Dose-specific effects of denosumab on serum calcium levels in patients with osteoporosis and various renal functions.

CONTEXT: Patients with osteoporosis and advanced chronic kidney disease (CKD) are at increased risk for hypocalcemia when initiating denosumab. It remains unclear if subsequent doses of denosumab pose similar hypocalcemia risk as the initial dose does. OBJECTIVES: To study dose-specific hypocalcemia risks of denosumab. DESIGN, SETTING, PATIENTS AND EXPOSURE: An observational study of 10,398 consecutive patients with varying renal function who received denosumab within Mass General Brigham healthcare system between 1/1/2016 and 2/29/2024. MAIN OUTCOMES AND MEASURES: Dose-specific effects of denosumab on serum calcium levels and incidence of hypocalcemia (albumin-corrected serum calcium level < 8.5 mg/dl). RESULTS: In 159 patients with sufficient data for three consecutive doses of denosumab, the initial dose of denosumab reduced serum calcium levels by an average of 0.34, 0.52, and 1.12 mg/dl, in patients with GFR of ≥60 (n=89), 30-59 (n=46) and < 30 (n=24) ml/min/1.73m2, respectively (p<0.001). Among patients with GFR of < 30 ml/min/1.73m2, the initial, second, and third dose of denosumab reduced serum calcium levels by an average of 1.12, 0.72, and 0.60 mg/dl, respectively (p=0.014).In a cohort of 325 patients with sufficient data for two doses of denosumab, a Kaplan-Meier analysis revealed a trend of higher incidence of hypocalcemia following the initial dose compared to the second dose in patients with GFR of < 30 ml/min/1.73m2. CONCLUSIONS: The magnitude of serum calcium decrease following subsequent dose(s) was smaller than that following the initial dose of denosumab among patients with osteoporosis and advanced CKD.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

Assessing Patient Values and Preferences to Inform the 2023 American College of Rheumatology/American College of Chest Physicians Interstitial Lung Disease Guidelines.

OBJECTIVE: Patient engagement is critical to clinical practice guideline (CPG) development. This work presents our approach to ascertaining patients' values and preferences to inform the American College of Rheumatology guidelines for screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We conducted a cross-sectional qualitative study of a purposefully sampled Patient Panel using a modified content analytic approach. The study team reviewed text transcripts from the Patient Panel discussion to identify themes and develop a clustered thematic schema. RESULTS: Twenty-one patients (75% women) participated, with a mean age of 53 years (range 33-73). Patients had one or more SARDs: systemic sclerosis (38%), Sjögren disease (38%), idiopathic inflammatory myopathy (33%), rheumatoid arthritis (24%), and mixed connective tissue disease (10%). We identified 10 themes in 4 thematic clusters: communication, screening and monitoring, treatment goals, and treatment adverse effects. Patients prioritized recognizing ILD symptoms, importance of ILD screening and close monitoring, goals of survival and improving quality of life, and willingness to accept treatment risks provided that there is close communication with providers. Patient representatives shared patients' priorities and insight at the Voting Panel meeting, influencing multiple guideline recommendations. CONCLUSION: Patient engagement fosters a holistic approach to CPG development, leading to recommendations aiming for the best clinical outcomes while prioritizing outcomes important for patients. The patient-identified themes played a critical role in ILD guideline development and provide core elements for shared decision-making as clinicians make management and therapeutic decisions with patients with SARD-associated ILD.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Zoledronic acid for hip fracture during initial hospitalization.

Inpatient zoledronic acid (IP-ZA) administered during the initial fracture hospitalization significantly improves the osteoporosis treatment rate. Clinical outcomes of IP-ZA after hip fracture remain uncertain. Here we report a cohort study that emulated a randomized controlled trial using real-world data and evaluated the risk of all-cause-mortality and radiologically confirmed subsequent new fractures among patients hospitalized for a hip fracture who had received IP-ZA as compared with propensity-matched controls. A total of 654 patients who had received IP-ZA and 6877 controls (for whom anti-osteoporosis treatment was indicated but no IP-ZA started during index hospitalization) were included in the study. The primary cohort comprised 652 IP-ZA patients (IP-ZA group) and 1926 matched controls (untreated group), with 71.7% female 92.1% White participants, with a mean age of 80.9 years. Cumulative all-cause mortality over the 24-month follow-up for the IP-ZA group was 12.3% and 20.7% for the untreated group (hazard ratio [HR], 0.62; 95% CI, 0.49-0.78, p < .001). A total of 585 (89.7%) patients in IP-ZA group received only a single dose of ZA during the 24 months, and the death rate of this single dose group was 13.3%, which was significantly lower than that of the untreated group (HR, 0.70; 95% CI, 0.55-0.89, p = .003). Rates of radiologically confirmed cumulative subsequent new vertebral fractures were 2.0% in the IP-ZA group and 5.4% in the untreated group (HR, 0.40; 95% CI, 0.22-0.71, p = .001). A similarly lower rate of new vertebral fractures was seen in the single dose subgroup (1.9% vs 5.4%; HR, 0.44; 95% 0.24-0.82, p = .008). IP-ZA, administered during the initial hospitalization for hip fracture, was associated with lower all-cause-mortality and risk of radiologically confirmed subsequent new vertebral fractures, and thus offers a mechanism to narrow the treatment gap in patients having sustained a hip fragility fracture.

