Non-targeted LC-MS/MS metabolomic profiling of human plasma uncovers a novel Mediterranean diet biomarker panel.

INTRODUCTION: Consumption of a Mediterranean diet (MD) has established health benefits, and the identification of novel biomarkers could enable objective monitoring of dietary pattern adherence. OBJECTIVES: The present investigation performed untargeted metabolomics on blood plasma from a controlled study of MD adherence, to identify novel blood-based metabolite biomarkers associated with the MD pattern, and to build a logistic regression model that could be used to characterise MD adherence. METHODS: A hundred and thirty-five plasma samples from n = 58 patients collected at different time points were available. Using a 14-point scale MD Score (MDS) subjects were divided into 'high' or 'low' MDS adherence groups and liquid chromatography-mass spectrometry (LC-MS/MS) was applied for analysis. RESULTS: The strongest association with MDS was pectenotoxin 2 seco acid (r = 0.53; ROC = 0.78), a non-toxic marine xenobiotic metabolite. Several lipids were useful biomarkers including eicosapentaenoic acid, the structurally related lysophospholipid (20:5(5Z,8Z,11Z,14Z,17Z)/0:0), a phosphatidylcholine (P-18:1(9Z)/16:0) and also xi-8-hydroxyhexadecanedioic acid. Two metabolites negatively correlated with MDS, these were the monoacylglycerides (0:0/16:1(9Z)/0:0) and (0:0/20:3(5Z,8Z,11Z)/0:0). By stepwise elimination we selected a panel of 3 highly discriminatory metabolites and developed a linear regression model which identified 'high MDS' individuals with high sensitivity and specificity [AUC (95% CI) 0.83 (0.76-0.97)]. CONCLUSION: Our study highlights the utility of metabolomics as an approach for developing novel panels of dietary biomarkers. Quantitative profiling of these metabolites is required to validate their utility for evaluating dietary adherence.

Capturing the whole-school food environment in primary schools.

OBJECTIVE: The school food environment (SFE) is an ideal setting for encouraging healthy dietary behaviour. We aimed to develop an instrument to assess whole-SFE, test the instrument in the school setting and demonstrate its use to make food environment recommendations. DESIGN: SFE literature and UK school food guidance were searched to inform instrument items. The instrument consisted of (i) an observation proforma capturing canteen areas systems, food presentation and monitoring of food intake and (ii) a questionnaire assessing food policies, provision and activities. The instrument was tested in schools and used to develop SFE recommendations. Descriptive analyses enabled narrative discussion. SETTING: Primary schools. PARTICIPANTS: An observation was undertaken at schools in urban and rural geographical regions of Northern Ireland of varying socio-economic status (n 18). School senior management completed the questionnaire with input from school caterers (n 16). RESULTS: The instrument captured desired detail and potential instrument modifications were identified. SFE varied. Differences existed between food policies and how policies were implemented and monitored. At many schools, there was scope to enhance physical eating environments (n 12, 67 %) and food presentation (n 15, 83 %); emphasise healthy eating through food activities (n 7, 78 %) and increase parental engagement in school food (n 9, 56 %). CONCLUSIONS: The developed instrument can measure whole-SFE in primary schools and also enabled identification of recommendations to enhance SFE. Further assessment and adaptation of the instrument are required to enable future use as a research tool or for self-assessment use by schools.

The feasibility of a peer support intervention to encourage adoption and maintenance of a Mediterranean diet in established community groups at increased CVD risk: the TEAM-MED EXTEND study: a pilot cluster randomised controlled trial.

