Biocompatibility and Safety Assessment of Combined Topical Ozone and Antibiotics for Treatment of Infected Wounds.

Wound infections with antibiotic-resistant bacteria, particularly the Gram-negative strains, pose a substantial health risk for patients with limited treatment options. Recently topical administration of gaseous ozone and its combination with antibiotics through portable systems has been demonstrated to be a promising approach to eradicate commonly found Gram-negative strains of bacteria in wound infections. However, despite the significant impact of ozone in treating the growing number of antibiotic-resistant infections, uncontrolled and high concentrations of ozone can cause damage to the surrounding tissue. Hence, before such treatments could advance into clinical usage, it is paramount to identify appropriate levels of topical ozone that are effective in treating bacterial infections and safe for use in topical administration. To address this concern, we have conducted a series of in vivo studies to evaluate the efficacy and safety of a portable and wearable adjunct ozone and antibiotic wound therapy system. The concurrent ozone and antibiotics are applied through a wound interfaced gas permeable dressing coated with water-soluble nanofibers containing vancomycin and linezolid (traditionally used to treat Gram-positive infections) and connected to a portable ozone delivery system. The bactericidal properties of the combination therapy were evaluated on an ex vivo wound model infected with Pseudomonas aeruginosa, a common Gram-negative strain of bacteria found in many skin infections with high resistance to a wide range of currently available antibiotics. The results indicated that the optimized combination delivery of ozone (4 mg h-1) and topical antibiotic (200 µg cm-2) provided complete bacteria eradication after 6 h of treatment while having minimum cytotoxicity to human fibroblast cells. Furthermore, in vivo local and systemic toxicity studies (e.g., skin monitoring, skin histopathology, and blood analysis) on pig models showed no signs of adverse effects of ozone and antibiotic combination therapy even after 5 days of continuous administration. The confirmed efficacy and biosafety profile of the adjunct ozone and antibiotic therapy places it as a strong candidate for treating wound infection with antimicrobial-resistant bacteria and further pursuing human clinical trials.

Declining Geographic Access to High-Volume Revision Total Hip Arthroplasty Surgeons: A National Medicare Analysis.

BACKGROUND: While trends in the economics of revision THA (revTHA) procedures have been well-described from the standpoint of both hospitals and surgeons, their population-level effects of these trends on patient access are not well-understood. METHODS: The Medicare fee-for-service provider utilization and payment public use files were used to extract data for primary and revTHA for beneficiaries between 2013 and 2019. Primary and revTHA procedures were identified using the Healthcare Common Procedure Coding System code; 27130 for primaries and 27132, 27134, 27137, or 27138 for revisions. Geospatial analyses were performed by aggregating surgeon practice locations at the level of individual counties, hospital service areas, and hospital referral regions. RESULTS: The number of high-volume primary THA surgeons within the Medicare population increased by 17.6% over the study period (3,838 in 2013 to 4,515 in 2019). Conversely, the number of high-volume revTHA surgeons decreased by 36.1% (178 in 2013 to 129 in 2019). Linear regression revealed a significant increase and decrease in high-volume primary (ß = 109.07, P ≤ .001) and revision (ß = -13.04, P = .011) THA surgeons, respectively. Over the study period, the number of counties with at least 1 high-volume primary THA surgeon increased by 6.1% (1,194 to 1,267), while the number of counties with at least 1 high-volume revTHA surgeon decreased by 30.2% (159 to 111). CONCLUSION: The present findings of declining geographic access may represent a consequence of shifting economic incentives and declining reimbursements for the care of complicated revTHA patients.

Validity of Risk Assessment Instruments Among Juveniles Who Sexually Offended: Victim Age Matters.

Research has identified meaningful subtypes among the heterogeneous population of juveniles who sexually offended (JSO). However, studies that test the validity of risk assessment tools with JSO subtypes are limited. This study compared JSO who offended against a child victim (JSO-C) and JSO who offended against an adolescent/adult victim (JSO-A) with regard to rates of recidivism and the predictive validity of two risk assessment tools (Estimate of Risk of Adolescent Sexual Offense Recidivism [ERASOR] and Juvenile Sexual Offender Assessment Protocol-II [J-SOAP-II]). Data were analyzed from case files of 185 JSO-C and 297 JSO-A aged 12 to 18 years (M = 14.11, SD = 1.44) from a consecutive sample of JSO with contact sexual offenses. A total of 34 (7.1%) juveniles reoffended sexually, with no significant difference between the subtypes. The present results suggest that the ERASOR, particularly the structured professional judgment, and to a lesser degree the J-SOAP-II are better suited to predicting sexual recidivism in JSO-A than in JSO-C.

