Online, low-volume meditation does not alter immune-related biomarkers.

Objectives: Prior studies of mindfulness meditation have demonstrated anti-inflammatory and immunoregulatory effects but whether meditation courses delivered online can exert similar effects is poorly understood. Barriers to large scale implementation of traditional mindfulness meditation programs has created an increased interest in the effect of less time- and resource-intensive online meditation courses. The purpose of this study was to determine whether a 6-week online mindfulness program with low time demands on nurses would lead to changes in gene expression, cytokine profiles, telomerase activity, and cortisol profiles. Methods: This was a randomized, parallel pilot study comparing an online mindfulness-based stress management program to an active control group from December 2018 to May 2019. Healthy nurses with above average levels of perceived stress were randomized to receive a 6-week online mindfulness-based stress management program including ≥5 min daily meditation practice or listen to relaxing music for ≥5 min daily as the control arm. Blood samples were collected at baseline and after 6 weeks, and various self-reported measures of stress, physical and emotional health were collected at baseline, after 6 weeks, and after 12 weeks. Whole transcriptome mRNA sequencing of whole blood at baseline and after 6 weeks was performed along with measurement of plasma IL-6, IL-8, IL-10, TNF-α, and IFN-γ. Peripheral blood mononuclear cells were isolated, and telomerase activity was measured. Diurnal salivary cortisol profiles were assessed at baseline and after 6 weeks. The primary outcome was change over time in a pre-determined set of 53 genes representative of the immune-related changes seen with stress, which was analyzed using a mixed linear model. Secondary outcomes included all other self-reported measures and biomarkers mentioned above. Results: A total of 61 nurses were randomized, with 52 having sufficient data to include in the final analysis. After 6 weeks, nurses in the control group reported significant reductions in stress as measured by the Perceived Stress Scale while those in the mindfulness group did not. However, after 12 weeks, the mindfulness group also showed a significant reduction in stress. When compared to the control group, no significant changes in RNA gene expression or any other biomarkers were observed in the nurses who participated in the mindfulness program. Conclusions: Our study found that this brief online mindfulness-based intervention was effective in reducing stress in nurses, albeit with a delayed effect compared to listening to relaxing music. Regarding immunoregulatory effects, there were no significant differences between treatment and control groups in transcriptomic or other tested biomarkers of immune function. This study provides evidence for a floor effect of mindfulness on transcriptional and circulating biomarkers of immune function.

Breakthrough SARS-CoV-2 Infections in Patients With Immune-Mediated Disease Undergoing B Cell-Depleting Therapy: A Retrospective Cohort Analysis.

OBJECTIVE: Patients with immune-mediated inflammatory diseases (IMIDs) receiving B cell-depleting therapy (BCDT) are among the most vulnerable to severe COVID-19, as well as the most likely to suboptimally respond to SARS-CoV-2 vaccines. However, little is known about the frequency or severity of breakthrough infection in this population. We retrospectively analyzed a large group of vaccinated IMID patients undergoing BCDT in order to identify breakthrough COVID-19 infections and assess their outcomes. METHODS: In this retrospective cohort study, the pharmacy records and COVID-19 registry at the Cleveland Clinic were searched using specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes to identify IMIDs patients who 1) received treatment with BCDT, 2) were vaccinated against SARS-CoV-2, and 3) experienced breakthrough infections. Each electronic medical record was reviewed to extract clinical data and outcomes. Univariate and multivariable logistic/proportional odds regression models were used to examine the risk factors for severe outcomes. RESULTS: Of 1,696 IMID patients receiving BCDT, 74 developed breakthrough COVID-19 prior to December 16, 2021. Outcomes were severe, with 29 patients hospitalized (39.2%), 11 patients requiring critical care (14.9%), and 6 deaths (8.1%). Outpatient anti-SARS-CoV-2 monoclonal antibodies were used to treat 21 patients, with 1 hospitalization and no deaths. A comparator analysis examining 1,437 unvaccinated IMID patients receiving BCDT over the same time period identified 57 COVID-19 cases (4.0%), with 28 requiring hospitalization (49.1%), including 7 deaths (12.3%). CONCLUSION: IMID patients receiving BCDT regardless of vaccine status appear to be vulnerable to infection with SARS-CoV-2, and use of BCDT is frequently associated with severe outcomes. Outpatient use of anti-SARS-CoV-2 monoclonal antibody therapy appears to be associated with enhanced clinical outcomes.

