The Benefit of an Umbrella Protocol: Reducing Challenges in Orthopedic Oncology Research.

Background: Orthopedic oncology research is hindered by the scarcity of musculoskeletal tumors and research administrative inefficiencies. This paper introduces observational research through an innovative institution-specific methodology-termed an umbrella protocol. This protocol outlines a comprehensive standard procedure to expedite ethical approval for future aligned studies, reducing administrative barriers to research. Methods: We developed an umbrella protocol at an academic center, involving meticulous methodological identification and coordination with the institutional review board (IRB) to adhere to local guidelines. The protocol encompasses identifying investigators, research objectives, study goals, and data and safety monitoring frameworks necessary for typical standards. Results: Implementation of the umbrella protocol took 110 days to achieve exemption status, following multiple discussions with the IRB and extensive revisions. At the authors institution, this protocol significantly reduces protocol review times from an average of six-to-eight weeks to nearly instantaneous, facilitating a streamlined research process. Additionally, we established a dedicated orthopedic oncology patient registry to enhance future research endeavors. Conclusions: The adoption of umbrella protocols represents a pioneering strategy in orthopedic oncology. This approach mitigates research administrative burdens and broadens research scope in the field. It underscores the necessity of IRB collaboration, methodological precision, and stringent data management. The article also reflects on the ethical implications and potential biases introduced by emerging technologies like artificial intelligence, advocating for diligent ethical oversight. The establishment of an umbrella protocol marks a significant step towards more efficient research methodologies, ultimately aiming to improve patient care and outcomes for individuals with rare musculoskeletal conditions.

Socioeconomic and insurance-related disparities in disease-specific survival among patients with metastatic bone disease.

BACKGROUND: Approximately 5% of cancer patients in the United States presented with metastatic bone disease (MBD) at diagnosis. Current study explores the disparities in survival for patients with MBD. METHODS: Patients with the diagnosis of MBD at presentation for the five most common primary anatomical sites were extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset (2010-2016). Kaplan-Meier and Cox Proportional Hazard models were used to evaluate survival, and prognostic factors for each cohort. Prognostic significance of socioeconomic status (SES) and insurance status were ascertained. RESULTS: The five most common anatomical-sites with MBD at presentation included "lung" (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal and urothelium" (n = 7718) and "colon" (n= 3068). Lower SES was an independent risk factor for worse disease-specific survival (DSS) for patients with MBD originating from lung, prostate, breast and colon. Lack of insurance was an independent risk factor for worse DSS for MBD patients with primary tumors in lung and breast. CONCLUSIONS: MBD patients from the five most common primary sites demonstrated SES and insurance-related disparities in disease-specific survival. This is the first and largest study to explore SES and insurance-related disparities among patients specifically afflicted with MBD. Our findings highlight vulnerability of patients with MBD across multiple primary sites to financial toxicity.

Sex, racial/ethnic and socioeconomic disparities in patients with metastatic bone disease.

BACKGROUND: We have analyzed sex, race/ethnicity or socioeconomic disparities in the incidence of metastatic bone disease (MBD). METHODS: Patients with the diagnosis of MBD at presentation for five most common primary anatomical sites was extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset. Mean incidence of MBD for different sex, racial/ethnic and socioeconomic groups were compared. RESULTS: The five most common anatomical sites with MBD at presentation include "lung: (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal" (n = 7718) and "colon" (n = 3068). There was an increase in incidence of MBD among cancers originating from prostate (annual percentage change [APC] 4.94), renal (APC 2.55), and colon (APC 3.21) (p < 0.05 for all). Non-Hispanic Blacks had higher incidence of MBD for prostate and breast primary sites (p < 0.001). Non-Hispanic American Indian Alaskan Native had higher incidence of MBD for cancers originating from renal (p < 0.001) and colon (p = 0.049). A higher incidence of MBD was seen in lower socioeconomic status (SES) groups for the selected sites (p < 0.001). CONCLUSIONS: These findings suggest that there are multiple sex-related, racial/ethnic and SES disparities in the incidence of MBD from the 5 most common primary sites. Higher incidence seen among lower SES suggests delay in diagnosis and limited access to screening modalities.

Patterns of Change Over Time in Knee Bone Shape Are Associated with Sex.