Does Increasing Patient Complexity Have an Effect on Medical Outcomes and Lengths-of-Stay after Total Knee Arthroplasty?

A greater number of medically complex patients with multiple comorbidities are now more readily considered for total knee arthroplasty (TKA). Therefore, the purpose of this study was to determine whether comorbidity burden, measured with the Elixhauser Comorbidity Index (ECI), correlated with 90-day medical complications and longer in-hospital lengths-of-stay (LOS) in TKA patients. The PearlDiver supercomputer was queried for all primary TKA patients in the Medicare Standard Analytic Files from 2005 to 2014 using International Classification of Disease, 9th edition codes. Patients were included based on ECI scores, ranging from 1 to 5. ECI 1 patients served as the control cohort, while ECI 2, 3, 4, and 5 patients were considered study cohorts. Each study cohort was matched based on age and gender to the control cohort, resulting in a total of 715,398 patients included for analysis (ECI 1, n = 144,072; ECI 2, n = 144,072; ECI 3, n = 144,072; ECI 4, n = 144,072; ECI 5, n = 139,110). Logistic regression analyses were performed to compare 90-day medical complications and Welch's t-tests were performed to compare LOS between the cohorts. Patients with higher ECI scores were more likely to develop medical complications and have longer LOS compared with matched patients in the control cohort. Compared with matched ECI 1 patients, patients with ECI scores of 2 (odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.14-1.24), 3 (OR: 1.27, 95% CI: 1.21-1.32), 4 (OR: 1.32, 95% CI: 1.27-1.38), and 5 (OR: 1.33, 95% CI: 1.27-1.39) were significantly more likely to develop 90-day medical complications. Additionally, the mean LOS of patients in the ECI 2 (2.59 ± 1.49 vs. 2.73 ± 1.52 days), ECI 3 (2.59 ± 1.49 vs. 2.88 ± 1.51 days; p < 0.001), ECI 4 (2.59 ± 1.49 vs. 3.01 ± 1.56 days; p < 0.001), and ECI 5 (2.61 ± 1.49 vs. 3.14 ± 1.61 days; p < 0.001) groups were significantly longer than the mean LOS in the control ECI 1 group. In an increasingly complex patient population, associations between comorbidities and outcomes after TKA procedures can guide providers on how to modify their pre- and postoperative care. These results demonstrate that higher ECI scores are associated with a greater likelihood of 90-day medical complications and longer in-hospital LOS.

Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry.

The International Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry (NCT01374360) was initiated to optimize patient management by collecting data regarding disease burden, progression, and clinical outcomes. Herein, we report updated baseline demographics, clinical characteristics, disease burden data, and observed trends regarding clone size in the largest cohort of Registry patients. Patients with available data as of July 2017 were stratified by glycosylphosphatidylinositol (GPI)-deficient granulocyte clone size (< 10%, ≥ 10%-< 50%, and ≥ 50%). All patients were untreated with eculizumab at baseline, defined as date of eculizumab initiation or date of Registry enrollment (if never treated with eculizumab). Outcomes assessed in the current analysis included proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVEs; including thrombotic events [TEs]), bone marrow failure (BMF), red blood cell (RBC) transfusions, and PNH-related symptoms. A total of 4439 patients were included, of whom 2701 (60.8%) had available GPI-deficient granulocyte clone size data. Among these, median clone size was 31.8% (1002 had < 10%; 526 had ≥ 10%-< 50%; 1173 had ≥ 50%). There were high proportions of patients with HDA (51.6%), history of MAVEs (18.8%), BMF (62.6%), RBC transfusion (61.3%), and impaired renal function (42.8%). All measures except RBC transfusion history significantly correlated with GPI-deficient granulocyte clone size. A large proportion of patients with GPI-deficient granulocyte clone size < 10% had hemolysis (9.7%), MAVEs (10.2%), HDA (9.1%), and/or PNH-related symptoms. Although larger GPI-deficient granulocyte clone sizes were associated with higher disease burden, a substantial proportion of patients with smaller clone sizes had history of MAVEs/TEs.

Comparison of food consumption and nutrient intake assessed with three dietary assessment methods: results of the German National Nutrition Survey II.

