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INTRODUCTION: Distinguishing between septic arthritis and crystal arthropathy flares can be challenging. The purpose of this study was to determine how the presence of synovial crystals affects the diagnostic criteria of septic arthritis. METHODS: A retrospective review identified patients undergoing joint aspirations to rule out native septic arthritis. Differences between septic arthritis presenting with and without synovial crystals were analyzed. A receiver-operating characteristic curve was plotted for laboratory markers to determine the area under the curve, or diagnostic accuracy, for septic arthritis and to evaluate thresholds that maximized sensitivity and specificity. RESULTS: There were 302 joint aspirations in 267 patients. Septic arthritis was diagnosed in 17.9% (54/302). Patients with synovial crystals were less likely to have septic arthritis (4.2% [5/119] vs. 26.8% [49/183], P < 0.0001). Septic arthritis in patients with no synovial crystals was associated with fever and a higher synovial white blood cell (WBC) count, synovial polymorphonuclear cell percentage (PMN%), serum WBC, and C-reactive protein (CRP) ( P < 0.05). Septic arthritis in patients with synovial crystals was only associated with inability to bear weight and a higher synovial WBC and CRP ( P < 0.05). Synovial PMN% was considered nondiagnostic of septic arthritis (area under the curve 0.56) in patients with crystals while synovial WBC and CRP had acceptable (0.76) and excellent (0.83) diagnostic utility, respectively. The WBC and CRP value thresholds that maximized sensitivity and specificity for septic arthritis were greater in patients with crystals (21,600 vs. 17,954 cells/µL and 125 vs. 69 mg/L, respectively). DISCUSSION: The presence of synovial crystals reduced the likelihood of septic arthritis and altered the laboratory diagnostic criteria. PMN% was nondiagnostic in the setting of synovial crystals.

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Physical activity is a first-line treatment for polycystic ovary syndrome (PCOS). Resistance or aerobic exercise improves metabolic complications, reproductive outcomes, and quality of life in PCOS. DNA methylation reprogramming during exercise may be the major modifier behind these changes. We sought to evaluate genome-wide DNA methylation changes after supervised resistance and aerobic exercise in women with PCOS. Exercises were performed in 56 women with PCOS (resistance, n = 30; aerobic, n = 26), for 16 weeks (wks), three times per week, in 50-minute to one-hour sessions. Anthropometric indices and hormonal and metabolic parameters were measured before and after training. Genome-wide leukocyte DNA methylation was analysed by Infinium Human MethylationEPIC 850K BeadChip microarrays (Illumina). Both resistance and aerobic exercise improved anthropometric indices, metabolic dysfunction, and hyperandrogenism in PCOS after the training programme, but no differences were observed between the two exercises. Resistance and aerobic exercise increased genome-wide DNA methylation, although resistance changed every category in the CpG island context (islands, shores, shelve, and open sea), whereas aerobic exercise altered CpG shores and the open sea. Using a stringent FDR (>40), 6 significantly differentially methylated regions (DMRs) were observed in the resistance exercise cohort and 14 DRMs in the aerobic cohort, all of which were hypermethylated. The increase in genome-wide DNA methylation may be related to the metabolic and hormonal changes observed in PCOS after resistance and aerobic exercise. Since the mammalian genome is hypermethylated globally to prevent genomic instability and ageing, resistance and aerobic exercise may promote health and longevity through environmentally induced epigenetic changes.

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Two low-cost pragmatic interventions (change in the options in the electronic health record; change in the electronic health record plus education plus feedback comparing prescribing with peers) to improve prescribing of guideline-concordant short antibiotic durations for children 2 years and older with uncomplicated acute otitis media were highly effective and results were sustained 18 months after discontinuation of the active components of the interventions.

