Статті в журналах з теми "Evaluation et Optimisation"

Impact of model-based operation of nutrient removing SBRs on the stability of activated sludge population was studied in this contribution. The optimal operation scenario found by the systematic model-based optimisation protocol of Sin et al. (Wat. Sci. Tech., 2004, 50(10), 97–105) was applied to a pilot-scale SBR and observed to considerably improve the nutrient removal efficiency in the system. Further, the process dynamics was observed to change under the optimal operation scenario, e.g. the nitrite route prevailed and also filamentous bulking was provoked in the SBR system. At the microbial community level as monitored by DGGE, a transient shift was observed to gradually take place parallel to the shift into the optimal operation scenario. This implies that the model-based optimisation of a nutrient removing SBR causes changes at the microbial community level. This opens future perspectives to incorporate the valuable information from the molecular monitoring of activated sludge into the model-based optimisation methodologies. In this way, it is expected that model-based optimisation approaches will better cover complex and dynamic aspects of activated sludge systems.

Cet article résume les apports du programme «Porcherie verte» dans l’évaluation globale intégrée des systèmes de production porcine, prenant en compte à différentes échelles les diverses dimensions pertinentes de la durabilité, au-delà des seuls impacts environnementaux. La comparaison multicritères de deux types de conduite d’élevage prend en compte l’ensemble des dimensions de la durabilité (environnement, société, économie) mais à une échelle restreinte à l’atelier d’élevage porcin. Comparativement aux animaux élevés sur caillebotis, les porcs élevés sur litière avec accès à une courette bénéficient d’un meilleur bien-être, ont de meilleures performances de croissance mais leurs carcasses peuvent être plus grasses. Leurs viandes peuvent avoir une moindre qualité technologique, mais une meilleure qualité sensorielle. Ce type de conduite produit nettement moins d’odeurs désagréables mais il est plus coûteux. Les produits peuvent cependant potentiellement être mieux valorisés par un label. La modélisation visant une optimisation au niveau de l’exploitation prend en compte les dimensions environnementales et économiques, mais pas sociétales, pour comparer différentes filières de gestion des effluents. L’échelle d’approche est plus large que dans l’étude précédente pour prendre en compte les interactions entre productions animales et végétales sur le territoire de l’exploitation qui correspond à un échelon décisionnel fondamental en agriculture. La filière «Lisier brut» conduit à la meilleure marge brute marginale, avec de bons bilans environnementaux, mais la production est limitée à 60 porcs à l’ha. Le traitement biologique du lisier sans séparation de phases permet d’augmenter la production de porcs mais détériore le bilan apparent de phosphore de l’exploitation et réduit significativement la marge brute par porc produit. La mise en œuvre d’un procédé de séparation de phases préalablement au traitement biologique du lisier permet d’augmenter encore la production de porcs en respectant des contraintes environnementales sur le phosphore, mais il réduit encore plus la marge brute par porc produit. Le compostage du lisier peut être une alternative au traitement biologique pour les petites exploitations, mais son bilan environnemental est médiocre. L’exportation du compost de lisier allège les bilans apparents de N et de P de l’exploitation mais ne change pas les émissions gazeuses. Il permet de maintenir une bonne marge brute, même aux chargements élevés. L’élevage de porcs sur litière permet de produire plus de porcs à l’ha mais au prix d’une dégradation de l’impact environnemental et d’une augmentation des coûts de production. Le compostage du fumier des litières permet d’augmenter la production de porcs à l’ha, mais uniquement en l’absence de contrainte environnementale sur le phosphore, et l’accroissement marginal de marge brute est faible. L’exportation du compost excédentaire permet d’augmenter encore la production de porcs en allégeant les bilans apparents de N et P, mais pas les émissions gazeuses. Parmi les filières avec traitement, qui autorisent des chargements élevés, le traitement biologique semble réaliser le meilleur compromis entre marge brute réalisée et impact sur l’environnement, si l’on néglige les transferts d’impacts hors de l’exploitation. Parmi les filières avec traitement et exportation, qui permettent des niveaux de chargement très élevés, le compostage de fumier semble cumuler les inconvénients en termes de marge brute et d’impacts environnementaux, si l’on néglige les transferts d’impacts hors de l’exploitation associés au traitement biologique. L’évaluation globale de l’impact environnemental des élevages porcins est restreinte à la dimension environnementale mais son échelle d’approche permet d’intégrer l’ensemble des impacts associés aux processus en amont de l’exploitation L’analyse de cycle de vie (ACV) est une méthode de choix pour faire cette évaluation et a été mise en œuvre pour comparer les impacts environnementaux de trois scénarios contrastés de production porcine. La production la plus intensive, suivant le scénario des bonnes pratiques agricoles, a le plus faible impact sur le changement climatique, mais le plus fort impact sur l’acidification. La production biologique, peu intensive, consomme beaucoup de surfaces, mais elle a le plus faible impact sur l’eutrophisation. De façon générale, les meilleurs compromis entre coûts de production et respect de l’environnement sont obtenus par les systèmes les plus économes en surface, qui utilisent au mieux les capacités du sol à produire de l’aliment pour les animaux et à recevoir leurs effluents. L’absence de lien au sol coûte cher en argent et en impact écologique.

Performance evaluation of counselors plays a vital role for education industry (schools, colleges, universities, and vocational colleges). The problem can be stated with the phrases; how to design reasonable and appropriate performance indicators? The objective of this research is to design an effective performance evaluation. The purpose of this study is to explore a new method of performance evaluation that combines strategic goals with personal development goals. The purpose of performance evaluation is to better motivate the enthusiasm of counselors. With the methodology, a new issue faced at modern colleges and universities is being resolved. Therefore, for explaining methodology, this study has carried out the application analysis of the fusion particle swarm algorithm (FPSA) in the performance evaluation of instructors. First, on the basis of comprehensive analysis of performance evaluation, it discusses the advantages and disadvantages of university performance evaluation. Secondly, particle swarm and fuzzy comprehensive evaluation methods are used in the research of instructor performance evaluation. Pass the superiority of this assessment system. Index parameter evaluation is from 2.5 to 3.0. The range indicates an excellent value. In result this improved particle swarm can be compared with the state of the art (Liu et al., 2019). In conclusive remarks, this study is to provide state-of-the-art study for the current research on the topic of instructor performance appraisal in colleges and universities.

Introduction Triage is a crucial tool for managing a Multiple Victim Incident (MVI). One particularly problematic issue is the communication of results to the chain of command and control. Favourable data exists to suggest that digital triage can improve some features of analogue triage. Within this context we have witnessed the emergence of the Valkyries Project, which is working to develop strategies to respond to MVIs, and especially cross-border incidents. To that end, an IT platform called “SIGRUN” has been created which distributes, in real time, all the information to optimise MVI management. A full-scale simulation, held on the Spain-Portugal border and featuring contributions from different institutions on both sides of the border, put to the test the role of information digitalisation in this type of incidents. Objective To evaluate the impact of the synchronous digitalisation of information on the optimal management of Multiple Victim Incidents. Method Clinical evaluation study carried out on a cross-border simulation between Spain and Portugal. A Minimum Data Set (MDS) was established by means of a modified Delphi by a group of experts. The digital platform “SIGRUN” integrated all the information, relaying it in real time to the chain of command and control. Each country assigned two teams that would carry out digital and analogue triage synchronously. Analogue triage variables were gathered by observers accompanying the first responders. Digital triage times were recorded automatically. Each case was evaluated and classified simultaneously by the two participating teams, to carry out a reliability study in a real time scenario. Results The total duration of the managing of the incident in the A group of countries involved compared to the B group was 72.5 minutes as opposed to 73 minutes. The total digital assistance triage (AT) time was 37.5 seconds in the digital group, as opposed to 32 minutes in the analogue group. Total evacuation (ET) time was 28 minutes in the digital group compared with 65 minutes in the analogue group. The average differences in total times between the analogue and the digital system, both for primary and secondary evaluation, were statistically significant: p = 0.048 and p = 0.000 respectively. For the “red” category, AT obtained a sensitivity of 100%, also for ET, while with regard to AT safety it obtained a PPV of 61.54% and an NPV of 100%, and for ET it obtained a PPV of 83.33% and an NPV of 100%. For the analogue group, for AT it obtained a sensitivity of 62.50%, for ET, 70%, for AT safety it obtained a PPV of 45.45% and an NPV of 92.31%, while for ET it obtained a PPV of 70% and an NPV of 92.50%. The gap analysis obtained a Kappa index of 0.7674. Conclusion The triage system using the developed digital tool demonstrated its validity compared to the analogue tool, as a result of which its use is recommended.

Cet article présente la mise en œuvre d’un modèle de mécanique des fluides numérique pour évaluer les performances de décantation de trois bassins de stockage des eaux pluviales situés dans le sud-ouest de l’Allemagne et qui ne respectent pas les règles de l’art allemandes (rapport longueur sur largeur trop petit, entrée en virage et présence d’un siphon en sortie). Après la modélisation hydraulique 3D de l’écoulement, un suivi lagrangien des particules en suspension est mis en œuvre afin d’évaluer l’abattement des bassins pour l’ensemble des vitesses de chute. La comparaison avec la méthode de Hazen permet de montrer que cette dernière est très imprécise pour évaluer les performances de décantation d’un bassin. En matière de conception, cette étude permet de montrer que les performances peuvent être améliorées en distribuant le débit d’entrée sur plusieurs orifices ou bien en mettant en place un déflecteur.

The manner of designing biogas plants is eagerly described by each and every seller or supplier of the respective technology. Numerous feasibility studies comprising forecasts of future operation featuring different quality levels have been written. However, it is rarely possible to obtain information comparing the anticipated future numbers and real values. Nevertheless, an evaluation of past operation of BGP is of utmost importance for calibration of the calculation methods used for designing of future BGPs. Information obtained on the basis of an evaluation is also useful for the purpose of verification of correct functionality of the equipment as well as optimisation of its operation with the objective of achieving the planned (or even better) values of profitability of each respective project. A comprehensive analysis of a biogas plant is a project sensitive to accuracy of inputs. Measurements of amounts and quality of the feed substrate throughout the whole year, which comprises numerous criteria, is highly demanding and complicated, and therefore the objective of this evaluation is to analyze the performance, production and consumption of the biogas plant in the course of a calendar year (Schulz et al., 2004). Power measuring tasks are performed using calibrated gauges (which are mostly used for invoicing purposes), thus ensuring accuracy and credibility of the input data.

It’s estimated that 2% patients attending our hospital are paediatric patients with learning disabilities (PPLD). PPLD may have multiple co-morbidities leading to complex medication regimens and adherence issues.1 PPLD/carers are relied upon to retain and relay medication regimens to healthcare professionals (HCPs) on admission and across care settings, highlighting the importance of PPLD/carers keeping a current written medications list. Medicines optimisation (MO) is defined as ‘a patient centred approach, focussing on getting the most benefit for patients from their medicines’.2 PPLD may have additional MO needs which HCP’s may not be aware.AimTo determine areas of MO for PPLD.ObjectivesDuring the audit period, the objectives were to gain baseline data;to identify if current written medication lists (CWML) were keptwhether compliance issues were faced at home andif so, was HCP advice sought, andif problems obtaining medicines from GPs were faced after discharge.Standards70% of PPLD had a CWML when attending hospital5% of PPLD had an adherence issue95% of PPLD with an adherence issue received advice from a HCP5% of PPLD had issues in obtaining heir medication from their GP on discharge.MethodStandards were agreed with specialist paediatric and lead research pharmacists. PPLD were selected using an inclusion/exclusion criteria. A data collection form was developed, piloted, and used by the pre-registration pharmacist to survey patients between 5th-16th/12/16. Data analysis was carried out on Microsoft Excel. This study did not require ethics approval.Results32% had a CWLM26% had an adherence issue40% sought HCP advice for adherence advice42% had issues with supplies from GP post discharge.19 PPLD were included in the audit, with an age range of 1–16 years. Medicines were predominantly managed by carers at home, with one adolescent co-managing with their carer. Written medication records included diary, phone notes, repeat prescription, outpatient letter and a drug chart. Adherence problems included poor dissolution of omeprazole tablets and poor taste of levetiracetam tablets. Four patients (21%) required an unplanned intervention by the pharmacist relating to medicines administration issues not picked up during previous consultations. Problems obtaining medicines from GPs included restricted GP’s Formulary and miscommunication.ConclusionNo standards were achieved, thus further improvement is required. The short duration and small sample size mean the data represents a snapshot. Recommendations from this audit are:PPLD with complex medication regimens should be encouraged to keep a current written medication record e.g. ‘my medication passport’ (record book) to facilitate medicines reconciliation on transfer of care.3Education e.g. presentations to HCPs on PPLD compliance issues including administration is paramount for enabling medicines optimisation.Clear, well documented medicines information during transfers of care can reduce medication risk and minimise error. An action plan is currently in progress to improve documentation on discharge. Further work is warranted into why HCP advice is not routinely sought by PPLD/carers.ReferencesJubraj B, Deakin A, Mills S, et al. Pharmacy consultations with patients with learning disabilities. The Pharmaceutical Journal 19 Jan 2016. http://www.pharmaceutical-journal.com/learning/learning-article/pharmacy-consultations-with-patients-with-learning-disabilities/20200330.articleRoyal Pharmaceutical Society. Medicines optimisation. Helping patients to make the most of medicines. Good Practice Guidance for Healthcare Professionals in England May 2013. https://www.hee.nhs.uk/sites/default/files/documents/helping-patients-make-the-most-of-their-medicines.pdfBarber S, Thakkar K, Marvin V, et al. Evaluation of my medication passport: A patient-completed aide-memoire designed by patients, for patients, to help towards medicines optimisation. BMJ Open 2014;4:e005608. doi:10.1136/bmjopen-2014-005608

This paper reviews the fundamentals of the Exergy Cost Theory, an energy cost accounting methodology to evaluate the physical costs of products of energy systems and their associated waste. Besides, a mathematical and computationally approach is presented, which will allow the practitioner to carry out studies on production systems regardless of their structural complexity. The exergy cost theory was proposed in 1986 by Valero et al. in their “General theory of exergy savings”. It has been recognized as a powerful tool in the analysis of energy systems and has been applied to the evaluation of energy saving alternatives, local optimisation, thermoeconomic diagnosis, or industrial symbiosis. The waste cost formation process is presented from a thermodynamic perspective rather than the economist’s approach. It is proposed to consider waste as external irreversibilities occurring in plant processes. A new concept, called irreversibility carrier, is introduced, which will allow the identification of the origin, transfer, partial recovery, and disposal of waste.

Abstract Introduction Frailty is a geriatric syndrome in which physiological systems have decreased reserve and resistance against stressors. Frailty is associated with polypharmacy, inappropriate prescribing and unfavourable clinical outcomes [1,2]. Aim To identify and evaluate studies of interventions designed to optimise the medications of frail older patients, aged 65 years or over, in secondary or acute care settings. Methods The protocol was registered and published on PROSPERO (CRD42019156623). A literature review was conducted across the following databases and trial registries: Medline, Scopus, Embase, Web of Science, Cochrane Library, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature Plus (CINAHL Plus), ClinicalTrials.gov, International Clinical Trials Registry Platform and Research Registry. All types of randomised controlled trials (RCTs) and non-randomised studies (NRSs) of interventions relating to any aspect of ‘medicines optimisation’, ‘medicines management’ or ‘pharmaceutical care’ to frail older inpatients (aged ≥ 65 years) were included. Eligible studies published in English were identified from the date of inception to October 2020. Screening and selection of titles, abstracts and full texts were followed by data extraction. Risk of bias was assessed using the Cochrane Collaboration ROB 2.0 tool for RCTs and risk of bias in non-randomized studies-of Interventions (ROBINS-I) tool for NRSs. Results 36 articles were identified and of these, three were eligible for inclusion (Figure 1). All included studies were RCTs. Although all included studies examined the effect of different types of interventions on different outcomes, they all concluded that medication optimisation interventions reduced suboptimal prescribing (measured as polypharmacy, inappropriate prescribing, and underuse) among frail older inpatients. The included studies used different tools to assess prescribing appropriateness; one used the STOPP criteria, one used STOPPFrail criteria and one employed inpatient/ outpatient geriatric evaluation and management according to published guidelines and Veterans Affairs (VA) hospital standards. Two of the included studies was assessed as having ‘some concerns’ of bias, and one was judged to be at ‘high risk’ of bias. Due to the heterogeneity of the included studies, a meta-analysis was not possible. Conclusion This systematic review demonstrates that medication optimisation interventions may improve medication appropriateness in frail older inpatients. Limitations include the small number of included studies and the exclusion of non-English language articles. However, this review highlights the paucity of evidence that examines impact of medication optimisation on quality of prescribing and clinical outcomes for frail older inpatients including hospitalisation, falls, quality of life and mortality. High-quality studies are needed to address this gap and to outline the framework of medication optimisation for this vulnerable cohort group. References 1. Clegg A, Young J, Life S, Rikket MO, Rockwood K. Frailty in Older People. Lancet. 2013;381(9868):752–62. 2. Fried, L. P. Tangen, C. M.Walston, J.Newman, A. B.Hirsch, C.Gottdiener et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2011; 56(3), 146–M15

BackgroundVancomycin is commonly used for treatment of severe Gram+ neonatal infections. Currently, even with the use of optimized dosing regimens and therapeutic drug monitoring (TDM), target attainment rates are abominable, leaving patients at risk for therapeutic failure and toxicity. Model-informed precision dosing (MIPD) offers a large potential to improve therapy in the individual patient.The aim of this study was to identify a suitable model for bedside MIPD by assessing the predictive performance of published population pharmacokinetic (popPK) models.MethodsA literature search was conducted to identify parametric popPK models. PK vancomycin data were retrospectively collected from NICU patients at the Radboud University Hospital, Nijmegen, The Netherlands. The model predictive performance was assessed by comparison of predictions to observations, calculation of bias (Mean Percentage Errors, MPE) and imprecision (Normalized Root Mean Squared Errors, NRMSE). Evaluations included both a priori (model covariate input) and a posteriori (model covariate and TDM concentration input) scenarios.Results265 TDM measurements from 65 neonates (median postmenstrual age:32 weeks [range:25–45 weeks]; median weight:1281g [range:597–5360g]; median serum creatinine:0,48 mg/dL [range:0,15–1,28 mg/dL]) were used for model evaluation. Six popPK models were evaluated1–6. A posteriori predictions of all models were consistently more accurate and precise compared to the a priori (starting dose) predictions. PopPK models of Frymoyer et al. and Capparelli et al. consistently performed best through all evaluations in both the a priori and a posteriori scenario (MPE ranging from -18 to 6,4% in a priori scenario and -6,5 to -3,8% in a posteriori scenario; NRMSE ranging from 34 to 40% in a priori scenario and 23 to 24% in a posteriori scenario).ConclusionLarge differences in predictive performance of popPK models were observed. Repeated therapeutic drug monitoring remains necessary to increase target attainment rate. Best performing models for bedside MIPD were identified in our patient population.ReferencesZhao W, Lopez E, Biran V, et al. ( 2013). Vancomycin continuous infusion in neonates: Dosing optimisation and therapeutic drug monitoring. Arch Dis Child;98(6):449–453.Capparelli EV, Lane JR, Romanowski GL, et al. ( 2001). The influences of renal function and maturation on vancomycin elimination in newborns and infants. J Clin Pharmacol, 41:927–934.De Cock RFW, Allegaert K, Brussee JM, et al. ( 2014). Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards a semi-physiological function for maturation in glomerular filtration. Pharm Res;31(10):2642–2654.Frymoyer A, Hersh AL, El-Komy MH, et al. ( 2014). Association between vancomycin trough concentration and area under the concentration-time curve in neonates. Antimicrob Agents Chemother, 58(11):6454–6461.Anderson BJ, Allegaert K, Van Den Anker JN, Cossey V, Holford NHG. ( 2006). Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance. Br J Clin Pharmacol;63(1):75–84.Germovsek E, Osborne L, Gunaratnam F, Lounis SA, Busquets FB, Sinha AK. ( 2019). Development and external evaluation of a population pharmacokinetic model for continuous and intermittent administration of vancomycin in neonates and infants using prospectively collected data. J Antimicrob Chemother, 1–9.Disclosure(s)R. Keizer is an employee and stockholder of InsightRX.

