Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study.

OBJECTIVE: To determine if patients that develop lingering neurologic symptoms of fatigue and "brain fog" after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology. DESIGN: In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function. RESULTS: PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion. CONCLUSIONS: Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19. (www. CLINICALTRIALS: gov; NCT04860869).

Community Water Fluoridation and Rate of Pediatric Fractures.

BACKGROUND: The effect of community water fluoridation on bone fragility and fracture has been inconclusive in the literature. The null hypothesis of this study was that no association was observed between water fluoride level and risk of fracture in children. METHODS: Community fluoridation data were obtained from the Centers for Disease Control and Prevention while data on fracture rates were obtained from the PearlDiver database. The rate of fracture type for each state was then compared with state-level fluoridation data using Pearson correlation coefficients and Wilcoxon rank-sum tests. RESULTS: Positive correlations were found between the percentage of state water fluoridation and fracture rates for both bone forearm fracture (BBFFx) and femur fracture. Fluoride levels had positive correlations with fracture rates for all fracture types. Increased fracture rates were found between states in the highest quartiles of percentage of state water fluoridation and fluoride water levels for supracondylar humerus fracture and BBFFx. CONCLUSIONS: A higher level of water fluoridation was associated with higher rates of supracondylar humerus fracture and BBFFx in children aged 4 to 10 years. These findings do not imply causality, but they suggest that additional investigation into the effect of fluoride on pediatric bone health may be indicated.

Posterior Fixation Without Debridement for Vertebral Body Osteomyelitis and Discitis: A 10-Year Retrospective Review.

BACKGROUND: Surgical treatment of vertebral osteomyelitis, discitis, and epidural abscesses is indicated in the setting of failure of antibiotic therapy, neurological deficits, epidural abscess, or spinal instability/deformity. Historically, surgical treatment mandated aggressive debridement and spinal stabilization. However, there is growing evidence that direct debridement may not be necessary and may contribute to morbidity. The purpose of this study was to evaluate the efficacy of posterior instrumentation without debridement in treating spinal infections. METHODS: A retrospective medical record review was performed to identify patients treated with posterior instrumentation for spontaneous spinal infections. Success of treatment was determined based on postoperative ambulatory status, surgical complications, and need for revision surgery. RESULTS: Twenty-seven patients treated with posterior-only long-segmented rigid fixation without formal debridement of infected material were included. The most common indications for surgical intervention included spinal instability (67%), neurologic compromise (67%), and failure of prolonged antibiotic treatment (63%). There were no recurrent deep infections in 21 of 22 patients who had long-term follow-up. Four patients required revision surgery, and 3 additional patients requested elective hardware removal. Postoperatively, 70% were ambulatory with no assistive devices postoperatively. CONCLUSIONS: Vertebral osteomyelitis/discitis are challenging medical problems. Single-stage long-segment fusion without formal debridement combined with antibiotics is effective in the management of spontaneous spinal infections. CLINICAL RELEVANCE: The present study suggests that acute instrumentation without anterior debridement is associated with a resolution of infection and improvements in neurologic deficits in patient with spontaneous spine infections.

Return to the Operating Room for Unplanned Pin Removal After Percutaneous Pinning of Supracondylar Humerus Fractures: A Retrospective Review.

