Upadacitinib in Rheumatoid Arthritis and Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs: Efficacy and Safety Through 5 Years (SELECT-NEXT).

OBJECTIVE: To report 5-year efficacy and safety of upadacitinib (UPA) in rheumatoid arthritis (RA) from the phase III long-term extension (LTE) of SELECT-NEXT. METHODS: Patients on stable conventional synthetic disease-modifying antirheumatic drugs were randomized to UPA 15 mg once daily (QD), UPA 30 mg QD, or placebo for 12 weeks. Following this, placebo-randomized patients were switched to UPA 15 mg QD or UPA 30 mg QD in the LTE; UPA-randomized patients continued their original dose. Blinding remained until dose switching from UPA 30 mg QD to UPA 15 mg QD because of approval of UPA 15 mg QD; the earliest switch occurred at week 168. Efficacy (as observed) and treatment-emergent adverse events (TEAEs) are reported through 5 years. RESULTS: Overall, 611 (92%) randomized patients entered the LTE; 271 (44%) discontinued the study drug by 5 years, primarily because of adverse events (16%). Clinical outcomes improved or were maintained at 5 years; 51% and 43% of patients achieved Clinical Disease Activity Index remission and 75% and 66% achieved Disease Activity Score in 28 joints based on C-reactive protein < 2.6 among those initially randomized to UPA 15 mg QD and UPA 30 mg QD, respectively. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria responses increased from week 60 through 5 years. Results were similar regardless of initial randomization to UPA or placebo. TEAEs, including TEAEs of special interest, were consistent with earlier analyses and other SELECT studies. Malignancies (excluding nonmelanoma skin cancer), major adverse cardiovascular events, and venous thromboembolic events were reported infrequently. No new safety signals were observed. CONCLUSION: The 5-year benefit-risk profile for UPA in RA remains favorable. (SELECT-NEXT; ClinicalTrials.gov: NCT02675426).

Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study.

BACKGROUND: Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study. METHODS: Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported. RESULTS: Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population. CONCLUSIONS: Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure. TRIAL REGISTRATION: NCT02049138.

MACE and VTE across upadacitinib clinical trial programmes in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

OBJECTIVES: To provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) phase 2b/3 upadacitinib clinical programmes. METHODS: Data were analysed and summarised from clinical trials of RA, PsA and AS treated with upadacitinib 15 mg once daily (QD) and 30 mg QD (as of 30 June 2021). Data from adalimumab (RA and PsA) and methotrexate (RA) arms were included as comparators. Adjudicated MACEs and VTE events were presented as exposure-adjusted rates per 100 patient-years (E/100 PY). Univariable Cox proportional hazard regression analyses assessed potential associations of risk factors for MACE and VTE. RESULTS: In total, 4298 patients received upadacitinib 15 mg (RA n=3209, PsA n=907 and AS n=182) and 2125 patients received upadacitinib 30 mg (RA n=1204 and PsA n=921). In patients with RA and PsA, rates of MACE (0.3-0.6 E/100 PY) and VTE (0.2-0.4 E/100 PY) were similar across upadacitinib doses; in patients with AS, no MACEs and one VTE event occurred. Most patients experiencing MACEs or VTE events had two or more baseline cardiovascular risk factors. Across RA and PsA groups, rates of MACEs and VTE events were similar. CONCLUSIONS: Rates of MACEs and VTE events with upadacitinib were consistent with previously reported data for patients receiving conventional synthetic and biologic disease-modifying anti-rheumatic drugs and comparable with active comparators adalimumab and methotrexate. Associated patient characteristics are known risk factors for MACEs and VTE events. TRIAL REGISTRATION NUMBERS: RA (SELECT-NEXT: NCT02675426; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847; SELECT-COMPARE: NCT02629159; SELECT-EARLY: NCT02706873, SELECT-CHOICE: NCT03086343), PsA (SELECT-PsA 2: NCT03104374; SELECT-PsA 1: NCT03104400), and AS (SELECT-AXIS 1: NCT03178487).

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.

OBJECTIVE: To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA. METHODS: We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations. RESULTS: Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.

OBJECTIVE: To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA. METHODS: We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations. RESULTS: Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Blood Pressure Trends in Patients With Seropositive Rheumatoid Arthritis Compared With Controls Without Rheumatoid Arthritis: A Retrospective Cohort Study.