Background: EP0042 was developed as an orally bioavailable potent inhibitor of FLT3 and Aurora kinases. Aurora kinases play an important role in acute myeloid leukemia (AML) and have been implicated in the development of resistance to FLT3 inhibitors (Joshi S et al. Cancer Cell 2021;39:999-1014, 8). Dual inhibition of FLT3 and Aurora kinase has been shown to overcome acquired resistance to selective FLT3 inhibition both in vitro and in vivo (Moore A et al. Leukemia 2012;26:1462-70; Tariq M et al. Br J Cancer 2021;125:966-74). Preliminary data from this ongoing Phase 1 study of EP0042 in relapsed/refractory AML were presented previously (Taussig et al. Blood 2022:140(Supplement 1): 6222-6223). Here we present further data from the dose finding and dose optimisation cohorts from the study. Methods The primary objective of this phase I/IIa, multi-centre study is to investigate safety/tolerability and to establish both the MTD and optimal dose of EP0042 when used as monotherapy, or in combination with established standard treatments in patients with AML, myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who have relapsed on or are refractory to previous therapy. Secondary objectives include PK characterisation and assessment of anti-tumour activity. Results As of July 13 th 2023, 38 patients (17 f/21 m) were enrolled across 9 different cohorts. Median age 72 years, range 25-84. Patients presented with relapsed/refractory AML (34), CMML (1) or MDS (3). 9 patients had FLT3 mutated AML at the point of entry (All FLT3 ITD). Patients were administered doses ranging from 40mg to 170mg, QD or BID, with different schedules, across 7 cohorts (Table 1). One Cycle = 28 days. 150mg BID 28/28 days was identified as the MTD with 2 DLTs identified, Grade 3 somnolence and ataxia, and Grade 3 encephalopathy. Two dose optimisation cohorts (Table 1) were subsequently initiated to further optimise the potential RP2D. These cohorts are currently ongoing. The median number of prior treatments was 2 (range 1-6). 12 patients received a prior FLT3 inhibitor including midostaurin, gilteritinib or sorafenib and 8/12 patients received ≥2 prior FLT3 inhibitors. 3 patients received prior ASCT. The most common treatment-emergent adverse events (TEAEs) ≥20% were: diarrhea (54.1%), fatigue (54.1%), febrile neutropenia (51.4%), decreased appetite (43.2%), dyspnea (35.1%), somnolence (29.7%), constipation (27.0%), ataxia (27.0%) and nausea (24.3%). 23.3% of TEAEs were > grade 3. The most common treatment related AEs (TRAEs, all grades ≥10%) were decreased appetite (29.7%), somnolence (29.7%), ataxia (27.0%), fatigue (24.3%), diarrhea (13.5%), nausea (13.5%) and dizziness (16.2%). No treatment-related death has been reported across all cohorts. Most events were manageable by temporary dose reductions and or/short interruptions. All events of ataxia and somnolence were reversible after a short treatment interruption. Across all cohorts, 18 patients achieved stable disease (SD) as best response (median no. of cycles = 3, range 1-11). 1 patient continued treatment for 11 cycles (100mg BID, FLT3wt) and another for 8 cycles (140 mg BID, FLT3-ITD) with clinical benefit. 1 patient achieved a best response of CR MRD- (150mg BID, FLT3wt) with aCRi first detected at C6D1 (2% blast, down from 38% at screening and 80% at C3D1) and confirmed with CR MRD- at C7D1 by flow cytometry. Treatment is still ongoing at C10 and patient remains transfusion independent for 4 months. Evidence of peripheral blast response was observed in 5 patients, with complete disappearance of peripheral blasts compared to baseline after a median time of 2 months on treatment. Data from the ongoing dose optimisation cohorts will be presented at the congress. Conclusions This extended data set confirms thatEP0042 has acceptable tolerability and safety. Two patient cohorts are ongoing to establish the optimum continuous dose regimen to take forward. Promising evidence of clinical benefit has been observed including a durable CR MRD-. This remission in a patient with FLT3 wild type AML indicates that EP0042 may have broader activity in AML, beyond FLT3 mutated disease. Dose optimisation cohorts are continuing to identify the RP2D. Further cohorts are planned for evaluation of EP0042 in combination with standard of care therapies.

BackgroundPatients with congenital adrenal hyperplasia (CAH) have low to no biosynthesis of cortisol and require lifelong cortisol replacement. Optimisation of hydrocortisone (HC, synthetic cortisol) therapy in this population is important, since too low or high cortisol concentrations increase the risk of adrenal crisis or Cushing’s syndrome1. HC has nonlinear pharmacokinetics (PK) caused by saturable binding to corticosteroid binding globulin (CBG)2. The objective of this analysis was to extend an established paediatric HC PK-model3 with dried blood spot (DBS) data in order to further characterise the binding behaviour of HC in children.MethodsA semi-mechanistic adult PK model for a novel HC formulation4 has previously been reduced to a paediatric model using sparse plasma samples from a phase III study in 24 patients with adrenal insufficiency5. Plasma and DBS concentrations of cortisol were collected and additional DBS HC concentrations were obtained from a follow-up study. The relation between plasma and DBS samples was characterised by a graphical evaluation, after which nonlinear mixed-effects modelling was applied using NONMEM 7.4.ResultsPlasma concentrations of cortisol were substantially higher than the corresponding DBS concentrations. The plasma/DBS ratio ranged between 2 to 8 within and between children, while the relation between the cortisol DBS concentrations and cortisol plasma concentrations showed nonlinear behaviour mirroring the nonlinear binding kinetics to CBG.ConclusionsOur graphical analysis identified substantial differences and high inter- and intraindividual variabilities between plasma and DBS samples. A nonlinear mixed-effects model is being set up to quantify these findings and allow for further prediction of HC exposure. Afterwards, effect biomarkers can be included in order to evaluate cortisol replacement therapy and to optimise the HC treatment in paediatric patients.ReferencesSpeiser PW, et al. J Clin Endocrinol Metab 2010;95(9):4133–4160.Lentjes EG, WM, et al:J Clin Endocrinol Metab. 1999;84(2):682–687.Melin J:Dissertation 2017.Melin J, et al:Clin Pharmacokinet. 2018;57(4):515–527.Neumann U. et al:Clin Endocrinol. 2018;88(1):21–29.Disclosure(s)Nothing to disclose

AimTo evaluate patient outcomes 2 years post switching Infliximab therapy from Infliximab originator molecule Remicade® to biosimilar Remsima®.MethodsPatients with PIBD who experienced induction with Remicade® therapy, were <18 years old at last follow-up and were receiving active treatment with Remsima® 2 years post switching were selected to be included for evaluation. Outcome measures included monitoring disease activity and treatment failure at baseline (before switching) and at selected time points up to 2 years post-switch. Disease activity was assessed looking at a range of parameters: disease activity scores; trough infliximab levels; haematological markers (HGB, platelets, WBC); LFTs (bilirubin, ALT, ALP); inflammatory markers (ESR, CRP) and faecal calprotectin levels. Patients who failed therapy were assessed for adverse reactions and infliximab antibody formation. Data was analysed with the Cochran Q test, repeated measures ANOVA test and Friedman test; with post-hoc Bonferroni and Wilcoxon Signed-Ranks tests if appropriate.ResultsData was available for 18 patients after exclusion criteria were applied. There was a significant increase in trough infliximab levels by the end of the period from an average of 5 ug/L to 12 ug/L at 2 years. The average dose/kg increased over 2 years by 1.5 mg/kg. Disease activity markers showed no changes between time points except a decrease in ALP levels from baseline to 1 year, but values remained within normal ranges. Four patients were discontinued from Remsima® due to side effects or loss of efficacy. The average time to treatment failure on Remsima® was 38 months (~19/20 doses). Three out of four patients developed infliximab antibodies, 2 of these patients went on to suffer adverse reactions; 1 exhibited joint pain which settled weeks after each infusion and the other developed an immediate infusion reaction in the form of a rash with urticaria on the 3rd infusion of Remsima®.ConclusionInfliximab biosimilars, such as Remsima®, were approved for use in PIBD by the EMA after studies in adult populations with rheumatic diseases.1 2 Induction studies have shown efficacy in PIBD but data on switching is limited and short-term.3 4 Our data shows no significant differences in clinical patient outcomes over a 2-year period in a cohort switched from Remicade® to Remsima®. In fact, a significant increase in trough infliximab levels in patients remaining on Remsima® suggests efficacy in producing therapeutic levels in PIBD patients. Increased levels may be explained by dose intensification used by the PIBD multi-disciplinary team (MDT), reflecting careful dose optimisation strategies used at this trust throughout the time period. Patients losing response were not unexpected and are likely not due to the biosimilar switch but rather due to the length of time the patients were on treatment. The small sample size and retrospective nature of this study mean larger cohort studies are required over prolonged time periods to confirm these findings. PIBD MDTs should continue to monitor patients for adverse reactions, particularly in those who develop infliximab antibodies.ReferencesPark W, Hrycaj P, Jeka S, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 2013;72:1605–1612.Yoo DH, Hrycaj P, Miranda P, et al. Extended report: a randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when co-administered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013;72:1613.Sieczkowska J, Jarzębicka D, Banaszkiewicz A, et al. Switching Between Infliximab Originator and Biosimilar in Paediatric Patients with Inflammatory Bowel Disease. Preliminary Observations. J Crohn’s Colitis 2016;10:127–132.Sieczkowska J, Jarzębicka D, Meglicka M, et al. Experience with biosimilar infliximab (CT-P13) in paediatric patients with inflammatory bowel diseases. Therap Adv Gastroenterol 2016;9:729–735.

Topicality. In modern conditions, the society feels a growing demand in products made from natural ingredients of high nutritional value. Such products include meat pastes, the quality of which depends on their recipe, technological processes, equipment, and modes of its operation. With the implementation of innovative technological regimes and new equipment, there is a necessity to determine and prognosticate the quality of food products at all stages of their production and sale. According to the mentioned above, as well as economic feasibility of using automated systems for technological processes management, there is a need to elaborate a new mathematical and analytical approach to assessing and prognosticating changes in the quality of meat paste with various additives. Aim and research methods. The aim of this research is to elaborate a method for modeling the material system state, based on differential equations of kinetics of biochemical processes, assessment, and prognostication of food quality. Research methods. The method of mathematical and analytical evaluation of the paste products quality is grounded on modified mathematical models, differential equations, visualisation of research results in the form of 3D graphs, obtained by using symbolic computer mathematics. The quality of new meat paste products is compared with the quality of the paste, which is assumed to be relatively optimal according to the main organoleptic parameters of sensory quality assessment and control sample. The control sample of the paste is cooked according to the classical technology, and the recipe (GSTU 4424:2005). The prototype samples are cooked according to the innovative technology, which involves adding mechanically deboned poultry meat to the main raw material. Results. New results of analytical and experimental studies of the quality of meat paste products, cooked according to the classic recipe with the use of mechanically deboned poultry meat, are offered. The method for determining the coefficients, included in the mathematical model for assessing the meat paste products quality, their analytical relation with the optimization parameter, is elaborated. The expediency of using modern methods of symbolic computer mathematics for solving and analysing differential equations, presenting results in 3D graphs, is proved. The conducted research makes it possible to prognosticate the quality of food products, to control possible changes in their recipe while using various additives, to carry out elaborating new paste products. Conclusions and discussion. Based on the results of theoretical and experimental studies, a new mathematical model for estimating the quality of meat paste products in the form of the first-order differential equation, is offered. Its analogue is the equations, recommended for modeling the processes of biochemical kinetics. It is proved that the computer programme of mathematical and analytical research and prognostication the foodstuff quality (Goots et al., 2018) is universal. The offered mathematical model makes it possible to envision the quality of meat paste products, based on organoleptic evaluation. With its help, it becomes possible to determine the vector of possible changes in product quality and its optimisation, while elaborating the 3D graph. Mathematical and analytical assessment of the new paste products quality highlights that the partial replacement of the main meat raw by mechanically deboned poultry meat, and in pastes, made according to classical technology and the GSTU recipe (4424:2005), does not really reduce the parameters of organoleptic evaluation. In some cases, they are even higher than in the control paste samples, and very close to optimal ones. This new mathematical and analytical approach to assessing the paste products quality is promising in new culinary products elaboration in the restaurant business.

AimIn March 2020, COVID-19 triggered an NHS directive to reduce face-to-face consultations and adapt to virtual clinics.1 Hospital pharmacies, each with their own model of care, quickly innovated to ensure patients received their medication safely.The aim of this study was to evaluate the provision of medications optimisation for paediatric patients following virtual outpatient consultations (VOC) and explore potential improvements for future implementations.MethodThis was a mixed method study using quantitative data; which reviewed medications sent to patients in red, amber, and green categories2 and qualitative data; using patient feedback, to evaluate the processes in three London hospitals. Pathway mapping (PM) sessions, with multidisciplinary team involvement, were conducted across these hospitals to identify areas for improvement and analyse gaps in services. Virtual PM sessions were attended by 30 representatives across the multidisciplinary team including: pharmacists, nurses, consultants, pharmacy technicians, post room attendants; and general, operational, and project managers.Semi-structured questionnaires were used to conduct one to one telephone interviews with patients’ families. A separate topic guide was used to interview General practitioners (GP) and primary care network (PCN) pharmacists. The audio recordings were transcribed as ‘intelligent verbatim’ and analysed using Nvivo. Braun and Clarke’s six phases approach was used to conduct an inductive thematic analysis.3 To improve the rigorousness of the study, more than 50% of the transcript were double coded.4As this was a service evaluation, ethics approval was not necessary. The project was registered with each hospital’s clinical audit department.ResultsThe three process maps were analysed and potential improvements for the medicines optimisation pathway were assessed by a paediatric pharmacy subgroup using ease-impact matrix. Potential improvements include: exploration and use of Electronic Prescription Service by secondary and tertiary care, improving communication through Information Technology systems between prescribers and hospital pharmacists, and the creation of a transparent standard operating procedure regarding medication supply following VOC.Seventy-one patients’ families across the sites were interviewed between January-May 2021 to reflect on their experience of receiving medications following a VOC. Four GPs and one PCN pharmacist were interviewed in May 2021 to assess on the impact of VOC on primary care.Key reflections from themes generated include the convenience of receiving medications from hospital pharmacies following VOC, satisfaction of the current process, including medicines packaging and medicines information provided to patients and their families.Other reflections included limitations of the current process and its implication on patient safety. Medicines information helplines and education provided by pharmacists were regarded by patients’ families and GPs as a valuable attribute.ConclusionPatients’ families appreciated the current model of care, however patients’ families and primary care healthcare professionals have identified both challenges and suggestions for improvement in delivering the current model. Future research should focus on a mixed mode of integrated care with green and amber medications2 prescribed directly to community pharmacies with clinical screening and counselling conducted by hospital pharmacists.ReferencesStevens S and Pritchard A. Important and urgent – next steps on NHS response to Covid-19. NHS England [Online]. 17 March 2020: Available at: https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/03/urgent-next-steps-on-nhs-response-to-covid-19-letter-simon-stevens.pdfGuy’s and St Thomas’ NHS Foundation Trust, Kings College Hospital NHS Foundation Trust, Lewisham and Greenwich NHS Trust. South East London Joint Medicines Formulary. netFormulary. [Online]. 2020: Available at: http://www.selondonjointmedicinesformulary.nhs.uk/Braun V and Clarke V. Using thematic analysis in psychology. Qualitative Research in Psychology 2006;3:77-101.Maher C, Hadfield M, Hutchings M, et al. Ensuring rigor in qualitative data analysis: a design research approach to coding combining NVivo with traditional material methods. International Journal of Qualitative Methods 2018;17:1-13.

Abstract This study focuses on the role of a clinical pharmacist in the optimisation of pharmacotherapy in the case of patients during pregnancy and its importance within the hospital sector in Slovakia. Retrospective evaluation of pharmacotherapy in pregnant patients with a focus on teratogenicity and appropriate drug selection was used. The hospital data were collected during 24 months from 22 female patients. The main observed outcome was health condition of the newborn, and it was expressed as healthy newborn, illness of the newborn, any congenital defect or malformation, spontaneous abortion, or unspecified information about the newborn. Based on a foetal risk assessment of used therapeutic agents from the Summary of Product Characteristics (SmPC), basal foetal and neonatal risk assessment (Briggs et al., 2017), and recommendations and related human past reports and supporting evidence studies, drugs were divided into two groups: confirmed foetal risk drugs and negative (nonconfirmed) foetal risk drugs. A total of 36.3% of the patients used two drugs. Patients most frequently used drugs during the first trimester (81.8%). During pregnancy, the most used drugs were for the nervous system (25.5%), anti-infective agents (23.6%), and respiratory therapeutic agents (14.5%). Of the 22 patients, 16 (73%) had healthy newborns, despite the use of therapeutic agents with different foetal-risk variations. In the group of therapeutic agents with confirmed risk, in some, negative effect on the newborn's health was clinically manifested. Spontaneous abortion was present after using norethisterone acetate and valproic acid; birth defect (unspecified) was present after usage of interferon β-1a and methylprednisolone sodium succinate. An illness (heart murmur) was present after the use of monohydrate sodium salt of metamizole. Another illness (Wilm's tumour) was present after the use of budesonide. Unspecified information about the newborn was observed in four cases after the use of prednisone, allopurinol, nadroparin, and fluvastatin.

