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Background Stenotrophomonas maltophilia is an opportunistic pathogen observed in both nosocomial and community-onset infections. S. maltophilia is intrinsically resistant to many currently available broad-spectrum antibiotics and is often not included in antimicrobial resistance surveillance studies or stewardship programs' guidelines. Methods A retrospective cohort study of patients with S. maltophilia bloodstream infection (BSI) in the United States was conducted using the 2010–2015 US Premier Healthcare Database. This study described patient characteristics, infection characteristics, antibiotic treatment, and discharge status. Results S. maltophilia was the most common carbapenem-resistant, gram-negative pathogen causing BSIs in this database. Of 486 unique patients with S. maltophilia BSI, 44.6% were assessed as community-onset, 95% of cultures were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and 84% were susceptible to fluoroquinolones; 39.1% of patients received a potentially effective antibiotic (fluoroquinolone, doxycycline, ceftazidime, minocycline, or TMP-SMX) during the empiric treatment period (≤3 days post–index culture date), whereas 85.8% received a potential effective antibiotics during the definitive treatment period. The most common antibiotic received as definitive treatment was levofloxacin (48.9%). TMP-SMX was used infrequently empirically (10.5%) and in 38.3% during the definitive period. Compared with BSIs caused by other carbapenem-resistant gram-negative pathogens, S. maltophilia BSIs were more likely to be community-onset, and were more likely to be discharged to home and to have a lower mortality rate. Conclusions This study demonstrated that patients at risk for S. maltophilia BSI are highly variable and that standard of care is not clearly defined, leading to questions regarding the appropriateness of antibiotic treatment among patients. Further efforts are needed to better recognize and treat S. maltophilia BSI. [ABSTRACT FROM AUTHOR]

Wind power generation has seen a dramatic increase in the 21st century and the Department of Energy (DOE) envisions that wind energy will become a much larger part of overall power generation in the U.S. by 2050. Wind turbines have continued to grow in size during the last few decades with towers commonly built at a height of 80 m for typical utility-scale turbines in the Unites States, and this is accompanied by certain transportation and logistics challenges. The newly proposed tall tower technology has been designed to be cost-effective in assembling towers as high as 140 m from precast concrete module components that are capable of transport on the U.S. road system. This paper presents an alternative wind tower design with potential for reducing the overall levelized cost of energy (LCOE); it evaluates a hexagonal precast concrete wind tower solution that facilitates use of a taller wind turbine generator for harvesting stronger, steadier, and more frequent wind resources to increase wind energy production and lower the overall LCOE. An integrated team of industry experts was consulted to support development of a stochastic life cycle cost model using a parametric estimate of the cost and fabrication and assembly schedules of this new wind tower design concept as well as forecasting the projected revenue to be created by the new technology. The study concludes that this new design concept is a commercially viable solution, with an estimated LCOE savings ranging from 2% to 4% compared with the typical 80 m turbine deployed in the United States, and it also provides wind power potential to previously untapped regions in the country. This paper helps to inform energy developers, manufacturers, and policy makers, both regionally and nationally, of a possible economically feasible wind tower design solution. [ABSTRACT FROM AUTHOR]

Background: The relationship between vitamin D status and mortality in patients with osteoarthritis (OA) is unknown. This study investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among American adults with OA., Methods: This study included 2556 adults with OA from the National Health and Nutrition Examination Survey (2001-2014). Death outcomes were ascertained by linkage to National Death Index (NDI) records through 31 December 2015. Cox proportional hazards model and two-piecewise Cox proportional hazards model were used to elucidate the nonlinear relationship between serum 25(OH)D concentrations and mortality in OA patients, and stratified analyses were performed to identify patients with higher mortality risk., Results: During 16,606 person-years of follow-up, 438 all-cause deaths occurred, including 74 cardiovascular disease (CVD)-related and 78 cancer deaths. After multivariable adjustment, lower serum 25(OH)D levels were significantly and nonlinearly associated with higher risks of all-cause and CVD mortality among participants with OA. Furthermore, we discovered L-shaped associations between serum 25(OH)D levels and all-cause and CVD mortality, with mortality plateauing at 54.40 nmol/L for all-cause mortality and 27.70 nmol/L for CVD mortality. Compared to participants with 25(OH)D levels below the inflection points, those with higher levels had a 2% lower risk for all-cause mortality (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.96-0.99) and 17% lower risk for CVD mortality (HR 0.83, 95% CI 0.72-0.95)., Conclusions: Nonlinear associations of serum 25(OH)D levels with all-cause and CVD mortality were observed in American patients with OA. The thresholds of 27.70 and 54.40 nmol/L for CVD and all-cause mortality, respectively, may represent intervention targets for lowering the risk of premature death and cardiovascular disease, but this needs to be confirmed in large clinical trials., (© 2022. The Author(s).)