BACKGROUND: Pin migration is a common complication associated with closed reduced and percutaneous pinning (CRPP) of supracondylar humerus fractures (SCHF) in children. Though this complication occurs frequently, little work has been done to elicit circumstances surrounding this complication. The purpose of this study was to evaluate patients with SCHF treated with percutaneous pins who needed to return to the operating room for pin removal. METHODS: This was a multicenter study involving children treated at 6 pediatric tertiary care centers between 2010 and 2020. Retrospective chart review was performed to identify children aged 3 to 10 years of age with a diagnosis of a SCHF. Current Procedural Terminology (CPT) codes were used to identify patients who underwent CRPP of their injuries. CPT codes for deep hardware removal requiring procedural sedation or anesthesia were used to identify patients who needed to return to the operating room for hardware removal. RESULTS: Between 2010 and 2020, 15 out of 7862 patients who were treated for SCHF at our 6 participating study centers experienced pin migration requiring a return to the operating room for pin removal, yielding a complication rate of 0.19%. Twelve (80%) of these injuries were Wilkins modification of the Gartland classification Type III, while the remaining injuries were Type II. 2-pin fixation constructs were used in nine (60%) children; 3-pin fixation constructs were used in 6 (40%) children. Pin migration was noted 23.2±7.0 days postoperatively at clinic follow-up. Four patients were noted to have multiple pins buried at follow-up. Four patients required 1-centimeter incisions for exposure of the buried pins, while surgeons were able to remove the buried pin with just a needle driver and blunt dissection in the remainder of patients. CONCLUSIONS: Pin migration is a common complication of closed reduction and percutaneous pinning of SCHF. There is variation in pin site management to prevent migration in the absence of underlying risk factors. LEVEL OF EVIDENCE: Level III.

Decision Making and Cost in Healthcare: The Patient Perspective.

Unsustainable spending and unsatisfactory outcomes have prompted a reanalysis of healthcare policy towards value. Several strategies have been proposed as part of this effort including cost sharing plans to shift costs to patients and gain-sharing models to shift risk to health systems. The patient perspective is rarely elicited in policy formation despite efforts to increase patient-centered care. We conducted a prospective study of 118 patients presenting to hand clinic to assess patient perspective of who should constrain treatment options (patient, physician, insurance company, hospital) and be responsible for costs in scenarios of clinical equipoise. We found that patients believed that insurance companies and hospitals should not constrain which treatment options are available to a patient and that physicians and patients should together influence the availability of treatment options. Patients were willing to cost share with insurance companies when choosing more expensive treatments or in the setting of non-life-threatening diseases. In addressing rising healthcare costs, patient perspectives can inform policies designed to increase value. Asking patients to cost share when choosing a more expensive treatment option in the setting of clinical equipoise could be a strategy for health systems to increase value. Level of Evidence: III (Journal of Surgical Orthopaedic Advances 32(1):023-027, 2023).

Nonsteroidal Anti-inflammatory Drugs in the Acute Post-operative Period Are Associated With an Increased Incidence of Pseudarthrosis, Hardware Failure, and Revision Surgery Following Single-level Spinal Fusion.

STUDY DESIGN: Retrospective study. SUMMARY OF BACKGROUND DATA: Research has shown that the use of NSAIDs and COX-2 inhibitors increases the risk of pseudoarthrosis following spinal fusion surgery. Pseudoarthrosis can lead to complications such as chronic pain and the need for additional surgeries. OBJECTIVE: The purpose of this study was to examine the relationship between NSAID and COX-2 inhibitor use and pseudarthrosis, hardware complications, and revision surgeries in patients undergoing posterior spinal instrumentation and fusion. METHODS: We queried the PearlDiver database using CPT and ICD-10 codes to identify patients between the ages of 50 and 85 who underwent posterior spinal instrumentation between 2016 and 2019 and experienced pseudarthrosis, hardware failure, or revision surgery. Information regarding age, Charlson Comorbidity Index, tobacco use, osteoporosis, and obesity were extracted from the database along with COX-2 or NSAID use during the first 6-week post-surgery period. Logistic regression was used to identify associations while adjusting for confounders. RESULTS: There were 178,758 patients included in the cohort; 9,586 experienced pseudarthrosis (5.36%), 2828 (1.58%) experienced hardware failure, and 10,457 (5.85%) patients underwent revision fusion surgery. Of these patients 23,602 (13.2%) filled NSAID and 5278 (2.95%) filled COX-2 prescriptions. A significantly higher proportion of patients using NSAIDs experienced pseudarthrosis, hardware failure, and revision surgery compared to patients not taking NSAIDs. COX-2 inhibitors were also associated with a significantly higher rate of pseudarthrosis, hardware failure, and revision surgery. Postoperative ketorolac use was not associated with these complications. Regression models demonstrated that both NSAIDs and COX-2 inhibitors were associated with statistically higher pseudarthrosis, hardware failure, and revision surgery rates. CONCLUSIONS: Both NSAID and COX-2 inhibitor use in the early post-surgical period may be associated with increased rates of pseudarthrosis, hardware failure, and revision surgery in patients undergoing posterior spinal instrumentation and fusion.

