To investigate the practices of healthcare professionals in relation to best practice recommendations for the multidisciplinary management of people with diabetes and periodontitis, focusing on two clinical behaviours: informing patients about the links between diabetes and periodontitis, and suggesting patients with poorly controlled diabetes go for a dental check-up.
Cross-sectional design utilising online questionnaires to assess self-reported performance and constructs from Social Cognitive Theory (SCT) and Normalisation Process Theory.
Primary care medical practices (n=37) in North East, North Cumbria and South West of England Clinical Research Networks.
96 general practitioners (GPs), 48 nurses and 21 healthcare assistants (HCAs).
Participants reported little to no informing patients about the links between diabetes and periodontitis or suggesting that they go for a dental check-up. Regarding future intent, both GPs (7.60±3.38) and nurses (7.94±3.69) scored significantly higher than HCAs (4.29±5.07) for SCT proximal goals (intention) in relation to informing patients about the links (p
Despite evidence-informed best practice recommendations, healthcare professionals currently report low levels of informing patients with diabetes about the links between diabetes and periodontitis and suggesting patients go for a dental check-up. However, healthcare professionals, particularly nurses, value these behaviours and consider them appropriate to their role. While knowledge of the evidence is important, future guidelines should consider different strategies to enable implementation of the delivery of healthcare interventions.
Retrospective studies conducted in psychiatric inpatient wards have shown a relation between the intensity of daylight in patient rooms and the length of stay, pointing to an antidepressant effect of ambient lighting conditions. Light therapy has shown a promising antidepressant effect when administered from a light box. The emergence of light-emitting diode (LED) technology has made it possible to build luminaires into rooms and to dynamically mimic the spectral and temporal distribution of daylight. The objective of this study is to investigate the antidepressant efficacy of a newly developed dynamic LED-lighting system installed in an inpatient ward.
In all, 150 inpatients with a major depressive episode, as part of either a major depressive disorder or as part of a bipolar disorder, will be included. The design is a two-arm 1:1 randomised study with a dynamic LED-lighting arm and a static LED-lighting arm, both as add-on to usual treatment in an inpatient psychiatric ward. The primary outcome is the baseline adjusted score on the 6-item Hamilton Depression Rating Scale at week 3. The secondary outcomes are the mean score on the Suicidal Ideation Attributes Scale at week 3, the mean score on the 17-item Hamilton Depression Rating Scale at week 3 and the mean score on the World Health Organisation Quality of Life-BREF (WHOQOL-BREF) at week 3. The spectral distribution of daylight and LED-light, with a specific focus on light mediated through the intrinsically photosensitive retinal ganglion cells, will be measured. Use of light luminaires will be logged. Assessors of Hamilton Depression Rating Scale scores and data analysts will be blinded for treatment allocation. The study was initiated in May 2019 and will end in December 2021.
No ethical issues are expected. Results will be published in peer-reviewed journals, disseminated electronically and in print and presented at symposia.
Brazil is a large country, with a population of mixed ethnic background and broad variation in dietary and physical activity traits across its five main regions. Because data on Brazilian women with polycystic ovary syndrome (PCOS) are still scarce, a nation-wide collaborative study was designed to determine the prevalence of metabolic and reproductive abnormalities and the presence of anxiety and depression in Brazilian women with PCOS. In addition, the study aims at describing how these characteristics are distributed across PCOS phenotypes and at detecting associations with regional demographic and lifestyle aspects, genetic variants, and epigenetic markers.
The Brazilian PCOS study is being conducted in the outpatient clinics of eight university hospitals within the public healthcare network (Unified Health System) across the country. Additional centres will be included following completion of the research ethics approval process. The sample includes women with PCOS according to Rotterdam criteria at inclusion in the study and a control group of healthy women matched by age, socioeconomic status and geographical region. Data will be collected in each centre and incorporated into a unified cloud database. Clinical, demographic, socioeconomic, psychological, metabolic, epigenetic and genotypic variables will be evaluated. The data resulting from this study will be useful to guide specific public strategies for primary and secondary prevention of metabolic and reproductive comorbidities in the PCOS population of Brazil.
The study protocol was approved by each local Research Ethics Committee. Written informed consent will be obtained from each participant. During data collection, analysis and publication, care will be taken to ensure confidentiality of participant information. Study results will be published in peer-reviewed journals and disseminated at international conferences. This research protocol was registered with the Research Ethics Committee of HCPA, through Plataforma Brasil.
