DICER ribonuclease removes harmful R-loops.

R-loops, which consist of a DNA-RNA hybrid and a displaced DNA strand, are known to threaten genome integrity. To counteract this, different mechanisms suppress R-loop accumulation by either preventing the hybridization of RNA with the DNA template (RNA biogenesis factors), unwinding the hybrid (DNA-RNA helicases), or degrading the RNA moiety of the R-loop (type H ribonucleases [RNases H]). Thus far, RNases H are the only nucleases known to cleave DNA-RNA hybrids. Now, we show that the RNase DICER also resolves R-loops. Biochemical analysis reveals that DICER acts by specifically cleaving the RNA within R-loops. Importantly, a DICER RNase mutant impaired in R-loop processing causes a strong accumulation of R-loops in cells. Our results thus not only reveal a function of DICER as an R-loop resolvase independent of DROSHA but also provide evidence for the role of multi-functional RNA processing factors in the maintenance of genome integrity in higher eukaryotes.

Causal relationships between pain, medical treatments, and knee osteoarthritis: A graphical causal model to guide analyses.

OBJECTIVE: Randomized controlled trials (RCTs) are a gold standard for estimating the benefits of clinical interventions, but their decision-making utility can be limited by relatively short follow-up time. Longer-term follow-up of RCT participants is essential to support treatment decisions. However, as time from randomization accrues, loss to follow-up and competing events can introduce biases and require covariate adjustment even for intention-to-treat effects. We describe a process for synthesizing expert knowledge and apply this to long-term follow-up of an RCT of treatments for meniscal tears in patients with knee osteoarthritis (OA). METHODS: We identified 2 post-randomization events likely to impact accurate assessment of pain outcomes beyond 5 years in trial participants: loss to follow-up and total knee replacement (TKR). We conducted literature searches for covariates related to pain and TKR in individuals with knee OA and combined these with expert input. We synthesized the evidence into graphical models. RESULTS: We identified 94 potential covariates potentially related to pain and/or TKR among individuals with knee OA. Of these, 46 were identified in the literature review and 48 by expert panelists. We determined that adjustment for 50 covariates may be required to estimate the long-term effects of knee OA treatments on pain. CONCLUSION: We present a process for combining literature reviews with expert input to synthesize existing knowledge and improve covariate selection. We apply this process to the long-term follow-up of a randomized trial and show that expert input provides additional information not obtainable from literature reviews alone.

Risk of fall or fracture with concomitant use of prescription opioids and other medications in osteoarthritis patients.

BACKGROUND: Osteoarthritis (OA) patients taking prescription opioids for pain are at increased risk of fall or fracture, and the concomitant use of interacting drugs may further increase the risk of these events. AIMS: To identify prescription opioid-related medication combinations associated with fall or fracture. MATERIALS & METHODS: We conducted a case-crossover-based screening of two administrative claims databases spanning 2003 through 2021. OA patients were aged 40 years or older with at least 365 days of continuous enrollment and 90 days of continuous prescription opioid use before their first eligible fall or fracture event. The primary analysis quantified the odds ratio (OR) between fall and non-opioid medications dispensed in the 90 days before the fall date after adjustment for prescription opioid dosage and confounding using a case-time-control design. A secondary analogous analysis evaluated medications associated with fracture. The false discovery rate (FDR) was used to account for multiple testing. RESULTS: We identified 41 693 OA patients who experienced a fall and 24 891 OA patients who experienced a fracture after at least 90 days of continuous opioid therapy. Top non-opioid medications by ascending p-value with OR > 1 for fall were meloxicam (OR 1.22, FDR = 0.08), metoprolol (OR 1.06, FDR >0.99), and celecoxib (OR 1.13, FDR > 0.99). Top non-opioid medications for fracture were losartan (OR 1.20, FDR = 0.80), alprazolam (OR 1.14, FDR > 0.99), and duloxetine (OR 1.12, FDR = 0.97). CONCLUSION: Clinicians may seek to monitor patients who are co-prescribed drugs that act on the central nervous system, especially in individuals with OA.

Thriving from Work Questionnaire: Dimensionality, reliability, and validity of the long and short form questionnaires.

