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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.
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Leucemia Mieloide Aguda , Receptores de Antígenos Quiméricos , Humanos , Linfócitos T , Subunidade alfa de Receptor de Interleucina-3/metabolismo , Chaperona BiP do Retículo Endoplasmático , Receptores de Antígenos Quiméricos/metabolismo , Leucemia Mieloide Aguda/patologiaRESUMO
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).
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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.
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Anti-Infecciosos , Bacteriemia , Farmácia , Humanos , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , HemoculturaRESUMO
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.
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Dieta Mediterrânea , Metabolômica , Humanos , Metabolômica/métodos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Biomarcadores , PlasmaRESUMO
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.
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Serviços de Alimentação , Instituições Acadêmicas , Irlanda do Norte , Inquéritos e Questionários , Política Nutricional , Dieta SaudávelRESUMO
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.
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Anti-Infecciosos , Gestão de Antimicrobianos , Doenças Transmissíveis , Humanos , Doenças Transmissíveis/tratamento farmacológico , Atenção à Saúde , Farmacêuticos , Antibacterianos/uso terapêuticoRESUMO
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.
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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.
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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.
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Leucemia , Receptores de Antígenos Quiméricos , Animais , Humanos , Imunossupressores , Imunoterapia Adotiva , Leucemia/terapia , Camundongos , Linfócitos T Citotóxicos , Microambiente TumoralRESUMO
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.
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Developing CAR T cells for acute myeloid leukemia (AML) has been hampered by a paucity of targets that are expressed on AML blasts and not on hematopoietic progenitor cells (HPCs). Here we demonstrate that GRP78 is expressed on the cell surface of primary AML blasts but not HPCs. To target GRP78, we generate T cell expressing a GRP78-specific peptide-based CAR, which show evidence of minimal fratricide post activation/transduction and antigen-dependent T cell differentiation. GRP78-CAR T cells recognize and kill GRP78-positive AML cells without toxicity to HPCs. In vivo, GRP78-CAR T cells have significant anti-AML activity. To prevent antigen-dependent T cell differentiation, we block CAR signaling and GRP78 cell surface expression post activation by using dasatinib during GRP78-CAR T cell manufacturing. This significantly improves their effector function in vitro and in vivo. Thus, targeting cell surface GRP78-positive AML with CAR T cells is feasible, and warrants further active exploration.
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Membrana Celular/metabolismo , Chaperona BiP do Retículo Endoplasmático/imunologia , Células-Tronco Hematopoéticas/imunologia , Leucemia Mieloide Aguda/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Animais , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Citotoxicidade Imunológica/efeitos dos fármacos , Dasatinibe/farmacologia , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/genética , Camundongos Endogâmicos NOD , Camundongos SCID , Linfócitos T/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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.
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Doenças Cardiovasculares , Dieta Mediterrânea , Humanos , Aconselhamento , Estudos de ViabilidadeRESUMO
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.
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Gestão de Antimicrobianos , Tratamento Farmacológico da COVID-19 , Humanos , Estudos Retrospectivos , Hospitalização , Antibacterianos/uso terapêuticoRESUMO
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 ).
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Comportamento Infantil , Saúde da Criança , Dieta , Promoção da Saúde/métodos , Serviços de Saúde Escolar , Criança , Comportamento Alimentar , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Qualidade de Vida , Instituições AcadêmicasRESUMO
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.
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Fatores Etários , Culinária/estatística & dados numéricos , Competência Mental/psicologia , Percepção , Criança , Dieta Saudável , Análise Fatorial , Humanos , Psicometria , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Accumulating evidence supports the role of a Mediterranean diet (MD) in cognition, with a greater adherence to a MD associated with reduced dementia risk. It is important to understand how best to achieve behaviour change towards a MD, particularly in non-Mediterranean and high-risk populations. The aim of this study was to evaluate the feasibility of a MD and lifestyle education intervention (THINK-MED) among older adults with cognitive impairment. METHODS: Qualitative interviews (Phase I), conducted with mild cognitive impairment (MCI) participants, evaluated the intervention materials to allow refinement before pilot testing. THINK-MED was a 12-month, pilot RCT (Phase II) whereby MCI participants were randomised into one of three groups: education on one occasion vs education staged and supported by a dietitian vs control. The primary outcome was a change in MD score. Secondary outcome measurements were collected to gather data on variability of the outcomes to inform a full trial power calculation and to test their acceptability. Slower recruitment rates necessitated a change in primary outcome to a revised focus primarily on feasibility. A sub-study of the same THINK-MED intervention and data collection measures was also conducted among community-dwelling participants with subjective cognitive impairment (SCI) (NCT03569319). RESULTS: A total of 20 participants (n = 15 MCI; n = 5 SCI) were enrolled in the THINK-MED study. However, there were 10 (50%) participants (n = 9 MCI; n = 1 SCI) who withdrew from the study. Although, those who remained in the intervention rated and evaluated their experience as generally positive, recruitment and retention, especially from a MCI population, was extremely challenging. This highlights the complex needs of this heterogeneous clinical cohort. Recruiting participants from a community-based sample with SCI was more feasible, reaching a wider audience in a shorter time period. There were challenges relating to data collection and incompleteness, with the occurrence of missing data particularly among the questionnaire-based assessments. CONCLUSIONS: Owing to the challenges with recruitment and retention of older adults with cognitive impairment in this study, it is difficult to confirm if this intervention is feasible. This research has highlighted considerations for a future trial, including a review of the recruitment strategies used and prioritisation of the outcome measures assessed. TRIAL REGISTRATION: Clinical trials registration NCT03265522 / NCT03569319.
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Alanina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Didesoxinucleosídeos/administração & dosagem , Emtricitabina/administração & dosagem , Esofagite Eosinofílica/complicações , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Tenofovir/administração & dosagem , Carga Viral/efeitos dos fármacos , Adulto , Alanina/administração & dosagem , Transtornos de Deglutição/etiologia , Quimioterapia Combinada , Esofagite Eosinofílica/diagnóstico , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Oxazinas , Piperazinas , Piridonas , Resultado do TratamentoRESUMO
The Mediterranean diet (MD) is a dietary pattern well-known for its benefits in disease prevention. Monitoring adherence to the MD could be improved by discovery of novel dietary biomarkers. The MEDiterranean Diet in Northern Ireland (MEDDINI) intervention study monitored the adherence of participants to the MD for up to 12 months. This investigation aimed to profile plasma metabolites, correlating each against the MD score of participants (n = 58). Based on an established 14-point scale MD score, subjects were classified into two groups ("low" and "high"). 1H-Nuclear Magnetic Resonance (1H-NMR) metabolomic analysis found that citric acid was the most significant metabolite (p = 5.99 × 10-4*; q = 0.03), differing between 'low' and 'high'. Furthermore, five additional metabolites significantly differed (p < 0.05; q < 0.35) between the two groups. Discriminatory metabolites included: citric acid, pyruvic acid, betaine, mannose, acetic acid and myo-inositol. Additionally, the top five most influential metabolites in multivariate models were also citric acid, pyruvic acid, betaine, mannose and myo-inositol. Metabolites significantly correlated with the consumption of certain food types. For example, citric acid positively correlated fruit, fruit juice and vegetable constituents of the diet, and negatively correlated with sweet foods alone or when combined with carbonated drinks. Citric acid was the best performing biomarker and this was enhanced by paired ratio with pyruvic acid. The present study demonstrates the utility of metabolomic profiling for effectively assessing adherence to MD and the discovery of novel dietary biomarkers.
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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.