ANCA-associated vasculitis presenting with isolated neurological manifestations in a patient with cocaine abuse: a case report and literature review.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare conditions predominantly affecting small vessels of skin, musculoskeletal, pulmonary, renal, and rarely central and peripheral nervous systems. Isolated neurological manifestations of AAV are uncommon and challenging to diagnose. Cocaine has been reported as a potential trigger for the development of AAV. There are only a few case reports of isolated neurological involvement in cocaine-induced AAV with poorly characterized histopathological features. We present a unique case of AAV with isolated neurological manifestations presenting with multiple cranial neuropathies, leptomeningeal enhancement on imaging and histopathologic evidence of small-vessel vasculitis in the leptomeninges and brain and extensive dural fibrosis in a patient with cocaine abuse. The patient's progressive neurological deficits were controlled after starting immunosuppression with rituximab and prednisone. We also reviewed the literature to provide the diagnostic overview of AAV and evaluate intervention options. To our knowledge, this is the first case of AAV with isolated neurological manifestations and histopathologic evidence of small-vessel vasculitis in a patient with cocaine abuse. Patients with multiple cranial neuropathies and meningeal involvement should be screened for AAV, especially if they have a history of cocaine abuse.

Relationship Between Self-Reported Restless Sleep and Objectively Measured Physical Activity in Adults With Knee Osteoarthritis.

OBJECTIVE: Despite the numerous health benefits of physical activity, inactivity is endemic among adults with knee osteoarthritis (OA). Because sleep quality may be a target in order to improve physical activity behavior, we investigated the cross-sectional relationship between restless sleep and physical activity in participants with or at risk for knee OA. METHODS: We analyzed accelerometer-measured physical activity and clinical data of participants included in the Osteoarthritis Initiative (OAI). We used multiple regression analysis to evaluate physical activity for participants, who were grouped by the reported frequency of restless sleep, and adjusted for demographic and medical confounders. RESULTS: Of the 1,892 OAI participants for whom complete data were available, 300 participants (16%) reported restless sleep ≥3 days in the past week. Participants who reported restless sleep for much of the time (3-4 days/week) and most of the time (5-7 days/week) had 11.9% and 23.7% less weekly minutes of moderately vigorous activity, respectively, compared to participants who reported rarely restless sleep (<1 day/week) (P for trend 0.021). These differences persisted after accounting for age, sex, race, body mass index, medical comorbidity, and knee OA severity and pain (P for trend 0.023). Differences related to restless sleep were largely attenuated by the presence of high depressive symptoms and low energy levels. CONCLUSION: Poor sleep quality is associated with less physical activity in persons with or at risk for knee OA. Future studies are needed to determine the mechanisms of how poor sleep and physical activity are related, how energy and depression mediate these relationships, and whether interventions that improve sleep quality might result in increased physical activity.

What Is an Important Difference in Gait Speed in Adults With Knee Osteoarthritis?

OBJECTIVE: Little is known regarding what difference in functional performance measures is significant in individuals with chronic medical disease. Our objective was to examine the important differences in gait speed in adults with radiographic knee osteoarthritis. METHODS: Functional performance was measured by gait speed using 20-meter and 400-meter walk tests performed at a self-selected usual pace among adults with radiographic knee osteoarthritis participating in the Osteoarthritis Initiative at baseline and 2 years later. Both distribution-based methods and anchor-based methods were used to calculate the important differences in gait speed. Anchor-based methods used the chair stand rate and self-reported function to estimate gait speed differences related to physical function. RESULTS: We included 2,527 participants with radiographic knee osteoarthritis. Distribution-based important difference estimates for the 20-meter walk ranged from 4.1 to 6.4 meters/minute and 400-meter walk estimates ranged from 2.9 to 6.5 meters/minute. Prevalent (cross-sectional) anchor-based estimates for the 20-meter walk ranged from 5.4 to 6.9 meters/minute and for the 400-meter walk ranged from 3.0 to 6.9 meters/minute. Longitudinal anchor-based estimates were deemed unreliable. Combining distribution-based with prevalent anchor-based methods showed that an important gait speed difference for the 20-meter walk is between 4.1 and 6.9 meters/minute and for the 400-meter walk is between 2.9 and 6.9 meters/minute. CONCLUSION: Our results found that the important difference in gait speed for the 20-meter walk and the 400-meter walk is consistent with important difference estimates for older adult populations. These findings can provide benchmarks for assessing and understanding functional performance outcomes when comparing exposure groups and can be used in designing future studies targeting adults with radiographic knee osteoarthritis.

