs), baroreflex sensitivity (BRS), heart rate variability (HRV) in time domains (standard deviation of all normal RR intervals (SDNN)) and frequency domains (high frequency/low frequency ratio), and electrochemical skin conductance (ESC). The diagnosis of CAN relied on abnormal CART results. Subjects were categorized into 4 groups, based on their assessment of cardiac autonomic function at 3-year follow-up, relative to the presence or absence of CAN at baseline assessment: Persistent absence of CAN; Resolution of CAN; Progression to CAN; and Persistent CAN. RESULTS: Participants with T2DM/prediabetes (n = 91/7) were categorized as: Persistent absence of CAN (n = 25), Resolution of CAN (n = 10), Progression to CAN (n = 18), and Persistent CAN (n = 45) groups. The Persistent absence of CAN group showed significant associations with SDNN. The Resolution of CAN group exhibited notable associations with mean HbA1C (follow-up), while the Progression to CAN group displayed a significant link with baseline estimated glomerular filtration rate. The Persistent CAN group demonstrated significant associations with SDNN and Sudoscan CAN risk score. Screening recommendations involve biennial to annual assessments based on risk levels, aiding in CAN detection and subsequent comprehensive and time-intensive autonomic function tests for confirmation. The study's findings offer improved risk categorization approaches for detecting CAN, which has relevance for shaping public health strategies.

Baroreflex Sensitivity as a Surrogate Biomarker for Concurrently Assessing the Severity of Arterial Stiffness and Cardiovascular Autonomic Neuropathy in Individuals with Type 2 Diabetes.

This study aimed to investigate whether baroreflex sensitivity (BRS) could serve as a reliable metric for assessing cardiovascular autonomic neuropathy (CAN) and concurrently act as a surrogate biomarker for evaluating the severity of arterial stiffness and CAN in individuals diagnosed with type 2 diabetes mellitus (T2DM). Participants underwent brachial-ankle pulse wave velocity (baPWV) as well as autonomic function evaluations encompassing the Sudoscan-based modified composite autonomic scoring scale (CASS), baroreflex sensitivity, and heart rate variability in time domains and frequency domains. Linear regression analysis was performed to evaluate the influence of independent variables on baPWV and modified CASS. Participants with higher baPWV values were older, with longer diabetes duration, lower body weight, body mass index, waist circumference, elevated systolic and diastolic blood pressure, and mean arterial blood pressure. They also exhibited a higher prevalence of retinopathy as the underlying disease and reduced estimated glomerular filtration rate. Multiple linear regression analysis revealed that age and BRS were significantly associated with baPWV while diabetes duration, UACR, and BRS were significantly associated with modified CASS. Our study confirms the significant association of BRS with baPWV and modified CASS in T2DM, highlighting its pivotal role in linking microvascular and macrovascular complications. This supports BRS as a surrogate marker for assessing both the severity of arterial stiffness and cardiovascular autonomic neuropathy in T2DM, enabling the early identification of complications.

Prognostic value of longitudinal HbA1c variability in predicting the development of diabetic sensorimotor polyneuropathy among patients with type 2 diabetes mellitus: A prospective cohort observational study.

AIMS/INTRODUCTION: This prospective cohort study aims to identify the optimal measure of glycated hemoglobin (HbA1c) variability and to explore its relationship with the development of new diabetic sensorimotor polyneuropathy (DSPN) in individuals with type 2 diabetes mellitus, building upon previous cross-sectional studies that highlighted a significant association between HbA1c visit-to-visit variability and DSPN. MATERIALS AND METHODS: In a prospective study, 321 participants diagnosed with type 2 diabetes mellitus underwent comprehensive clinical assessments, neurophysiologic studies, and laboratory evaluations at enrollment and follow-up. Various indices, including HbA1c standard deviation (HbA1c SD), coefficient of variation (HbA1c CV), HbA1c change score (HbA1c HVS), and average real variability (HbA1c ARV), were employed to calculate the visit-to-visit variability HbA1c based on 3 month intervals. The investigation focused on examining the associations between these indices and the development of new DSPN. RESULTS: The average follow-up duration was 16.9 ± 6.9 months. The Cox proportional hazards model identified age (P = 0.001), diabetes duration (P = 0.024), and HbA1C ARV (P = 0.031) as the sole factors associated with the development of new DSPN. Furthermore, the cumulative risk of developing DSPN over 1 year demonstrated a significant association with HbA1C ARV (P = 0.03, log-rank test). CONCLUSIONS: Apart from age and diabetes duration, HbA1c variability emerged as a robust predictor for the occurrence of new DSPN. Among the various measures of HbA1c variability evaluated, HbA1c ARV demonstrated the highest potential as a reliable indicator for anticipating the onset of new DSPN.

