Proportion and associated factors of meeting the 2018 Physical Activity Guidelines for Americans in adults with or at risk for knee osteoarthritis.

OBJECTIVES: Evaluate the prevalence of meeting the updated 2018 Physical Activity Guidelines for Americans (150 unbouted minutes in moderate-to-vigorous intensity physical activity [MVPA]) and determine cross-sectional factors associated with Guideline attainment in a community-based cohort of adults with or at elevated risk for knee osteoarthritis (OA). METHODS: Physical activity was monitored for 1 week in a subset of Osteoarthritis Initiative (OAI) participants with or at increased risk for knee OA. Accelerometer-measured weekly MVPA minutes were calculated; sociodemographic (age, sex, race, education, and working status) and health-related (body mass index [BMI], comorbidity, depressive symptoms, radiographic knee OA, and frequent knee symptoms) factors were assessed. We evaluated the prevalence of meeting 2018 Guidelines and used multivariate partial proportional odds model to identify factors associated with Guideline attainment, controlling for other factors in the model. RESULTS: Among 1922 participants (age 65.1 [standard deviation 9.1] years, BMI 28.4 [4.8] kg/m2, 55.2% women), 44.1% men and 22.2% women met the 2018 PA Guidelines. Adjusted cross-sectional factors associated with not-meeting 2018 Guidelines were: women, older age, higher BMI, non-Whites, depressive symptoms, not working, and frequent knee symptoms. CONCLUSION: In community-recruited adults with or at high risk for knee OA, more than 50% of men and nearly 80% of women failed to achieve the 2018 recommended level of at least 150 weekly unbouted minutes of MVPA. Study findings support gender and racial disparity in Guideline attainment and suggest addressing potentially modifiable factors (e.g., BMI, depressive symptoms, and frequent knee symptoms) to optimize benefits in PA-promoting interventions.

Preferences for physical activity: a conjoint analysis involving people with chronic knee pain.

OBJECTIVE: To investigate individual preferences for physical activity (PA) attributes in adults with chronic knee pain, to identify clusters of individuals with similar preferences, and to identify whether individuals in these clusters differ by their demographic and health characteristics. DESIGN: An adaptive conjoint analysis (ACA) was conducted using the Potentially All Pairwise RanKings of all possible Alternatives (PAPRIKA) method to determine preference weights representing the relative importance of six PA attributes. Cluster analysis was performed to identify clusters of participants with similar weights. Chi-square and ANOVA were used to assess differences in individual characteristics by cluster. Multinomial logistic regression was used to assess associations between individual characteristics and cluster assignment. RESULTS: The study sample included 146 participants; mean age 65, 72% female, 47% white, non-Hispanic. The six attributes (mean weights in parentheses) are: health benefit (0.26), enjoyment (0.24), convenience (0.16), financial cost (0.13), effort (0.11) and time cost (0.10). Three clusters were identified: Cluster 1 (n = 33): for whom enjoyment (0.35) is twice as important as health benefit; Cluster 2 (n = 63): for whom health benefit (0.38) is most important; and Cluster 3 (n = 50): for whom cost (0.18), effort (0.18), health benefit (0.17) and enjoyment (0.18) are equally important. Cluster 1 was healthiest, Cluster 2 most self-efficacious, and Cluster 3 was in poorest health. CONCLUSIONS: Patients with chronic knee pain have preferences for PA that can be distinguished effectively using ACA methods. Adults with chronic knee pain, clustered by PA preferences, share distinguishing characteristics. Understanding preferences may help clinicians and researchers to better tailor PA interventions.

Reallocating time spent in sleep, sedentary behavior and physical activity and its association with pain: a pilot sleep study from the Osteoarthritis Initiative.