Biologic initiation rates in systemic-naive psoriasis patients after first-line apremilast versus methotrexate use.

Aim: To compare rates of biologic initiation after commencing treatment with apremilast (APR) versus methotrexate (MTX) in systemic-naive patients with psoriasis (PsO). Methods: This was a retrospective cohort study of systemic-naive patients with PsO who initiated treatment with APR or MTX between 1 January 2015 and 31 March 2018. Outcomes: Adjusted rates of biologic initiation during follow-up were compared by logistic and Cox regressions. Results: APR initiators had 58% lower likelihood of biologic initiation (odds ratio: 0.42; 95% CI: 0.37-0.48; p < 0.001), lower adjusted biologic initiation rate (14.4% [95% CI: 13.2-15.7%] vs 28.6% [95% CI: 26.8-30.5%]), lower risk of biologic initiation (hazard ratio: 0.45; 95% CI: 0.40-0.51; p < 0.001) compared with MTX initiators. Conclusion: Systemic-naive patients with PsO have a lower rate of biologic initiation over 1 year following APR initiation.

Disparities in healthcare in psoriatic arthritis: an analysis of 439 patients from 13 countries.

OBJECTIVES: Patient care can vary substantially by country. The objective was to explore differences in psoriatic arthritis (PsA) across countries for disease activity, impact and treatments. METHODS: A cross-sectional analysis of 13 countries from the Remission/Flare in PsA study (NCT03119805) of consecutive adult patients with definite PsA was performed. Countries were classified into tertiles by gross domestic product (GDP)/capita. Disease activity (Disease Activity in PsA, DAPSA and Minimal Disease Activity, MDA) and their components, disease impact (patient-reported outcomes) and biological disease-modifying antirheumatic drugs (bDMARDs) were analysed per country and compared between the three tertiles of GDP/capita by parametric and non-parametric tests. We also explored the percentage of patients with significant disease activity (DAPSA >14) and no ongoing bDMARD prescription. RESULTS: In 439 patients (50.6% male, mean age 52.3 years, mean disease duration 10.1 years), disease activity and disease impact were higher in the lowest GDP/capita countries. DAPSA remission and MDA were attained in the lowest tertile in 7.0% and 18.4% patients, vs 29.1% and 49.5% in the middle tertile and 16.8% and 41.3% in the high tertile, respectively (all p<0.001). bDMARDs use was similar in the tertiles (overall mean 61%). The overall rate of patients with DAPSA >14 and no bDMARDs was 18.5%, and was higher in lower GDP/capita countries (p=0.004). CONCLUSION: PsA patients from countries with the lowest GDP/capita, despite similar use of bDMARDs, were more likely to have high disease activity and worse disease impact. There is a need for more equity in healthcare.

Cardiorenal risk of celecoxib compared with naproxen or ibuprofen in arthritis patients: insights from the PRECISION trial.

AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs, both prescribed and over the counter. The long-term cardiovascular safety of NSAIDs in patients with arthritis has engendered controversy. Concerns remain regarding the relative incidence and severity of adverse cardiorenal effects, particularly in arthritis patients with established cardiovascular (CV) disease or risk factors for disease as illustrated by the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen) trial participants (NCT00346216).We further investigated whether the selective COX-2 Inhibitor celecoxib has a superior cardiorenal safety profile compared with ibuprofen or naproxen in the PRECISION population. METHODS AND RESULTS: Twenty-four thousand eighty-one patients who required NSAIDs for osteoarthritis or rheumatoid arthritis (RA) and had increased CV risk randomly received celecoxib, ibuprofen, or naproxen. The current pre-specified secondary analysis assessed the incidence, severity, and NSAID-related risk of the pre-specified composite cardiorenal outcome (adjudicated renal event, hospitalization for congestive heart failure, or hospitalization for hypertension) in the intention-to-treat (ITT) population. An on-treatment analysis assessed safety in those taking the study medication. Following a mean treatment duration of 20.3 ± 16.0 months and a mean follow-up of 34.1 ± 13.4 months, the primary cardiorenal composite outcome occurred in 423 patients (1.76%) in the ITT population. Of these 423 patients, 118 (28%) were in the celecoxib, 166 (39%) in the ibuprofen, and 139 (33%) in the naproxen group. In a multivariable Cox regression model adjusted for independent clinical variables, celecoxib showed a significantly lower risk compared with ibuprofen [hazard ratio (HR) 0.67, confidence interval (CI) 0.53-0.85, P = 0.001) and a trend to lower risk compared with naproxen (HR 0.79, CI 0.61-1.00, P = 0.058). In the ITT analysis, clinically significant renal events occurred in 220 patients with events rates of 0.71%, 1.14%, and 0.89% for celecoxib, ibuprofen, and naproxen, respectively (P = 0.052), while in the on-treatment analysis the rates were 0.52%, 0.91%, and 0.78% (P &lt; 0.001). CONCLUSION: In the current era, long-term NSAID use was associated with few cardiorenal events in arthritis patients. At the doses studied, celecoxib displayed fewer renal events and hence more favourable cardiovascular safety compared with ibuprofen or naproxen. These results have considerable clinical implications for practitioners managing individuals with chronic arthritis pain and high risk of impaired renal function and/or heart failure.Clinical Trial Registration: NCT00346216.

