Development and Validation of a Treatment Algorithm for Osteoarthritis Pain Management in Patients With End-Stage Kidney Disease Undergoing Hemodialysis.

Background: Although osteoarthritis is common in the hemodialysis population and leads to poor health outcomes, pain management is challenged by the absence of clinical guidance. A treatment algorithm was developed and validated to aid hemodialysis clinicians in managing osteoarthritis pain. Objective: The objective was to develop and validate a treatment algorithm for managing osteoarthritis pain in patients undergoing hemodialysis. Design: A validation study was conducted based on Lynn's method for content validation. Setting: To develop and validate a treatment algorithm, interviews were conducted virtually by the primary researcher with clinicians from various institutions across the Greater Toronto and Hamilton Area in Ontario. Patients: The treatment algorithm was developed and validated for the management of osteoarthritis pain in patients on hemodialysis. Patients were not involved in the development or validation of the tool. Measurements: The algorithm was measured for content and face validity. Content validity was measured by calculating the content validity index of each component (I-CVI) of the algorithm and the overall scale validity index (S-CVI). Face validity was assessed by calculating the percentage of positive responses to the face validity statements. Methods: A draft algorithm was developed based on literature searches and expert opinion and validated by interviewing nephrology and pain management clinicians. Through consecutive rounds of 1:1 interviews, content and face validity were assessed by asking participants to rate the relevance of each component of the algorithm and indicate their level of agreeability with a series of statements. Following each round, the I-CVI of the algorithm as well as the S-CVI was calculated and the percentage of positive responses to the statements was determined. The research team revised the algorithm in response to the findings. The final algorithm provides a stepwise approach to the non-pharmacologic and pharmacologic management of pain, including topical, oral, and opioid use. Results: A total of 18 clinicians from 7 institutions across the Greater Toronto and Hamilton Area were interviewed (10 pharmacists, 5 nurse practitioners, and 3 physicians). The average S-CVI of the algorithm across all 3 rounds was 0.93. At least 78% of participants provided positive responses to the face validity statements. Limitations: An algorithm was developed based on input from clinicians working in the province of Ontario, limiting the generalizability of the algorithm across provinces. In addition, the algorithm did not include the perspectives of primary care providers or patients/caregivers. Conclusions: An algorithm for the management of osteoarthritis pain in the hemodialysis population was developed and validated through expert review to standardize practices and encourage clinicians to use evidence-based treatments and address the psychosocial symptoms of pain. As the algorithm possesses a high degree of content and face validity, it may improve osteoarthritis pain management among patients undergoing hemodialysis. Future research will assess the implementation of the algorithm across hemodialysis settings.