OBJECTIVE: Rheumatoid arthritis (RA) conveys an increased risk of cardiovascular disease (CVD), making it imperative that traditional CVD risk factors are well controlled. This study compared blood pressure (BP) trends over 13 years among patients with seropositive RA and patients without RA who received care within a large health care system in Minnesota. METHODS: This retrospective cohort study compared 774 patients with seropositive RA and 3254 patients without RA who were matched on sex and year of birth (±5 years) and observed between 2005 and 2017. Generalized estimating equation models were used for longitudinal analyses, with adjustment for demographics, body mass index, smoking status, Charlson Comorbidity Index, number of BP measurements, and number of antihypertensive and oral glucocorticoid medications. RESULTS: Patients both with and without RA had a mean age of 55 and were predominately female (78% with RA; 79% without RA). The mean follow-up was 6.3 (SD 3.4) years for patients with RA and 7.2 (SD 3.3) years for patients without RA. Overall, systolic BP, diastolic BP, and the number of prescribed antihypertensive medications did not differ between groups. Patients with RA were more likely to be current smokers compared with patients without RA (23% vs 11%; P < 0.01) and were less likely to have serum lipid measurements (75% vs 85%; P < 0.01). CONCLUSION: BP was similarly controlled in patients with seropositive RA and patients without RA. However, diastolic BP in patients with RA was trending up in most recent years. Patients with RA were also more likely to smoke compared with controls and were less likely to have serum lipid measurements.

The Effects of Glucosamine and Chondroitin Sulfate on Gut Microbial Composition: A Systematic Review of Evidence from Animal and Human Studies.

Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus Bacteroides in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in Desulfovibrio piger species, an increase in Bacteroidales S24-7 family, and a decrease in Lactobacillus. We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.

Daily Sampling Reveals Personalized Diet-Microbiome Associations in Humans.

Diet is a key determinant of human gut microbiome variation. However, the fine-scale relationships between daily food choices and human gut microbiome composition remain unexplored. Here, we used multivariate methods to integrate 24-h food records and fecal shotgun metagenomes from 34 healthy human subjects collected daily over 17 days. Microbiome composition depended on multiple days of dietary history and was more strongly associated with food choices than with conventional nutrient profiles, and daily microbial responses to diet were highly personalized. Data from two subjects consuming only meal replacement beverages suggest that a monotonous diet does not induce microbiome stability in humans, and instead, overall dietary diversity associates with microbiome stability. Our work provides key methodological insights for future diet-microbiome studies and suggests that food-based interventions seeking to modulate the gut microbiota may need to be tailored to the individual microbiome. Trial Registration: ClinicalTrials.gov: NCT03610477.

Prescription Medication Use Among Community-Based U.S. Adults With Chronic Low Back Pain: A Cross-Sectional Population Based Study.

Many classes of medications have been evaluated in chronic low back pain (cLBP), however their utilization in the community remains unclear. We examined patterns of prescription medication use among Americans with cLBP in a nationally representative, community-based sample. The Back Pain Survey was administered to a representative sample of U.S. adults aged 20 to 69 years (N = 5,103) during the 2009 to 2010 cycle of the National Health and Nutrition Examination Survey. cLBP was defined as self-reported pain in the area between the lower posterior margin of the ribcage and the horizontal gluteal fold on most days for at least 3 months (N = 700). Home-based interviews with pill bottle verification were used to capture commonly prescribed medications for chronic pain. Among the sample of U.S. adults with cLBP aged 20 to 69 years, 36.9% took at least 1 prescription pain medication in the past 30 days; of them, 18.8% used opioids, 9.7% nonsteroidal anti-inflammatory drugs, 8.5% muscle relaxants, and 6.9% gabapentin or pregabalin. Nonpain antidepressants and hypnotics were used by 17.8% and 4.7%, respectively. Opioids were used long-term in 76.9% of cases (median = 2 years) and were frequently coadministered with antidepressants, benzodiazepines, or hypnotics. Ninety-four percent of prescription opioids in the cLBP population were used by individuals with less than a college education. Opioids were the most widely used prescription analgesic class in community-based U.S. adults with cLBP and were often coadministered with other central nervous system-active medications. Opioid use was highly prevalent among less educated Americans with cLBP. PERSPECTIVE: Because prescription opioid use is an issue of national concern, we examined pain-related prescription medication use in community-dwelling U.S. adults with cLBP. Opioids were the most common prescription pain medication, typically used long-term, in combination with other central nervous system-active agents, and disproportionately among individuals with less than a college education.

Population-Wide Associations between Common Viral Pathogens and Self-Reported Arthritis: NHANES 2009-2012.