OBJECTIVE: Being physically active has broad health benefits for people with osteoarthritis (OA), including pain relief. Increasing physical activity (PA) requires reducing time in other behaviors within a fixed 24-h day. We examined the potential benefits in relation to pain from trading time in one type of wake or sleep behavior for another. METHOD: In this cross-sectional study, we used isotemporal logistic regression models to examine the estimated effect on pain from replacing time in one behavior with equal time in another, controlling for sociodemographic and health factors. Stratified analysis was conducted by the report of restless sleep. Sleep and wake behaviors [sedentary behavior (SB), light PA, moderate PA] were monitored by accelerometer in a pilot study of 185 Osteoarthritis Initiative (OAI) participants. Outcomes were bodily pain interference and knee pain. RESULTS: Moderate PA substituted for an equivalent time in sleep or other types of wake behaviors was most strongly associated with lower odds of pain (bodily pain interference odds reduced 21-25%, knee pain odds reduced 17-20% per 10-min exchange). These beneficial associations were particularly pronounced in individuals without restless sleep, but not in those with restless sleep, especially for bodily pain interference. CONCLUSION: Interventions promoting moderate physical activities may be most beneficial to address pain among people with or at high risk for knee OA. In addition to encouraging moderate-intensity PA, pain management strategies may also include the identification and treatment of sleep problems.

Fatigue, patient reported outcomes, and objective measurement of physical activity in systemic lupus erythematosus.

OBJECTIVE: Fatigue is a common symptom in systemic lupus erythematosus (SLE), and engaging in physical activity may reduce fatigue. We aimed to characterize relationships between fatigue, other health status measures assessed with the Patient Reported Outcomes Measurement Information System (PROMIS) instruments, and accelerometer-based physical activity measurements in patients with SLE. The internal consistency of each PROMIS measure in our SLE sample was also evaluated. METHODS: This cross-sectional study analyzed 123 adults with SLE. The primary fatigue outcome was Fatigue Severity Scale score. Secondary outcomes were PROMIS standardized T-scores in seven health status domains. Accelerometers were worn for seven days, and mean daily minutes of light, moderate/vigorous, and bouted (10 minutes) moderate/vigorous physical activity were estimated. Cronbach's alpha was determined for each PROMIS measure to assess internal consistency. Relationships between Fatigue Severity Scale, PROMIS, and physical activity were summarized with Spearman partial correlation coefficients (r), adjusted for average daily accelerometer wear time. RESULTS: Mean Fatigue Severity Scale score (4.3, SD 1.6) was consistent with clinically relevant levels of fatigue. Greater daily and bouted moderate/vigorous physical activity minutes correlated with lower Mean Fatigue Severity Scale score (r = -0.20, p = 0.03 and r = -0.30, p = 0.0007, respectively). For PROMIS, bouted moderate/vigorous physical activity minutes correlated with less fatigue (r = -0.20, p = 0.03). PROMIS internal consistency was excellent, with Cronbach's alpha > 0.90 for each domain. Mean PROMIS T-scores for fatigue, pain interference, anxiety, sleep disturbance, sleep-related impairment, and physical function were worse than reported for the general US population. More moderate/vigorous physical activity minutes were associated with less pain interference (r = -0.22, p = 0.01). Both light physical activity and moderate/vigorous physical activity minutes correlated with better physical function (r = 0.19, p = 0.04 and r = 0.25, p = 0.006, respectively). CONCLUSION: More time spent in moderate/vigorous physical activity was associated with less fatigue (Fatigue Severity Scale and PROMIS), less pain interference, and better physical function (PROMIS). PROMIS had excellent internal consistency in our SLE sample, and six of seven PROMIS measures indicated poorer average health status in SLE patients compared with the general US population.

Sedentary behavior and blood pressure control among osteoarthritis initiative participants.

OBJECTIVE: To examine the association between sedentary behavior and blood pressure (BP) among Osteoarthritis Initiative (OAI) participants. DESIGN: We conducted a cross-sectional analysis of the OAI 48-month visit participants whose physical activity was measured using accelerometers. Participants were classified into four quartiles according to the percentage of wear time that was sedentary (<100 activity counts per min). Users of antihypertensive medications or non-steroidal anti-inflammatory drugs (NSAIDs) were excluded. Our main outcomes were systolic and diastolic blood pressures (SBP and DBP) and "elevated BP" defined as BP ≥ 130/85 mm Hg. RESULTS: For this study cohort (N = 707), mean BP was 121.4 ± 15.6/74.7 ± 9.5 mm Hg and 33% had elevated BP. SBP had a graded association with increased sedentary time (P for trend = 0.02). The most sedentary quartile had 4.26 mm Hg higher SBP (95% confidence interval (CI), 0.69-7.82; P = 0.02) than the least sedentary quartile, adjusting for age, moderate-to-vigorous (MV) physical activity, and other demographic and health factors. The probability of having elevated BP significantly increased in higher sedentary quartiles (P for trend = 0.046). There were no significant findings for DBP. CONCLUSION: A strong graded association was demonstrated between sedentary behavior and increased SBP and elevated BP, independent of time spent in MV physical activity. Reducing daily sedentary time may lead to improvement in BP and reduction in cardiovascular risk.

