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ObjectivesTo determine the incidence of osteoarthrits (OA) in patients with atopic disease compared with matched non-exposed patients.MethodsWe conducted a retrospective cohort study with propensity score matching using claims data from Optum’s de-identified Clinformatics Data Mart (CDM) (January 2003 to June 2019) and electronic health record data from the Stanford Research Repository (STARR) (January 2010 to December 2020). We included adult patients without pre-existing OA or inflammatory arthritis who were exposed to atopic disease or who were non-exposed. The primary outcome was the development of incident OA.ResultsIn Optum CDM, we identified 117 346 exposed patients with asthma or atopic dermatitis (mean age 52 years; 60% female) and 1 247 196 non-exposed patients (mean age 50 years; 48% female). After propensity score matching (n=1 09 899 per group), OA incidence was higher in patients with asthma or atopic dermatitis (26.9 per 1000 person-years) compared with non-exposed patients (19.1 per 1000 person-years), with an adjusted odds ratio (aOR) of 1.58 (95% CI 1.55 to 1.62) for developing OA. This effect was even more pronounced in patients with both asthma and atopic dermatitis compared with non-exposed patients (aOR=2.15; 95% CI 1.93 to 2.39) and in patients with asthma compared with patients with chronic obstructive pulmonary disease (aOR=1.83; 95% CI 1.73 to 1.95). We replicated our results in an independent dataset (STARR), which provided the added richness of body mass index data. The aOR of developing OA in patients with asthma or atopic dermatitis versus non-exposed patients in STARR was 1.42 (95% CI 1.36 to 1.48).ConclusionsThis study demonstrates an increased incidence of OA in patients with atopic disease. Future interventional studies may consider targeting allergic pathways for the prevention or treatment of OA.

To quantify the total hospital costs associated with the treatment of lower extremity long-bone fracture aseptic and septic unhealed fracture, to determine if insurance adequately covers these costs, and to examine whether insurance type correlates with barriers to accessing care.Retrospective cohort study.Academic Level II trauma center.All patients undergoing operative treatment of OTA/AO classification 31, 32, 33, 41, 42, and 43 fractures between 2012 and 2020 at a single Level II trauma center with minimum of 1-year follow-up.The primary outcome was the total cost of treatment for all hospital-based episodes of care. Distance traveled from primary residence was measured as a surrogate for barriers to care.One hundred seventeen patients with uncomplicated fracture healing, 82 with aseptic unhealed fracture, and 44 with septic unhealed fracture were included in the final cohort. The median cost of treatment for treatment of septic unhealed fracture was $148,318 [interquartile range(IQR) 87,241-256,928], $45,230 (IQR 31,510-68,030) for treatment of aseptic unhealed fracture, and $33,991 (IQR 25,609-54,590) for uncomplicated fracture healing. The hospital made a profit on all patients with commercial insurance, but lost money on all patients with public insurance. Among patients with unhealed fracture, those with public insurance traveled 4 times further for their care compared with patients with commercial insurance (P = 0.004).Septic unhealed fracture of lower extremity long-bone fractures is an outsized burden on the health care system. Public insurance for both septic and aseptic unhealed fracture does not cover hospital costs. The increased distances traveled by our Medi-Cal and Medicare population may reflect the economic disincentive for local hospitals to care for publicly insured patients with unhealed fractures.Economic Level V. See Instructions for Authors for a complete description of levels of evidence.