OBJECTIVE: Persistent infectious agents have been implicated in chronic and recurrent inflammation, which may trigger or worsen many types of arthritis. Our objective was to determine whether exposure to herpes simplex virus (HSV) and human papillomavirus (HPV) is associated with self-reported arthritis among US adults. METHODS: We used data from two consecutive cycles of the National Health and Nutrition Examination Survey (NHANES) from 2009 until 2012 (N of examined adults ages 20-69 = 9483). Participants were classified as having arthritis by self-report. Viral serology for HSV-1 and HSV-2 and HPV PCR studies from oral rinse and vaginal swabs were available for analysis. We compared HSV-1 and HSV-2 seropositivity as well as oral and vaginal HPV DNA positivity between participants with self-reported arthritis vs. those without, adjusting for age, gender, race, income, education, BMI, and the use of immunosuppressive medications. We used three comparator outcomes, gout, kidney stones, and hypertension, to evaluate whether the associations were specific or not to arthritis. RESULTS: Arthritis was associated with older age, female gender, non-Hispanic White and Non-Hispanic Black race, higher BMI, and lower socioeconomic status. HSV-2 seropositivity, but not HSV-1 seropositivity, was independently associated with arthritis after adjustment for age, gender, race, income, education, BMI, and the use of immunosuppressive medications: AOR 1.48 (1.10-1.99). Oral HPV DNA positivity was also independently associated with arthritis: AOR 1.63 (1.17-2.28). After adjustment, there was no statistically significant difference in vaginal HPV DNA positivity between those with vs. those without arthritis: AOR 1.22 (0.90-1.66). There were no significant associations between viral exposures and any of the comparator outcomes. CONCLUSIONS: HSV-2 seropositivity and oral HPV DNA positivity were associated with self-reported arthritis and not with comparator outcomes, after adjustment for multiple potential confounders. These findings should be confirmed in longitudinal studies.

Pathogenic Citrulline-Multispecific B Cell Receptor Clades in Rheumatoid Arthritis.

OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) have proven highly useful as biomarkers for rheumatoid arthritis (RA). However, composition and functionality of the associated autoreactive B cell repertoire have not been directly assessed. We aimed to selectively investigate citrullinated autoantigen-specific B cell receptors (BCRs) involved in RA and initiate studies on their pathogenicity. METHODS: Blood samples were obtained from patients in a University of Minnesota cohort with ACPA-positive RA (n = 89). Tetramer sets bearing citrullinated filaggrin peptide cfc1 or citrullinated α-enolase peptide were constructed to specifically capture autoreactive B cells from the unaltered, polyclonal repertoire in RA patients. Citrullinated peptide tetramer-bound B cells were subjected to flow cytometric cell sorting and single-cell IGH, IGK, and IGL gene sequencing for B cell lineage determinations. BCR gene sequences were also expressed as recombinant monoclonal antibodies (mAb) for direct evaluation of citrullinated autoantigen binding and effector functionality. RESULTS: Using citrullinated peptide tetramer enrichment to investigate single autoreactive blood B cells, we identified biased V-region gene usage and conserved junction arrangements in BCRs from RA patients. Parsimonious clustering of related immunoglobulin gene nucleotide sequences revealed clonal expansions of rare individual B cell clades, in parallel with divergent sequence mutations. Correspondingly, recombinant mAb generated from such BCR lineages demonstrated citrulline-dependent cross-reactivity extending beyond the citrullinated peptides used for B cell capture. A pair of citrullinated autoantigen-specific mAb with cross-reactive binding profiles also promoted arthritis in mice. CONCLUSION: Our findings suggest that broad ACPA specificities in RA arise from a restricted repertoire of evolving citrulline-multispecific B cell clades with pathogenic potential.

Epidemiology of Chronic Low Back Pain in US Adults: Data From the 2009-2010 National Health and Nutrition Examination Survey.

OBJECTIVE: To describe the epidemiologic characteristics and associations with increased health care utilization in US adults with chronic low back pain (LBP). METHODS: The National Health and Nutrition Examination Survey 2009-2010 was administered to adults ages 20-69 years (n = 5,103). Chronic LBP was defined as pain in the area between the lower posterior margin of the rib cage and the horizontal gluteal fold, with a history of pain lasting almost every day for at least 3 months. Demographic and behavioral characteristics were compared between those with chronic LBP and those without. Factors associated with ≥10 health care visits per year were evaluated in the chronic LBP subgroup (n = 700). RESULTS: Chronic LBP associations with adjusted odds ratios (ORadj ) ≥2 included age 50-69 years, less than high school education, annual household income <$20,000, income from disability, depression, sleep disturbances, and medical comorbidities. Subjects with chronic LBP were more likely to be covered by government-sponsored insurance plans (ORadj 3.23 [95% confidence interval (95% CI) 2.19-4.75] for Medicaid and ORadj 2.25 [95% CI 1.57-3.22] for Medicare; P < 0.0001), and visited health care providers more frequently (ORadj 3.35 [95% CI 2.40-4.67] for ≥10 health care visits in the past year; P < 0.0001). In the chronic LBP subgroup, adjusted ORs ≥2 were found for associations between ≥10 visits per year and unemployment, income from disability, depression, and sleep disturbances. CONCLUSION: US adults with chronic LBP are socioeconomically disadvantaged, make frequent health care visits, and are often covered by government-sponsored health insurance. The clustering of behavioral, psychosocial, and medical issues should be considered in the care of Americans with chronic LBP.