Background: Urinary tract infections (UTIs) are the most common infections caused by Gram-negative bacteria and represent a major healthcare burden. Carbapenem-resistant (CR) strains of Enterobacterales and non-lactose fermenting pathogens further complicate treatment approaches., Methods: We conducted a retrospective analysis of the US Premier Healthcare Database (2014-2019) in hospitalised adults with a UTI to estimate the healthcare burden of Gram-negative CR UTIs among patients with or without concurrent bacteraemia., Results: Among the 47,496 patients with UTI analysed, CR infections were present in 2076 (4.4%). Bacteraemia was present in 24.5% of all UTI patients, and 1.7% of these were caused by a CR pathogen. The most frequent CR pathogens were Pseudomonas aeruginosa (49.4%) and Klebsiella pneumoniae (14.2%). Patients with CR infections had a significantly longer hospital length of stay (LOS) (median [range] 8 [5-12] days vs 6 [4-10] days, P < 0.001), were less likely to be discharged home (38.4% vs 51.0%, P < 0.001), had a higher readmission rate (22.6% vs 13.5%, P < 0.001), and had greater LOS-associated charges (mean US$ 91,752 vs US$ 66,011, P < 0.001) than patients with carbapenem-susceptible (CS) infections, respectively. The impact of CR pathogens was greater in patients with bacteraemia (or urosepsis) and these CR urosepsis patients had a significantly higher rate of mortality than those with CS urosepsis (10.5% vs 6.0%, P < 0.001)., Conclusions: Among hospitalised patients with UTIs, the presence of a CR organism and bacteraemia increased the burden of disease, with worse outcomes and higher hospitalisation charges than disease associated with CS pathogens and those without bacteraemia.

Objective: Ospemifene is a nonsteroidal selective estrogen receptor modulator (SERM) for the treatment of moderate symptomatic vulvar and vaginal atrophy (VVA) due to menopause. A postauthorization safety study is currently examining the incidence of venous thromboembolism (VTE) among postmenopausal women receiving ospemifene or other SERM (raloxifene, bazedoxifene, or tamoxifen, for noncancer indications), or with untreated VVA., Methods: This interim analysis used the US MarketScan Commercial and Medicare Supplemental claims database from 2013 to 2017 to identify incident VTE. The incidence rate and 95% confidence interval of VTE during the first continuous course of treatment (or continuous untreated time for the untreated cohort) were calculated for each cohort overall and by age group, with sensitivity analyses examining incidence in the short term (up to 90 days) and long term (all available follow-up, regardless of treatment changes)., Results: Analyses included 8,188 ospemifene users, 11,777 other SERM users, and 220,242 women with untreated VVA. The incidence per 1,000 person-years and 95% confidence interval of VTE were 3.7 (1.7-7.1) for ospemifene, 11.5 (8.9-14.6) for other SERM, and 11.3 (10.8-11.7) for untreated VVA. Stratification by age and altering the time frame for analysis produced results with similar patterns to the primary analysis., Conclusions: This interim analysis of an ongoing study suggests a favorable safety profile for ospemifene with respect to VTE. Comparative analyses with covariate adjustment will be performed when data accrual is complete.

Background: Although griseofulvin is currently considered the primary antifungal agent used to treat tinea capitis in many countries, increasingly higher doses and longer durations of treatment are becoming necessary to achieve effective treatment. Alternative antifungal therapies with shorter/simpler treatment regimens may be important to develop for this indication., Objective: To compare the efficacy and safety of a new pediatric formulation of terbinafine hydrochloride oral granules with griseofulvin oral suspension in the treatment of tinea capitis., Method: Children (4-12 years of age) with clinically diagnosed and potassium hydroxide microscopy-confirmed tinea capitis were randomized in two identical studies (trial 1, trial 2) to once-daily treatment with terbinafine (5-8 mg/kg; n = 1040) or griseofulvin administered per label (10-20 mg/kg; n = 509) for a period of 6 weeks followed by 4 weeks of follow-up. End-of-study complete cure (negative fungal culture and microscopy with Total Signs and Symptoms Score [TSSS] = 0), and mycologic (negative culture and microscopy) and clinical cure (TSSS = 0) were primary and secondary efficacy variables, respectively. Efficacy analysis was based on pooled data using modified intent-to-treat population (those who received at least one dose of study drug and had positive baseline fungal culture, N = 1286). Safety assessments included monitoring of the frequency and severity of adverse events (AEs)., Results: Rates of complete cure and mycologic cure were significantly higher for terbinafine than for griseofulvin (45.1% vs 39.2% and 61.5% vs 55.5%, respectively; P < .05). A majority (86.7%) of patients received griseofulvin, 10 to 19.9 mg/kg per day; complete cure rate was not found to be higher among patients who received griseofulvin more than 20 mg/kg per day compared with those who received less than 20 mg/kg per day. Complete cure rate was statistically significantly greater for terbinafine compared to griseofulvin in trial 1 (46.23% vs 34.01%) but not in trial 2 (43.99% vs 43.46%). On the basis of pooled data, clinical cure was higher for terbinafine than for griseofulvin, but the difference was not found to be statistically significant (P = .10). Subgroup analyses revealed that terbinafine was significantly better than griseofulvin for all cure rates--mycologic, clinical, and complete--among patients with Trichophyton tonsurans but not Microsporum canis (P < .001). For M. canis, mycologic and clinical cure rates were significantly better with griseofulvin than with terbinafine (P < .05). Approximately 50% of patients in each group reported an AE; almost all were mild or moderate in severity. Nasopharyngitis, headache, and pyrexia were most common in both groups. There were no drug-related serious AEs, no deaths, and no significant effects on weight or laboratory parameters, including liver transaminases., Limitations: In retrospect, a difference in the distribution of infecting microorganisms between the two trials was a limitation. Stringent adherence to griseofulvin doses recommended by prescribing information but smaller than those used in current clinical practice, and exclusion of adjuvant therapies such as shampoos or topical agents, which are routinely used in practice, are other limitations., Conclusions: Data from this largest pediatric trial of terbinafine to date indicate that terbinafine is efficacious and well tolerated in the treatment of tinea capitis. Terbinafine is an effective alternative to griseofulvin against T. tonsurans tinea capitis.