Community pharmacists' perspectives on assessing kidney function and medication dosing for patients with advanced chronic kidney disease: A qualitative study using the theoretical domains framework.

Background: The kidneys are responsible for the elimination of many drugs. Chronic kidney disease (CKD) is common, and medications may require adjustment to avoid adverse outcomes. Despite the availability of kidney drug dosing resources, people with CKD are at risk of inappropriate drug prescribing. Community pharmacists are in the ideal position to mitigate harm from inappropriate prescribing in this population. Methods: In this qualitative study, community pharmacists were interviewed on their perspective on kidney function assessment and dose adjustment in people with advanced CKD (estimated glomerular filtration rate <30 mL/min/1.73 m2). The theoretical domains framework for targeting behavioural change was used to inform the interview guide and analysis. Purposeful sampling was employed until data saturation. Semistructured virtual interviews were audio-recorded, transcribed verbatim and uploaded into NVIVO 12 Pro to facilitate thematic analysis. Deductive and inductive iterative coding approaches were employed to determine categories and themes. Results: Twelve pharmacists were interviewed, with a mean age of 42 years and 16 years of experience. Four themes comprising 10 categories were identified to influence kidney function assessment and dosing, including resources (information access, technology, references), environment (pharmacy infrastructure, practice setting), reflection (triggers, experience and training, collaboration) and leadership and governance (pharmacist role, advocacy). Feedback on an optimal CKD tool was collected, and enabling themes (categories) for implementation included knowledge and skills (education, training) and reflection (role, support, integration). Conclusions: Findings will inform the interventions needed to improve implementation of kidney assessment and dosing of high-risk medications in people with kidney impairment into community pharmacy practice. Can Pharm J (Ott) 2023;156:xx-xx.

Method To Visualize the Intratumor Distribution and Impact of Gemcitabine in Pancreatic Ductal Adenocarcinoma by Multimodal Imaging.

Gemcitabine (dFdC) is a common treatment for pancreatic cancer; however, it is thought that treatment may fail because tumor stroma prevents drug distribution to tumor cells. Gemcitabine is a pro-drug with active metabolites generated intracellularly; therefore, visualizing the distribution of parent drug as well as its metabolites is important. A multimodal imaging approach was developed using spatially coregistered mass spectrometry imaging (MSI), imaging mass cytometry (IMC), multiplex immunofluorescence microscopy (mIF), and hematoxylin and eosin (H&E) staining to assess the local distribution and metabolism of gemcitabine in tumors from a genetically engineered mouse model of pancreatic cancer (KPC) allowing for comparisons between effects in the tumor tissue and its microenvironment. Mass spectrometry imaging (MSI) enabled the visualization of the distribution of gemcitabine (100 mg/kg), its phosphorylated metabolites dFdCMP, dFdCDP and dFdCTP, and the inactive metabolite dFdU. Distribution was compared to small-molecule ATR inhibitor AZD6738 (25 mg/kg), which was codosed. Gemcitabine metabolites showed heterogeneous distribution within the tumor, which was different from the parent compound. The highest abundance of dFdCMP, dFdCDP, and dFdCTP correlated with distribution of endogenous AMP, ADP, and ATP in viable tumor cell regions, showing that gemcitabine active metabolites are reaching the tumor cell compartment, while AZD6738 was located to nonviable tumor regions. The method revealed that the generation of active, phosphorylated dFdC metabolites as well as treatment-induced DNA damage primarily correlated with sites of high proliferation in KPC PDAC tumor tissue, rather than sites of high parent drug abundance.

An Investigation into the Prediction of the Plasma Concentration-Time Profile and Its Interindividual Variability for a Range of Flavin-Containing Monooxygenase Substrates Using a Physiologically Based Pharmacokinetic Modeling Approach.