Economic Evaluation of Timely Versus Delayed Use of Tumor Necrosis Factor Inhibitors for Treatment of Psoriatic Arthritis in the US.

INTRODUCTION: The present study aimed to evaluate clinical outcomes and costs associated with timely versus delayed use of tumor necrosis factor inhibitors (TNFis) among patients with moderately to severely active psoriatic arthritis (PsA) with and without moderate/severe psoriasis (Ps) from a US payer's perspective. METHODS: An economic model evaluated PsA patients initially treated with a TNFi (timely TNFi use) or apremilast (delayed TNFi use). Patients without joint (American College of Rheumatology 20%, [ACR20]) improvement either switched TNFis or initiated one. ACR20 responses were evaluated for all patients and skin responses by Psoriasis Area Severity Index 75% (PASI75) for those with concomitant PsA and Ps. Published randomized controlled trials and publicly available databases provided model inputs. Effectiveness measures included 1-year responses and number needed to treat (NNT). Direct costs, costs per responder, and incremental costs per responder were calculated. RESULTS: After 1 year, timely TNFi-treated patients had higher ACR20 responses (70.4% vs. 59.6%) and lower NNTs (1.42 vs. 1.68) compared with delayed use. Among PsA + Ps patients, timely TNFi use was associated with higher ACR20 + PASI75 responses (41.0% vs. 30.0%) and lower NNTs (2.44 vs. 3.33). Cost per ACR20 responder was higher ($56,492 vs. $52,835) among PsA patients without Ps; with concomitant Ps, cost per ACR20 + PASI75 responder was lower for timely TNFi use ($100,954 vs. $111,686). Incremental costs per responder for timely versus delayed TNFi were $76,823 in PsA and $71,791 in PsA and Ps. CONCLUSION: Timely use of TNFis is a cost-effective strategy for the management of PsA based on improvements in both joint and/or skin disease. FUNDING: AbbVie Inc.

Type 2 diabetes and osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Observational studies have reported an association between type 2 diabetes and osteoarthritis (OA) development and progression. However no systematic review of the literature exists assessing whether this association is consistently true. We aimed to systematically review the association between type 2 diabetes and the presence, development, and progression of OA. METHODS: We searched MEDLINE, SCOPUS, EMBASE, the Web of Science, and Grey Literature (through August 2014) for prospective cohort, cross-sectional, and case-control studies with confidence intervals (CI) that reported an association between type 2 diabetes and impaired glucose tolerance (IGT) and the development or presence of OA of any joint. RESULTS: Ten studies and fourteen ratios were included in the analysis. The pooled population size in our meta-regression was 16,742 patients. Type 2 diabetes was significantly associated with the development or presence of OA (OR; 1·21, 95% CI: 1·02-1·41). In the subset of 7 studies that did control for weight or BMI there was an increased odds of OA associated with type 2 diabetes was (OR: 1·25, 95% CI: 1·05-1·46) from a smaller pool of patients (n=7156). CONCLUSIONS: Type 2 diabetes is associated with the development and presence of radiographic and symptomatic OA even when controlling for body mass index and weight.

