Cardiomyocyte orientation recovery at micrometer scale reveals long-axis fiber continuum in heart walls.

Coordinated cardiomyocyte contraction drives the mammalian heart to beat and circulate blood. No consensus model of cardiomyocyte geometrical arrangement exists, due to the limited spatial resolution of whole heart imaging methods and the piecemeal nature of studies based on histological sections. By combining microscopy and computer vision, we produced the first-ever three-dimensional cardiomyocyte orientation reconstruction across mouse ventricular walls at the micrometer scale, representing a gain of three orders of magnitude in spatial resolution. We recovered a cardiomyocyte arrangement aligned to the long-axis direction of the outer ventricular walls. This cellular network lies in a thin shell and forms a continuum with longitudinally arranged cardiomyocytes in the inner walls, with a complex geometry at the apex. Our reconstruction methods can be applied at fine spatial scales to further understanding of heart wall electrical function and mechanics, and set the stage for the study of micron-scale fiber remodeling in heart disease.

Determinants of pharmacists' confidence to participate in antimicrobial stewardship: A confirmatory factor analysis.

AIM: Pharmacists are essential members of hospital antimicrobial stewardship (AMS) teams. A lack of self-perceived confidence can limit pharmacists' involvement and contributions. Pharmacists working in AMS have reported a lack of confidence. There is currently a lack of validated measures to assess pharmacists' self-perceived confidence when working in AMS and contributors to this confidence. This study aimed to identify variables contributing to pharmacist self-perceived confidence and validate an AMS hospital pharmacist survey tool using confirmatory factor analysis (CFA). METHODS: Responses from a survey of Australian and French hospital pharmacists were used to undertake CFA and path analysis on factors related to pharmacists' self-perceived confidence. It was hypothesized that pharmacists' self-perceived confidence would be impacted by time working in AMS, perceived importance of AMS programmes, perceived barriers to participating in AMS and current participation. RESULTS: CFA demonstrated a good model fit between the factors. Items included in the model loaded well to their respective factors with acceptable reliability. Path analysis demonstrated that time working in AMS had a significant impact on pharmacists' self-perceived confidence, while perceived barriers had a negatively significant relationship. Pharmacy participation in AMS and perceived importance of AMS programmes had a non-significant impact. CONCLUSION: Findings demonstrated that the survey tool showed good validity and identified factors that can impact pharmacists' self-perceived confidence when working in hospital AMS programmes. Having a validated survey tool can identify factors that can reduce pharmacists' self-perceived confidence. Strategies can then be developed to address these factors and subsequently improve pharmacists' self-perceived confidence.

Development of an international survey tool to measure confidence and current antimicrobial stewardship practices of hospital pharmacists.

BACKGROUND: Pharmacists are identified as key members of hospital antimicrobial stewardship (AMS) teams in international guidelines. Developing an international standardized tool to measure hospital pharmacists' confidence and practices of AMS will encourage knowledge sharing and better networking between hospital pharmacists internationally. OBJECTIVES: To develop a survey tool that can be used internationally to assess pharmacists' knowledge, confidence, perceived barriers and current AMS practices. METHODS: A project team was formed to refine the survey tool that was initially used in a previous survey study. Following revision by the project team, a revised survey tool was sent to the ESCMID Study Group for Antimicrobial Stewardship (ESGAP). Feedback from the ESGAP members was considered by the project team to finalize the survey tool. RESULTS: A total of 88 changes were made to the survey tool after revision by the project team. A total of 43/216 (19.9%) of ESGAP members provided feedback on the survey tool, which led to a further 19 revisions. ESGAP members were agreeable to the questions in the survey tool, with >50% agreeing that each question was suitable. The final survey tool consisted of 42 questions, reduced from 72 questions in the original survey. CONCLUSIONS: An international survey tool to measure hospital pharmacists' confidence and practices of AMS was developed. This tool will help the wider hospital pharmacy community in conducting local studies on current AMS practices and to identify areas where further support is needed. Use of a standardized survey tool will also allow individual regions/countries to compare their data with other countries to identify potential quality improvement programmes.

An international inventory of antimicrobial stewardship (AMS) training programmes for AMS teams.

BACKGROUND: Healthcare professionals are increasingly expected to lead antimicrobial stewardship (AMS) initiatives. This role in complex healthcare environments requires specialized training. OBJECTIVES: Little is known about the types of AMS training programmes available to clinicians seeking to play a lead role in AMS. We aimed to identify clinicians' awareness of AMS training programmes, characteristics of AMS training programmes available and potential barriers to participation. METHODS: AMS training programmes available were identified by members of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) via an online survey and through an online search in 2018. Individual training programme course coordinators were then contacted (September-October 2018) for data on the target audience(s), methods of delivery, intended outcomes and potential barriers to accessing the training programme. RESULTS: A total of 166/250 ESGAP members (66%) responded to the survey, nominating 48 unique AMS training programmes. An additional 32 training programmes were identified through an online search. AMS training programmes were from around the world. Less than half (44.4%) of respondents were aware of one or more AMS training programmes available, with pharmacists more aware compared with medical doctors and other professionals (73% versus 46% and 25%, respectively). AMS training programmes were most commonly delivered online (59%) and aimed at medical doctors (46%). Training costs and a lack of recognition by health professional societies were the most frequently cited barriers to participation in AMS training programmes. CONCLUSIONS: The development of a systematic inventory of AMS training programmes around the globe identifies opportunities and limitations to current training available. Improving access and increasing awareness amongst target participants will support improved education in AMS.