This study aimed to evaluate the feasibility of a peer support intervention to encourage adoption and maintenance of a Mediterranean diet (MD) in established community groups where existing social support may assist the behaviour change process. Four established community groups with members at increased Cardiovascular Disease (CVD) risk and homogenous in gender were recruited and randomised to receive either a 12-month Peer Support (PS) intervention (PSG) (n 2) or a Minimal Support intervention (educational materials only) (MSG) (n 2). The feasibility of the intervention was assessed using recruitment and retention rates, assessing the variability of outcome measures (primary outcome: adoption of an MD at 6 months (using a Mediterranean Diet Score (MDS)) and process evaluation measures including qualitative interviews. Recruitment rates for community groups (n 4/8), participants (n 31/51) and peer supporters (n 6/14) were 50 %, 61 % and 43 %, respectively. The recruitment strategy faced several challenges with recruitment and retention of participants, leading to a smaller sample than intended. At 12 months, a 65 % and 76·5 % retention rate for PSG and MSG participants was observed, respectively. A > 2-point increase in MDS was observed in both the PSG and the MSG at 6 months, maintained at 12 months. An increase in MD adherence was evident in both groups during follow-up; however, the challenges faced in recruitment and retention suggest a definitive study of the peer support intervention using current methods is not feasible and refinement based on the current feasibility study should be incorporated. Lessons learned during the implementation of this intervention will help inform future interventions in this area.

CooC11 and CooC7: the development and validation of age appropriate children's perceived cooking competence measures.

BACKGROUND: Learning cooking skills during childhood and adolescence is associated with positive dietary outcomes in adulthood as well as being tracked from adolescence to adulthood. In addition studies have found that perceived competence to be a greater motivator to perform a behaviour than actual competence. However, a lack of validated tools that effectively measure behavioural and dietary changes including cooking confidence in children is a limitation. Therefore, this research aimed to develop and validate age-appropriate perceived cooking competence measures for younger and older primary school aged children. METHODS: Two measures of perceived Cooking Competence (CooC11 and CooC7) for older (8-12 years) and younger (6-7 years) children were developed from a critical evaluation of publically available recommendations and expert consultation. The cooking skills within the measures were illustrated by a graphic designer in consultation with a chef and reviewed in an iterative manner by the research team. The measures were piloted for clarity, ease of use and initial face validity. Multiple studies were used for both CooC11 and CooC7 to establish psychometric properties of the measures, temporal stability, internal consistency reliability, construct validity, as well as responsiveness to change for CooC11. Analysis included Exploratory Factor Analysis, Confirmatory Factor Analysis, Intraclass Correlation Coefficients, Pearson's Correlations, ANOVAs and Cronbach's Alphas. RESULTS: Both measures had high levels of face validity and received positive user feedback. Two factors were shown in both measures with the measures showing excellent temporal stability (ICC > 0.9) and good internal consistency (Cronbach's Alphas > 0.7). Both measures showed initial discriminant validity, with significant differences (P< 0.001) between those who reported assisting their parents with dinner preparation and those who did not. Additionally, CooC11 was significantly correlated with an adult cooking measure and had a significant responsiveness to change (P< 0.01). CONCLUSIONS: The CooC11 and CooC7 are the first validated age-appropriate measures for assessing children's perceived Cooking Competence for ages 8-12 and 6-7 years respectively. They can be used to evaluate the efficacy of children's cooking intervention studies or school nutrition education programmes.

Food environment intervention improves food knowledge, wellbeing and dietary habits in primary school children: Project Daire, a randomised-controlled, factorial design cluster trial.