Surgeon-Estimated Blood Loss Is Discordant With Calculated Blood Loss in Acetabular and Pelvic Fracture Surgery.

OBJECTIVES: To compare blood loss as estimated by surgeon-estimated blood loss (EBL), the Gross formula, and the HB equation in open pelvic and acetabular surgery. DESIGN: Retrospective cohort study. SETTING: Single Level I academic trauma center. PATIENTS: We included 710 patients 18-89 years of age who underwent acetabular or pelvic surgery between 2008 and 2018 for the management of fracture. INTERVENTION: Surgical treatment for the management of acetabular or pelvic fracture and blood transfusion when deemed clinically appropriate in the perioperative setting. MAIN OUTCOME MEASURES: Surgeon EBL and calculated blood loss (using the Gross formula, a Gross formula derivative, and the HB equation with both Moore and Nadler blood volume estimations). RESULTS: One hundred ninety-two patients (27%) received intraoperative blood transfusions. Surgeon EBL significantly differed from all formulas except the Gross/Nadler and the modified Gross/Nadler calculations. Gross and HB calculation methods yielded similar results in the overall cohort but yielded significantly different results in the subgroup analysis. Use of a corrective transfusion factor mildly improved correlation of the Gross equation with EBL. At high levels of blood loss, surgeon EBL predictions became more discordant with calculated blood loss values. When assessing only patients who did not receive transfusions, concordance improved. CONCLUSION: Blood loss in pelvic and acetabular surgery is challenging to quantify, and this study demonstrates discordance between formula predictions and surgeon-estimated blood loss. At higher levels of blood loss, this discrepancy worsens. This exploratory study highlights the need for the development of improved methods of quantifying blood loss in orthopaedic trauma surgery. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Patient-Reported Outcome Measurement Information System (PROMIS) Scores in Pediatric Idiopathic Toe Walkers.

BACKGROUND: Idiopathic toe walking (ITW) can result in early contact with the health care system and be distressing for patients and their families. The natural history of ITW is poorly characterized. Deciding how and when to intervene can be difficult.Patient-reported outcomes are utilized in the clinical setting to assess patient factors and indications that may better inform treatment plans. Patient-Reported Outcomes Measurement Information System (PROMIS) is an instrument designed to collect patient-reported outcomes. Minimum clinically important differences in PROMIS metrics have been established to facilitate clinical relevance and utility of these metrics. The purpose of this study was to characterize the patient perspective of ITW by utilizing the PROMIS scores. METHODS: Retrospective chart review was performed to identify children aged 5 to 17 with a diagnosis of ITW treated at a single tertiary care center between 2017 and 2020. Inclusion criteria were a diagnosis of ITW and completion of a PROMIS questionnaire. Exclusion criteria were neurologic disease, autism, and previous surgical treatment. Demographic, physical exam, treatment, and available motion analysis data were collected. PROMIS scores for the following domains were available: Mobility, Peer Relationships, and Pain Interference. RESULTS: Forty-five children were enrolled. Seventy-three percent of PROMIS scores were patient reported while the remainder were parent reported. PROMIS score means for the cohort by domain were Mobility: 45.2±8.2 ( P <0.000); Peer Relationships: 46.4±11.6 ( P =0.047); and Pain Interference: 47.4±9.5 ( P =0.67). Motion analysis data, available for 11 children, noted age-matched gait velocity negatively correlated ( rs =-0.652, P =0.03) with Peer Relationships. No correlations were found between other aspects of gait, body mass index, or limitations in dorsiflexion and PROMIS domains. Parents reported lower Mobility scores than children did. There were no other significant differences between patient-reported and parent-reported PROMIS scores. PROMIS scores did not differ significantly between those <10 years and those ≥10 years. CONCLUSION: In this cohort of 45 otherwise healthy children without other neurologic diagnoses, there are both clinically and statistically significant differences in PROMIS means between our cohort and the healthy age-matched population. These differences manifested in worse peer relationships and mobility scores. LEVEL OF EVIDENCE: Level IV.