Wound closure after wide, local excision of an appendicular soft‐tissue sarcoma (STS) can be challenging. This study evaluates the value of magnetic resonance imaging (MRI)‐based tumour parameters in planning wound closure. A total of 71 patients with a primary limb‐based STS, excluding vascular or osseous involvement, excluding the shoulder or hand and hip or foot were included. Axial MRI images were used to measure the circumferences and cross‐sectional areas of the limb, bone, and tumour. The tumour diameter, length, and depth at the level of maximal tumour dimension were measured to identify the tumour's relative contribution to the planning of optimal wound closure management through primary closure (PC) or reconstructive surgery (RS). Eighteen patients required planned wound RS. Wound complications occurred in 14% overall. Tumours, which were closed by PC, were of significantly greater depth, shorter radial diameter, and shorter tumour circumference relative to those closed by RS. On multivariate analysis, tumour depth was the greatest contributory factor in predicting type of wound closure. A quantitative analysis of MRI‐based tumour parameters demonstrates tumour depth as the most predictive factor in planning for the type of wound closure and may prove beneficial in providing greater insight into planned wound management of sarcoma resection.
The association between osteoporosis and atherosclerosis remains controversial. We sought to define the relationship between carotid intima-media thickness and bone mineral density (BMD) in individuals of Vietnamese background.
Cross-sectional study in Ho Chi Minh City, Vietnam.
The study involved 1460 individuals (559 men) aged 50 years and older (average age 59 years) who were randomly recruited from the community.
BMD at the femoral neck and lumbar spine was measured by dual-energy X-ray absorptiometry (Hologic, Waltham, Massachusetts, USA). Carotid intima-media thickness (cIMT) was measured using a Philips Ultrasonography (HD7XE). The presence of atherosclerotic plaque was ascertained for each individual. The association between cIMT and BMD was analysed by a multiple linear regression model.
In unadjusted analysis, cIMT was positively associated with femoral neck BMD in men (p=0.005), but not in women (p=0.242). After adjusting for age, smoking, diabetes and hypertension, the association remained statistically significant in men (partial R2=0.005; p=0.015) but not in women (partial R2=0.008; p=0.369). When the analysis was limited to individuals aged 60 years and older, the association between cIMT and BMD was no longer statistically significant. There was no statistically significant association between cIMT and lumbar spine BMD in either men or women.
In Vietnamese individuals aged 50 years and older, there is a clinically non-significant but statistically significant association between carotid intima-media thickness and BMD in men, not in women.
We describe an approach to rapidly adapt and implement an education and skills improvement intervention to address the needs of family caregivers of functionally impaired veterans—Helping Invested Families Improve Veterans’ Experience Study (HI‐FIVES).
Prior to implementation in eight sites, a multidisciplinary study team made systematic adaptations to the curriculum content and delivery process using input from the original randomized controlled trial (RCT); a stakeholder advisory board comprised of national experts in caregiver education, nursing, and implementation; and a veteran/caregiver engagement panel. To address site‐specific implementation barriers in diverse settings, we applied the Replicating Effective Programs implementation framework.
Adaptations to HI‐FIVES content and delivery included identifying core/noncore curriculum components, reducing instruction time, and simplifying caregiver recruitment for clinical settings. To enhance curriculum flexibility and potential uptake, site personnel were able to choose which staff would deliver the intervention and whether to offer class sessions in person or remotely. Curriculum materials were standardized and packaged to reduce the time required for implementation and to promote fidelity to the intervention.
The emphasis on flexible intervention delivery and standardized materials has been identified as strengths of the adaptation process. Two key challenges have been identifying feasible impact measures and reaching eligible caregivers for intervention recruitment.
This systematic implementation process can be used to rapidly adapt an intervention to diverse clinical sites and contexts. Nursing professionals play a significant role in educating and supporting caregivers and care recipients and can take a leading role to implement interventions that address skills and unmet needs for caregivers.
Robotic guidance (RG) and computer-assisted navigation (NV) have seen increased adoption in instrumented spine surgery over the last decade. Although there exists some evidence that these techniques increase radiological pedicle screw accuracy compared with conventional freehand (FH) surgery, this may not directly translate to any tangible clinical benefits, especially considering the relatively high inherent costs. As a non-randomised, expertise-based study, the European Robotic Spinal Instrumentation Study aims to create prospective multicentre evidence on the potential comparative clinical benefits of RG, NV and FH in a real-world setting.