Prescribing trends of oral anticoagulants in England over the last decade: a focus on new and old drugs and adverse events reporting.

Direct-acting oral anticoagulants (DOACs) are replacing conventional VKA (vitamin K antagonist, i.e., warfarin) for various indications where a therapeutic anticoagulant effect is desired. We evaluated the prescribing patterns of the DOACs and warfarin, cost implications of the increasing DOACs prescribing, and deduce the reporting of serious and fatal events, during 2009-2019 in primary care England. Prescriptions and fatal or serious adverse events reporting data, between 2009 and 2019 were analysed, using linear regression to examine the trends in prescriptions, costs, and serious and fatal events reporting. We also compared the prescribing trends of four direct-acting oral anticoagulants and warfarin, normalised to per 1000 clinical commissioning group (CCG) patient population for the year 2019 to better understand the regional differences in DOACs prescribing. The overall use of any DOACs (as a proportion of total anticoagulants) increased from 16% in 2015 to 62% in 2019 with an average increase of 87% (95% CI 83.1, 90.5) per year. The reporting of serious and fatal events associated with DOACs decreased by 6% (95% CI 12.5, - 0.1) per year. Apixaban is by far the most prescribed with an average drug cost increasing to 156% (95% CI 140, 172) per year. In England, the lowest anticoagulant prescribing region was Greater London whereas the highest prescribing regions were Yorkshire and Humber for DOACs and the East Midlands for warfarin. Interestingly, Lancashire, Merseyside, and Cheshire showed a higher usage for warfarin over DOACs. The differing prescription patterns could be a result of changes in national guidelines and increasing population. Nevertheless, DOACs appear to make an increasing contribution to total anticoagulant prescription items and costs.

Effectiveness of interventions to improve adverse drug reaction reporting by healthcare professionals over the last decade: A systematic review.

BACKGROUND: Various strategies have been studied in the literature to address the significant underreporting of adverse drug reactions (ADRs) in healthcare systems worldwide. OBJECTIVES: We conducted a systematic review of the literature that assessed the impact of various strategies to improve ADR reporting published in the last decade and compared this with the strategies identified in a previous systematic review. METHODS: MEDLINE and EMBASE databases were used to retrieve papers published from 01 July 2010 to 17 June 2019. We included papers in the English language that investigated the quantitative impact of strategies used to improve ADR reporting. RESULTS: A total of 10,021 articles were retrieved using our search criteria, of which 13 met the inclusion criteria. Multifaceted strategies resulted in a point estimate increase in ADR reporting of 9.26-fold (-2.21-17.11, 95% CI) versus 7.19-fold (-5.29-32.68, 95% CI) for single interventions. Using electronic reporting tools was more commonly identified as an interventional strategy with a point estimate increase of 13.69-fold (-5.29-32.68, 95%CI) versus 4.42-fold (0.66-8.19, 95% CI) for traditional educational methods. The quality of the majority of publications included in this review was low. CONCLUSIONS: Developments in digital technology in the last decade has led to the increased use of electronic reporting tools to improve ADR reporting. Higher quality studies investigating the impact of these electronic methods are needed to fully explore its role in improving ADR reporting.

Venous thromboembolism in critically ill COVID-19 patients receiving prophylactic or therapeutic anticoagulation: a systematic review and meta-analysis.

Many aspects of care such as management of hypercoagulable state in COVID-19 patients, especially those admitted to intensive care units is challenging in the rapidly evolving pandemic of novel coronavirus disease 2019 (COVID-19). We seek to systematically review the available evidence regarding the anticoagulation approach to prevent venous thromboembolism (VTE) among COVID-19 patients admitted to intensive care units. Electronic databases were searched for studies reporting venous thromboembolic events in patients admitted to the intensive care unit receiving any type of anticoagulation (prophylactic or therapeutic). The pooled prevalence (and 95% confidence interval [CI]) of VTE among patients receiving anticoagulant were calculated using the random-effects model. Subgroup pooled analyses were performed with studies reported prophylactic anticoagulation alone and with studies reported mixed prophylactic and therapeutic anticoagulation. We included twelve studies (8 Europe; 2 UK; 1 each from the US and China) in our systematic review and meta-analysis. All studies utilized LMWH or unfractionated heparin as their pharmacologic thromboprophylaxis, either prophylactic doses or therapeutic doses. Seven studies reported on the proportion of patients with the previous history of VTE (range 0-10%). The pooled prevalence of VTE among ICU patients receiving prophylactic or therapeutic anticoagulation across all studies was 31% (95% CI 20-43%). Subgroup pooled analysis limited to studies reported prophylactic anticoagulation alone and mixed (therapeutic and prophylactic anticoagulation) reported pooled prevalences of VTE of 38% (95% CI 10-70%) and 27% (95% CI 17-40%) respectively. With a high prevalence of thromboprophylaxis failure among COVID-19 patients admitted to intensive care units, individualised rather than protocolised VTE thromboprophylaxis would appear prudent at interim.