BACKGROUND: Evidence suggests that dietary intake of UK children is suboptimal. As schools provide an ideal natural environment for public health interventions, effective and sustainable methods of improving food knowledge and dietary habits in this population must be identified. Project Daire aimed to improve children's health-related quality of life, wellbeing, food knowledge and dietary habits via two multi-component interventions. METHODS: Daire was a randomised-controlled, factorial design trial evaluating two interventions across four arms. Primary schools in Northern Ireland were randomised to one of four 6-month intervention arms: i) 'Nourish', ii) 'Engage', iii) 'Nourish' and 'Engage' and iv) Control (Delayed). 'Nourish' was an intervention aiming to alter the whole-school food environment, provide food-related experiences and exposure to locally produced foods. 'Engage' was an age-appropriate, cross-curricular educational intervention on food, agriculture, nutrition science and related careers. Primary outcomes were emotional and behavioural wellbeing and health-related quality of life. A number of secondary outcomes, including dietary intake, cooking competence and food-related knowledge, were also measured. RESULTS: Fifteen schools from areas of varying socio-economic status participated in the randomised trial. A total of 903 (n = 445 aged 6-7 years and n = 458 aged 10-11 years) primary school pupils took part. Total Difficulties Score improved in all pupils (6-7 and 10-11 year old pupils) who received the 'Nourish' intervention compared with those that did not (adjusted difference in mean = - 0.82; 95% CI -1.46, - 0.17; P < 0.02). No statistically significant difference in Health-Related Quality of Life was observed. The 'Nourish' intervention also produced some changes in school-based dietary behaviour, which were most apparent in the 10-11 year old pupils. The 'Nourish' intervention also produced improvements in understanding of food labels (adjusted difference in mean = 0.15; 95% CI 0.05, 0.25; P < 0.01) and knowledge of vegetables in season (adjusted difference in mean = 0.29; 95% CI 0.01,0.56; P = 0.04) whilst an increased willingness to try new foods and improved perceived cooking competence was also observed. CONCLUSIONS: Improvements in childhood emotional and behavioural wellbeing, dietary intake, knowledge about food, cooking skills and willingness to try new foods were associated with the 'Nourish' whole-school food environment intervention. Exploration of the sustainability and long-term effectiveness of such whole-school food interventions should be conducted. TRIAL REGISTRATION: National Institute of Health (NIH) U.S. National Library of Medicine Clinical Trials.gov (ID: NCT04277312 ).

The effectiveness of peer-supported interventions for encouraging dietary behaviour change in adults: a systematic review.

OBJECTIVE: There is an urgent need to find effective methods of supporting individuals to make dietary behaviour changes. Peer-supported interventions (PSI) have been suggested as a cost-effective strategy to support chronic disease self-management. However, the effect of PSI on dietary behaviour is unclear. The present systematic review aimed to assess the effectiveness of PSI for encouraging dietary behaviour change in adults and to consider intervention characteristics linked with effectiveness. DESIGN: Electronic databases were searched until June 2018 for randomised controlled trials assessing the effectiveness of PSI compared with an alternative intervention and/or control on a dietary related outcome in adults. Following title and abstract screening, two reviewers independently screened full texts and data were extracted by one reviewer and independently checked by another. Results were synthesised narratively. SETTING: Randomised controlled trials.ParticipantsAdult studies. RESULTS: The fifty-four included studies varied in participants, intervention details and results. More PSI reported a positive or mixed effect on diet than no effect. Most interventions used a group model and were lay-led by peer supporters. Several studies did not report intervention intensity, fidelity and peer training and support in detail. Studies reporting positive effects employed more behaviour change techniques (BCT) than studies reporting no effect; however, heterogeneity between studies was considerable. CONCLUSIONS: As evidence was mixed, further interventions need to assess the effect of PSI on dietary behaviour, describe intervention content (theoretical basis, BCT, intensity and peer training/support) and include a detailed process evaluation.

Development of a peer support intervention to encourage dietary behaviour change towards a Mediterranean diet in adults at high cardiovascular risk.

BACKGROUND: Mediterranean diet (MD) interventions are demonstrated to significantly reduce cardiovascular disease (CVD) risk but are typically resource intensive and delivered by health professionals. There is considerable interest to develop interventions that target sustained dietary behaviour change and that are feasible to scale-up for wider public health benefit. The aim of this paper is to describe the process used to develop a peer support intervention to encourage dietary behaviour change towards a MD in non-Mediterranean adults at high CVD risk. METHODS: The Medical Research Council (MRC) and Behaviour Change Wheel (BCW) frameworks and the COM-B (Capability, Opportunity, Motivation, Behaviour) theoretical model were used to guide the intervention development process. We used a combination of evidence synthesis and qualitative research with the target population, health professionals, and community health personnel to develop the intervention over three main stages: (1) we identified the evidence base and selected dietary behaviours that needed to change, (2) we developed a theoretical basis for how the intervention might encourage behaviour change towards a MD and selected intervention functions that could drive the desired MD behaviour change, and (3) we defined the intervention content and modelled outcomes. RESULTS: A theory-based, culturally tailored, peer support intervention was developed to specifically target behaviour change towards a MD in the target population. The intervention was a group-based program delivered by trained peer volunteers over 12-months, and incorporated strategies to enhance social support, self-efficacy, problem-solving, knowledge, and attitudes to address identified barriers to adopting a MD from the COM-B analysis. CONCLUSIONS: The MRC and BCW frameworks provided a systematic and complementary process for development of a theory-based peer support intervention to encourage dietary behaviour change towards a MD in non-Mediterranean adults at high CVD risk. The next step is to evaluate feasibility, acceptability, and diet behaviour change outcomes in response to the peer support intervention (change towards a MD and nutrient biomarkers) using a randomized controlled trial design.

