Correction: Inhibition of the Growth Factor MDK/Midkine by a Novel Small Molecule Compound to Treat Non-Small Cell Lung Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0071093.].

Multisite Study of the Management of Musculoskeletal Infection After Trauma: The MMUSKIT Study.

Background: The optimal duration and choice of antibiotic for fracture-related infection (FRI) is not well defined. This study aimed to determine whether antibiotic duration (≤6 vs >6 weeks) is associated with infection- and surgery-free survival. The secondary aim was to ascertain risk factors associated with surgery- and infection-free survival. Methods: We performed a multicenter retrospective study of patients diagnosed with FRI between 2013 and 2022. The association between antibiotic duration and surgery- and infection-free survival was assessed by Cox proportional hazard models. Models were weighted by the inverse of the propensity score, calculated with a priori variables of hardware removal; infection due to Staphylococcus aureus, Staphylococcus lugdunensis, Pseudomonas or Candida species; and flap coverage. Multivariable Cox proportional hazard models were run with additional covariates including initial pathogen, need for flap, and hardware removal. Results: Of 96 patients, 54 (56.3%) received ≤6 weeks of antibiotics and 42 (43.7%) received >6 weeks. There was no association between longer antibiotic duration and surgery-free survival (hazard ratio [HR], 0.95; 95% CI, .65-1.38; P = .78) or infection-free survival (HR, 0.77; 95% CI, .30-1.96; P = .58). Negative culture was associated with increased hazard of reoperation or death (HR, 3.52; 95% CI, 1.99-6.20; P < .001) and reinfection or death (HR, 3.71; 95% CI, 1.24-11.09; P < .001). Need for flap coverage had an increased hazard of reoperation or death (HR, 3.24; 95% CI, 1.61-6.54; P = .001). Conclusions: The ideal duration of antibiotics to treat FRI is unclear. In this multicenter study, there was no association between antibiotic treatment duration and surgery- or infection-free survival.

Can gas and infection coexist in the intervertebral disc? A retrospective analysis of percutaneously biopsied suspected discitis-osteomyelitis cases.

OBJECTIVES: To retrospectively evaluate the correlation between intradiscal gas and infection in patients percutaneously biopsied for suspected discitis-osteomyelitis. MATERIALS AND METHODS: We retrospectively reviewed all CT-guided discitis-osteomyelitis biopsies performed between 2002 and 2022. Two independent trained musculoskeletal radiologists evaluated for presence of gas on CT and/or MRI within 1 week of the biopsy. Disagreements were resolved by a third musculoskeletal radiologist. CT was considered the gold standard for the detection of intradiscal gas. Pathology, microbiology, and imaging and clinical follow-up were used as the gold standard for presence of infection. Interrater agreement on CT and MRI, sensitivity, and positive predictive value were calculated, using the presence of gas as an indicator (test positive) for "no infection." RESULTS: There were 284 biopsies in 275 subjects (mean age 58 ± 1.0 (range 4-99) years; 101 (37%) females and 174 (63%) males). Of the biopsies, 12 (4%) were cervical, 80 (28%) were thoracic, 192 (68%) were lumbar, and 200 (70%) were considered true discitis-osteomyelitis based on pathology, imaging, and clinical follow-up. Interrater agreement was excellent for CT (kappa = 0.83) and poor for MRI (kappa = - 0.021). The presence of gas had a 94% specificity and 76% negative predictive value for the absence of infection. CONCLUSION: CT is the preferred method for detecting intradiscal gas. The presence of gas means that discitis-osteomyelitis is unlikely. If intradiscal gas is present in the setting of discitis-osteomyelitis, the gas bubbles tend to be smaller and fewer in number.

"Putting the power back into community": A mixed methods evaluation of a chronic hepatitis B training course for the Aboriginal health workforce of Australia's Northern Territory.