Patients are allocated in a non-randomised, non-blinded fashion to the RG, NV or FH arms. Adult patients that are to undergo thoracolumbar pedicle screw instrumentation for degenerative pathologies, infections, vertebral tumours or fractures are considered for inclusion. Deformity correction and surgery at more than five levels represent exclusion criteria. Follow-up takes place at 6 weeks, as well as 12 and 24 months. The primary endpoint is defined as the time to revision surgery for a malpositioned or loosened pedicle screw within the first postoperative year. Secondary endpoints include patient-reported back and leg pain, as well as Oswestry Disability Index and EuroQOL 5-dimension questionnaires. Use of analgesic medication and work status are recorded. The primary analysis, conducted on the 12-month data, is carried out according to the intention-to-treat principle. The primary endpoint is analysed using crude and adjusted Cox proportional hazards models. Patient-reported outcomes are analysed using baseline-adjusted linear mixed models. The study is monitored according to a prespecified monitoring plan.
The study protocol is approved by the appropriate national and local authorities. Written informed consent is obtained from all participants. The final results will be published in an international peer-reviewed journal.
Clinical Trials.gov registry NCT03398915; Pre-results, recruiting stage.
Multimorbidity and polypharmacy are major risk factors for potentially inappropriate prescribing (eg, overprescribing and underprescribing), and systematic medication reviews are complex and time consuming. In this trial, the investigators aim to determine if a systematic software-based medication review improves medication appropriateness more than standard care in older, multimorbid patients with polypharmacy.
Optimising PharmacoTherapy In the multimorbid elderly in primary CAre is a cluster randomised controlled trial that will include outpatients from the Swiss primary care setting, aged ≥65 years with ≥three chronic medical conditions and concurrent use of ≥five chronic medications. Patients treated by the same general practitioner (GP) constitute a cluster, and clusters are randomised 1:1 to either a standard care sham intervention, in which the GP discusses with the patient if the medication list is complete, or a systematic medication review intervention based on the use of the 'Systematic Tool to Reduce Inappropriate Prescribing'-Assistant (STRIPA). STRIPA is a web-based clinical decision support system that helps customise medication reviews. It is based on the validated ‘Screening Tool of Older Person’s Prescriptions’ (STOPP) and ‘Screening Tool to Alert doctors to Right Treatment’ (START) criteria to detect potentially inappropriate prescribing. The trial’s follow-up period is 12 months. Outcomes will be assessed at baseline, 6 and 12 months. The primary endpoint is medication appropriateness, as measured jointly by the change in the Medication Appropriateness Index (MAI) and Assessment of Underutilisation (AOU). Secondary endpoints include the degree of polypharmacy, overprescribing and underprescribing, the number of falls and fractures, quality of life, the amount of formal and informal care received by patients, survival, patients’ quality adjusted life years, patients’ medical costs, cost-effectiveness of the intervention, percentage of recommendations accepted by GPs, percentage of recommendation rejected by GPs and patients’ willingness to have medications deprescribed.
The ethics committee of the canton of Bern in Switzerland approved the trial protocol. The results of this trial will be published in a peer-reviewed journal.
Swiss National Science Foundation, National Research Programme (NRP 74) ‘Smarter Healthcare’.
Clinicaltrials.gov (NCT03724539), KOFAM (Swiss national portal) (SNCTP000003060), Universal Trial Number (U1111-1226-8013).
Childhood obesity is a public health challenge. There is evidence for associations between parents’ feeding behaviours and childhood obesity risk. Primary care provides a unique opportunity for delivery of infant feeding interventions for childhood obesity prevention. Implementation strategies are needed to support infant feeding intervention delivery. The Choosing Healthy Eating for Infant Health (CHErIsH) intervention is a complex infant feeding intervention delivered at infant vaccination visits, alongside a healthcare professional (HCP)-level implementation strategy to support delivery.
This protocol provides a description of a non-randomised feasibility study of an infant feeding intervention and implementation strategy, with an embedded process evaluation and economic evaluation. Intervention participants will be parents of infants aged ≤6 weeks at recruitment, attending a participating HCP in a primary care practice. The intervention will be delivered at the infant’s 2, 4, 6, 12 and 13 month vaccination visits and involves brief verbal infant feeding messages and additional resources, including a leaflet, magnet, infant bib and sign-posting to an information website. The implementation strategy encompasses a local opinion leader, HCP training delivered prior to intervention delivery, electronic delivery prompts and additional resources, including a training manual, poster and support from the research team. An embedded mixed-methods process evaluation will examine the acceptability and feasibility of the intervention, the implementation strategy and study processes including data collection. Qualitative interviews will explore parent and HCP experiences and perspectives of delivery and receipt of the intervention and implementation strategy. Self-report surveys will examine fidelity of delivery and receipt, and acceptability, suitability and comprehensiveness of the intervention, implementation strategy and study processes. Data from electronic delivery prompts will also be collected to examine implementation of the intervention. A cost–outcome description will be conducted to measure costs of the intervention and the implementation strategy.
