Frailty and Risk of Serious Infections in Patients With Rheumatoid Arthritis Treated With Biologic or Targeted-Synthetic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs. METHODS: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA. Patients' baseline frailty risk score was calculated using a Claims-Based Frailty Index (≥0.2 defined as frail) 12 months prior to drug initiation. The primary outcome was time to serious infection; secondarily, we examined time-to-any infection and all-cause hospitalizations. We used Cox proportional hazards to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs) and assessed the significance of interaction terms between frailty status and drug class. RESULTS: A total of 57,980 patients, mean (±SD) age 48.1 ± 10.1 were included; 48,139 (83%) started TNFi, 8,111 (14%) non-TNFi biologics, and 1,730 (3%) JAKi. Among these, 3,560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (adjusted hazard ratio [95% CI] 1.5, 1.2-1.9) and 40% higher risk of inpatient admissions (1.4 [1.3-1.6]) compared with nonfrail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to nonfrail patients among those on TNFi (1.2 [1.1-1.3]) or non-TNFi (1.2 [1.0-1.4]) or JAKi (1.4 [1.0-2.0]). CONCLUSION: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with biologic or targeted-synthetic DMARDs.

Optimizing Medication Use in Older Adults With Rheumatic Musculoskeletal Diseases: Deprescribing as an Approach When Less May Be More.

The world population is aging, and the rheumatology workforce must be prepared to care for medically complex older adults. We can learn from our colleagues and experts in geriatrics about how to best manage multimorbidity, polypharmacy, geriatric syndromes, and shifting priorities of older adults in the context of delivering care for rheumatic and musculoskeletal diseases (RMDs). Polypharmacy, a common occurrence in an aging population with multimorbidity, affects half of older adults with RMDs and is associated with increased risk of morbidity and mortality. In addition, potentially inappropriate medications that should be avoided under most circumstances is common in the RMD population. In recent years, deprescribing, known as the process of tapering, stopping, discontinuing, or withdrawing drugs, has been introduced as an approach to improve appropriate medication use among older adults and the outcomes that are important to them. As the rheumatology patient population ages globally, it is imperative to understand the burden of polypharmacy and the potential of deprescribing to improve medication use in older adults with RMDs. We encourage the rheumatology community to implement geriatric principles, when possible, as we move toward becoming an age-friendly health care specialty.

Additional risk factors associated with thrombosis and pregnancy morbidity in a unique cohort of antiphospholipid antibody-positive patients.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition with significant morbidity. The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis, venous thrombosis, and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies (aPLs)-positive carriers. METHODS: This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital. Among 453 patients screened, 297 patients had persistent positive aPL. We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients. And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations. The levels of circulating markers of neutrophil extracellular traps (NETs) (cell-free DNA and citrullinated histone H3 [Cit-H3]) were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients. RESULTS: Additional risk factors associated with arterial thrombosis among aPL-positive carriers included: smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408-15.637, P  = 0.0001), hypertension (OR = 2.368, 95% CI = 1.249-4.491, P  = 0.008), and the presence of underlying autoimmune disease (OR = 4.401, 95% CI = 2.387-8.113, P < 0.001). Additional risks associated with venous thrombosis among aPL carriers included: smoking (OR = 4.594, 95% CI = 1.681-12.553, P  = 0.029) and the presence of underlying autoimmune disease (OR = 6.330, 95% CI = 3.355-11.940, P < 0.001). The presence of underlying autoimmune disease (OR = 3.301, 95% CI = 1.407-7.744, P  = 0.006) is the additional risk, which demonstrated a significant association with APS pregnancy morbidity. Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases. Furthermore, control neutrophils that are conditioned with APS patients'sera have more pronounced NET release compared with those treated with aPL carriers'sera without underlying autoimmune diseases. CONCLUSIONS: We identified several potential additional risk factors for APS clinical manifestations among a large cohort of Chinese aPL carriers. Our data may help physicians to risk stratify aPL-positive Asian patients.