Our recent paper demonstrated the ability to predict in vivo clearance of flavin-containing monooxygenase (FMO) drug substrates using in vitro human hepatocyte and human liver microsomal intrinsic clearance with standard scaling approaches. In this paper, we apply a physiologically based pharmacokinetic (PBPK) modeling and simulation approach (M&S) to predict the clearance, area under the curve (AUC), and Cmax values together with the plasma profile of a range of drugs from the original study. The human physiologic parameters for FMO, such as enzyme abundance in liver, kidney, and gut, were derived from in vitro data and clinical pharmacogenetics studies. The drugs investigated include itopride, benzydamine, tozasertib, tamoxifen, moclobemide, imipramine, clozapine, ranitidine, and olanzapine. The fraction metabolized by FMO for these drugs ranged from 21% to 96%. The developed PBPK models were verified with data from multiple clinical studies. An attempt was made to estimate the scaling factor for recombinant FMO (rFMO) using a parameter estimation approach and automated sensitivity analysis within the PBPK platform. Simulated oral clearance using in vitro hepatocyte data and associated extrahepatic FMO data predicts the observed in vivo plasma concentration profile reasonably well and predicts the AUC for all of the FMO substrates within 2-fold of the observed clinical data; seven of the nine compounds fell within 2-fold when human liver microsomal data were used. rFMO overpredicted the AUC by approximately 2.5-fold for three of the nine compounds. Applying a calculated intersystem extrapolation scalar or tissue-specific scalar for the rFMO data resulted in better prediction of clinical data. The PBPK M&S results from this study demonstrate that human hepatocytes and human liver microsomes can be used along with our standard scaling approaches to predict human in vivo pharmacokinetic parameters for FMO substrates.

An Investigation into the Prediction of in Vivo Clearance for a Range of Flavin-containing Monooxygenase Substrates.

Flavin-containing monooxygenases (FMO) are metabolic enzymes mediating the oxygenation of nucleophilic atoms such as nitrogen, sulfur, phosphorus, and selenium. These enzymes share similar properties to the cytochrome P450 system but can be differentiated through heat inactivation and selective substrate inhibition by methimazole. This study investigated 10 compounds with varying degrees of FMO involvement to determine the nature of the correlation between human in vitro and in vivo unbound intrinsic clearance. To confirm and quantify the extent of FMO involvement six of the compounds were investigated in human liver microsomal (HLM) in vitro assays using heat inactivation and methimazole substrate inhibition. Under these conditions FMO contribution varied from 21% (imipramine) to 96% (itopride). Human hepatocyte and HLM intrinsic clearance (CLint) data were scaled using standard methods to determine the predicted unbound intrinsic clearance (predicted CLint u) for each compound. This was compared with observed unbound intrinsic clearance (observed CLint u) values back calculated from human pharmacokinetic studies. A good correlation was observed between the predicted and observed CLint u using hepatocytes (R2 = 0.69), with 8 of the 10 compounds investigated within or close to a factor of 2. For HLM the in vitro-in vivo correlation was maintained (R2 = 0.84) but the accuracy was reduced with only 3 out of 10 compounds falling within, or close to, twofold. This study demonstrates that human hepatocytes and HLM can be used with standard scaling approaches to predict the human in vivo clearance for FMO substrates.

An Evaluation of Medication Reconciliation in an Outpatient Nephrology Clinic.

Background: Accreditation Canada recognizes medication reconciliation as a key required organizational practice (ROP) to enhance patient safety. Patients with chronic kidney disease (CKD) carry a high risk for adverse drug events due to multiple co-morbidities, using many medications, and being cared for by many practitioners. Data evaluating the benefits of ambulatory medication reconciliation (AmbMR) in patients with advanced CKD is limited. Methods: We retrospectively evaluated types and rates of medication discrepancies and their potential index for patient harm using the Cornish classification system in a cohort of consecutive non-dialysis-dependent CKD stage 5 patients who received AmbMR. Results: AmbMR was conducted 225 times on 115 patients during the study period. One hundred eighty medication discrepancies were identified. The most common discrepancy identified was incorrect drug followed by discrepant dose, discrepant frequency, and drug omission. Sixty-three percent of discrepancies were classified as unlikely to cause patient discomfort or clinical deterioration, 36% were classified as likely to cause moderate harm, and one percent was classified as potential to cause serious harm. Conclusion: Medication discrepancies are common in patients with advanced CKD. Nearly a quarter of patients may experience moderate discomfort or clinical deterioration from discrepancies. Our study showed that in patients with non-dialysis-dependent CKD stage 5, the risk of patient harm associated with medication discrepancies can be reduced by conducting AmbMR.

