Development of a Needs Assessment for Low-income Seniors in Cleveland Ohio: A student-driven Interprofessional Approach.

BACKGROUND AND OBJECTIVE: Older persons with low socioeconomic status in the United States have different and unique health needs compared to younger persons. As part of a student-led, interprofessional partnership, we performed a needs assessment of community dwelling older persons with low socioeconomic status in an urban location within Ohio, USA. METHODS: Three entities participated in the needs assessment: a student-run health clinic, a Federally Qualified Health Center, and an apartment complex of the study population. Health professional students from medical, dental, nursing, social work, nutrition, and physician assistant programs led the needs assessment process. The process consisted of multiple phases, which included preliminary literature review, survey development, data collection, and analysis. The final survey was multidisciplinary, with six content areas covered in 37 items. RESULTS: One hundred nineteen survey responses were received, and multiple areas of need were identified including food insecurity, dental care access, and mental health. 93% of participants had at least one unmet health need and 39% of respondents met our classification for high need. The needs of the local study population had key differences from previously published data in more generalized populations of older community-dwelling individuals in the United States, notably lower utilization of dental care (43% vs. 66%), increased prevalence of possible food insecurity (30% vs. 17%), and increased use of age-appropriate preventive cancer screening services. CONCLUSIONS: Multiple areas of need were successfully identified through a student-led interprofessional needs assessment. Future student teams can address the identified needs, again through interprofessional collaborations. This process may have unique benefits to help build robust community-academic partnerships, while fostering interprofessional collaborative opportunities among healthcare students.

Scaling-up RADseq methods for large datasets of non-invasive samples: Lessons for library construction and data preprocessing.

Genetic non-invasive sampling (gNIS) is a critical tool for population genetics studies, supporting conservation efforts while imposing minimal impacts on wildlife. However, gNIS often presents variable levels of DNA degradation and non-endogenous contamination, which can incur considerable processing costs. Furthermore, the use of restriction-site-associated DNA sequencing methods (RADseq) for assessing thousands of genetic markers introduces the challenge of obtaining large sets of shared loci with similar coverage across multiple individuals. Here, we present an approach to handling large-scale gNIS-based datasets using data from the spotted hyena population inhabiting the Ngorongoro Crater in Tanzania. We generated 3RADseq data for more than a thousand individuals, mostly from faecal mucus samples collected non-invasively and varying in DNA degradation and contamination level. Using small-scale sequencing, we screened samples for endogenous DNA content, removed highly contaminated samples, confirmed overlap fragment length between libraries, and balanced individual representation in a sequencing pool. We evaluated the impact of (1) DNA degradation and contamination of non-invasive samples, (2) PCR duplicates and (3) different SNP filters on genotype accuracy based on Mendelian error estimated for parent-offspring trio datasets. Our results showed that when balanced for sequencing depth, contaminated samples presented similar genotype error rates to those of non-contaminated samples. We also showed that PCR duplicates and different SNP filters impact genotype accuracy. In summary, we showed the potential of using gNIS for large-scale genetic monitoring based on SNPs and demonstrated how to improve control over library preparation by using a weighted re-pooling strategy that considers the endogenous DNA content.

The Corticosteroid Meniscectomy Trial of Extended-Release Triamcinolone Injection After Arthroscopic Partial Meniscectomy: Protocol for a Double-Blind Randomized Controlled Trial.