The Relationship between Polypharmacy and Physical Activity in Those with or at Risk of Knee Osteoarthritis.

OBJECTIVES: Physical activity is associated with improved pain, functional status, and less disability in persons with knee osteoarthritis (KOA). Because polypharmacy is related to several adverse health outcomes in older persons, we hypothesized that it might also be associated with decreased physical activity in those with KOA. This study evaluates the relationship between the number of prescription medications and weekly moderate to vigorous physical activity (MVPA). DESIGN: We used hierarchical median quantile regression analysis to examine the cross-sectional association between the number of prescription medications taken in the past 30 days and the median objectively measured MVPA minutes controlling for demographic and clinical variables. SETTING: Four Osteoarthritis Initiative (OAI) recruitment centers in Providence, Rhode Island; Columbus, Ohio; Baltimore, Maryland; and Pittsburgh, Pennsylvania. PARTICIPANTS: Accelerometer monitoring occurred in 2,127 OAI participants. Of these, 1,889 participants had 4 or more days of valid physical activity monitoring data and complete medication/covariate data. Data were collected at the 48-month OAI follow-up visit (2008-2010). MEASUREMENTS: The outcome was weekly minutes of MVPA measured with an accelerometer. Number/type of prescribed medications and covariate data (age, sex, race/ethnicity, body mass index, presence of comorbidities, pain, depressive symptoms, and radiographic KOA severity) were taken from the public OAI database. Polypharmacy was defined as taking five or more prescribed medications. RESULTS: The prevalence of polypharmacy in the study population was 28.2%. Each additional prescription medication was related to a decrease of 3.6 minutes (95% confidence interval [CI] = -4.8 to -2.1) in median weekly MVPA minutes. Participants meeting the polypharmacy criterion exhibited a decrease of 12.6 minutes (95% CI = -21.2 to -4.7) in median weekly MVPA minutes compared with those not meeting the criterion. CONCLUSION: An increased number of prescription medications and polypharmacy are associated cross-sectionally with decreased MVPA in adults with KOA. Further study is necessary to establish the causal nature of this association.

Osteoarthritis physical activity care pathway (OA-PCP): results of a feasibility trial.

BACKGROUND: To obtain information on feasibility and acceptability, as well as preliminary data on efficacy, of an Osteoarthritis Physical activity Care Pathway (OA-PCP). METHODS: This was a single group pilot study involving 60 participants with symptomatic, physician diagnosed knee or hip OA, recruited from primary care clinics. Participants self-reported completing less than 150 min per week of moderate-to-vigorous physical activity (MVPA) at baseline. The 3-month OA-PCP intervention involved 3 physical activity (PA) coaching calls (focused on goal setting), three check-in emails and linkage with community-based or online resources to support PA. Efficacy outcomes were collected at baseline and 4-month follow-up. The primary efficacy outcome was minutes of MVPA, assessed via accelerometer. Secondary outcomes included minutes of light intensity activity, sedentary minutes, step counts, and Western Ontario and McMaster Universities (WOMAC) pain and function subscales. Participants were also asked to rate the helpfulness of the OA-PCP intervention on a scale of 0-10. Differences in efficacy outcomes between baseline and 4-month follow-up were assessed using paired t-tests. RESULTS: Among participants beginning the study, 88% completed follow-up assessments and ≥ 90% completed each of the intervention calls. Average daily minutes of MVPA was 8.0 at baseline (standard deviation (SD) = 9.9) and 8.9 at follow-up (SD = 12.1, p = 0.515). There were no statistically significant changes in light intensity activity, sedentary time or step counts. The mean WOMAC pain score improved from 8.1 (SD = 3.6) at baseline to 6.2 (SD = 3.8) at follow-up (p < 0.001); the mean WOMAC function score improved from 26.2 (SD = 13.2) to 20.2 (SD = 12.5; p < 0.001). The mean rating of helpfulness was 7.6 (SD = 2.5). CONCLUSIONS: Results supported the feasibility and acceptability of the study, and participants reported clinically relevant improvements in pain and function. PA metrics did not improve substantially. Based on these results and participant feedback, modifications including enhanced self-monitoring are being made to increase the impact of the OA-PCP intervention on PA behavior. TRIAL REGISTRATION: NCT03780400, December 19, 2018.