Translating policy into practice: a case study in the secondary prevention of coronary heart disease.

BACKGROUND: This paper focuses on the relationships between health 'policy' as it is embodied in official documentation, and health 'practice' as reported and reflected on in the talk of policy-makers, health professionals and patients. The specific context for the study involves a comparison of policies relating to the secondary prevention of coronary heart disease (CHD) in the two jurisdictions of Ireland - involving as they do a predominantly state funded (National Health Service) system in the north and a mixed health-care economy in the south. The key question is to determine how the detail of health policy as contained in policy documents connects to and gets translated into practice and action. METHODS: The data sources for the study include relevant health-care policy documents (N=5) and progress reports (N=6) in the two Irish jurisdictions, and semi-structured interviews with a range of policy-makers (N=28), practice nurses (14), general practitioners (12) and patients (13) to explore their awareness of the documents' contents and how they saw the impact of 'policy' on primary care practice. RESULTS: The findings suggest that although strategic policy documents can be useful for highlighting and channelling attention to health issues that require concerted action, they have little impact on what either professionals or lay people do. CONCLUSION: To influence the latter and to encourage a systematic approach to the delivery of health care it seems likely that contractual arrangements - specifying tasks to be undertaken and methods for monitoring and reporting on activity - are required.

A systematic review of explanatory factors of barriers and facilitators to improving asthma management in South Asian children.

BACKGROUND: South Asian children with asthma are less likely to receive prescriptions and more likely to suffer uncontrolled symptoms and acute asthma admissions compared with White British children. Understanding barriers are therefore vital in addressing health inequalities. We undertook a systematic review identifying explanatory factors for barriers and facilitators to asthma management in South Asian children. South Asians were defined as individuals of Indian, Pakistani or Bangladeshi descent. METHODS: Data Sources - Medline, HMIC, EMBASE, ASSIA, Web of Science, BNI, CINAHL, PsycINFO, OpenSIGLE, CRD, Scopus, NHS Evidence, Cochrane Library, Campbell Collaboration, RCPCH, ATS, ERS, Asthma UK, Google Scholar & Asthma Guidelines (BTS, GINA, ATS, Monash, NAEPP, Singapore & New Zealand) to August 2013.Inclusion Criteria - Qualitative, quantitative or mixed methods research with primary focus on identifying explanations for barriers and/or facilitators to asthma management in South Asian children aged 0-18 years with diagnosed/suspected asthma and/or carers and/or healthcare professionals.Data Extraction - Three authors independently reviewed, selected & extracted eligible articles with disagreements resolved by research team discussion. RESULTS: 15 studies encompassing 25,755 children, 18,483 parents/carers and 239 healthcare professionals were included. Barriers and explanatory factors identified were:1. Lack of asthma knowledge in families and healthcare professionals.2. Under-use of preventer medications.3. Non-acceptance/denial of asthma.4. Over-reliance on Emergency Department management.5. Communication problems.6. Non-adherence to medication.7. Use of complementary therapies.Little facilitators regarding asthma management were identified. CONCLUSIONS: Several key issues were identified as likely to be ethnic-specific to South Asian families, rather than a reflection of minority status: impact of parental and professional knowledge and beliefs, health service utilisation pattern explanations and the impact of prejudice and stigmatisation. Other explanations such as language barriers are not strictly ethnic specific but instead reflect a minority position.Further research is required to identify why barriers exist, the mechanisms by which they impact on asthma management and how they can be overcome. Furthermore, understanding the difference between barriers and explanations that are ethnic-specific and those that are related to being a minority will enable the application of generic system-wide interventions where ethnicity is not the issue and ethnically-tailored interventions where needed.