Contexte: Bien que l'arthrose soit fréquente et qu'elle entraîne de mauvais résultats de santé chez les patients en hémodialyse, la gestion de la douleur liée à l'arthrose est limitée par l'absence de directives cliniques. Un algorithme de traitement a été développé et validé afin d'aider les cliniciens en hémodialyse à gérer la douleur liée à l'arthrose chez leurs patients. Objectifs: Développer et valider un algorithme de traitement pour la prise en charge de la douleur liée à l'arthrose chez les patients en hémodialyse. Conception: Étude de validation menée en utilisant la méthode de Lynn pour la validation du contenu. Cadre: Pour élaborer et valider l'algorithme, le chercheur principal a mené des entrevues en mode virtuel avec des cliniciens de divers établissements de Hamilton et de la région du Grand Toronto (Ontario). Sujets: L'algorithme de traitement a été développé et validé pour la prise en charge de la douleur liée à l'arthrose chez les patients en hémodialyse. Ces derniers n'ont pas participé au développement ou à la validation de l'outil. Mesures: La validité du contenu et la validité apparente de l'algorithme ont été évaluées. La validité du contenu a été mesurée en calculant l'indice de validité de chaque composante (I-CVI) de l'algorithme, ainsi que l'indice de validité à l'échelle globale (S-CVI). La validité apparente a été évaluée en calculant le pourcentage de réponses positives aux énoncés de validité apparente. Méthodologie: Une ébauche de l'algorithme a été développée à partir de recherches de littérature scientifique et d'avis d'experts, puis validée lors d'entretiens avec des cliniciens en néphrologie et en gestion de la douleur. Afin d'évaluer la validité du contenu et la validité apparente de l'algorithme, les cliniciens ont participé à des séries consécutives d'entretiens individuels où ils devaient évaluer la pertinence de chaque composante de l'algorithme et indiquer leur niveau d'accord avec une série d'énoncés. L'indice de validité du contenu de chaque composante (I-CVI) de l'algorithme, l'indice de validité de l'échelle globale (S-CVI) et le pourcentage de réponses positives aux énoncés ont été calculés après chaque tour. L'algorithme a ensuite été révisé par l'équipe de recherche en réponse aux résultats. L'algorithme final fournit une approche par étapes pour la gestion non pharmacologique et pharmacologique (traitement local, oral, opioïdes) de la douleur. Résultats: En tout, 18 cliniciens provenant de 7 établissements de Hamilton et de la région du Grand Toronto ont été interviewés (10 pharmaciens, 5 infirmières praticiennes et 3 médecins). L'indice S-CVI moyen de l'algorithme pour les trois séries d'entrevues était de 0,93. Au moins 78 % des participants ont fourni des réponses positives aux énoncés de validité apparente. Limites: L'algorithme a été élaboré à partir des données fournies par des cliniciens travaillant dans la province de l'Ontario, ce qui limite sa généralisabilité dans les autres provinces. Aussi, l'algorithme n'inclut pas le point de vue des prestataires de soins primaires ou des patients/soignants. Conclusion: Un algorithme de prise en charge de la douleur liée à l'arthrose chez les patients en hémodialyse a été développé et validé par des experts afin de normaliser les pratiques et d'encourager les cliniciens à utiliser des traitements fondés sur les preuves et à traiter les symptômes psychosociaux de la douleur. L'algorithme ayant montré un degré élevé de validité du contenu et de validité apparente, il a ainsi le potentiel d'améliorer la gestion de la douleur liée à l'arthrose chez les patients en hémodialyse. Les recherches à venir évalueront l'application de l'algorithme dans divers contextes d'hémodialyse.

Policies in Canada fail to address disparities in access to person-centred osteoarthritis care: a content analysis.

BACKGROUND: Women are disproportionately impacted by osteoarthritis (OA) but less likely than men to access OA care, particularly racialized women. One way to reduce inequities is through policies that can influence healthcare services. We examined how OA-relevant policies in Canada address equitable, person-centred OA care for women. METHODS: We used content analysis to extract data from English-language OA-relevant documents referred to as policies or other synonymous terms published in 2000 or later identified by searching governmental and other web sites. We used summary statistics to describe policy characteristics, person-centred care using McCormack's six-domain framework, and mention of OA prevalence, barriers and strategies to improve equitable access to OA care among women. RESULTS: We included 14 policies developed from 2004 to 2021. None comprehensively addressed all person-centred care domains, and few addressed individual domains: enable self-management (50%), share decisions (43%), exchange information (29%), respond to emotions (14%), foster a healing relationship (0%) and manage uncertainty (0%). Even when mentioned, content offered little guidance for how to achieve person-centred OA care. Few policies acknowledged greater prevalence of OA among women (36%), older (29%) or Indigenous persons (29%) and those of lower socioeconomic status (14%); or barriers to OA care among those of lower socioeconomic status (50%), in rural areas (43%), of older age (37%) or ethno-cultural groups (21%), or women (21%). Four (29%) policies recommended strategies for improving access to OA care at the patient (self-management education material in different languages and tailored to cultural norms), clinician (healthcare professional education) and system level (evaluate OA service equity, engage lay health leaders in delivering self-management programs, and offer self-management programs in a variety of formats). Five (36%) policies recommended research on how to improve OA care for equity-seeking groups. CONCLUSIONS: Canadian OA-relevant policies lack guidance to overcome disparities in access to person-centred OA care for equity-seeking groups including women. This study identified several ways to strengthen policies. Ongoing research must identify the needs and preferences of equity-seeking persons with OA, and evaluate the impact of various models of service delivery, knowledge needed to influence OA-relevant policy.

Medication Deprescribing in Patients Receiving Hemodialysis: A Prospective Controlled Quality Improvement Study.