BackgroundInternational experts recommended pazopanib to treat a 9 year old boy with a recurrent desmoid tumour. The tumour had progressed, leading to blockage of the airway and dysphagia. The child had previously received three lines of intravenous chemotherapy as well as surgery and local radiotherapy. Treatment intent was to give an effective oral therapy with minimal side effects aiming to maintain a reasonable quality of life and prevent further life threatening respiratory compromise. As the child had an unsafe swallow, the drug would need to be given via a gastrostomy tube.Pharmacy InputA literature review was completed to establish the evidence to support the use and dose of pazopanib to treat desmoid type tumours in children.1 2 Attempts made to find a commercial supply of pazopanib liquid yielded no results. In the absence of any data or experience from other principal children’s cancer centres in the UK, first principles were used to review the physico-chemical properties of the molecule. Given the highly insoluble nature of pazopanib, an extemporaneous formulation for a pazopanib suspension was developed using Orasweet®, by adapting a formula suggested by the University of Oklahoma.3 A risk assessment for the preparation process was completed and a mini isolator was re-commissioned for this purpose following appropriate testing by Quality Control. The Department of Pharmacology at Newcastle University were contacted to establish if therapeutic drug level analysis might be possible. Local approval for pazopanib use was obtained from the Drug and Therapeutic Group and an IFR was submitted to NHS England.ChallengesIt was challenging to establish a dose regimen since the recommended paediatric dose from Phase I studies of pazopanib were dependent on the formulation used.1 4 Pharmacokinetic sampling was not possible as no assay had been developed in the UK. The lack of availability of any commercial or compassionate use liquid preparation meant that the only way of giving the drug to this child was to prepare an extemporaneous preparation, despite paucity of evidence to support the stability of the preparation. Funding was not approved by NHS England; local funding was agreed.Outcome and DiscussionThe child commenced treatment with the suspension in October 2018, administered via the gastrostomy tube. By July 2019 the patient had completed 10 cycles of therapy. Treatment was well tolerated. Minor side effects included abdominal and leg pain, vomiting, and a change in hair colour. The patient has had a good clinical response and a recent scan has shown substantial improvements in morphological appearance and size of the tumour.These results indicate that a locally prepared extemporaneous oral chemotherapy suspension can be successfully used to deliver treatment for a rare type of children’s cancer. Pharmacy colleagues from across the department collaborated to facilitate this novel treatment option.ReferencesGlade Bender J, Lee A, Reid J, et al. Phase I pharmacokinetic and pharmacodynamic study of pazopanib in children with soft tissue sarcoma and other refractory solid tumors: a children’s oncology group phase I consortium report. JCO 2011;31:3034–3043.Agresta L, Lee H, Turpin B, et al. Pazopanib therapy for desmoid tumors in adolescent and young adult patients. Pediatr Blood Cancer 2018;65:e26968.Allen L Jr. Pazopanib 50 mg/ml oral suspension. US Pharm 2015;40:61–62.Heath E, Forman K, Malburg L, et al. A phase I pharmacokinetic and safety evaluation of oral pazopanib dosing administered as crushed tablet or oral suspension in patients with advanced solid tumors. Invest New Drugs 2012;30:1566–1574.

Chronic Obstructive Pulmonary Disease (COPD) is a chronic lung condition distinguished by structural changes and mucus build-up which causes dyspnoea. COPD is universally diagnosed by a spirometry test. A Forced Expiratory Volume in one second (FEV1)/Forced Vital Capacity (FVC) of <0.7, is often used to justify COPD diagnosis (Hopkinson et al., 2019, Brit Med J, 366, l4486). Reliance on spirometry tests alone may only highlight airway obstruction and not identify other consequences of COPD like impaired gas exchange which is implicated in the development of postoperative pulmonary complications. Cardio-pulmonary exercise testing (CPET) provides a more detailed look into the pathophysiology of COPD and is routinely used in perioperative settings to determine a patient’s fitness for surgery. The aims of this study were to 1) identify the number of bladder cancer patients with undiagnosed COPD, and 2) compare COPD-related CPET variables between bladder cancer patients medically diagnosed with COPD (COPDMED) who had the potential to be diagnosed at the time of CPET (COPDCPET) and those without COPD (non-COPD). All testing was performed per the American Thoracic Society/American College of Chest Physicians guidelines (2003, Am J Resp Crit Care Med, 167, 211-277). COPD-related CPET variables recorded included Minute Ventilation (V̇E; L·min-1), Peak Oxygen Consumption (V̇O2peak; mL·kg-1·min-1), the Anaerobic Threshold (AT; mL·kg-1·min-1), Ventilatory Equivalence for Carbon Dioxide (V̇E/V̇CO2), Breathing Reserve (BR; %). Eighty-two patients with bladder cancer (COPDMED [n=9], non-COPD [n=73]) underwent preoperative spirometry and CPET. In the non-COPD patients, 21 (29%) had an FEV1/FVC< 0.7, indicative of COPD and thus groups as COPDCPET. Within the COPDCPET group, 8 (40%) had an FEV1 between 50-70% of predicted which indicated moderate COPD. There was no difference found in all CPET variables measured between COPDMED and COPDCPET (P > 0.05). When COPDMED and COPDCPET were combined and compared against the non-COPD, there was a difference found in their median (95% CI) V̇Erest (13.3 [12.3-14.2] vs 11.75 [11.2-12.6] L·min-1, P = 0.02, g = 0.28). V̇O2peak (14.95 [13.64-18.12] vs 17.16 [16.35-19.11] mL·kg-1·min-1, P = 0.049, g = 0.29). V̇E/V̇CO2 at the AT (38 [36-40] vs 36 [34-37], P = 0.04, g = 0.49). There was also a difference in mean +/- SD BR (36 +/- 17 % vs 47 +/- 14 %, P = 0.004, g = 0.69). This study demonstrates the underdiagnosis of COPD in perioperative settings. Future research should assess the use of targeted COPD optimisation preoperatively.

IntroductionInfants and children with congenital heart defects are reliant on medicines to treat the symptoms of heart failure whilst they wait for corrective or palliative surgery. Medicines optimisation for this group of patients is a complex and challenging concept. This is because there are many factors that need to be considered to ensure the effective and safe use of these medicines.Infants and children undergo significant physiological and pharmacological changes over a relatively short period of time.1 In addition, this group of patients also present challenges for the safe administration of these medicines at home.2 Failure to optimise these medicines may result in reduced symptom control with negative effects on health outcomes for the family and child.The aim of this service evaluation was to identify whether patients attending for day case diagnostic catheter procedures on the children’s cardiology ward could benefit from having their medicines optimised during their hospital visit.MethodData was collected prospectively over a period of 7 months from August 2019 to March 2020. Patients were included if they attended the children’s cardiology ward for a day case diagnostic cardiac catheter during the study period. In addition, they needed to be taking at least one long-term medicine at home.A pharmacist with experience in children’s medicines conducted a medication review with the family during their attendance. This included a consultation about which medicines were being taken at home, and listening to the experience that the family had from using their medicines. Medicines were then reviewed using up to date information such as weight, test results and medicines information resources. Anonymous data was kept using a Microsoft Excel® spreadsheet.ResultsIn total, 175 patients were assessed for inclusion during the study period. 57 families were found to be administering a long-term medicine at home and had their medicines reviewed. Subsequently, 13 patients had their medicines optimised.The most common recommendation was to increase the dose of a medicine for an up to date weight or because of failure to control symptoms (n=11). This was frequently seen with medicines such as aspirin, captopril and diuretics.In addition, more subtle and unexpected interventions regarding medication safety at home were also identified (n=2). For example, one family were found to be ten times under dosing their child due to an unidentified change in strength of liquid medication from primary care. Another family described their difficulty with crushing and dispersing tablets to administer using a nasogastric tube. This resulted in a block tube that required an additional hospital visit to have a new tube inserted. Additional action was taken to report and rectify these medication errors.ConclusionThis project has demonstrated the value that can be gained from a pharmacist providing ongoing reviews of medicines used by families when they attend a children’s cardiology centre. Day case admissions in a specialist hospital may be seen as low priority to professionals. However, this is an ideal opportunity to provide support to families who use medicines at home.ReferencesKearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology--drug disposition, action, and therapy in infants and children. New England Journal of Medicine 2003;349:1157-1167.NHS England and NHS Improvement. The NHS patient safety strategy. Safer culture, safer systems, safer patients. 2019. [Cited: 14th August 2021]. Available at: https://www.england.nhs.uk/patient-safety/the-nhs-patient-safety-strategy/

Abstract Introduction Research active healthcare organisations and staff have been shown to significantly improve performance and patient outcomes1. Undertaking research is a core element of the pharmacist role, however many pharmacists report not having the skills, knowledge and/or resources to take part2. There are many opportunities for the delivery of transformational research within primary care, however pharmacy team engagement is lacking. Aim To explore the barriers and facilitators to research engagement within a Clinical Commissioning Group (CCG) Medicines Optimisation team. Methods Twelve focus groups, guided by a semi-structured topic guide, were held over MS Teams between October 2021 and February 2022. 37 participants (pharmacists, pharmacy technicians and administrative support roles) attended and discussed topics relating to their experiences of engaging with research, as well as what helped or hindered them. Detailed notes were taken and analysed using Thematic Analysis. Following this inductive analysis, which aimed to capture all themes arising from the data, the Consolidated Framework for Implementation Research (CFIR)3 was applied. This helped to categorise the barriers and facilitators into domains which influence to what extent research is undertaken. The analysis was validated by the CCG team. This study was deemed to be service evaluation and therefore no ethical approval was needed. Results Three core themes emerged: People, Place and Practicalities. Individuals felt they had limited knowledge and capabilities in the field of research, despite having an internal motivation to engage in research activity. The perception of research was often linked in peoples’ thoughts to academia or secondary care/ acute Trusts or lab-based, and therefore not really something they would engage with in their current role. A lack of research culture, leadership and visibility of projects were all thought to hinder the team. A clear need for training and education in research (what it is, how it can be done, and available tools) was expressed, as well as appropriate resource allocation. Mapping to the CFIR illustrated that most barriers fell within the inner setting (i.e. the organisation itself) and with the process of conducting research, such as limited time, lack of encouragement from champions and poor feedback from projects. Enablers were also identified which included advice offered by external organisations, dissemination about work conducted in other primary care organisations and beliefs about the benefits of being research active. Discussion/Conclusion Participants perceived there to be many more barriers to research engagement than enablers, and these ranged from challenges with the individual projects, the process of conducting research within the organisation, things about the person themselves, their organisation or the wider setting of primary care. Areas for improvement were identified, mainly through increased training, visibility of projects and interested people, development of champions and role models, and stronger links with academia. This study was conducted with only one CCG and therefore further work needs to explore the experience within other integrated care boards and across secondary and community practice. References 1. Hanney, S., Boaz, A., Soper, B. and Jones, T. Engagement in research: an innovative three-stage review of the benefits for health-care performance. Health Services and Delivery Research, 2013;1(8). ISSN (print) 2050-4349 2. Crilly P, Patel N, Ogunrinde A, Berko D, Kayyali R. Community Pharmacists’ Involvement in Research in the United Kingdom. Pharmacy. 2017;5(3):48. https://doi.org/10.3390/pharmacy5030048 3. Damschroder, L.J., Aron, D.C., Keith, R.E. et al. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implementation Sci 2009;4:50. https://doi.org/10.1186/1748-5908-4-50

Abstract Introduction Literature searching has revealed a lack of high-quality research outlining the use of tools or checklists in hospitalised patients. Additionally, few tools identified relate directly to clinical pharmacy practice. The tools identified focus on specific disciplines (e.g. critical care) or specific tasks (e.g. handover). The MA2VER2ICK Tool is a novel clinical pharmacy tool which has recently undergone review and adaptation.[1] The tool is unique as it is comprehensive and applicable to all hospitalised patients, regardless of clinical discipline. The intended purpose of the tool is to assist clinical pharmacists in comprehensive pharmaceutical care planning. Aim Demonstrate the utility of the MA2VER2ICK tool in pharmaceutical care planning, by outlining the type and frequency of drug-related problems occurring in hospitalised patients. Methods A prospective, observational, cross-sectional study was conducted in a 560-bed acute university teaching hospital. Clinical pharmacists adopted the tool in their daily practice, in a mixed medical-surgical inpatient population, over four weeks. All drug-related problems identified were recorded and assigned to the applicable category within the tool, by the clinical pharmacist. Additionally, all drug-related problems were retrospectively assigned to applicable categories of the Pharmaceutical Care Network Europe Classification for Drug Related Problems Version 9.1,[2] for comparison, by two independent researchers. Results All identified drug-related problems identified were successfully categorised using the MA2VER2ICK Tool. In total, 753 drug-related problems were identified in 180 patients over four weeks, with 233 patient-pharmacist encounters occurring. The mean age of patients was 68.9±16 years, while 51.7% (93/180) were female and 48.3% (87/180) were male. The mean number of drug-related problems identified per patient was 4.2±3.6. The highest number of drug-related problems experienced by an individual was 20, while 17 patients experienced no drug-related problem. The majority of drug-related problems identified using the tool related to medication reconciliation (52.7%; 397/753), followed by prescription endorsement and administration (17.3%; 130/753) and pharmacotherapy optimisation (9.3%; 70/753). In comparison with the MA2VER2ICK Tool, the Pharmaceutical Care Network Europe classification system has a much larger range of categories for assigning drug-related problems. Despite this, a proportion of identified drug-related problems 1.6% (12/753) could not be categorised using this tool, while there were also several categories within the tool 43.2% (19/44) whereby no drug-related problems were assigned. Conclusion This study demonstrates that the MA2VER2ICK Tool is a robust clinical pharmacy tool, that is effective and practical in assisting clinical pharmacists with the identification of drug-related problems and thus is a useful guide to facilitate pharmaceutical care planning at the patient’s bedside. This is in comparison with the Pharmaceutical Care Network Europe classification system, which has less utility as a clinical pharmacy tool, but is better placed as a research instrument. Despite demonstrating the usefulness of the MA2VER2ICK Tool in identifying drug-related problems, the clinical significance of those identified was not assessed during this study. However, data collection occurred in real time, facilitating the identification of actual and potential problems, thus reducing the likelihood of underestimating the incidence rate. References 1. O’Donovan C, Henman M, McManamly C et al. A mixed-methods review and adaptation of a novel clinical pharmacy tool: The MA2VER2ICK Tool Study. 2024. International Journal of Pharmacy Practice. 2024;32(S1):i45. 2. PCNE Classification for Drug-Related Problems V9.1: Pharmaceutical Care Network Europe; 2020 [cited 06 December 2023]. Available from: https://www.pcne.org/upload/files/417_PCNE_classification_V9-1_final.pdf

Background and AimConcentrated standardised parenteral nutrition (CSPN) may reduce the delay in commencing parenteral nutrition (PN) in preterm infants compared with conventional individualised PN. Optimisation of early nutrition, with emphasis on earlier commencement of PN to include amino acids and addition of lipids within 24 hours of birth, ameliorates early postnatal growth failure.1 2 Cumulative nutritional deficit often seen in significantly preterm infants may lead to poor neurodevelopmental outcome.3 4 CSPN was introduced in our neonatal unit in December 2017 with the objective of improving early nutrition. The aim of this service evaluation was to assess the suitability of CSPN and its impact on the growth of preterm infants in our tertiary level neonatal unit.MethodsIn December 2017, the neonatal PN provided was switched from individualised PN to CSPN based on a modified ‘SCAMP’ regimen. Retrospective and prospective growth parameter data was collected for infants receiving PN within 24 hours of birth born between September to November 2017 (individualised PN arm) and from September to November 2018 (CSPN arm). Infants were excluded if they died or transferred out of the local neonatal service before day 28 of life, or died before transitioning from PN to full enteral feeds. Weight and head circumference at birth, 28 days old and 36 weeks corrected gestation/discharge were converted to z scores using the LMS method. The Mann-Whitney test was used to compare continuous data. Annual PN expenditure, and wastage of ordered PN, before and after the switch to CSPN, was calculated using the pharmacy stock management system, pharmacist and finance records.Results20 infants (mean gestational age 28 weeks) and 21 infants (mean gestational age 29.6 weeks) were included in the CSPN and individualised PN groups respectively. There were no differences in demographic data of each group. CSPN was commenced earlier (median 8 hours old (n=20)) than individualised PN (median 25 hours old (n=19)), (U=42, p<0.0001). There was no statistical difference in the change in weight z score from birth at 28 days old (median -0.47 (n=20) CSPN vs -0.66 (n=19) individualised PN, U=178.5, p=0.75) and at 36 weeks corrected gestation/discharge (median -0.72 (n=20) CSPN vs -0.86 (n=21) individualised PN, U=106, p=0.7). There was insufficient data collected to analyse effect on head circumference. Replacing individualised PN with CSPN resulted in a 37% reduction in procurement costs, despite an increase in the wastage of ordered PN from 7.2% to 8.5%.ConclusionA PN strategy using concentrated standardised PN can be implemented successfully in a tertiary neonatal unit setting in the United Kingdom and allows earlier commencement of PN. Use of CSPN appeared to have no adverse effect on weight gain, although small sample size may account for the lack of statistical significance in improvement of weight z score seen. Improved rates of head circumference documentation for our patients are required. Introducing CSPN resulted in a considerable reduction in procurement costs, and identifying strategies to minimise wastage of CSPN bags would further improve cost-effectiveness.ReferencesMorgan C, McGowan P, Herwitker S, et al. Postnatal head growth in preterm infants: a randomised controlled parenteral nutrition study. Pediatrics 2014;133:e120–8.Moyses HE, Johnson MJ, Leaf AA, et al. Early parenteral nutrition and growth outcomes in preterm infants: a systematic review and meta-analysis. Am J Clin Nutr 2013;97:816–26.Ehrenkranz RA, Dusick AM, Vohr BR, et al. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006;117:1253–61.Dusick AM, Poindexter BB, Ehrenkranz RA, et al. Growth failure in the preterm infant: can we catch up?Semin Perinatol 2003;27:302–10.