A randomized trial of a motivational interviewing intervention to increase lifestyle physical activity and improve self-reported function in adults with arthritis.

BACKGROUND: Arthritis is a leading cause of chronic pain and functional limitations. Exercise is beneficial for improving strength and function and decreasing pain. We evaluated the effect of a motivational interviewing-based lifestyle physical activity intervention on self-reported physical function in adults with knee osteoarthritis (KOA) or rheumatoid arthritis (RA). METHODS: Participants were randomized to intervention or control. Control participants received a brief physician recommendation to increase physical activity to meet national guidelines. Intervention participants received the same brief baseline physician recommendation in addition to motivational interviewing sessions at baseline, 3, 6, and 12 months. These sessions focused on facilitating individualized lifestyle physical activity goal setting. The primary outcome was change in self-reported physical function. Secondary outcomes were self-reported pain and accelerometer-measured physical activity. Self-reported KOA outcomes were evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for KOA (WOMAC scores range from 0 to 68 for function and 0 to 20 for pain) and the Health Assessment Questionnaire (HAQ) for RA. Outcomes were measured at baseline, 3, 6, 12, and 24 months. Multiple regression accounting for repeated measures was used to evaluate the overall intervention effect on outcomes controlling for baseline values. RESULTS: Participants included 155 adults with KOA (76 intervention and 79 control) and 185 adults with RA (93 intervention and 92 control). Among KOA participants, WOMAC physical function improvement was greater in the intervention group compared to the control group [difference = 2.21 (95% CI: 0.01, 4.41)]. WOMAC pain improvement was greater in the intervention group compared to the control group [difference = 0.70 (95% CI: -0.004, 1.41)]. There were no significant changes in physical activity. Among RA participants, no significant intervention effects were found. CONCLUSION: Participants with KOA receiving the lifestyle intervention experienced modest improvement in self-reported function and a trend toward improved pain compared to controls. There was no intervention effect for RA participants. Further refinement of this intervention is needed for more robust improvement in function, pain, and physical activity.

Patients Less Likely to Lose Weight Following a Knee Replacement: Results From the Osteoarthritis Initiative.

BACKGROUND: Knee replacement typically results in reduced pain and improved function, but it is unclear if these improvements lead to weight loss. OBJECTIVE: The purpose of this study was to examine weight change patterns preoperatively and postoperatively among overweight/obese knee replacement patients. METHODS: The study evaluated 210 overweight/obese patients from the Osteoarthritis Initiative who underwent a knee replacement during an 8-year longitudinal study. Average annual weight changes during 1- to 2-year intervals prior to, including, and subsequent to knee replacement were categorized as loss (≥-2.5%), maintain (>-2.5% to <2.5%), and gain (≥2.5%). Weight changes across time intervals were compared using logistic regression with generalized estimating equations, adjusting for demographic, health, and knee factors. RESULTS: On average, patients lost -0.6 kg/y during the interval when the surgery was performed, but weight gain (0.9 kg/y) in the initial postoperative interval represented an overall net weight gain (0.3 kg/y) compared with presurgery. Continued weight gain (0.3 kg/y) was also seen among patients with additional follow-ups. Patients were significantly less likely to have a meaningful weight loss in the time interval immediately following the surgery compared with the interval in which the surgery took place (odds ratio, 0.37; 95% confidence interval, 0.18-0.79). CONCLUSIONS: Overweight and obese patients initially lost weight during the interval including knee replacement; however, they were less likely to lose more than 2.5% of their weight in the 1 to 2 years immediately after the surgery. Knee replacement patients may benefit from weight management interventions both preoperatively and postoperatively.