Challenges of defining acute kidney injury.

BACKGROUND: Until recently, there was a lack of a uniform definition for acute kidney injury (AKI). The 'acute renal injury/acute renal failure syndrome/severe acute renal failure syndrome' criteria, the Risk - Injury - Failure - Loss of kidney function - End stage renal disease (RIFLE) criteria and the Acute Kidney Injury Network (AKIN) classification were the most recent proposals. AIM: To compare the performance of the different AKI definitions. DESIGN AND METHODS: Application of the three most recent AKI definitions to 41 972 critically ill ICU patients and comparison of their performance. RESULTS: Incidence and outcome of AKI varied depending on the criteria. The RIFLE and AKIN classification led to similar total incidences of AKI (35.9 vs. 35.4%) but different incidences and outcomes of the individual AKI stages. Multivariate analysis showed that the different stages of AKI were independently associated with mortality. The worst stage of AKI was associated with an increased odds ratio for mortality of 1.59-2.27. Non-surgical admission, maximum number of associated failed organ systems, emergency surgery and mechanical ventilation were consistently associated with the highest risk of hospital mortality. The proposed AKI definitions differ in the cut-off values of serum creatinine, the suggested time frame, the approach towards patients with missing baseline values and the method of classifying patients on renal replacement therapy. All classifications can miss patients with definite AKI. CONCLUSION: The three most recent definitions of AKI confirmed a correlation between severity of AKI and outcome but have limitations and the potential to miss patients with definite AKI. These limitations need to be considered when using the criteria in clinical practice.

Prognosis of acute renal failure: an evaluation of proposed consensus criteria.

OBJECTIVES: To validate the recently proposed criteria for acute renal injury (ARI), acute renal failure syndrome (ARFS) and severe acute renal failure syndrome (SARFS) and to evaluate the significance of other prognostic factors. DESIGN AND SETTING: Retrospective analysis of the Riyadh ICU Program database of patients admitted to 22 ICUs in UK and Germany between 1989 and 1998. PATIENTS: Included in the study were 41,972 patients, of whom 7,522 (17.9%) had ARI, 2,641 (6.3%) had ARFS and 1,747 (4.2%) had SARFS. RESULTS: Patients with ARI, ARFS or SARFS had a hospital mortality of 29.5%, 49.2% or 63.0%, respectively, compared to 10.3% among patients without acute renal failure. In the presence of contemporaneous failure of any other organs on the day of acute renal failure, hospital mortality increased to 73.3%, 76.2%, 72.1% and 18%, respectively. Multivariate analysis showed that non-surgical admission, need for emergency surgery, development of acute renal failure during stay in ICU, need for mechanical ventilation and the number of other failed organ systems had a greater impact on prognosis than the need for renal replacement therapy. CONCLUSIONS: The proposed criteria for ARI, ARFS and SARFS correlated with mortality, but other factors had a greater impact on prognosis. Renal replacement therapy did not increase the risk of hospital mortality among patients with acute renal failure.

Reduction in mortality after inappropriate early discharge from intensive care unit: logistic regression triage model.

OBJECTIVE: To develop a predictive model to triage patients for discharge from intensive care units to reduce mortality after discharge. DESIGN: Logistic regression analyses and modelling of data from patients who were discharged from intensive care units. SETTING: Guy's hospital intensive care unit and 19 other UK intensive care units from 1989 to 1998. PARTICIPANTS: 5475 patients for the development of the model and 8449 for validation. MAIN OUTCOME MEASURES: Mortality after discharge and power of triage model. RESULTS: Mortality after discharge from intensive care was up to 12.4%. The triage model identified patients at risk from death on the ward with a sensitivity of 65.5% and specificity of 87.6%, and an area under the receiver operating curve of 0.86. Variables in the model were age, end stage disease, length of stay in unit, cardiothoracic surgery, and physiology. In the validation dataset the 34% of the patients identified as at risk had a discharge mortality of 25% compared with a 4% mortality among those not at risk. CONCLUSIONS: The discharge mortality of at risk patients may be reduced by 39% if they remain in intensive care units for another 48 hours. The discharge triage model to identify patients at risk from too early and inappropriate discharge from intensive care may help doctors to make the difficult clinical decision of whom to discharge to make room for a patient requiring urgent admission to the unit. If confirmed, this study has implications on the provision of resources.