Comprehensive treatment of psoriatic arthritis: managing comorbidities and extraarticular manifestations.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis that can lead to decreased health-related quality of life and permanent joint damage leading to functional decline. In addition to joint and skin manifestations, both psoriasis and PsA are associated with numerous comorbidities and extraarticular/cutaneous manifestations, which may influence the physician's choice of therapy. The objectives of this review are (1) to identify comorbidities in patients with PsA based on the available evidence; (2) to examine the effects of these comorbidities or extraarticular/cutaneous manifestation on the management of patients with PsA as well as the selection of therapy; and (3) to highlight research needs around comorbidities and treatment paradigms. This review is part of a treatment recommendations update initiated by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

Oral or transdermal opioids for osteoarthritis of the knee or hip.

BACKGROUND: Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older people. Opioids may be a viable treatment option if people have severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory. This is an update of a Cochrane review first published in 2009. OBJECTIVES: To determine the effects on pain, function, safety, and addiction of oral or transdermal opioids compared with placebo or no intervention in people with knee or hip osteoarthritis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL (up to 28 July 2008, with an update performed on 15 August 2012), checked conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials that compared oral or transdermal opioids with placebo or no treatment in people with knee or hip osteoarthritis. We excluded studies of tramadol. We applied no language restrictions. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate. We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain and function, and risk ratios for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. MAIN RESULTS: We identified 12 additional trials and included 22 trials with 8275 participants in this update. Oral oxycodone was studied in 10 trials, transdermal buprenorphine and oral tapentadol in four, oral codeine in three, oral morphine and oral oxymorphone in two, and transdermal fentanyl and oral hydromorphone in one trial each. All trials were described as double-blind, but the risk of bias for other domains was unclear in several trials due to incomplete reporting. Opioids were more beneficial in pain reduction than control interventions (SMD -0.28, 95% CI -0.35 to -0.20), which corresponds to a difference in pain scores of 0.7 cm on a 10-cm visual analogue scale (VAS) between opioids and placebo. This corresponds to a difference in improvement of 12% (95% CI 9% to 15%) between opioids (41% mean improvement from baseline) and placebo (29% mean improvement from baseline), which translates into a number needed to treat (NNTB) to cause one additional treatment response on pain of 10 (95% CI 8 to 14). Improvement of function was larger in opioid-treated participants compared with control groups (SMD -0.26, 95% CI -0.35 to -0.17), which corresponds to a difference in function scores of 0.6 units between opioids and placebo on a standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10. This corresponds to a difference in improvement of 11% (95% CI 7% to 14%) between opioids (32% mean improvement from baseline) and placebo (21% mean improvement from baseline), which translates into an NNTB to cause one additional treatment response on function of 11 (95% CI 7 to 14). We did not find substantial differences in effects according to type of opioid, analgesic potency, route of administration, daily dose, methodological quality of trials, and type of funding. Trials with treatment durations of four weeks or less showed larger pain relief than trials with longer treatment duration (P value for interaction = 0.001) and there was evidence for funnel plot asymmetry (P value = 0.054 for pain and P value = 0.011 for function). Adverse events were more frequent in participants receiving opioids compared with control. The pooled risk ratio was 1.49 (95% CI 1.35 to 1.63) for any adverse event (9 trials; 22% of participants in opioid and 15% of participants in control treatment experienced side effects), 3.76 (95% CI 2.93 to 4.82) for drop-outs due to adverse events (19 trials; 6.4% of participants in opioid and 1.7% of participants in control treatment dropped out due to adverse events), and 3.35 (95% CI 0.83 to 13.56) for serious adverse events (2 trials; 1.3% of participants in opioid and 0.4% of participants in control treatment experienced serious adverse events). Withdrawal symptoms occurred more often in opioid compared with control treatment (odds ratio (OR) 2.76, 95% CI 2.02 to 3.77; 3 trials; 2.4% of participants in opioid and 0.9% of participants control treatment experienced withdrawal symptoms). AUTHORS' CONCLUSIONS: The small mean benefit of non-tramadol opioids are contrasted by significant increases in the risk of adverse events. For the pain outcome in particular, observed effects were of questionable clinical relevance since the 95% CI did not include the minimal clinically important difference of 0.37 SMDs, which corresponds to 0.9 cm on a 10-cm VAS.

Opioid therapy for treating rheumatoid arthritis pain.