Do Inactive Older Adults Who Increase Physical Activity Experience Less Disability: Evidence From the Osteoarthritis Initiative.

BACKGROUND: Physical inactivity is a leading risk factor for developing disability. Although randomized clinical trials have demonstrated improving physical activity can reduce this risk in older adults with arthritis, these studies did not specifically evaluate inactive adults. OBJECTIVES: The aim of this study was to evaluate the relationship of changes in physical activity with disability changes among initially inactive adults with or at high risk of knee osteoarthritis from Osteoarthritis Initiative. METHODS: Inactive persons were identified at baseline based on the US Department of Health and Human Services classification (no [zero] 10-minute session of moderate-to-vigorous [MV] activity over 1 week) from objective accelerometer monitoring. Two years later, physical activity change status was classified as follows: (1) met Federal physical activity guidelines (≥150 MV minutes/week acquired in bouts ≥10 minutes), (2) insufficiently increased activity (some but <150 MV bout minutes/week), or (3) remained inactive. Disability at baseline and 2 years was assessed by Late Life Disability Instrument limitation and frequency scores. Multiple regression evaluated the relationship of physical activity change status with baseline-to-2-year changes in disability scores adjusting for socioeconomics, health factors, and baseline disability score. RESULTS: Increased physical activity showed a graded relationship with improved disability scores in Late Life Disability Instrument limitation (P < 0.001) and frequency scores (P = 0.027). While increasing MV activity to guideline levels showed the greatest reduction, even insufficiently increased physical activity was related to reduced disability. CONCLUSIONS: Findings support advice to increase MV physical activity to reduce disability among inactive adults with or at high risk of knee osteoarthritis, even when guidelines are not met.

Physical Activity Minimum Threshold Predicting Improved Function in Adults With Lower-Extremity Symptoms.

OBJECTIVE: To identify an evidence-based minimum physical activity threshold to predict improved or sustained high function for adults with lower-extremity joint symptoms. METHODS: Prospective multisite data from 1,629 adults, age ≥49 years with symptomatic lower-extremity joint pain/aching/stiffness, participating in the Osteoarthritis Initiative accelerometer monitoring substudy were clinically assessed 2 years apart. Improved/high function in 2-year gait speed and patient-reported outcomes (PROs) were based on improving or remaining in the best (i.e., maintaining high) function quintile compared to baseline status. Optimal thresholds predicting improved/high function were investigated using classification trees for the legacy federal guideline metric requiring 150 minutes/week of moderate-vigorous (MV) activity in bouts lasting 10 minutes or more (MV-bout) and other metrics (total MV, sedentary, light intensity activity, nonsedentary minutes/week). RESULTS: Optimal thresholds based on total MV minutes/week predicted improved/high function outcomes more strongly than the legacy or other investigated metrics. Meeting the 45 total MV minutes/week threshold had increased relative risk (RR) for improved/high function (gait speed RR 1.8, 95% confidence interval [95% CI] 1.6, 2.1 and PRO physical function RR 1.4, 95% CI 1.3, 1.6) compared to less active adults. Thresholds were consistent across sex, body mass index, knee osteoarthritis status, and age. CONCLUSION: These results supported a physical activity minimum threshold of 45 total MV minutes/week to promote improved or sustained high function for adults with lower-extremity joint symptoms. This evidence-based threshold is less rigorous than federal guidelines (≥150 MV-bout minutes/week) and provides an intermediate goal towards the federal guideline for adults with lower-extremity symptoms.