Limb loss leads to significant disability. Prostheses may mitigate this disability but are not readily accessible in low- and middle-income countries (LMICs). Cost-effectiveness data related to prosthesis provision in resource-constrained environments such as Tanzania is greatly limited.This study aimed to compare the cost-effectiveness of a prosthesis intervention compared with that of no prosthesis for persons with transfemoral amputations in an LMIC.This is a prospective cohort study.Thirty-eight patients were prospectively followed up. Clinical improvement with prosthesis provision was measured using EuroQuol-5D, represented as quality-adjusted life years gained. Direct and indirect costs were measured. The primary outcome was incremental cost per quality-adjusted life year, measured at 1 year and projected over a lifetime using a Markov model. Reference case was set as a single prosthesis provided without replacement from a payer perspective. Additional scenarios included the societal perspective and replacement of the prosthesis. Uncertainty was measured with one-way probabilistic sensitivity analysis.From the payer perspective, the incremental cost-effectiveness ratio (ICER) was $242 for those without prosthetic replacement over a lifetime, and the ICER was $390 for those with prosthetic replacement over a lifeime. From the societal perspective, prosthesis provision was both less expensive and more effective. One-way sensitivity analysis demonstrated the ICER remained below the willingness to pay threshold up to prosthesis costs of $763.These findings suggest prosthesis provision in an LMIC may be cost-effective, but further studies with long-term follow up are needed to validate the results.

While surgeons in low and middle-income countries have increasing experience with intramedullary nailing (IMN), external fixation (EF) continues to be commonly used for the management of open tibial fractures. We examined outcomes with extended follow-up of the participants enrolled in a clinical trial comparing these treatments.Adults who were ≥18 years old with acute AO/OTA type-42 open tibial shaft fractures were randomly assigned to statically locked, hand-reamed IMN or uniplanar EF. These participants were reevaluated 3 to 5 years after treatment. The primary outcome was death or reoperation for the treatment of deep infection, nonunion, or malalignment. Unresolved complications such as persistent fracture-related infection, nonunion, or malalignment were collected and analyzed. Secondary outcomes included the EuroQol-5 Dimension-3 Level (EQ-5D-3L) questionnaire, the Function IndeX for Trauma (FIX-IT) score, radiographic alignment, and the modified Radiographic Union Scale for Tibial fractures (mRUST).Of the originally enrolled 240 participants,126 (67 managed with IMN and 59 managed with EF) died or returned for follow-up at a mean of 4.0 years (range, 2.9 to 5.2 years). Thirty-two composite primary events occurred, with rates of 23.9% and 27.1% in the IMN and EF groups, respectively. Six of these events (3 in the IMN group and 3 in the EF group) were newly detected after the original 1-year follow-up. Unresolved complications in the form of chronic fracture-related infection or nonunion were present at long-term follow-up in 25% of the participants who sustained a primary event. The EQ-5D-3L index scores were similar between the 2 groups and only returned to preinjury levels after 1 year among patients without complications or those whose complications resolved.This observational study extended follow-up for a clinical trial assessing IMN versus EF for the treatment of open tibial fractures in sub-Saharan Africa. At a mean of 4 years after injury, fracture-related infection and nonunion became chronic conditions in nearly a quarter of the participants who experienced these complications, regardless of reintervention.Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

This investigation develops a predictive model for loss of alignment (LOA) following fixation of open tibia fractures.An analysis was performed of adults with diaphyseal open tibia fractures randomized to intramedullary nailing (IMN) or external fixation (EF) followed at 6, 12, 24, and 52 weeks postoperatively. Demographic data were collected at baseline. Pre-injury and follow-up EuroQol 5-Dimensions (EQ-5D) and pain score were measured. Radiographs, taken postoperatively and in follow-up, were assessed for coronal and sagittal angulation, and used to calculate the modified Radiographic Union Scale for Tibia fractures (mRUST). LOA was defined as an increase in angulation5° by one year follow-up. Fracture comminution was defined using AO/OTA classification. Putative risk factors were assessed for association with LOA using bivariate logistic regression. Adjusted associations with LOA were estimated using multivariable logistic regression and marginal analysis.Analyses included 129 patients (70 IMN, 59 EF), majority male, of mean age 33 years (range 17.7-73) and body mass index (BMI) 25.2 (range 15.5-45.1), with 48% Type A, 41% Type B, and 11% Type C fractures (AO/OTA classification). The likelihood of LOA with EF increased with greater fracture comminution; 45.21% (p0.001), 77.50% (p0.001), and 100% LOA for Type A, B, and C fractures respectively. Relative risk of LOA for EF compared to IMN was 3.87 (95% CI 1.36, 11.02), 3.75 (95% CI 1.77, 7.92), and 5.76 for Type A, B, and C fractures, respectively. Compared to patients who lost alignment, patients without LOA had improved fracture healing (p = 0.003) and higher EQ-5D scores (p = 0.03) at one year.Increasing age and BMI are associated with LOA and segmental fracture amplifies the protective effect of IMN versus EF. The importance of LOA as a surrogate outcome after operative treatment of open tibial fractures is supported by its association with inferior radiographic and functional patient outcomes.

