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Objective: To assess the health care utilization and cost of illness for osteoarthritis (OA) patients taking pain medications. Specifically, the goals were to estimate the direct health care and indirect costs of OA. Methods: A claims database of privately insured patients was used to identify OA patients. Prescription drug pain treatments included tramadol, cyclooxygenase-II inhibitors, and nonsteroidal anti-inflammatory drugs. Mean annual per patient costs were calculated from an employer's perspective. Results: OA patients were prescribed multiple drugs simultaneously and/or sequentially to manage pain. OA patients had a number of prevalent comorbid conditions. Average annual direct medical, drug, and indirect work loss costs were $8601, $2941, and $4603, respectively. Conclusions: There was a substantial payer burden associated with OA resulting from the drug, medical, and disability costs and OA-related comorbidities and high concomitant medication utilization. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to compare the medical services utilization and average annual direct (ie, medical and medication) and indirect (ie, work-loss) costs for employees with painful conditions to a random sample ('average employee'). METHODS: An employer administrative claims database (approximately 600,000 insured lives) was used to identify patients with ICD-9 codes for painful conditions. Direct costs were total employer medical and medication costs and indirect costs were associated with medically related absenteeism days and disability claims. RESULTS: Among employees with painful conditions, total costs were 1.5 to 3.5 times as high (P < 0.01) as those of the average employee (ie, 7088 US dollars to 16,874 US dollars compared with 4,849 US dollars) depending on the painful condition. CONCLUSIONS: Painful conditions are costly to employers, and better management/treatment of such conditions may help reduce the associated employer economic burden. [ABSTRACT FROM AUTHOR]

A 10-y-old spayed female Cavalier King Charles Spaniel dog was presented to the Veterinary Teaching Hospital because of recurrent chronic abscesses on the distal pelvic limbs, fever, lethargy, lameness of unknown etiology, and chronic pancreatitis. Sterile nodular panniculitis was diagnosed after an extensive workup, and the dog initially responded to immunosuppressive therapy, but relapse and spread of cutaneous lesions and acute lameness occurred after 11 mo, and euthanasia was elected. Postmortem examination confirmed hyalinizing pancreatic adenocarcinoma with pancreatitis, panniculitis, polyarthritis (PPP), and osteomyelitis. Histopathology and bacterial and fungal cultures were supportive of a sterile process, specifically the PPP syndrome, which is a rare, potentially life-threatening, systemic manifestation of pancreatic disease in both people and animals. To our knowledge, a clinicopathologic description of a hyalinizing pancreatic adenocarcinoma associated with this rare syndrome has not been reported previously in a dog., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Although the Schnur Sliding Scale (SSS) was not intended to be used by third-party payors, it has become the national standard for coverage decisions regarding macromastia treatment in patients of all ages. Adolescents were neither included in the cohort that created the SSS nor represented in subsequent validation studies., Methods: In this prospective study, health-related quality of life surveys were administered to girls and young women 12 to 21 years of age before and after reduction mammaplasty to treat macromastia. The SSS was used preoperatively to estimate the amount of tissue to be resected. Before and after surgery, participants completed the Short Form-36, version 2 (SF-36); the Rosenberg Self-Esteem Scale (RSES); the Breast-Related Symptoms Questionnaire (BRSQ); and the Eating Attitudes Test-26. Demographic data were compared, and linear regressions were used to evaluate the effect of resection amounts meeting the SSS value on survey scores., Results: Resection amounts fell below the SSS for 39 patients and above the SSS for 255 patients. The 2 groups had no differences in mean age or body mass index. Both groups had significant postoperative survey score improvements on the RSES, BRSQ, and 7 of 8 SF-36 domains (all P < 0.05). The groups had comparable postoperative survey scores on the RSES, BRSQ, and 8 of 8 SF-36 domains (all P > 0.05)., Conclusions: Adolescents undergoing reduction mammaplasty above and below the SSS experienced comparable physical and psychosocial benefits. These findings underscore the need for third-party payors to broaden coverage for adolescent reduction mammaplasty, as the common coverage cutoff has no effect on overall postoperative benefit., Clinical Question/level of Evidence: Risk, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [ 18 F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose - 2-[ 18 F]fluoro-2-deoxytrehalose ([ 18 F]FDT) - is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of [ 18 F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [ 18 F]FDT from the most globally-abundant organic 18 F-containing molecule, [ 18 F]FDG. The full, pre-clinical validation of both production method and [ 18 F]FDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade [ 18 F]FDT directly from the widely-available clinical reagent [ 18 F]FDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer., (© 2024. The Author(s).)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for the largest human pandemic in 100 years. Thirty-four vaccines are currently approved for use worldwide, and approximately 67% of the world population has received a complete primary series of one, yet countries are dealing with new waves of infections, variant viruses continue to emerge, and breakthrough infections are frequent secondary to waning immunity. Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23]) in an established African green monkey model of disease. Animals were vaccinated with V591 or the control vaccine (an equivalent MV-vectored vaccine with an irrelevant antigen) intramuscularly using a prime/boost schedule, followed by challenge with an early pandemic isolate of SARS-CoV-2 at 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well as S-specific T cells. Following the challenge, V591-vaccinated animals had lower infectious virus and viral (v) RNA loads in mucosal secretions and stopped shedding virus in these secretions earlier. vRNA loads were lower in these animals in respiratory and gastrointestinal tract tissues at necropsy. This correlated with a lower disease burden in the lungs as quantified by PET/CT at early and late time points post-challenge and by pathological analysis at necropsy.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the largest human pandemic in 100 years. Even though vaccines are currently available, countries are dealing with new waves of infections, variant viruses continue to emerge, breakthrough infections are frequent, and vaccine hesitancy persists. This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2. The candidate vaccine was used to vaccinate African green monkeys (AGMs). All vaccinated AGMs developed robust antigen-specific immune responses. After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs., Competing Interests: C.G., A.M., and N.E. are inventors on a patent application describing measles-vectored vaccine candidates against SARS-CoV-2. All other authors declare no financial or non-financial competing interests.