Comparison of Subjective and Objective Measures of Sedentary Behavior Using the Yale Physical Activity Survey and Accelerometry in Patients With Rheumatoid Arthritis.

BACKGROUND: Sedentary behavior is associated with increased risk of functional decline and disability. Individuals with rheumatoid arthritis (RA) spend more time sedentary than healthy adults. Self-reported assessment of sedentary behavior has not been well-developed in this patient population. METHODS: 172 adults with RA wore an accelerometer for 7 days and completed a modified version of the Yale Physical Activity Survey (YPAS). YPAS-derived sedentary estimates included 1) daily sitting categories (<3, 3 to 6, 6 to 8, >8 hours/day), 2) continuous daily sedentary time calculated by subtracting hours spent sleeping or in physical activity from a 24-hour day, and 3) rank order of YPAS-derived continuous daily sedentary time. Each estimate was compared with objective accelerometer-derived sedentary time using linear regression and Bland-Altman analysis. RESULTS: A significant relationship was observed between accelerometer-derived sedentary time and all 3 estimates. Bland-Altman plot demonstrated systematic bias, however Bland-Altman plot of rank-order demonstrated that the ranked YPAS-derived continuous estimate was an unbiased predictor of ranked accelerometer sedentary time though limits of agreement were wide. CONCLUSIONS: This patient-reported approach using the YPAS shows promise to be a useful tool to identify the most sedentary patients. Providing a practical and accurate tool may increase the frequency sedentary behavior is assessed by clinicians.

Replacing acid alpha-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers.

Pompe disease (type II glycogen storage disease) is an autosomal recessive disorder caused by a deficiency of lysosomal acid alpha-glucosidase (GAA) leading to the accumulation of glycogen in the lysosomes primarily in cardiac and skeletal muscle. The recombinant human GAA (rhGAA) is currently in clinical trials for enzyme replacement therapy of Pompe disease. Both clinical data and the results of preclinical studies in our knockout model of this disease show that rhGAA is much more effective in resolving the cardiomyopathy than the skeletal muscle myopathy. By contrast, another form of human GAA--transgenic enzyme constitutively produced in liver and secreted into the bloodstream of knockout mice (Gaa-/-)--completely prevented both cardiac and skeletal muscle glycogen accumulation. In the experiments reported here, the transgenic enzyme was much less efficient when delivered to skeletal muscle after significant amounts of glycogen had already accumulated. Furthermore, the transgenic enzyme and the rhGAA have similar therapeutic effects, and both efficiently clear glycogen from cardiac muscle and type I muscle fibers, but not type II fibers. Low abundance of proteins involved in endocytosis and trafficking of lysosomal enzymes combined with increased autophagy in type II fibers may explain the resistance to therapy.

Habitual prospective memory in schizophrenia.

BACKGROUND: Prospective memory (PM), the act of remembering that something has to be done in the future without any explicit prompting to recall, provides a useful framework with which to examine problems in internal-source monitoring. This is because it requires distinguishing between two internally-generated processes, namely the intention to perform an action versus actual performance of the action. In habitual tasks, such as taking medicine every few hours, the same PM task is performed regularly and thus it is essential that the individual is able to distinguish thoughts (i.e., thinking about taking the medicine) from actions (i.e., actually taking the medicine). METHODS: We assessed habitual PM in patients with schizophrenia by employing a laboratory analogue of a habitual PM task in which, concurrently with maneuvering a ball around an obstacle course (ongoing activity), participants were to turn over a counter once during each trial (PM task). After each trial, participants were asked whether they had remembered to turn the counter over. RESULTS: Patients with schizophrenia made a disproportionate number of errors compared to controls of reporting that a PM response had been made (i.e., the counter turned over) after an omission error (i.e., the counter was not turned over). There was no group difference in terms of reporting that an omission error occurred (i.e., forgetting to turn over the counter) when in fact a PM response had been made. CONCLUSION: Patients with schizophrenia displayed a specific deficit distinguishing between two internally-generated sources, attributable to either poor source monitoring or temporal discrimination.