What's New in Pediatric Septic Arthritis? A Review of Pertinent Clinical Questions.

BACKGROUND: The evaluation and treatment of children with septic arthritis (SA) is challenging and requires an organized approach to address the spectrum of pathogens which appear to aggregate in age-specific groups. Although evidence-based guidelines have recently been published for the evaluation and treatment of children with acute hematogenous osteomyelitis, there is a relative dearth of literature devoted exclusively to SA. METHODS: Recently published guidance for the evaluation and treatment of children with SA was reviewed and evaluated with respect to pertinent clinical questions to summarize what is new in this area of practice for pediatric orthopaedic surgeons. RESULTS: Evidence suggests that there is a profound difference between children with primary SA and those who have contiguous osteomyelitis. This disruption of the commonly accepted paradigm of a continuum of osteoarticular infections has important implications in the evaluation and treatment of children with primary SA. Clinical prediction algorithms have been established to help determine the applicability of magnetic resonance imaging during the evaluation of children suspected to have SA. Antibiotic duration for SA has been recently studied with some evidence in favor of short-course parenteral followed by short-course oral therapy may be successful if the pathogen is not methicillin-resistant Staphylococcus aureus . CONCLUSION: Recent studies of children with SA have provided better guidance for evaluation and treatment to improve diagnostic accuracy, processes of evaluation, and clinical outcomes. LEVEL OF EVIDENCE: Level 4.

Comparison of Procalcitonin With Commonly Used Biomarkers and Algorithms for Evaluating Suspected Pediatric Musculoskeletal Infection in the Emergency Department.

INTRODUCTION: It is difficult to distinguish between children with infectious versus noninfectious conditions of the musculoskeletal system during initial evaluation. Clinical predictive algorithms potentially support this effort but not without limitations. Procalcitonin (PCT) has been proposed as a biomarker to help differentiate infection from noninfection. This study evaluates the adoption and utility of PCT during initial infection evaluations and assesses test characteristics of commonly used parameters and algorithms. METHODS: PCT was introduced for initial laboratory evaluation of the suspected musculoskeletal infection. Prospective enrollment occurred from July 2020 to November 2021 with 3 cohorts established after a retrospective review of final diagnoses at the end of treatment: 1) deep infection, 2) superficial infection, and 3) noninfection. Univariate and multivariate logistic regression analysis of parameters and diagnoses was performed. Test characteristics of individual and aggregated parameters were assessed. RESULTS: Among 258 children evaluated, 188 (72.9%) had PCT drawn during the evaluation. An increase of PCT acquisition from 67.8% to 82.4% occurred over the study timeframe. Eighty-five children were prospectively studied, including those with deep infection (n=21); superficial infection (n=10), and noninfection (n=54). Test characteristics of parameters showed accuracy ranging from 48.2% to 85.9%. PCT >0.1 ng/mL independently predicted deep infection in 84.7% of cases, outperforming white blood cell, C-reactive protein (CRP), and absolute neutrophil count. Using study thresholds for CRP, erythrocyte sedimentation rate, PCT, and Temp improved accuracy to 89.4%. CONCLUSIONS: PCT is a potentially useful biomarker during the initial assessment of children suspected to have a musculoskeletal infection. Systematic evaluation using a combination of parameters improves the accuracy of assessment and assists predictive judgment under uncertainty. PCT <0.1 ng/mL, erythrocyte sedimentation rate <18 mm/hr, CRP <3.3 mg/dL, and temperature <37.8°C should reasonably reassure clinicians that deep musculoskeletal infection is less likely, given the high negative predictive value and collective accuracy of these parameters. LEVEL OF EVIDENCE: Level III - Retrospective cohort comparison.

Primary Septic Arthritis in Children Demonstrates Presumed and Confirmed Varieties Which Require Age-specific Evaluation and Treatment Strategies.