Recent Changes in Anemia Management: The Kidney Disease Improving Global Outcomes (KDIGO) Anemia Guideline versus the Canadian Society of Nephrology (CSN).

The management of anemia is important for health outcomes for people with chronic kidney disease (CKD). Global evidenced-based guidelines must be placed in the Canadian context to be relevant to guide practice. This paper summarizes the response of the Canadian Society of Nephrology to global anemia management guidelines in CKD and the implications for practice.

Metabolism-driven in vitro/in vivo disconnect of an oral ERɑ VHL-PROTAC.

Targeting the estrogen receptor alpha (ERα) pathway is validated in the clinic as an effective means to treat ER+ breast cancers. Here we present the development of a VHL-targeting and orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of ERα. In vitro studies with this PROTAC demonstrate excellent ERα degradation and ER antagonism in ER+ breast cancer cell lines. However, upon dosing the compound in vivo we observe an in vitro-in vivo disconnect. ERα degradation is lower in vivo than expected based on the in vitro data. Investigation into potential causes for the reduced maximal degradation reveals that metabolic instability of the PROTAC linker generates metabolites that compete for binding to ERα with the full PROTAC, limiting degradation. This observation highlights the requirement for metabolically stable PROTACs to ensure maximal efficacy and thus optimisation of the linker should be a key consideration when designing PROTACs.

Canadian Society of Nephrology commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD.

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for anemia management in patients with chronic kidney disease provides the structural and evidence base for the Canadian Society of Nephrology commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 11 of the 61 KDIGO guideline statements. Specifically, we agreed that a therapeutic trial of iron is appropriate in cases in which a reduction in erythropoiesis-stimulating agent (ESA) dosage or avoidance of ESA and transfusion is desired, transferrin saturations are >30%, and ferritin concentrations are >500 µg/L. However, we concluded that there is insufficient evidence to support an upper target or threshold for ferritin and transferrin saturation levels. We agree with the initiation of ESA treatment when hemoglobin (Hb) level is 90-100 g/L; however, we specifically state that an acceptable range for Hb level is 95-115 g/L, with a target of 100-110 g/L, and add caution to individualization above this range due to concerns regarding the safety of ESAs. We agree that ESAs should be used with considerable caution in patients with active malignancy, history of stroke, or history of malignancy, and we suggest initiating ESA therapy at Hb level of 90 g/L and to aim for a Hb level in the range of 90-105 g/L. The reader is encouraged to note the level of evidence and review the entire KDIGO anemia guideline to interpret the guideline statements and commentary appropriately.

Oral sodium thiosulfate as maintenance therapy for calcific uremic arteriolopathy: a case series.

BACKGROUND: Calcific uremic arteriolopathy (CUA) is a rare but serious disorder affecting 4% of dialysis patients. Intravenous sodium thiosulfate (IV STS) has been shown as an effective treatment. In Canada, the average cost of IV STS is about CAD 12,000 per month, while the cost of compounded oral STS is CAD 45 per month. METHODS: Prospective cohort where all patients diagnosed with CUA during the year 2011 were included. They were treated initially with IV STS. Afterwards, each patient had a baseline bone scan and was started on oral STS for a total of 6 months followed by a repeat bone scan. A single radiologist, blinded to the dates of both scans for a given patient, read all scans. RESULTS: Four patients were studied. The intravenous dose used was 25 g three times a week for an average duration of 131 days. After the maintenance therapy, 2 patients developed further regression of the lesions, 1 had stable lesions, and 1 got worse; however, nonadherence to the drug was confirmed. The oral medication was well tolerated with no reported side effects. CONCLUSION: Oral STS, after IV STS, seems to stabilize, or even improve CUA lesions, and therefore could be useful as maintenance therapy, especially since its cost is much more reasonable than IV STS and due to the ongoing shortage of the IV formulation.

Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer.

Removal of the basic piperazine nitrogen atom, introduction of a solubilising end group and partial reduction of the triazolopyridazine moiety in the previously-described lead androgen receptor downregulator 6-[4-(4-cyanobenzyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (1) addressed hERG and physical property issues, and led to clinical candidate 6-(4-{4-[2-(4-acetylpiperazin-1-yl)ethoxy]phenyl}piperidin-1-yl)-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine (12), designated AZD3514, that is being evaluated in a Phase I clinical trial in patients with castrate-resistant prostate cancer.

Ferric Derisomaltose Evaluation in Patients with Non-Dialysis-Dependent Chronic Kidney Disease or Peritoneal Dialysis.

Background: Iron deficiency anemia is common in patients with advanced chronic kidney disease (CKD). Ferric derisomaltose (FDI) enables iron repletion in a single dose, unlike other forms of iron for IV administration, which require multiple doses. Protocols are commonly used with other IV irons, but there are limited Canadian data for FDI, and no protocol exists. Objectives: To evaluate the efficacy and safety of FDI for patients with CKD and to ascertain information related to its use in Canadian provinces. Methods: This retrospective cohort study involved patients with non-dialysis-dependent CKD (NDD-CKD) and patients undergoing peritoneal dialysis (PD) who received FDI in a tertiary hospital in Nova Scotia between June 2020 and May 2021. Each patient was followed for a minimum of 6 months. The efficacy outcomes were the changes from baseline in hemoglobin, transferrin saturation (TSAT), and ferritin after the first dose of FDI and at 3 and 6 months. The safety outcomes were the frequency and types of adverse reactions to FDI. Electronic surveys were sent to 33 Canadian renal pharmacists to gather information about FDI use, dosing, administration, monitoring, funding, and safety in their respective organizations. Results: A total of 52 infusions were administered to 35 patients during the study period. The median times between doses 1 and 2 and between doses 2 and 3 were 19.1 and 6.6 weeks, respectively. The median change from baseline to first post-FDI follow-up blood work was significant for hemoglobin (9.0 g/L, p = 0.023), TSAT (11 percentage points, p < 0.001), and ferritin (271.4 µg/L, p < 0.001). Median darbepoetin doses decreased from baseline to 6 months (p < 0.001). Three adverse reactions occurred. At least 15 (65%) of the 23 survey respondents reported that FDI was funded by their province or was listed on their hospital drug formulary. Conclusion: This study provides evidence that FDI is an effective and safe treatment for anemia in NDD-CKD and PD patients.

