Tobacco smoking and somatic mutations in human bronchial epithelium.

Tobacco smoking causes lung cancer1-3, a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA4,5. The profound effects of tobacco on the genome of lung cancer cells are well-documented6-10, but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell; massively increasing the variance both within and between subjects; and generating several distinct mutational signatures of substitutions and of insertions and deletions. A population of cells in individuals with a history of smoking had mutational burdens that were equivalent to those expected for people who had never smoked: these cells had less damage from tobacco-specific mutational processes, were fourfold more frequent in ex-smokers than current smokers and had considerably longer telomeres than their more-mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had two or even three drivers. Thus, tobacco smoking increases mutational burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.

Novel therapies in juvenile idiopathic arthritis.

PURPOSE OF REVIEW: This review summarises the major novel treatment options for children with juvenile idiopathic arthritis (JIA) since the pandemic, reflecting not only on advancements in therapeutics but also approach to management and research. RECENT FINDINGS: Several recent international paediatric trials have been important in advancing understanding of JIA and furthering available treatment options. Biologic and small molecule agents were demonstrated to be effective and safe in recalcitrant or severe JIA (including extra-articular complications), mirroring the adult equivalent diseases. SUMMARY: Although joint and overall health have vastly improved for young people with JIA, ongoing international collaboration, critical review of treatment strategies and high quality research are essential to optimize outcomes.

Utilization, Expenditure, and Treatment Patterns Associated With Calcitonin Gene-Related Peptide Monoclonal Antibodies Reimbursed Subject to a Managed Access Protocol in Ireland.

OBJECTIVES: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are novel high-cost treatments for the prevention of migraine. This study presents data on utilization, expenditure, and treatment patterns with CGRP mAbs available under a managed access protocol in Ireland, to a cohort of treatment refractory patients (failed 3 or more previous treatments) with chronic migraine. METHODS: Data were extracted from the Primary Care Reimbursement Service High Tech claims database and special drug request online system and analyzed using Microsoft Excel and SAS. Treatment persistence was evaluated by refill patterns, and adherence was evaluated using the proportion of days covered method. Expenditure data were extracted directly from the database. RESULTS: Between September 1, 2021 and April 30, 2023, 1517 applications for reimbursement approval for a CGRP mAb were received; 1458 (96.1%) were approved for reimbursement. Total expenditure on CGRP mAbs in year 1 (September 1, 2021 to August 31, 2022) was €3.2 million. The majority of patients initiated treatment with fremanezumab (60.8%) or erenumab (37.1%). Almost 90% of patients were considered adherent, and treatment persistence was high, with more than 75% of patients receiving more than 12 months of treatment in our 18-month study time frame. CONCLUSIONS: This study demonstrates the importance of active health technology management, after reimbursement, in enabling cost-effective use of high-cost treatments while providing budget certainty for the healthcare payer. High levels of adherence and persistence suggest that treatment is successfully targeted in situations which unmet clinical need is greatest.

Cannabis donation as a harm reduction strategy: a case study.

BACKGROUND: The United States (US) continues to experience unprecedented rates of overdose mortality and there is increased need to identify effective harm reduction practices. Research from Canada describes cannabis donation through harm reduction agencies as an adjunctive strategy to mitigate the negative consequences of more harmful drugs. This case study describes the operational logistics, feasibility, and potential benefits of a cannabis donation program that was operated through a harm reduction program in rural Michigan. CASE PRESENTATION: We applied a community driven research approach to gather information from harm reduction program staff about the implementation and evolution of cannabis donation efforts in Michigan. We also examined 20-months (September 2021 through May 2023) of administrative data from a cannabis company to compare the sale and donation of cannabis products. Ten cannabis-experienced harm reduction clients received cannabis donations, with clinical staff determining client interest and appropriateness, and providing weekly pick-up or delivery. To expand product availability and sustainability, we examined administrative data from a commercialcannabis company that volunteered to provide donations. This administrative data suggests that while flower products constitute most of the adult and medical sales, edible, oil, and topical products predominated donations. Further, cost analysis suggests that donations represent only 1% of total gross sales and account for much less than the expected yearly donation amount. CONCLUSIONS: Research suggests there is potential to reduce alcohol and drug use related harms of more dangerous substances through substitution with cannabis. This case study is the first to document cannabis donation as a harm reduction practice in the US and suggests potential for sustainability dependent on state laws. Findings from this case study provide a starting point for inquiry into cannabis donation as a harm reduction strategy in the US; future research is needed to fully understand the individual-level outcomes, public health impacts, necessary legal regulations, and best practices for cannabis donation programs through harm reduction organizations.