Trends in Management of Pediatric Distal Radius Buckle Fractures.

BACKGROUND: Distal radius buckle fractures (DRBFx) represent nearly half of the pediatric wrist injuries. DRBFx are stable injury patterns that can typically be successfully managed with brief immobilization. The purpose of this study was to evaluate opinions and preferences of pediatric orthopaedic specialists regarding the management of DRBFx. METHODS: The POSNA Trauma Quality, Safety, and Value Initiative (QSVI) Committee developed a 20-question survey regarding the treatment of DRBFx in children. The survey was sent twice to all active and candidate POSNA members in June 2020 (n=1487). Questions focused on various aspects of treatment, including type and length of immobilization, follow-up, and radiographs and on potential concerns regarding patient/family satisfaction and pain control, medicolegal concerns, misdiagnosis, and mismanagement. RESULTS: A total of 317 participants completed the survey (response rate=21.3%). In all, 69% of all respondents prefer to use a removable wrist splint, with 76% of those in practice <20 years preferring removable wrist splints compared with 51% of those in practice >20 years (χ 2 =21.7; P <0.01). Overall, 85% of participants utilize shared decision-making in discussing management options with patients and their families. The majority of participants felt that the risk of complications associated with DRBFx was very low, but concern for misdiagnosis and mismanagement have required some respondents to perform closed or open reductions. CONCLUSIONS: In 2020, the majority of respondents treat DRBFx with removable splints (69%) for 3 or fewer weeks (55%), minimal follow-up (85%), and no reimaging (64%). This marks a dramatic shift from the 2012 POSNA survey when only 29% of respondents used removable splinting for DRBFx. LEVEL OF EVIDENCE: Level II.

Salmonella Osteomyelitis in a Pediatric Patient with a Proximal Humerus Fracture: A Case Report.

CASE: A 5-year-old previously healthy girl sustained a left proximal humerus fracture after a fall from a trampoline. The injury was initially treated nonoperatively, but during routine follow-up, the patient was found to have a previously unrecognized bony erosion at the fracture site. Workup was negative for neoplasm but instead demonstrated Salmonella osteomyelitis. The patient underwent debridement and treatment with antibiotics. CONCLUSION: This is an unusual presentation of a humerus fracture in a child with concomitant Salmonella osteomyelitis. Osteomyelitis is an important diagnostic consideration when considering bony erosions in the pediatric patient, even in those patients without apparent risk factors.

Outcome Metrics in the Treatment of Carpal Tunnel Syndrome: A Systematic Review.

BACKGROUND: The purpose of this systematic review was to determine the metrics used to assess outcomes after treatment for carpal tunnel syndrome. METHODS: We performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines of level I and II randomized controlled trials of treatment for carpal tunnel syndrome. We searched the PubMed/MEDLINE electronic database for studies on treatment of carpal tunnel syndrome from January 2008 to January 2018. A total of 105 studies were included in the final analysis. The metrics used to assess outcomes in each studies were collected, compared, and described. RESULTS: Nearly all the studies used a patient-reported outcome measure (PROM) to assess outcomes (94%). The most common PROMs used were the Boston Carpal Tunnel Questionnaire (60%) and the Visual Analog Scale for pain (51%). Electrophysiological testing and physical examination were also commonly used to assess outcomes (50% and 46%, respectively). Cost, sleep, and return to activities of daily living were assessed in a minority of studies (1%, 1%, and 5%, respectively). CONCLUSIONS: Successful treatment of carpal tunnel syndrome is commonly defined based on a PROM, highlighting recent efforts to measure outcomes from the patient's perspective. Other patient-centered metrics such as return to work and sleep quality, however, were rarely reported, whereas objective measures such as nerve conduction studies were prevalent. Further work is needed to determine patients' preferred method of measuring outcomes after treatment for carpal tunnel syndrome to inform goal-directed decision-making and treatment.