INTRODUCTION: Thriving from Work is defined as the state of positive mental, physical, and social functioning in which workers' experiences of their work and working conditions enable them to thrive in their overall lives, contributing to their ability to achieve their full potential at work, at home, and in the community. The purpose of this study was to develop a psychometrically-sound questionnaire measuring the positive contribution that work can have on one's well-being both at, and outside of, their work. METHODS: We used both a qualitative and quantitative approach of item reduction, domain mapping dimensionality testing, development of "long-" and "short-" versions of the questionnaire, reliability, and construct and criterion validity testing. This was established in two independent online samples of US based workers (n = 1550, n = 500). RESULTS: We developed a bi-factor model 30-item long-form and a uni-factorial 8-item short-version. The long-form measures both the latent construct of Thriving from Work and six domains (psychological/emotional; work-life integration; social; experience of work; basic needs; health). Both long- and short- forms were found to have high empirical reliability (0.93  and 0.87 respectively). The short-form captures 94% of variance of the long-form. Construct and criterion validity were supported. Test-retest reliability was high. CONCLUSIONS: The Thriving from Work Questionnaire appears to be a valid and reliable measure of work-related well-being in United States workers. Further testing is needed to refine and test the instrument in specific industries, unique worker populations, and across geographic regions.

The influence of meniscal pathology in the incidence of knee osteoarthritis: a review.

IMPORTANCE: Knee osteoarthritis (OA) is a common cause of pain and disability in older persons, affecting approximately 14 million individuals in the USA. Meniscal damage is also common in this age group with a prevalence of 35% in a middle-aged and older community sample and 82% in persons with evidence of radiographic knee osteoarthritis. This paper systematically reviews evidence on the association of meniscal pathology and incident radiographic knee OA. OBSERVATIONS: We included 15 articles, published between 2013 and 2021, assessing the relationship between meniscal pathology and OA incidence (Fig. 1). The menisci are crucial load-bearing structures, and the resulting increase in biomechanical stress due to meniscal damage increases the risk for OA development. While some discrepancies are present in the literature, a clinically meaningful association has been generally established between the presence of a meniscal tear or meniscal extrusion and subsequent development of incident OA. Of note, larger radial tears as well as complex and more severe tears exhibit the strongest association with the development of incident OA. The relationship between other features of meniscal morphology-such as meniscal volume and meniscal coverage-and incident OA is less clearly documented. CONCLUSIONS AND RELEVANCE: The early detection of meniscal pathology can be used to trigger preventative and therapeutic strategies designed to avert or delay knee OA in this at-risk population.

Grinding, Clicking, and Pivot Pain Resolve in Most Patients After Knee Arthroscopy.

PURPOSE: To determine whether knee arthroscopy alleviates the symptom constellation of knee grinding/clicking, catching/locking, and pivot pain. METHODS: One-year follow-up data from 584 consecutive subjects who underwent knee arthroscopy from August 2012 to December 2019 were collected prospectively. Subjects reported frequency of knee grinding/clicking, catching/locking, and/or pivot pain preoperatively and 1 and 2 years postoperatively. A single surgeon performed each procedure and documented all intraoperative pathology. We measured the postoperative resolution or persistence of these symptoms and used multivariable regression models to identify preoperative demographic and clinical variables that predicted symptom persistence. We also assessed changes in the Pain, Activities of Daily Living, and Quality of Life subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Postoperative symptom resolution was more likely for grinding/clicking (65.6%) and pivot pain (67.8%) than for catching/locking (44.1%). Smoking status, overweight/obesity, absence of meniscal tear, and number of compartments with focal cartilage lesions predicted persistence of 1 or more patient-reported knee symptoms. KOOS subscale scores consistently improved by at least one standard deviation. Individuals who had resolution of patient-reported knee symptoms exhibited roughly 2-fold improvements in KOOS Pain, ADL and Quality of Life scores compared with those whose symptoms persisted. Persistence of pivot pain was associated with the least improvement of the 3 KOOS subscales. CONCLUSIONS: Two in three patients with grinding/clicking or pivot pain experience symptom resolution after knee arthroscopy, although catching/locking is more likely to persist. Smoking status, overweight/obesity, absence of meniscal tear, and number of compartments with focal cartilage lesions predict symptom persistence after knee arthroscopy. LEVEL OF EVIDENCE: Therapeutic Level IV, retrospective cohort analysis of prospective data.