Protective effects of ethnic enclaves: Testing pathways to alcohol use and use disorders in Mexican American young adults.

Ethnic enclave residence is associated with decreased risk for drinking and related problems, but less is known about the mechanisms that explain this association. Informed by theories of social control, we used a multilevel framework to examine whether negative attitudes toward drinking mediated associations between ethnic enclave residence (i.e., neighborhood linguistic isolation) and alcohol outcomes among Mexican American young adults (N = 628) in Southern California. Model 1 assessed mediation effects in the pathways from linguistic isolation to current drinking and alcohol use disorder (AUD). Model 2 adjusted for parental drinking attitudes and neighborhood alcohol availability. There were differential associations by gender in direct effects of linguistic isolation and negative drinking attitudes on both drinking and AUD. Among women only, linguistic isolation was related to greater abstinence and decreased AUD after accounting for social control proxies of parent attitudes and alcohol availability. Young adults' own drinking attitudes did not mediate relationships between linguistic isolation and alcohol outcomes. This study offers evidence on the importance of disaggregating Hispanic national groups by gender to uncover social mechanisms within ethnic enclave settings for tailored supports in reducing risk of drinking and alcohol-related harms.

Twitter promotion is associated with higher citation rates of cardiovascular articles: the ESC Journals Randomized Study.

The association between the dissemination of scientific articles on Twitter and online visibility (as assessed by the Altmetric Score) is still controversial, and the impact on citation rates has never been rigorously addressed for cardiovascular medicine journals using a randomized design. The ESC Journals Study randomized 695 papers published in the ESC Journal Family (March 2018-May 2019) for promotion on Twitter or to a control arm (with no active tweeting from ESC channels) and aimed to assess whether Twitter promotion was associated with an increase in citation rates (primary endpoint) and of the Altmetric Score. This is the final analysis including 694 articles (one paper excluded due to retraction). After a median follow-up of 994 days (interquartile range: 936-1063 days), Twitter promotion of articles was associated with a 1.12 (95% confidence interval: 1.08-1.15) higher rate of citations, and this effect was independent of the type of article. Altmetric Attention Score and number of users tweeting were positive predictors for the number of citations. A social media strategy of Twitter promotion for cardiovascular medicine papers seems to be associated with increased online visibility and higher numbers of citations.

White wine phenolics: current methods of analysis.

White wine phenolic analyses are less common in the literature than analyses of red wine phenolics. Analytical techniques for white wine phenolic analyses using spectrophotometric, chromatographic, spectroscopic, and electrochemical methods are reported. The interest of research in this area combined with the advances in technology aimed at the winemaking industry are promoting the establishment of novel approaches for identifying, quantifying, and classifying phenolic compounds in white wine. This review article provides an overview of the current research into white wine phenolics through a critical discussion of the analytical methods employed. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Lrig1 expression identifies airway basal cells with high proliferative capacity and restricts lung squamous cell carcinoma growth.