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress-a relationship that is continually being defined. Many studies investigating the effects of chronic stress on neuroinflammation in rodent models have identified significant changes in inflammatory modulators, including nuclear factor-κB (NF-κB) and toll-like receptors (TLRs), and cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6. This suggests that these are key inflammatory factors in the chronic stress response, which may contribute to the establishment of anxiety and depression-like symptoms. The behavioral and neurological effects of modulating inflammatory factors through gene knockdown (KD) and knockout (KO), and conventional and alternative medicine approaches, are discussed.

Background: Staphylococcus pseudintermedius and S. aureus are bacterial species of importance in veterinary medicine. The increasing incidence of antibiotic resistance necessitates the implementation of novel treatment modalities. Fluorescent light energy (FLE) is used as an adjunctive and primary treatment for canine pyoderma. However, no in vitro studies exist investigating its bactericidal effects against S. pseudintermedius or S. aureus., Objectives: To determine the bactericidal effects of FLE on S. pseudintermedius and S. aureus isolates., Materials and Methods: Two meticillin-susceptible S. pseudintermedius (MSSP) isolates, three meticillin-resistant S. pseudintermedius (MRSP) isolates and one meticillin-resistant S. aureus (MRSA) isolate were studied. A commercially available blue light-emitting diode (bLED) lamp and photoconverting hydrogel FLE system was used. All bacteria were exposed to five conditions following inoculation: (i) no treatment (control); (ii) blue light (bLED) once; (iii) bLED twice consecutively; (iv) FLE (bLED and photoconverting hydrogel) once; and (v) FLE (bLED and photoconverting hydrogel) twice consecutively. Each individual exposure was 2 min long., Results: No statistically significant differences (p < 0.05) were found for any treatment group when each bacterial isolate was evaluated individually, MSSP isolates were grouped, MRSP isolates were grouped, when all S. pseudintermedius isolates were combined, or when all isolates of both Staphylococcus species were combined., Conclusions and Clinical Relevance: While clinical success is reported when using FLE to treat Staphylococcus infections in animals, no in vitro antibacterial efficacy was identified for S. pseudintermedius or S. aureus under experimental conditions. The clinical success observed with FLE may be the result of a more complex in vivo response., (© 2024 ESVD and ACVD.)