The Association of Sacro-Femoro-Pubic Angle and Postoperative Dislocation Following Total Hip Arthroplasty.

BACKGROUND: Spino-pelvic orientation may affect dislocation risk following total hip arthroplasty (THA). It can be measured on lateral lumbo-pelvic radiographs. The sacro-femoro-pubic (SFP) angle, measured on an antero-posterior (AP) pelvis radiograph, is a reliable proxy for pelvic tilt, a measurement of spino-pelvic orientation measured on a lateral lumbo-pelvic radiograph. The purpose of this study was to investigate the relationship between SFP angle and dislocation following THA. METHODS: An Institutional Review Board-approved retrospective case-control study was conducted at a single academic center. We matched 71 dislocators (cases) to 71 nondislocators (controls) following THA performed by 1 of 10 surgeons between September 2001 and December 2010. Two authors (readers) independently calculated SFP angle from single preoperative AP pelvis radiographs. Readers were blinded to cases and controls. Conditional logistic regressions were used to identify factors differentiating cases and controls. RESULTS: The data did not show a clinically relevant or statistically significant difference in SFP angles after adjusting for gender, American Society of Anesthesiologists classification, prosthetic head size, age at time of THA, measurement laterality, and surgeon. CONCLUSION: We did not find an association between preoperative SFP angle and dislocation following THA in our cohort. Based on our data, SFP angle as measured on a single AP pelvis radiograph should not be used to assess dislocation risk prior to THA.

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.

Multimodal prediction of pain and functional outcomes 6 months following total knee replacement: a prospective cohort study.

BACKGROUND: Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence and impact around the globe. In the U.S., the rising prevalence of knee OA has been paralleled by an increase in annual rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, post-operative trajectories of pain and functional status vary substantially; a significant minority of patients report ongoing pain and impaired function following TKA. A number of studies have identified sets of biopsychosocial risk factors for poor post-TKA outcomes (e.g., comorbidities, negative affect, sensory sensitivity), but few prospective studies have systematically evaluated the unique and combined influence of a broad array of factors. METHODS: This multi-site longitudinal cohort study investigated predictors of 6-month pain and functional outcomes following TKA. A wide spectrum of relevant biopsychosocial predictors was assessed preoperatively by medical history, patient-reported questionnaire, functional testing, and quantitative sensory testing in 248 patients undergoing TKA, and subsequently examined for their predictive capacity. RESULTS: The majority of patients had mild or no pain at 6 months, and minimal pain-related impairment, but approximately 30% reported pain intensity ratings of 3/10 or higher. Reporting greater pain severity and dysfunction at 6 months post-TKA was predicted by higher preoperative levels of negative affect, prior pain history, opioid use, and disrupted sleep. Interestingly, lower levels of resilience-related "positive" psychosocial characteristics (i.e., lower agreeableness, lower social support) were among the strongest, most consistent predictors of poor outcomes in multivariable linear regression models. Maladaptive profiles of pain modulation (e.g., elevated temporal summation of pain), while not robust unique predictors, interacted with psychosocial risk factors such that the TKA patients with the most pain and dysfunction exhibited lower resilience and enhanced temporal summation of pain. CONCLUSIONS: This study underscores the importance of considering psychosocial (particularly positively-oriented resilience variables) and sensory profiles, as well as their interaction, in understanding post-surgical pain trajectories.

A Provider Perspective of Psychosocial Predictors of Upper-Extremity Vascularized Composite Allotransplantation Success.