BACKGROUND: Lung squamous cell carcinoma (LUSC) accounts for a significant proportion of cancer deaths worldwide, and is preceded by the appearance of progressively disorganised pre-invasive lesions in the airway epithelium. Yet the biological mechanisms underlying progression of pre-invasive lesions into invasive LUSC are not fully understood. LRIG1 (leucine-rich repeats and immunoglobulin-like domains 1) is downregulated in pre-invasive airway lesions and invasive LUSC tumours and this correlates with decreased lung cancer patient survival. METHODS AND RESULTS: Using an Lrig1 knock-in reporter mouse and human airway epithelial cells collected at bronchoscopy, we show that during homeostasis LRIG1 is heterogeneously expressed in the airway epithelium. In basal airway epithelial cells, the suspected cell of origin of LUSC, LRIG1 identifies a subpopulation of progenitor cells with higher in vitro proliferative and self-renewal potential in both the mouse and human. Using the N-nitroso-tris-chloroethylurea (NTCU)-induced murine model of LUSC, we find that Lrig1 loss-of-function leads to abnormally high cell proliferation during the earliest stages of pre-invasive disease and to the formation of significantly larger invasive tumours, suggesting accelerated disease progression. CONCLUSION: Together, our findings identify LRIG1 as a marker of basal airway progenitor cells with high proliferative potential and as a regulator of pre-invasive lung cancer progression. This work highlights the clinical relevance of LRIG1 and the potential of the NTCU-induced LUSC model for functional assessment of candidate tumour suppressors and oncogenes.

Moving from nature to nurture: a systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis.

OBJECTIVES: JIA is the most common paediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanism and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA. METHODS: Four databases (MEDLINE, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature) were searched from inception to January 2020. Study quality was rated using the Newcastle-Ottawa Scale. Pooled estimates for each environmental factor were generated using a random-effects, inverse-variance method, where possible. The remaining environmental factors were synthesized in narrative form. RESULTS: This review includes 66 environmental factors from 39 studies (11 cohort and 28 case-control studies) over 45 years. Study sample sizes ranged from 41 to 1.9 million participants. Eight environmental factors from ten studies were meta-analysed. Caesarean section delivery was associated with increased JIA risk [pooled odds ratio (OR) 1.11, 95% CI: 1.01, 1.22]. Conversely, presence (vs absence) of siblings (pooled OR 0.60, 95% CI: 0.44, 0.81) and maternal prenatal smoking (pooled OR 0.70, 95% CI: 0.58, 0.84) were associated with decreased JIA risk. CONCLUSION: This review identifies several environmental factors associated with JIA and demonstrates the huge breadth of environmental research undertaken over five decades. We also highlight the challenges of combining data collected over this period due to limited between study comparability, evolution in healthcare and social practices, and changing environment, which warrant consideration when planning future studies.

Aerosolized drug delivery in awake and anesthetized children to treat bronchospasm.

Bronchospasm is a common respiratory adverse event in pediatric anesthesia. First-line treatment commonly includes inhaled salbutamol. This review focuses on the current best practice to deliver aerosolized medications to awake as well as anesthetized pediatric patients and discusses the advantages and disadvantages of various administration techniques. Additionally, we detail the differences between various airway devices used in anesthesia. We highlight the unmet need for innovation of orally inhaled drug products to deliver aerosolized medications during pediatric respiratory critical events such as bronchospasm. It is therefore important that clinicians remain up to date with the best clinical practice for aerosolized drug delivery in order to prevent and efficiently treat pediatric patients experiencing life-threatening respiratory emergencies.

A history of neurosurgical capabilities in the United States Pacific Command: from World War II to present.

Neurosurgery has benefited from innovations as a result of military conflict. The volume and complexity of injuries sustained on the battlefield require medical teams to triage, innovate, and practice beyond their capabilities in order to treat wartime injuries. The neurosurgeons who practiced in the Pacific Command (PACOM) during World War II, the Korean War, and the War in Vietnam built upon field operating room knowledge and influenced the logistics of treating battle-injured patients in far-forward environments. Modern-day battles are held on new terrain, and the military neurosurgeon must adapt. War in the PACOM uniquely presented significant obstacles due to geographic isolation, ultimately accelerating the growth and adaptability of military neurosurgery and medical evacuation. The advancements in infrastructure and resource mobilization made during PACOM conflicts continue to inform modern-day practices and provide insight for future conflicts. In this historical article, the authors review the development and evolution of neurosurgical care, forward surgical teams, and mobile field hospitals with surgical capabilities through US conflicts in the PACOM.