Background: Meniscal tear in older adults often accompanies knee osteoarthritis and is commonly treated with arthroscopic partial meniscectomy (APM) when patients have persistent pain after a trial of physical therapy. Cross-sectional evidence suggests that synovitis is associated with baseline pain in this patient population, but little is known about the relationship between synovitis and postoperative recovery or progression of knee osteoarthritis. Purpose/Hypothesis: Intra-articular extended-release triamcinolone may reduce inflammation and thereby improve outcomes and slow disease progression. This article presents the rationale behind the Corticosteroid Meniscectomy Trial (CoMeT) and describes its study design and implementation strategies. Study Design: Randomized controlled trial. Methods: CoMeT is a 2-arm, 3-center, randomized placebo-controlled trial designed to establish the clinical efficacy of extended-release triamcinolone administered via intra-articular injection immediately after APM. The primary outcome is change in Knee injury and Osteoarthritis Outcome Score Pain subscore at 3-month follow-up. Synovial biopsy, joint fluid aspirate, and urine and blood sample analyses will examine the associations between various objective measures of baseline inflammation and pre- and postoperative outcome measures and clinical responses to triamcinolone intervention. Quantitative 3-T magnetic resonance imaging will evaluate cartilage and meniscal composition and 3-dimensional bone shape to detect early joint degeneration. Results: We discuss methodologic innovations and challenges. Conclusion: To our knowledge, this is the first randomized double-blind clinical trial that will analyze the effect of extended-release triamcinolone acetonide on pain, magnetic resonance imaging measures of structural change and effusion/synovitis, soluble biomarkers, and synovial tissue transcriptomics after APM.

Does Screening for Depressive Symptoms Help Optimize Duloxetine Use in Knee Osteoarthritis Patients With Moderate Pain? A Cost-Effectiveness Analysis.

OBJECTIVE: Duloxetine is a treatment approved by the US Food and Drug Administration for both osteoarthritis (OA) pain and depression, though uptake of duloxetine in knee OA management varies. We examined the cost-effectiveness of adding duloxetine to knee OA care in the absence or presence of depression screening. METHODS: We used the Osteoarthritis Policy Model, a validated computer microsimulation of knee OA, to examine the value of duloxetine for patients with knee OA who have moderate pain by comparing 3 strategies: 1) usual care, 2) usual care plus duloxetine for patients who screen positive for depression on the Patient Health Questionnaire 9 (PHQ-9), and 3) usual care plus universal duloxetine. Outcome measures included quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. Model inputs, drawn from the published literature and national databases, included annual cost of duloxetine ($721-937); average pain reduction for duloxetine (17.5 points on the Western Ontario and McMaster Universities Osteoarthritis Index pain scale [0-100]), and likelihood of depression remission with duloxetine (27.4%). We considered 2 willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY. We varied parameters related to the PHQ-9 and the cost of duloxetine, efficacy, and toxicities to address uncertainty in model inputs. RESULTS: The screening strategy led to an additional 17 QALYs per 1,000 subjects and increased costs by $289/subject (ICER = $17,000/QALY). Universal duloxetine led to an additional 31 QALYs per 1,000 subjects and $1,205 per subject (ICER = $39,300/QALY). Under the majority of sensitivity analyses, universal duloxetine was cost-effective at the $100,000/QALY threshold. CONCLUSION: The addition of duloxetine to usual care for knee OA patients with moderate pain, regardless of depressive symptoms, is cost-effective at frequently used WTP thresholds.

Societal Cost of Opioid Use in Symptomatic Knee Osteoarthritis Patients in the United States.

OBJECTIVE: Symptomatic knee osteoarthritis (SKOA) is a chronic, disabling condition, requiring long-term pain management; over 800,000 SKOA patients in the US use opioids on a prolonged basis. We aimed to characterize the societal economic burden of opioid use in this population. METHODS: We used the Osteoarthritis Policy Model, a validated computer simulation of SKOA, to estimate the opioid-related lifetime and annual cost generated by the US SKOA population. We included direct medical, lost productivity, criminal justice, and diversion costs. We modeled the SKOA cohort with a mean ± SD age of 54 ± 14 years and Western Ontario and McMaster Universities Osteoarthritis Index pain score of 29 ± 17 (0-100, 100 = worst). We estimated annual costs of strong ($1,381) and weak ($671) opioid regimens using Medicare fee schedules, Red Book, the Federal Supply Schedule, and published literature. The annual lost productivity and criminal justice costs of opioid use disorder (OUD), obtained from published literature, were $11,387 and $4,264, per-person, respectively. The 2015-2016 Medicare Current Beneficiary Survey provided OUD prevalence. We conducted sensitivity analyses to examine the robustness of our estimates to uncertainty in input parameters. RESULTS: Assuming 5.1% prevalence of prolonged strong opioid use, the total lifetime opioid-related cost generated by the US SKOA population was estimated at $14.0 billion, of which only $7.45 billion (53%) were direct medical costs. CONCLUSION: Lost productivity, diversion, and criminal justice costs comprise approximately half of opioid-related costs generated by the US SKOA population. Reducing prolonged opioid use may lead to a meaningful reduction in societal costs that can be used for other public health causes.