A qualitative analysis exploring preferred methods of peer support to encourage adherence to a Mediterranean diet in a Northern European population at high risk of cardiovascular disease.

BACKGROUND: Epidemiological and randomised controlled trial evidence demonstrates that adherence to a Mediterranean diet (MD) can reduce cardiovascular disease (CVD) risk. However, methods used to support dietary change have been intensive and expensive. Peer support has been suggested as a possible cost-effective method to encourage adherence to a MD in at risk populations, although development of such a programme has not been explored. The purpose of this study was to use mixed-methods to determine the preferred peer support approach to encourage adherence to a MD. METHODS: Qualitative (focus groups) and quantitative methods (questionnaire and preference scoring sheet) were used to determine preferred methods of peer support. Sixty-seven high CVD risk participants took part in 12 focus groups (60% female, mean age 64 years) and completed a questionnaire and preference scoring sheet. Focus group data were transcribed and thematically analysed. RESULTS: The mean preference score (1 being most preferred and 5 being least preferred) for group support was 1.5, compared to 3.4 for peer mentorship, 4.0 for telephone peer support and 4.0 for internet peer support. Three key themes were identified from the transcripts: 1. Components of an effective peer support group: discussions around group peer support were predominantly positive. It was suggested that an effective group develops from people who consider themselves similar to each other meeting face-to-face, leading to the development of a group identity that embraces trust and honesty. 2. Catalysing Motivation: participants discussed that a group peer support model could facilitate interpersonal motivations including encouragement, competitiveness and accountability. 3. Stepping Stones of Change: participants conceptualised change as a process, and discussed that, throughout the process, different models of peer support might be more or less useful. CONCLUSION: A group-based approach was the preferred method of peer support to encourage a population at high risk of CVD to adhere to a MD. This finding should be recognised in the development of interventions to encourage adoption of a MD in a Northern European population.

Arsenic remediation by formation of arsenic sulfide minerals in a continuous anaerobic bioreactor.

Arsenic (As) is a highly toxic metalloid that has been identified at high concentrations in groundwater in certain locations around the world. Concurrent microbial reduction of arsenate (As(V) ) and sulfate (SO4 (2-) ) can result in the formation of poorly soluble arsenic sulfide minerals (ASM). The objective of this research was to study As biomineralization in a minimal iron environment for the bioremediation of As-contaminated groundwater using simultaneous As(V) and SO4 (2-) reduction. A continuous-flow anaerobic bioreactor was maintained at slightly acidic pH (6.25-6.50) and fed with As(V) and SO4 (2-) , utilizing ethanol as an electron donor for over 250 d. A second bioreactor running under the same conditions but lacking SO4 (2-) was operated as a control to study the fate of As (without S). The reactor fed with SO4 (2-) removed an average 91.2% of the total soluble As at volumetric rates up to 2.9 mg As/(L · h), while less than 5% removal was observed in the control bioreactor. Soluble S removal occurred with an S to As molar ratio of 1.2, suggesting the formation of a mixture of orpiment- (As2 S3 ) and realgar-like (AsS) solid phases. Solid phase characterization using K-edge X-ray absorption spectroscopy confirmed the formation of a mixture of As2 S3 and AsS. These results indicate that a bioremediation process relying on the addition of a simple, low-cost electron donor offers potential to promote the removal of As from groundwater with naturally occurring or added SO4 (2-) by precipitation of ASM.

Clinical importance of bilateral disease in patients with papillary thyroid cancer.