BACKGROUND: Knee osteoarthritis (OA) is more common in females than in males; however, the biological mechanisms for the difference in sex in patients with knee OA are not well understood. Knee shape is associated with OA and with sex, but the patterns of change in the bone's shape over time and their relation to sex and OA are unknown and may help inform how sex is associated with shape and OA and whether the effect is exerted early or later in life.Questions/purposes (1) Does knee shape segregate stably into different groups of trajectories of change (groups of knees that share similar patterns of changes in bone shape over time)? (2) Do females and males have different trajectories of bone shape changes? (3) Is radiographic OA at baseline associated with trajectories of bone shape changes? METHODS: We used data collected from the NIH-funded Osteoarthritis Initiative (OAI) to evaluate a cohort of people aged 45 to 79 years at baseline who had either symptomatic knee OA or were at high risk of having it. The OAI cohort included 4796 participants (58% females; n = 2804) at baseline who either had symptomatic knee OA (defined as having radiographic tibiofemoral knee OA and answering positively to the question "have you had pain, aching or stiffness around the knee on most days for at least one month during the past 12 months") or were at high risk of symptomatic knee OA (defined as having knee symptoms during the prior 12 months along with any of the following: overweight; knee injury; knee surgery other than replacement; family history of total knee replacement for OA; presence of Heberden's nodes; daily knee bending activity) or were part of a small nonexposed subcohort. From these participants, we limited the eligible group to those with radiographs available and read at baseline, 2 years, and 4 years, and randomly selected participants from each OAI subcohort in a manner to enrich representation in the study of the progression and nonexposed subcohorts, which were smaller in number than the OA incidence subcohort. From these patients, we randomly sampled 473 knees with radiographs available at baseline, 2 years, and 4 years. We outlined the shape of the distal femur and proximal tibia on radiographs at all three timepoints using statistical shape modelling. Five modes (each mode represents a particular type of knee bone shape variation) were derived for the proximal tibia and distal femur's shape, accounting for 78% of the total variance in shape. Group-based trajectory modelling (a statistical approach to identify the clusters of participants following a similar progression of change of bone shape over time, that is, trajectory group) was used to identify distinctive patterns of change in the bone shape for each mode. We examined the association of sex and radiographic OA at baseline with the trajectories of each bone shape mode using a multivariable polytomous regression model while adjusting for age, BMI, and race. RESULTS: Knee bone shape change trajectories segregated stably into different groups. In all modes, three distinct trajectory groups were derived, with the mean posterior probabilities (a measure of an individual's probability of being in a particular group and often used to characterize how well the trajectory model is working to describe the population) ranging from 84% to 99%, indicating excellent model fitting. For most of the modes of both the femur and tibia, the intercepts for the three trajectory groups were different; however, the rates of change were generally similar in each mode. Females and males had different trajectories of bone shape change. For Mode 1 in the femur, females were more likely to be in trajectory Groups 3 (odds ratio 30.2 [95% CI 12.2 to 75.0]; p < 0.001) and 2 than males (OR 4.1 [95% CI 2.3 to 7.1]; p < 0.001); thus, females had increased depth of the intercondylar fossa and broader shaft width relative to epicondylar width compared with males. For Mode 1 in the tibia, females were less likely to be in trajectory Group 2 (OR 0.5 [95% CI 0.3 to 0.9]; p = 0.01) than males (that is, knees of females were less likely to display superior elevation of tibial plateau or decreased shaft width relative to head width). Radiographic OA at baseline was associated with specific shape-change trajectory groups. For Mode 1 in the femur, knees with OA were less likely to be in trajectory Groups 3 (OR 0.4 [95% CI 0.2 to 0.8]; p = 0.008) and 2 (OR 0.6 [95% CI 0.3 to 1.0]; p = 0.03) than knees without OA; thus, knees with OA had decreased depth of the intercondylar fossa and narrower shaft width relative to epicondylar width compared with knees without OA. For Mode 1 in the tibia, knees with OA were not associated with trajectory. CONCLUSIONS: The shapes of the distal femur and proximal tibia did not change much over time. Sex and baseline knee radiographic OA status are associated with the trajectory of change in the bone's shape, suggesting that both may contribute earlier in life to the associations among trajectories observed in older individuals. Future studies might explore sex-related bone shape change earlier in life to help determine when the sex-specific shapes arise and also the degree to which these sex-related shapes are alterable by injury or other events. LEVEL OF EVIDENCE: Level III, prognostic study.

Rheumatologists' Approaches to Diagnosis and Treatment of Depression.

OBJECTIVE: We examined rheumatologists' approaches to and perceptions of depression in everyday practice. METHODS: A questionnaire was mailed to 470 practicing rheumatologists in California; 226 were included in the final analyses. Respondents provided information on demographics, practice characteristics, and attitudes, perceptions, and practices related to depression. Logistic regression models were constructed to assess the relationship of rheumatologists' personal and practice characteristics with their depression-related practices. RESULTS: Fifty-one percent of respondents reported that at least half of their patients had depression. Nearly all providers (99%) reported addressing mental health issues during some visits. Rheumatologists were about equally likely to prescribe antidepressants, refer to a psychiatrist, or return the patient to the primary care physician, with roughly 60% often applying each of the 3 strategies. Respondents identified access to services and patients' resistance to mental health diagnoses as major barriers to effective depression management. In logistic regression models, greater number of patient visits per week, greater percentage of patients with fibromyalgia, and private practice setting were associated with more prescription of antidepressants (P < 0.05). CONCLUSIONS: Depression is common in rheumatologic practice, yet systems for identification, treatment, and referral of depressed patients are not universal. Rheumatologists' awareness of the need for mental health services is high, but they may lack the confidence, time, and/or referral networks to provide consistently effective care for depressed patients. Improving depression care in rheumatology may require a combination of clinician-level interventions (e.g., enhanced behavioral health training) and practice-level reforms (e.g., collaborative care).

Association of serum uric acid and incident nonspine fractures in elderly men: the Osteoporotic Fractures in Men (MrOS) study.

Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and elevated levels may cause arthritis and kidney stones. Conversely, UA also appears to function as an antioxidant and may protect against the oxidative stress associated with aging and disease. We performed a prospective fracture case-cohort study to understand the relation of UA and fracture risk in older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. In the cohort of 5994 men aged 65 years and older attending the baseline MrOS examination, we evaluated a subgroup 1680 men in a case-cohort study design. The analytic group included 387 men with incident nonspine fractures (73 hip) and a random sample of 1383. Serum UA was measured in baseline serum samples. Modified proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of hip and nonspine fracture in men for serum UA. Models were adjusted for age, race, clinic site, body mass index, vitamin D, parathyroid hormone, walking speed, Physical Activity Scale for the Elderly (PASE) score, frailty, and total. Subjects with incident nonspine fractures were older, had lower total hip bone mineral density (BMD), and higher serum phosphorus. There was an 18% decreased risk of nonspine fractures (95% confidence interval [CI] 0.71-0.93; p = 0.003) per 1 SD increase of baseline serum and 34% decreased risk of nonspine fractures in quartile 4 of UA versus quartiles 1, 2, and 3 (95% CI 0.49-0.89; p = 0.028) compared with nonfracture cases after multivariate adjustment. Hip fractures were not significantly associated with UA. Total hip BMD was significantly higher in the group of men with high UA levels compared with lower UA levels and increased linearly across quartiles of UA after multivariate adjustment (p for trend = 0.002). In summary, higher serum UA levels were associated with a reduction in risk of incident nonspine fractures but not hip fractures and higher hip BMD.

Increasing incidence of shoulder arthroplasty in the United States.

BACKGROUND: The number of total shoulder arthroplasties performed in the United States increased slightly between 1990 and 2000. However, the incidence of shoulder arthroplasty in recent years has not been well described. The purpose of the present study was to examine recent trends in shoulder hemiarthroplasty and total shoulder arthroplasty along with the common reasons for these surgical procedures in the United States. METHODS: We modeled the incidence of shoulder arthroplasty from 1993 to 2008 with use of the Nationwide Inpatient Sample. On the basis of hemiarthroplasty and total shoulder arthroplasty cases that were identified with use of surgical procedure codes, we conducted a design-based analysis to calculate national estimates. RESULTS: While the annual number of hemiarthroplasties grew steadily, the number of total shoulder arthroplasties showed a discontinuous jump (p < 0.01) in 2004 and increased with a steeper linear slope (p < 0.01) since then. As a result, more total shoulder arthroplasties than hemiarthroplasties have been performed annually since 2006. Approximately 27,000 total shoulder arthroplasties and 20,000 hemiarthroplasties were performed in 2008. More than two-thirds of total shoulder arthroplasties were performed in adults with an age of sixty-five years or more. Osteoarthritis was the primary diagnosis for 43% of hemiarthroplasties and 77% of total shoulder arthroplasties in 2008, with fracture of the humerus as the next most common primary diagnosis leading to hemiarthroplasty. CONCLUSIONS: The number of shoulder arthroplasties, particularly total shoulder arthroplasties, is growing faster than ever. The use of reverse total arthroplasty, which was approved by the United States Food and Drug Administration in November 2003, may be part of the reason for the greater increase in the number of total shoulder arthroplasties. A long-term follow-up study is warranted to evaluate total shoulder arthroplasty in terms of patient outcomes, safety, and implant longevity.

The relationship of estrogen receptor-alpha and -beta genes with osteoarthritis of the hand.

OBJECTIVE: We examined reported associations between radiographic hand osteoarthritis (OA) and single-nucleotide polymorphisms (SNP) in 2 candidate genes associated with OA in other joints: estrogen receptor alpha (ESR1) and beta (ESR2). METHODS: In 539 Framingham Offspring Study participants (49% men; mean age 61 +/- 9 yrs) joint-specific radiographic hand OA was defined as Kellgren/Lawrence (K/L) scores >or= 2 in the first carpometacarpal joint (CMC), distal interphalangeal joints (DIP), first-digit interphalangeal joint (IP), or proximal interphalangeal joints (PIP). Four SNP were genotyped for ESR1 (PvuII-rs2234693, XbaI-rs9340799, rs2077647, and rs1801132) and 4 for ESR2 (rs1256031, rs1256034, rs1256059, rs944460). Logistic regression analyses were performed to evaluate the relationships between genotypes and hand OA, adjusting for age, sex, height, and weight. RESULTS: Radiographic hand OA was identified in at least one investigated joint of DIP (39%), PIP (33%), and first CMC (40%). There was no evidence of association between OA and genotype at any polymorphism. We found no significant association between our OA phenotypes or generalized or severe generalized OA as defined by Ushiyama and heterozygosity for rs2234693 and rs9340799, although in metaanalysis with the former study this heterozygosity remained significantly associated with generalized or severe generalized OA. CONCLUSION: We found no significant association between hand OA and the investigated polymorphisms of ESR1 or ESR2 despite published reports of association and a priori hypotheses implicating their potential roles. However, we could not absolutely exclude associations with rs2234693, rs9340799, or rs944460.