PURPOSE: Comparison of food consumption, nutrient intake and underreporting of diet history interviews, 24-h recalls and weighed food records to gain further insight into specific strength and limitations of each method and to support the choice of the adequate dietary assessment method. METHODS: For 677 participants (14-80 years) of the German National Nutrition Survey II confidence intervals for food consumption and nutrient intake were calculated on basis of bootstrapping samples, Cohen's d for the relevance of differences, and intraclass correlation coefficients for the degree of agreement of dietary assessment methods. Low energy reporters were identified with Goldberg cut-offs. RESULTS: In 7 of 18 food groups diet history interviews showed higher consumption means than 24-h recalls and weighed food records. Especially mean values of food groups perceived as socially desirable, such as fruit and vegetables, were highest for diet history interviews. For "raw" and "cooked vegetables", the diet history interviews showed a mean consumption of 144 and 109 g/day in comparison with 68 and 70 g/day in 24-h recalls and 76 and 75 g/day in weighed food records, respectively. For "fruit", diet history interviews showed a mean consumption of 256 g/day in comparison with 164 g/day in 24-h recalls and 147 g/day in weighed food records. No major differences regarding underreporting of energy intake were found between dietary assessment methods. CONCLUSIONS: With regard to estimating food consumption and nutrient intake, 24-h recalls and weighed food records showed smaller differences and better agreement than pairwise comparisons with diet history interviews.

Survey of Patient Insurance Status on Access to Specialty Foot and Ankle Care Under the Affordable Care Act.

BACKGROUND: The purpose of this study was to assess the effect of insurance type (Medicaid, Medicare, and private insurance) on access to foot and ankle surgeons for total ankle arthroplasty. METHODS: We called 240 foot and ankle surgeons who performed total ankle arthroplasty in 8 representative states (California, Massachusetts, Ohio, New York, Florida, Georgia, Texas, and North Carolina). The caller requested an appointment for a fictitious patient to be evaluated for a total ankle arthroplasty. Each office was called 3 times to assess the responses for Medicaid, Medicare, and BlueCross. From each call, we recorded appointment success or failure and any barriers to an appointment, such as need for a referral. RESULTS: Patients with Medicaid were less likely to receive an appointment compared to patients with Medicare (19.8% vs 92.0%, P < .0001) or BlueCross (19.8% vs 90.4%, P < .0001) and experienced more requests for referrals compared to patients with Medicare (41.9% vs 1.6%, P < .0001) or BlueCross (41.9% vs 4%, P < .0001). Waiting periods were longer for patients with Medicaid compared to those with Medicare (22.6 days vs 11.7 days, P = .004) or BlueCross (22.6 days vs 10.7 days, P = .001). Reimbursement rates did not correlate with appointment success rate or waiting period. CONCLUSION: Despite the passage of the PPACA, patients with Medicaid continue to have difficulty finding a surgeon who will provide care, increased need for a primary care referral, and longer waiting periods for appointments. LEVEL OF EVIDENCE: Level II, prognostic study.

Decoding properties of tRNA leave a detectable signal in codon usage bias.

MOTIVATION: The standard genetic code translates 61 codons into 20 amino acids using fewer than 61 transfer RNAs (tRNAs). This is possible because of the tRNA's ability to 'wobble' at the third base to decode more than one codon. Although the anticodon-codon mapping of tRNA to mRNA is a prerequisite for certain codon usage indices and can contribute to the understanding of the evolution of alternative genetic codes, it is usually not determined experimentally because such assays are prohibitively expensive and elaborate. Instead, the codon reading is approximated from theoretical inferences of nucleotide binding, the wobble rules. Unfortunately, these rules fail to capture all of the nuances of codon reading. This study addresses the codon reading properties of tRNAs and their evolutionary impact on codon usage bias. RESULTS: Using three different computational methods, the signal of tRNA decoding in codon usage bias is identified. The predictions by the methods generally agree with each other and compare well with experimental evidence of codon reading. This analysis suggests a revised codon reading for cytosolic tRNA in the yeast genome (Saccharomyces cerevisiae) that is more accurate than the common assignment by wobble rules. The results confirm the earlier observation that the wobble rules are not sufficient for a complete description of codon reading, because they depend on genome-specific factors. The computational methods presented here are applicable to any fully sequenced genome. AVAILABILITY: By request from the author. CONTACT: alexander.roth@isb-sib.ch.