This study received approval from the Clinical Research Ethics Committee of the Cork Teaching Hospitals. Study findings will be disseminated via peer-reviewed publications and conference presentations.
Extended criteria donor (ECD) livers are increasingly accepted for transplantation in an attempt to reduce the gap between the number of patients on the waiting list and the available number of donor livers. ECD livers; however, carry an increased risk of developing primary non-function (PNF), early allograft dysfunction (EAD) or post-transplant cholangiopathy. Ischaemia-reperfusion injury (IRI) plays an important role in the development of these complications. Machine perfusion reduces IRI and allows for reconditioning and subsequent evaluation of liver grafts. Single or dual hypothermic oxygenated machine perfusion (DHOPE) (4°C–12°C) decreases IRI by resuscitation of mitochondria. Controlled oxygenated rewarming (COR) may further reduce IRI by preventing sudden temperature shifts. Subsequent normothermic machine perfusion (NMP) (37°C) allows for ex situ viability assessment to facilitate the selection of ECD livers with a low risk of PNF, EAD or post-transplant cholangiopathy.
This prospective, single-arm study is designed to resuscitate and evaluate initially nationwide declined ECD livers. End-ischaemic DHOPE will be performed for the initial mitochondrial and graft resuscitation, followed by COR of the donor liver to a normothermic temperature. Subsequently, NMP will be continued to assess viability of the liver. Transplantation into eligible recipients will proceed if all predetermined viability criteria are met within the first 150 min of NMP. To facilitate machine perfusion at different temperatures, a perfusion solution containing a haemoglobin-based oxygen carrier will be used. With this protocol, we aim to transplant extra livers. The primary endpoint is graft survival at 3 months after transplantation.
This protocol was approved by the medical ethical committee of Groningen, METc2016.281 in August 2016 and registered in the Dutch Trial registration number
The purpose of this study is to characterise the composition of a dehydrated amnion and chorion graft and investigate how factors released from this graft interact with cells important to the wound microenvironment using in vitro models. Characterisation was completed by proteomic analysis of growth factors and cytokines, evaluation of matrix components and protease inhibition, immunohistochemistry, and in vitro release of key growth factors and cytokines. To evaluate the effect of released factors on cells found within the microenvironment, in vitro assays including: cell proliferation, migration, gene expression, protein production, and intracellular pathway activation were used; additionally, responses of fibroblasts in the context of inflammation were measured. We found that released factors from dehydrated amnion/chorion membranes (dACM) stimulated cell proliferation, migration, and altered gene and protein expression profiles of cells important for wound repair in vitro. When cells were cultured in the presence of pro‐inflammatory cytokines, the addition of releasate from dACM resulted in an altered production of cytokines, including a reduction of pro‐inflammatory regulated on activation, normal T cell expressed and secreted (RANTES). In sum, the results presented here characterise the components of dACM, and in vitro studies were used to evaluate interactions of dACM with cell types important in wound healing.
Poor road and communication infrastructure pose major challenges to tuberculosis (TB) control in many regions of the world. TB surveillance and patient support often fall to community health workers (CHWs) who may lack the time or knowledge needed for this work. To meet the End TB Strategy goal of reducing TB incidence by 90% by 2035, the WHO calls for intensified research and innovation including the rapid uptake of new tools, interventions and strategies. Technologies that ‘leapfrog’ infrastructure challenges and support CHWs in TB control responsibilities have the potential to dramatically change TB outcomes in remote regions. Such technologies may strengthen TB control activities within challenged national tuberculosis treatment and control programmes (NTPs), and be adapted to address other public health challenges. The deployment of innovative technologies needs to be differentially adapted to context-specific factors. The Drone Observed Therapy System (DrOTS) project was launched in Madagascar in 2017 and integrates a bundle of innovative technologies including drones, digital adherence monitoring technology and mobile device-based educational videos to support TB control.
This mixed-methods study gathers and analyses cultural perceptions of the DrOTS project among key stakeholders: patients, community members, CHWs, village chiefs and NTP–DrOTS mobile health teams. Data from questionnaires, semistructured interviews, focus group discussions (FGD) and ethnographic observation gathered from June 2018 to June 2019 are thematically analysed and compared to identify patterns and singularities in how DrOTS stakeholders perceive and interact with DrOTS technologies, its enrolment processes, objectives and team.