BACKGROUND: Chronic hepatitis B (CHB) is endemic in the Aboriginal and Torres Strait Islander population of Australia's Northern Territory. Progression to liver disease can be prevented if holistic care is provided. Low health literacy amongst health professionals is a known barrier to caring for people living with CHB. We co-designed and delivered a culturally safe "Managing hepatitis B" training course for the Aboriginal health workforce. Here, we present an evaluation of the course. OBJECTIVES: 1. To improve course participants CHB-related knowledge, attitudes, and clinical practice. 2. To evaluate the "Managing hepatitis B" training course. 3. To enable participants to have the skills and confidence to be part of the care team. METHODS: We used participatory action research and culturally safe principles. We used purpose-built quantitative and qualitative evaluation tools to evaluate our "Managing hepatitis B" training course. We integrated the two forms of data, deductively analysing codes, grouped into categories, and assessed pedagogical outcomes against Kirkpatrick's training evaluation framework. RESULTS: Eight courses were delivered between 2019 and 2023, with 130 participants from 32 communities. Pre- and post-course questionnaires demonstrated statistically significant improvements in all domains, p<0.001 on 93 matched pairs. Thematic network analysis demonstrated high levels of course acceptability and significant knowledge acquisition. Other themes identified include cultural safety, shame, previous misinformation, and misconceptions about transmission. Observations demonstrate improvements in post-course engagement, a deep understanding of CHB as well as increased participation in clinical care teams. CONCLUSIONS: The "Managing hepatitis B" training course led to a sustained improvement in the knowledge and attitudes of the Aboriginal health workforce, resulting in improved care and treatment uptake for people living with CHB. Important non-clinical outcomes included strengthening teaching and leadership skills, and empowerment.

Racial Disparities in Periprosthetic Joint Infections after Primary Total Joint Arthroplasty: A Retrospective Study.

In the United States, racial disparities have been observed in complications following total joint arthroplasty (TJA), including readmissions and mortality. It is unclear whether such disparities also exist for periprosthetic joint infection (PJI). The clinical data registry of a large New England hospital system was used to identify patients who underwent TJA between January 2018 and December 2021. The comorbidities were evaluated using the Elixhauser Comorbidity Index (ECI). We used Poisson regression to assess the relationship between PJI and race by estimating cumulative incidence ratios (cIRs) and 95% confidence intervals (CIs). We adjusted for age and sex and examined whether ECI was a mediator using structural equation modeling. The final analytic dataset included 10,018 TJAs in 9681 individuals [mean age (SD) 69 (10)]. The majority (96.5%) of the TJAs were performed in non-Hispanic (NH) White individuals. The incidence of PJI was higher among NH Black individuals (3.1%) compared with NH White individuals (1.6%) [adjusted cIR = 2.12, 95%CI = 1.16-3.89; p = 0.015]. Comorbidities significantly mediated the association between race and PJI, accounting for 26% of the total effect of race on PJI incidence. Interventions that increase access to high-quality treatments for comorbidities before and after TJA may reduce racial disparities in PJI.

Fatal ampicillin-sulbactam anaphylaxis in a 34-year-old male.

A 34-year-old man receiving his first dose of ampicillin-sulbactam for osteomyelitis in a hospital setting experienced fatal drug-induced anaphylaxis.

Executive Summary: Periprosthetic Joint Infection-Current Clinical Challenges.

Over the last several decades, periprosthetic joint infection (PJI) has been increasing in incidence and is occurring in more complex patients. While there have been advances in both surgical and medical treatment strategies, there remain important gaps in our understanding. Here, we share our current approaches to the diagnosis and management of PJI, focusing on frequent clinical challenges and collaborative interdisciplinary care. The more detailed review including diagnosis, surgical considerations, and a detailed antimicrobial discussion is presented in the online version.

"The most culturally safe training I've ever had": the co-design of a culturally safe Managing hepatitis B training course with and for the Aboriginal health workforce of the Northern Territory of Australia.

