Influence of Body Weight Category on Outcomes in Candidemia Patients Treated With Anidulafungin

BACKGROUND: Case reports and pharmacokinetic data suggest off-label echinocandin dosing may be needed to reach adequate serum concentrations in obese patients. Few outcome studies exist evaluating this population. OBJECTIVES: Of this study were to (1) determine the association of body mass index (BMI) with clinical outcomes of candidemia patients on standard doses of anidulafungin and (2) characterize fungal infections by body weight. METHODS: A retrospective cohort was conducted to evaluate hospitalized patients treated for candidemia with anidulafungin at Food and Drug Administration-labeled dosing for at least 72 hours from January 1, 2014, through January 31, 2018. Candidemia was diagnosed by blood culture or T2 magnetic resonance (T2MR). Patients were compared according to BMI category. RESULTS: One hundred seventy-three patients were included. CONCLUSION: There was no difference detected in mortality among patients with candidemia across BMI category. Larger studies are needed to confirm whether standard doses of anidulafungin are sufficient for candidemia in obese patients

Respiratory culture nudge improves antibiotic prescribing for Moraxella catarrhalis and Haemophilus influenzae lower respiratory tract infections

We compared optimal antibiotic prescribing before and after implementing an interpretive β-lactamase microbiology comment for Haemophilus influenzae and Moraxella catarrhalis in lower respiratory-tract infections. The postintervention group was associated with 5-fold increased odds of optimal de-escalation (adjusted odds ratio, 5.03; 95% confidence interval, 2.57-9.87)

Optimizing preoperative antibiotics in patients with β-lactam allergies: A role for pharmacy

PURPOSE: Patients with a reported β-lactam allergy (BLA) are often given alternative perioperative antibiotic prophylaxis, increasing risk of surgical site infections (SSIs), acute kidney injury (AKI), and Clostridioides difficile infection (CDI). The purpose of this study was to implement and evaluate a pharmacist-led BLA clarification interview service in the preoperative setting. METHODS: A pharmacist performed BLA clarification telephone interviews before elective procedures from November 2018 to March 2019. On the basis of allergy history and a decision algorithm, first-line preoperative antibiotics, alternative antibiotics, or allergy testing referral was recommended. The pharmacist intervention (PI) group was compared to a standard of care (SOC) group who underwent surgery from November 2017 to March 2018. RESULTS: Eighty-seven patients were included, with 50 (57%) and 37 (43%) in the SOC and PI groups, respectively. The most common surgeries included orthopedic surgery in 41 patients (47%) and neurosurgery in 17 patients (20%). In the PI group, all BLA labels were updated after interview. Twenty-three patients were referred for allergy testing, 12 of the 23 (52%) completed BLA testing, and penicillin allergies were removed for 9 of the 12 patients. Overall, 28 of the 37 (76%) pharmacy antibiotic recommendations were accepted. Cefazolin use significantly increased from 28% to 65% after the intervention (P = 0.001). SSI occurred in 5 (10%) patients in the SOC group and no patients in the PI group (P = 0.051). All of these SSIs were associated with alternative antibiotics. Incidence of AKI and CDI was similar between the groups. No allergic reactions occurred in either group. CONCLUSION: Implementation of a pharmacy-driven BLA reconciliation significantly increased β-lactam preoperative use without negative safety outcomes

The long-term sustainability of a respiratory culture nudge

Resource-intensive interventions and education are susceptible to a lack of long-term sustainability and regression to the mean. The respiratory culture nudge changed reporting to Commensal Respiratory Flora only: No S. aureus/MRSA or P. aeruginosa. This study demonstrated sustained reduction in broad-spectrum antibiotic duration and long-term sustainability 3 years after implementation

"Women's rights, the European Court and Supranational Constitutionalism"

This analysis examines supranational constitutionalism in the European Union. In particular, the study focuses on the role of the European Court of Justice in the creation of women’s rights. I examine the interaction between the Court and member state governments in legal integration, and also the integral role that women’s advocates – both individual activists and groups – have played in the development of EU social provisions. The findings suggest that this litigation dynamic can have the effect of fueling the integration process by creating new rights that may empower social actors and EU organizations, with the ultimate effect of diminishing member state government control over the scope and direction of EU law. This study focuses specifically on gender equality law, yet provides a general framework for examining the case law in subsequent legal domains, with the purpose of providing a more nuanced understanding of supranational governance and constitutionalism

Early Short Course Corticosteroids in Hospitalized Patients with COVID-19

BACKGROUND: There is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. METHODS: We conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up. RESULTS: We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively.The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (8 vs. 5 days, p \u3c 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.41; 95% CI [0.22 - 0.77]). CONCLUSION: An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes

COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases.