Rationale & Objective: Patients treated with dialysis are commonly prescribed multiple medications (polypharmacy), including some potentially inappropriate medications (PIMs). PIMs are associated with an increased risk of medication harm (eg, falls, fractures, hospitalization). Deprescribing is a solution that proposes to stop, reduce, or switch medications to a safer alternative. Although deprescribing pairs well with routine medication reviews, it can be complex and time-consuming. Whether clinical decision support improves the process and increases deprescribing for patients treated with dialysis is unknown. This study aimed to test the efficacy of the clinical decision support software MedSafer at increasing deprescribing for patients treated with dialysis. Study Design: Prospective controlled quality improvement study with a contemporaneous control. Setting & Participants: Patients prescribed ≥5 medications in 2 outpatient dialysis units in Montréal, Canada. Exposures: Patient health data from the electronic medical record were input into the MedSafer web-based portal to generate reports listing candidate PIMs for deprescribing. At the time of a planned biannual medication review (usual care), treating nephrologists in the intervention unit additionally received deprescribing reports, and patients received EMPOWER brochures containing safety information on PIMs they were prescribed. In the control unit, patients received usual care alone. Analytical Approach: The proportion of patients with ≥1 PIMs deprescribed was compared between the intervention and control units following a planned medication review to determine the effect of using MedSafer. The absolute risk difference with 95% CI and number needed to treat were calculated. Outcomes: The primary outcome was the proportion of patients with one or more PIMs deprescribed. Secondary outcomes include the reduction in the mean number of prescribed drugs and PIMs from baseline. Results: In total, 195 patients were included (127, control unit; 68, intervention unit); the mean age was 64.8 ± 15.9 (SD), and 36.9% were women. The proportion of patients with ≥1 PIMs deprescribed in the control unit was 3.1% (4/127) vs 39.7% (27/68) in the intervention unit (absolute risk difference, 36.6%; 95% CI, 24.5%-48.6%; P < 0.0001; number needed to treat = 3). Limitations: This was a single-center nonrandomized study with a type 1 error risk. Deprescribing durability was not assessed, and the study was not powered to reduce adverse drug events. Conclusions: Deprescribing clinical decision support and patient EMPOWER brochures provided during medication reviews could be an effective and scalable intervention to address PIMs in the dialysis population. A confirmatory randomized controlled trial is needed.

Patients treated with dialysis are commonly prescribed multiple medications, some of which are potentially inappropriate medications (PIMs). PIMs can increase a patient's pill burden and are associated with an increased risk of harm (some examples include falls, fractures, and hospitalization). Deprescribing is a proposed solution that aims to highlight medications that can be stopped, reduced, or switched to a safer option, under supervision of a health care provider. We aimed to determine if a quality improvement intervention in the dialysis unit could increase deprescribing compared to usual care. The study took place in 2 outpatient hemodialysis units where usual care involves nurses and nephrologists performing medication reviews twice a year. The intervention was a deprescribing report that was generated with the help of a software tool called MedSafer, along with brochures for patients with information on PIMs they were taking. In the intervention unit, we increased the number of patients who had a medication safely deprescribed by 36.6% more than on the control unit. Although the study was small, a future larger study in dialysis patients might show that a computer software such as MedSafer can prevent harmful complications from taking too many medications.

Drug stewardship in chronic kidney disease to achieve effective and safe medication use.

People living with chronic kidney disease (CKD) often experience multimorbidity and require polypharmacy. Kidney dysfunction can also alter the pharmacokinetics and pharmacodynamics of medications, which can modify their risks and benefits; the extent of these changes is not well understood for all situations or medications. The principle of drug stewardship is aimed at maximizing medication safety and effectiveness in a population of patients through a variety of processes including medication reconciliation, medication selection, dose adjustment, monitoring for effectiveness and safety, and discontinuation (deprescribing) when no longer necessary. This Review is aimed at serving as a resource for achieving optimal drug stewardship for patients with CKD. We describe special considerations for medication use during pregnancy and lactation, during acute illness and in patients with cancer, as well as guidance for the responsible use of over-the-counter drugs, herbal remedies, supplements and sick-day rules. We also highlight inequities in medication access worldwide and suggest policies to improve access to quality and essential medications for all persons with CKD. Further strategies to promote drug stewardship include patient education and engagement, the use of digital health tools, shared decision-making and collaboration within interdisciplinary teams. Throughout, we position the person with CKD at the centre of all drug stewardship efforts.