Longitudinal artificial intelligence-based deep learning models for diagnosis and prediction of the future occurrence of polyneuropathy in diabetes and prediabetes.

OBJECTIVE: The objective of this study was to develop artificial intelligence-based deep learning models and assess their potential utility and accuracy in diagnosing and predicting the future occurrence of diabetic distal sensorimotor polyneuropathy (DSPN) among individuals with type 2 diabetes mellitus (T2DM) and prediabetes. METHODS: In 394 patients (T2DM=300, Prediabetes=94), we developed a DSPN diagnostic and predictive model using Random Forest (RF)-based variable selection techniques, specifically incorporating the combined capabilities of the Clinical Toronto Neuropathy Score (TCNS) and nerve conduction study (NCS) to identify relevant variables. These important variables were then integrated into a deep learning framework comprising Convolutional Neural Networks (CNNs) and Long Short-Term Memory (LSTM) networks. To evaluate temporal predictive efficacy, patients were assessed at enrollment and one-year follow-up. RESULTS: RF-based variable selection identified key factors for diagnosing DSPN. Numbness scores, sensory test results (vibration), reflexes (knee, ankle), sural nerve attributes (sensory nerve action potential [SNAP] amplitude, nerve conduction velocity [NCV], latency), and peroneal/tibial motor NCV were candidate variables at baseline and over one year. Tibial compound motor action potential amplitudes were used for initial diagnosis, and ulnar SNAP amplitude for subsequent diagnoses. CNNs and LSTMs achieved impressive AUC values of 0.98 for DSPN diagnosis prediction, and 0.93 and 0.89 respectively for predicting the future occurrence of DSPN. RF techniques combined with two deep learning algorithms exhibited outstanding performance in diagnosing and predicting the future occurrence of DSPN. These algorithms have the potential to serve as surrogate measures, aiding clinicians in accurate diagnosis and future prediction of DSPN.

Exploring the role of anticipatory postural adjustment duration within APA2 subphase as a potential mediator between clinical disease severity and fall risk in Parkinson's disease.

Introduction: People with Parkinson's Disease (PD) often show reduced anticipatory postural adjustments (APAs) before voluntary steps, impacting their stability. The specific subphase within the APA stage contributing significantly to fall risk remains unclear. Methods: We analyzed center of pressure (CoP) trajectory parameters, including duration, length, and velocity, throughout gait initiation. This examination encompassed both the postural phase, referred to as anticipatory postural adjustment (APA) (APA1, APA2a, APA2b), and the subsequent locomotor phases (LOC). Participants were instructed to initiate a step and then stop (initiating a single step). Furthermore, we conducted assessments of clinical disease severity using the Unified Parkinson's Disease Rating Scale (UPDRS) and evaluated fall risk using Tinetti gait and balance scores during off-medication periods. Results: Freezing of gait (FOG) was observed in 18 out of 110 participants during the measurement of CoP trajectories. The Ramer-Douglas-Peucker algorithm successfully identified CoP displacement trajectories in 105 participants (95.5%), while the remaining 5 cases could not be identified due to FOG. Tinetti balance and gait score showed significant associations with levodopa equivalent daily dose, UPDRS total score, disease duration, duration (s) in APA2a (s) and LOC (s), length in APA1 (cm) and APA2b (cm), mediolateral velocity in APA1 (X) (cm/s), APA2a (X) (cm/s), APA2b (X) (cm/s) and LOC (X) (cm/s), and anterior-posterior velocity in APA2a (Z) (cm/s) and APA2b (Z) (cm/s). Multiple linear regression revealed that only duration (s) in APA2a and UPDRS total score was independently associated with Tinetti gait and balance score. Further mediation analysis showed that the duration (s) in APA2a served as a mediator between UPDRS total score and Tinetti balance and gait score (Sobel test, p = 0.047). Conclusion: APA2 subphase duration mediates the link between disease severity and fall risk in PD, suggesting that longer APA2a duration may indicate reduced control during gait initiation, thereby increasing fall risk.

Development and Comparison of Treatment Decision Tools for Glucocorticoid-Induced Osteoporosis.