Abstract. The Community Atmosphere–Biosphere Land Exchange model (CABLE) is a land surface model (LSM) that can be applied stand-alone and provides the land surface–atmosphere exchange within the Australian Community Climate and Earth System Simulator (ACCESS). We describe new developments that extend the applicability of CABLE for regional and global carbon–climate simulations, accounting for vegetation responses to biophysical and anthropogenic forcings. A land use and land cover change module driven by gross land use transitions and wood harvest area was implemented, tailored to the needs of the Coupled Model Intercomparison Project 6 (CMIP6). Novel aspects include the treatment of secondary woody vegetation, which benefits from a tight coupling between the land use module and the Population Orders Physiology (POP) module for woody demography and disturbance-mediated landscape heterogeneity. Land use transitions and harvest associated with secondary forest tiles modify the annually resolved patch age distribution within secondary vegetated tiles, in turn affecting biomass accumulation and turnover rates and hence the magnitude of the secondary forest sink. Additionally, we implemented a novel approach to constrain modelled GPP consistent with the coordination hypothesis and predicted by evolutionary theory, which suggests that electron-transport- and Rubisco-limited rates adjust seasonally and across biomes to be co-limiting. We show that the default prior assumption – common to CABLE and other LSMs – of a fixed ratio of electron transport to carboxylation capacity at standard temperature (Jmax, 0∕Vcmax, 0) is at odds with this hypothesis; we implement an alternative algorithm for dynamic optimisation of this ratio such that coordination is achieved as an outcome of fitness maximisation. The results have significant implications for the magnitude of the simulated CO2 fertilisation effect on photosynthesis in comparison to alternative estimates and observational proxies. These new developments enhance CABLE's capability for use within an Earth system model and in stand-alone applications to attribute trends and variability in the terrestrial carbon cycle to regions, processes and drivers. Model evaluation shows that the new model version satisfies several key observational constraints: (i) trend and interannual variations in the global land carbon sink, including sensitivities of interannual variations to global precipitation and temperature anomalies; (ii) centennial trends in global GPP; (iii) coordination of Rubisco-limited and electron-transport-limited photosynthesis; (iv) spatial distributions of global ET, GPP, biomass and soil carbon; and (v) age-dependent rates of biomass accumulation in boreal, temperate and tropical secondary forests. CABLE simulations agree with recent independent assessments of the global land–atmosphere flux partition that use a combination of atmospheric inversions and bottom-up constraints. In particular, there is agreement that the strong CO2-driven sink in the tropics is largely cancelled by net deforestation and forest degradation emissions, leaving the Northern Hemisphere (NH) extratropics as the dominant contributor to the net land sink.

AimTo establish the views of adolescent patients with learning disabilities and their carers, of the patient-held medication passport (My Medication Passport-MMP). MethodsA questionnaire was devised to find out if patients/carers thought a patient-held record of their medications (the MMP) was useful and to suggest improvements as appropriate. The MMP is a patient-held record of medicines use available as a passport sized booklet.1 MMPs were distributed to patients and carers for them to read and review at a patient focus group. Ethics approval was not required for this study.Results20 questionnaires were sent and a total of 17 completed questionnaires were returned (85% response rate). 70% (n=12) of the questionnaires were completed by carers, 24% (n=4) by family members and 1% (n=1) by a patient. 100% (n=17) of carers/patients who reviewed the MMP found it useful. When asked about features they liked about MMP; Seven carers noted the MMP was easy to use; four carers felt MMP was a good way to keep (personal) medicines information up to date; with three further clarifying that it could be used as a ‘concise way of keep track (of medicines)’ and two specified they liked that ‘all the information is in one book’. When Patients/carers were asked for ways MMP could be improved; two carers asked for more space to document past medication, including an area to ‘keep track of the behaviours and how it is exhibited because of the medication’; one carer noted that ‘some youngsters would benefit from more visual learning’ and one asked for a version to be made available via app on smart phone. Limitations included a small sample with limited exposure to MMP. The patient group sampled may not be representative.ConclusionPassports as tools aim to help patients better manage their medicines and have been successfully used in a patient with learning disability.2 It is encouraging to see that this small group of patients with learning disability find the MMP useful. Suggested adaptations to MMP for this patient group included it being more visual, and having areas for past medication. Other trials of MMP have suggested that it may require a section surrounding medicines administration. Patients have since been directed to the MMP app which can be downloaded onto a smartphone. There are many opportunities for future work including conducting an evaluation of the MMP in use over time and across different sectors, and to determine what patients actually record in the MMP.ReferencesBarber S, et al. Evaluation of My Medication Passport: a patient-completed aide-memoire designed by patients, for patients, to help towards medicines optimisation. BMJ Open4(8). https://bmjopen.bmj.com/content/4/8/e005608Jubraj B. Use of a medication passport in a disabled child seen across many care settings. BMJ Case Reports. 25 February 2015; http://casereports.bmj.com/content/2015/bcr-2014-208033Save

Abstract. Triggered by recent developments from laboratory and field studies regarding major NOx sink pathways in the troposphere, this study evaluates the influence of chemical uncertainties in NOx sinks for global NOx distributions calculated by the IMAGESv2 chemistry-transport model, and quantifies their significance for top-down NOx emission estimates. Our study focuses on five key chemical parameters believed to be of primary importance, more specifically, the rate of the reaction of NO2 with OH radicals, the newly identified HNO3-forming channel in the reaction of NO with HO2, the reactive uptake of N2O5 and HO2 by aerosols, and the regeneration of OH in the oxidation of isoprene. Sensitivity simulations are performed to estimate the impact of each source of uncertainty. The model calculations show that, although the NO2+OH reaction is the largest NOx sink globally accounting for ca. 60% of the total sink, the reactions contributing the most to the overall uncertainty are the formation of HNO3 in NO+HO2, leading to NOx column changes exceeding a factor of two over tropical regions, and the uptake of HO2 by aqueous aerosols, in particular over East and South Asia. Emission inversion experiments are carried out using model settings which either minimise (MINLOSS) or maximise (MAXLOSS) the total NOx sink, both constrained by one year of OMI NO2 column data from the DOMINO v2 KNMI algorithm. The choice of the model setup is found to have a major impact on the top-down flux estimates, with 75% higher emissions for MAXLOSS compared to the MINLOSS inversion globally. Even larger departures are found for soil NO (factor of 2) and lightning (1.8). The global anthropogenic source is better constrained (factor of 1.57) than the natural sources, except over South Asia where the combined uncertainty primarily associated to the NO+HO2 reaction in summer and HO2 uptake by aerosol in winter lead to top-down emission differences exceeding a factor of 2. Evaluation of the emission optimisation is performed against independent satellite observations from the SCIAMACHY sensor, with airborne NO2 measurements of the INTEX-A and INTEX-B campaigns, as well as with two new bottom-up inventories of anthropogenic emissions in Asia (REASv2) and China (MEIC). Neither the MINLOSS nor the MAXLOSS setup succeeds in providing the best possible match with all independent datasets. Whereas the minimum sink assumption leads to better agreement with aircraft NO2 profile measurements, consistent with the results of a previous analysis (Henderson et al., 2012), the same assumption leads to unrealistic features in the inferred distribution of emissions over China. Clearly, although our study addresses an important issue which was largely overlooked in previous inversion exercises, and demonstrates the strong influence of NOx loss uncertainties on top-down emission fluxes, additional processes need to be considered which could also influence the inferred source.

Abstract Introduction Research drives safe and cost-effective practice, innovation and quality care. The national workforce directive calls for integration of research into healthcare roles1; however, pharmacist research is typically undertaken by a minority of highly motivated individuals2. Inclusion of research learning outcomes in all three Royal Pharmaceutical Society (RPS) curricula make it an essential component of pharmacist practice throughout career development; however, prospective consultant pharmacists may lack confidence in demonstrating capability3. Aim To describe research experience, perceptions of barriers and enablers, and confidence with meeting RPS research learning outcomes in pharmacists across all sectors and stages of career development in the North of England. Methods A cross-sectional survey, designed and piloted using Jisc Online Surveys, was circulated by email to Health Education England (HEE) North School of Pharmacy and Medicines Optimisation (SoPMO)* mailing list subscribers and posted on social media for completion during March 2023. Data were collected on demographics, research qualifications and research experience. Respondents were asked to prioritise barriers and enablers from existing literature according to personal experience. Confidence with meeting research learning outcomes in the Post-registration Foundation, Core Advanced and Consultant Pharmacist curricula was self-assessed using a 5-point Likert scale. Descriptive statistics were performed using Microsoft Excel®. The NHS Health Research Authority tool confirmed ethical approval was not required for this service evaluation. A Data Protection Impact Assessment was completed. *now North West SoPMO and North East and Yorkshire SoPMO, NHS England Workforce Training and Education Results There were 250 responses from pharmacists in all seven North of England Integrated Care Systems. Respondents had been practising for a median of 14 years. 54 (22%) had a postgraduate qualification with a research component and 162 (65%) had experience of research and/or quality improvement. 164 (67%) had no protected time for research and 200 (80%) did not routinely discuss research during annual appraisal. Lack of time within working hours was the most frequently reported ‘top three’ barrier (171, 68%), followed by prioritisation of clinical duties (128, 51%) and lack of knowledge (79, 32%). Key enablers were protected time (158, 63%) and access to mentorship (154, 62%). The proportion who self-assessed as ‘confident’ or ‘really confident’ that they could provide evidence to demonstrate all research learning outcome(s) in each curriculum was 106 (42%) for Post-registration Foundation; 52 (21%) for Core Advanced and 22 (9%) for Consultant Pharmacist. Discussion/Conclusion Despite 85% of respondents practising for 5 years or more, confidence in meeting the most fundamental research learning outcome in the Post-registration Foundation curriculum was low and decreased across the continuum of practice. Barriers and enablers were perceived around capability (knowledge and skills), opportunity (protected time; prioritisation of clinical duties) and motivation (access to mentorship). Limitations include a potential over-estimation of confidence, due to pharmacists with research experience being more likely to complete the survey, and the use of self-reporting, which relies on respondent introspection. Initial Education and Training (IET) reforms will better equip future pharmacists for research; however, coordinated strategies, simultaneously addressing identified barriers, are required to bridge the skill gap for much of the existing workforce. References 1. NHS England » NHS People Plan. [cited 2022 Dec 16]. Retrieved from https://www.england.nhs.uk/ournhspeople/ 2. Lowrie R, Morrison G, Lees R et al. Research is ‘a step into the unknown’: an exploration of pharmacists’ perceptions of factors impacting on research participation in the NHS. BMJ Open. 2015;5(12):e009180 3. Forsyth P, Radley A, Marra F et al. Are UK pharmacists ready for consultant-level practice? A cross-sectional survey of self-assessed development needs. Int J Pharm Pract. 2022;30(6):559-566

Abstract My presentation will describe our work on the discovery, nonclinical antitumor properties, mechanism of action (MOA), identification of initial target patient population, and early clinical development of NXP-800. We discovered this agent in our academic drug discovery centre at ICR following our initial identification of the ‘bisamide’ hit CCT245232 from a diverse ~200,000-compound library using an innovative, imaging-based (ArrayScan™) phenotypic screen for inhibitors of the HSF1-mediated activation of the heat shock response in U2OS human osteosarcoma cells. Subsequent multiparameter medicinal chemistry optimisation of the bisamide series, containing the N,N′-4-methyl-1,3-phenylenediamide core, focused on establishing the cell-based SAR for both inhibition of cell proliferation and linked HSF-1 mediated HSP72 induction in the sensitive ARID1A-mutant, platinum-resistant SK-OV-3 human ovarian carcinoma cell line. This generated our orally bioavailable, in vivo-active lead compound and chemical tool CCT251236 – exhibiting oral antitumor efficacy in the SK-OV-3 human ovarian cancer xenograft model in nude mice (Cheeseman et al J Med Chem 60 180-201 2017). Final multiparameter optimization yielded the clinical development candidate CCT361814/NXP800 (Pasqua et al J Med Chem 66 5907-36 2023). With the screening hit bisamide compound already active in the single to low double digit nanomolar range, the early focus was on improving kinetic solubility while retaining the desired antiproliferative and linked HSF1 pathway inhibitory activity together with simultaneous optimisation of PK/PD properties to maximize oral antitumour efficacy; finally requiring modification to the fluorobisamide NXP800 to eliminate PGP-mediated efflux and achieve optimal PK/PD, Pharmacologic Audit Trail, antitumor efficacy and tolerability. In view of these properties, its clean safety panel profile, clear therapeutic index and acceptable dose-to-human prediction, NXP800 was progressed into clinical development. Evaluation in a mini-panel of human cancer cell lines and tumor xenografts revealed high sensitivity to NXP800 in ARIDIA-deficient human ovarian cancer models, confirmed in the large Sanger cancer cell line panel and in isogenic pair systems. Activity exceeded that of cisplatin in both platinum-sensitive and platinum-resistant ARID1A-mutant ovarian cancer xenograft models. By RNA-Seq we identified two sets of consistent, major gene expression profile changes in human cancer cell lines exposed to NXP800, namely: 1) the expected changes in HSF1-regulated genes, together with 2) activation of the integrated stress response (ISR), including ATF4-regulated gene expression. This latter did not indicate a global stress response to NXP800 as we saw no activation of the unfolded protein response (UPR). Physiologically, ISR activation is mediated by phosphorylation of EIF2α which is tightly regulated by four stress-controlled kinases, GCN2, HRI, PKR and PERK. Using each of systematic siRNA knockdown or pharmacologic inhibition by two small-molecule tool compounds from different chemotypes, we discovered that GCN2 alone was necessary and sufficient for ISR activation and cell growth inhibition by NXP800 in SK-OV-3 ovarian cancer cells. Also, orthogonal siRNA depletion or pharmacologic inhibition of GCN2 both markedly reduced the antiproliferative activity of NXP800 in these cells. Global phospho-proteome analysis demonstrated defined changes in response to NXP800 which were reversed by co-treatment with a GCN2 inhibitor. Other follow-on studies at the protein level demonstrated that pharmacological concentrations of NXP800 induced GCN2-dependent phosphorylation of EIF2α, inhibition of global cap-dependent protein translation, and selective translation of ATF4 – a transcription factor that activates downstream genes such as CHAC1 and CHOP in the ISR – both in ARID1A-mutant human ovarian cells in vitro and in corresponding tumor xenograft models in vivo. Using siRNA silencing, we showed that prevention of ATF4 induction substantially reduced the antiproliferative response of SK-OV-3 human ovarian carcinoma cells to NXP800 treatment. Controls used in these experiments included a closely matched, inactive regioisomer. Furthermore, we showed that ISR induction by NXP800 inhibited HSF1 activation, in SK-OV-3 cells, confirming the mechanistic link between ISR activation and inhibition of HSF1-mediated transcription. We further showed that GCN2 activation was not due to the canonical mechanism of amino acid starvation. In summary, we used an HSF1 pathway-focused phenotypic screen to discover the mechanistically novel, first-in-class drug NXP800, which acts potently on ARID1A-mutant, human ovarian cancer cells to stimulate GCN2 and thereby activate the ISR pathway, leading to ATF4 induction and inhibition of HSF1-mediated gene transcription in ARID1A-mutant, platinum-resistant human ovarian cancer cells. Through this mechanism, NXP800 shows highly promising activity in models of this cancer type, including potent inhibition of proliferation in vitro and substantial regression of tumor xenografts in vivo. Studies are currently underway to determine precisely how NXP800 stimulates GCN2 activity and the role of ARID1A deficiency in its pharmacological effects. Recent ChIP-Seq studies are informing on the molecular interactions between ARID1A mutation and the expression of ISR/ATF4 and HSF1-regulated genes. With Nuvectis Pharma, the Phase 1a dose escalation study has been completed and a multicentre Phase 1b expansion cohort study in ARID1A-mutated, platinum-resistant ovarian cancer – a high unmet medical need – has been initiated (NCT05226507) in collaboration with the GOG Foundation and the European Network of Gynaecological Oncological Trial Group (ENGOT). FDA has issued a Fast Track designation to NXP800 in this setting. In addition, NXP800 shows therapeutic potential in non-clinical models of endometrial, gastro-intestinal and bile duct cancer, with FDA Orphan Drug status granted in the last of these indications. Citation Format: Paul Workman. From targeted phenotypic screen to NXP800: A clinical stage activator of the integrated stress response for the treatment of ARID1A-mutated ovarian carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr IA014.

Abstract Introduction The Clinical Commissioning Group (CCG) Medicines Optimisation workplan for 2021-22 had a focus on reducing harm from opioids.1,2 In particular, asking GP practices to identify and review two cohorts of patients: those on a combination of oxycodone and amitriptyline or similar high-risk combinations, and those over the age of 65 prescribed fentanyl transdermal patches. Practices were then expected to consider actions on how to reduce the risk for patients and also to provide feedback to the CCG on how the reviews had progressed. Aim We aimed to understand the outcomes, challenges and learning points experienced by practices in reviewing these patients. Methods Sixty practices were invited to participate. A feedback form was received from each practice that completed either or both reviews (covering anonymised outcomes of each review, challenges encountered, and practice-level learning points / changes made). Quantitative data were collated for each action, and feedback comments were categorised into broad groups. No patient details were collected. As this project was a service evaluation, ethical approval was not required. Results Forty-three practices completed the review of the combination of oxycodone and amitriptyline, though 5 of these had no patients to review. Overall, 185 patients were identified. Of these, 21 (11%) patients had the combination prescribing ceased, 22 (12%) were commenced on a reduction plan, and another 46 (25%) have been made aware of the risk and to report respiratory symptoms. Forty-three practices completed the fentanyl review, though one of these had no patients to review. Overall, 272 patients over 65 years were identified with 64 (24%) invited for a review with their GP or other allied health professional, 39 (14%) patients were put on a fentanyl patch dose reduction plan, and 14 (5%) had prescribing ceased. Practices reported various difficulties encountered with these reviews, including patient engagement in making changes to their pain medication which patients are reluctant to reduce; counselling and raising awareness of long-term effects of opioids to help gain patient understanding; how to manage complex patients who had been stable on their regimen over many years; and that it was time consuming to regularly check in with the patient and plan reduction regimens. Changes made by practices included recording risks discussed with patient in their medical record for easier future review; ensuring regular reviews, including by practice-based pharmacists, of patients prescribed opioids; trying to make time to see patients face to face; raising awareness of the risks of prescribing amitriptyline alongside oxycodone e.g. serotonin syndrome; and recognising that a collaborative process and patient engagement is necessary. Discussion/Conclusion The actions undertaken by practices link into national recommendations,1 with some GP feedback similar to the challenges and opportunities to improve patient safety on opioid use as reported elsewhere.3 Even with this small targeted patient cohort, this work demonstrates difficulties encountered by GPs in refraining from opioid prescribing. Other limitations of this small-scale review include lack of certainty whether reductions in opioid prescribing were always clinically appropriate, and reliance on practice feedback. References 1. Taylor S, Annand F, Burkinshaw P, Greaves F, Kelleher M, Knight J, et al. Dependence and withdrawal associated with some prescribed medicines: an evidence review. Public Health England, London. 2019. 2. Regulation 28 Report to prevent future deaths. Available at: https://www.judiciary.uk/wp-content/uploads/2019/11/Graham-Saffery-2019-0301_Redacted.pdf (accessed 20 March 2023) 3. Punwasi R, de Kleijn L, Rijkels-Otters JBM, Veen M, Chiarotto A, Koes B. General practitioners’ attitudes towards opioids for non-cancer pain: a qualitative systematic review. BMJ Open 2022;12:e054945.