Patient and Spine Surgeon Perceptions on Shared Decision-Making in the Treatment of Older Adults Undergoing Corrective Surgery for Adult Spinal Deformity.

STUDY DESIGN: Retrospective. OBJECTIVE: To understand patients' and spine surgeons' perspectives about decision-making around surgery for adult spinal deformity. SUMMARY OF BACKGROUND DATA: Surgery for correction of adult spinal deformity is often beneficial; however, in over 20% of older adults (≥ 65 yrs of age), outcomes from surgery are less desirable. MATERIALS AND METHODS: We conducted semistructured, in-depth interviews with six patients and five spine surgeons. Two investigators independently coded the transcripts using constant comparative method, as well as an integrative, team-based approach to identify themes. RESULTS: Patients themes: 1) patients felt surgery was their only choice because they were running out of time to undergo invasive procedures; 2) patients mentally committed to surgery prior to the initial encounter with their surgeon and contextualized the desired benefits while minimizing the potential risks; 3) patients felt that the current decision support tools were ineffective in preparing them for surgery; and 4) patients felt that pain management was the most difficult part of recovery from surgery. Surgeons themes: 1) surgeons varied substantially in their interpretations of shared decision-making; 2) surgeons did not consider patients' chronological age as a major contraindication to undergoing surgery; 3) there is a goal mismatch between patients and surgeons in the desired outcomes from surgery, where patients prioritize complete pain relief whereas surgeons prioritize concrete functional improvement; and 4) surgeons felt that patient expectations from surgery were often established prior to their initial surgery visit, and frequently required recalibration. CONCLUSION: Older adult patients viewed the decision to have surgery as time-sensitive, whereas spine surgeons expressed the need for recalibrating patient expectations and balancing the risks and benefits when considering surgery. These findings highlight the need for improved understanding of both sides of shared decision-making which should involve the needs and priorities of older adults to help convey patient-specific risks and choice awareness. LEVEL OF EVIDENCE: 3.

Variables Associated With Response to Therapy in Patients With Interstitial Pneumonia With Autoimmune Features.

BACKGROUND/OBJECTIVE: We have limited knowledge regarding characteristics of patients with interstitial pneumonia with autoimmune features (IPAF) that are associated with response to immunosuppression. In this study, we used published IPAF criteria to characterize features associated with response to treatment. METHODS: We conducted a single-center medical records review study of 63 IPAF patients to evaluate for serological, clinical, and morphological characteristics that are associated with response to immunosuppression. Response was defined as % relative functional vital capacity decline of less than 10% and absence of death or lung transplant within the first year of continuous immunosuppressive therapy. Nonparametric measures of association and multivariate logistic regression were used to evaluate the relationship between baseline characteristics and immunosuppressive response. RESULTS: There was a trend of greater progression among men, ever smokers, those negative for antisynthetase antibodies, and those with usual interstitial pneumonia radiographic pattern, but no statistically significant relationship was found between baseline serological, clinical, or morphological features and response to immunosuppression. Patients on combination therapy with mycophenolate mofetil and prednisone had less disease progression (p = 0.018) than those on regimens that did not include both of these medications. CONCLUSIONS: In our cohort, baseline clinical assessment did not identify which patients with IPAF will respond to immunosuppressive therapy. Combination therapy with mycophenolate mofetil and prednisone was associated with lack of disease progression in our IPAF patients, including in IPAF-usual interstitial pneumonia. Further studies are needed to evaluate which IPAF patients would benefit from immunosuppressive therapy, antifibrotic therapy, or a combination of both.

Association of Breast Implants with Nonspecific Symptoms, Connective Tissue Diseases, and Allergic Reactions: A Retrospective Cohort Analysis.