BACKGROUND: There is uncertainty involved in the evaluation and treatment of children suspected to have septic arthritis particularly when no causative pathogen is confirmed. This study evaluates children with primary septic arthritis to refine the processes of evaluation and treatment and improve the rate of pathogen confirmation. METHODS: Children suspected to have septic arthritis from 2009 to 2019 were retrospectively studied. Diagnosis of primary septic arthritis, defined as hematogenous joint infection without associated osteomyelitis, was established by clinical evaluation, radiology and laboratory results, including joint fluid analysis. Excluded cases were categorized by etiology. Children with primary septic arthritis were divided into confirmed and presumed cohorts for statistical comparison. RESULTS: A total of 355 children (average age 4.4 y, range 0.05 to 18 y) were initially treated as septic arthritis. Eighty-seven (24.5%) were excluded due to other conditions, including 34 (9.6%) with noninfectious conditions. Among 268 children with primary septic arthritis, 134 were confirmed and 134 were presumed. A higher rate of 16S polymerase chain reaction (PCR) acquisition (71.6% vs. 45.5%) occurred in the confirmed cohort. Overall yield for various methods of pathogen identification were 27 of 239 (11.3%) by blood culture, 83 of 268 (31.0%) by joint fluid culture and 85 of 157 (54.1%) by PCR. PCR identified a pathogen in 87.5% of children with confirmed septic arthritis. Antibiotic pretreatment was associated with a lower rate of joint fluid culture positivity. Pathogens aggregated within specific age groups. The 4 to 9-year-old age group displayed the widest spectrum of pathogens with limited predictability. CONCLUSIONS: This study emphasizes the need for systematic processes of evaluation and treatment for children suspected to have primary septic arthritis, including minimization of antibiotic pretreatment, age-based empiric antibiotic selection, and sufficient follow-up to ensure noninfectious conditions are distinguished in culture-negative cases. Extended observation, before intervention, may be appropriate for some children. LEVEL OF EVIDENCE: Level III-retrospective control study.

Primary Septic Arthritis Among Children 6 to 48 Months of Age: Implications for PCR Acquisition and Empiric Antimicrobial Selection.

INTRODUCTION: Primary septic arthritis requires unique evaluation and treatment considerations for children in the 6- to 48-month age range because of the spectrum of identified pathogens and high rate of negative cultures. The purpose of this study is to evaluate primary septic arthritis in this age group in order to differentiate children with infection caused by Kingella kingae from those with other confirmed pathogens and those with no identified pathogen. METHODS: Preschool children who underwent multidisciplinary evaluation and treatment for septic arthritis between 2009 and 2019 were retrospectively studied. Three cohorts were established for comparison of clinical and laboratory features of primary septic arthritis: (1) confirmed K. kingae, (2) confirmed other pathogen, and (3) presumed (without identified pathogen). RESULTS: Among 139 children with septic arthritis, 40 (29%) were confirmed K. kingae, 29 (21%) other pathogen, and 70 (50%) presumed. Children with Kingella and those with presumed septic arthritis had significantly lower initial C-reactive protein (4.8 and 4.5 vs. 9.3 mg/dL) and fewer febrile hospital days (0.2 and 0.4 vs. 1.3 d) than children with other confirmed pathogens. Children with other pathogens had higher rates of bacteremia (38% vs. 0%) and positive joint fluid cultures (86% vs. 15%) than that of children with Kingella. The rate of polymerase chain reaction (PCR) acquisition was 38 of 40 (95.0%) Kingella cases, 18 of 29 (62.1%) other pathogen cases, and 33 of 70 (47.1%) presumed cases. CONCLUSIONS: K. kingae was the most commonly identified pathogen among 6-month to 4-year-old children. The Kingella and other identified pathogens in this study serve to guide empiric antimicrobial recommendations for this age range. Because of similarities between children with septic arthritis because of K. kingae and those with no identified pathogen, it is likely that an unrecognized burden of Kingella resides in culture negative cases, particularly if no PCR is sent. Systematic evaluation, including PCR acquisition, and a high index of suspicion for K. kingae are recommended to thoroughly evaluate septic arthritis in preschool children. LEVEL OF EVIDENCE: Level III-Retrospective cohort comparison.

Pediatric Type II Supracondylar Humerus Fractures: Factors Associated With Successful Closed Reduction and Immobilization.