PURPOSE: We performed a qualitative study to understand the psychosocial factors associated with success in upper-extremity vascularized composite allotransplantation from the perspective of transplant providers. METHODS: We recruited 13 providers actively involved in upper-extremity vascularized composite allotransplantation. Participants included physicians, nurses, social workers, occupational therapists, and research administrators. We conducted semistructured face-to-face focus group interviews using a guide that explored providers' perceptions of qualities contributing to transplant outcome. Topics included social support networks and their influence on recovery, barriers to treatment compliance and successful posttransplant rehabilitation, and the process of setting patients' expectations. We performed a thematic analysis that produced a list of themes, subthemes, and proposed hypotheses explaining how the themes related to the study's guiding questions. RESULTS: The analysis identified numerous factors that contribute to transplant success: (1) recipients' prior experiences modify their ability to cope and adapt after transplantation, (2) behaviors and characteristics such as positivity influence candidacy and may be predictive of successful outcomes, and (3) social support is essential for improved function and compliance. The provider care team cited difficulty in predicting recipient compliance and in setting realistic expectations. CONCLUSIONS: Motivated recipients with developed coping and resiliency, a positive attitude, and stable, physically-able caregivers are perceived by providers to have greater success after transplantation. CLINICAL RELEVANCE: Findings from this work may help providers determine optimal candidates for upper-extremity vascularized composite allotransplantation.

Diagnosis and Management of Lumbar Spinal Stenosis: A Review.

Importance: Lumbar spinal stenosis is a prevalent and disabling cause of low back and leg pain in older persons, affecting an estimated 103 million persons worldwide. Most are treated nonoperatively. Approximately 600 000 surgical procedures are performed in the US each year for lumbar spinal stenosis. Observations: The prevalence of the clinical syndrome of lumbar spinal stenosis in US adults is approximately 11% and increases with age. The diagnosis can generally be made based on a clinical history of back and lower extremity pain that is provoked by lumbar extension, relieved by lumbar flexion, and confirmed with cross-sectional imaging, such as computed tomography or magnetic resonance imaging (MRI). Nonoperative treatment includes activity modification such as reducing periods of standing or walking, oral medications to diminish pain such as nonsteroidal anti-inflammatory drugs (NSAIDs), and physical therapy. In a series of patients with lumbar spinal stenosis followed up for up to 3 years without operative intervention, approximately one-third of patients reported improvement, approximately 50% reported no change in symptoms, and approximately 10% to 20% of patients reported that their back pain, leg pain, and walking were worse. Long-term benefits of epidural steroid injections for lumbar spinal stenosis have not been demonstrated. Surgery appears effective in carefully selected patients with back, buttock, and lower extremity pain who do not improve with conservative management. For example, in a randomized trial of 94 participants with symptomatic and radiographic degenerative lumbar spinal stenosis, decompressive laminectomy improved symptoms more than nonoperative therapy (difference, 7.8 points; 95% CI, 0.8-14.9; minimum clinically important difference, 10-12.8) on the Oswestry Disability Index (score range, 0-100). Among persons with lumbar spinal stenosis and concomitant spondylolisthesis, lumbar fusion increased symptom resolution in 1 trial (difference, 5.7 points; 95% CI, 0.1 to 11.3) on the 36-Item Short Form Health Survey physical dimension score (range, 0-100), but 2 other trials showed either no important differences between the 2 therapies or noninferiority of lumbar decompression alone compared with lumbar decompression plus spinal fusion (MCID, 2-4.9 points). In a noninferiority trial, 71.4% treated with lumbar decompression alone vs 72.9% of those receiving decompression plus fusion achieved a 30% or more reduction in Oswestry Disability Index score, consistent with the prespecified noninferiority hypothesis. Fusion is associated with greater risk of complications such as blood loss, infection, longer hospital stays, and higher costs. Thus, the precise indications for concomitant lumbar fusion in persons with lumbar spinal stenosis and spondylolisthesis remain unclear. Conclusions and Relevance: Lumbar spinal stenosis affects approximately 103 million people worldwide and 11% of older adults in the US. First-line therapy is activity modification, analgesia, and physical therapy. Long-term benefits from epidural steroid injections have not been established. Selected patients with continued pain and activity limitation may be candidates for decompressive surgery.

Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity: A Randomized Clinical Trial.

Importance: Some weight loss and exercise programs that have been successful in academic center-based trials have not been evaluated in community settings. Objective: To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021. Interventions: Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months. Main Outcomes and Measures: The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight. Results: Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, -0.6; 95% CI, -1.0 to -0.1; P = .02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was -7.7 kg (8%) in the diet and exercise group (n = 289) and -1.7 kg (2%) in the attention control group (n = 273) (mean difference, -6.0 kg; 95% CI, -7.3 kg to -4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise). Conclusions and Relevance: Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02577549.