Climate Change and Medical Education: An Integrative Model.

Medical schools face a challenge when trying to include new topics, such as climate change and health (CCH), in their curricula because of competing demands from more traditional biomedical content. At the same time, an understanding of CCH topics is crucial for physicians as they have clear implications for clinical practice and health care delivery. Although some medical schools have begun to incorporate CCH into curricula, the inclusion usually lacks a comprehensive framework for content and implementation. The authors propose a model for integrating CCH into medical school curricula using a practical, multistakeholder approach designed to mitigate competition for time with existing content by weaving meaningful CCH examples into current curricular activities. After the authors identified stakeholders to include in their curricular development working group, this working group determined the goals and desired outcomes of the curriculum; aligned those outcomes with the school's framework of educational objectives, competencies, and milestones; and strove to integrate CCH goals into as many existing curricular settings as possible. This article includes an illustration of the proposed model for one of the curricular goals (understanding the impacts of climate change on communities), with examples from the CCH curriculum integration that began in the fall of 2020 at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. The authors have found that this approach does minimize competition for time with existing content and allows mapping of content to existing curricular competencies and milestones, while encouraging a broad understanding of CCH in the context of individual patients, populations, and communities. This model for curricular integration can be applied to other topics such as social determinants of health, health equity, disability studies, and structural racism.

Utilization of glucocorticoids among White and Black patients with systemic lupus erythematosus: Observations from the enrollment visit of a prospective registry.

BACKGROUND: Black patients with systemic lupus erythematosus (SLE) face higher rates of morbidity and mortality compared to White patients. Long-term glucocorticoid use has been associated with worse health outcomes among patients with SLE. We sought to quantify chronic glucocorticoid use among Black and White patients with SLE within a prospective registry. METHODS: Using enrollment data from a registry at a large academic institution, we compared glucocorticoid use among Black and White patients with SLE. Multivariable logistic regression of race and glucocorticoid use was performed, adjusting for covariates exhibiting a bivariate association with glucocorticoids at significance level p < 0.10. RESULTS: 114 White participants (mean age 45; standard deviation (SD) 15) and 59 Black participants (mean age 42; SD 14) were analyzed. White participants had mean SLEDAI-2K score of 3.7 (SD 5.2). Black participants had mean SLEDAI-2K scores of 6.3 (SD 6.0). Among Black participants, 43 (72%) utilized glucocorticoids compared to White participants 39 (34%) (unadjusted odds ratio (OR) 5.17; 95% confidence interval (CI) 2.59-10.33). We did not observe differences between unadjusted hydroxychloroquine (OR 0.69; 95% CI 0.28-1.65) or conventional disease-modifying anti-rheumatic drug (cDMARD) (OR 1.07; 95% CI 0.57-2.01) utilization among Black and White participants. SLEDAI-2K, disability, recent hospitalization, and past or present hydroxychloroquine or cDMARD use were included in a logistic regression model. Adjusting for covariates, Black participants were more likely to be on glucocorticoids (adjusted OR 5.69; 95% CI 2.17-14.96); p = 0.0004). CONCLUSION: Adjusting for disease activity and other medications, Black patients had more exposure to chronic glucocorticoids than White patients in the Cleveland Clinic SLE registry. These patients may face increased glucocorticoid-related morbidity, which could contribute significantly to long-term health outcomes and utilization of health care resources. Future research in larger, more diverse registries should be conducted to further characterize patterns of glucocorticoid use.