Background: Drug interactions are significant considerations for intradermal testing (IDT). Trazodone (TRZ) is an anxiolytic and selective histaminergic (H 1 ) antagonist with no interaction in human prick tests; however, interaction in canine IDT is unknown., Hypothesis/objectives: Trazodone will not adversely affect intradermal histamine reactions in dogs., Animals: Fourteen nonanxious, nonatopic, healthy client-owned dogs were enrolled in this randomised, blinded, cross-over study., Materials and Methods: Dogs were randomised to receive low-dose TRZ (4 mg/kg) (Teva Pharmaceuticals), high-dose TRZ (8 mg/kg) or no TRZ per os two hours before intravenous sedation with dexmedetomidine (5 mcg/kg) (Dexdomitor; Zoetis). Intradermal testing was performed with five quadrupling dilutions of histamine (1:100,000 to 1:25,600,000 w/v; Greer) and 0.9% saline (Hospira), observing a minimum two weeks washout period between treatments. Two observers, who were blinded to treatment and the identity of the injections, evaluated each test using previously established subjective and objective methods., Results: The mean wheal diameter of histamine 1:1,600,000 w/v was significantly smaller with low-dose TRZ (4 mg/kg) compared to the control group (p = 0.048; repeated measures ANOVA with post hoc Tukey's test). For all other histamine dilutions and saline, mean wheal diameter was not significantly different among groups. There were no significant differences in the subjective scores of all histamine dilutions and saline (p > 0.05; Friedman test)., Conclusion and Clinical Relevance: A single oral dose of TRZ does not adversely affect intradermal histamine reactions in dogs., (© 2023 ESVD and ACVD.)

Background: Tuberous breast deformity is a nondiagnostic, descriptive term for a congenital breast difference that becomes apparent at puberty. Although the negative physical and psychosocial effects of macromastia and breast asymmetry are established, no studies to date have explored the impact of tuberous breasts on health-related quality of life (HRQoL) outcomes using a robust sample size., Methods: In this cross-sectional study, HRQoL surveys were administered to adolescent women with tuberous breasts and healthy female controls, aged 12-21 years. Surveys included the Short-Form 36v2, Rosenberg Self-Esteem Scale, and Eating Attitudes Test-26. Demographics were compared, and linear regressions were fit to determine the effect of tuberous breast deformity on survey scores, with body mass index (BMI) category as a covariate., Results: Thirty-four patients with tuberous breasts and 264 controls participated. Patients with tuberous breasts had higher mean BMI than controls ( P  < 0.05). After adjusting for differences in BMI category, patients with tuberous breasts scored lower than controls on the Rosenberg Self-Esteem Scale and in Short-Form 36v2 domains related to physical and psychological health ( P  < 0.05, all). Compared with controls, patients with tuberous breasts had a higher mean score on the Eating Attitudes Test-26 ( P  < 0.05)., Conclusions: Tuberous breast deformity may negatively impact patients' physical and psychosocial HRQoL and increase their risk for disordered eating and higher BMIs. It is imperative that healthcare providers and third-party payors understand tuberous breast deformity is not just a cosmetic issue and tailor care and coverage policies accordingly., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. This work was supported in part by the Plastic Surgery Foundation (grant number: 192776; July 2011)., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the most common cause of death in people living with human immunodeficiency virus (HIV). Intra-dermal Bacille Calmette-Guérin (BCG) delivery is the only licensed vaccine against tuberculosis; however, it offers little protection from pulmonary tuberculosis in adults and is contraindicated in people living with HIV. Intravenous BCG confers protection against Mtb infection in rhesus macaques; we hypothesized that it might prevent tuberculosis in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. Here intravenous BCG-elicited robust airway T cell influx and elevated plasma and airway antibody titres in both SIV-infected and naive animals. Following Mtb challenge, all 7 vaccinated SIV-naive and 9 out of 12 vaccinated SIV-infected animals were protected, without any culturable bacteria detected from tissues. Peripheral blood mononuclear cell responses post-challenge indicated early clearance of Mtb in vaccinated animals, regardless of SIV infection. These data support that intravenous BCG is immunogenic and efficacious in SIV-infected animals., (© 2023. The Author(s).)

Macromastia is a common condition that can lead to physical pain, emotional burden, and behavioral impairment, with significant decrements in quality of life. Reduction mammaplasty offers the only effective treatment of symptomatic macromastia, and patients experience significant improvements in their physical and psychosocial health through surgical correction. Although symptoms typically arise during adolescence, most women seeking surgical intervention do not undergo reduction mammaplasty until their fifth decade of life. Providers often delay surgery due to speculative concerns about emotional immaturity, postoperative breast regrowth, and future lactation performance. The strict guidelines related to age and body mass index imposed by insurance companies further restrict the options available to younger patients with macromastia. This review offers an evidence-based approach to treating macromastia in younger patients. After more than 15 years of treatment and research centered on adolescents and young adults with macromastia led by the senior author (B.I.L.), a pediatric plastic surgeon, we have found that reduction mammaplasty is a safe and effective treatment option for this patient population. It is our hope that our work will enable care providers to make data-supported decisions when treating younger patients with symptomatic macromastia., Competing Interests: Conflict of Interest: None declared., (Copyright © 2023 International Society of Plastic and Aesthetic Nurses. All rights reserved.)