Contexte: L'anémie ferriprive est fréquente chez les patients atteints d'insuffisance rénale chronique avancée (IRC). Une seule dose de dérisomaltose ferrique (FDI) permet au niveau de fer de se rétablir, contrairement à d'autres formes de fer administrées par IV qui nécessitent, elles, plusieurs doses. Des protocoles sont couramment utilisés avec d'autres fers administrés par IV, mais les données canadiennes sur le FDI sont limitées et il n'existe aucun protocole. Objectifs: Évaluer l'efficacité et l'innocuité du FDI chez les patients atteints d'IRC et vérifier les informations relatives à son utilisation dans les provinces du Canada. Méthodes: Cette étude de cohorte rétrospective comprenait des patients atteints d'IRC sans dialyse (NDD-IRC) et des patients sous dialyse péritonéale (DP) ayant reçu du FDI dans un hôpital de soins tertiaires de la Nouvelle-Écosse entre juin 2020 et mai 2021. Chaque patient a fait l'objet d'un suivi pendant au moins 6 mois. Les résultats d'efficacité étaient les changements par rapport à la base de trois mesures après la première dose de FDI et à 3 et 6 mois, soit l'hémoglobine, la saturation de la transferrine (TSAT) et la ferritine. Les résultats d'innocuité étaient la fréquence et les types de réactions indésirables au FDI. Des sondages ont été envoyés par voie électronique à 33 pharmaciens canadiens spécialisés en néphrologie afin de recueillir des renseignements sur l'utilisation, le dosage, l'administration, la surveillance, le financement et l'innocuité du FDI dans leurs organismes respectifs. Résultats: Au total, 52 perfusions ont été administrées à 35 patients au cours de la période d'étude. Les délais médians entre les doses 1 et 2, et entre les doses 2 et 3 étaient respectivement de 19,1 et 6,6 semaines. Le changement médian entre la base et le premier bilan sanguin de suivi post-FDI était important pour l'hémoglobine (9,0 g/L, p = 0,023), le TSAT (11 points de pourcentage, p < 0,001) et la ferritine (271,4 µg/L, p < 0,001). Les doses médianes de darbépoétine ont diminué par rapport à la base à 6 mois (p < 0,001). Trois effets indésirables se sont produits. Au moins 15 des 23 répondants au sondage (65 %) ont déclaré que le FDI était financé par leur province ou figurait sur les listes de médicaments des hôpitaux. Conclusion: Cette étude fournit des preuves que le FDI est un traitement efficace et sûr de l'anémie chez les patients NDD-IRC et PD.

Hyperkalemia: Prevalence, Predictors and Emerging Treatments.

It is well established that an elevated potassium level (hyperkalemia) is associated with a risk of adverse events including morbidity, mortality and healthcare system cost. Hyperkalemia is commonly encountered in many chronic conditions including kidney disease, diabetes and heart failure. Furthermore, hyperkalemia may result from the use of renin-angiotensin-aldosterone system inhibitors (RAASi), which are disease-modifying treatments for these conditions. Therefore, balancing the benefits of optimizing treatment with RAASi while mitigating hyperkalemia is crucial to ensure patients are optimally treated. In this review, we will briefly discuss the definition, causes, epidemiology and consequences of hyperkalemia. The majority of the review will be focused on management of hyperkalemia in the acute and chronic setting, emphasizing contemporary approaches and evolving data on the relevance of dietary restriction and the use of novel potassium binders.

The PARP1 Inhibitor AZD5305 Impairs Ovarian Adenocarcinoma Progression and Visceral Metastases in Patient-derived Xenografts Alone and in Combination with Carboplatin.

PARP inhibitors (PARPi) have changed the management of patients with ovarian cancer and their effectiveness has been demonstrated especially in homologous recombination repair-deficient tumors. These first-generation drugs target PARP1, but also PARP2 and other family members potentially responsible for adverse effects that limit their therapeutic potential and restrict their use in combination with chemotherapeutic agents. We investigated ovarian cancer patient-derived xenografts (OC-PDXs) to assess whether malignant progression could be impaired by a novel inhibitor selective for PARP1 (AZD5305) and to assess the potential of its combination with carboplatin (CPT), the standard-of-care for patients with ovarian cancer. In BRCA-mutated OC-PDXs, AZD5305 achieved greater tumor regressions and longer duration of response as well as a superior impairment of visceral metastasis and improved survival benefit compared with the first-generation dual PARP1/2 inhibitors. The combination of AZD5305 plus CPT was more efficacious than single agents. Subcutaneously growing tumors experienced regression that persisted after therapy stopped. Combination efficacy was greater against tumors that did not respond well to platinum, even at a dose at which AZD5305 monotherapy was ineffective. The combination therapy impaired metastatic dissemination and significantly prolonged the lifespan of mice bearing OC-PDXs in their abdomen. This combination benefit was evident even when CPT was used at suboptimal doses, and was superior to full-dose platinum treatment. These preclinical studies demonstrate that the PARP1-selective inhibitor AZD5305 retains and improves the therapeutic benefit of the first-generation PARPi, providing an opportunity to maximize benefits for this class of anticancer agents. Significance: Selective PARP1i AZD5305 can exceed the efficacy of first-generation PARPi, which target both PARP1 and PARP2, and potentiates the efficacy of CPT when given in combination. AZD5305 alone or in combination with platinum delayed visceral metastasis, ultimately extending the lifespan of OC-PDX-bearing mice. These preclinical models mimic the progression of the disease occurring in patients after debulking surgery, and are translationally relevant.