BACKGROUND: The Aboriginal health workforce provide responsive, culturally safe health care. We aimed to co-design a culturally safe course with and for the Aboriginal health workforce. We describe the factors which led to the successful co-design, delivery, and evaluation of the "Managing hepatitis B" course for the Aboriginal health workforce. METHODS: A Participatory Action Research approach was used, involving ongoing consultation to iteratively co-design and then develop course content, materials, and evaluation tools. An Aboriginal and Torres Strait Islander research and teaching team received education in chronic hepatitis B and teaching methodologies. Pilot courses were held, in remote communities of the Northern Territory, using two-way learning and teach-back methods to further develop the course and assess acceptability and learnings. Data collection involved focus group discussions, in-class observations, reflective analysis, and use of co-designed and assessed evaluation tools. RESULTS: Twenty-six participants attended the pilot courses. Aboriginal and Torres Strait Islander facilitators delivered a high proportion of the course. Evaluations demonstrated high course acceptability, cultural safety, and learnings. Key elements contributing to success and acceptability were acknowledging, respecting, and integrating cultural differences into education, delivering messaging and key concepts through an Aboriginal and Torres Strait Islander lens, using culturally appropriate approaches to learning including storytelling and visual teaching methodologies. Evaluation of culturally safe frameworks and findings from the co-design process led to the creation of a conceptual framework, underpinned by meeting people's basic needs, and offering a safe and comfortable environment to enable productive learning with attention to the following: sustenance, financial security, cultural obligations, and gender and kinship relationships. CONCLUSIONS: Co-designed education for the Aboriginal health workforce must embed principles of cultural safety and meaningful community consultation to enable an increase in knowledge and empowerment. The findings of this research can be used to guide the design of future health education for First Nations health professionals and to other non-dominant cultures. The course model has been successfully transferred to other health issues in the Northern Territory.

Prevalence and Risk Factors for School-Associated Transmission of SARS-CoV-2.

Importance: School-associated SARS-CoV-2 transmission is described as uncommon, although the true transmission rate is unknown. Objective: To identify the SARS-CoV-2 secondary attack rate (SAR) in schools and factors associated with transmission. Design, Setting, and Participants: This cohort study examined the risk of school-based transmission of SARS-CoV-2 among kindergarten through grade 12 students and staff in 10 Massachusetts school districts during 2 periods: fall 2020/spring 2021 (F20/S21) and fall 2021 (F21). School staff collected data on SARS-CoV-2 index cases and school-based contacts, and SAR was defined as the proportion of contacts acquiring SARS-CoV-2 infection. Exposure: SARS-CoV-2. Main Outcomes and Measures: Potential factors associated with transmission, including grade level, masking, exposure location, vaccination history, and Social Vulnerability Index (SVI), were analyzed using univariable and multivariable logistic regression models. Results: For F20/S21, 8 school districts (70 schools, >33 000 students) were included and reported 435 index cases (151 staff, 216 students, and 68 missing role) with 1771 school-based contacts (278 staff, 1492 students, and 1 missing role). For F21, 5 districts (34 schools, >18 000 students) participated and reported 309 index cases (37 staff, 207 students, and 65 missing role) with 1673 school-based contacts (107 staff and 1566 students). The F20/S21 SAR was 2.2% (lower bound, 1.6%; upper bound, 26.7%), and the F21 SAR was 2.8% (lower bound, 2.6%; upper bound, 7.4%). In multivariable analysis, during F20/S21, masking was associated with a lower odds of transmission compared with not masking (odds radio [OR], 0.12; 95% CI, 0.04-0.40; P < .001). In F21, classroom exposure vs out-of-classroom exposure was associated with increased odds of transmission (OR, 2.47; 95% CI, 1.07-5.66; P = .02); a fully vaccinated vs unvaccinated contact was associated with a lower odds of transmission (OR, 0.04; 95% CI, 0.00-0.62; P < .001). In both periods, a higher SVI was associated with a greater odds of transmission. Conclusions and Relevance: In this study of Massachusetts schools, the SAR for SARS-CoV-2 among school-based contacts was low during 2 periods, and factors associated with transmission risk varied over time. These findings suggest that ongoing surveillance efforts may be essential to ensure that both targeted resources and mitigation practices remain optimal and relevant for disease prevention.

Periprosthetic Joint Infection: Current Clinical Challenges.

Over the last several decades, periprosthetic joint infection has been increasing in incidence and is occurring in more complex patients. While there have been advances in both surgical and medical treatment strategies, there remain important gaps in our understanding. Here, we share our current approaches to the diagnosis and management of periprosthetic joint infection, focusing on frequent clinical challenges and collaborative interdisciplinary care.

Evaluation of Hepatitis C Treatment Outcomes Among Patients Enrolled in Outpatient Parenteral Antibiotic Therapy-Boston, Massachusetts, 2016-2021.

In our Boston-based outpatient parenteral antibiotic therapy (OPAT) program between 2016 and 2021, we found that a low proportion of patients with active hepatitis C virus (HCV) were prescribed HCV treatment by their OPAT provider and few achieved sustained virologic response. Clinicians should consider concurrent HCV treatment during OPAT.