PURPOSE: The debate on the treatment of type IIa supracondylar humerus fractures has yet to be resolved. The purpose of this study was to assess the factors associated with successful closed reduction and immobilization and to assess the efficacy of a novel radiographic "hourglass" angle measurement in the management of type IIa supracondylar humerus fractures within the pediatric population. METHODS: An institutional review board-approved retrospective review of all children who underwent closed reduction and casting or splinting of an isolated type IIa supracondylar humerus fractures treated at 2 pediatric hospitals from January 1, 2009 to August 31, 2016. Analyzed radiographic parameters included Baumann angle (BA), humerocondylar angle (HCA), perpendicular distance (PD) from the anterior humeral line to the capitellum, and the hourglass angle (HGA). These parameters were measured on injury radiographs (XR), postreduction XR, and at the first and final follow-up XR. The success of closed reduction was defined as maintenance of an acceptable reduction without a secondary procedure. The interobserver reliability was calculated. RESULTS: There were 77 elbows treated with closed reduction and long-arm cast or splint immobilization. Of those closed reductions, 76.62% of elbows (59/77) maintained their reduction alignment and did not require surgical treatment for percutaneous pinning. In this series, the BA was not significantly different following closed reduction ([INCREMENT]1.04 degrees; P=0.081); however, the PD ([INCREMENT]1.89 mm), HGA ([INCREMENT]7.38 degrees), and HCA ([INCREMENT]5.07 degrees) had significant improvement following closed reduction (P<0.001 for all). The use of procedural sedation during reduction was strongly associated with success, 83.05% (49/59) with sedation compared with 55.56% (10/18) success without sedation (P=0.025). Furthermore, fractures that underwent a secondary procedure had 6.20 degrees less HGA following a closed reduction (P=0.016) and required additional follow-up visits (P=0.0037). The success of type IIa supracondylar humerus fractures did not significantly differ based on sex (P=0.5684), laterality (P=0.6975), mechanism of injury (P>0.9999), location of care-emergency department versus clinic (P=0.1160), or type of fracture immobilization (P=0.7411). The mean HGA in normal elbows was 177.8 degrees. The interobserver reliability for HCA was poor [intraclass correlation coefficient (ICC)=0.342]; fair for BA (ICC=0.458); and excellent for both PD and HGA (ICC=0.769 and 0.805, respectively) (P<0.001 for all). CONCLUSIONS: Improved and acceptable radiographic parameters were achieved by a closed reduction in the majority of minimally displaced type IIa fractures treated by closed reduction and immobilization in this series. HCA upon presentation was significantly greater in successful cases, and failure to improve and maintain HGA and PD following closed reduction was associated with loss of reduction. Procedural sedation during reduction was strongly associated with success. The HGA and PD were consistent parameters used to determine effective management of type IIa fractures. This study adds support for a nonoperative closed reduction under sedation with immobilization of selected type IIa supracondylar humerus fractures.

Validation and Modification of a Severity of Illness Score for Children With Acute Hematogenous Osteomyelitis.

BACKGROUND: Children with osteomyelitis demonstrate a wide spectrum of illness. Objective measurement of severity is important to guide resource allocation and treatment decisions, particularly for children with advanced illness. The purpose of this study is to validate and improve a previously published severity of illness scoring system for children with acute hematogenous osteomyelitis (AHO). METHODS: Children with AHO were prospectively studied during evaluation and treatment by a multidisciplinary team who provided care according to evidence-based guidelines to reduce variation. A severity of illness score was calculated for each child and correlated with surrogate measures of severity. Univariate analysis was used to assess the significance of each parameter within the scoring model along with new parameters, which were evaluated to improve the model. The scoring system was then modified by the addition of band count to replace respiratory rate. The modified score was calculated and applied to the prospective cohort followed by correlation with the surrogate measures of severity. RESULTS: One hundred forty-eight children with AHO were consecutively studied. The original severity of illness score correlated well with length of stay and other established measures of severity. Band percent of the white blood cell differential ≥1.5% was found to be significantly associated with severity and chosen to replace respiratory rate in the model. The modified calculated severity scores correlated well with the chosen surrogate measures and significantly differentiated children with osteomyelitis on the basis of causative organism, length of stay, intensive care, surgeries, bacteremia, and disseminated or multifocal disease. CONCLUSIONS: The findings of this study validate the previously published severity of illness scoring tool in large cohort of children who were prospectively evaluated. The replacement of respiratory rate with band count improved the scoring system.