Development and Validation of Patient Education Tools for Deprescribing in Patients on Hemodialysis.

Background: Deprescribing is a patient-centered solution to reducing polypharmacy in patients on hemodialysis (HD). In a deprescribing pilot study, patients were hesitant to participate due to limited understanding of their own medications and their unfamiliarity with the concept of deprescribing. Therefore, patient education materials designed to address these knowledge gaps can overcome barriers to shared decision-making and reduce hesitancy regarding deprescribing. Objective: To develop and validate a medication-specific, patient education toolkit (bulletin and video) that will supplement an upcoming nationwide deprescribing program for patients on HD. Methods: Patient education tools were developed based on the content of previously validated deprescribing algorithms and literature searches for patients' preferences in education. A preliminary round of validation was completed by 5 clinicians to provide feedback on the accuracy and clarity of the education tools. Then, 3 validation rounds were completed by patients on HD across 3 sites in Vancouver, Winnipeg, and Toronto. Content and face validity were evaluated on a 4-point and 5-point Likert scale, respectively. The content validity index (CVI) score was calculated after each round, and revisions were made based on patient feedback. Results: A total of 105 patients participated in the validation. All 10 education tools achieved content and face validity after 3 rounds. The CVI score was 1.0 for most of the tools, with 0.95 being the lowest value. Face validity ranged from 72% to 100%, with majority scoring above 90%. Conclusion: Ten patient education tools on deprescribing were developed and validated by patients on HD. These validated, medication-specific education tools are the first of its kind for patients on HD and will be used in a nationwide implementation study alongside the validated deprescribing algorithms developed by our research group.

Contexte: La déprescription est une solution axée sur le patient pour réduire la polypharmacie chez les patients sous hémodialyse (HD). Dans une étude pilote sur la déprescription, les patients ont hésité à participer en raison de leur compréhension limitée de leurs propres médicaments et de leur manque de connaissance du concept de déprescription. Par conséquent, du matériel éducatif conçu pour combler ces lacunes dans les connaissances des patients pourrait surmonter les obstacles à la prise de décision partagée et réduire les hésitations à l'égard de la déprescription. Objectifs: Développer et valider une trousse d'information (bulletin et vidéo) pour les patients portant sur les médicaments. Cette trousse viendra compléter un futur programme national de déprescription pour les patients sous HD. Méthodologie: Des outils d'éducation pour les patients ont été développés à partir du contenu d'algorithmes de déprescription validés précédemment et de recherches documentaires sur les préférences des patients en matière d'éducation. Une ronde préliminaire de validation a été complétée par cinq cliniciens afin d'obtenir des commentaires sur l'exactitude et la clarté des outils d'éducation. Trois cycles de validation ont ensuite été réalisés par des patients sous HD dans trois sites: Vancouver, Winnipeg et Toronto. La validité du contenu et la validité apparente ont été évaluées à l'aide d'échelles de Likert à 4 et 5 points, respectivement. L'indice de validité du contenu (IVC) a été calculé après chaque ronde et des révisions ont été effectuées en fonction des commentaires des patients. Résultats: En tout, 105 patients ont participé à la validation. La validité du contenu et la validité apparente ont été atteintes pour les dix outils d'éducation après trois rondes auprès des patients. L'IVC s'établissait à 1,0 pour la plupart des outils évalués; 0,95 était la valeur d'indice la plus faible. La validité apparente variait entre 72% et 100%, la majorité des outils ayant obtenu un score supérieur à 90%. Conclusion: Dix outils d'éducation pour les patients portant sur la déprescription ont été développés et validés par des patients sous HD. Ces outils d'éducation validés portant spécifiquement sur les médicaments sont les premiers du genre conçus pour les patients sous HD. Ils seront utilisés dans le cadre d'une étude nationale de mise en œuvre, parallèlement aux algorithmes validés de déprescription qui ont été développés par notre groupe de recherche.

