Bacteriophage therapy and current delivery strategies for orthopedic infections: A SCOPING review.

OBJECTIVES: Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have not been systematically summarized. METHODS: Following PRISMA-ScR guidelines, we conducted a SCOPING review through September 1st, 2023, of MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central. RESULTS: In total, 77 studies were included, of which 19 (24.7%) were in vitro studies, 17 (22.1%) were animal studies, and 41 (53.2%) were studies in humans. A total of 137 contemporary patients receiving phage therapy are described. CONCLUSIONS: Direct phage delivery remains the most studied form of phage therapy, notably in prosthetic joint infections, osteomyelitis, and diabetic foot ulcers. Available evidence describing phage therapy in humans suggests favorable outcomes for orthopedic infections, though this evidence is composed largely of low-level descriptive studies. Several phage delivery devices have been described, though a lack of comparative and in-human evidence limits their therapeutic application. Limitations to the use of phage therapy for orthopedic infections that need to be overcome include a lack of understanding related to optimal dosing and phage pharmacokinetics, bacterial heterogeneity in an infection episode, and phage therapy toxicity.

Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.

Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.

Minimization of preventable drug waste through use of a vial combination calculator tool.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: This project aimed to determine whether a supportive calculator that automates the vial selection process might offer a practical and efficient method of reducing pharmaceutical expenditures through minimizing preventable drug waste in outpatient pharmacy settings from fiscal year (FY) 2021 to FY 2023. SUMMARY: Drug waste is a substantial target of cost-saving efforts in the areas of oncology and autoimmune therapy, which involve use of a vast number of high-cost medications packaged in single-dose vials of varying strength. To facilitate selection of the optimal combination of medication vials and thereby minimize preventable drug waste, a Microsoft Excel-based calculator was developed for use by staff of a large oncology pharmacy network. Twenty-three high-cost chemotherapy and monoclonal antibody medications were identified as initial targets for the drug waste prevention initiative. After dissemination and implementation of the calculator and provision of monthly pharmacy staff education, the dollar value of preventable drug waste and the number of suboptimal vial combination selections were reduced by 51% ($412,300) and 54% (315 selections), respectively, in fiscal year 2022 and further reduced by 46% ($183,400) and 27% (71 selections), respectively, in fiscal year 2023. CONCLUSION: After implementation of an automated vial selection tool, preventable drug waste and the quantity of suboptimal vial combination selections were markedly reduced across 11 outpatient compounding pharmacies.

Authorship Patterns in the Orthopaedic Journals of Low-Income and Lower-Middle-Income Countries.

Background: Extensive research collaborations exist between researchers from high-income countries (HICs) and those from low-income countries (LICs) and lower-middle-income countries (LMICs). Previous research has suggested that authors from LICs and LMICs are underrepresented as first and last authors in the orthopaedic literature on local populations, particularly in LICs. We present a bibliometric analysis of authorship solely in studies published in orthopaedic journals that are based in LICs and LMICs. Methods: The Global Index Medicus was queried, and all articles published from January 1, 2010, to December 31, 2021, in journals with a focus on orthopaedic surgery that were based in an LIC or an LMIC were included. Logistic regressions were calculated to assess the predictors of local authorship. Results: Over 92% of studies included in our analysis had first or last authors from LICs or LMICs. In terms of study type, the majority (89%) of studies were clinical, although largely of low-level evidence (78% of clinical studies were case reports, case series, or descriptive studies). None received funding. LIC or LMIC first authorship and last authorship were less likely for most types of nonclinical studies. LIC or LMIC first authorship was more likely when there were more study authors. LIC or LMIC first authorship and last authorship were less likely when there were more countries affiliated with the study authors. Finally, when compared with studies with only LIC or LMIC authors, those with a combination of HIC and LIC or LMIC authors had significantly lower rates of LIC or LMIC first authorship (93.3% versus 62.5%) and last authorship (97.7% versus 70.8%). Conclusions: Our study presents one of the first analyses to assess authorship patterns in the orthopaedic literature of locally published journals in LICs and LMICs. Future studies are needed to contextualize our findings within a broader bibliometric landscape in order to better address the ongoing challenges to building research capacity in LICs and LMICs. Clinical Relevance: Our study highlights important observations regarding authorship in international, collaborative research in orthopaedics.