Evaluation of "Test to Return" after COVID-19 Diagnosis in a Massachusetts Public School District.

BACKGROUND: Per Centers for Disease Control and Prevention guidance, students with COVID-19 may end isolation after 5 days if symptoms are improving; some individuals may still be contagious. Rapid antigen testing identifies possibly infectious virus. We report on a test-to-return (TTR) program in a Massachusetts school district to inform policy decisions about return to school after COVID-19. METHODS: During the 2021-2022 Omicron BA.1 surge, students with COVID-19 could return on day 6-10 if they met symptom criteria and had a negative rapid test; students with positive rapid tests and those who declined TTR remained isolated until day 11. TTR positivity rates were compared by grade level, vaccination status, symptom status, and day of infection. RESULTS: 31.4% of students had a positive TTR rapid test; there were no differences by grade or vaccination status. Ever-symptomatic students were more likely to have a positive rapid test (75/174 [43.1%] vs 18/104 [17.3%]). For ever-symptomatic students, TTR positivity decreased by day of infection. CONCLUSIONS: A substantial proportion of students may still be contagious 6 days after onset of COVID-19 infection. TTR programs may increase or reduce missed school days, depending on when return is otherwise allowed (day 6 or 11). The impact of TTR programs on school-associated transmission remains unknown.

External validation of a predictive algorithm for in-hospital and 90-day mortality after spinal epidural abscess.

BACKGROUND CONTEXT: Mortality in patients with spinal epidural abscess (SEA) remains high. Accurate prediction of patient-specific prognosis in SEA can improve patient counseling as well as guide management decisions. There are no externally validated studies predicting short-term mortality in patients with SEA. PURPOSE: The purpose of this study was to externally validate the Skeletal Oncology Research Group (SORG) stochastic gradient boosting algorithm for prediction of in-hospital and 90-day postdischarge mortality in SEA. STUDY DESIGN/SETTING: Retrospective, case-control study at a tertiary care academic medical center from 2003 to 2021. PATIENT SAMPLE: Adult patients admitted for radiologically confirmed diagnosis of SEA who did not initiate treatment at an outside institution. OUTCOME MEASURES: In-hospital and 90-day postdischarge mortality. METHODS: We tested the SORG stochastic gradient boosting algorithm on an independent validation cohort. We assessed its performance with discrimination, calibration, decision curve analysis, and overall performance. RESULTS: A total of 212 patients met inclusion criteria, with a short-term mortality rate of 10.4%. The area under the receiver operating characteristic curve (AUROC) of the SORG algorithm when tested on the full validation cohort was 0.82, the calibration intercept was -0.08, the calibration slope was 0.96, and the Brier score was 0.09. CONCLUSIONS: With a contemporaneous and geographically distinct independent cohort, we report successful external validation of a machine learning algorithm for prediction of in-hospital and 90-day postdischarge mortality in SEA.

Rates and Outcomes of Periprosthetic Joint Infection in Persons Who Inject Drugs.

BACKGROUND: The risk of periprosthetic joint infection (PJI) is higher in persons who inject drugs (PWID) after total joint arthroplasty (TJA), though reported rates vary widely. This study was designed to assess outcomes of TJA in PWID and to describe factors associated with improved PJI outcomes among PWID. METHODS: A retrospective matched cohort study was performed using a 1:4 match among those with and those without a history of injection drug use (IDU) undergoing TJA. Demographic, surgical, and outcome variables were compared in multivariate logistic regressions to determine PJI predictors. Kaplan-Meier analyses were constructed to characterize the difference in survival of patients who did not have PJI or undergo joint explantation between PWID and the matching cohort. RESULTS: PWID had a 9-fold increased risk of PJI compared to the matched cohort (odds ratio 9.605, 95% CI 2.781-33.175, P < .001). Ten of 17 PWID whose last use was within 6 months (active use) of primary TJA had a PJI, while 7 of 41 PWID who did not have active use developed a PJI. Of PWID with PJI, treatment failure was seen in 15 of 17, while in patients who did not have an IDU history, 5 of 8 with PJI had treatment failure. CONCLUSION: IDU is a significant risk factor for PJI following TJA. Future work investigating the effect of a multidisciplinary support team to assist in cessation of IDU and to provide social support may improve outcomes and reduce morbidity in this vulnerable population.