Electronic Medical Record Use and Satisfaction Among Pediatric Orthopaedic Surgeons.

INTRODUCTION: Electronic medical record (EMR) use among pediatric orthopaedic surgeons has evolved substantially within the past decade. In response to the Patient Protection and Affordable Care Act, large hospitals and tertiary pediatric medical centers rapidly acquired and implemented EMRs with uncertainty as to the potential impact on patient care and operational efficiency of subspecialists. This study reviews the background and regulatory framework for Meaningful Use of EMR and assesses the current landscape of EMR utilization by pediatric orthopaedic surgeons. METHODS: In 2015, the Practice Management Committee distributed a survey regarding EMR use and satisfaction to members of the Pediatric Orthopaedic Society of North America. Survey responses from 324 members were used to analyze levels of satisfaction by EMR platform and practice type and to consider drivers of satisfaction or dissatisfaction of end users. RESULTS: Although there were no differences in overall satisfaction based on vendor or practice type, significant differences were noted for 5 specific parameters of satisfaction, including: usefulness of templates, efficiency of practice workflow, information services support, number of logon events, and speed of the system. A user/vendor map is provided to facilitate networking among providers and groups utilizing common EMR platforms to help bring about rational improvements in EMR functionality for the future. CONCLUSIONS: Substantial effort needs to be made to improve subspecialty-specific EMR documentation, order entry, research tools, and clinical workflows to enhance the processes of care for children with orthopaedic conditions in the era of EMR. LEVEL OF EVIDENCE: Level IV.

Multivariate Air Pollution Prediction Modeling with partial Missingness.

Missing observations from air pollution monitoring networks have posed a longstanding problem for health investigators of air pollution. Growing interest in mixtures of air pollutants has further complicated this problem, as many new challenges have arisen that require development of novel methods. The objective of this study is to develop a methodology for multivariate prediction of air pollution. We focus specifically on tackling different forms of missing data, such as: spatial (sparse sites), outcome (pollutants not measured at some sites), and temporal (varieties of interrupted time series). To address these challenges, we develop a novel multivariate fusion framework, which leverages the observed inter-pollutant correlation structure to reduce error in the simultaneous prediction of multiple air pollutants. Our joint fusion model employs predictions from the Environmental Protection Agency's Community Multiscale Air Quality (CMAQ) model along with spatio-temporal error terms. We have implemented our models on both simulated data and a case study in South Carolina for 8 pollutants over a 28-day period in June 2006. We found that our model, which uses a multivariate correlated error in a Bayesian framework, showed promising predictive accuracy particularly for gaseous pollutants.

Towards integrated surveillance of zoonoses: spatiotemporal joint modeling of rodent population data and human tularemia cases in Finland.

BACKGROUND: There are an increasing number of geo-coded information streams available which could improve public health surveillance accuracy and efficiency when properly integrated. Specifically, for zoonotic diseases, knowledge of spatial and temporal patterns of animal host distribution can be used to raise awareness of human risk and enhance early prediction accuracy of human incidence. METHODS: To this end, we develop a spatiotemporal joint modeling framework to integrate human case data and animal host data to offer a modeling alternative for combining multiple surveillance data streams in a novel way. A case study is provided of spatiotemporal modeling of human tularemia incidence and rodent population data from Finnish health care districts during years 1995-2012. RESULTS: Spatial and temporal information of rodent abundance was shown to be useful in predicting human cases and in improving tularemia risk estimates in 40 and 75% of health care districts, respectively. The human relative risk estimates' standard deviation with rodent's information incorporated are smaller than those from the model that has only human incidence. CONCLUSIONS: These results support the integration of rodent population variables to reduce the uncertainty of tularemia risk estimates. However, more information on several covariates such as environmental, behavioral, and socio-economic factors can be investigated further to deeper understand the zoonotic relationship.

Differentiation of Deep Venous Thrombosis Among Children With or Without Osteomyelitis.