BACKGROUND: Despite improvements in the management of rheumatoid arthritis (RA), pain control is often inadequate even when inflammation is well controlled. OBJECTIVES: To assess the efficacy and safety of opioid analgesics for treating pain in patients with RA. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE for studies to May 2010. We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of articles. SELECTION CRITERIA: Studies were included if they were randomized or quasi-randomized controlled trials (RCTs or CCTs) which compared opioid therapy to another therapy (active or placebo) for pain in patients with RA. Outcomes of interest were pain, adverse effects, function and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion, extracted the data, and performed a risk of bias assessment. MAIN RESULTS: Eleven studies (672 participants) were included in the review. Four studies assessed the efficacy of single doses of various opioid and non-opioid analgesics; a pooled analysis of these studies was not performed but in each study opioids reduced pain more than placebo. There were no differences between analgesic drugs in these studies.Seven studies were between one and six weeks in duration and assessed six different oral opioids (dextropropoxyphene, codeine, tramadol, tilidine, pentazocine, morphine), either alone or combined with non-opioid analgesics. The only strong opioid investigated was controlled-release morphine sulphate, in a single study with 20 participants. Six studies compared an opioid to placebo. Opioids were superior to placebo in patient-reported global impression of change (3 studies, 324 participants: relative risk (RR) 1.44, 95% CI 1.03 to 2.03) but not for the number of withdrawals due to inadequate analgesia (4 studies, 345 participants: RR 0.82, 95% CI 0.34 to 2.0). Adverse events (most commonly nausea, vomiting, dizziness and constipation) were more frequent in patients receiving opioids compared to placebo (4 studies, 371 participants: odds ratio 3.90, 95% CI 2.31 to 6.56); the pooled risk ratio for withdrawal due to adverse events was 2.67 (3 studies, 331 participants: 95% CI 0.52 to 13.75). One study compared an opioid (codeine with paracetamol) to an NSAID (diclofenac) and found no difference in efficacy or safety between interventions. AUTHORS' CONCLUSIONS: There is limited evidence that weak oral opioids may be effective analgesics for some patients with RA, but adverse effects are common and may offset the benefits of this class of medications. There is insufficient evidence to draw conclusions regarding the use of weak opioids for longer than six weeks, or the role of strong opioids.

Plantar shear stress distribution in patients with rheumatoid arthritis: relevance to foot pain.

BACKGROUND: Rheumatoid arthritis is an autoimmune disease that causes chronic, progressive joint inflammation; it commonly affects the joints of the feet. Biomechanical alterations and daily pain in the foot are the common outcomes of the disease. Earlier studies focusing on plantar pressure in such patients reported increased vertical loading along with peak pressure-pain associations. However, footwear designed according to the pressure profiles did not relieve symptoms effectively. We examined plantar shear and pressure distribution in patients with rheumatoid arthritis and compared the findings with those of controls, and we investigated a potential relationship between foot pain and local shear stresses. METHODS: A custom-built platform was used to collect plantar pressure and shear stress data from nine patients with rheumatoid arthritis and 14 control participants. Seven patients reported the presence of pain under their feet. Pressure-time and shear-time integral values were also calculated. RESULTS: Peak pressure, pressure-time integral, resultant shear-time integral, and mediolateral shear stress magnitudes were higher in the complication group (P < .05). An association between peak shear-time integral and maximum pain locations was observed. CONCLUSIONS: Increased mediolateral shear stresses under the rheumatoid foot might be attributable to gait instability in such patients. A correlation between the locations of maximum shear-time integral and pain indicate the clinical significance of plantar shear in patients with rheumatoid arthritis.

Oral or transdermal opioids for osteoarthritis of the knee or hip.