Impact of premorbid oral anticoagulant use on survival in patients with traumatic intracranial hemorrhage.

OBJECTIVE: Although oral anticoagulant use has been implicated in worse outcomes for patients with a traumatic brain injury (TBI), prior studies have mostly examined the use of vitamin K antagonists (VKAs). In an era of increasing use of direct oral anticoagulants (DOACs) in lieu of VKAs, the authors compared the survival outcomes of TBI patients on different types of premorbid anticoagulation medications with those of patients not on anticoagulation. METHODS: The authors retrospectively reviewed the records of 1186 adult patients who presented at a level I trauma center with an intracranial hemorrhage after blunt trauma between 2016 and 2022. Patient demographics; comorbidities; and pre-, peri-, and postinjury characteristics were compared based on premorbid anticoagulation use. Multivariable Cox proportional hazards regression modeling of mortality was performed to adjust for risk factors that met a significance threshold of p < 0.1 on bivariate analysis. RESULTS: Of 1186 patients with a traumatic intracranial hemorrhage, 49 (4.1%) were taking DOACs and 53 (4.5%) used VKAs at the time of injury. Patients using oral anticoagulants were more likely to be older (p < 0.001), to have a higher Charlson Comorbidity Index (p < 0.001), and to present with a higher Glasgow Coma Scale (GCS) score (p < 0.001) and lower Injury Severity Score (ISS; p < 0.001) than those on no anticoagulation. Patients using VKAs were more likely to undergo reversal than patients using DOACs (53% vs 31%, p < 0.001). Cox proportional hazards regression demonstrated significantly increased hazard ratios (HRs) for VKA use (HR 2.204, p = 0.003) and DOAC use (HR 1.973, p = 0.007). Increasing age (HR 1.040, p < 0.001), ISS (HR 1.017, p = 0.01), and Marshall score (HR 1.186, p < 0.001) were associated with an increased risk of death. A higher GCS score on admission was associated with a decreased risk of death (HR 0.912, p < 0.001). CONCLUSIONS: Patients with a traumatic intracranial injury who were on oral anticoagulant therapy before injury demonstrated higher mortality rates than patients who were not on oral anticoagulation after adjusting for age, comorbid conditions, and injury presentation.

FDG PET/CT and thyroid biopsy leads to neurosarcoidosis diagnosis.

We present a unique case of neurosarcoidosis diagnosed based on thyroid biopsy and FDG PET (Fluorodeoxyglucose positron emission tomography) imaging. A patient presented for a second opinion after being placed in hospice for rapidly progressing dementia, presumed to be due to Creutzfeldt Jakob disease despite negative workup and was unable to perform activities of daily life or communicate with his wife. The patient underwent a workup including whole-body FDG PET, which showed hypermetabolic lymph nodes as well as a hypermetabolic nodule in the thyroid. Biopsy of the lymph nodes was nondiagnostic, but the thyroid biopsy tissue yielded a diagnosis of sarcoid. After ruling out other causes and reviewing the tissue pathology, the patient was diagnosed with systemic sarcoidosis with neurological involvement and started on infliximab with rapid improvement.

Epidemiology of Gunshot-Related Spinal Injuries and Related Risk Factors for In-Hospital Mortality in the United States from 2015-2019: A National Trauma Data Bank Analysis.