BackgroundFemur fracture patients require significant in-hospital care. The burden incurred by caregivers of such patients amplifies the direct costs of these injuries and remains unquantified. Aim Here we aim to establish the in-hospital economic burden faced by informal caregivers of femur fracture patients. Methods 70 unique caregivers for 46 femoral shaft fracture patients were interviewed. Incurred economic burden was determined by the Human Capital Approach, using standardized income data to quantify productivity loss (in $USD). Linear regression assessed the relationship between caregiver burden and patient time-in-hospital.ResultsThe average economic burden incurred was $149, 9% of a caregiver’s annual income and positively correlated with patient time in hospital (p

There exists an unmet need for locally relevant and sustainable orthopedic research in low- and middle-income countries. Partnerships between high-income countries and low- and middle-income countries can bridge gaps in resources, knowledge, infrastructure, and skill. This article presents a select list of models for high-income countries/low- and middle-income countries research partnerships including academic partnerships, international research consortia, professional society-associated working groups, and nongovernmental organization partnerships. Models that produce research with lasting legacy are those that promote mutually beneficial partnerships over individual gains.

Introduction. The objective of this systematic review with meta-analysis is to determine whether prophylactic local antibiotics prevent surgical site infections (SSIs) in instrumented spinal fusions and traumatic fracture repair. A secondary objective is to investigate the effect of vancomycin, a common local antibiotic of choice, on the microbiology of SSIs. Methods. An electronic search of PubMed, EMBASE, and Web of Science databases and major orthopedic surgery conferences was conducted to identify studies that (1) were instrumented spinal fusions or fracture repair and (2) had a treatment group that received prophylactic local antibiotics. Both randomized controlled trials (RCTs) and comparative observational studies were included. Meta-analysis was performed separately for randomized and nonrandomized studies with subgroup analysis by study design and antibiotic. Results. Our review includes 44 articles (30 instrumented spinal fusions and 14 fracture repairs). Intrawound antibiotics significantly decreased the risk of developing SSIs in RCTs of fracture repair (RR 0.61, 95% CI: 0.40–0.93, I2 = 32.5%) but not RCTs of instrumented spinal fusion. Among observational studies, topical antibiotics significantly reduced the risk of SSIs in instrumented spinal fusions (OR 0.34, 95% CI: 0.27–0.43, I2 = 52.4%) and in fracture repair (OR 0.49, 95% CI: 0.37–0.65, I2 = 43.8%). Vancomycin powder decreased the risk of Gram-positive SSIs (OR 0.37, 95% CI: 0.27–0.51, I2 = 0.0%) and had no effect on Gram-negative SSIs (OR 0.95, 95% CI: 0.62–1.44, I2 = 0.0%). Conclusions. Prophylactic intrawound antibiotic administration decreases the risk of SSIs in fracture surgical fixation in randomized studies. Therapeutic efficacy in instrumented spinal fusion was seen in only nonrandomized studies. Vancomycin appears to be an effective agent against Gram-positive pathogens. There is no evidence that local vancomycin powder is associated with an increased risk for Gram-negative infection.