COVID-19 Outcomes in Patients Undergoing B Cell Depletion Therapy and Those with Humoral Immunodeficiency States: A Scoping Review.

BACKGROUND: The role of humoral immunity has been well established in reducing infection risk and facilitating viral clearance in patients with COVID-19. However, the relationship between specific antibody responses and severity of COVID-19 is less well understood. METHODS: To address this question and identify gaps in knowledge, we utilized the methodology of a scoping review to interrogate risk of infection and clinical outcomes of COVID-19 in patients with iatrogenic and inborn humoral immunodeficiency states based on existing literature. RESULTS: Among patients with iatrogenic B-cell depletion, particularly with agents targeting CD20, our analysis found increased risk of severe COVID-19 and death across a range of underlying disease states. Among patients with humoral inborn errors of immunity with COVID-19, our synthesis found that patients with dysregulated humoral immunity, predominantly common variable immunodeficiency (CVID), may be more susceptible to severe COVID-19 than patients with humoral immunodeficiency states due to X-linked agammaglobulinemia and other miscellaneous forms of humoral immunodeficiency. There were insufficient data to appraise the risk of COVID-19 infection in both populations of patients. CONCLUSIONS: Our work identifies potentially significant predictors of COVID-19 severity in patients with humoral immunodeficiency states and highlights the need for larger studies to control for clinical and biologic confounders of disease severity.

The Value of Total Knee Replacement in Patients With Knee Osteoarthritis and a Body Mass Index of 40 kg/m2 or Greater : A Cost-Effectiveness Analysis.

BACKGROUND: Total knee replacement (TKR) is an effective and cost-effective strategy for treating end-stage knee osteoarthritis. Greater risk for complications among TKR recipients with a body mass index (BMI) of 40 kg/m2 or greater has raised concerns about the value of TKR in this population. OBJECTIVE: To assess the value of TKR in recipients with a BMI of 40 kg/m2 or greater using a cost-effectiveness analysis. DESIGN: Osteoarthritis Policy Model to assess long-term clinical benefits, costs, and cost-effectiveness of TKR in patients with a BMI of 40 kg/m2 or greater. DATA SOURCES: Total knee replacement parameters from longitudinal studies and published literature, and costs from Medicare Physician Fee Schedules, the Healthcare Cost and Utilization Project, and published data. TARGET POPULATION: Recipients of TKR with a BMI of 40 kg/m2 or greater in the United States. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: Total knee replacement. OUTCOME MEASURES: Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. RESULTS OF BASE-CASE ANALYSIS: Total knee replacement increased QALYs by 0.71 year and lifetime medical costs by $25 200 among patients aged 50 to 65 years with a BMI of 40 kg/m2 or greater, resulting in an ICER of $35 200. Total knee replacement in patients older than 65 years with a BMI of 40 kg/m2 or greater increased QALYs by 0.39 year and costs by $21 100, resulting in an ICER of $54 100. RESULTS OF SENSITIVITY ANALYSIS: In TKR recipients with a BMI of 40 kg/m2 or greater and diabetes and cardiovascular disease, ICERs were below $75 000 per QALY. Results were most sensitive to complication rates and preoperative pain levels. In the probabilistic sensitivity analysis, at a $55 000-per-QALY willingness-to-pay threshold, TKR had a 100% and 90% likelihood of being a cost-effective strategy for patients aged 50 to 65 years and patients older than 65 years, respectively. LIMITATION: Data are derived from several sources. CONCLUSION: From a cost-effectiveness perspective, TKR offers good value in patients with a BMI of 40 kg/m2 or greater, including those with multiple comorbidities. PRIMARY FUNDING SOURCE: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.