Hypertension poses a significant global burden due to low adherence to antihypertensive medications. Hypertension treatment aims to bring blood pressure within physiological ranges and reduce the risk of cardiovascular disease and organ damage associated with high blood pressure. It is estimated that around 1.13 billion people have hypertension, accounting for 13% of all fatalities worldwide. The World Health Organization aims to reduce this number by 25% by 2025 compared to the baseline year of 2010.1,2 Despite the availability of effective antihypertensive medications and decreased main risk factors, achieving optimal blood pressure control remains challenging for various reasons, including apparent drug resistance and poor compliance.3,4 One of the contributing factors to poor blood pressure control is the difficulty in predicting which antihypertensive medication will be most effective for a specific patient. An individualized approach to hypertension treatment, considering risk factors, pharmacokinetic properties, genetic phenotypes, and other patient-specific characteristics, holds promise. Pharmacogenomics and other 'omics' technologies can help identify genetic signals indicative of a favorable or unfavorable response to specific antihypertensive drugs. By conducting research in this field, we can better understand how to optimize blood pressure response using different classes of antihypertensive medications.4 Pharmacogenetics studies the genetic basis of medication response variability, particularly the influence of genetic factors on drug metabolism. In recent years, simple nucleotide polymorphisms (SNPs) have emerged as the primary genetic variation markers. High-throughput genotyping approaches can detect SNPs, which are widespread throughout the genome, often involve substitutions, and rarely result in mutations. SNPs in drug-metabolizing enzymes have been reliable indicators for dose-related treatment decisions. Genetic studies conducted over the past two decades have identified various genetic polymorphisms associated with hypertension, including changes in the number of tandem repeats, microsatellites, single nucleotide polymorphisms (SNPs), and insertions/deletions (I/D). These studies have also revealed significant inter-individual variability in responsiveness to antihypertensive medications, highlighting the importance of pharmacogenomic research and the potential for individualized pharmacological therapy. Genetic factors may contribute to a 30-50% increase in blood pressure.5 A comprehensive approach is required to advance personalized medicine, incorporating data and insights from genomic, genetic, and proteomic sciences. This applies to both approved medications and therapeutic candidates in various stages of clinical trials. Personalized medicine aims to administer the right drug to the right patient at the right time and dosage. By embracing this concept, we can significantly improve hypertension treatment outcomes.6 The goal of personalized therapy for hypertension is to identify the most effective drug for reducing a patient's blood pressure. Conversely, an opposing viewpoint argues that individualized treatment helps eliminate the risks of adverse drug reactions and the use of ineffective medications. The issue of adherence problems further emphasizes the need for modifying hypertension treatment. As a result, personalized medicine, which tailors medical approaches and treatment plans to individual patient characteristics, is projected to become the standard of care in the future.7 Antihypertensive pharmacogenomics research aims to improve cardiovascular disease (CVD) outcomes in treated hypertensive patients by identifying genetic factors that influence the variability in antihypertensive response. Although these genetic variables account for approximately 50% of blood pressure variation across populations, specific genes responsible for a significant portion of this variation have yet to be identified. The complexity of the condition is attributed to the influence of alleles at different loci through various pathways and the impact of environmental factors on the manifestation of the blood pressure phenotype. There is evidence supporting the hypothesis that genetics may contribute to individual variations in how people respond to blood pressure-lowering drugs. By incorporating genetic information, pharmacogenomics can provide insights into personalized treatment approaches. However, further research is needed to uncover the specific genes and pathways involved. Improving our understanding of the genetic basis of antihypertensive response variability holds excellent potential for optimizing hypertension treatment. Personalized medicine, driven by pharmacogenomics, can revolutionize the management of hypertension and enhance patient outcomes.8 A previously published study revealed that the response to angiotensin-converting enzyme (ACE) inhibitors was less favorable in black participants than in Caucasians. The study involved 56 white patients (aged 22 to 51) with untreated essential hypertension from the East Anglia region of the United Kingdom. These patients were alternately administered four major antihypertensive medications (beta-blockers, diuretics, calcium antagonists, and blockers). The study demonstrated that only 22 out of 56 patients initially achieved the target blood pressure with their initial treatment. However, when the best response was considered, the number increased to 41 out of 56 patients, supporting the notion that each patient's response to antihypertensive treatment is unique. This study highlighted that ethnicity alone is insufficient to indicate who will benefit from a particular therapy.9 Genetic differences in relation to several antihypertensive medications and their efficacy have been investigated. Two recent studies examined the ACE insertion-deletion (ID) variant, one focusing on blood pressure response and the other on myocardial infarction (MI) and stroke. Neither study found significant pharmacogenetic associations with the use of ACE inhibitors. These findings were consistent with prior research on lisinopril, but a previous study on fosinopril reported significant associations between fosinopril and ACE (ID) regarding blood pressure response. Establishing a firm scientific foundation is essential but insufficient for developing clinically useful antihypertensive pharmacogenetics. Clinicians must adopt a new paradigm to appropriately and routinely utilize genetic information in the clinical setting.10,11 The concept of pre-prescription genotyping is gaining attention in the treatment of various conditions. For example, by detecting CYP450 gene variants, pre-prescription genotyping can help determine the optimal dose of serotonin reuptake inhibitors. This approach can enhance treatment outcomes and minimize adverse reactions by tailoring medication regimens to individual patients.12,13 Further research and a shift in clinical practice are necessary to fully realize the potential of antihypertensive pharmacogenetics and personalized medicine in optimizing hypertension treatment and improving patient care.14 Two recent European studies examining the perspectives of healthcare professionals and patients revealed generally optimistic expectations regarding the potential benefits of genetic testing in terms of customizing drug dosages and minimizing side effects. However, some patients expressed concerns about the stress and anxiety associated with testing, as well as potential violations of confidentiality. Patients also emphasized their preference for pharmacogenetic services provided by experts confident in their ability to interpret and apply the results. Therefore, the perception of risk-benefit must align for individualized therapy to be effective in the initial treatment of hypertension. The rise of direct-to-consumer genetic screening has made genetic information more accessible to individuals without involving healthcare professionals initially. As this industry develops, it may help people become more comfortable with pharmacogenetics, viewing their genetic information as a tool for optimizing therapy. However, research collaborations and study designs need to be adapted to fully harness the potential of personalized medicine. Comprehensive biobanks and registries that provide accessible data, standardized phenotyping methods, and analytical tools are essential. Incorporating novel information from investigator-initiated studies into ongoing clinical trials and cohorts based on demographic data would further enhance these resources.15,16 Enhancing the understanding of "-omics" technologies is crucial for biomedical researchers, physicians, patients, legislators, healthcare organizations, and consumers to develop and implement personalized medicine, reducing the burden of hypertension on the public health system and its associated complications. Targeted educational initiatives in the field of "-omics," focusing on both new and experienced scholars, should emphasize team approaches by involving subject matter experts from related fields. Early achievements in this field would help construct a compelling narrative for personalized medicine that all stakeholders can easily understand. This shift would promote greater reliance on prediction models, facilitating the integration of personalized medicine as a cornerstone of medical education, surpassing traditional case studies.17-19 By addressing these considerations and fostering interdisciplinary collaboration, personalized medicine can revolutionize the management of hypertension and improve patient outcomes. References Ashiq K, Ashiq S, Shehzadi N. Hyperuricemia and its association with hypertension: risk factors and management. Pakistan Heart J. 2022;55(2):200-1. Shahbaz SAZ, Nazar MS, Umar A, Tariq MA, ul Haq I, Junaid M. Evaluation of hypertension awareness among general population in Bahawalpur, Pakistan: a cross sectional study. Int J Pharm Integ Health Sci. 2023;4(1):100-17. Savoia C, Volpe M, Grassi G, Borghi C, Agabiti Rosei E, Touyz RM. Personalized medicine—a modern approach for the diagnosis and management of hypertension. Clin Sci. 2017;131(22):2671-85. Cooper-DeHoff RM, Johnson JA. Hypertension pharmacogenomics: in search of personalized treatment approaches. Nat Rev Nephrol. 2016;12(2):110-22. Bhardwaj S, Balgir PP, Goel RK. Pharmacogenomics and personalized management of hypertension. J Crit Rev. 2015;2(2):1-6. Oliveira-Paula GH, Pereira SC, Tanus-Santos JE, Lacchini R. Pharmacogenomics and hypertension: current insights. Pharmacogenomics Pers Med. 2019:341-59. Byrd JB. Personalized medicine and treatment approaches in hypertension: current perspectives. Integr Blood Press Control. 2016;9:59-67. Turner ST, Bailey KR, Fridley BL, Chapman AB, Schwartz GL, Chai HS, et al. Genomic association analysis suggests chromosome 12 locus influencing antihypertensive response to thiazide diuretic. Hypertension. 2008;52(2):359-65. Dickerson JC, Hingorani AD, Ashby MJ, Palmer CR, Brown MJ. Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet. 1999;353(9169):2008-13. Filigheddu F, Argiolas G, Bulla E, Troffa C, Bulla P, Fadda S, et al. Clinical variables, not RAAS polymorphisms, predict blood pressure response to ACE inhibitors in Sardinians. Pharmacogenomics. 2008;9(10):1419-27. Schelleman H, Klungel O, Witteman J, Breteler M, Hofman A, Van Duijn C, et al. Interaction between polymorphisms in the renin–angiotensin–system and angiotensin-converting enzyme inhibitor or β-blocker use and the risk of myocardial infarction and stroke. Pharmacogenomics J. 2008;8(6):400-7. Arnett DK, Davis BR, Ford CE, Boerwinkle E, Leiendecker-Foster C, Miller MB, et al. Pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment: the Genetics of Hypertension-Associated Treatment (GenHAT) study. Circulation. 2005;111(25):3374-83. Stavroulakis GA, Makris TK, Krespi PG, Hatzizacharias AN, Gialeraki AE, Anastasiadis G, et al. Predicting response to chronic antihypertensive treatment with fosinopril: the role of angiotensin-converting enzyme gene polymorphism. Cardiovasc Drugs Ther. 2000;14:427-32. de Leon J, Arranz MJ, Ruano G. Pharmacogenetic testing in psychiatry: a review of features and clinical realities. Clinics Lab Med. 2008;28(4):599-617. Fargher EA, Eddy C, Newman W, Qasim F, Tricker K, Elliott RA, et al. Patients’ and healthcare professionals’ views on pharmacogenetic testing and its future delivery in the NHS. Pharmacogenomics. 2007 Nov;8(11):1511-9. Ho D, Quake SR, McCabe ER, Chng WJ, Chow EK, Ding X, Gelb BD, Ginsburg GS, Hassenstab J, Ho CM, Mobley WC. Enabling technologies for personalized and precision medicine. Trends Biotechnol. 2020;38(5):497-518. Ashiq S, Ashiq K, Shabana SU, Qayyum M, Sadia H. Prevalence and role of different risk factors with emphasis on genetics in development of pathophysiology of coronary artery disease (CAD). Pak Heart J. 2020;52(4):279-87. Ashiq S, Ashiq K. The association of apolipoprotein-E (APOE) gene polymorphisms with coronary artery disease: a systematic review and meta-analysis. Egyptian J Med Human Genetics. 2021;22(1):1-8. Ashiq S, Ashiq K. Genetic perspective of the congenital heart disease. Pak Heart J. 2020;53(3):210-2.

Background:Adalimumab (ADL) is typically self-administered every 2 weeks (W) as a subcutaneous (s.c.) injection by patients (pts) for diverse indications, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (PsO). Conflicting evaluations of local tolerance to formulations containing citrate buffer have created insecurities among health care professionals and pts.1,2Objectives:To evaluate local tolerance of SDZ-ADL (GP2017), a biosimilar ADL with low citrate concentration (1.2 mM),3 in 466 healthy volunteers (HV) and 408 pts (RA: 177 and PsO: 231 including PsA: 52) from four phase I pharmacokinetic (PK) and two phase III confirmatory studies.Methods:HV evaluated their injection site pain (ISP) using a Visual Analogue Scale (VAS) of 0–100 mm. HV received a single 40 mg/0.8 mL s.c. injection and pts received SDZ-ADL every 2W during 48–51W duration of study. Injection site reactions (ISR) as well as adverse events (AEs) were assessed by investigators during the clinical studies. Details of study designs have been reported previously.4–7Results:Overall, 456 (97.9%) HV experienced no ISR. Ten HV experienced ISR. These were mostly of mild intensity; only 1 (0.2%) had an ISR of moderate intensity. 96.6% of HV experienced no pain (VAS score 0–4 mm)8 at 1-hour post-dose (Figure 1). In the phase III studies, a low number of ISR/ISP events were observed, which decreased during the course of study. Detailed results are provided in Table 1. No ISR/ISP led to treatment or study discontinuation in any study.Conclusion:The proportion of HV and pts experiencing ISR and ISP after administration of SDZ-ADL was low, with no events leading to treatment or study discontinuation. These results call into question the clinical impact of citrate and its concentration in ADL formulations on the incidence and intensity of ISP.References:[1]Nash et al. Rheumatol Ther. 2016;3:257–70.[2]NHS. Regional medicines optimisation committee briefing, best value biologicals: adalimumab update 6. July 2019. https://www.sps.nhs.uk/wp-content/uploads/2019/07/Adalimumab-RMOC-Briefing-6.pdf.[3]https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761071lbl.pdf.[4]Blauvelt A, et al. Br J Dermatol. 2018;179:623–31.[5]Wiland P, et al. BioDrugs 2020;34:809–23.[6]Richter OV, et al. Expert Opin Biol Ther. 2019;19:1057–64.[7]Richter OV, et al. Expert Opin Biol Ther. 2019;19:1075–83.[8]Hawker GA, et al. Arthritis Care Res. 2011;63:240–52.Figure 1.Proportion of HV with ISP in phase I PK studiesTable 1.ISP and ISR results from phase I PK and phase III confirmatory studiesPhase I PK studiesStudy101(N=73)102(N=108)103(N=178)104(N=107)Pooled studies (N=466)VAS scores (mm) at 1-hour post-doseMean (SD)0.89 (2.07)0.07 (0.52)1.03 (1.71)1.03 (2.49)0.79 (1.84)Median00100ISR scores at 1-hour post-dose, n (%)None73 (100)106 (98.2)178 (100)99 (92.5)456 (97.9)Mild0 (0)1 (0.9)0 (0)8 (7.5)9 (1.9)Moderate0 (0)1 (0.9)0 (0)0 (0)1 (0.2)Phase III confirmatory studiesADACCESS5* (PsO and PsA pts)ADMYRA6* (RA pts)W0–17 (N=231)W0–51 (N=168; including pts re-randomised to continue SDZ-ADL after W17)W0–24 (N=177)W0–48 (N=177; all pts continued SDZ-ADL after W24)DosageInduction 80 mg W0, then 40 mg EoW s.c.40 mg EoW s.c.40 mg EoW s.c.40 mg EoW s.c.Study duration, W17512448AEs - ISR, n (%), events15 (6.5), 349 (5.4), 267 (4.0), 117 (4.0), 12Mild14 (6.1), 309 (5.4), 267 (4.0), 117 (4.0), 12Moderate1 (0.4), 4000AEs - ISP (reported as ISR), n (%)3 (1.3)1 (0.6)2 (1.1)2 (1.1)*ADACCESS and ADMYRA were switch studies, therefore, only pts exposed to SDZ-ADL throughout the study period are included here. EoW, every other week, N, number of HV or ptsDisclosure of Interests:Piotr Wiland Speakers bureau: Celltrion, Celgene, Eli Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Consultant of: Celltrion, Celgene, Eli Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Andrew Blauvelt Speakers bureau: AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma., Consultant of: AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma., Lena Lemke Employee of: Hexal AG, Oliver von Richter Employee of: Hexal AG, Alison Balfour Employee of: Hexal AG, Fabricio Furlan Employee of: Hexal AG, Norman Gaylis: None declared

IntroductionFirst described by Wallis et al. in 2001 for the assessment of TB drugs, the direct mycobacterial growth inhibition assay (MGIA) offers a tractable ex vivo tool measuring the combined influences of host immunity, strain virulence and intervention effects. Over the past 13 years, we have led efforts to adapt the direct MGIA for the assessment of TB vaccines including optimisation, harmonisation and validation of BCG vaccine-induced responses as a benchmark, as well as assay transfer to institutes worldwide.MethodsWe have performed a systematic review on the primary published literature describing the development and applications of the direct MGIA from 2001 to June 2023 in accordance with the PRISMA reporting guidelines.ResultsWe describe 63 studies in which the direct MGIA has been applied across species for the evaluation of TB drugs and novel TB vaccine candidates, the study of clinical cohorts including those with comorbidities, and to further understanding of potential immune correlates of protection from TB. We provide a comprehensive update on progress of the assay since its conception and critically evaluate current findings and evidence supporting its utility, highlighting priorities for future directions.DiscussionWhile further standardisation and validation work is required, significant advancements have been made in the past two decades. The direct MGIA provides a potentially valuable tool for the early evaluation of TB drug and vaccine candidates, clinical cohorts, and immune mechanisms of mycobacterial control.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023423491.