BACKGROUND: Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly. Opioids may be a viable treatment option if patients suffer from severe pain or if other analgesics are contraindicated. However, the evidence about their effectiveness and safety is contradictory. OBJECTIVES: To determine the effects on pain and function and the safety of oral or transdermal opioids as compared with placebo or no intervention in patients with osteoarthritis of the hip or knee. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL (up to 28 July 2008), checked conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA: Studies were included if they were randomised or quasi-randomised controlled trials that compared oral or transdermal opioids with placebo or no treatment in patients with osteoarthritis of the knee or hip. Studies of tramadol were excluded. No language restrictions were applied. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate. Standardised mean differences (SMDs) and 95% confidence intervals (CI) were calculated for pain and function, and risk ratios for safety outcomes. Trials were combined using inverse-variance random-effects meta-analysis. MAIN RESULTS: Ten trials with 2268 participants were included. Oral codeine was studied in three trials, transdermal fentanyl and oral morphine in one trial each, oral oxycodone in four, and oral oxymorphone in two trials. Overall, opioids were more effective than control interventions in terms of pain relief (SMD -0.36, 95% CI -0.47 to -0.26) and improvement of function (SMD -0.33, 95% CI -0.45 to -0.21). We did not find substantial differences in effects according to type of opioid, analgesic potency (strong or weak), daily dose, duration of treatment or follow up, methodological quality of trials, and type of funding. Adverse events were more frequent in patients receiving opioids compared to control. The pooled risk ratio was 1.55 (95% CI 1.41 to 1.70) for any adverse event (4 trials), 4.05 (95% CI 3.06 to 5.38) for dropouts due to adverse events (10 trials), and 3.35 (95% CI 0.83 to 13.56) for serious adverse events (2 trials). Withdrawal symptoms were more severe after fentanyl treatment compared to placebo (SMD 0.60, 95% CI 0.42 to 0.79; 1 trial). AUTHORS' CONCLUSIONS: The small to moderate beneficial effects of non-tramadol opioids are outweighed by large increases in the risk of adverse events. Non-tramadol opioids should therefore not be routinely used, even if osteoarthritic pain is severe.

Consensus on a core set of domains for psoriatic arthritis.

A psoriatic arthritis (PsA) module was convened at OMERACT 8 in order to achieve consensus on the core domains that should be included in randomized controlled trials and longitudinal observational cohorts of subjects with PsA. Following a plenary session at which current status of measures used to assess PsA were reviewed, and discussion at breakout groups, the group achieved consensus on 6 core domains: peripheral joint activity, skin activity, pain, patient global assessment, physical function, and health-related quality of life. In addition the following domains were considered important but not mandatory: spinal disease, dactylitis, enthesitis, fatigue, nail disease, radiography, physician global assessment, and acute-phase reactants. A research agenda was proposed to include development and validation of instruments for the domains where none existed, and in particular further research was recommended for the following areas: magnetic resonance imaging and ultrasound of joints, enthesitis, skin and synovial tissue analysis, and "participation."

Development of a preliminary index that predicts adverse events after total knee replacement.

OBJECTIVE: We undertook this study to assess the relationships between hospital characteristics, volume of procedures, and perioperative outcomes after total knee replacement (TKR), and to use this information to construct a simple predictive index for perioperative outcomes that incorporates hospital- and patient-level characteristics. METHODS: We studied Medicare beneficiaries who underwent TKR in 4 US states in 2000. Orthopedic surgery administrators from hospitals caring for patients in this sample were surveyed about a range of hospital characteristics. The relationships between these hospital characteristics, patient variables, and 90-day postoperative adverse events (including death, pulmonary embolus, pneumonia, deep wound infection, and acute myocardial infarction) were assessed using generalized estimating equations adjusting for hospital volume. These relationships were assessed in low- and high-risk patient groups. Variables from the final multivariate model were used to create an index that was tested against 90-day adverse event rates. RESULTS: Three hundred twenty-seven (3.6%) of the patients undergoing TKR in our sample experienced an adverse event. In the final multivariate regression models, variables that predicted adverse perioperative events included low hospital volume (fewer than 23 TKRs in the Medicare population per year), absence of a preoperative teaching program, fewer TKRs conducted in a dedicated orthopedic surgery operating room, patient age >70 years, male sex, and at least 1 comorbid condition. The effect of volume on perioperative adverse events was evident both in patients with few risk factors and in patients with several risk factors. An index including the 6 patient and hospital variables discriminated well, with adverse events occurring in 2.0% (95% confidence interval [95% CI] 1.4-2.7%) of patients in the lowest risk category and in 7.4% (95% CI 4.5-12.3%) of patients in the highest risk category (P for trend < 0.001). The index predicted adverse event rates both in hospitals with a low volume of TKRs and in those with a high volume of TKRs. CONCLUSION: Characteristics of hospital care, procedure volume, and patient-level factors are all associated with perioperative outcomes of TKR. A preliminary index combining hospital characteristics and volume is moderately predictive of adverse perioperative outcomes. The index is predictive of outcome in low- and high-volume hospitals.