BACKGROUND: Given the rising media attention regarding various adverse conditions attributed to breast implants, the authors examined the association between breast implantation and the risk of being diagnosed with connective tissue diseases, allergic reactions, and nonspecific constitutional complaints in a cohort study with longitudinal follow-up. METHODS: Women enrolled in a regional military health care system between 2003 and 2012 were evaluated in this retrospective cohort study. A propensity score was generated to match women who underwent breast implantation with women who did not undergo breast implantation. The propensity score included age, social history, health care use, comorbidities, and medication use. Outcomes assessed included International Classification of Diseases, Ninth Revision, diagnoses codes for (1) nonspecific constitutional symptoms, (2) nonspecific cardiac conditions, (3) rheumatoid arthritis and systemic lupus erythematosus, (4) other connective tissue diseases, and (5) allergic reactions. RESULTS: Of 22,063 women included in the study (513 breast implants and 21,550 controls), we propensity score-matched 452 breast implant recipients with 452 nonrecipients. Odds ratios and 95 percent confidence intervals in breast implant recipients compared to nonrecipients were similar, including nonspecific constitutional symptoms (OR, 0.77; 95 percent CI, 0.53 to 1.13), nonspecific cardiac conditions (OR, 0.97; 95 percent CI, 0.69 to 1.37), rheumatoid arthritis and systemic lupus erythematosus (OR, 0.66; 95 percent CI, 0.33 to 1.31), other connective tissue diseases (OR, 1.02; 95 percent CI, 0.78 to 1.32), and allergic reactions (OR, 1.18; 95 percent CI, 0.84 to 1.66). CONCLUSIONS: Women with breast implants did not have an increased likelihood of being diagnosed with nonspecific constitutional symptoms, connective tissue disorders, and/or allergic reaction conditions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Do Decision Aids Benefit Patients with Chronic Musculoskeletal Pain? A Systematic Review.

OBJECTIVE: To review the effect of patient decision aids for adults making treatment decisions regarding the management of chronic musculoskeletal pain. METHODS: We performed a systematic review of randomized controlled trials of adults using patient decision aids to make treatment decisions for chronic musculoskeletal pain in the outpatient setting. RESULTS: Of 477 records screened, 17 met the inclusion criteria. Chronic musculoskeletal pain conditions included osteoarthritis of the hip, knee, or trapeziometacarpal joint and back pain. Thirteen studies evaluated the use of a decision aid for deciding between surgical and nonsurgical management. The remaining four studies evaluated decision aids for nonsurgical treatment options. Outcomes included decision quality, pain, function, and surgery utilization. The effects of decision aids on decision-making outcomes were mixed. Comparing decision aids with usual care, all five studies that examined knowledge scores found improvement in patient knowledge. None of the four studies that evaluated satisfaction with the decision-making process found a difference with use of a decision aid. There was limited and inconsistent data on other decision-related outcomes. Of the eight studies that evaluated surgery utilization, seven found no difference in surgery rates with use of a decision aid. Five studies made comparisons between different types of decision aids, and there was no clearly superior format. CONCLUSIONS: Decision aids may improve patients' knowledge about treatment options for chronic musculoskeletal pain but largely did not impact other outcomes. Future efforts should focus on improving the effectiveness of decision aids and incorporating nonpharmacologic and nonsurgical management options.

Pharmacotherapies in Geriatric Chronic Pain Management.

Pharmacologic management of chronic pain in older adults is one component of the multimodal, interdisciplinary management of this complex condition. In this article, we summarize several of the key barriers to effective pharmacologic management in older adults and review the existing (albeit limited) evidence for its effectiveness and safety, especially in a medically complex population with multimorbidity. This review covers topical formulations, acetaminophen, oral nonsteroidal antiinflammatory drugs, and adjuvant therapies. The article concludes with a suggested approach to managing chronic pain in the older patient, incorporating goals and expectations for treatment as well as careful monitoring of medication adjustments.

A Prospective Study of Back Pain and Risk of Falls Among Older Community-dwelling Women.