Peri-Prosthetic Joint Infection in Patients Prescribed Suppressive Antibiotic Therapy Undergoing Primary Total Joint Arthroplasty: A 1:4 Case Control Matched Study.

Background: Oral suppressive antibiotic therapy (SAT) has emerged as a potential means to increase rates of infection-free survival in many complex peri-prosthetic joint infection (PJI) cases after total joint arthroplasty (TJA). The purpose of the present study is to evaluate the risk of PJI of a new primary TJA in patients on oral SAT. Patients and Methods: A retrospective matched cohort study from five hospitals in a 20-year period within a large hospital network was performed. Inclusion criteria consisted of patients over age 18 undergoing primary TJA, with any order for oral long-term (>6 months duration) SAT, and minimum of one-year clinical follow-up. Patients were matched 1:4 on age, gender, body mass index (BMI), hip or knee surgery, diabetes mellitus, smoking status, and indication for primary TJA. Student t-test, Fisher exact, and χ2 tests were utilized for group comparisons. Our study was powered to detect a 10.5% increase in PJI incidence compared with a 1% baseline rate of PJI. Results: We identified 45 TJA in 33 patients receiving SAT, which were matched to 180 control cases. There was no difference in the rate of development of PJI at any time point within follow-up between the SAT cohort and control group (2.22% vs. 1.11%; p = 0.561). Conclusions: We found a 2.22% rate of PJI in a cohort of patients receiving SAT identified over a 20-year period. As the clinical scenario of primary TJA while on SAT is rare but likely to become more prevalent, future large-scale studies can be performed to better clarify rates and risk of PJI in this population.

Predictors of reoperation after surgery for spinal epidural abscess.

BACKGROUND CONTEXT: Spinal epidural abscess is a rare but severe condition with high rates of postoperative adverse events. PURPOSE: The objective of the study was to identify independent prognostic factors for reoperation using two datasets: an institutional and national database. STUDY DESIGN/SETTING: Retrospective Review. PATIENT SAMPLE: Database 1: Review of five medical centers from 1993 to 2016. Database 2: The National Surgical Quality Improvement Program (NSQIP) was queried between 2012 and 2016. OUTCOME MEASURES: Thirty-day and ninety-day reoperation rate. METHODS: Two independent datasets were reviewed to identify patients with spinal epidural abscesses undergoing spinal surgery. Multivariate analyses were used to determine independent prognostic factors for reoperation while including factors identified in bivariate analyses. RESULTS: Overall, 642 patients underwent surgery for a spinal epidural abscess in the institutional cohort, with a 90-day unplanned reoperation rate of 19.9%. In the NSQIP database, 951 patients were identified with a 30-day unplanned reoperation rate of 12.3%. On multivariate analysis in the NSQIP database, cervical spine abscess was the only factor that reached significance for 30-day reoperation (OR=1.71, 95% CI=1.11-2.63, p=.02, Area under the curve (AUC)=0.61). On multivariate analysis in the institutional cohort, independent prognostic factors for 30-day reoperation were: preoperative urinary incontinence, ventral location of abscess relative to thecal sac, cervical abscess, preoperative wound infection, and leukocytosis (AUC=0.65). Ninety-day reoperation rate also found hypoalbuminemia as a significant predictor (AUC=0.66). CONCLUSION: Six novel independent prognostic factors were identified for 90-day reoperation after surgery for a spinal epidural abscess. The multivariable analysis fairly predicts reoperation, indicating that there may be additional factors that need to be uncovered in future studies. The risk factors delineated in this study through the use of two large cohorts of spinal epidural abscess patients can be used to improve preoperative risk stratification and patient management.

A Case Series of Rifabutin Use in Staphylococcal Prosthetic Infections.