BACKGROUND: Children with osteomyelitis are at risk for deep venous thrombosis (DVT). This study evaluates the characteristics of DVT among children to differentiate between those with and without osteomyelitis. METHODS: Children with DVT of any cause were studied between 2008 and 2016. Children with DVT and osteomyelitis were compared with those with DVT without osteomyelitis. Another comparison cohort included children with osteomyelitis but without DVT. Comorbidities, severity of illness (SOI), and clinical course were compared between cohorts. RESULTS: DVT was identified in 224 children, a prevalence of 2.5 per 10,000 children. Among those with DVT, 28 (12.1%) had osteomyelitis. The DVT rate among 466 children with osteomyelitis was 6.0%. Children with osteomyelitis and DVT had greater SOI (9.1 vs. 2.7), bacteremia rate (82.1% vs. 38.4%), methicillin-resistant Staphylococcus aureus rate (89.3% vs. 21.2%), surgeries per child (2.1 vs. 0.7), and intensive care unit admission rate (67.9% vs. 5.9%) than that of children without DVT (P<0.00001). Of 196 children who had DVT without osteomyelitis, 166 (84.7%) had comorbidities including defined hypercoagulability (27 or 13.8%). Children with DVT due to osteomyelitis were without comorbidities or hypercoagulability (P<0.00001). The rate of pulmonary embolism was similar for children with DVT with or without osteomyelitis (3/28, or 10.7% vs. 18/196, or 9.2%). CONCLUSIONS: Children with DVT and osteomyelitis differ substantially from other children with DVT by the absence of comorbidities or post-thrombotic syndrome. They also differ from children with osteomyelitis without DVT by higher SOI, methicillin-resistant S. aureus rate, and occurrence of intensive care. Awareness of for the characteristics of DVT among children with osteomyelitis will reduce delay to diagnostic ultrasound and improve anticoagulation management which must be carefully coordinated given the high rate of surgery of these children. LEVEL OF EVIDENCE: Level II-prognostic, retrospective cohort comparison.

A Novel Classification System Based on Dissemination of Musculoskeletal Infection is Predictive of Hospital Outcomes.

BACKGROUND: Musculoskeletal infections (MSKIs) are a common cause of pediatric hospitalization. Children affected by MSKI have highly variable hospital courses, which seem to depend on infection severity. Early stratification of infection severity would therefore help to maximize resource utilization and improve patient care. Currently, MSKIs are classified according to primary diagnoses such as osteomyelitis, pyomyositis, etc. These diagnoses, however, do not often occur in isolation and may differ widely in severity. On the basis of this, the authors propose a severity classification system that differentiates patients based on total infection burden and degree of dissemination. METHODS: The authors developed a classification system with operational definitions for MSKI severity based on the degree of dissemination. The operational definitions were applied retrospectively to a cohort of 202 pediatric patients with MSKI from a tertiary care children's hospital over a 5-year period (2008 to 2013). Hospital outcomes data [length of stay (LOS), number of surgeries, positive blood cultures, duration of antibiotics, intensive care unit LOS, number of days with fever, and number of imaging studies] were collected from the electronic medical record and compared between groups. RESULTS: Patients with greater infection dissemination were more likely to have worse hospital outcomes for LOS, number of surgeries performed, number of positive blood cultures, duration of antibiotics, intensive care unit LOS, number of days with fever, and number of imaging studies performed. Peak C-reactive protein, erythrocyte sedimentation rate, white blood cell count, and temperature were also higher in patients with more disseminated infection. CONCLUSIONS: The severity classification system for pediatric MSKI defined in this study correlates with hospital outcomes and markers of inflammatory response. The advantage of this classification system is that it is applicable to different types of MSKI and represents a potentially complementary system to the previous practice of differentiating MSKI based on primary diagnosis. Early identification of disease severity in children with MSKI has the potential to enhance hospital outcomes through more efficient resource utilization and improved patient care. LEVEL OF EVIDENCE: Level II-prognostic study.

Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.

Background: Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. Material and methods: ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA. Results: The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively. Conclusion(s): ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue.

Spatial small area smoothing models for handling survey data with nonresponse.