Methods of Quantifying Intraoperative Blood Loss in Orthopaedic Trauma Surgery: A Systematic Review.

OBJECTIVES: To collect and present the recently published methods of quantifying blood loss (BL) in orthopaedic trauma. DATA SOURCES: A systematic review of English-language literature in PubMed, Cochrane Library, and Scopus databases was conducted according to the PRISMA guidelines on articles describing the methods of determining BL in orthopaedic trauma published since 2010. STUDY SELECTION: English, full-text, peer-reviewed articles documenting intraoperative BL in an adult patient population undergoing orthopaedic trauma surgery were eligible for inclusion. DATA EXTRACTION: Two authors independently extracted data from the included studies. Articles were assessed for quality and risk of bias using the Cochrane Collaboration's tool for assessing risk of bias and ROBINS-I. DATA SYNTHESIS: The included studies proved to be heterogeneous in nature with insufficient data to make data pooling and analysis feasible. CONCLUSIONS: Eleven methods were identified: 6 unique formulas with multiple variations, changes in hemoglobin and hematocrit levels, measured suction volume and weighed surgical gauze, transfusion quantification, cell salvage volumes, and hematoma evacuation frequency. Formulas included those of Gross, Mercuriali, Lisander, Sehat, Foss, and Stahl, with Gross being the most common (25%). All formulas used blood volume estimation, determined by equations from Nadler (94%) or Moore (6%), and measure change in preoperative and postoperative blood counts. This systematic review highlights the variability in BL estimation methods published in current orthopaedic trauma literature. Methods of quantifying BL should be taken into consideration when designing and evaluating research.

An Unusual Presentation of Osteogenesis Imperfecta: A Case Report.

CASE: We report an 18-year-old patient with a clinical phenotype consistent with severe osteogenesis imperfecta (OI) with frequent fractures, short stature, shortening and bowing of extremities, and unusual radiographic features of severe fibrous dysplasia, including lytic lesions and a "ground-glass" appearance. Genetic testing for the patient was notable for a c.119C>T (p.Ser40Leu) variant in exon 1 of IFITM5 and a c.676C>A (Pro226Thr) variant in exon 5 of CREB3L1. CONCLUSION: This unusual skeletal presentation was in the setting of a rare IFITM5 mutation and represents a unique case of severe OI.

An Unusual Presentation of Inflammatory Shoulder Arthritis Associated with Nivolumab: A Case Report.

CASE: A 68-year-old woman with a history of stage IIIC (T3bN1bM0) melanoma with metastases to her right axilla status after 10 cycles of nivolumab presented with right shoulder pain. Radiographs showed a progressive erosive glenohumeral joint lesion. The workup was negative for metastasis and infection. Her clinical and radiographic findings were consistent with erosive arthritis. The patient underwent shoulder hemiarthroplasty and experienced substantial improvements. CONCLUSION: This is an unusual case of inflammatory arthritis associated with nivolumab, an antiprogrammed cell death protein 1, and is an important reminder of the musculoskeletal toxicities associated with immunotherapies.

Patient Willingness to Pay for Faster Return to Work or Smaller Incisions.