ABSTRACT: A cancer-related factor that is not included in papillary thyroid cancer (PTC) prognostic scoring systems is bilaterality. While it may seem that bilaterality should be considered during the management of PTC, its clinical importance has been debated. This controversy exists because the extent of surgery for PTC has not been found to affect survival in low-risk individuals, despite their potential for PTC bilaterality. We sought to determine if PTC bilaterality is a cancer prognosticator based upon its association with known clinical and pathological PTC prognosticators, and MACIS scores. In this article we discuss our findings and their potential clinical implications.

Infliximab in ulcerative colitis: the impact of preoperative treatment on rates of colectomy and prescribing practices in the province of British Columbia, Canada.

BACKGROUND: Approximately 20% of patients with ulcerative colitis will require surgical treatment. Recent data suggest that infliximab may reduce the need for surgery in patients with severe ulcerative colitis. However, it is unclear whether data from these small trials will translate to reduced colectomy rates in populations with ulcerative colitis. OBJECTIVE: The purpose of this study was to determine the impact of infliximab on the rates of colectomy for ulcerative colitis and the prescribing practices for infliximab in British Columbia, Canada. DESIGN: We retrospectively reviewed data from 4 province-wide population-based databases maintained by the British Columbia Ministry of Health, a central registry, a hospital separations file, a physician payment file, and a pharmaceutical file. Data were collected from April 1, 2001, to March 31, 2010. SETTINGS: This investigation was conducted at the University of British Columbia. PATIENTS: All patients aged 18 to 75 with ulcerative colitis were included and identified using a validated strategy with International Classification of Diseases 9/10 codes. Patients with severe ulcerative colitis were defined by treatment with a course of corticosteroids during the study period. Patients treated with infliximab were identified using the provincial pharmaceutical file. MAIN OUTCOME MEASURES: The primary outcome was surgery determined by an International Classification of Diseases 9/10 code for partial or total colectomy. RESULTS: Between 2001 and 2010, 7227 subjects were identified with ulcerative colitis. The number of subjects with severe ulcerative colitis was 2537. For general ulcerative colitis, rates of colectomy decreased from 9.97% to 8.88% in the preinfliximab era (2003-2004) and postinfliximab era (2008-2009; p = 0.03). For severe ulcerative colitis, there was no significant difference in colectomy rates (9.97% vs 11.14%; p = 0.18). The highest rate of infliximab prescription was found to be in the provincial health region that encompasses the tertiary academic centers of the province. LIMITATIONS: Although the overall number of patients in this analysis is sizeable, the number of patients who were prescribed infliximab during the study period is relatively modest, which may have impacted trends. CONCLUSIONS: In the severe ulcerative colitis population, there has been no change in the colectomy rate over time despite the introduction of infliximab.

Implementation of a pharmacy-driven rapid bacteremia response program.

PURPOSE: This report describes a comprehensive pharmacy-driven rapid bacteremia response program. SUMMARY: This novel program positioned the pharmacy department at a large, community health system to receive and respond to critical microbiologic diagnostic testing results, 24/7/365. The program empowered pharmacists to provide centralized, comprehensive care including assessing blood culture Gram stain results, adjusting antibiotic therapy per protocol, ordering repeat blood cultures, analyzing and interpreting rapid molecular diagnostic test results, placing orders for contact isolation, and communicating antibiotic recommendations to the treatment team. In the first year after program implementation, 2,282 blood culture Gram stains and 2,046 rapid diagnostic test results were called in to the pharmacy department. The program reduced the median time to effective therapy in patients who did not already have active antimicrobial orders from over 10 hours to less than 1 hour. Based on the Gram stain results, antibiotics were started per protocol in 34.2% of patients. Based on the rapid molecular diagnostic test results, adjustments were made to antibiotic regimens in 55.7% of cases after discussion with a provider. Of these adjustments, 39.9% were for escalation of antibiotics and 37.7% were for de-escalation of antibiotics. CONCLUSION: By expanding the scope of pharmacy practice, barriers to optimizing clinical care were overcome.

The feasibility and acceptability of a rewards system based on food purchasing behaviour in secondary school cashless canteens: the Eat4Treats (E4T) cluster feasibility, non-randomised, controlled intervention study.