Hip fracture is a serious complication of osteoporosis affecting approximately 300 000 Americans per year and is associated with a 20%-30% 1-year mortality rate. Most patients with hip fracture are elderly (average age, 80-81 years), with multiple underlying medical conditions and are often unable to timely attend post-hospitalization outpatient follow-up to initiate anti-osteoporosis treatment. As a result, only ~10% of post­hip fracture patients receive treatment for underlying osteoporosis. We have previously reported that zoledronic acid (ZA) administered during initial fracture hospitalization (IP-ZA) is safe and can effectively improve the osteoporosis treatment rate to 70%. The present study analyzed the clinical outcomes of 652 patients who had sustained hip fractures and were treated with IP-ZA and 1926 matched controls and revealed significantly reduced rates of all-cause mortality and vertebral compression fracture (VCF) during a 2-year follow-up period. Of note, nearly 90% of the treated patients received only a single dose of ZA (namely, IP-ZA), suggesting that, for most patients, the only opportunity to receive anti-osteoporosis treatment was during the index fracture hospitalization. Importantly, reduced mortality and VCF rates were readily seen in this single-dose group of patients. Our data suggest that IP-ZA is beneficial for osteoporotic hip fracture.

Interplay Between Systemic Inflammation, Myocardial Injury, and Coronary Microvascular Dysfunction in Rheumatoid Arthritis: Results From the LiiRA Study.

BACKGROUND: Coronary microvascular dysfunction as measured by myocardial flow reserve (MFR) is associated with increased cardiovascular risk in rheumatoid arthritis (RA). The objective of this study was to determine the association between reducing inflammation with MFR and other measures of cardiovascular risk. METHODS AND RESULTS: Patients with RA with active disease about to initiate a tumor necrosis factor inhibitor were enrolled (NCT02714881). All subjects underwent a cardiac perfusion positron emission tomography scan to quantify MFR at baseline before tumor necrosis factor inhibitor initiation, and after tumor necrosis factor inhibitor initiation at 24 weeks. MFR <2.5 in the absence of obstructive coronary artery disease was defined as coronary microvascular dysfunction. Blood samples at baseline and 24 weeks were measured for inflammatory markers (eg, high-sensitivity C-reactive protein [hsCRP], interleukin-1b, and high-sensitivity cardiac troponin T [hs-cTnT]). The primary outcome was mean MFR before and after tumor necrosis factor inhibitor initiation, with Δhs-cTnT as the secondary outcome. Secondary and exploratory analyses included the correlation between ΔhsCRP and other inflammatory markers with MFR and hs-cTnT. We studied 66 subjects, 82% of which were women, mean RA duration 7.4 years. The median atherosclerotic cardiovascular disease risk was 2.5%; 47% had coronary microvascular dysfunction and 23% had detectable hs-cTnT. We observed no change in mean MFR before (2.65) and after treatment (2.64, P=0.6) or hs-cTnT. A correlation was observed between a reduction in hsCRP and interleukin-1b with a reduction in hs-cTnT. CONCLUSIONS: In this RA cohort with low prevalence of cardiovascular risk factors, nearly 50% of subjects had coronary microvascular dysfunction at baseline. A reduction in inflammation was not associated with improved MFR. However, a modest reduction in interleukin-1b and no other inflammatory pathways was correlated with a reduction in subclinical myocardial injury. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02714881.

A Fracture Liaison Service to Address Vitamin D Deficiency for Patients Hospitalized for Osteoporotic Fracture.