Long-term Glucocorticoid (GC) use results in compromised bone strength and fractures, and several treatment recommendations have been developed to prevent fractures, but none have been validated in a real-world setting. This study aims to create a treatment decision tool and compares this tool to the treatment suggestions from the American College of Rheumatology (ACR), International Osteoporosis Foundation and European Calcified Tissue Society (IOF-ECTS), and GC-adjusted Fracture Risk Assessment Tool (GC-FRAX), above the intervention threshold. We utilized registry data gathered at Chang Gung Memorial Hospital at Kaohsiung, Taiwan, between September 2014 and April 2021. This research is a single-center, observational, and case-controlled study. We recruited participants using prednisone for at least 2.5 mg/day or the equivalent dose for over 3 months, excluding those younger than 40, those with malignancies, or those currently undergoing anti-osteoporosis therapy. The primary endpoint was new fragility fractures within 3 years, including morphometric vertebral fractures detected at baseline and with a follow-up thoracic-lumbar spine X-ray. Participants were randomly allocated into derivation and validation sets. We developed the Steroid-Associated Fracture Evaluation (SAFE) tool in the derivation cohort by assessing the weights of exploratory variables via logistic regression. Prediction performance was compared in the validation set by the receiver operating characteristic (ROC) curve, the area under the curve (AUC), and sensitivity and specificity. A total of 424 treatment-naïve subjects were enrolled, and 83 (19.6%) experienced new fractures within 3 years. The final formula of the SAFE tool includes osteoporosis (1 point), an accumulated GC dose ≥ 750 mg within 6 months (or equivalent prednisolone of ≥4.5 mg/day for 6 months) (1 point), a BMI ≥ 23.5 (1 point), previous fractures (1 point), and elderliness of ≥70 years (2 points). In the validation set, a treatment decision based on the SAFE ≥ 2 points demonstrated an AUC of 0.65, with a sensitivity/specificity/accuracy of 75.9/54.0/58.9, with an ACR of 0.56 (100.0/11.0/31.0), IOF-ECTS 0.61 (75.9/46.0/52.7), and GC-FRAX 0.62 (82.8/42.0/51.2). Among current GIOP recommendations, the SAFE score serves as an appropriate treatment decision tool with increased accuracy and specificity.

The association among leukocyte apoptosis, autoantibodies and disease severity in systemic lupus erythematosus.

BACKGROUND: Both apoptosis and autoantibodies are important factors associated with disease activity in the pathogenesis of systemic lupus erythematosus (SLE). This study tested the hypothesis that increased leukocyte apoptosis is associated with elevated levels of autoantibodies and the disease activity of SLE. METHODS: Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 23 patients with SLE. Leukocyte apoptosis was also evaluated in nine patients with Sjogren's syndrome (SJS) and in 20 volunteer subjects. Titers of common autoantibodies and the disease activity index (SLEDAI-2 k) of the SLE patients were also determined. RESULTS: Except for annexin V and APO 2.7 of monocytes and late apoptosis (annexin V+7-ADD) of lymphocytes, apoptosis in the total and in subsets of leukocytes were significantly higher in SLE patients than in controls (all p<0.05, post hoc analysis). The mean percentage of late apoptosis of leukocytes (annexin V+7-AAD) positively correlated with levels of anti-Ro52/60 (r=0.513, p<0.01), anti-La (r=0.439, p=0.04), and anti-Mi-2 (r=0.492, p=0.02), and inversely correlated with both C3 and C4 levels, although not statistically significant. The percentage of APO2.7 of CD19+ cells positively correlated with SLEDAI-2 K score (p=0.01). CONCLUSIONS: Leukocyte apoptosis is significantly higher in patients with SLE and correlates well with the levels of several autoantibodies. The APO2.7 of B-lymphocyte (CD19+) cells positively correlates with the disease activity of SLE.

Non-adherence to anti-osteoporotic medications in Taiwan: physician specialty makes a difference.

Adherence to anti-osteoporotic regimens gradually decreases over time. We hypothesized that the determinants of non-compliance or non-persistence at different times vary and identified these differences. We used an outpatient database to retrieve information on anti-osteoporotic medications prescribed by a medical centre in southern Taiwan during 2001-2007. Compliance was defined as a medication possession ratio (MPR) ≥80 %. Persistence was determined as continuous use, allowing for a refill gap of 30 days. A multivariate Cox regression model evaluated potential predictors of non-adherence. A total of 3589 patients were included. In the multivariate analyses, non-compliance for both year 1 and year 2 was more likely in patients with non-vertebral non-hip fractures, respiratory disorders, prescription of the first anti-osteoporotic regimen by an orthopedist; and less likely in patients with follow-up bone densitometry and switched regimens. Risks for non-persistence at year 1 and year 2 were generally similar to those for non-compliance; insurance coverage and malignancy were associated with a lower risk of non-persistence at year 1 and year 2, respectively. In the subgroup with an MPR ≥80 % at year 1, an index prescription by an orthopedist was the only independent predictor of non-compliance and non-persistence at year 2. In conclusion, the positive or negative determinants of non-adherence were different at year 1 and year 2, which indicated that clinicians might deliver effective interventions to improve adherence via different precautions annually. This study also provided evidence that physician specialty had a significant effect on adherence to osteoporosis care.