Ethics approval was obtained from the National Bioethics Research Committee of Madagascar and Stony Brook University institutional review board. Study results will be submitted for peer-reviewed publication. In Madagascar, results will be presented in person to Ministry and other Malagasy decision-makers through the Institut Pasteur de Madagascar.
This study is designed to foreground the voices of patients and potential patients in the DrOTS programme. CHW participants in this study also supported the design of study information sessions and recruitment strategies. One member of the mobile health team provided detailed input on the wording and content of FGD and interview guides. Study findings will be presented via a report in French and Malagasy to CHW, mobile health team and other village-level participants who have email/internet access.
Adverse pregnancy outcomes, such as hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM) and preterm birth have been linked to maternal cardiovascular disease in later life. Pre-eclampsia (PE) is associated with an increased risk of postpartum microalbuminuria, but there is no clear consensus on whether HDP increases the risk of maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Similarly, it is uncertain whether GDM, preterm birth and delivery of low birth-weight infants independently predict the risk of maternal renal disease in later life. The aims of this proposed systematic review and meta-analysis are to summarise the available evidence examining the association between adverse outcomes of pregnancy (HDP, GDM, preterm birth, delivery of low birth-weight infant) and later maternal renal disease and to synthesise the results of relevant studies.
A systematic search of PubMed, EMBASE and Web of Science will be undertaken using a detailed prespecified search strategy. Two authors will independently review the titles and abstracts of all studies, perform data extraction and appraise the quality of included studies using a bias classification tool. Original case–control and cohort studies published in English will be considered for inclusion. Primary outcomes of interest will be CKD and ESKD; secondary outcomes will be hospitalisation for renal disease and deaths from renal disease. Meta-analyses will be performed to calculate the overall pooled estimates using the generic inverse variance method. The systematic review will follow the Meta-analyses Of Observational Studies in Epidemiology guidelines.
This systematic review and meta-analysis will be based on published data, and thus there is no requirement for ethics approval. The results will be shared through publication in a peer reviewed journal and through presentations at academic conferences.
To promote uniformity in measuring adherence to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, a reporting guideline for diagnostic and prognostic prediction model studies, and thereby facilitate comparability of future studies assessing its impact, we transformed the original 22 TRIPOD items into an adherence assessment form and defined adherence scoring rules. TRIPOD specific challenges encountered were the existence of different types of prediction model studies and possible combinations of these within publications. More general issues included dealing with multiple reporting elements, reference to information in another publication, and non-applicability of items. We recommend our adherence assessment form to be used by anyone (eg, researchers, reviewers, editors) evaluating adherence to TRIPOD, to make these assessments comparable. In general, when developing a form to assess adherence to a reporting guideline, we recommend formulating specific adherence elements (if needed multiple per reporting guideline item) using unambiguous wording and the consideration of issues of applicability in advance.
To explore the role of the novel cardiac output response to stress (CORS), test in the current diagnostic pathway for heart failure and the opportunities and challenges to potential implementation in primary care.
Qualitative study using semistructured in-depth interviews which were audio recorded and transcribed verbatim. Data from the interviews were analysed thematically using an inductive approach.
Newcastle upon Tyne, UK.
Fourteen healthcare professionals (six males, eight females) from primary (general practitioners (GPs), nurses, healthcare assistant, practice managers) and secondary care (consultant cardiologists).
Four themes relating to opportunities and challenges surrounding the implementation of the new diagnostic technology were identified. These reflected that the adoption of CORS test would be an advantage to primary care but the test had barriers to implementation which include: establishment of clinical utility, suitability for immobile patients and cost implication to GP practices.
The development of a simple non-invasive clinical test to accelerate the diagnosis of heart failure in primary care maybe helpful to reduce unnecessary referrals to secondary care. The CORS test has the potential to serve this purpose; however, factors such as cost effectiveness, diagnostic accuracy and seamless implementation in primary care have to be fully explored.
Electronic cigarettes (e-cigarettes) which utilise prefilled ‘pods’ (pod devices) entered the US market in 2015. One brand, JUUL, captured more than half the e-cigarette market in early 2018, and the US Food and Drug Administration recently warned its manufacturer about adolescent uptake. This is the first qualitative study to describe distinct features of pod devices that appear to contribute to their popularity among young people.