This work presents statistical models of the variability of plasma in the topside ionosphere based on observations made by the European Space Agency’s (ESA) Swarm satellites. The models were developed in the “Swarm Variability of Ionospheric Plasma” (Swarm-VIP) project within the European Space Agency's Swarm+4D-Ionosphere framework. The configuration of the Swarm satellites, their near-polar orbits and the data products developed, enable studies of the spatial variability of the ionosphere at multiple scale sizes. The statistical modelling technique of Generalised Linear Modelling was used to create models of both the electron density and measures of the variability of the plasma structures at horizontal spatial scales between 20 km and 100 km. Despite being developed using the Swarm data, the models provide predictions that are independent of these data. Separate models were created for low, middle, auroral and polar latitudes. The models make predictions based on heliogeophysical variables, which act as proxies for the solar and geomagnetic processes. The first and most significant term in the majority of the models was a proxy for solar activity. The most common second term varied with the latitudinal region. This was the Solar Zenith Angle (SZA) in the polar region, a measure of latitude in the auroral region, solar time in the mid-latitude region and a measure of latitude in the equatorial region. Other, less significant terms in the models covered a range of proxies for the solar wind, geomagnetic activity and location. In this paper the formulation, optimisation and evaluation of these models is discussed. The models show very little bias, with a mean error of zero to two decimal places in 14 out of 20 cases. The models capture some, but not all, of the trends present in the data, with Pearson correlation coefficients of up to 0.75 between the observations and the model predictions. The models also capture some, but not all, of the variability of the ionospheric plasma, as indicated by the precision, which ranged between 0.20 and 0.83. The addition of the thermospheric density as an explanatory variable in the models improved the precision in the polar and auroral regions. It is suggested that, if the thermosphere could be observed at a higher spatial resolution, then even more of the variability of the plasma structures could be captured by statistical models. The formulation and optimisation of the models are presented in this paper. The capability of the model in reproducing the expected climatological features of the topside ionosphere, in supporting GNSS-based ionospheric observations and the performance of the model against TIE-GCM, are provided in a companion paper (Spogli et al., 2023).

Bin packing problem (BPP) is a combinatorial optimization problem with a wide range of applications in fields such as financial budgeting, load balancing, project management, supply chain management. Harmony search algorithm (HSA) is widely used for various real-world and engineering problems due to its simplicity and efficient problem solving capability. Literature shows that basic HSA needs improvement in search capability as the performance of the algorithm degrades with increase in the problem complexity. This paper presents HSA with improved exploration and exploitation capability coupled with local iterative search based on random swap operator for solving BPP. The study uses the despotism based approach presented by Yadav et al. (2012) [Yadav P., Kumar R., Panda S.K., Chang, C. S. (2012). An intelligent tuned harmony search algorithm for optimisation. Information Sciences, 196, 47-72.] to divide Harmony memory (HM) into two categories which helps to maintain balance between exploration and exploitation. Secondly, local iterative search explores multiple neighborhoods by exponentially swapping components of solution vectors. A problem specific HM representation, HM re-initialization strategy and two adaptive PAR strategies are tested. The performance of proposed HSA is evaluated on 180 benchmark instances which consists of 100, 200 and 500 objects. Evaluation metrics such as best, mean, success rate, acceleration rate and improvement measures are used to compare HSA variations. The performance of the HSA with iterative local search outperforms other two variations of HSA.

Background: Pharmacotherapy is the cornerstone of treatment for heart failure with reduced ejection fraction (HFrEF). The Canadian Cardiovascular Society and Canadian Heart Failure Society have defined guideline-directed medical therapy (GDMT) as 4 foundational medications. Despite strong recommendations for use of GDMT in HFrEF, current practice alignment with guidelines is unknown. Objectives: The primary objectives were to determine the proportion of patients for whom optimized GDMT for HFrEF was prescribed, to describe the doses of foundational medications achieved, and to describe any documented rationale limiting the optimization of GDMT. The secondary objectives were to describe documented pharmacist activities outside of scheduled multidisciplinary appointments at the heart function clinic (HFC) and to describe heart failure–related hospital encounters in 2021. Methods: A retrospective cohort study using medical records of patients with HFrEF who were receiving treatment at the Regina HFC as of December 31, 2021, was conducted. Results: Of the 129 patients included in the study, 61 (47.3%) were prescribed optimized GDMT. Specifically, within the individual foundational medication classes, 82.2% (106/129), 80.6% (104/129), 79.1% (102/129), and 74.4% (96/129) of patients received optimized therapy with a renin– angiotensin system inhibitor, mineralocorticoid receptor antagonist, β-blocker, and sodium–glucose cotransporter 2 inhibitor, respectively. Documented rationale was not available in 35.8% (38/106) of instances of suboptimal utilization of GDMT and in 41.7% (60/144) of instances of suboptimal dosing of GDMT. The most common documented rationale for suboptimal utilization was intolerance to the medication (33.0% [35/106]), and the most common rationale for suboptimal dosing was intolerance to dose increases (57.6% [83/144]). Pharmacists documented a total of 553 patient care activities for 58.9% (76/129) of the patients, outside scheduled multidisciplinary appointments in the HFC. Sixteen patients (12.4%) had heart failure–related hospital encounters a total of 31 times in 2021. Conclusions: Although many patients were receiving the benefits of multidisciplinary care at the Regina HFC, there remained a treatment gap in the use of GDMT for HFrEF. These findings will be used to inform strategies to improve clinic processes, including efficient identification of patients requiring optimization of GDMT, who would benefit the most from multidisciplinary care. Keywords: heart failure with reduced ejection fraction, guideline-directed medical therapy, heart function clinic, multidisciplinary clinic, pharmacist activities, hospitalization RÉSUMÉ Contexte : La pharmacothérapie est la pierre angulaire du traitement de l’insuffisance cardiaque avec fraction d’éjection réduite (ICFEr). La Société cardiovasculaire du Canada et la Société canadienne d’insuffisance cardiaque ont défini le traitement médical fondé sur les lignes directrices (TMFLD) selon 4 médicaments fondamentaux. Malgré de fortes recommandations pour l’utilisation du TMFLD dans l’ICFEr, l’alignement actuel de la pratique sur les lignes directrices est inconnu. Objectifs : Les objectifs principaux étaient de déterminer la proportion de patients pour lesquels un TMFLD optimisé pour l’ICFEr avait été prescrit, de décrire les doses obtenues et de décrire les justifications documentées limitant l’optimisation du TMFLD. Les objectifs secondaires, quant à eux, étaient de décrire les activités documentées du pharmacien en dehors des rendez-vous prévus à la clinique multidisciplinaire de fonction cardiaque et de recenser les consultations hospitalières liées à l’insuffisance cardiaque au cours de l’année civile 2021. Méthodes : Cette étude de cohorte rétrospective se basait sur les dossiers médicaux de patients atteints d’ICFEr qui recevaient un traitement à la clinique de fonction cardiaque de Regina au 31 décembre 2021. Résultats : Sur les 129 patients inclus dans l’étude, 61 d’entre eux (47,3 %) ont reçu un TMFLD optimisé. Plus précisément, en ce qui concerne les classes de médicaments fondamentaux, 82,2 % (106/129) ont reçu un traitement optimal avec un inhibiteur du système rénine-angiotensine, 80,6 % (104/129) avec un antagoniste des récepteurs minéralocorticoïdes, 79,1 % (102/129) avec un β-bloquant et 74,4 % (96/129) avec un inhibiteur sodique du cotransporteur de glucose 2. Dans 35,8 % (38/106) des cas d’utilisation sous-optimale du TMFLD et dans 41,7 % (60/144) des cas de dosage sous-optimal de celui-ci, la justification documentée était indisponible. Lorsqu’elles étaient documentées, les justifications les plus courantes étaient l’intolérance, respectivement, à l’utilisation d’un médicament (33.0% [35/106]) et à l’augmentation de la dose (57,6 % [83/144]). Les pharmaciens ont consigné un total de 553 activités de soins aux patients pour 58,9 % (76/129) des patients en dehors des rendez-vous multidisciplinaires prévus dans la clinique de fonction cardiaque. Seize (12,4 %) des patients ont été hospitalisés pour une insuffisance cardiaque 31 fois au total en 2021. Conclusion : Bien que de nombreux patients bénéficiaient des soins multidisciplinaires à la clinique de fonction cardiaque de Regina, une lacune subsistait dans le traitement par rapport à l’utilisation du TMFLD pour l’ICFEr. Ces résultats seront utilisés pour éclairer les stratégies visant à améliorer les processus cliniques, y compris l’identification efficace des patients nécessitant une optimisation du TMFLD, qui bénéficieraient le plus de soins multidisciplinaires. Mots-clés : insuffisance cardiaque avec fraction d’éjection réduite, traitement médical fondé sur les lignes directrices, clinique de la fonction cardiaque, clinique multidisciplinaire, activités du pharmacien, hospitalisation

Abstract Background In radiotherapy inaccuracy in organ at risk (OAR) delineation can impact treatment plan optimisation and treatment plan evaluation. Brouwer et al. showed significant interobserver variability (IOV) in OAR delineation in head and neck cancer (HNC) and published international consensus guidelines (ICG) for OAR delineation in 2015. The aim of our study was to evaluate IOV in the presence of these guidelines. Methods HNC radiation oncologists (RO) from each Belgian radiotherapy centre were invited to complete a survey and submit contours for 5 HNC cases. Reference contours (OARref) were obtained by a clinically validated artificial intelligence-tool trained using ICG. Dice similarity coefficients (DSC), mean surface distance (MSD) and 95% Hausdorff distances (HD95) were used for comparison. Results Fourteen of twenty-two RO (64%) completed the survey and submitted delineations. Thirteen (93%) confirmed the use of delineation guidelines, of which six (43%) used the ICG. The OARs whose delineations agreed best with the OARref were mandible [median DSC 0.9, range (0.8–0.9); median MSD 1.1 mm, range (0.8–8.3), median HD95 3.4 mm, range (1.5–38.7)], brainstem [median DSC 0.9 (0.6–0.9); median MSD 1.5 mm (1.1–4.0), median HD95 4.0 mm (2.3–15.0)], submandibular glands [median DSC 0.8 (0.5–0.9); median MSD 1.2 mm (0.9–2.5), median HD95 3.1 mm (1.8–12.2)] and parotids [median DSC 0.9 (0.6–0.9); median MSD 1.9 mm (1.2–4.2), median HD95 5.1 mm (3.1–19.2)]. Oral cavity, cochleas, PCMs, supraglottic larynx and glottic area showed more variation. RO who used the consensus guidelines showed significantly less IOV (p = 0.008). Conclusions Although ICG for delineation of OARs in HNC exist, they are only implemented by about half of RO participating in this study, which partly explains the delineation variability. However, this study highlights that guidelines alone do not suffice to eliminate IOV and that more effort needs to be done to accomplish further treatment standardisation, for example with artificial intelligence.

Abstract Background Medication review is a core aspect of medicine optimisation, yet existing models of review vary substantially in structure and content and are not necessarily easy to implement in clinical practice. This study aimed to use evidence from the existing literature to identify key medication review components and use this to inform the design of an improved review model. Methods A systematic review was conducted (PROSPERO: CRD42018109788) to identify randomised control trials of stand-alone medication review in adults (18+ years). The review updated that by Huiskes et al. (BMC Fam Pract. 18:5, 2017), using the same search strategy implemented in MEDLINE and Embase. Studies were assessed using the Cochrane risk of bias tool. Key review components were identified, alongside relevant clinical and health service outcomes. A working group (patients, doctors and pharmacists) developed the model through an iterative consensus process (appraisal of documents plus group discussions), working from the systematic review findings, brief evidence summaries for core review components and examples of previous models, to agree on the main purpose of the review model, overarching model structure, review components and supporting material. Results We identified 28 unique studies, with moderate bias overall. Consistent medication review components included reconciliation (26 studies), safety assessment (22), suboptimal treatment (19), patient knowledge/preferences (18), adherence (14), over-the-counter therapy (13) and drug monitoring (10). There was limited evidence from studies for improvement in key clinical outcomes. The review structure was underpinned by patient values and preferences, with parallel information gathering and evaluation stages, feeding into the final decision-making and implementation. Most key components identified in the literature were included. The final model was considered to benefit from a patient-centred, holistic approach, which captured both patient-orientated and medication-focused problems, and aligned with traditional consultation methods thus facilitating implementation in practice. Conclusions The Bristol Medication Review Model provides a framework for standardised delivery of structured reviews. The model has the potential for use by all healthcare professionals with relevant clinical experience and is designed to offer flexibility of implementation not limited to a particular healthcare setting.