Firearm injuries in the U.S. pose a significant public health burden, but data on gunshot wounds (GSWs) specifically involving the spine are scarce. We examined epidemiological trends in GSWs to the spine and associated spinal cord injury (SCI) and mortality rates. This was a cross-sectional study of data from level I-III trauma centers in the U.S. participating in the American College of Surgeons National Trauma Data Bank (ACS NTDB) in 2015-2019. We identified adult and pediatric patients presenting with GSW and evaluated those with Abbreviated Injury Scale codes indicating spinal involvement and SCI. We assessed in-hospital mortality and GSW-related SCI. A total of 5,021,316 patients were enrolled in the ACS NTDB. Of the 107,233 patients (2.1% of total) presenting with GSW, 9023 (8.4%) patients had spine involvement. Overall rates of GSW and spinal GSW were similar across years. The most common cause of spinal GSW injury was assault (86.7%). The cervical spine was involved in 24.2% of patients, thoracic spine in 42.8%, and lumbar spine in 39.7%. Cervical SCI was present in 8.7% of all spinal GSW (35.7% of cervical GSW), thoracic SCI in 17.4% (40.6% of thoracic GSW), and lumbar SCI in 8.1% (20.3% of lumbar GSW). The mean patient age was 29.0 ± 12.2 years, 88.5% were male, 62.4% were black, 23.7% were white, and 13.9% were another race. Blood alcohol content was ≥0.08 in 12.1%, and illicit drugs were positive in 24.4%. In-hospital mortality was high in patients with spinal GSWs (8.1%), and mortality was significantly higher with cervical involvement (18.1%), cervical SCI (30.7%), or thoracic incomplete SCI (13.6%) on univariate analysis. On multi-variate analysis of age (excluding patients <16 years of age), sex, Injury Severity Score (ISS), complete SCI, and spinal area of involvement, only greater patient age (age 40-65 years: adjusted odds ratio [aOR] 1.52, 95% confidence interval [CI] 1.09-2.11, p = 0.014; age >65 years: aOR 3.90, 95% CI 2.10-7.27, p < 0.001) and higher ISS (ISS 9-15: aOR 6.65, 95% CI 2.38-18.54, p < 0.001; ISS 16-24: aOR 18.13, 95% CI 6.65-49.44, p < 0.001; ISS >24: aOR 68.44, 95% CI 25.39-184.46, p < 0.001) were independently associated with in-hospital mortality risk after spinal GSW. These results demonstrate that spinal GSW is not uncommon and that older patients with more severe systemic injuries have higher in-hospital mortality risk.

Long-term outcomes among adults with Langerhans cell histiocytosis.

Advances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective record review of 219 adults (aged ≥18 years) with LCH. Most common presentation was multisystem (34.2%), followed by single-system pulmonary (32%), unifocal (28.3%), and single-system multifocal (5.5%) LCH. Risk organ involvement (the liver, spleen, or bone marrow) was seen in 8.7% of cases, and 40 of 88 (45.5%) tested cases were BRAFV600E. At a median follow-up of 74 months, 5-year progression-free survival (PFS) was 58.3% and estimated median PFS was 83 months. Median overall survival (OS) was not reached; 5- and 10-year OS rates were 88.7% and 74.5%, respectively. Risk organ involvement was associated with worse PFS (hazard ratio [HR], 4.5) and OS (HR, 10.8). BRAFV600E was not associated with risk organ involvement or survival. When compared with matched unaffected US population, individuals with LCH had a significantly higher risk of overall mortality (standardized mortality ratio [SMR], 2.66), specifically among those aged <55 years at diagnosis (SMR, 5.94) and those with multisystem disease (SMR, 4.12). Second cancers occurred in 16.4% cases, including diverse hematologic and solid organ malignancies. LCH-associated deaths constituted 36.1% of deaths and occurred within 5 years of diagnosis. After 5 years, non-LCH causes of death, including second cancers, chronic obstructive pulmonary disease, and cardiovascular diseases, predominated. Our study highlights, to our knowledge, for the first time, that adults with LCH experience early and late mortality from non-LCH causes and the need for development of targeted survivorship programs to improve outcomes.

Outcomes of Adolescent T-condylar Fractures: Kids Do Not Always Make You Look Good.