Qualitative interview study of young adults who had used pod devices. Participants were recruited from Facebook, other social media, street recruitment and via snowball sampling.
Participants were from California, with most from the San Francisco Bay Area.
Young adults (aged 18–29 years) using multiple tobacco products (cigarettes, e-cigarettes and/or smokeless tobacco) were recruited. Of the sample of 60 participants, 24 were included in this analysis: 10 who reported experience with pod devices and 14 who used other non-pod e-cigarette devices.
Ten participants had used a pod device in the past year. Of the pod device users, seven still used a pod device at the time of the interview and five did so daily. Nearly all (n=9) pod device users smoked cigarettes in the past month; none were daily smokers. The 14 participants who used non-pod devices provided a point of comparison. Participants highlighted some distinct aspects of pod devices that facilitated use, including their aesthetic similarity to personal electronics, high levels of nicotine delivery with distinct psychoactive effects, more discreet and shorter duration use sessions, and greater social acceptability than more ostentatious non-pod e-cigarettes.
Pod devices’ unique characteristics likely encourage pod device uptake among young people. Limitations on advertising in youth channels, flavours and distribution, and education about nicotine addiction may decrease initiation among young people and non-smokers.
To empirically assess the relation between study characteristics and prognostic model performance in external validation studies of multivariable prognostic models.
On 16 October 2018, we searched electronic databases for systematic reviews of prognostic models. Reviews from non-overlapping clinical fields were selected if they reported common performance measures (either the concordance (c)-statistic or the ratio of observed over expected number of events (OE ratio)) from 10 or more validations of the same prognostic model.
Study design features, population characteristics, methods of predictor and outcome assessment, and the aforementioned performance measures were extracted from the included external validation studies. Random effects meta-regression was used to quantify the association between the study characteristics and model performance.
We included 10 systematic reviews, describing a total of 224 external validations, of which 221 reported c-statistics and 124 OE ratios. Associations between study characteristics and model performance were heterogeneous across systematic reviews. C-statistics were most associated with variation in population characteristics, outcome definitions and measurement and predictor substitution. For example, validations with eligibility criteria comparable to the development study were associated with higher c-statistics compared with narrower criteria (difference in logit c-statistic 0.21(95% CI 0.07 to 0.35), similar to an increase from 0.70 to 0.74). Using a case-control design was associated with higher OE ratios, compared with using data from a cohort (difference in log OE ratio 0.97(95% CI 0.38 to 1.55), similar to an increase in OE ratio from 1.00 to 2.63).
Variation in performance of prognostic models across studies is mainly associated with variation in case-mix, study designs, outcome definitions and measurement methods and predictor substitution. Researchers developing and validating prognostic models should realise the potential influence of these study characteristics on the predictive performance of prognostic models.
by Rachel J. Roth Flach, Chunyan Su, Eliza Bollinger, Christian Cortes, Andrew W. Robertson, Alan C. Opsahl, Timothy M. Coskran, Kevin P. Maresca, Edmund J. Keliher, Phillip D. Yates, Albert M. Kim, Amit S. Kalgutkar, Leonard BuckbinderMyeloperoxidase (MPO) is a highly abundant protein within the neutrophil that is associated with lipoprotein oxidation, and increased plasma MPO levels are correlated with poor prognosis after myocardial infarct. Thus, MPO inhibitors have been developed for the treatment of heart failure and acute coronary syndrome in humans. 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide PF-06282999 is a recently described selective small molecule mechanism-based inactivator of MPO. Here, utilizing PF-06282999, we investigated the role of MPO to regulate atherosclerotic lesion formation and composition in the Ldlr-/- mouse model of atherosclerosis. Though MPO inhibition did not affect lesion area in Ldlr-/- mice fed a Western diet, reduced necrotic core area was observed in aortic root sections after MPO inhibitor treatment. MPO inhibition did not alter macrophage content in and leukocyte homing to atherosclerotic plaques. To assess non-invasive monitoring of plaque inflammation, [18F]-Fluoro-deoxy-glucose (FDG) was administered to Ldlr-/- mice with established atherosclerosis that had been treated with clinically relevant doses of PF-06282999, and reduced FDG signal was observed in animals treated with a dose of PF-06282999 that corresponded with reduced necrotic core area. These data suggest that MPO inhibition does not alter atherosclerotic plaque area or leukocyte homing, but rather alters the inflammatory tone of atherosclerotic lesions; thus, MPO inhibition could have utility to promote atherosclerotic lesion stabilization and prevent atherosclerotic plaque rupture.