BACKGROUND: Using rewards may be an effective method to positively influence children's eating behaviour but evidence to date is limited, particularly in older children. The cashless canteen systems in schools provides a unique opportunity to implement a food-based reward scheme but intervention development work and feasibility testing is needed. The overall aim of the E4T feasibility study was to examine the feasibility and acceptability of implementing a rewards scheme based on the food purchasing behaviour of pupils in cashless canteens in secondary schools. METHODS: A non-randomised, controlled, parallel-group cluster feasibility study conducted in four secondary schools (two intervention and two control) serving areas of the highest social deprivation in Northern Ireland. During the 4-month trial, pupils earned points for foods purchased at the school canteen, with better nutritional choices having a higher value. Pupils could exchange the points they earned for rewards (e.g. stationery, vouchers, sports equipment) via the E4T website. Qualitative and quantitative data was collected from year 9 and 10 pupils (boys and girls aged 12-14 years), teachers and canteen staff to address the feasibility questions. RESULTS: Two intervention (one urban, one rural) and one control (urban) school completed the study. Seventy-one percent of 12-14-year-old pupils consented to take part; 1% of parents opted their child out of the study. Questionnaire completion rates were high (6 and 11% of questionnaires were partially completed at baseline and follow-up respectively). Collecting data on food consumed in the canteen was challenging logistically. Focus groups with pupils indicated that the overall concept of E4T was well received and there was a high degree of satisfaction with the rewards available. Pupils and teachers made several suggestions for improvements. CONCLUSIONS: E4T was successfully implemented as a result of collaboration between schools, school canteens and cashless canteen providers working with a multidisciplinary research team. It was acceptable to pupils, teachers and canteen staff. The findings suggest a few areas for refining implementation and evaluation processes that would need to be considered in the design of a larger trial, particularly resources required to streamline implementation and ways to optimise pupil engagement. TRIAL REGISTRATION: Under review with https://www. CLINICALTRIALS: gov (retrospective registration-reg number and weblink to be added).

Peptide-scFv antigen recognition domains effectively confer CAR T cell multiantigen specificity.

The emergence of immune escape is a significant roadblock to developing effective chimeric antigen receptor (CAR) T cell therapies against hematological malignancies, including acute myeloid leukemia (AML). Here, we demonstrate feasibility of targeting two antigens simultaneously by combining a GRP78-specific peptide antigen recognition domain with a CD123-specific scFv to generate a peptide-scFv bispecific antigen recognition domain (78.123). To achieve this, we test linkers with varying length and flexibility and perform immunophenotypic and functional characterization. We demonstrate that bispecific CAR T cells successfully recognize and kill tumor cells that express GRP78, CD123, or both antigens and have improved antitumor activity compared to their monospecific counterparts when both antigens are expressed. Protein structure prediction suggests that linker length and compactness influence the functionality of the generated bispecific CARs. Thus, we present a bispecific CAR design strategy to prevent immune escape in AML that can be extended to other peptide-scFv combinations.

The Norton Healthcare electronic antimicrobial stewardship program: An opt-out approach to antimicrobial stewardship.

PURPOSE: To describe the Norton Healthcare electronic antimicrobial stewardship program (E-ASP), a novel prospective audit and feedback approach that leverages the electronic medical record to overcome efficiency barriers. Additionally, to describe an accompanying opt-out antimicrobial stewardship approach that addresses provider nonresponsiveness. SUMMARY: Prospective audit and feedback is recommended by antimicrobial stewardship guidelines; however, execution can be difficult due to labor requirements, delays in communication, and provider nonparticipation. The Norton E-ASP was developed to address these issues by reliably identifying target patients, documenting assessments, streamlining recommendation delivery, promoting handoff, and providing automated tracking of recommendation responses. Opt-out stewardship allows recommendations to be implemented if not rejected after 24 hours. CONCLUSION: A 25% reduction in target antimicrobial use has been achieved and sustained with the program. Use of the Norton E-ASP, including opt-out antimicrobial stewardship, broadened the reach and furthered the impact of infectious diseases pharmacists. Successes of this program justified addition of 3 full-time infectious diseases pharmacist positions at a large community health system. This strategy may serve as a model for tele-antimicrobial stewardship or other pharmacy recommendations.