BACKGROUND: Optimal treatment for pediatric and adolescent T-condylar fractures remains poorly understood. We sought to assess how functional outcomes and range of motion (ROM) after surgical fixation of T-condylar fractures are affected by patient and surgical factors. METHODS: This is a retrospective cohort study of 52 patients with operatively treated T-condylar fractures at a single tertiary pediatric referral center between 2003 and 2021. All patients younger than 18 at the time of injury with a radiographically confirmed diagnosis were included. RESULTS: Fifty-two T-condylar fractures were included, with a mean patient age of 12.9 years (SD, 2.8). The cohort was 65% male. Nine (19%) fractures were open, 46% (24/52) were AO type C2, and 33% (17/52) occurred in skeletally mature individuals. The surgical approach was through olecranon osteotomy in 29% (15/52) of patients, and fixation included anatomically specific plates and screws in 42% (22/52) of patients. In our cohort, 46% (24/52) achieved good outcomes based on Jarvis ROM criteria and 42% (22/52) achieved good to excellent results based on Roberts functional criteria. The median loss of ROM was 58 degrees at 6 weeks, 20 degrees at 3 and 6 months, and 8 degrees at 1 year postoperatively. We observed a complication rate of 54% (28/52). Patients undergoing adult-type plate fixation had better postoperative range of motion at 6 weeks (ROM loss 52 vs. 80 degrees, P =0.03) and 3 months (10 vs. 35 degrees P =0.004) compared with pediatric-type fixation and trended towards better functional outcomes. We did not identify significant differences in functional outcome scores or complication rates with respect to surgical approach or skeletal maturity. CONCLUSIONS: Surgical fixation of pediatric and adolescent T-condylar fractures achieved a good to excellent functional outcome in only a minority of patients (46% Jarvis / 42% Roberts) with a high rate of postoperative complications (54%). Future work is needed to elucidate optimal treatment to minimize complications and achieve the best functional outcomes in these challenging fractures. LEVEL OF EVIDENCE: Level-IV.

BRAF V600E is associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis.

In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.

Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity.

PET/CT is used to evaluate relapsed/refractory non-Hodgkin lymphoma (NHL) prior to chimeric antigen receptor T-cell (CAR-T) infusion at two time points: pre-leukapheresis (pre-leuk) and pre-lymphodepletion chemotherapy (pre-LD). We hypothesized that changes in PET/CT between these time points predict outcomes after CAR-T. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and other metrics were calculated from pre-leuk and pre-LD PET/CT scans in patients with NHL who received axicabtagene ciloleucel, and assessed for association with outcomes. Sixty-nine patients were analyzed. While single time point PET/CT characteristics were not associated with risk of PD or death, increases from pre-leuk to pre-LD in parenchymal MTV, nodal MTV, TLG of the largest lesion, and total number of lesions were associated with increased risk of death (p < 0.05 for all). LASSO analysis identified increasing extranodal MTV and increasing TLG of the largest lesion as strong predictors of death (AUC 0.74). Greater pre-LD total MTV was associated with higher risk of grade 3+ immune effector cell-associated neurotoxicity syndrome (ICANS) (p = 0.042). Increasing metabolic disease burden during CAR-T manufacturing is associated with increased risk of progression and death. A two variable risk score stratifies prognosis prior to CAR-T infusion and may inform risk-adapted strategies.

Malignant Histiocytosis Comprises a Phenotypic Spectrum That Parallels the Lineage Differentiation of Monocytes, Macrophages, Dendritic Cells, and Langerhans Cells.

Malignant histiocytoses (MHs), or the 'M group' of the Histiocyte Society classification, are characterized by neoplastic histiocytes with large pleomorphic nuclei. MH encompasses the diagnoses of histiocytic sarcoma, interdigitating dendritic cell sarcoma, and Langerhans cell sarcoma. We aimed to define the phenotypic spectrum of MH and examine the genotypic features across this spectrum. Using immunohistochemistry, we arranged the 22 cases into 4 subtypes that correspond to the lines of differentiation from monocytic and dendritic cell precursors as follows: (1) macrophage (n = 5): CD68+, CD163+, CD14+, and Factor 13a+; (2) monocyte-macrophage (n = 5): CD68+, CD163+, CD14+, S100+, and OCT2+; (3) dendritic cell (n = 6): CD68+, CD11c+, S100+, lysozyme+, ZBTB46+, and CD1a/langerin < 5%; and (4) Langerhans cell (n = 6): CD68+, CD11c+, S100+, ZBTB46+, CD1a+, and langerin+. The phenotypic subtypes align with those seen in low-grade histiocytic neoplasms as follows: MH-macrophage type correlates with Erdheim-Chester disease phenotype; MH-monocyte-macrophage type with Rosai-Dorfman disease phenotype, and MH-Langerhans cell type with Langerhans cell histiocytosis. Activating mutations in MAPK-pathway genes were identified in 80% of MH cases; 29% had mutations in the PI3k-AKT-mTOR pathway and 59% had mutations in epigenetic modulating genes. Strong expression of cyclin D1 was present in all cases, whereas p-ERK and p-AKT were not uniformly expressed. Eight of 22 (36%) MH cases were proven to be clonally related to a prior B-cell lymphoma. Defining the phenotypic spectrum of MH provides a guide to diagnosis and allows further exploration into the potential biological and clinical significance.

Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation.

Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based 'omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks.

Neurological Manifestations of Histiocytic Disorders.

PURPOSE OF REVIEW: Histiocytic disorders, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD), are rare neoplasms that may present with a spectrum of neurologic involvement. Diagnostic delay is common due to heterogeneity in presentation and challenging pathology. RECENT FINDINGS: Recent advances in the treatment of these diseases targeted towards mutations in the MAP kinase pathway have led to an improved prognosis in these patients with neurologic involvement. It is critical for clinicians to have a high index of suspicion to allow for early targeted treatment and optimize neurologic outcomes. A systematic approach to diagnosis is presented in this article to allow for accurate diagnosis of these rare diseases.

Putative Protein Interactome of the Rhomboid Protease RHBDL4.

The physiological functions of the rhomboid-related protein 4 (RHBDL4) are emerging, but their molecular details remain unclear. Because increased expression of RHBDL4 has been clinically linked to poorer outcomes in cancer patients, this association urgently demands a better understanding of RHBDL4. To elucidate the molecular interactions and pathways that RHBDL4 may be involved in, we conducted proximity-dependent biotin identification (BioID) assays. Our analyses corroborated several of the expected protein interactors such as the transitional endoplasmic reticulum (ER) ATPase VCP/p97 (TERA), but they also described novel putative interactors including IRS4, PGAM5, and GORS2. Using proximity-ligation assays, we validated VCP/p97, COPB, and VRK2 as proteins that are in proximity to RHBDL4. Overall, our results support the emerging functions of RHBDL4 in ER quality control and also point toward putative RHBDL4 functions in protein membrane insertion and membrane organization and trafficking.

Successful treatment of non-Langerhans cell histiocytosis with the MEK inhibitor trametinib: a multicenter analysis.

Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are rare non-Langerhans cell histiocytoses (non-LCHs), for which therapeutic options are limited. MAPK pathway activation through BRAFV600E mutation or other genomic alterations is a histiocytosis hallmark and correlates with a favorable response to BRAF inhibitors and the MEK inhibitor cobimetinib. However, there has been no systematic evaluation of alternative MEK inhibitors. To assess the efficacy and safety of the MEK inhibitor trametinib, we retrospectively analyzed the outcomes of 26 adult patients (17 with ECD, 5 with ECD/RDD, 3 with RDD, and 1 with ECD/LCH) treated with orally administered trametinib at 4 major US care centers. The most common treatment-related toxicity was rash (27% of patients). In most patients, the disease was effectively managed at low doses (0.5-1.0 mg trametinib daily). The response rate of the 17 evaluable patients was 71% (73% [8/11] without a detectable BRAFV600E achieving response). At a median follow-up of 23 months, treatment effects were durable, with a median time-to-treatment failure of 37 months, whereas the median progression-free and overall survival were not reached (at 3 years, 90.1% of patients were alive). Most patients harbored mutations in BRAF (either classic BRAFV600E or other BRAF alterations) or alterations in other genes involved in the MAPK pathway, eg, MAP2K, NF1, GNAS, or RAS. Most patients required lower than standard doses of trametinib but were responsive to lower doses. Our data suggest that the MEK inhibitor trametinib is an effective treatment for ECD and RDD, including those without the BRAFV600E mutation.