This case series describes seven patients who received rifabutin in place of rifampin combined with conventional antimicrobial therapy for treatment of hardware-associated staphylococcal infections. Infection recurrence, defined as need for unplanned surgical intervention within the evaluable follow up period after starting rifabutin, occurred in two patients. Two patients experienced possible treatment-associated adverse effects. Findings support future work to examine rifabutin use, when rifampin is not suitable, for adjunctive treatment of staphylococcal hardware infections. IMPORTANCE This work evaluates real-world data and clinical outcomes when rifabutin is used in place of rifampin for adjunctive management of staphylococcal hardware-associated infections. This is the second case study looking at this specific use of rifabutin, signifying the current lack of clinical data in this area. Assessing use of rifabutin in this capacity is clinically important given its lower propensity for drug interactions compared to rifampin.

First-generation oral antivirals against SARS-CoV-2.

BACKGROUND: Oral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization for the treatment of mild-to-moderate COVID-19 in non-hospitalized patients who are at high risk for clinical progression. OBJECTIVES: To provide a clinical practice overview of first-generation oral antiviral agents against SARS-CoV-2. SOURCES: References for this review were identified through searches of PubMed, Google Scholar, bioRxiv, medRxiv, regulatory drug agencies, and pharmaceutical companies' websites up to 16 February 2022. CONTENT: Molnupiravir and nirmatrelvir and ritonavir have been authorized for use in nonhospitalized individuals with mild-to-moderate COVID-19 who are at high risk for progression. In clinical trials, molnupiravir reduced the frequency of hospitalization or death by 3% (relative risk reduction 30%), and nirmatrelvir and ritonavir by 6% (relative risk reduction 89%). Their use in clinical practice requires early administration, review of drug-drug interactions (nirmatrelvir and ritonavir), considerations of embryo-fetal toxicity (molnupiravir), and compliance with ingestion of a high number of pills. Knowledge gaps include the efficacy of these agents in vaccinated, hospitalized, or immunosuppressed individuals with prolonged SARS-CoV-2 persistence. IMPLICATIONS: First-generation oral antivirals represent progress in therapeutics against SARS-CoV-2, but also pose new challenges in clinical practice. Further advances in the development of new drugs are required.

Outcomes of Concurrent Endocarditis and Periprosthetic Joint Infection: A Retrospective Case Series of 16 Patients.

Introduction Concurrent diagnosis of periprosthetic joint infection (PJI) of total hip arthroplasty (THA) or total knee arthroplasty (TKA) with infectious endocarditis is a devastating clinical scenario infrequently documented in the literature. To date, no studies have fully described the orthopedic and infectious outcomes of patients with these concurrent diagnoses. The purpose of this study was to conduct a case series of patients with these diagnoses and document the orthopedic and infectious outcomes so that surgeons may effectively counsel patients regarding the gravity of the condition and the expected course of treatment. Methods This study is a retrospective case series using patient data from five hospitals within an academic healthcare system in the northeastern United States. Cases of concurrent endocarditis and THA or TKA PJI with a minimum of one-year follow-up were identified from January 2000 to January 2021. Basic statistics such as means, standard deviations, and percentages were used to identify trends within our series. Kaplan-Meier survivorship curves with log-rank tests were performed to determine if there were any differences in two-year mortality and joint survival (defined as needing explant) between patients who had cardiac surgery prior to surgical management for their PJI and those who had surgical management for PJI prior to cardiac surgery. Results A total of 18 joints in 16 patients with endocarditis and concurrent TKA or THA PJI were identified. All PJIs were managed surgically, with 14/18 (77.77%) of joint infections initially being managed by debridement, antibiotics, and implant retention (DAIR) and 4/18 (22.22%) of joint infections initially being managed by explant. Within the first six months of PJI diagnosis, 25% (4/16) of patients died of complications related to their infection, and one additional patient died of bacteremia just over a year after the initial PJI diagnosis. Of the 18 PJIs, 72.23% (13/18) had treatment failure, defined as any outcome equal to or worse than requiring chronic suppressive antibiotics for the infection. Due to low statistical power, we were not able to identify any differences in two-year mortality from PJI diagnosis (p=0.311) or joint survival (in terms of requiring explant) (p=0.420) depending on whether cardiac surgery or DAIR was performed first. Conclusions Concurrent infectious endocarditis and prosthetic joint infection is associated with high morbidity and mortality. Patients with these concurrent infections should be counseled that not only the associated mortality rate is high, but also the surgical treatment of their PJI has a high rate of treatment failure, including an explant following an initial DAIR, an explant with retained spacer, or a requirement of lifelong antibiotic suppression.