Satisfaction With a Virtual Learning Collaborative Aimed at Implementing Treat-to-Target in Rheumatoid Arthritis.

OBJECTIVE: Limited information is available concerning experiences of participants in a virtual learning collaborative (LC), and little qualitative data or participant feedback on how this format can be improved. One prior in-person LC in rheumatology successfully improved adherence with treat-to-target (TTT) for RA. We conducted a virtual LC on TTT and herein report on participant satisfaction. METHODS: We conducted a virtual LC with 18 rheumatology practices from across the United States during 2020 to 2021. The LC included a virtual kickoff meeting and monthly videoconferences, accompanied by data submission and feedback. At the conclusion of the LC, we surveyed the 45 LC participants concerning individual experience and satisfaction. RESULTS: All sites and 78% of participants responded to the surveys. The LC included small and large practices, 14 academic and 4 nonacademic, and respondents ranged in their roles: 24 physicians, 5 nurses or nurse practitioners, 3 administrators, and 3 other roles. Overall, 94% of respondents indicated they were either somewhat or very satisfied with the LC, and 94% said they would recommend a similar LC to a colleague. Aspects of the LC described as "very useful" included a kickoff meeting, intersite discussion, and monthly speakers; however, digital tools such as the Web site and meeting recordings were not found useful. CONCLUSIONS: Virtual LCs are feasible, and participants reported strong satisfaction. Virtual LCs were highly valued by rheumatologists, trainees, and their practice staffs. Potential topics were identified for future LCs that could improve the quality of care delivered to rheumatology patients.

Provider perspectives on the provision of safe, equitable, trauma-informed care for intimate partner violence survivors during the COVID-19 pandemic: a qualitative study.

BACKGROUND: Early research suggests the COVID-19 pandemic worsened intimate partner violence (IPV) in the US. In particular, stay-at-home orders and social distancing kept survivors in close proximity to their abusers and restricted access to resources and care. We aimed to understand and characterize the impact of the pandemic on delivery of IPV care in Boston. METHODS: We conducted individual interviews with providers of IPV care and support in the Greater Boston area, including healthcare workers, social workers, lawyers, advocates, and housing specialists, who continued to work during the COVID-19 pandemic. Using thematic analysis, we identified themes describing the challenges and opportunites providers faced in caring for survivors during the pandemic. RESULTS: Analysis of 18 interviews yielded four thematic domains, encompassing 18 themes and nine sub-themes. Thematic analysis revealed that the pandemic posed an increased threat to survivors of IPV by exacerbating external stressors and leading to heightened violence. On a system level, the pandemic led to widespread uncertainty, strained resources, amplified inequities, and loss of community. On an individual level, COVID-19 restrictions limited survivors' abilities to access resources and to be safe, and amplified pre-existing inequities, such as limited technology access. Those who did not speak English or were immigrants experienced even more difficulty accessing resources due to language and/or cultural barriers. To address these challenges, providers utilized video and telephone interactions, and stressed the importance of creativity and cooperation across different sectors of care. CONCLUSIONS: While virtual care was essential in allowing providers to care for survivors, and also allowed for increased flexibility, it was not a panacea. Many survivors faced additional obstacles to care, such as language barriers, unequal access to technology, lack of childcare, and economic insecurity. Providers addressed these barriers by tailoring services and care modalities to an individual's needs and circumstances. Going forward, some innovations of the pandemic period, such as virtual interactions and cooperation across care sectors, may be utilized in ways that attend to shifting survivor needs and access, thereby improving safe, equitable, and trauma-informed IPV care.

Perceived Success in Upper-Extremity Vascularized Composite Allotransplantation: A Qualitative Study.