Arthritis prevalence and activity limitations in older adults.

OBJECTIVE: To evaluate the prevalence of arthritis and activity limitations among older Americans by assessing their demographic, ethnic, and economic characteristics. METHODS: Data from the Asset and Health Dynamic Survey Among the Oldest Old (AHEAD), a national probability sample of community-dwelling adults born before 1924, were analyzed cross-sectionally. Arthritis that resulted in a physician's visit or a joint replacement not associated with a hip fracture was ascertained by self-report. RESULTS: The prevalence of arthritis in older adults ranged from 25% in non-Hispanic whites to 40% in non-Hispanic blacks to 44% in Hispanics. A higher prevalence of arthritis was associated with less education as well as lower income and less wealth. The prevalence of limitations in activities of daily living (ADL) among non-Hispanic white, non-Hispanic black, and Hispanic adults who reported arthritis only was 29%, 30%, and 37%, respectively, and increased to 48%, 57%, and 56%, respectively, among those reporting arthritis plus other chronic conditions, after adjustment for age and sex. CONCLUSION: Non-Hispanic black and Hispanic older adults reported having arthritis at a substantially higher frequency than did non-Hispanic whites. In addition, Hispanics reported higher rates of ADL limitations than did non-Hispanic whites with comparable disease burden. Further study is needed to confirm and elucidate the reasons for these racial and economic disparities in older populations.

European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients.

Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 % (dual) and 96.7 % (triple); graft survival was 92.7 % (dual) and 91.7 % (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 % (dual) and 24.8 % (triple); difference 2.6 %, 95 % CI [-9.4 %-12.9 %], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 % (dual) and 10.7 % (triple). The overall adverse events profile was similar; leukopenia (1.6 % vs 11.6 %, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 % (dual) and 93.6 % (triple); graft survival was 91.8 % (dual) and 90.7 % (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.

A pilot study on the effects of exercise in patients with systemic lupus erythematosus.

OBJECTIVE: A pilot study was designed to assess the efficacy and safety of different exercise therapies on patient-reported fatigue and functional status. METHODS: Ten patients with systemic lupus erythematosus (SLE) were randomly placed in either an aerobic exercise group (group 1: n = 5) or a range of motion/muscle strengthening (ROM/MS) exercise group (group 2: n = 5). Outcome measures assessed at baseline and the end of the study were fatigue, functional status, disease activity, cardiovascular fitness, isometric strength, bone mineral density (BMD) of the lumbar spine and femoral neck, and parathyroid hormone and osteocalcin as representative bone biochemical markers for bone resorption and bone formation, respectively. RESULTS: Both aerobic and ROM/MS types of exercise were safe and did not worsen SLE disease activity. Patients in both exercise groups showed some improvement in fatigue, functional status, cardiovascular fitness, and muscle strength. Both groups showed increased bone turnover, but BMD was unchanged. Eighty percent of the patients met the compliance standard for the study. CONCLUSIONS: This pilot study shows the feasibility of exercise for SLE patients. The potential value of this approach shows promise in the routine management of these patients.

Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia.