Lupus-prone B6.Nba2 male and female mice display anti-DWEYS reactivity and a neuropsychiatric phenotype.

OBJECTIVE: Neuropsychiatric lupus (NPSLE), a manifestation of the autoimmune disease systemic lupus erythematosus (SLE), is characterized by psychiatric symptoms including anxiety and depression and upregulated autoantibodies. The B6.Nba2 spontaneous mouse model develops SLE, but has not previously been tested for NPSLE. METHODS: We investigated the NPSLE phenotype in male and female B6.Nba2 mice (n = 12 each) and age- and sex-matched B6 controls (n = 10 each) via behavioral assessments for anxiety, depression, and memory deficits. Serum anti-dsDNA, anti-nRNP, anti-DWEYS peptide reactive IgG autoantibody levels and soluble TWEAK levels were determined by ELISA. Hippocampal regions were stained for activated microglia and neurons. RESULTS: Both male and female B6.Nba2 mice showed elevated anti-dsDNA IgG, anti-nRNP IgG and anti-DWEYS reactive antibodies, elevated serum soluble TWEAK levels, and a strong anxiety and depression phenotype (p < 0.05-0.0001). Male B6.Nba2 mice developed this phenotype at a slightly older age than females. Female B6.Nba2 mice displayed reduced numbers of neurons in the hippocampal region compared to female B6 controls (p < 0.05). CONCLUSION: The B6.Nba2 mouse model recapitulates many known NPSLE phenotypes, making it a promising model to investigate the development of NPSLE in the context of SLE.

Association between changes in muscle strength and pain in persons with meniscal tear and osteoarthritis.

Objective: Strengthening-based physical therapy (PT) is frequently recommended for persons with knee osteoarthritis (OA) and meniscal tear. On average, knee OA patients experience pain improvement while undergoing PT, but whether these changes are accompanied by changes in muscle strength remains an important research question. Design: We used data from subjects randomized to PT in the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial. Key elements, measured at baseline and 3 months, included quadriceps and hamstrings strength (in pounds) and Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale (0-100; 100 worst). We examined the linear association between change in strength and change in pain over 3 months. Results: 111 subjects (mean age 57.1, average baseline hamstrings strength 27.5 (SD 14.7), average baseline KOOS 48.0 (SD 17.0)) experienced an average increase in hamstring strength of 3.5 lbs (SD 9.4) and an average decrease in KOOS Pain of 17.1 points (SD 17.4). The correlation between change in hamstrings strength and change in KOOS Pain was weak (Pearson r = 0.17; 95% CI-0.016-0.345). A multivariable linear regression model adjusting for baseline pain showed that a 10-pound increase in hamstrings strength was associated with a 2.9-point (95% CI-0.05-5.9) reduction in KOOS Pain. The association between changes in quadriceps strength and pain was even weaker than that for hamstrings pain. Conclusion: We observed small increases in strength and weak associations between strengthening and pain relief, suggesting that pain relief achieved during PT likely arises from multiple factors beyond strengthening alone.

Cost-effectiveness of dental antibiotic prophylaxis in total knee arthroplasty recipients with type II diabetes mellitus.