able des matières Résumés. 140 Agenda Formation en Radioprotection JRANF 2021 Ouagadougou. 140 RPF 1 Rappel des unités de doses. 140 RPF 2 Risques déterministes et stochastiques. 140 RPF 3 Mesure pratique des niveaux d’exposition en RX et. 140 RPF 4 Niveaux comparés de doses observés en radiologie diagnostique et interventionnelle, échelle de risques comparés. 140 RPF 5 Rappel des principes de la radioprotection: justification des actes et optimisation. 140 RPF 6 Méthodes d’optimisation en radiologie conventionnelle. 140 RPF 7 Méthodes d’optimisation en tomodensitométrie. 140 RPF 8 Cas particuliers de la femme enceinte, de l’enfant et de la radiologie interventionnelle. 141 RPF 9 Guidelines et Justification des actes en pratique courante. 141 RPF 10 Mission et rôle des PCR dans les services d’imagerie. 141 RPF 11 Notion des NRD et mise en œuvre des NRD en Afrique. 141 FORMATION DES : EPU, CONFERENCES ET ATELIERS. 142 IMAGERIE DE L’HYDROCEPHALIE CHRONIQUE DE L’ADULTE AFRICAIN.. 142 IRM CARDIAQUE. 142 FAISABILITE EN AFRIQUE, INDICATIONS, TECHNIQUE ET RESULTATS. 142 COROSCANNER. 142 FAISABILITE EN AFRIQUE, INDICATIONS, TECHNIQUE ET RESULTATS. 142 SCANNER DE PERFUSION : ENJEUX ET PERSPECTIVES. 143 L'IMAGERIE POSTMORTEM COMME ALTERNATIVE FACE AUX DE RESISTANCES SOCIALES A L'AUTOPSIE 144 INTELLIGENCE ARTIFICIELLE ET IMAGERIE MEDICALE. 144 RADIOLOGIE INTERVENTIONNELLE DU RACHIS : INFILTRATION, BIOPSIE DISCO VERTEBRALE, CIMENTOPLASTIE 144 ECHOGRAPHIE TRANSFRONTANELLAIRE / COMMENT JE LA REALISE ET QUOI RECHERCHER. 145 ATELIER SUR L’IMAGERIE DU ROCHER. 145 CLASSIFICATION O-RADS DES MASSES ANNEXIELLES A L’ECHOGRAPHIE ET A L’IRM... 146 MALFORMATIONS CEREBRALES EN ECHOGRAPHIE ANTENATALE. 146 OCCLUSIONS INTESTINALES DU GRELE DE L’ADULTE. 147 IMAGERIE DES URGENCES TRAUMATIQUES ABDOMINALES. 147 IMAGERIE DES APPENDICITES AIGUES. 148 IMAGERIE DU FOIE ET DES VOIES BILIAIRES. 148 IMAGERIE DES INFECTIONS URINAIRES DE L’ENFANT. 149 IMAGERIE DE LA PATHOLOGIE DES VOIES BILIAIRES. 149 IMAGERIE DE LA PANCREATITE AIGUE. 150 HYPERDENSITE EN VERRE DEPOLI : LESION ELEMENTAIRE TDM DOMINANTE DANS LA PNEUMOPATHIE A COVID 19 MAIS AUSSI DANS D’AUTRES AFFECTIONS. 150 PRESENTATION 2IMEDS SARL. 150 COMMUNICATIONS ORALES. 152 CO.01 : Aspects radiologiques des séquelles de tuberculose pulmonaire de l’adulte à Conakry. 152 CO.02 : Séroprévalence du virus de l’hépatite virale B dans la cohorte des PVVIH suivis dans le service des maladies infectieuses du CHU YO.. 152 CO.03 : Evaluation de la qualité des traitements endodontiques réalisés au Centre Municipal de Santé Bucco-Dentaire de Ouagadougou. 153 CO.04 : Facteurs limitant la prévention de la carie dentaire au niveau des prestataires de soins du premier échelon : enquête au district sanitaire de Dô, Burkina Faso. 153 CO.05 : Profils clinique, diagnostique des patients hospitalisés dans le service de rhumatologie du Centre Hospitalier Universitaire de Bogodogo. 154 CO.06 : Morbidité et mortalité des nouveau-nés réanimés en salle de naissance au Centre Hospitalier Universitaire Régional de Ouahigouya (Burkina Faso). 154 CO.07 : Apport de l’imagerie dans le diagnostic et les facteurs étiologiques de la lithiase urinaire chez l’adulte 155 CO.08 : Les profils de la déficience visuelle au Centre Hospitalier Universitaire Yalgado Ouédraogo : à propos de 501 cas 156 CO.09 : Pression intra-oculaire chez les enfants mélanodermes examinés sous anesthésie générale au Centre Hospitalier Universitaire Yalgado Ouédraogo. 156 CO.10 : Anomalie de la jonction pyélo-uretérale : Aspects diagnostique et thérapeutique au Centre Hospitalier Universitaire SOURO SANOU.. 156 CO.11 : Prise en charge de l’uretère rétro-cave au Centre Hospitalier Universitaire SOURO SANOU : à propos de deux observations. 157 CO.12 : Carcinome occulte de la thyroïde révèle par une métastase fronto-pariétale : à propos d’un cas. 157 CO.13 : Les suppurations rénales et péri rénales au Centre Hospitalier Universitaire SOURO SANOU de Bobo-Dioulasso : aspects diagnostiques et thérapeutiques. 158 CO.14 : Tumeur mixte épithéliale et stromale du rein chez un patient hémodialysé chronique. 158 CO.15 : Facteurs limitant la réalisation de la charge virale chez les PVVIH à l’hôpital de jour du CHU Yalgado OUEDRAOGO 159 CO.16 : Facteurs prédictifs de la mortalité au cours de la fibrillation atriale : suivi de 256 cas. 159 CO.17 : Le port du sac est-il un facteur associé à la lombalgie chez l’enfant ?. 160 CO.18 : Etude des facteurs de récidive au cours des ténosynovites de De Quervain ?. 160 CO.19 : L’arthropathie tabétique : une affection à ne pas oublier. 161 CO.20 : Fracture du rocher au CHU Yalgado Ouédraogo : à propos de 25 cas. 161 CO.21 : Aspect tomodensimètre des spondylolisthésis ; à propos de 48 cas colligés au CHU de Cocody 162 CO.22 : Amputation de membres dans le service d’Orthopédie - Traumatologie du Centre Hospitalier Universitaire Yalgado Ouédraogo : à propos de 113 cas. 162 CO.23 : Profil scanographique et épidémiologique des fractures maxillo-faciales à l’hôpital Sominé Dolo de Mopti (Mali) 163 CO.24 : Fractures du poignet : aspects épidémiologiques, anatomocliniques et thérapeutiques dans le service d’Orthopédie-Traumatologie du CHU-YO de janvier 2015 à décembre 2018 à propos de 357 cas. 164 CO.25 : Tumeurs autour du genou de l’adulte, aspects épidémiologiques, diagnostiques, thérapeutiques et évolutifs au CHU Yalgado Ouédraogo et à l’hôpital protestant Schiphra. 164 CO.26 : Post traitement en tomodensitométrie thoracique diagnostique et thérapeutique : connaissance et pratique dans les hôpitaux de référence en Côte-d’Ivoire. 165 CO.27 : La sclérose mésiotemporale. 165 CO.28 : Syndrome d’interruption de la tige pituitaire, une cause rare d’hypopituitarisme : à propos d’un cas au CNHU-HKM de Cotonou au Bénin. 165 CO.29 : Indications du scanner cérébral chez les patients présentant un traumatisme crânien léger. 166 CO.30 : Evènements nucléaires en pratique hospitalière à Abidjan : état des lieux et prise en soins. 166 CO.31 : Utérus didelphe imperméable chez une jeune femme hypofertile, à Ouagadougou, Burkina Faso 167 CO.32 : Pseudo kystes du pancréas : aspects épidémiologiques, cliniques, thérapeutiques et évolutifs 167 CO.33 : Point de vue des médecins du Burkina Faso sur la télé expertise mobile en cancérologie. 168 CO.34 : Comparaison des niveaux de référence diagnostiques basés sur l’indication à ceux par région anatomique des scanners des adultes à Yaoundé. 168 CO.35 : Optimisation des doses délivrées au scanner multi barets dans les services de radiologie au Burkina Faso. 169 CO.36 : Développement de la dosimétrie biologique et application à des travailleurs médicaux et aux enfants exposes au scanner. 169 CO.37 : Effets secondaires immédiats des produits de contraste iodés au scanner : une étude effectuée à Abidjan (Côte d'ivoire). 170 CO.38 : Connaissances en radioprotection des travailleurs exposés aux rayonnements ionisants en milieu médical en Afrique Francophone Subsaharienne. 170 CO.39 : Problématique du coût et d’accès au scanner multi-détecteur au Cameroun : une étude mixte séquentielle et explicative. 171 CO.40 : Evaluation des doses administrées aux patients adultes en médecine nucléaire en 2020 au Centre Hospitalier Universitaire Yalgado Ouédraogo. 172 CO.41 : Enquête sur l’application de la prescription raisonnée des examens radiographiques standards : cas des CHU de Lomé (Togo). 172 CO.42 : Evaluation de la satisfaction des médecins de la pratique de la radiologie au Togo. 173 CO.43 : Aspects tomodensitométriques et clinico-épidémiologiques de la pneumopathie COVID-19 au CHME le Luxembourg à Bamako (Mali). 173 CO.44 : Sensibilité du scanner dans le diagnostic de la pneumonie à SARS – COV 2 à propos de 229 cas 174 CO.45 : Aspects TDM thoracique initial des patients suspects de Covid-19. 174 CO.46 : Connaissance et pratique des mesures de protection contre la COVID-19 dans le service d’imagerie médicale du Centre Hospitalier Universitaire Départemental Borgou-Alibori (CHUD/B-A). 175 CO.47 : Contribution diagnostique du scanner multi barrette lors de la première vague de Covid 19 ; expérience de la Polyclinique Internationale de Ouagadougou. 175 CO.48 : Imagerie thoracique et PCR positive au cours de la pneumopathie à Covid 19 du Centre d’Isolement du CHU Bogodogo. 176 CO.49 : Titre : Association entre stade clinique et signes scanographiques de la COVID-19 à Hôpital Gynéco-Obstétrique et Pédiatrique de Douala, Cameroun. 176 CO.50 : Titre : Comparaison des caractéristiques de la tomodensitométrie thoracique chez les femmes enceintes, et non enceintes atteintes de COVID-19 à l’Hôpital Gynéco-Obstétrique et Pédiatrique de Douala, Cameroun 177 CO.51 : Aspects épidémiologiques et orientations étiologiques des hypersignaux T2 de la substance blanche cérébrale à Lomé. 178 CO.52 : Aspects du polygone de Willis à l’IRM 3D TOF dans les AVC ischémiques au CHU d’Angré. 178 CO.53 : Aspects épidémiocliniques et IRM des pathologies sellaires et para sellaires à propos de 38 cas colligés au CHU d’Angré. 179 CO.54: Morphologie du processus styloïde de l’os temporal au scanner à Parakou. 179 CO.55: Apport de l’angioscanner des troncs supraoptiques dans le bilan étiologique des accidents vasculaires cérébraux 180 CO.56 : Evaluation de l’interprétation des scanners encéphaliques en urgence neurologique au CHU d’Angré 180 CO.57 : Infiltrations lombaires sous guidage tomodensitométrique dans la prise en charge de la lombosciatalgie à DAKAR (SENEGAL). 181 CO.58: Apport de l’angioscanner dans le diagnostic des pathologies des troncs supra aortiques : à propos de 96 cas colligés à Abidjan. 182 CO.59: Aspects IRM des compressions médullaires dans la région du GBEKE à propos de 20 cas. 182 CO.60 : Profil remnologique des lésions cérébrales au Togo. 183 CO.61 : Etude radioclinique des AVC au Niger. 183 CO.62 : Evaluation de la gestion des rendez-vous et l’expérience patient au service d’imagerie médicale du CHU d’Angré 184 CO.63 : Intérêt de la scintigraphie rénale à l’acide Diéthylènetriamine-penta-acétique marqué au technétium 99 métastable dans l’exploration des reins muets à l’uroscanner. 184 CO.64: Echographie Doppler des vaisseaux de la tête du nerf optique dans le glaucome primitif à angle ouvert du sujet jeune Togolais à propos de 30 cas. 185 CO.65: Activité tomodensitométrique de garde au Centre Hospitalier Universitaire (CHU) de Cocody- Abidjan (RCI) : à propos de 723 cas colliges. 185 CO.66 : Tuberculose orbitaire : une localisation inhabituelle. 186 CO.67: Embolie pulmonaire : analyse des critères de prescriptions et d’interprétations scanographiques à Abidjan 186 CO.68 : Apport de l’échographie doppler dans le diagnostic et la prise en charge des varicocèles ; à propos de 32 cas 187 CO.69 : Chemodectome de la bifurcation carotidienne : à propos de deux cas. 187 CO.70 : Apport de l’écho doppler pénien dans la stratégie diagnostique des dysfonctions érectiles. 188 CO.71 : Aspects IRM de la non compaction du ventricule gauche (NCVG) : à propos de 3 cas et revue de la littérature 188 CO.72: Audit clinique cible de la prise en charge de l’embolie pulmonaire au Centre Hospitalier Universitaire de Tengandogo (CHUT). 189 CO.73 : Évaluation tomodensitométrique de la maladie thrombo-embolique thoracique au centre d’imagerie médicale du CHU de Treichville : à propos de 93 cas. 189 CO.74 : Titre : Aspects scanographiques de l’origine des troncs supra-aortiques à Ouagadougou. 190 CO.75 : Évaluation de la pertinence des demandes et des protocoles de réalisation d’angioscanner pour embolie pulmonaire à Yaoundé. 190 CO.76 : Echo doppler transcrânien chez les drépanocytaires SS à Niamey : Profil vélocimétrique. 191 CO.77 : Aspects échographiques des manifestations abdominales de la drépanocytose chez l’enfant homozygote SS à Niamey. 192 CO.78 : Thème : Carcinome mammaire papillaire intra-kystique du prolongement axillaire observé à l’hôpital moulins/Yzeure. 193 CO.79 : Aspects radiographiques de la tuberculose pulmonaire chez les enfants infectés par le VIH au CHU Souro Sanou de Bobo-Dioulasso, Burkina Faso. 193 CO.80 : Place de l’échographie dans la prise en charge des pathologies pédiatriques en milieu chirurgical 194 CO.81 : La tomosynthèse combinée à la mammographie standard dans le diagnostic des tumeurs mammaires au Centre Hospitalier SUD FRANCILIEN en 2018. 194 CO.82 : Titre : aspects cliniques radiologiques et histologiques d’un kyste épidermique chez une femme 195 CO.83: Titre : plaie crânio-cérébrale pénétrante par une barre de fer chez un enfant. 196 CO.84: La pratique de l’IRM mammaire à Ouagadougou. 196 CO.85 : L’apport de l’IRM du sein dans les écoulements mamelonnaires. 197 CO.86 : Approche diagnostique en imagerie des cancers rénaux pédiatriques au CHU de Treichville. 197 CO.87 : Imagerie du sein de la femme jeune de moins de 35 ans au CHU de Treichville. 198 CO.88 : Aspects épidémio-clinique et IRM de l’endométriose pelvienne à Abidjan. 198 CO.89 : Cancer du sein au Burkina Faso. Et si la bataille se gagnait avant le bloc opératoire et les salles de chimiothérapie ? 199 CO.90 : Corrélation radio-histologique des lésions mammaires à propos de 140 cas à l’unité de sénologie du service de radiodiagnostic et d’imagerie médicale du CHU de Treichville (Abidjan). 199 CO.91 : Apport de l’échographie transfontanellaire dans le diagnostic des pathologies neurologiques néonatale au CHU de BOGODOGO.. 200 CO.92 : L’hystérosalpingographie (HSG) pathologique en pratique quotidienne. 200 CO.93 : Titre : Apport de l’Échographie dans le diagnostic de circulaire du cordon ombilical 201 CO.94 : Corrélation du score TIRADS et l’histologie des nodules thyroïdiens : étude descriptive et revue de la littérature 201 CO.95 : Profil radiologique, épidémiologique et clinique des traumatismes fermés du thorax au CHU Gabriel Touré 202 CO.96 : Aspects radiographiques des lésions ostéo-articulaires de l’ulcère de Buruli dans les régions du centre de la Côte d’Ivoire. 202 Issa KONATE. 203 Adresse email : ikttata6@gmail.com.. 203 CO.97 : Pathologies ostéoarticulaires au service de radiologie CHU Pédiatrique CH. DE GAULLE de Ouagadougou, à propos de singularités étiologiques. 203 CO.98: Biopsie sous tomodensitométrie des lésions disco vertébrales : à propos de 15 cas au CIMR à Abidjan (Côte-d’Ivoire). 203 CO.99 : Apport de l’imagerie par résonance magnétique dans le diagnostic des pathologies du genou à l’Hôpital Saint Camille de Ouagadougou (HOSCO) à propos de 319 cas. 204 CO.100 : Apport de l’Imagerie par Résonance Magnétique dans l’exploration des pathologies du genou à Ouagadougou 204 CO.101: Apport de l’imagerie par résonance magnétique dans les douleurs du compartiment antérieur du genou : à propos de 84 genoux. 205 CO.102 : Profil IRM de la pathologie traumatique de la colonne cervicale au Togo. 206 CO.103 : Ergonomie de poste et troubles musculo-squelettiques chez les radiologues dans la pratique de l’échographie en Côte -d’Ivoire. 206 CO.104 : Aspects TDM des traumatismes du rachis : à propos de 52 cas. 207 Introduction : 207 Les traumatismes du rachis sont graves, mettant en jeu le pronostic vital et fonctionnel. L’objectif de notre étude était de décrire les aspects TDM des traumatismes du rachis. 207 Patients et méthode : 207 Il s’agit d’une étude prospective, transversale, descriptive sur 18 mois incluant 52 patients avec un âge moyen de 38,54 ans. Les AVP représentaient 51,9% des circonstances de survenue. Nous avons comparé les résultats de la radiographie à ceux de la TDM et confronter le degré de recul du mur postérieur à la TDM à l’existence de signes neurologiques. 207 CO.105 : Caractéristiques céphalométriques d’une population burkinabè. 207 CO.106: Les déviations fronto-axiales du genou : Aspects épidémiologiques, cliniques et radiologiques à propos de 350 cas. 208 CO.107 : Aspects échographiques et tomodensitométriques des cancers du pancréas : à propos de 42 cas au CHU Campus de Lomé. 208 CO.108 : Imagerie des urgences abdominales non traumatiques chez l’adulte : 209 Enquête qualitative auprès des médecins du service des urgences à Limbe. 209 CO 109 : Ponction-aspiration de l’abcès hépatique sous guidage échographique au CHU du point G.. 209 Auteurs: A. KONE, Y. KONE, M. CAMARA, M. KONATE, Y. COULIBALY, A. B. COULIBALY, S. SIDIBE. 209 CO.110 : Apport de l’imagerie dans le diagnostic du pseudokyste post traumatique du pancréas chez l’enfant 210 CO.111 : Diagnostic à l’imagerie des occlusions par volvulus du colon pelvien chez l’adulte. 210 CO.112 : Corps étranger intra et extra luminale digestif révélé par une occlusion intestinale aigüe : à propos d’un cas au CHU-YO.. 211 CO 113 : Apport de l’imagerie dans le diagnostic des tumeurs retro péritonéales de l’enfant. 211 CO.114 : Place de la TDM dans le diagnostic étiologique des Cholestases Extra Hépatiques (CEH) à Bouaké 212 CO.115 : Profil IRM du cancer du rectum au Centre Hospitalier d’Angré, Abidjan/Côte-d’Ivoire. 212 CO.116 : Tumeurs bénignes de la vésicule biliaire : un petit rappel sur des pathologies rares et souvent méconnues. 213 CO.117 : Performance diagnostique du Fibroscale pour l’évaluation la fibrose du foie au cours des hépatopathies chroniques. 214 CO.118 : Aspects BILI IRM dans les pathologies des voies biliaires ; à propos de 76 cas colligés à Abidjan 214 CO.119 : GIST rétropéritonéal, une localisation exceptionnelle d’une tumeur rare. A propos d’un cas à Ouagadougou et revue de la littérature. 215 CO.120 : Bilan scanographique de resécabilité des cancers du pancréas : à propos de 30 cas. 215 CO.121 : Apport de l’échographie dans le suivi des personnes vivants avec le virus de l’hépatite B. 216 CO.122 : Anatomie modale et variantes anatomiques du tronc cœliaque à l’angioscanner abdominale 216 CO.123 : Cavernome portal et thrombophilie constitutionnelle : à propos d’un cas de déficit congénital en protéine S et C et une double mutation génétique au Burkina Faso et revue de la littérature. 217 CO.124 : Drainage biliaire externe (DBE) guidé par imagerie : technique et résultats. 217 CO.125 : Aspects tomodensitométriques des cancers coliques à Bouaké à propos de 32 cas. 218 CO.126 : La radiologie interventionnelle en pratique libérale à Dakar. 218 CO.127 : Embolisation d’hémostase par du fil de suture. 219 COMMMUNICATIONS AFFICHEES. 220 POSTERS. 220 01 : Péritonite secondaire à la perforation colique par une arête de poisson. 220 03 : L’utilisation de l’Imagerie par Résonance Magnétique pour vérifier l’âge des footballeurs adolescents lors du tournoi U17 UFOA B 2021. 221 04 : Hernie hiatale du nourrisson : à propos d’un cas. 221 05 : Encéphalite limbique auto-immune : à propos d’un cas. 222 06 : Anévrysme de l’aorte découverte par dysphagie chronique : à propos de un cas. 222 07 : Hémarthrose surinfectée révélatrice d’une hémophilie A modérée. 223 CA.8 : Une pandiaphysite au cours d’une ostéarthromyosite chronique. 223 9 : Apport de l’imagerie en coupes dans le diagnostic du diverticule urétral de la femme : à propos d’un cas révélé par une rétention aiguë d’urine. 224 10 : Balle fongique de la cavité nasale mimant une rhinolithiase. 224 11 : Agénésie de la rotule : à propos de deux cas. 225 12 : L’imagerie médicale dans le bilan diagnostique du syndrome de Klippel Trenaunay : à propos d’un cas 225 13 : Apport de l’imagerie devant une monoarthrite du genou droit révélant une maladie de gaucher type I 226 14 : Le lupus érythémateux systémique de l’enfant : à propos de 3 cas. 226 15 : Neurotoxicité du gadolinium : Que dit la littérature ?. 227 16 : Forme rare du dysraphisme spinal fermé : la diastématomyélie. 228 17 : Tronc aortico-pulmonaire commun chez un enfant de 4 ans. 229 18 : Aspects épidémiologiques, cliniques, thérapeutiques et évolutifs du néphroblastome dans le service d’oncologie pédiatrique du Centre Hospitalier Universitaire Charles de Gaulle : De novembre 2009 au 31 décembre 2020 229 19 : Une récidive d‘AVC sous forme d’un Locked-In Syndrome. 230 20 : Coudure congénitale de verge traitée par la procédure de Nesbitt au CHU Souro Sanou de Bobo-Dioulasso. A propos d’une observation. 230 21 : Spondylodiscite infectieuse : tuberculose et/ou brucellose chez un jeune patient immunocompétent 231 22 : Etude de l’évolution de la consommation des antibiotiques au Centre Hospitalier Universitaire Yalgado Ouédraogo (CHU-YO) de 2015 à 2019. 232 23 : Evaluation des performances de l’Indiko Plus® à l’unité de biochimie du CHU Pédiatrique Charles De Gaulle de Ouagadougou. 232 24 : Apport de l’imagerie médicale dans le diagnostic des lésions osseuses de la drépanocytose chez l’enfant 233 25 : Myxome intra musculaire du grand adducteur de la cuisse : à propos d’un cas. 234 26 : Pseudo-anévrisme post-traumatique d’une branche de la carotide externe gauche. 234 27 : Tumeur bénigne (angiomyolipome) du psoas : à propos d'un cas découvert au Centre Hospitalier et Universitaire de Bouaké et une revue de la littérature. 235 Correspondant : 235 Issa KONATE. 235 Email : ikttata6@gmail.com.. 235 28 : Grossesse abdominale de datation tardive à propos d’un cas. 235 29 : Fracture hépatique et pancréas associée post-traumatique : à propos d’un cas au CHU Tengandogo (Burkina Faso). 235 30 : La maladie de FARH : à propos d’un cas (POSTER). 236 31 :: Aspect échographique du fibromatosis colli : à propos d’une observation à l’hôpital Sominé Dolo de Mopti au Mali 236 32 : Le tératome retro péritonéal d’un nourrisson au CHU Point G.. 237 33 : Incidentalome surrénalien révélant une tuberculose surrénalienne au scanner. 237 34 : Association hydranencéphalie et syndrome de DANDY WALKER une malformation cérébrale rare et mortelle 238 35 : Topographie et morphométrie de l’appendice vermiforme normal chez l’adulte à Ouagadougou : étude scanographique. 238 36 : Un épisode de mal convulsif révélant la maladie de FAHR. 239 37: Fistule carotidocaverneuse directe : Diagnostic et prise en charge endovasculaire à propos d’un cas et revue de la littérature. 239 38 : Chondrosarcome laryngé : à propos de 2 cas. 240 39: Abcès retro pharyngé de l’adulte par ingestion de corps étrangers : à propos de 2 cas au centre hospitalier universitaire régional de Ouahigouya. 240 40 : Tumeur papillaire du sac endolymphatique au niveau du rocher : à propos d’un cas. 241 41 :: Le fibromatosis colli : à propos de deux cas cliniques. 241 42 : Aspects clinique et IRM de l’ischémie médullaire à Lomé : une série de trois cas. 242 43 : Première expérience en radiothérapie sur un accélérateur linéaire Halcyon 2.0 au centre de radiothérapie Muk et Maseb à Kinshasa en pleine pandémie de Covid-19. 242 44 : Syndrome de Casse-Noisette ou Nutcraker syndrome : à propos d’un cas au CNHU-HKM de Cotonou au Bénin 243 45 : Évaluation des TDM thoraciques et de la PCR au cours de la COVID19 à Yaoundé. 243 46 : Bilan analytique des mémoires pour l’obtention du Diplôme d’études spécialisées en radiodiagnostic et imagerie médicale au Burkina Faso. 244 Mot de bienvenue du comité d’organisation JRANF 2021. 245 Comité d’organisation. 246 Résumé du programme. 247 Liste des EPU, des Conférences et des Ateliers. 253

AbstractHardware‐based sensing frameworks such as cooperative fuel research engines are conventionally used to monitor research octane number (RON) in the petroleum refining industry. Machine learning techniques are employed to predict the RON of integrated naphtha reforming and isomerisation processes. A dynamic Aspen HYSYS model was used to generate data by introducing artificial uncertainties in the range of ±5% in process conditions, such as temperature, flow rates, etc. The generated data was used to train support vector machines (SVM), Gaussian process regression (GPR), artificial neural networks (ANN), regression trees (RT), and ensemble trees (ET). Hyperparameter tuning was performed to enhance the prediction capabilities of GPR, ANN, SVM, ET and RT models. Performance analysis of the models indicates that GPR, ANN, and SVM with R2 values of 0.99, 0.978, and 0.979 and RMSE values of 0.108, 0.262, and 0.258, respectively performed better than the remaining models and had the prediction capability to capture the RON dependence on predictor variables. ET and RT had an R2 value of 0.94 and 0.89, respectively. The GPR model was used as a surrogate model for fitness function evaluations in two optimisation frameworks based on genetic algorithm and particle swarm method. Optimal parameter values found by the optimisation methodology increased the RON value by 3.52%. The proposed methodology of surrogate‐based optimisation will provide a platform for plant‐level implementation to realise the concept of industry 4.0 in the refinery.