OBJECTIVE: Tardive dyskinesia is a movement disorder affecting 20%-40% of patients treated chronically with neuroleptic drugs. The dopamine supersensitivity hypothesis cannot account for the time course of tardive dyskinesia or for the persistence of tardive dyskinesia and the associated structural changes after neuroleptics are discontinued. The authors hypothesized that neuroleptics enhance striatal glutamatergic neurotransmission by blocking presynaptic dopamine receptors, which causes neuronal damage as a consequence of oxidative stress. METHOD: CSF was obtained from 20 patients with schizophrenia, 11 of whom had tardive dyskinesia. Markers for oxidative stress, including superoxide dismutase, lipid hydroperoxide, and protein carbonyl groups, and markers for excitatory neurotransmission, including N-acetylaspartate, N-acetylaspartylglutamate, aspartate, and glutamate, were measured in the CSF specimens. Patients were also rated for tardive dyskinesia symptoms with the Abnormal Involuntary Movement Scale. RESULTS: Tardive dyskinesia patients had significantly higher concentrations of N-acetylaspartate, N-acetylaspartylglutamate, and aspartate in their CSF than patients without tardive dyskinesia when age and neuroleptic dose were controlled for. The significance of the higher levels of protein-oxidized products associated with tardive dyskinesia did not pass Bonferroni correction, however. Tardive dyskinesia symptoms correlated positively with markers of excitatory neurotransmission and protein carbonyl group and negatively with CSF superoxide dismutase activity. CONCLUSIONS: These findings suggest that there are elevated levels of oxidative stress and glutamatergic neurotransmission in tardive dyskinesia, both of which may be relevant to the pathophysiology of tardive dyskinesia.

Impact of joint impairment on disability-specific domains at four years.

The objective of this study was to assess the longitudinal impact of joint impairment on overall disability and crossing domain-specific thresholds for physical activity, mobility, dexterity, instrumental activities of daily living (IADL), and activities of daily living (ADL) that are associated with use of long-term care. This 4-year longitudinal study observed 484 persons older than age 60. Logistic regression assessed the contribution of demographics, psychological mediators, lower- and upper-extremity joint impairment, and comorbidities to increased domain-specific self-reported disability above a threshold associated with use of long-term care. Lower-extremity joint impairment and age predicted crossing thresholds by year 4 in physical activity, mobility, IADL, and ADL disability that were associated with use of long-term care. Lower-extremity joint impairment is a strong risk factor for future disability that is associated with use of long-term care.

Predictors of decline in manual performance in older adults.

OBJECTIVE: To determine factors that predict decline in manual performance using a multivariate model of determinants of functional limitation. DESIGN: Longitudinal observational study. SETTINGS: Ambulatory general medicine clinics, residences of homebound individuals, and a continuing care retirement community. PARTICIPANTS: Subjects were 485 persons more than 60 years of age and included continuing care retirement community (CCRC) residents (n = 215), chronically homebound older persons (n = 65), and ambulatory older adults (n = 205). Mean age at baseline was 78 years. MEASUREMENT: Independent variables included demographics, physician measures of upper-extremity joint impairment, comorbidities derived from physical examination and chart abstract, self-assessed arthritis pain, depression, and anxiety. The major dependent variable was 2-year decline in timed manual performance below a threshold associated with need for long-term care services. RESULTS: The proportion of subjects who exceed a Timed Manual Performance Test threshold of 350 seconds increased slowly from baseline through Year 4 for all age groups but rose rapidly from Year 4 to Year 6 for the oldest group (> 85 years at baseline). Using a discrete survival model, we found that age, education, grip strength, and psychological status predicted crossing the manual performance threshold within a 2-year period. CONCLUSIONS: The findings, coupled with earlier findings that upper extremity joint impairment predicted both grip strength and manual performance, suggest that joint impairment may be an important risk factor for future functional limitation. Since diminished hand function has been shown to predict dependency, development and testing of interventions to maintain or restore upper extremity joint function and reduce pain would appear to be a high research priority.

Role of growth hormone status in the outcome of total knee replacement.

The objective was to assess whether the aging related, variable decline in growth hormone influences total knee replacement outcome. In this prospective cohort study, consecutive patients who underwent unilateral total knee replacement and who met criteria were enrolled from the practice of 1 orthopaedic surgeon at a university hospital. Participants were evaluated 1 month before and 3 months after total knee replacement. Evaluators were not involved in patient care. The primary outcome measure was the Medical Outcome Study 36-item Short Form Health Survey Physical Functioning Scale score 3 months after total knee replacement. In a multiple regression analysis performed to assess the influence of growth hormone status, controlling for social support, body mass index, gender, previous reconstruction, mental health, motivation, and baseline physical functioning, only mental health contributed significantly to outcome. Mental health accounted for 18% of outcome variance. Growth hormone levels did not predict functional status after total knee replacement. Psychological status contributes significantly to total knee replacement physical functional outcome.