Multi-center, pragmatic, cluster-randomized, controlled trial of standardized peritoneal dialysis (PD) training versus usual care on PD-related infections (the TEACH-PD trial): trial protocol.

BACKGROUND: Peritoneal dialysis (PD)-related infections, such as peritonitis, exit site, and tunnel infections, substantially impair the sustainability of PD. Accordingly, PD-related infection is the top-priority research outcome for patients and caregivers. While PD nurse trainers teach patients to perform their own PD, PD training curricula are not standardized or informed by an evidentiary base and may offer a potential approach to prevent PD infections. The Targeted Education ApproaCH to improve Peritoneal Dialysis outcomes (TEACH-PD) trial evaluates whether a standardized training curriculum for PD nurse trainers and incident PD patients based on the International Society for Peritoneal Dialysis (ISPD) guidelines reduces PD-related infections compared to usual training practices. METHODS: The TEACH-PD trial is a registry-based, pragmatic, open-label, multi-center, binational, cluster-randomized controlled trial. TEACH-PD will recruit adults aged 18 years or older who have not previously undergone PD training at 42 PD treatment units (clusters) in Australia and New Zealand (ANZ) between July 2019 and June 2023. Clusters will be randomized 1:1 to standardized TEACH-PD training curriculum or usual training practice. The primary trial outcome is the time to the first occurrence of any PD-related infection (exit site infection, tunnel infection, or peritonitis). The secondary trial outcomes are the individual components of the primary outcome, infection-associated catheter removal, transfer to hemodialysis (greater than 30 days and 180 days), quality of life, hospitalization, all-cause death, a composite of transfer to hemodialysis or all-cause death, and cost-effectiveness. Participants are followed for a minimum of 12 months with a targeted average follow-up period of 2 years. Participant and outcome data are collected from the ANZ Dialysis and Transplant Registry (ANZDATA) and the New Zealand Peritoneal Dialysis (NZPD) Registry. This protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. DISCUSSION: TEACH-PD is a registry-based, cluster-randomized pragmatic trial that aims to provide high-certainty evidence about whether an ISPD guideline-informed standardized PD training curriculum for PD nurse trainers and adult patients prevents PD-related infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT03816111. Registered on 24 January 2019.

The role of C-H and C-C stretching modes in the intrinsic non-radiative decay of triplet states in a Pt-containing conjugated phenylene ethynylene.

The intrinsic non-radiative decay (internal conversion) from the triplet excited state in phosphorescent dyes can be described by a multi-phonon emission process. Since non-radiative decay of triplet excitons can be a significant process in organic light-emitting diodes, a detailed understanding of this decay mechanism is important if the overall device efficiency is to be controlled. We compare a deuterated Pt(II)-containing phenylene ethynylene with its non-deuterated counterpart in order to investigate which phonon modes control to the non-radiative decay path. We observe that deuteration does not decrease the non-radiative decay rate. A Franck-Condon analysis of the phosphorescence spectra shows that the electronic excitation is coupled strongly to the breathing mode of the phenyl ring and the C≡C carbon stretching modes, while high-energy C-H or C-D stretching modes play an insignificant role. We, therefore, associate the internal conversion process with the carbon-carbon stretching vibrations.