BACKGROUND: Back pain and falls are common health conditions among older U.S. women. The extent to which back pain is an independent risk factor for falls has not been established. METHODS: We conducted a prospective study among 6,841 community-dwelling U.S. women at least 65 years of age from the Study of Osteoporotic Fractures (SOF). Baseline questionnaires inquired about any back pain, pain severity, and frequency in the past year. During 1 year of follow-up, falls were summed from self-reports obtained every 4 months. Two outcomes were studied: recurrent falls (≥2 falls) and any fall (≥1 fall). Associations of back pain and each fall outcome were estimated with risk ratios (RRs) and 95% confidence intervals (CIs) from multivariable log-binomial regression. Adjustments were made for age, education, smoking status, fainting history, hip pain, stroke history, vertebral fracture, and Geriatric Depression Scale. RESULTS: Most (61%) women reported any back pain. During follow-up, 10% had recurrent falls and 26% fell at least once. Any back pain relative to no back pain was associated with a 50% increased risk of recurrent falls (multivariable RR = 1.5, 95% CI: 1.3, 1.8). Multivariable RRs for recurrent falls were significantly elevated for all back pain symptoms, ranging from 1.4 (95% CI: 1.1, 1.8) for mild back pain to 1.8 (95% CI: 1.4, 2.3) for activity-limiting back pain. RRs of any fall were also significantly increased albeit smaller than those for recurrent falls. CONCLUSIONS: Older community-dwelling women with a recent history of back pain are at increased risk for falls.

Exposure to High-Risk Medications is Associated With Worse Outcomes in Older Veterans With Chronic Pain.

BACKGROUND: Chronic pain is common, costly and leads to significant morbidity in older adults, yet there are limited data on medication safety. The authors sought to evaluate the association of incident high-risk medication in the elderly (HRME) with mortality, emergency department (ED) or hospital care among older adults with chronic pain. METHODS: A retrospective Veterans Health Administration cohort study was conducted examining older veterans with chronic pain diagnoses and use of incident HRME (opioids, skeletal muscle relaxants, antihistamines and psychotropics). Outcomes evaluated included all-cause mortality, ED visits or inpatient hospital care. Descriptive statistics summarized variables for the overall cohort, the chronic pain cohort and those with and without HRME. Separate generalized linear mixed-effect regression models were used to examine the association of incident HRME on each outcome, controlling for potential confounders. RESULTS: Among 1,807,404 veterans who received Department of Veterans Affairs care in 2005 to 2006, 584,066 (32.3%) had chronic pain; 45,945 veterans with chronic pain (7.9%) had incident HRME exposure. The strongest significant associations of incident HRME were for high-risk opioids with all-cause hospitalizations (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.95-2.23), skeletal muscle relaxants with all-cause ED visits (OR 2.62, 95% CI 2.52-2.73) and mortality (OR 0.80, 95% CI 0.74-0.86), antihistamines with all-cause ED visits (OR 2.82 95% CI 2.72-2.95) and psychotropics with all-cause hospitalizations (OR 2.15, 95% CI 1.96-2.35). CONCLUSIONS: Our data indicate that incident HRME is associated with clinically important adverse outcomes in older veterans with chronic pain and highlight the importance of being judicious with prescribing certain classes of drugs in this vulnerable population.

Ageism, negative attitudes, and competing co-morbidities--why older adults may not seek care for restricting back pain: a qualitative study.

BACKGROUND: Back pain, the most common type of pain reported by older adults, is often undertreated for reasons that are poorly understood, especially in minority populations. The objective of this study was to understand older adults' beliefs and perspectives regarding care-seeking for restricting back pain (back pain that restricts activity). METHODS: We used data from a diverse sample of 93 older adults (median age 83) who reported restricting back pain during the past 3 months. A semi-structured discussion guide was used in 23 individual interviews and 16 focus groups to prompt participants to share experiences, beliefs, and attitudes about managing restricting back pain. Transcripts were analyzed in an iterative process to develop thematic categories. RESULTS: Three themes for why older adults may not seek care for restricting back pain were identified: (1) beliefs about the age-related inevitability of restricting back pain, (2) negative attitudes toward medication and/or surgery, and (3) perceived importance of restricting back pain relative to other comorbidities. No new themes emerged in the more diverse focus groups. CONCLUSIONS: Illness perceptions (including pain-related beliefs), and interactions with providers may influence older adults' willingness to seek care for restricting back pain. These results highlight opportunities to improve the care for older adults with restricting back pain.