Background: The rise of diabetes and traumatic injury has increased limb loss-related morbidity in low- and middle-income countries (LMICs). Despite this, the majority of amputees in LMICs have no access to prosthetic devices, and the magnitude of prosthesis impact on quality of life (QOL ) and function has not been quantified. Objectives: Quantify the impact of prostheses on QOL and function in Tanzanian transfemoral amputees. Method: A prospective cohort study was conducted. Transfemoral amputees at Muhimbili Orthopaedic Institute were assessed twice before and three times after prosthetic fitting using EuroQol-5D-3L (EQ-5D-3L), Prosthetic Limb Users Survey of Mobility (PLUS-M), 2-minute walk test (2MWT) and Physiologic Cost Index (PCI). Data were analysed for change over time. Subgroup analysis was performed for amputation aetiology (vascular or non-vascular) and prosthesis use. Results: Amongst 30 patients, EQ-5D, PLUS-M and 2MWT improved after prosthesis provision ( p < 0.001). EuroQol-5D increased from 0.48 to 0.85 at 1 year ( p < 0.001). EuroQol-5D and 2MWT were higher in non-vascular subgroup ( p < 0.030). At 1-year, 84% of non-vascular and 44% of vascular subgroups reported using their prosthesis ( p = 0.068). Conclusion: Prosthesis provision to transfemoral amputees in an LMIC improved QOL and function. This benefit was greater for non-vascular amputation aetiologies. Quality of life and function returned to pre-prosthesis levels with discontinued use of prosthesis.

Objectives The incidence of hip fracture is high and increasing globally due to an aging population. Morbidity and mortality from these injuries are high at baseline and worse without prompt surgical treatment to facilitate early mobilization. Due to resource constraints, surgeons in low-income countries often must adapt available materials to meet these surgical needs. The objective of this study is to assess functional outcomes after surgical fixation of intertrochanteric femur fractures with the Surgical Implant Generation Network (SIGN) intramedullary nail augmented by a lateral SIGN plate. Design Prospective case series. Setting Juba Teaching Hospital, Tertiary Referral Hospital for South Sudan. Participants Adult patients with intertrochanteric hip fractures. Intervention SIGN nail augmented by a lateral plate. Main outcome measurements Primary outcome was hip function as measured by a modified Harris Hip Score (mHHS) at 1-year after surgery. Secondary endpoints were the occurrence of reoperation or infection at 1-year after surgery. Results Thirty patients were included, 16 (53%) men and 14 (47%) women, with a mean age of 62 years. Fractures were classified as AO/OTA Type 31A1 in 12 (40%) patients, 31A2 in 15 (50%) patients, and 31A3 in 3 (10%) patients. Mean mHHS at 1-year was 75.10 ± 21.2 with 76% categorized as excellent or good scores. There was 1 (3%) infection and 2 (7%) reoperations. Conclusions The SIGN nail augmented by a lateral plate achieved good or excellent hip function in the majority of patients with intertrochanteric hip fractures. This may be a suitable alternative to conventional implants for hip fracture patients in low-resource settings to allow mobilization.

Introduction Proximal tibia fracture dislocations (PTFDs) are a subset of plateau fractures with little in the literature since description by Hohl (1967) and classification by Moore (1981). We sought to evaluate reliability in diagnosis of fracture-dislocations by traumatologists and to compare their outcomes with bicondylar tibial plateau fractures (BTPFs). Methods This was a retrospective cohort study at 14 level 1 trauma centers throughout North America. In all, 4771 proximal tibia fractures were reviewed by all sites and 278 possible PTFDs were identified using the Moore classification. These were reviewed by an adjudication board of three traumatologists to obtain consensus. Outcomes included inter-rater reliability of PTFD diagnosis, wound complications, malunion, range of motion (ROM), and knee pain limiting function. These were compared to BTPF data from a previous study. Results Of 278 submitted cases, 187 were deemed PTFDs representing 4% of all proximal tibia fractures reviewed and 67% of those submitted. Inter-rater agreement by the adjudication board was good (83%). Sixty-one PTFDs (33%) were unicondylar. Eleven (6%) had ligamentous repair and 72 (39%) had meniscal repair. Two required vascular repair. Infection was more common among PTFDs than BTPFs (14% vs 9%, p = 0.038). Malunion occurred in 25% of PTFDs. ROM was worse among PTFDs, although likely not clinically significant. Knee pain limited function at final follow-up in 24% of both cohorts. Conclusions PTFDs represent 4% of proximal tibia fractures. They are often unicondylar and may go unrecognized. Malunion is common, and PTFD outcomes may be worse than bicondylar fractures.