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OBJECTIVE: To compare the effectiveness of 2 interventions in improving prescribing of guideline-concordant durations of therapy for acute otitis media (AOM). STUDY DESIGN: This was a quasi-experimental mixed methods analysis that compared a bundled quality improvement intervention consisting of individualized audit and feedback, education, and electronic health record (EHR) changes to an EHR-only intervention. The bundle was implemented in 3 pediatric clinics from January to August 2020 and an EHR-only intervention was implemented in 6 family medicine clinics. The primary outcome measure was prescription of an institutional guideline-concordant 5-day duration of therapy for children ≥2 years of age with uncomplicated AOM. Propensity score matching and differences-in-differences analysis weighted with inverse probability of treatment were completed. Implementation outcomes were assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance Framework. Balance measures included treatment failure and recurrence. RESULTS: In total, 1017 encounters for AOM were included from February 2019 to August 2020. Guideline-concordant prescribing increased from 14.4% to 63.8% (difference = 49.4%) in clinics that received the EHR-only intervention and from 10.6% to 85.2% (difference = 74.6%) in clinics that received the bundled intervention. In the adjusted analysis, the bundled intervention improved guideline-concordant durations by an additional 26.4% (P < .01) compared with the EHR-only intervention. Providers identified EHR-prescription field changes as the most helpful components. There were no differences in treatment failure or recurrence rates between baseline and either intervention. CONCLUSIONS: Both interventions resulted in improved prescribing of guideline-concordant durations of antibiotics. The bundled intervention improved prescribing more than an EHR-only intervention and was acceptable to providers.

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OBJECTIVE: To study the global DNA methylation pattern in spermatozoa of patients with varicocele as well as investigate their semen quality. DESIGN: Prospective observational case-control study. SETTING: University-affiliated hospital. PATIENT(S): A total of 26 men with varicocele and 26 fertile men without the disorder. INTERVENTIONS: Analysis of semen quality and sperm DNA methylation patterns. MAIN OUTCOME MEASURE(S): Semen quality evaluated by semen analysis, and sperm DNA methylation patterns investigated using the Infinium MethylationEPIC BeadChip platform. RESULT(S): Men with varicocele displayed decreased semen quality. The sperm DNA methylation analysis showed that men with varicocele exhibit global hypomethylation in comparison with the control group. A total of 59 differentially methylated CpG sites were identified, most of them hypomethylated in the varicocele group. In regional analyses, 1,695 DNA regions were differentially methylated in men with varicocele. These regions show associations with gamete generation, meiotic and meiosis cell cycle, and semen quality based on gene ontology analysis. CONCLUSION(S): Gene ontology results suggest that changes in methylation may be associated with the low semen quality phenotype observed in some varicocele patients because the observed differentially methylated regions in varicocele patients are related to male reproductive pathways. Additionally, the varicocele grade may influence the magnitude of global sperm DNA methylation change. To our knowledge, this is the first report analyzing changes at a regional or CpG-specific level in men with varicocele.

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OBJECTIVE: To determine the frequency that non-first-line antibiotics, safety-net antibiotic prescriptions (SNAPS), and longer than recommended durations of antibiotics were prescribed for children ≥2 years of age with acute otitis media and examine patient and system level factors that contributed to these outcomes. STUDY DESIGN: Children age ≥2 years with acute otitis media seen at Denver Health Medical Center outpatient locations from January to December 2018 were included. The percentages of patients who received first-line antibiotics, SNAPs, and recommended durations of antibiotics were determined. Factors associated with non-first-line and longer than recommended antibiotic durations were evaluated using multivariate logistic regression modeling. RESULTS: Of the 1025 visits evaluated, 98.0% were prescribed an antibiotic; only 4.5% of antibiotics were SNAPs. Non-first-line antibiotics were prescribed to 18.8% of patients. Most antibiotic durations (94.1%) were longer than the institution recommended 5 days and 54.3% were ≥10 days. Private insurance was associated with non-first-line antibiotics (aOR, 1.89; 95% CI, 1; 14-3.14, P = .01). Patients who were younger (2-5 years; aOR 2.01; 95% CI, 1.32-3.05; P < .001) or seen in emergency/urgent care sites (aOR, 1.73; 95% CI, 1.26-2.38; P < .001) were more likely to receive ≥10 days of antibiotic compared with those in pediatric clinics. CONCLUSIONS: Antibiotic stewardship interventions that emphasize the duration of antibiotic therapy as well as the use of SNAPs or observation may be higher yield than those focusing on first-line therapy alone. Numerous system and patient level factors are associated with off-guideline prescribing.