Priority strategies to reduce socio-gendered inequities in access to person-centred osteoarthritis care: Delphi survey.

OBJECTIVES: Osteoarthritis (OA) prevalence, severity and related comorbid conditions are greater among women compared with men, but women, particularly racialised women, are less likely than men to access OA care. We aimed to prioritise strategies needed to reduce inequities in OA management. DESIGN: Delphi survey of 28 strategies derived from primary research retained if at least 80% of respondents rated 6 or 7 on a 7-point Likert scale. SETTING: Online. PARTICIPANTS: 35 women of diverse ethno-cultural groups and 29 healthcare professionals of various specialties from across Canada. RESULTS: Of the 28 initial and 3 newly suggested strategies, 27 achieved consensus to retain: 20 in round 1 and 7 in round 2. Respondents retained 7 patient-level, 7 clinician-level and 13 system-level strategies. Women and professionals agreed on all but one patient-level strategy (eg, consider patients' cultural needs and economic circumstances) and all clinician-level strategies (eg, inquire about OA management needs and preferences). Some discrepancies emerged for system-level strategies that were more highly rated by women (eg, implement OA-specific clinics). Comments revealed general support among professionals for system-level strategies provided that additional funding or expanded scope of practice was targeted to only formally trained professionals and did not reduce funding for professionals who already managed OA. CONCLUSIONS: We identified multilevel strategies that could be implemented by healthcare professionals, organisations or systems to mitigate inequities and improve OA care for diverse women.

Patients' experiences of medication management while navigating ongoing care between outpatient services: A qualitative case study of patients on hemodialysis.

Background: Patients on hemodialysis have complex medical diagnoses and medication regimens, requiring access to numerous health services and consultation with various healthcare providers. While interprofessional collaboration can optimize care among hemodialysis patients, these patients commonly experience medication-related problems and frequent hospitalizations resulting from miscommunications and mismanagement of medications. Objectives: This study aims to capture the lived experiences of patients on hemodialysis to reveal their medication management needs as they navigate ongoing care between various outpatient services. Methods: A qualitative methodology was used to explore the perspectives of hemodialysis patients. One-on-one, in-person, semi-structured interviews were conducted at an outpatient hemodialysis clinic located inside an urban teaching hospital. English-speaking adults 18 years and older who have been followed at the clinic for at least three months were selected through random, convenience sampling. Interviews were recorded and transcribed verbatim. Patients were recruited and data were collected iteratively and continued until data saturation was reached. Data was analyzed through the lens of the Picker Principles of Patient Centered Care using a general inductive approach. Results: A total of nine interviews were conducted. Two major themes, medication management and care navigation, were identified. Though patients had a wealth of knowledge about their medications, and they were motivated to self-manage their medications to enhance their well-being, they experienced barriers with medication management. Patients further expressed challenges with navigating care and spoke of the importance of having good rapport with healthcare providers who are attentive to their needs. Conclusions: The results revealed a need for improved support for self-care and interprofessional collaboration to possibly reduce the burden of medications and care fragmentation experienced by patients and improve continuity of care for patients.

Multi-level strategies to improve equitable timely person-centred osteoarthritis care for diverse women: qualitative interviews with women and healthcare professionals.