A Logic Model Framework for Planning an International Refugee Health Research, Evaluation, and Ethics Committee.

Collaborative approaches to supporting the health of refugees and other newcomer populations in their resettlement country are needed to address the complex medical and social challenges they may experience after arrival. Refugee health professionals within the Society of Refugee Healthcare Providers (SRHP)-the largest medical society dedicated to refugee health in North America-have expressed interest in greater research collaborations across SRHP membership and a need for guidance in conducting ethical research on refugee health. This article describes a logic model framework for planning the SRHP Research, Evaluation, and Ethics Committee. A logic model was developed to outline the priorities, inputs, outputs, outcomes, assumptions, external factors, and evaluation plan for the committee. The short-term outcomes include (1) establish professional standards in refugee health research, (2) support evaluation of existing refugee health structures and programs, and (3) establish and disseminate an ethical framework for refugee health research. The SRHP Research, Evaluation, and Ethics Committee found the logic model to be an effective planning tool. The model presented here could support the planning of other research committees aimed at helping to achieve health equity for resettled refugee populations.

Age of onset and alcohol and cannabis use disorders among Mexican American young adults: Robust substance-specific effects of early use as a risk factor.

We investigated the substance-specific and cross-substance risk associated with early onset (before age 15) of drunkenness and cannabis use in the subsequent development of alcohol (AUD) and cannabis use disorder (CUD) in Mexican American young adults. Survival analyses employed Cox proportional hazards models for AUD and CUD, separately. In cross-risk analyses, we modeled estimates for those participants reporting lifetime use of both substances. Early onset of drunkenness and early onset of cannabis use were associated with shorter time to AUD and CUD, respectively, even after accounting for psychiatric disorders. While there were no cross-risk associations, adjusting for psychiatric disorders and early onset cannabis use attenuated the association of early drunkenness with AUD.

Outcomes of COVID-19-positive acute coronary syndrome patients: A multisource electronic healthcare records study from England.

BACKGROUND: Patients with underlying cardiovascular disease and coronavirus disease 2019 (COVID-19) infection are at increased risk of morbidity and mortality. OBJECTIVES: This study was designed to characterize the presenting profile and outcomes of patients hospitalized with acute coronary syndrome (ACS) and COVID-19 infection. METHODS: This observational cohort study was conducted using multisource data from all acute NHS hospitals in England. All consecutive patients hospitalized with diagnosis of ACS with or without COVID-19 infection between 1 March and 31 May 2020 were included. The primary outcome was in-hospital and 30-day mortality. RESULTS: A total of 12 958 patients were hospitalized with ACS during the study period, of which 517 (4.0%) were COVID-19-positive and were more likely to present with non-ST-elevation acute myocardial infarction. The COVID-19 ACS group were generally older, Black Asian and Minority ethnicity, more comorbid and had unfavourable presenting clinical characteristics such as elevated cardiac troponin, pulmonary oedema, cardiogenic shock and poor left ventricular systolic function compared with the non-COVID-19 ACS group. They were less likely to receive an invasive coronary angiography (67.7% vs 81.0%), percutaneous coronary intervention (PCI) (30.2% vs 53.9%) and dual antiplatelet medication (76.3% vs 88.0%). After adjusting for all the baseline differences, patients with COVID-19 ACS had higher in-hospital (adjusted odds ratio (aOR): 3.27; 95% confidence interval (CI): 2.41-4.42) and 30-day mortality (aOR: 6.53; 95% CI: 5.1-8.36) compared to patients with the non-COVID-19 ACS. CONCLUSION: COVID-19 infection was present in 4% of patients hospitalized with an ACS in England and is associated with lower rates of guideline-recommended treatment and significant mortality hazard.

A restrictive versus liberal transfusion strategy to prevent myocardial injury in patients undergoing surgery for fractured neck of femur: a feasibility randomised trial (RESULT-NOF).