Objective: Type II diabetes mellitus (T2DM) is prevalent in knee osteoarthritis (OA) patients undergoing total knee arthroplasty (TKA) and increases risk for prosthetic joint infection (PJI). We examined the cost-effectiveness of antibiotic prophylaxis (AP) before dental procedures to reduce PJI in TKA recipients with T2DM. Design: We used the Osteoarthritis Policy Model, a validated computer simulation of knee OA, to compare two strategies among TKA recipients with T2DM (mean age 68 years, mean BMI 35.4 kg/m2): 1) AP before dental procedures and 2) no AP. Outcomes included quality-adjusted life expectancy (QALE) and lifetime medical costs. We used published efficacy of AP. We report incremental cost-effectiveness ratios (ICERs) and considered strategies with ICERs below well-accepted willingness-to-pay (WTP) thresholds cost-effective. We conducted sensitivity analyses to examine the robustness of findings to uncertainty in model input parameters. We used a lifetime horizon and healthcare sector perspective. Results: We found that AP added 1.0 quality-adjusted life-year (QALY) and $66,000 for every 1000 TKA recipients with T2DM, resulting in an ICER of $66,000/QALY. In sensitivity analyses, reduction of the probability of PJI, T2DM-associated risk of infection, or attribution of infections to dental procedures by 50% resulted in ICERs exceeding $100,000/QALY. Probabilistic sensitivity analyses showed that AP was cost-effective in 32% and 58% of scenarios at WTP of $50,000/QALY and $100,000/QALY, respectively. Conclusions: AP prior to dental procedures is cost-effective for TKA recipients with T2DM. However, the cost-effectiveness of AP depends on the risk of PJI and efficacy of AP in this population.

A consensus-based process identifying physical therapy and exercise treatments for patients with degenerative meniscal tears and knee OA: the TeMPO physical therapy interventions and home exercise program.

BACKGROUND: Knee osteoarthritis (OA) is prevalent and often associated with meniscal tear. Physical therapy (PT) and exercise regimens are often used to treat OA or meniscal tear, but, to date, few programs have been designed specifically for conservative treatment of meniscal tear with concomitant knee OA. Clinical care and research would be enhanced by a standardized, evidence-based, conservative treatment program and the ability to study the effects of the contextual factors associated with interventions for patients with painful, degenerative meniscal tears in the setting of OA. This paper describes the process of developing both a PT intervention and a home exercise program for a randomized controlled clinical trial that will compare the effectiveness of these interventions for patients with knee pain, meniscal tear and concomitant OA. METHODS: This paper describes the process utilized by an interdisciplinary team of physical therapists, physicians, and researchers to develop and refine a standardized in-clinic PT intervention, and a standardized home exercise program to be carried out without PT supervision. The process was guided in part by Medical Research Council guidance on intervention development. RESULTS: The investigators achieved agreement on an in-clinic PT intervention that included manual therapy, stretching, strengthening, and neuromuscular functional training addressing major impairments in range of motion, musculotendinous length, muscle strength and neuromotor control in the major muscle groups associated with improving knee function. The investigators additionally achieved agreement on a progressive, protocol-based home exercise program (HEP) that addressed the same major muscle groups. The HEP was designed to allow patients to perform and progress the exercises without PT supervision, utilizing minimal equipment and a variety of methods for instruction. DISCUSSION: This multi-faceted in-clinic PT program and standardized HEP provide templates for in-clinic and home-based care for patients with symptomatic degenerative meniscal tear and concomitant OA. These interventions will be tested as part of the Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial. TRIAL REGISTRATION: The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004 on February 14, 2017. TeMPO was also approved by the Institutional Review Board at Partners HealthCare/Brigham and Women's Hospital.

The TeMPO trial (treatment of meniscal tears in osteoarthritis): rationale and design features for a four arm randomized controlled clinical trial.

BACKGROUND: Meniscal tears often accompany knee osteoarthritis, a disabling condition affecting 14 million individuals in the United States. While several randomized controlled trials have compared physical therapy to surgery for individuals with knee pain, meniscal tear, and osteoarthritic changes (determined via radiographs or magnetic resonance imaging), no trial has evaluated the efficacy of physical therapy alone in these subjects. METHODS: The Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial is a four-arm multi-center randomized controlled clinical trial designed to establish the comparative efficacy of two in-clinic physical therapy interventions (one focused on strengthening and one containing placebo) and two protocolized home exercise programs. DISCUSSION: The goal of this paper is to present the rationale behind TeMPO and describe the study design and implementation strategies, focusing on methodologic and clinical challenges. TRIAL REGISTRATION: The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004 . on February 14, 2017.