PURPOSE: We performed a qualitative study to understand psychosocial factors associated with perceived success of upper-extremity vascularized composite allotransplantation (VCA). We interviewed transplant recipients and their primary caregivers. METHODS: We recruited 4 upper-extremity VCA recipients and primary caregivers for 3 of them. We conducted semistructured face-to-face interviews using a guide that explored participants' transplantation experiences. Topics included comparison of pretransplant and posttransplant expectations, reflections on factors contributing to the success of the transplant experience, and posttransplant rehabilitation and functioning. We performed a thematic analysis that produced a list of themes, subthemes, and proposed hypotheses explaining how the themes related to the study's guiding questions. RESULTS: Participants described several factors as contributing to the success of the transplant experience, including developing realistic expectations about posttransplant function and lifelong immunosuppression, support from one's community and particularly the primary caregiver, and framing the experience in a positive light. Social, aesthetic, and other values unique to the hands, as opposed to prosthetics, motivated recipients to undergo VCA despite its inherent risk and uncertainties. CONCLUSIONS: Despite inherent challenges, undergoing VCA was viewed as worthwhile to regain benefits unique to hands. Participants met the challenges of the transplant process through setting realistic expectations, strong social support, and a positive perspective. CLINICAL RELEVANCE: Findings from this work may help clinicians and prospective patients to prepare for and set appropriate expectations of VCA.

Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review.

Importance: Osteoarthritis (OA) is the most common joint disease, affecting an estimated more than 240 million people worldwide, including an estimated more than 32 million in the US. Osteoarthritis is the most frequent reason for activity limitation in adults. This Review focuses on hip and knee OA. Observations: Osteoarthritis can involve almost any joint but typically affects the hands, knees, hips, and feet. It is characterized by pathologic changes in cartilage, bone, synovium, ligament, muscle, and periarticular fat, leading to joint dysfunction, pain, stiffness, functional limitation, and loss of valued activities, such as walking for exercise and dancing. Risk factors include age (33% of individuals older than 75 years have symptomatic and radiographic knee OA), female sex, obesity, genetics, and major joint injury. Persons with OA have more comorbidities and are more sedentary than those without OA. The reduced physical activity leads to a 20% higher age-adjusted mortality. Several physical examination findings are useful diagnostically, including bony enlargement in knee OA and pain elicited with internal hip rotation in hip OA. Radiographic indicators include marginal osteophytes and joint space narrowing. The cornerstones of OA management include exercises, weight loss if appropriate, and education-complemented by topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs) in those without contraindications. Intra-articular steroid injections provide short-term pain relief and duloxetine has demonstrated efficacy. Opiates should be avoided. Clinical trials have shown promising results for compounds that arrest structural progression (eg, cathepsin K inhibitors, Wnt inhibitors, anabolic growth factors) or reduce OA pain (eg, nerve growth factor inhibitors). Persons with advanced symptoms and structural damage are candidates for total joint replacement. Racial and ethnic disparities persist in the use and outcomes of joint replacement. Conclusions and Relevance: Hip and knee OA are highly prevalent and disabling. Education, exercise and weight loss are cornerstones of management, complemented by NSAIDs (for patients who are candidates), corticosteroid injections, and several adjunctive medications. For persons with advanced symptoms and structural damage, total joint replacement effectively relieves pain.

Intra-articular Corticosteroid Injections for the Treatment of Hip and Knee Osteoarthritis-related Pain: Considerations and Controversies with a Focus on Imaging-Radiology Scientific Expert Panel.

Current management of osteoarthritis (OA) is primarily focused on symptom control. Intra-articular corticosteroid (IACS) injections are often used for pain management of hip and knee OA in patients who have not responded to oral or topical analgesics. Recent case series suggested that negative structural outcomes including accelerated OA progression, subchondral insufficiency fracture, complications of pre-existing osteonecrosis, and rapid joint destruction (including bone loss) may be observed in patients who received IACS injections. This expert panel report reviews the current understanding of pain in OA, summarizes current international guidelines regarding indications for IACS injection, and considers preinterventional safety measures, including imaging. Potential profiles of those who would likely benefit from IACS injection and a suggestion for an updated patient consent form are presented. As of today, there is no established recommendation or consensus regarding imaging, clinical, or laboratory markers before an IACS injection to screen for OA-related imaging abnormalities. Repeating radiographs before each subsequent IACS injection remains controversial. The true cause and natural history of these complications are unclear and require further study. To determine the cause and natural history, large prospective studies evaluating the risk of accelerated OA or joint destruction after IACS injections are needed. However, given the relatively rare incidence of these adverse outcomes, any clinical trial would be challenging in design and a large number of patients would need to be included.