BACKGROUND: The optimum transfusion strategy in patients with fractured neck of femur is uncertain, particularly if there is coexisting cardiovascular disease. METHODS: We conducted a prospective, single-centre, randomised feasibility trial of two transfusion strategies. We randomly assigned patients undergoing surgery for fractured neck of femur to a restrictive (haemoglobin, 70-90 g L-1) or liberal (haemoglobin, 90-110 g L-1) transfusion strategy throughout their hospitalisation. Feasibility outcomes included: enrolment rate, protocol compliance, difference in haemoglobin, and blood exposure. The primary clinical outcome was myocardial injury using troponin estimations. Secondary outcomes included major adverse cardiac events, postoperative complications, duration of hospitalisation, mortality, and quality of life. RESULTS: We enrolled 200 (22%) of 907 eligible patients, and 62 (31%) showed decreased haemoglobin (to 90 g L-1 or less) and were thus exposed to the intervention. The overall protocol compliance was 81% in the liberal group and 64% in the restrictive group. Haemoglobin concentrations were similar preoperatively and at postoperative day 1 but lower in the restrictive group on day 2 (mean difference [MD], 7.0 g L-1; 95% confidence interval [CI], 1.6-12.4). Lowest haemoglobin within 30 days/before discharge was lower in the restrictive group (MD, 5.3 g L-1; 95% CI, 1.7-9.0). Overall, 58% of patients in the restrictive group received no transfusion compared with 4% in the liberal group (difference in proportion, 54.5%; 95% CI, 36.8-72.2). The proportion with the primary clinical outcome was 14/26 (54%, liberal) vs 24/34 (71%, restrictive), and the difference in proportion was -16.7% (95% CI, -41.3 to 7.8; P=0.18). CONCLUSION: A clinical trial of two transfusion strategies in hip fracture with a clinically relevant cardiac outcome is feasible. CLINICAL TRIAL REGISTRATION: NCT03407573.

GLP-1 vasodilatation in humans with coronary artery disease is not adenosine mediated.

BACKGROUND: Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect. METHODS: We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT) (n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time-Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR). RESULTS: There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G - 0.23 s (0.27) versus group GT - 0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: - 20.83 mmHg s (24.54 vs. - 21.20 mmHg s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine - 2.0 ng/ml (- 117.1, 14.8) versus - 0.5 ng/ml (- 19.6, 9.4); p = 0.60. CONCLUSION: The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation. TRIAL REGISTRATION: The local research ethics committee approved the study (National Research Ethics Service-NRES Committee, East of England): REC reference 14/EE/0018. The study was performed according to institutional guidelines, was registered on http://www.clinicaltrials.gov (unique identifier: NCT03502083) and the study conformed to the principles outlined in the Declaration of Helsinki.

Twitter promotion predicts citation rates of cardiovascular articles: a preliminary analysis from the ESC Journals Randomized Study.

AIMS: The association between the dissemination of scientific articles on Twitter and online visibility (including Altmetric score) is still controversial and the impact on citation rates has never been addressed for cardiovascular medicine journals. METHODS AND RESULTS: The ESC Journals Study randomized 696 papers published in the ESC Journals family (March 2018-May 2019) for promotion on Twitter or to a control arm (with no active tweeting from ESC channels) and aimed to assess if Twitter promotion was associated with an increase in citation rate (primary endpoint) and Altmetric score. This is a preliminary analysis of 536 articles (77% of total) published until December 2018 (therefore, papers published at least 6 months before collecting citation and Altmetrics data). In the analysis of the primary endpoint, Twitter promotion of articles was associated with a 1.43 (95% confidence interval 1.29-1.58) higher rate of citations, and this effect was independent of the type of article. Both Altmetric score and number of users tweeting were positively associated with the number of citations in both arms, with evidence of a stronger association (interaction) in the Twitter arm. CONCLUSION: Therefore, a social media strategy of Twitter promotion for cardiovascular medicine papers seems to be associated with increased online visibility and higher number of citations. The final analysis will include 696 papers and 2-year scientific citation rate and is estimated to be concluded in March 2021.