Context: Addressing vitamin D deficiency (VDD) is important for fracture secondary prevention. Objectives: To explore the function of a fracture liaison service (FLS) to address VDD. Design Setting and Patients: An observational study of patients admitted to the Massachusetts General Hospital with fractures between January 1, 2016, and October 31, 2023, cared for by the FLS. Intervention: Ergocalciferol 50 000 international units (50ku-D2) oral daily for 3 to 7 days. Main Outcomes Measures: VDD prevalence. Efficacy of inpatient daily 50ku-D2 in raising serum 25-hydroxyvitamin D (25OHD) levels. Results: Of the 2951 consecutive patients, 724 (24.53%) had VDD (defined by 25OHD ≤ 19 ng/mL). Men (252/897, or 28.09%) were more likely than women (472/2054, or 22.98%) to have VDD (P = .003). VDD was seen in 41.79% (117/280), 24.41% (332/1360), and 20.98% (275/1311) of patients of aged ≤59, 60 to 79, and ≥80 years, respectively (P < .00001). Of the 1303 patients with hip fractures, 327 (25.09%) had VDD, which was associated with a longer length of stay (8.37 ± 7.35 vs 7.23 ± 4.78 days, P = .009) and higher trend of 30-day-readmission rate (13.63% vs 18.35%, P = .037). In a cohort of 32 patients with complete data, each dose of 50ku-D2 increased serum 25OHD by 3.62 ± 2.35 ng/mL without affecting serum calcium or creatinine levels. Conclusion: VDD was seen in nearly 25% of Massachusetts General Hospital FLS patients and more prevalent in male and younger patients. VDD was associated with longer length of stay and higher 30-day-readmission risk in patients with hip fracture. Daily 50ku-D2 appeared to be a practical way to quickly replete vitamin D in the inpatient setting.

Enhancing Faculty Development Through Compiled Verbal Feedback on Clinical Teaching From Trainees.

OBJECTIVE: Feedback from fellows-in-training (FITs) is important for faculty development and to enrich clinical teaching. We sought to evaluate the effectiveness of traditional online evaluations and a novel compiled verbal feedback mechanism. METHODS: An annual feedback system was implemented in our rheumatology division in which FITs provided verbal feedback on all faculty to a facilitator who compiled, deidentified, and shared the feedback with individual faculty members. FITs also completed standard online annual evaluations of faculty. FITs and faculty completed surveys assessing the perceived effectiveness and confidentiality of each feedback mechanism. RESULTS: Thirteen of 15 eligible faculty and all 4 eligible FITs completed both surveys. Responses by FITs and faculty regarding the quality of online evaluations were generally unfavorable or neutral. Faculty responses regarding compiled verbal feedback were more favorable in all questions and significantly more favorable with respect to the feedback's ability to explain strengths (54% favorable for online evaluations vs 100% for compiled verbal feedback), the feedback's specificity (0% vs 54%), and the feedback's actionable nature (15% vs 62%). All FITs' responses regarding quality of compiled verbal feedback were favorable. FITs had concerns regarding confidentiality with both online evaluations (0% favorable) and compiled verbal feedback (25% favorable), though FITs had less concern for future faculty interactions with compiled verbal feedback (100% favorable) than with online evaluations (0% favorable). CONCLUSION: Compiled verbal feedback by FITs produced more actionable and effective feedback for faculty, with less concerns regarding future faculty interactions compared with traditional online evaluations. Further study of this method across different programs and institutions is warranted.

Clinically Recognized Depression and Mental Health Treatment in a Single Center Cohort of Patients with Systemic Sclerosis.

Introduction: In this study, we investigated the prevalence of depression, depression treatment, and symptom burden in patients with systemic sclerosis (SSc) and examined their associations with the center for epidemiologic studies depression scale revised (CESD-R) scores. Methods: The Prospective Registry in Scleroderma at Massachusetts General Hospital (PRISM) is a longitudinal registry of patients with SSc. Among participants with CESD-R score ≥ 16, indicating possible depression, a chart review was performed for mental health diagnoses and treatments. We examined the relation of demographic and clinical factors to the presence of mental health diagnoses or treatment using logistic regression. We evaluated the association of SSc symptoms and the COVID-19 pandemic with a CESD-R score using quantile regression. Results: Of 214 patients enrolled in PRISM, 129 participants (38% diffuse and 59% limited) completed at least one CESD-R questionnaire. In the first survey, 29% had possible depression (CESD - R ≥ 16) and 16% had probable depression (CESD - R ≥ 23). Of 20 participants with probable depression, 90% received treatment for a mood disorder. In a multivariable logistic regression model among participants with CESD - R ≥ 16, none of the evaluated variables (CESD-R score, age, gender, employment status, race, and ethnicity) was associated with mental health diagnosis or treatment. Higher baseline dyspnea index, modified Rodnan skin score, and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal total score and subscores were associated with higher CESD-R score. Conclusion: In this single-center cross-sectional study, 16% of participants had significant depressive symptoms. Dyspnea, extent of skin involvement, and gastrointestinal symptoms were associated with depression symptoms.