Mobile health clinics in the United States.

BACKGROUND: Mobile health clinics serve an important role in the health care system, providing care to some of the most vulnerable populations. Mobile Health Map is the only comprehensive database of mobile clinics in the United States. Members of this collaborative research network and learning community supply information about their location, services, target populations, and costs. They also have access to tools to measure, improve, and communicate their impact. METHODS: We analyzed data from 811 clinics that participated in Mobile Health Map between 2007 and 2017 to describe the demographics of the clients these clinics serve, the services they provide, and mobile clinics' affiliated institutions and funding sources. RESULTS: Mobile clinics provide a median number of 3491 visits annually. More than half of their clients are women (55%) and racial/ethnic minorities (59%). Of the 146 clinics that reported insurance data, 41% of clients were uninsured while 44% had some form of public insurance. The most common service models were primary care (41%) and prevention (47%). With regards to organizational affiliations, they vary from independent (33%) to university affiliated (24%), while some (29%) are part of a hospital or health care system. Most mobile clinics receive some financial support from philanthropy (52%), while slightly less than half (45%) receive federal funds. CONCLUSION: Mobile health care delivery is an innovative model of health services delivery that provides a wide variety of services to vulnerable populations. The clinics vary in service mix, patient demographics, and relationships with the fixed health system. Although access to care has increased in recent years through the Affordable Care Act, barriers continue to persist, particularly among populations living in resource-limited areas. Mobile clinics can improve access by serving as a vital link between the community and clinical facilities. Additional work is needed to advance availability of this important resource.

Editorial Commentary: Degenerative Meniscal Tear: Sojourn to the Oracle.

Degenerative meniscal tears are prevalent and give rise to more than 400,000 arthroscopic partial meniscectomies annually in the United States. These lesions often occur in the setting of knee osteoarthritis and are generally regarded as a component of the tissue damage (to cartilage, meniscus, bone, synovium among others) that comprises osteoarthritis. A wide array of clinicians, ranging from orthopaedic surgeons to general practitioners, regularly encounter symptomatic degenerative meniscal tears, especially among patients with knee osteoarthritis. Clinical evidence suggests that initial treatment for these injuries should be nonoperative, with arthroscopic partial meniscectomy reserved for those whose pain persists despite physical therapy.

Professional language use by alumni of the Harvard Medical School Medical Language Program.

BACKGROUND: Despite the growing number of patients with limited English proficiency in the United States, not all medical schools offer medical language courses to train future physicians in practicing language-concordant care. Little is known about the long-term use of non-English languages among physicians who took language courses in medical school. We conducted a cross-sectional study to characterize the professional language use of Harvard Medical School (HMS) alumni who took a medical language course at HMS and identify opportunities to improve the HMS Medical Language Program. METHODS: Between October and November 2019, we sent an electronic survey to 803 HMS alumni who took a medical language course at HMS between 1991 and 2019 and collected responses. The survey had questions about the language courses and language use in the professional setting. We analyzed the data using descriptive statistics and McNemar's test for comparing proportions with paired data. The study was determined not to constitute human subjects research. RESULTS: The response rate was 26% (206/803). More than half of respondents (n = 118, 57%) cited their desire to use the language in their future careers as the motivation for taking the language courses. Twenty-eight (14%) respondents indicated a change from not proficient before taking the course to proficient at the time of survey whereas only one (0.5%) respondent changed from proficient to not proficient (McNemar's p-value < 0.0001). Respondents (n = 113, 56%) reported that clinical electives abroad influenced their cultural understanding of the local in-country population and their language proficiency. Only 13% (n = 27) of respondents have worked in a setting that required formal assessments of non-English language proficiency. CONCLUSIONS: HMS alumni of the Medical Language Program reported improved language proficiency after the medical language courses' conclusion, suggesting that the courses may catalyze long-term language learning. We found that a majority of respondents reported that the medical language courses influenced their desire to work with individuals who spoke the language of the courses they took. Medical language courses may equip physicians to practice language-concordant care in their careers.