Background: Value-based health care models such as bundled payments and accountable care organizations can penalize health systems and physicians for excess costs leading to low-value care. Health systems can minimize these extra costs by constraining diagnostic (eg, magnetic resonance imaging utilization) or treatment options with debatable necessity in the setting of clinical equipoise. Instead of restricting more expensive treatments, it is plausible that health systems could instead recoup the extra costs of these treatments by charging patients supplementary out-of-pocket charges (cost sharing). The primary aim of this exploratory study was to assess hand surgery patient willingness to pay supplementary out-of-pocket charges for a procedure that theoretically leads to an earlier return to work or smaller incisions when there are 2 procedures that lead to similar results (clinical equipoise). Methods: A total of 122 patients completed a questionnaire that included demographic information, a financial distress assessment, a series of scenarios asking patients the degree to which they are willing to pay extra for the procedure choice, as well as their perspective of how much insurers should be responsible for these additional costs. Results: Patients were willing to pay out-of-pocket to some degree for a procedure that leads to earlier return to work and smaller incision size when compared with a similar alternative procedure, but noted that insurers should bear a greater burden of costs. Approximately 10% of patients were willing to pay maximum amounts ($2500+) for earlier return to work (3, 7, and 14 days earlier) and smaller incision sizes of any length. Conclusions: Some patients may be willing to pay out-of-pocket and cost share for procedures that lead to earlier return to work and smaller incisions in the setting of clinical equipoise. As such, when developing and implementing alternative payment models, health systems could potentially offer services with debatable necessity in the setting of equipoise for a supplementary out-of-pocket charge.

The obstetrical research landscape: a cross-sectional analysis of clinical trials from 2007-2020.

Background: Obstetrical complications affect more than a third of women globally, but are underrepresented in clinical research. Little is known about the comprehensive obstetrical clinical trial landscape, how it compares with other fields, or factors associated with the successful completion of obstetrical trials. Objective: This study aimed to characterize obstetrical clinical trials registered on ClinicalTrials.gov with the primary objective of identifying features associated with early discontinuation and results reporting. Study Design: This is a cross-sectional study with descriptive, logistic regression and Cox regression analyses of clinical trials registered on ClinicalTrials.gov. Our primary exposure variables were trial focus (obstetrical or nonobstetrical) and trial funding (industry, United States government, or academic). We conducted additional exploratory analyses of other trial features including design, enrollment, and therapeutic focus. We examined the associations of exposure variables and other trial features with 2 primary outcomes: early discontinuation and results reporting. Results: We downloaded data for all studies (N=332,417) registered on ClinicalTrials.gov from October 1, 2007, to March 9, 2020, from the Aggregate Analysis of ClinicalTrials.gov database. We excluded studies with a noninterventional design (n=63,697) and those registered before October 1, 2007 (n=45,209). A total of 4276 obstetrical trials (1.9%) (ie, interventional studies) and 219,235 nonobstetric trials (98.1%) were compared. Among all trials, 2.8% of academic-funded trials, 1.9% of United States government-funded trials, and 0.4% of industry-funded trials focused on obstetrics. The quantity of obstetrical trials increased over time (10.8% annual growth rate). Compared with nonobstetrical trials, obstetrical trials had a greater risk of early discontinuation (adjusted hazard ratio, 1.40; 95% confidence interval, 1.21-1.62; P<.0001) and similar odds of results reporting (adjusted odds ratio, 0.89; 95% confidence interval, 0.72-1.10; P=.19). Among obstetrical trials funders after controlling for confounding variables, United States government-funded trials were at the lowest risk of early discontinuation (United States government, adjusted hazard ratio, 0.23; 95% confidence interval, 0.07-0.69; P=.009; industry reference; academic, adjusted hazard ratio, 1.04; 95% confidence interval, 0.62-1.74; P=.88). Academic-funded trials had the lowest odds of results reporting after controlling for confounding variables (academic institutions, adjusted odds ratio, 0.39; 95% confidence interval, 0.22-0.68; P=.0009; industry reference; United States government, adjusted odds ratio, 1.06; 95% confidence interval, 0.53-2.09; P=.87). Conclusion: Obstetrical trials represent only 1.9% of all clinical trials in ClinicalTrials.gov and have comparatively poor completion. All stakeholders should commit to increasing the number of obstetrical trials and improving their completion and dissemination to ensure clinical research reflects the obstetrical burden of disease and advances maternal health.