Illicit Substance Use in US Adults With Chronic Low Back Pain.

STUDY DESIGN: A population-based cross-sectional survey. OBJECTIVE: The aim of this study was to compare the prevalence of illicit drug use among US adults with and without chronic low back pain (cLBP). SUMMARY OF BACKGROUND DATA: Although addictive medications, such as opioids and benzodiazepines, are frequently prescribed to patients with cLBP, little is known about illicit drug use among Americans with cLBP. METHODS: We used data from the back pain survey, administered to a representative sample of US adults aged 20 to 69 years (N = 5103) during the 2009 to 2010 cycle of the National Health and Nutrition Examination Survey (NHANES). Participants with pain in the area between the lower posterior margin of the ribcage and the horizontal gluteal fold for at least 3 months were classified as having cLBP (N = 700). The drug use questionnaire was self-administered in a private setting, and included data on lifetime and current use of marijuana or hashish, cocaine, heroin, and methamphetamine. Chi-square tests, one-way analysis of variance, and logistic regression, adjusted for age, gender, race, and level of education, were used for comparisons. RESULTS: About 46.5% of US adults with cLBP used marijuana versus 42% of those without cLBP [Adjusted odds ratio (aOR) 1.36, 95% confidence interval (95% CI) 1.06-1.74]. About 22% versus 14% used cocaine (aOR 1.80, 95% CI 1.45-2.24), 9% versus 5% used methamphetamine (aOR 2.03, 95% CI 1.30-3.16), and 5% versus 2% used heroin (aOR 2.43, 95% CI 1.44-4.11). Subjects with cLBP who reported lifetime illicit drug use were more likely to have an active prescription for opioid analgesics than those without illicit drug use history: 22.5% versus 15.3%, P = 0.018. CONCLUSION: cLBP in community-based US adults was associated with higher odds of using marijuana, cocaine, heroin, and methamphetamine. Prescription opioid analgesic use was more common in cLBP sufferers with a history of illicit drug use. LEVEL OF EVIDENCE: 2.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee

To develop an evidence- based guideline for the comprehensive management of osteoarthritis (OA) as a collabora-tion between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommenda-tions for the management of hand, hip, and knee OA.Methods. We identied clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benets and harms of available educational, behavioral, psychosocial, physical, mind- body, and pharmacologic therapies for OA. Grading of Recommen-dations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, includ-ing rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations.Results. Based on the available evidence, either strong or conditional recommendations were made for or against the ap-proaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self- efcacy and self- management programs, tai chi, cane use, hand orthoses for rst carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exer-cises, yoga, cognitive behavioral therapy, kinesiotaping for rst CMC OA, orthoses for hand joints other than the rst CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, du-loxetine, and tramadol.Conclusion. This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision- making that accounts for patients' values, preferences, and comor-bidities. These recommendations should not be used to limit or deny access to therapies

Sustainability and effectiveness of a quality improvement project to improve handoffs to night float residents in an internal medicine residency program.

BACKGROUND: Handoff is the process in which patient care is transitioned from one provider to another. In teaching hospitals, handoffs are frequent, and resident duty hour restrictions have increased the use of night float staff. To date, few studies have focused on long-term sustainability and effectiveness of a handoff quality improvement project. OBJECTIVE: The objective of our resident-driven quality improvement project was to evaluate the effectiveness and sustainability of a standardized template for handoff quality in a community hospital internal medicine program. METHODS: We used a multistep continuous quality improvement approach. Problems in the handoff process were identified through process mapping and anonymous needs assessment of the residents. A group of residents and faculty identified problems during biweekly discussions, created a standardized template, and adopted a new handoff process. We audited handoffs and surveyed residents at 3 and 9 months after implementation to assess effectiveness and sustainability. RESULTS: Before the intervention, only 40% of residents reported regular morning handoff. Using the standardized template, statistically significant, sustained improvements were seen in morning handoff frequency (59% preintervention, 90% at 3 months, 89% at 9 months), along with decreases in unreported overnight events (84% preintervention, 58% at 3 months, 50% at 9 months) and uncertainty about decisions because of poor handoffs (72% preintervention, 49% at 3 months, 37% at 9 months). Statistically significant decreases in missed content (69%-46%) and copy-and-paste behavior (78%-38%) at 3 months were not sustained. CONCLUSIONS: We demonstrated sustained improvements in unreported events and uncertainty caused by poor handoffs. Initial improvements in missed content and copy-and-paste behavior that were not sustained suggest a need for ongoing reinforcement and monitoring of handoff quality.