AbstractThe increasing CO2 concentration in the atmosphere and the resulting climate change require an immediate and efficient reduction of anthropogenic carbon-dioxide emission. This target can be achieved by the usage of CO2-neutral fuels even with current technologies (Schemme et al. in Int J Hydrogen Energy 45:5395–5414, 2020). Diesel engines in particular are amongst the most efficient prime movers. Using oxymethylene-dimethyl-ether (OME) it is possible to solve the hitherto existing Soot-NOx-Trade-off. OME has bounded oxygen in the molecular chain. This reduces the formation of soot, but equally the calorific value. But in considerance of the physical and chemical properties of OME, it could be useful to optimize the standard diesel engine into an OME engine. As a result, single-cylinder tests were performed to obtain a detailed analysis of the differences between OME3-5 and commercially available DIN EN 590 Diesel. Based on the fact that OME has gravimetrically less than half the calorific value of diesel, twice the fuel mass must be injected for the same energy release in the combustion chamber. Therefore, at the beginning of the investigations, a variation of the injector flow rate was carried out by means of different nozzle hole diameters. The evaluation of the results included the fundamental differences in the combustion characteristics of both fuels and the determination of efficiency-increasing potentials in the conversion of OME3-5. Due to the lower ignition delay and the shorter combustion time of OME, potentials in the optimisation of the injection setting became apparent. Higher energy flows over the combustion chamber wall were noticeable in operation with OME. To get to the bottom of this, the single-cylinder investigations were supported by tests on the optically accessible high-pressure chamber and the single-cylinder transparent engine. The optical images showed a narrower cone angle and greater penetration depth of the OME injection jet compared to the diesel injection jet. This confirmed the results from the single-cylinder tests. This provides further potential in the design of the injector nozzle to compensate for these deficits. Overall, this work shows that operation with OME in a classic diesel engine is possible without any significant loss in efficiency and with little effort in the hardware. However, it is also possible to achieve more efficient use of the synthetic fuel with minor adjustments.

AbstractSince the mid '80s, compiler writers for functional languages (especially lazy ones) have been writing papers about identifying and exploiting thunks and lambdas that are used only once. However, it has proved difficult to achieve both power and simplicity in practice. In this paper, we describe a new, modular analysis for a higher order language, which is both simple and effective. We prove the analysis sound with respect to a standard call-by-need semantics, and present measurements of its use in a full-scale, state-of-the-art optimising compiler. The analysis finds many single-entry thunks and one-shot lambdas and enables a number of program optimisations. This paper extends our preceding conference publication (Sergey et al. 2014 Proceedings of the 41st Annual ACM SIGPLAN-SIGACT Symposium on Principles of Programming Languages (POPL 2014). ACM, pp. 335–348) with proofs, expanded report on evaluation and a detailed examination of the factors causing the loss of precision in the analysis.

Introduction Although our postmodern (media) society should provide room for diversity and otherness (Greer and Jewkes), some people are not integrated but rather excluded. Social exclusion can be defined as the discrepancy of the wish of being part of a society and its possibilities to be part of it and contains feelings or experiences of physically or emotionally exclusion from others (Burchardt et al.; Riva and Eck). It is not really known what or who is responsible for social exclusion (Hills et al.), but it is certain that it is not that rare phenomenon — especially in social media. Here, digital engagement characteristics (likes, follows, shares, and comments) are important to build up, renew, and strengthen different forms of relationships. But if users do not receive any feedback, the risk of feeling social excluded increases. In this context, adolescents and young adults as the primary audience are the focus of interest. They seem to be especially vulnerable when it comes to social ostracism within social media and its potential negative psychological effects (Timeo et al.). The variety of social exclusion allows multiple perspectives on the topic. Hereafter we focus on young people with cancer. This life-threatening disease can increase the risk of being excluded. Cancer as a chronic illness and its negative effects on people’s lives, such as potential death, long-term and late effects, private and social burdens (Hilgendorf et al.), show an obvious otherness compared to the healthy peer, which might push ostracism effects and social exclusion of young people within social media to a new level. We actually can see a large number of (included) young cancer patients and survivors using social media for information sharing, exchanging ideas, networking, and addressing their unmet needs of the real world (Chou et al.; Chou and Moskowitz; Ruckenstuhl et al.; Perales et al.). Especially Instagram is becoming more present in social cancer communication (Stage et al.), though it actually increasingly represents cheerful, easy-going content (Hu et al.; Waterloo et al.). Judging by the number of cancer-related hashtags, we can see more and more public cancer bloggers thematise cancer illness on Instagram. But less is known about the actual content posted by cancer bloggers on Instagram. This leads us to the question, to what extent is cancer content found and included or excluded on public Instagram profiles of German speaking cancer bloggers? And is there a difference between biography descriptions with visible cancer references and posted motifs, captions and hashtags? Chronic Illnesses, Identities, and Social Networks Chronic illnesses such as cancer not only affect the body, but also impact on the identity of those affected. It is understood as life-changing with both short-term and long-term effects on the identity-forming process and on the already developed identity (Bury; Charmaz; Leventhal et al.). With their diagnosis, adolescents and young adults face a double challenge: they have to cope with the typical developmental changes of this age group and they have to negotiate these changes against the background of a life-threatening illness (Makros and McCabe; Zebrack and Isaacso). Miller shows three levels of identity for young cancer patients (pre-cancer identity, patient identity, and post-cancer identity), which are used regularly and flexibly by those affected in their interaction with the social network in order to maintain relationships and to minimise communicative misunderstandings. Moreover, the negotiation of the self within the social network and its expectations, especially towards convalescent people, can lead to paradoxical situations and identities of young people with cancer (Jones et al.). Although therapeutic measures are completed and patients may be discharged as cured, physical, cognitive, and emotional challenges with regard to the illness (e.g. fatigue, loss of performance, difficulty concentrating) still have to be overcome. These challenges, despite recovery, cause those affected to feel they still belong to a cancer group which they have actually largely outgrown medically and therapeutically, and also continually remind them of their present difference from the healthy peer group. To minimise these differences, narratives are the means for those affected to negotiate their new illness-related identity with their network (Hyde). These processes can be digitally transformed on blogs or to age-appropriate social network sites (SNS), which enable users to record and communicate experiences and emotions in an uncomplicated, situational manner and with fewer inhibitions (Kim and Gilham). Cancer contents on SNS are called autopathography and can serve as a means of self-expression, whilst at the same time stimulating communication and networking and thus significantly influencing identity and identity development in the chronic disease process (Rettberg; Ressler et al.; Abrol et al.; Stage). The possibility of recording and archiving private moments in a digital environment through photos and texts creates a visual diary. Here, illness recordings are not just motifs, but also part of an identity process by accepting the self as being ill (Nesby and Salamonsen; Tembeck). Instagram-Exclusive Positivity Instagram is the most popular social media network amongst 14-29 year olds in Germany (Beisch et al.). It presents itself as a highly visual structured platform. Furthermore, both posts and stories are dominated by content with innocuous motifs (Hu et al.). Additionally, the visual culture on Instagram is supported by integrated image optimisations such as filters and therefore often associated with high aesthetic standards (Waterloo et al.). This encourages the exchange of idealised self-presenting and self-advertising content (Lee et al.; Lup et al.; Sheldon and Bryant). The positive tone of the shared motifs and captions can also be explained by larger, sometimes anonymous networks on Instagram. The principle of non-reciprocal following of public accounts increasingly creates weak ties, which can additionally encourage the sharing of positively connoted content due to the anonymity (Lin et al.; Waterloo et al.). The posting of negative moods or image motifs to anonymous followers does not seem to be socially standardised, due to the associated intimate thoughts and feelings (Bazarova). In addition, users are aware of the public framework in which they address intimate topics and discourses (Bazarova and Choi). Internal platform standards and technical possibilities thus create a particular posting culture: an environment that is—due to its strong visual-aesthetic structure and anonymous follower-based networks—almost exclusively positive. However, these assumptions and findings are based on a general posting culture, which is usually not focussed on niche topics like cancer. Previous studies show that SNS are used for exchange and networking, especially by young cancer patients (Chou and Moskowitz; Perales et al.). Studies from online SNS disease-related self-help groups show that weak ties in illness situations are considered beneficial when it comes to self-disclosure, seeking help, and support (Wright et al.; Love et al.; Donovan et al.). In addition, Instagram is part of the so-called “vital media” (Stage et al.), which means it is very important for young cancer patients to share cancer-related material. But despite these research findings less is known about the content shared by German-speaking bloggers who have visible cancer references in their Instagram biography. Do they include a serious, even life-threatening illness on a platform that actually stands for positivity, or do they follow the invisible platform regulations in their posted content and statements and exclude it by themselves? The specific objectives of this explorative study were (a) to obtain a descriptive analysis of the manner in which cancer bloggers post content on Instagram, and (b) to determine the extent to which most applied practices exclude the posting of certain negatively connoted motives and emotions associated with cancer. Methodology For the study, 142 German-speaking cancer bloggers (14–39 years of age) with public accounts and visible cancer references in their biography were researched on Instagram. The sample was divided into posts (7,553) and stories (4,117). The content was examined using a standardised content analysis and a code book with relevant categories (motifs, body presences, emotions, captions, emojis; ICR Cronbach’s alpha = 0.85). Measured by the value of the content posted, the story users, at 23 years of age, were comparatively much younger than the post users, at 30 years of age. The sample was predominantly female in both posts (81%) and stories (99%). The most common form of cancer was breast cancer (posts: 28%; stories: 29%), followed by brain tumors (posts: 19%; stories: 16%) and leukaemia (posts: 4%; stories: 19%). Most content was shared by people who were actively involved in treatment – 46% of posts and 54% of stories. Completed treatments were more common in posts (39%) than in stories (19%). At the time of data collection, the Instagram entries were explicitly open to the public, and no registration was required. The content, not the individual, was analysed to minimise the risk for the bloggers and to prevent them from violations of privacy and autonomy by third parties. Furthermore, the entries were assigned unidentifiable numbers to ensure that no tracing is possible (Franzke et al.). Results The sample consists of public cancer blogger accounts who document everyday experiences for their network in images and videos. The following results are shown for posts (P) and stories (S). Motifs and Bodies Looking at the evaluation of the image motifs, the selfie predominates both in posts, with 20.7 per cent, and stories, with 32.8 per cent. Other popular photo motifs are pictures of food (P: 10.2%; S: 11.0%), activities (P: 7.2%; S: 7.7%), landscapes (P: 6.3%; S: 7.1%), and of/with family and friends (P: 12.5%; S: 6.0%). Photos in medical or clinical settings are rare, with one per cent in the posts and three per cent in the stories. Looking at the bodies and faces displayed, a comparatively normal to positive image of the bloggers that were studied can be observed. Most of the people in the posts present themselves with hair (81.3%), wear make-up (53.3%) and smile at the camera (64.1%). A similar trend can also be seen in the stories. Here 63.8 per cent present themselves with hair, 62.7 per cent with make-up and 55.3 per cent with happy facial expressions. In contrast, scars (P: 1.6%; S: 4.4%) or amputations (P: 0.2%; S: 0.1%) are hardly ever shown. Thus, possible therapy-accompanying symptoms, such as alopecia, ports for chemotherapy, or amputations (e.g. mastectomy in the case of breast cancer) are rarely or hardly ever made visible by cancer bloggers. Captions, Hashtags, and Emojis Similar to the motifs, everyday themes dominate in the captions of the images, such as the description of activities (P: 23.2%; S: 18.0%), food (P: 8.2%; S: 9.3%), or beauty/fashion (P: 6.2%; S: 10.2%). However, information on the current health status of the person affected can be found under every tenth photo, both in the stories and in the posts. Hashtags are mainly found amongst the posts with 81.5 per cent. In keeping with the caption, normal themes were also chosen here, divided into the categories of activities (17.7%), beauty/fashion (7.6%), food (5.8%), and family/friends (4.8%). Illness-specific hashtags (e.g. #cancer, #survivor, or #chemo) were chosen in 15.6 per cent. In addition, the cancer bloggers in this study used emojis in 74 per cent of their posts. In the stories, however, only 28.2 per cent of the content was tagged with emojis. The most common category is smileys & people (P: 46.8%; S: 52.8%), followed by symbols (e.g. hearts, ribbons) (P: 21.1%; S: 26.5%), and animals & nature (P: 17.0%; S: 14.2%). Emotions In captions, hashtags and emojis, emotions were divided into positive (e.g. joy, fighting spirit), neutral (e.g. simple narration of the experience), and negative (e.g. fear, anger). It is noticeable that in all three categories predominantly and significantly positive or neutral words and images were used to describe emotional states or experiences. In the case of captions, 40.4 per cent of the posts and 43.9 per cent of the stories could be classified as positive. For the hashtags, the values were 18.7 per cent (P) and 43 per cent (S), and for the emojis 60 per cent (P) and 65.7 per cent (S). In contrast, there were hardly any negative moods (captions P: 5.7%, S: 5.8%; hashtags P: 4.4%, S: 0.7%; emojis P: 8.7%, S: 6.4%). Although the disease status (e.g. active in therapy or completed) had less impact on emotional messages, a significant connection with the applied thematic areas could be observed. Thus, it is apparent that medical and/or therapeutic aspects tend to be described with positive and negative words and hashtags, e.g. the current health status (χ²(3) = 795.44, p =.000, φ = 0.346) or the topics of illness/health via hashtag (χ²(3) = 797.67, p =.000, φ = 0.361). Topics such as food (χ²(3) = 20.49, p =.000, φ = 0.056) or beauty/fashion (χ²(3) = 51.52, p =.000, φ = 0.092) are recognisably more impersonal from an emotional perspective. Discussion A Digital Identity Paradox Drugs, chemotherapy, setbacks, physical impairments, or anxiety are issues that usually accompany cancer patients during treatment and also in remission. Looking at the content posted by German-speaking cancer bloggers on Instagram, illness-related images and words are comparatively rare. The bloggers show their normal, mostly cancer-free world, in which negative and illness-related content does not seem to fit. Although they clearly draw attention to their illness through their biography, this is not or only rarely addressed. Therefore, it can be stated that cancer as a topic is excluded by choice by the bloggers examined. Neither motifs, captions, nor hashtags make the illness visible. This seems paradoxical because the content and biography appear to contradict each other. And yet, the content studied only shows what Jones et al. and Miller have already described: their identity paradox, or multiple identities. The digital acceptance of one's own illness and solidarity with (anonymous) fellow sufferers is clearly given through the disclosure in the biography, but yet a normal and healthy online ego—comparable to the peer group and equal to their own illness identity—is aspired to. It seems as if those affected have to switch their identity back and forth. The awareness that they are already different in real life (in this case, ill) encourages the users examined to show a normal, age-appropriate life—at least online, which is why we speak of an identity paradox 2.0. Based on our data, the obvious otherness of being ill—and in this context the potential higher risk of digital ostracism effects (Greer and Jewkes; Timeo et al.)—can be a reason for self-exclusion of the cancer topic, in order not to be excluded by a healthy peer. The Standard Creates the Content The positive tone that can be found in almost every second post can be explained by the platform standards and practices themselves (Waterloo et al.). Thus, smiling faces in a public environment correspond more to this than sadness, anger, or despair. Although disease-related topics in captions are also provided with negatively connoted language, they do not have a determining influence on the public self-image of the blogger and their life and the illness. The strong visual culture on Instagram does not leave much scope for "other", perhaps more authentic serious content. The fact that published content has the potential to talk about cancer and to make one’s own experience with the disease transparent is proven by blogs (Kim and Gilham). Instagram does not currently seem to be particularly suitable for public profiles to make serious illness narratives about cancer. Conclusion It remains to be noted that public cancer blogs attempt to include a serious topic on Instagram. But with regard to the data, we can see a form of (maybe unconsciously) self-chosen exclusion of illness narratives. The reasons might vary. On the one hand, cancer bloggers want to belong to a healthy peer group, and expressing a visible otherness would exclude them. Therefore, they try to reduce the higher risk potential of ostracism effects. On the other hand, internal Instagram regulations and standards create an environment which can strengthen the bloggers' posting behaviours: young people, especially, post life-affirming and life-related content. This also helps them to cope with crisis situations and to avoid being dominated by a life-threatening disease. Further research on cancer on Instagram is needed to determine to what extent this is desired, and whether an awareness of this paradox exists or develops intuitively. 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