Objectives: To compare clinical and radiographic outcomes following antegrade versus retrograde intramedullary nailing of infraisthmic femoral shaft fractures. Design: Secondary analysis of prospective cohort study. Setting: Tertiary hospital in Tanzania. Participants: Adult patients with infraisthmic diaphyseal femur fractures. Intervention: Antegrade or retrograde SIGN intramedullary nail. Outcomes: Health-related quality of life (HRQOL), radiographic healing, knee range of motion, pain, and alignment (defined as less than or equal to 5 degrees of angular deformity in both coronal and sagittal planes) assessed at 6, 12, 24, and 52 weeks postoperatively. Results: Of 160 included patients, 141 (88.1%) had 1-year follow-up and were included in analyses: 42 (29.8%) antegrade, 99 (70.2%) retrograde. Antegrade-nailed patients had more loss of coronal alignment (P = .026), but less knee pain at 6 months (P = .017) and increased knee flexion at 6 weeks (P = .021). There were no significant differences in reoperations, HRQOL, hip pain, knee extension, radiographic healing, or sagittal alignment. Conclusions: Antegrade nailing of infraisthmic femur fractures had higher incidence of alignment loss, but no detectable differences in HRQOL, pain, radiographic healing, or reoperation. Retrograde nailing was associated with increased knee pain and decreased knee range of motion at early time points, but this dissipated by 1 year. To our knowledge, this is the first study to prospectively compare outcomes over 1 year in patients treated with antegrade versus retrograde SIGN intramedullary nailing of infraisthmic femur fractures. Level of Evidence: III

Introduction: Interest in clinical rotations in low- and middle-income countries (LMICs) has grown among high-income country (HIC) orthopaedic residents. This study addresses the following questions: (1) What motivates HIC surgical residents to rotate in LMICs? (2) What is the impact of rotations on HIC residents? (3) What are the LMIC partner perceptions of HIC collaboration? Materials and Methods: A search strategy of multiple databases returned 3,740 unique articles pertaining to HIC surgical resident motivations for participating in rotations in LMICs or the LMIC host perspective. Data extraction was dually performed using meta-ethnography, the qualitative equivalent of meta-analysis. Results: Twenty-one studies were included in the final analysis. HIC residents were primarily motivated to rotate in LMICs by altruistic intent, with greatest impact on professional development. LMIC partners mostly valued HIC sustained investment and educational opportunities for LMIC partners. From LMIC's perspective, potential harm from collaboration arose from system-level and individual-level discordance between HIC and LMIC expectations and priorities. HIC priorities included the following: (1) adequate operative time, (2) exposure to varied pathology, and (3) mentorship. LMIC priorities included the following: (1) avoiding competition with HIC residents for surgical cases, (2) that HIC groups not undermine LMIC internal authority, (3) that HIC initiatives address local LMIC needs, and (4) that LMIC partners be included as authors on HIC research initiatives. Both HIC and LMIC partners raised ethical concerns regarding collaboration and perceived HIC residents to be underprepared for their LMIC rotation. Discussion: This study synthesizes the available literature on HIC surgical resident motivations for and impact of rotating in LMICs and the LMIC host perception of collaboration. Three improvement categories emerged: that residents (1) receive site-specific preparation before departure, (2) remain in country long enough to develop site-specific skills, and (3) cultivate flexibility and cultural humility. Specific suggestions based on synthesized data are offered for each concept and can serve as a foundation for mutually beneficial international electives in LMICs for HIC orthopaedic trainees.