Leukemia's Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy.

In recent years, there has been an emphasis on harnessing the immune system for therapeutic interventions. Adoptive cell therapies (ACT) have emerged as an effective option for B-cell derived hematological malignancies. Despite remarkable successes with ACT, immune dysregulation and the leukemia microenvironment can critically alter clinical responses. Therefore, preclinical modeling can contribute to the advancement of ACT for leukemias. Human xenografts, the current mainstay of ACT in vivo models, cannot evaluate the impact of the immunosuppressive leukemia microenvironment on adoptively transferred cells. Syngeneic mouse models utilize murine tumor models and implant them into immunocompetent mice. This provides an alternative model, reducing the need for complicated breeding strategies while maintaining a matched immune system, stromal compartment, and leukemia burden. Syngeneic models that evaluate ACT have analyzed the complexity of cytotoxic T lymphocytes, T cell receptor transgenics, and chimeric antigen receptors. This review examines the immunosuppressive features of the leukemia microenvironment, discusses how preclinical modeling helps predict ACT associated toxicities and dysfunction, and explores publications that have employed syngeneic modeling in ACT studies for the improvement of therapy for leukemias.

Missed Pneumococcal Vaccination Opportunities in Adults With Invasive Pneumococcal Disease in a Community Health System.

Background: Adult vaccination programs are suboptimal. Methods: Pneumococcal vaccination history, and healthcare contact were assessed in patients with invasive pneumococcal disease. Results: Of the 229 cases, 14% were vaccinated. Observed mortality was 20.1%. Conclusions: Numerous missed vaccination opportunities were identified.

Antimicrobial stewardship in patients with confirmed coronavirus disease 2019 (COVID-19).

Hospitalized coronavirus disease 2019 (COVID-19) patients receiving antibiotics (n = 173) were retrospectively assigned to the early or late discontinuation groups. The length of therapy was shorter in the early discontinuation group (3 vs 7 days; P < .0001). Mortality rates (14.3% vs 20.7%; P = .316) and length of stay (7 vs 9 days; P = .063) were similar.

Limited impact of a nudge comment in promoting de-escalation to first-generation cephalosporins in urinary tract infections.

In this study, we evaluated the impact of a microbiology nudge on de-escalation to first-generation cephalosporins in hospitalized patients with urinary tract infections secondary to Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolates with minimum inhibitory concentrations (MICs) ≤ 16 µg/mL. De-escalation to first generation-cephalosporins was uncommon at MICs = 4-16 µg/mL.

Fluoroquinolone stewardship at a community health system: A decade in review.

Objective: To describe inpatient fluoroquinolone use and susceptibility data over a 10-year period after the implementation of an antimicrobial stewardship program (ASP) led by an infectious diseases pharmacist starting in 2011. Design: Retrospective surveillance study. Setting: Large community health system. Methods: Fluoroquinolone use was quantified by days of therapy (DOT) per 1,000 patient days (PD) and reported quarterly. Use data are reported for inpatients from 2016 to 2020. Levofloxacin susceptibility is reported for Pseudomonas aeruginosa and Escherichia coli for inpatients from 2011 to 2020 at a 4 adult-hospital health system. Results: Inpatient fluoroquinolone use decreased by 74% over a 5-year period, with an average decrease of 3.45 DOT per 1,000 PD per quarter (P < .001). Over a 10-year period, inpatient levofloxacin susceptibility increased by 57% for P. aeruginosa and by 15% for E. coli. P. aeruginosa susceptibility to levofloxacin increased by an average of 2.73% per year (P < .001) and had a strong negative correlation with fluoroquinolone use, r = -0.99 (P = .002). E. coli susceptibility to levofloxacin increased by an average of 1.33% per year (P < .001) and had a strong negative correlation with fluoroquinolone use, r = -0.95 (P = .015). Conclusions: A substantial decrease in fluoroquinolone use and increase in P. aeruginosa and E. coli levofloxacin susceptibility was observed after implementation of an antimicrobial stewardship program. These results demonstrate the value of stewardship services and highlight the effectiveness of an infectious diseases pharmacist led antimicrobial stewardship program.