Restricting back pain and subsequent mobility disability in community-living older persons.

OBJECTIVES: To evaluate the relationship between back pain severe enough to restrict activity (restricting back pain) and subsequent mobility disability in community-living older persons. DESIGN: Prospective cohort study. SETTING: Greater New Haven, Connecticut. PARTICIPANTS: Community-living men and women aged 70 and older (n = 709). MEASUREMENTS: Restricting back pain and mobility disability (defined as needing help with or unable to walk one-quarter of a mile, climb a flight of stairs, or lift and carry 10 pounds) were assessed during monthly telephone interviews for up to 159 months. The association between restricting back pain and subsequent mobility disability was evaluated using a recurrent-events Cox model. Secondary analyses evaluated the association between restricting back pain and mobility disability for two or more consecutive months (persistent mobility disability). Additional analyses were repeated in participants without baseline mobility disability. RESULTS: The event rate for mobility disability was 7.26 per 100-person months (95% confidence interval (CI) = 6.89-7.64). Mobility disability episodes lasted for a median of 2 months (interquartile range (IQR) 1-4). In a recurrent-event Cox regression analysis, after adjusting for 11 covariates, restricting back pain was strongly associated with mobility disability (hazard ratio (HR) = 3.23, 95% CI = 2.87-3.64). The association was maintained when the outcome was defined as persistent mobility disability (adjusted HR = 3.63, 95% CI = 3.15-4.20) and when participants with baseline mobility disability were omitted (adjusted HR = 3.71, 95% CI = 3.22-4.28). CONCLUSION: Restricting back pain was strongly associated with mobility disability. Interventions that prevent or ameliorate restricting back pain may be effective for reducing the burden of mobility disability in older persons.

Management of persistent pain in the older patient: a clinical review.

IMPORTANCE: Persistent pain is highly prevalent, costly, and frequently disabling in later life. OBJECTIVE: To describe barriers to the management of persistent pain among older adults, summarize current management approaches, including pharmacologic and nonpharmacologic modalities; present rehabilitative approaches; and highlight aspects of the patient-physician relationship that can help to improve treatment outcomes. This review is relevant for physicians who seek an age-appropriate approach to delivering pain care for the older adult. EVIDENCE ACQUISITION: Search of MEDLINE and the Cochrane database from January 1990 through May 2014, using the search terms older adults, senior, ages 65 and above, elderly, and aged along with non-cancer pain, chronic pain, persistent pain, pain management, intractable pain, and refractory pain to identify English-language peer-reviewed systematic reviews, meta-analyses, Cochrane reviews, consensus statements, and guidelines relevant to the management of persistent pain in older adults. FINDINGS: Of the 92 identified studies, 35 evaluated pharmacologic interventions, whereas 57 examined nonpharmacologic modalities; the majority (n = 50) focused on older adults with osteoarthritis. This evidence base supports a stepwise approach with acetaminophen as first-line therapy. If treatment goals are not met, a trial of a topical nonsteroidal anti-inflammatory drug, tramadol, or both is recommended. Oral nonsteroidal anti-inflammatory drugs are not recommended for long-term use. Careful surveillance to monitor for toxicity and efficacy is critical, given that advancing age increases risk for adverse effects. A multimodal approach is strongly recommended-emphasizing a combination of both pharmacologic and nonpharmacologic treatments to include physical and occupational rehabilitation, as well as cognitive-behavioral and movement-based interventions. An integrated pain management approach is ideally achieved by cultivating a strong therapeutic alliance between the older patient and the physician. CONCLUSIONS AND RELEVANCE: Treatment planning for persistent pain in later life requires a clear understanding of the patient's treatment goals and expectations, comorbidities, and cognitive and functional status, as well as coordinating community resources and family support when available. A combination of pharmacologic, nonpharmacologic, and rehabilitative approaches in addition to a strong therapeutic alliance between the patient and physician is essential in setting, adjusting, and achieving realistic goals of therapy.