Background Open tibia fractures are a major source of disability in low- and middle-income countries (LMICs) due to the high incidence of complications, particularly infection and chronic osteomyelitis. One proposed adjunctive measure to reduce infection is prophylactic local antibiotic delivery, which can achieve much higher concentrations at the surgical site than can safely be achieved with systemic administration. Animal studies and retrospective clinical studies support the use of gentamicin for this purpose, but no high-quality clinical trials have been conducted to date in high- or low-income settings. Methods We describe a protocol for a pilot study conducted in Dar es Salaam, Tanzania, to assess the feasibility of a single-center masked randomized controlled trial to compare the efficacy of locally applied gentamicin to placebo for the prevention of fracture-related infection in open tibial shaft fractures. Discussion The results of this study will inform the design and feasibility of a definitive trial to address the use of local gentamicin in open tibial fractures. If proven effective, local gentamicin would be a low-cost strategy to reduce complications and disability from open tibial fractures that could impact care in both high- and low-income countries. Trial registration ClinicalTrials.gov, Registration # NCT03559400; Registered June 18, 2018.

Objective Osteoarthritis (OA), the leading cause of joint failure, is characterized by breakdown of articular cartilage and remodeling of subchondral bone in synovial joints. Despite the high prevalence and debilitating effects of OA, no disease-modifying drugs exist. Increasing evidence, including genetic variants of the interleukin 4 (IL-4) and IL-4 receptor genes, implicates a role for IL-4 in OA, however, the mechanism underlying IL-4 function in OA remains unknown. Here, we investigated the role of IL-4 in OA pathogenesis. Methods Il4-, myeloid-specific-Il4ra-, and Stat6-deficient and control mice were subjected to destabilization of the medial meniscus to induce OA. Macrophages, osteoclasts, and synovial explants were stimulated with IL-4 in vitro, and their function and expression profiles characterized. Results Mice lacking IL-4, IL-4Ra in myeloid cells, or STAT6 developed exacerbated cartilage damage and osteophyte formation relative to WT controls. In vitro analyses revealed that IL-4 downregulates osteoarthritis-associated genes, enhances macrophage phagocytosis of cartilage debris, and inhibits osteoclast differentiation and activation via the type I receptor. Conclusion Our findings demonstrate that IL-4 protects against osteoarthritis in a myeloid and STAT6-dependent manner. Further, IL-4 can promote an immunomodulatory microenvironment in which joint-resident macrophages polarize towards an M2 phenotype and efficiently clear pro-inflammatory debris, and osteoclasts maintain a homeostatic level of activity in subchondral bone. These findings support a role for IL-4 modulation of myeloid cell types in maintenance of joint health and identify a pathway that could provide therapeutic benefit for osteoarthritis.

Objective To synthesize extant literature on the cost-effectiveness of prosthetic interventions and explore applicability to low- and middle-income country (LMIC) settings. Data Sources A systematic literature review using subject headings including “prosthetics,” “amputation,” and “cost analysis” was performed with PubMed, Embase, and Web of Science search engines, yielding 1194 articles. An additional 22 articles were identified via backward citation searching for 1144 total after duplicate removal. The search was last run in May of 2019. Study Selection Studies were included if they conducted an economic analysis of an upper or lower extremity prosthetic device. Studies were excluded if (1) full text was unavailable in English; (2) study was a systematic review or meta-analysis; or (3) study did not have a prosthetic comparison group. Using DistillerSR software, 2 authors independently conducted title and abstract screening. One author conducted full-text screening. The proportion of initially identified studies that met final inclusion criteria was 1% (12 of 1144). Data Extraction Data were dually extracted by 2 authors and reviewed by 3 additional authors. Data Synthesis All included studies (N=12) examined lower extremity amputations comparing advanced technology. No studies were conducted in LMICs. Comparable data between studies demonstrated (1) the cost-effectiveness of microprocessor- over nonmicroprocessor-controlled knees for transfemoral amputation in high-income settings; (2) equivocal findings regarding osseointegrated vs socket-suspended prostheses; and (3) increased cost for ICEX and modular socket systems over patellar tendon–bearing socket systems with no functional improvement. Conclusions There are few prosthetic cost analyses in the literature. Additional analyses are needed to determine the direct and indirect costs associated with prosthetic acquisition, fitting, and maintenance; the costs of amputee rehabilitation; and long-term economic and quality-of-life benefits. Such studies may guide future prosthetic and rehabilitative care, especially in resource-austere settings where prosthetic needs are greatest.