Spatial smoothing models play an important role in the field of small area estimation. In the context of complex survey designs, the use of design weights is indispensable in the estimation process. Recently, efforts have been made in these spatial smoothing models, in order to obtain reliable estimates of the spatial trend. However, the concept of missing data remains a prevalent problem in the context of spatial trend estimation as estimates are potentially subject to bias. In this paper, we focus on spatial health surveys where the available information consists of a binary response and its associated design weight. Furthermore, we investigate the impact of nonresponse as missing data on a range of spatial models for different missingness mechanisms and different degrees of missingness by means of an extensive simulation study. The computations were performed in R, using INLA and other existing packages. The results show that weight adjustment to correct for missingness has a beneficial effect on the bias in the missing at random setting for all models. Furthermore, we estimate the geographical distribution of perceived health at the district level based on the Belgian Health Interview Survey (2001). Copyright © 2017 John Wiley & Sons, Ltd.

Key Concepts of Musculoskeletal Infection.

Over the past few decades, musculoskeletal infections have increased in both incidence and severity. The clinical manifestations of musculoskeletal infections range from isolated osteomyelitis to multisite infections with systemic complications. Although this increased incidence of musculoskeletal infections correlates with the increased incidence of methicillin-resistant Staphylococcus aureus infections, other nonresistant infectious organisms have been associated with severe musculoskeletal infections; this finding supports the likelihood that an antibiotic resistance profile is not a major factor in bacterial virulence. Instead, a multitude of virulence factors allow infectious organisms to manipulate and evade the immune response of the host. Organisms such as S aureus and Streptococcus pyogenes are able to hijack the acute phase response of the host, which allows for protected proliferation and dissemination. The serum factors produced by the acute phase response, including interleukin-6, C-reactive protein, erythrocytes/fibrinogen, and platelets, can be used to assess musculoskeletal infection severity and monitor treatment. Bacterial genome sequencing has identified virulence factors in a wide variety of clinical manifestations of musculoskeletal infections and may help identify targets for clinical therapy. Currently, however, the management of musculoskeletal infections relies on accurate organism identification and a thorough recognition of the sites of infection and the tissues that are involved. MRI aids in the localization of musculoskeletal infection and identification of sites that require surgical débridement.

Pediatric Orthopaedic Workforce in 2014: Current Workforce and Projections for the Future.

BACKGROUND: The changing nature of the United States (US) health care system has prompted debate concerning the physician supply. The basic questions are: do we have an adequate number of surgeons to meet current demands and are we training the correct number of surgeons to meet future demands? The purpose of this analysis was to characterize the current pediatric orthopaedic workforce in terms of supply and demand, both present and future. METHODS: Databases were searched (POSNA, SF Match, KID, MGMA) to determine the current pediatric orthopaedic workforce and workforce distribution, as well as pediatric orthopaedic demand. RESULTS: The number of active Pediatric Orthopaedic Society of North America (POSNA) members increased over the past 20 years, from 410 in 1993 to 653 in 2014 (155% increase); however, the density of POSNA members is not equally distributed, but correlates to population density. The number of estimated pediatric discharges, orthopaedic and nonorthopaedic, has remained relatively stable from 6,348,537 in 1997 to 5,850,184 in 2012. Between 2003 and 2013, the number of pediatric orthopaedic fellows graduating from Accreditation Council for Graduate Medical Education and non-Accreditation Council for Graduate Medical Education programs increased from 39 to 50 (29%), with a peak of 67 fellows (71%) in 2009. DISCUSSION: Although predicting the exact need for pediatric orthopaedic surgeons (POS) is impossible because of the complex interplay among macroeconomic, governmental, insurance, and local factors, some trends were identified: the supply of POS has increased, which may offset the expected numbers of experienced surgeons who will be leaving the workforce in the next 10 to 15 years; macroeconomic factors influencing demand for physician services, driven by gross domestic product and population growth, are expected to be stable in the near future; expansion of the scope of practice for POS is expected to continue; and further similar assessments are warranted. LEVEL OF EVIDENCE: Level II-economic and decision analysis.

Spatiotemporal multivariate mixture models for Bayesian model selection in disease mapping.