Medication Regimen Complexity and Hospital Readmission in Older Adults With Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is characterized by high rates of hospital admissions and readmissions. However, there is a scarcity of research into medication-related factors predicting such outcomes in this patient group. OBJECTIVE: To evaluate the effect of medication regimen complexity at hospital discharge on subsequent readmissions and their timing in older adults with CKD. METHODS: This was a 12-month retrospective cohort study of 204 older (⩾65 years) CKD patients in an Australian tertiary care hospital. Medication regimen complexity was quantified using the 65-item medication regimen complexity index (MRCI). The outcomes were the occurrence of readmission in 30 days and time to readmission within 12 months. Logistic regression was used to identify factors predicting 30-day readmission, and a competing risks proportional subdistribution hazard model, accounting for deaths, was used for factors predicting time to readmission. RESULTS: Overall, 50 (24%) patients, predominantly men (72%), were readmitted within 30 days of follow-up. MRCI was not significantly associated with 30-day readmission (odds ratio [OR] = 1.27; 95% CI = 0.94-1.73). The median (interquartile range) time to readmission within 12 months was 145 (31-365) days. On a multivariate analysis, a 10-unit increase in MRCI was associated with a shorter time to readmission within 12 months (subdistribution HR = 1.18; 95% CI = 1.01-1.36). Conclusion and Relevance: Medication regimen complexity was not significantly associated with 30-day readmission; however, it was associated with a significantly shorter time to 12-month readmission in older CKD patients. This finding highlights the importance of medication regimen complexity as a potential target for medical interventions to reduce readmission risks.

Evaluation of a chronic kidney disease risk assessment service in community pharmacies.

AIM: Targeted 'opportunistic' screening might be a sustainable approach for the early detection of people with undiagnosed chronic kidney disease (CKD). The aim of this study was to implement and evaluate a CKD risk assessment service in the community pharmacy setting. METHODS: Twenty-four pharmacies in Tasmania, Australia participated in this study. Targeted people were aged between 50 and 74 years, with at least one CKD risk factor. The QKidney risk calculator was used to estimate the participants' 5-year percentage risk of developing moderate-severe CKD. Participants identified with ≥3% risk were referred to their general practitioner (GP) and followed-up after 9 months. Laboratory data was collected from a pathology provider. The main outcome measures were rates of GP referral uptake and of participants who underwent estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (ACR) measurement. RESULTS: We analyzed data for 389 screened participants, of whom 203 (52.1%) had ≥3% 5-year risk of developing moderate-severe CKD and were referred to their GP. Follow-up was successful for 126 participants and showed low (27%) GP referral uptake. Analysis of the pathology data revealed suboptimal kidney testing in participants with ≥3% risk, with eGFR and ACR tests performed for only 52.7% and 25.1% of these participants, respectively. CONCLUSIONS: There is significant scope for improving early detection of CKD via implementation of a community pharmacy-based CKD risk assessment service. However, a healthcare system that encourages inter-professional collaboration between community pharmacists and GPs, and provides a robust referral pathway is needed to optimize the effectiveness of this service.

Adherence assessment practices in haemodialysis settings: A qualitative exploration of nurses and pharmacists' perspectives.

AIMS AND OBJECTIVES: To explore clinician assessment of patient adherence and identify strategies to improve adherence assessment practices in haemodialysis settings. BACKGROUND: Patients with chronic kidney disease undergoing haemodialysis are typically prescribed complex regimens; as such, they are at high risk of medication nonadherence. Current clinical practices focus on prescribing medications; however, little attention is paid to measuring and ensuring patient adherence to their prescribed treatments. DESIGN: A qualitative study. METHODS: Semi-structured individual interviews were conducted in November and December 2016, with 12 nurses and 6 pharmacists, working in Australian haemodialysis settings. The study was conducted and reported in accordance with COREQ guidelines. RESULTS: Participants were 25-60 years old and had 1-27 years of experience in dialysis. Seven themes related to assessing adherence were identified: prioritisation of resources, interplay between workload and available time, awareness of formalised adherence measures and training deficits, concerns about practicality/suitability of adherence measures, communication of assessment services, patient participation and trust. Three themes related to strategies for improving adherence assessment practices were identified: formalisation of adherence assessment process, integration of assessment processes and tools into routine, and use of multidisciplinary support to assess and promote adherence. CONCLUSIONS: Current adherence assessment practices could be improved through formalisation and integration of the assessment process into dialysis unit policy/procedures. Additionally, as barriers to assessing adherence were identified at organisational, professional and patient levels, there is a need to address barriers from each level in order to improve adherence assessment practices in haemodialysis settings. RELEVANCE TO CLINICAL PRACTICE: This qualitative study highlights the challenges and practical ways by which adherence assessment practices could be improved in haemodialysis settings. This would encourage renal clinicians to actively participate in adherence assessment and promotion activities to ensure patients benefit from their therapies.