Tuberculosis (TB) continues to be one of the deadliest infectious diseases in the world, causing ~1.5 million deaths every year. The World Health Organization initiated an End TB Strategy that aims to reduce TB-related deaths in 2035 by 95%. Recent research goals have focused on discovering more effective and more patient-friendly antibiotic drug regimens to increase patient compliance and decrease emergence of resistant TB. Moxifloxacin is one promising antibiotic that may improve the current standard regimen by shortening treatment time. Clinical trials and in vivo mouse studies suggest that regimens containing moxifloxacin have better bactericidal activity. However, testing every possible combination regimen with moxifloxacin either in vivo or clinically is not feasible due to experimental and clinical limitations. To identify better regimens more systematically, we simulated pharmacokinetics/pharmacodynamics of various regimens (with and without moxifloxacin) to evaluate efficacies, and then compared our predictions to both clinical trials and nonhuman primate studies performed herein. We used GranSim, our well-established hybrid agent-based model that simulates granuloma formation and antibiotic treatment, for this task. In addition, we established a multiple-objective optimization pipeline using GranSim to discover optimized regimens based on treatment objectives of interest, i.e., minimizing total drug dosage and lowering time needed to sterilize granulomas. Our approach can efficiently test many regimens and successfully identify optimal regimens to inform pre-clinical studies or clinical trials and ultimately accelerate the TB regimen discovery process., Competing Interests: None., (Copyright: © 2023 Budak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bacille Calmette-Guerin (BCG), the only approved Mycobacterium tuberculosis (Mtb) vaccine, provides limited durable protection when administered intradermally. However, recent work revealed that intravenous (i.v.) BCG administration yielded greater protection in macaques. Here, we perform a dose-ranging study of i.v. BCG vaccination in macaques to generate a range of immune responses and define correlates of protection. Seventeen of 34 macaques had no detectable infection after Mtb challenge. Multivariate analysis incorporating longitudinal cellular and humoral immune parameters uncovered an extensive and highly coordinated immune response from the bronchoalveolar lavage (BAL). A minimal signature predicting protection contained four BAL immune features, of which three remained significant after dose correction: frequency of CD4 T cells producing TNF with interferon γ (IFNγ), frequency of those producing TNF with IL-17, and the number of NK cells. Blood immune features were less predictive of protection. We conclude that CD4 T cell immunity and NK cells in the airway correlate with protection following i.v. BCG., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Pre-existing HIV infection increases tuberculosis (TB) risk in children. Antiretroviral therapy (ART) reduces, but does not abolish, this risk in children with HIV. The immunologic mechanisms involved in TB progression in both HIV-naive and HIV-infected children have not been explored. Much of our current understanding is based on human studies in adults and adult animal models. In this study, we sought to model childhood HIV/Mycobacterium tuberculosis (Mtb) coinfection in the setting of ART and characterize T cells during TB progression. Macaques equivalent to 4 to 8 year-old children were intravenously infected with SIVmac239M, treated with ART 3 months later, and coinfected with Mtb 3 months after initiating ART. SIV-naive macaques were similarly infected with Mtb alone. TB pathology and total Mtb burden did not differ between SIV-infected, ART-treated and SIV-naive macaques, although lung Mtb burden was lower in SIV-infected, ART-treated macaques. No major differences in frequencies of CD4 + and CD8 + T cells and unconventional T cell subsets (Vγ9+ γδ T cells, MAIT cells, and NKT cells) in airways were observed between SIV-infected, ART-treated and SIV-naive macaques over the course of Mtb infection, with the exception of CCR5+ CD4 + and CD8 + T cells which were slightly lower. CD4 + and CD8 + T cell frequencies did not differ in the lung granulomas. Immune checkpoint marker levels were similar, although ki-67 levels in CD8 + T cells were elevated. Thus, ART treatment of juvenile macaques, 3 months after SIV infection, resulted in similar progression of Mtb and T cell responses compared to Mtb in SIV-naive macaques., Competing Interests: The authors declare no conflict of interest.