It is often the case that researchers wish to simultaneously explore the behavior of and estimate overall risk for multiple, related diseases with varying rarity while accounting for potential spatial and/or temporal correlation. In this paper, we propose a flexible class of multivariate spatio-temporal mixture models to fill this role. Further, these models offer flexibility with the potential for model selection as well as the ability to accommodate lifestyle, socio-economic, and physical environmental variables with spatial, temporal, or both structures. Here, we explore the capability of this approach via a large scale simulation study and examine a motivating data example involving three cancers in South Carolina. The results which are focused on four model variants suggest that all models possess the ability to recover simulation ground truth and display improved model fit over two baseline Knorr-Held spatio-temporal interaction model variants in a real data application.

Competitive intramolecular C-C vs. C-O bond coupling reactions toward C6 ring-fused 2-pyridone synthesis.

An interesting competitive C-C vs. C-O bond coupling reaction on N,3,5-trisubstituted pyridones is reported. These coupling reactions provided selective access to C- or O-ring-fused pyridones, both at the challenging C6-pyridone position. 1,6-C-Annulated pyridones were generally achieved in good yields with excellent chemoselectivity under Pd(0) conditions. On the other hand, full C6-regioselective Csp(2) aryloxylation was achieved under oxidative coupling promoted by silver salts to access 5,6-O-annulated pyridones. Based on various experiments and observations, mechanistic evidence of these competitive reactions was provided and it was proposed that C-O bond formation proceeded through radical cyclization. These processes were performed under mild reaction conditions and offer an efficient and attractive methodology to selectively access a large scope of C-arylated and O-arylated pyridones of biological interest.

The Clinical Usefulness of Polymerase Chain Reaction as a Supplemental Diagnostic Tool in the Evaluation and the Treatment of Children With Septic Arthritis.

INTRODUCTION: Culture-negative septic arthritis occurs frequently in children. The supplemental use of polymerase chain reaction (PCR) techniques improves the detection of bacteria in the joint fluid. This study evaluates the clinical utility of PCR at a tertiary pediatric medical center. METHODS: Children with septic arthritis were studied prospectively from 2012 to 2014. Culture results and clinical infection parameters were recorded. PCR was performed whenever sufficient fluid was available from the joint aspiration. A statistical comparison was made for the rates of identification of the causative organism by these methods. A subgroup analysis was performed to assess the correspondence of clinical and laboratory parameters with the results of joint fluid culture and PCR. RESULTS: Ninety-nine children with septic arthritis were enrolled consecutively. A broad range of parameter results was identified among these children with an average of 3.6 of 6 parameters per child that met thresholds of infection. Joint fluid cultures were positive in 34 of 97 (35.1%) children from whom they were sent. Among the 68 children from whom the material was sent for PCR, the result was positive in 32 (47.1%). The combination of blood culture, joint fluid culture, and PCR resulted in bacterial detection in 49 of 97 (50.5%) children. PCR improved the rate of detection of Kingella kingae markedly when compared with joint fluid culture. PCR results were available at an average of 14.6 days after the acquisition of joint fluid. 16S PCR results were reported at an average of 17.5 days, whereas Kingella PCR took 5.1 days. DISCUSSION: PCR provides supplemental information for diagnostic confirmation through an increased rate of detection of bacteria. The timing of results and the inability to provide antibiotic sensitivity are factors that limit its clinical usefulness currently.

Spatio-temporal Bayesian model selection for disease mapping.

Spatio-temporal analysis of small area health data often involves choosing a fixed set of predictors prior to the final model fit. In this paper, we propose a spatio-temporal approach of Bayesian model selection to implement model selection for certain areas of the study region as well as certain years in the study time line. Here, we examine the usefulness of this approach by way of a large-scale simulation study accompanied by a case study. Our results suggest that a special case of the model selection methods, a mixture model allowing a weight parameter to indicate if the appropriate linear predictor is spatial, spatio-temporal, or a mixture of the two, offers the best option to fitting these spatio-temporal models. In addition, the case study illustrates the effectiveness of this mixture model within the model selection setting by easily accommodating lifestyle, socio-economic, and physical environmental variables to select a predominantly spatio-temporal linear predictor.

The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy.

Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost-effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium-term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS 'Payment by Results' database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non-SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5-year post-treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13-fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56-fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real-life data for future cost-effectiveness analyses related to the treatment for chronic HCV infection.