Crystal Structure-Guided Design of Bisubstrate Inhibitors and Photoluminescent Probes for Protein Kinases of the PIM Family.

We performed an X-ray crystallographic study of complexes of protein kinase PIM-1 with three inhibitors comprising an adenosine mimetic moiety, a linker, and a peptide-mimetic (d-Arg)6 fragment. Guided by the structural models, simplified chemical structures with a reduced number of polar groups and chiral centers were designed. The developed inhibitors retained low-nanomolar potency and possessed remarkable selectivity toward the PIM kinases. The new inhibitors were derivatized with biotin or fluorescent dye Cy5 and then applied for the detection of PIM kinases in biochemical solutions and in complex biological samples. The sandwich assay utilizing a PIM-2-selective detection antibody featured a low limit of quantification (44 pg of active recombinant PIM-2). Fluorescent probes were efficiently taken up by U2OS cells and showed a high extent of co-localization with PIM-1 fused with a fluorescent protein. Overall, the developed inhibitors and derivatives represent versatile chemical tools for studying PIM function in cellular systems in normal and disease physiology.

British Association of Critical Care Nurses: Evidence-based consensus paper for oral care within adult critical care units.

BACKGROUND: Patients who are critically ill are at increased risk of hospital acquired pneumonia and ventilator associated pneumonia. Effective evidence based oral care may reduce the incidence of such iatrogenic infection. AIM: To provide an evidence-based British Association of Critical Care Nurses endorsed consensus paper for best practice relating to implementing oral care, with the intention of promoting patient comfort and reducing hospital acquired pneumonia and ventilator associated pneumonia in critically ill patients. DESIGN: A nominal group technique was adopted. A consensus committee of adult critical care nursing experts from the United Kingdom met in 2018 to evaluate and review the literature relating to oral care, its application in reducing pneumonia in critically ill adults and to make recommendations for practice. An elected national board member for the British Association of Critical Care Nurses chaired the round table discussion. METHODS: The committee focused on 5 aspects of oral care practice relating to critically ill adult patients. The evidence was evaluated for each practice within the context of reducing pneumonia in the mechanically ventilated patient or pneumonia in the non-ventilated patient. The five practices included the frequency for oral care; tools for oral care; oral care technique; solutions used and oral care in the non-ventilated patient who is critically ill and is at risk of aspiration. The group searched the best available evidence and evaluated this using the Grading of Recommendations Assessment, Development, and Evaluation system to assess the quality of evidence from high to very low, and to formulate recommendations as strong, moderate, weak, or best practice consensus statement when applicable. RESULTS: The consensus group generated recommendations, delineating an approach to best practice for oral care in critically ill adult patients. Recommendations included guidance for frequency and procedure for oral assessment, toothbrushing, and moisturising the mouth. Evidence on the use of chlorhexidine is not consistent and caution is advised with its routine use. CONCLUSION: Oral care is an important part of the care of critically ill patients, both ventilated and non-ventilated. An effective oral care programme reduces the incidence of pneumonia and promotes patient comfort. RELEVANCE TO CLINICAL PRACTICE: Effective oral care is integral to safe patient care in critical care.

Direct oral anticoagulants uptake and an oral anticoagulation paradox.

Oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation is underutilised. One of the impediments to warfarin therapy is the frequent monitoring required, usually at a specialised warfarin clinic. The advent of direct oral anticoagulants (DOACs) facilitates OAC therapy without an onerous monitoring regimen. This benefit may result in the more significant adoption of DOACs in areas without a warfarin clinic. This study analysed national administrative data for reimbursed pharmacy claims to assess OAC prescribing from 2010 to 2017 and compared the use of DOACs in areas with warfarin clinics compared to those without. Over the study period, the number of patients on OAC increased by 84%, due to a rapid increase in DOAC prescribing. The findings demonstrate that DOACs have resulted in an increase in the overall uptake of OAC therapy in Ireland. However, the increased utilisation was not evidently related to populations underserved by warfarin clinics.