MOTIVATION: COVID-19 has several distinct clinical phases: a viral replication phase, an inflammatory phase, and in some patients, a hyper-inflammatory phase. High mortality is associated with patients developing cytokine storm syndrome. Treatment of hyper-inflammation in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce mortality. RESULTS: We analyzed the changes in the gene expression, pathways and putative mechanisms induced by SARS-CoV2 in NHBE, and A549 cells, as well as COVID-19 lung vs. their respective controls. We used these changes to identify FDA approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. We identified methylprednisolone (MP) as a potential leading therapy. The results were then confirmed in five independent validation data sets including Vero E6 cells, lung and intestinal organoids, as well as additional patient lung sample vs. their respective controls. Finally, the efficacy of MP was validated in an independent clinical study. Thirty-day all-cause mortality occurred at a significantly lower rate in the MP-treated group compared to control group (29.6% vs. 16.6%, p = 0.027). Clinical results confirmed the in silico prediction that MP could improve outcomes in severe cases of COVID-19. A low number needed to treat (NNT = 5) suggests MP may be more efficacious than dexamethasone or hydrocortisone. AVAILABILITY: iPathwayGuide is available at https://ipathwayguide.advaitabio.com/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

The Effects of Acute Beetroot Juice Ingestion on Exercise and Cognitive Performance in Female Athletes

Nitrate-rich beetroot juice can enhance intense exercise performance which is attributed to enhanced skeletal muscle contractility. However, limited data exist in females and it is unknown whether dietary nitrate has an ergogenic effect in this population. PURPOSE: To investigate the potential effects of acute nitrate ingestion on a battery of exercise performance and cognitive tests before and after fatiguing intermittent running exercise. METHODS: Fifteen female team-sport athletes were assigned in a randomized, double-blind, crossover design to consume nitrate-rich beetroot juice (BR; 12 mmol of nitrate) and nitrate-depleted beetroot juice (PL; 0.10 mmol of nitrate) 2.5 h prior to performing the exercise protocol, with a washout period of 7 days between trials. Running 10 m and 20 m sprint split times, sprint reaction time, upper- and lower-body power, handgrip strength, and cognitive flexibility were measured before and after the Yo-Yo intermittent recovery level 1 (Yo-Yo IR1) test, during which performance and rate of perceived exertion were recorded. RESULTS: There were no significant differences in any performance outcome or cognitive flexibility (P \u3e 0.05). CONCLUSION: These findings indicate that acute nitrate ingestion does not influence performance in sprints, intermittent running, power, strength, or cognitive function in young adult female team-sport athletes

Food insecurity and the role of food assistance programs in supporting diet quality during the COVID-19 pandemic in Massachusetts

BackgroundEconomic and supply chain shocks resulting from the COVID-19 pandemic in 2020 led to substantial increases in the numbers of individuals experiencing food-related hardship in the US, with programs aimed at addressing food insecurity like the Supplemental Nutrition Assistance Program (SNAP) and food pantries seeing significant upticks in utilization. While these programs have improved food access overall, the extent to which diet quality changed, and whether they helped mitigate diet quality disruptions, is not well understood.ObjectiveTo evaluate food insecurity, food pantry and/or SNAP participation associations with both diet quality as well as perceived disruptions in diet during the COVID-19 pandemic among Massachusetts adults with lower incomes.MethodsWe analyzed complete-case data from 1,256 individuals with complete data from a cross-sectional online survey of adults (ages 18 years and above) living in Massachusetts who responded to “The MA Statewide Food Access Survey” between October 2020 through January 2021. Study recruitment and survey administration were performed by The Greater Boston Food Bank. We excluded respondents who reported participation in assistance programs but were ineligible (n = 168), those who provided straightlined responses to the food frequency questionnaire component of the survey (n = 34), those with incomes above 300% of the federal poverty level (n = 1,427), those who completed the survey in 2021 (n = 8), and those who reported improved food insecurity (n = 55). Current dietary intake was assessed via food frequency questionnaire. Using Bayesian regression models, we examined associations between pandemic food insecurity, perceived disruption in diet, diet quality, and intakes of individual foods among those who completed a survey in 2020. We assessed interactions by pantry and SNAP participation to determine whether participation moderated these relationships.ResultsIndividuals experiencing food insecurity reported greater disruption in diet during the pandemic and reduced consumption of healthy/unhealthy foods. Pantry participation attenuated significant associations between food insecurity and lower consumption of unhealthy (b = −1.13 [95% CI −1.97 to −0.31]) and healthy foods (b = −1.07 [−1.82 to −0.34]) to null (unhealthy foods: −0.70 [−2.24 to 0.84]; healthy foods: 0.30 [−1.17 to 1.74]), whereas SNAP participation attenuated associations for healthy foods alone (from −1.07 [−1.82 to −0.34] to −0.75 [−1.83 to 0.32]). Results were robust to choice of prior as well as to alternative modeling specifications.ConclusionAmong adults with lower incomes, those experiencing food insecurity consumed less food, regardless of healthfulness, compared to individuals not experiencing food insecurity. Participation in safety-net programs, including SNAP and pantry participation, buffered this phenomenon. Continued support of SNAP and the food bank network and a focus on access to affordable healthy foods may simultaneously alleviate hunger while improving nutrition security

Low- Versus High-Dose Methylprednisolone in Adult Patients With Coronavirus Disease 2019: Less Is More

Background: Corticosteroids use in severe coronavirus disease 2019 (COVID-19) improves survival; however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC). Methods: This was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on November 17, 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (September 1 to November 15, 2020) were compared to the LDC group (November 30, 2020 to January 20, 2021). High-dose corticosteroids was defined as 80 mg of methylprednisolone daily in 2 divided doses, and LDC was defined as 32-40 mg of methylprednisolone daily in 2 divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events. Results: Four-hundred seventy patients were included: 218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, P = .712). This finding remained intact when controlling for additional variables (odds ratio, 0.947; confidence interval, 0.515-1.742; P = .861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (P \u3c .001). No differences were noted in any of the other secondary outcomes. Conclusions: Low-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19