Sex Differences in Pain and Quantitative Sensory Testing in Patients With Rheumatoid Arthritis.

OBJECTIVE: Women with rheumatoid arthritis (RA) have higher pain and worse functional outcomes compared to men, even when treated with similar medications. The objective of this study was to identify sex differences in pain intensity, pain interference, and quantitative sensory tests (QST), which are independent of inflammation, in patients with RA. METHODS: This study is a post hoc analysis of participants in the Central Pain in Rheumatoid Arthritis cohort. Pain intensity was assessed using a 0-10 numeric rating scale. Pain interference was measured using a Patient-Reported Outcomes Measurement Information System computerized adaptive test. QST included pressure pain detection thresholds, temporal summation, and conditioned pain modulation. Women and men were compared using multiple linear regression, adjusted for age, education, race, research site, depression, obesity, RA disease duration, swollen joint count, and C-reactive protein. RESULTS: Mean ± SD pain intensity was 5.32 ± 2.29 among women with RA, compared to 4.60 ± 2.23 among men with RA (adjusted difference 0.83 [95% confidence interval (95% CI) 0.14, 1.53]). Women with RA had lower pressure pain detection thresholds at the trapezius (adjusted difference -1.22 [95% CI -1.73, -0.72]), wrist (adjusted difference -0.57 [95% CI -1.07, -0.06]), and knee (adjusted difference -1.10 [95% CI -2.00, -0.21]). No statistically significant differences in pain interference, temporal summation, and conditioned pain modulation were observed. CONCLUSION: Women reported higher pain intensity and lower pressure pain detection thresholds (higher pain sensitivity) than men. However, pain interference, temporal summation, and conditioned pain modulation did not differ between men and women.

Virtual Learning and Assessment in Rheumatology Fellowship Training: Objective Structured Clinical Examination Revisited.

OBJECTIVE: With the onset of the COVID-19 pandemic, an annual multi-institutional face-to-face rheumatology objective structured clinical examination (ROSCE) was transformed into a virtual format. The educational goals of the virtual ROSCE (vROSCE) were to reproduce the educational value of the previous in-person ROSCE, providing a valuable formative assessment of rheumatology training activities encompassing the 6 Accreditation Council for Graduate Medical Education (ACGME) core competencies for fellows-in-training (FITs). This article describes the novel design, feasibility, and stakeholder value of a vROSCE. METHODS: Through an established collaboration of 5 rheumatology fellowship training programs, in February 2021, a vROSCE was created and conducted using a Zoom platform. Station development included learning objectives, FIT instructions, faculty proctor instructions, and a checklist by which to provide structured formative feedback. An anonymous, optional web-based survey was sent to FIT participants to evaluate the experience. RESULTS: Twenty-three rheumatology FITs from 5 institutions successfully rotated through 6 stations in the vROSCE. Immediate feedback was given to each FIT using standardized rubrics structured around ACGME core competencies. A total of 65% of FITs (15 of 23) responded to the survey, and 93% of survey respondents agreed or strongly agreed that the vROSCE was a helpful educational activity and identified individualized opportunities for improvement. CONCLUSION: A vROSCE is an innovative, feasible, valuable, and well-received educational technology tool. The vROSCE enriched rheumatology FITs' education and offered collaborative learning experiences across institutions.

Incorporating Telemedicine in Rheumatology Fellowship Training Programs: Needs Assessment, Curricular Intervention, and Evaluation.