Prevalence of and risk factors for Human Immunodeficiency Virus (HIV) infection in entrants and residents of an Ethiopian prison.

BACKGROUND: Prisoners generally have a higher prevalence of HIV infection compared to the general population from which they come. Whether this higher prevalence reflects a higher HIV prevalence in those entering prisons or intramural transmission of HIV within prisons or both is unclear. Any of these possibilities would increase the prevalence found in resident prisoners above that in the general population. Moreover, comparisons of HIV prevalence in entrants and residents and in men and women in African prisons are not well documented. The purpose of this study was to estimate and compare the prevalence and risk factors for HIV infection amongst both male as well as female and entrant and resident prisoners in a large Ethiopian Federal Prison. METHODS: We studied consenting prisoners cross-sectionally from August 2014 through November 2016. Prison entrants were screened continuously for HIV infection and its associated risk factors and residents were screened in two waves one year apart. HIV was diagnosed at the prison hospital laboratory based on the Ethiopian national HIV rapid antibody testing protocol. An external, internationally-accredited reference laboratory confirmed results. Agreement of results between the laboratories were assessed. RESULTS: A total of 10,778 participants were screened for HIV. Most participants were young (median age of 26 years, IQR: 21-33), male (84%), single (61%), literate (89%), and urban residents (91%) without prior incarceration (96%). Prevalence of HIV was 3.4% overall. Rates of HIV (p = 0.80) were similar in residents and entrants in wave 1 and in entrants in both waves, but were 1.9-fold higher (5.4% vs 2.8%) in residents than entrants in wave 2 (both p<0.001). At entrance to the prison women were more likely to be HIV+ than men (5.5% in women vs 2.5% in men, p< 0.001). In contrast resident women were less likely to be HIV+, but this difference was not statistically significant (3.2% in women vs 4.3% in men, p = 0.125). Other risk factors associated with HIV infection were increasing age (p<0.001), female gender (p<0.001), marital status (never vs other categories, p = 0.016), smaller number of rooms in their houses pre-imprisonment (p = 0.031), TB diagnosis ever (p<0.001), number of lifetime sex partners (especially having 2-10, p<0.001), and genital ulcer (p = 0.037). CONCLUSIONS: Prevalence of HIV in the residents at this large, central Ethiopian prison was higher than that estimated for the general population and lower than in many other studies from other smaller Ethiopian prisons. A higher prevalence in residents than in entrants were found only in our second wave of screening after one year of continuous screening and treatment, possibly representing increased willingness of residents at increased risk of HIV to participate in the second wave. Thus, this findings did not clearly support intramural transmission of HIV or the effectiveness of screening to reduce prevalence. Finally, the higher HIV prevalence in women than men requires that they be similarly screened and treated for HIV infection.

Evaluation of Low- and Middle-Income Country Authorship in the Global Orthopaedic Literature.

INTRODUCTION: Extensive research collaborations exist between high-income countries and low- and middle-income countries (LMICs), although prior work has raised concerns regarding equitable representation among LMIC authors. The goal of this bibliometric analysis was to characterize LMIC authorship among indexed orthopaedic journals and identify factors contributing to disparities in representation. METHODS: We identified all articles appearing in orthopaedic journals indexed in MEDLINE and Journal Citation Reports with a focus on LMICs or cohorts between 2009 and 2018. All articles describing research conducted in LMICs or research focused on applications to cohorts in LMIC(s) were included. Author affiliation, article characteristics, and impact factor were assessed for 1,573 articles. Logistic regression models created to identify predictors of LMIC authorship. RESULTS: We identified few studies published in indexed journals focused exclusively on LICs. Funded studies were less likely to have LMIC last authors. Compared with articles published in lower impact factor journals, those in journals with a higher impact factor were less likely to have a LMIC first or last author. The greater the number of countries represented per study, the less likely it had a LMIC first or last author. CONCLUSION: Our study highlights persistent disparities in authorship from LMICs in indexed orthopaedic journals.