MnTE-2-PyP disrupts Staphylococcus aureus biofilms in a novel fracture model.

Biofilm-associated infections in orthopedic surgery lead to worse clinical outcomes and greater morbidity and mortality. The scope of the problem encompasses infected total joints, internally fixed fractures, and implanted devices. Diagnosis is difficult. Cultures are often negative, and antibiotic treatments are ineffective. The infections resist killing by the immune system and antibiotics. The organized matrix structure of extracellular polymeric substances within the biofilm shields and protects the bacteria from identification and immune cell action. Bacteria in biofilms actively modulate their redox environment and can enhance the matrix structure by creating an oxidizing environment. We postulated that a potent redox-active metalloporphyrin MnTE-2-PyP (chemical name: manganese (II) meso-tetrakis-(N-methylpyridinium-2-yl) porphyrin) that scavenges reactive species and modulates the redox state to a reduced state, would improve the effect of antibiotic treatment for a biofilm-associated infection. An infected fracture model with a midshaft femoral osteotomy was created in C57B6 mice, internally fixed with an intramedullary 23-gauge needle and seeded with a biofilm-forming variant of Staphylococcus aureus. Animals were divided into three treatment groups: control, antibiotic alone, and combined antibioticplus MnTE-2-PyP. The combined treatment group had significantly decreased bacterial counts in harvested bone, compared with antibiotic alone. In vitro crystal violet assay of biofilm structure and corresponding nitroblue tetrazolium assay for reactive oxygen species (ROS) demonstrated that MnTE-2-PyP decreased the biofilm structure and reduced ROS in a correlated and dose-dependent manner. The biofilm structure is redox-sensitive in S. aureus and an ROS scavenger improved the effect of antibiotic therapy in model of biofilm-associated infections.

Patients Should Define Value in Health Care: A Conceptual Framework.

The main tenet of value-based health care is delivering high-quality care that is centered on the patient, improving health, and minimizing cost. Collaborative decision-making frameworks have been developed to help facilitate delivering care based on patient preferences (patient-centered care). The current value-based health care model, however, focuses on improving population health and overlooks the individuality of patients and their preferences for care. We highlight the importance of eliciting patient preferences in collaborative decision making and describe a conceptual framework that incorporates individual patients' preferences when defining value.

Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk.

RATIONALE: Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered. OBJECTIVES: To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women. METHODS: Characteristics of participants with low volumetric bone mineral density (vBMD) were identified and related to COPD and other risk factors. We tested associations of sex and COPD with both vBMD and fractures adjusting for age, race, body mass index (BMI), smoking, and glucocorticoid use. MEASUREMENTS AND MAIN RESULTS: vBMD by calibrated quantitative computed tomography (QCT), visually scored vertebral fractures, and severity of lung disease were determined from chest CT scans of 3,321 current and ex-smokers in the COPDGene study. Low vBMD as a surrogate for osteoporosis was calculated from young adult normal values. Male smokers had a small but significantly greater risk of low vBMD (2.5 SD below young adult mean by calibrated QCT) and more fractures than female smokers. Low vBMD was present in 58% of all subjects, was more frequent in those with worse COPD, and rose to 84% among subjects with very severe COPD. Vertebral fractures were present in 37% of all subjects and were associated with lower vBMD at each Global Initiative for Chronic Obstructive Lung Disease stage of severity. Vertebral fractures were most common in the midthoracic region. COPD and especially emphysema were associated with both low vBMD and vertebral fractures after adjustment for steroid use, age, pack-years of smoking, current smoking, and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated QCT identified more subjects with abnormal values than the standard dual-energy X-ray absorptiometry in a subset of subjects and correlated well with prevalent fractures. CONCLUSIONS: Male smokers, with or without COPD, have a significant risk of low vBMD and vertebral fractures. COPD was associated with low vBMD after adjusting for race, sex, BMI, smoking, steroid use, exacerbations, and age. Screening for low vBMD by using QCT in men and women who are smokers will increase opportunities to identify and treat osteoporosis in this at-risk population.