OBJECTIVE: To increase the confidence of rheumatology fellows in training (FITs) in delivering virtual care (VC) and prepare them for independent practice, we developed educational materials addressing gaps in their skills. METHODS: We identified gaps in telemedicine skills based on FIT performance in a virtual rheumatology objective structured clinical examination (vROSCE) station on VC delivery using video teleconference technology and survey (survey 1) responses. We created educational materials including videos of "mediocre" and "excellent" VC examples, discussion/reflection questions, and a document summarizing key practices. We measured change in the confidence levels of FITs for delivering VC with a post-intervention survey (survey 2). RESULTS: Thirty-seven FITs (19 first-year, 18 second- plus third-year fellows) from 7 rheumatology fellowship training programs participated in a vROSCE and demonstrated gaps in skills mapping to several Rheumatology Telehealth Competency domains. Confidence levels of FITs improved significantly from survey 1 to survey 2 for 22 of 34 (65%) questions. All participating FITs found the educational materials helpful for learning and reflecting on their own VC practice; 18 FITs (64%) qualified usefulness as "moderately" or "a lot." Through surveying, 17 FITs (61%) reported implementing skills from the instructional videos into VC visits. CONCLUSION: Continually assessing our learners' needs and creating educational materials addressing gaps in training are requisite. Using a vROSCE station, needs assessments, and targeted learning with videos and discussion-guidance materials enhanced the confidence level of FITs in VC delivery. It is imperative to incorporate VC delivery into fellowship training program curricula to ensure breadth in skills, attitudes, and knowledge of new entrants into the rheumatology workforce.

Safety of Inpatient Zoledronic Acid in the Immediate Postfracture Setting.

CONTEXT: Zoledronic acid (ZA) administered during the initial hospitalization for a fragility fracture improves the osteoporosis pharmacotherapy rate. Distinguishing the safety profile of inpatient ZA (IP-ZA) in this context is crucial if this approach is to be widely adopted. OBJECTIVE: To study the acute safety profile of IP-ZA. METHODS: An observational study of patients admitted to the Massachusetts General Hospital with fragility fractures who were eligible to receive IP-ZA. Patients were treated with or without IP-ZA. Acetaminophen, either as a single pre-ZA dose or standing multiple-doses-per-day regimen for 48 hours or longer after ZA infusion, was also administered along with protocolized vitamin D and calcium supplementation. Changes in body temperature, serum creatinine, and serum calcium were measured. RESULTS: A total of 285 consecutive patients, meeting inclusion and exclusion criteria, are included in this analysis; 204 patients received IP-ZA. IP-ZA treatment was associated with a transient mean rise of body temperature of 0.31 °C on the day following its administration. Temperatures above 38 °C were seen in 15% of patients in the IP-ZA group and 4% in the nontreated group. Standing multiple-doses-per-day but not a single pre-ZA dose of acetaminophen effectively prevented this temperature increase. IP-ZA did not affect serum creatinine levels. Mean levels of serum total calcium and albumin-corrected calcium decreased by 0.54 mg/dL and 0.40 mg/dL, respectively, at their nadirs (Day 5). No patient experienced symptomatic hypocalcemia. CONCLUSION: IP-ZA along with standing multiple-doses-per-day acetaminophen, administered to patients in the immediate postfracture period, is not associated with significant acute adverse effects.

Pain Mechanisms Associated With Disease Activity in Patients With Rheumatoid Arthritis Treated With Disease-Modifying Antirheumatic Drugs: A Regression Tree Analysis.

OBJECTIVE: Although pain affects the assessment of disease activity in patients with rheumatoid arthritis (RA), pain is not always directly related to peripheral joint inflammation. Peripheral and central nervous system regulatory mechanisms also affect pain perception. We used regression tree methodology to identify mechanisms most predictive of disease activity after disease-modifying antirheumatic drug (DMARD) treatment. METHODS: Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28) in 176 patients with RA, before and after starting a DMARD. Quantitative sensory testing (QST), including pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation (CPM), were used to assess pain mechanisms. Regression tree methodology was used to determine the QST modalities most predictive of DAS28 after DMARD treatment. RESULTS: This analysis identified 4 groups defined by baseline DAS28 category and either knee PPT (a combined measure of peripheral and central nervous system dysregulation) or CPM (a measure of descending pain inhibition). Among patients starting with low/moderate disease activity, lower knee PPT (PPT ≤ 4.65 kgf) most strongly predicted higher posttreatment disease activity (group 1 mean DAS28 2.8 [SD 1.0] vs group 2 mean DAS28 3.5 [SD 1.0]). Among patients starting with high baseline disease activity, less efficient descending pain modulation (CPM ≤ 1.55) most strongly predicted higher posttreatment disease activity (group 3 mean DAS28 3.4 [SD 1.4] vs group 4 mean DAS28 4.6 [SD 1.1]). CONCLUSION: These results highlight the importance of identifying and treating aberrant peripheral and central pain regulation in patients with RA starting or switching DMARD therapy.