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Honey bees can be found all around the world and fulfill key pollination roles within their natural ecosystems, as well as in agriculture. Most species are typically docile, and most interactions between humans and bees are unproblematic, despite their ability to inject a complex venom into their victims as a defensive mechanism. Nevertheless, incidences of bee stings have been on the rise since the accidental release of Africanized bees to Brazil in 1956 and their subsequent spread across the Americas. These bee hybrids are more aggressive and are prone to attack, presenting a significant healthcare burden to the countries they have colonized. To date, treatment of such stings typically focuses on controlling potential allergic reactions, as no specific antivenoms against bee venom currently exist. Researchers have investigated the possibility of developing bee antivenoms, but this has been complicated by the very low immunogenicity of the key bee toxins, which fail to induce a strong antibody response in the immunized animals. However, with current cutting-edge technologies, such as phage display, alongside the rise of monoclonal antibody therapeutics, the development of a recombinant bee antivenom is achievable, and promising results towards this goal have been reported in recent years. Here, current knowledge on the venom biology of Africanized bees and current treatment options against bee envenoming are reviewed. Additionally, recent developments within next-generation bee antivenoms are presented and discussed.

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OBJECTIVES: The incidence of cutaneous abscesses has increased markedly since the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Injection drug use is a risk factor for abscesses and may affect the microbiology and treatment of these infections. In a cohort of patients hospitalized with cutaneous abscesses in the era of CA-MRSA, the objectives were to compare the microbiology of abscesses between injection drug users and non-injection drug users and evaluate antibiotic therapy started in the emergency department (ED) in relation to microbiologic findings and national guideline treatment recommendations. METHODS: This was a secondary analysis of two published retrospective cohorts of patients requiring hospitalization for acute bacterial skin infections between January 1, 2007, and May 31, 2012, in seven academic and community hospitals in Colorado. In the subgroup of patients with cutaneous abscesses, microbiologic findings and the antibiotic regimens started in the ED were compared between injection drug users and non-injection drug users. Antibiotic regimens involving multiple agents, lack of activity against MRSA, or an agent with broad Gram-negative activity were classified as discordant with Infectious Diseases Society of America (IDSA) guideline treatment recommendations. RESULTS: Of 323 patients with cutaneous abscesses, 104 (32%) occurred in injection drug users. Among the 235 cases where at least one microorganism was identified by culture, S. aureus was identified less commonly among injection drug users compared with non-injection drug users (55% vs. 75%, p = 0.003), with similar patterns observed for MRSA (33% vs. 47%, p = 0.054) and methicillin-susceptible S. aureus (17% vs. 26%, p = 0.11). In contrast to S. aureus, streptococcal species (53% vs. 25%, p < 0.001) and anaerobic organisms (29% vs. 10%, p < 0.001) were identified more commonly among injection drug users. Of 88 injection drug users and 186 non-injection drug users for whom antibiotics were started in the ED, the antibiotic regimens were discordant with IDSA guideline recommendations in 47 (53%) and 101 (54%), respectively (p = 0.89). In cases where MRSA was ultimately identified, the antibiotic regimen started in the ED lacked activity against this pathogen in 14% of cases. CONCLUSIONS: Compared with non-injection drug users, cutaneous abscesses in injection drug users were less likely to involve S. aureus, including MRSA, and more likely to involve streptococci and anaerobes; however, MRSA was common in both groups. Antibiotic regimens started in the ED were discordant with national guidelines in over half of cases and often lacked activity against MRSA when this pathogen was present.

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