BACKGROUND: Women are more likely to develop osteoarthritis (OA), and have greater OA pain and disability compared with men, but are less likely to receive guideline-recommended management, particularly racialized women. OA care of diverse women, and strategies to improve the quality of their OA care is understudied. The purpose of this study was to explore strategies to overcome barriers of access to OA care for diverse women. METHODS: We conducted qualitative interviews with key informants and used content analysis to identify themes regarding what constitutes person-centred OA care, barriers of OA care, and strategies to support equitable timely access to person-centred OA care. RESULTS: We interviewed 27 women who varied by ethno-cultural group (e.g. African or Caribbean Black, Chinese, Filipino, Indian, Pakistani, Caucasian), age, region of Canada, level of education, location of OA and years with OA; and 31 healthcare professionals who varied by profession (e.g. family physician, nurse practitioner, community pharmacist, physio- and occupational therapists, chiropractors, healthcare executives, policy-makers), career stage, region of Canada and type of organization. Participants within and across groups largely agreed on approaches for person-centred OA care across six domains: foster a healing relationship, exchange information, address emotions, manage uncertainty, share decisions and enable self-management. Participants identified 22 barriers of access and 18 strategies to overcome barriers at the patient- (e.g. educational sessions and materials that accommodate cultural norms offered in different languages and formats for persons affected by OA), healthcare professional- (e.g. medical and continuing education on OA and on providing OA care tailored to intersectional factors) and system- (e.g. public health campaigns to raise awareness of OA, and how to prevent and manage it; self-referral to and public funding for therapy, greater number and ethno-cultural diversity of healthcare professionals, healthcare policies that address the needs of diverse women, dedicated inter-professional OA clinics, and a national strategy to coordinate OA care) levels. CONCLUSIONS: This research contributes to a gap in knowledge of how to optimize OA care for disadvantaged groups including diverse women. Ongoing efforts are needed to examine how best to implement these strategies, which will require multi-sector collaboration and must engage diverse women.

Identifying strategies that support equitable person-centred osteoarthritis care for diverse women: content analysis of guidelines.

INTRODUCTION: Women are disproportionately impacted by osteoarthritis (OA) but less likely than men to access early diagnosis and management, or experience OA care tailored through person-centred approaches to their needs and preferences, particularly racialized women. One way to support clinicians in optimizing OA care is through clinical guidelines. We aimed to examine the content of OA guidelines for guidance on providing equitable, person-centred care to disadvantaged groups including women. METHODS: We searched indexed databases and websites for English-language OA-relevant guidelines published in 2000 or later by non-profit organizations. We used manifest content analysis to extract data, and summary statistics and text to describe guideline characteristics, person-centred care (PCC) using a six-domain PCC framework, OA prevalence or barriers by intersectional factors, and strategies to improve equitable access to OA care. RESULTS: We included 36 OA guidelines published from 2003 to 2021 in 8 regions or countries. Few (39%) development panels included patients. While most (81%) guidelines included at least one PCC domain, guidance was often brief or vague, few addressed exchange information, respond to emotions and manage uncertainty, and none referred to fostering a healing relationship. Few (39%) guidelines acknowledged or described greater prevalence of OA among particular groups; only 3 (8%) noted that socioeconomic status was a barrier to OA care, and only 2 (6%) offered guidance to clinicians on how to improve equitable access to OA care: assess acceptability, availability, accessibility, and affordability of self-management interventions; and employ risk assessment tools to identify patients without means to cope well at home after surgery. CONCLUSIONS: This study revealed that OA guidelines do not support clinicians in caring for diverse persons with OA who face disadvantages due to intersectional factors that influence access to and quality of care. Developers could strengthen OA guidelines by incorporating guidance for PCC and for equity that could be drawn from existing frameworks and tools, and by including diverse persons with OA on guideline development panels. Future research is needed to identify multi-level (patient, clinician, system) strategies that could be implemented via guidelines or in other ways to improve equitable, person-centred OA care. PATIENT OR PUBLIC CONTRIBUTION: This study was informed by a team of researchers, collaborators, and thirteen diverse women with lived experience, who contributed to planning, and data collection, analysis and interpretation by reviewing study materials and providing verbal (during meetings) and written (via email) feedback.

Strategies to Improve Equitable Access to Early Osteoarthritis Diagnosis and Management: An updated Review.

Though osteoarthritis (OA) affects millions of people worldwide, many fail to access recommended early, person-centered OA care, particularly women who are disproportionately impacted by OA. A prior review identified few strategies to improve equitable access to early diagnosis and management for multiple disadvantaged groups. We aimed to update that review with literature published in 2010 or later on strategies to improve OA care for disadvantaged groups including women. We identified only 11 eligible studies, of which only 2 (18%) focused on women only. Other disadvantaged groups targeted in the largely US-based studies included patients who are Black, Spanish-speaking, rural, and adults aged 60 years and older. All studies evaluated interventions targeted to patients; 4 (36%) assessed video decision aids, and 7 (63.6%) assessed in-person, video, or telephone self-management education. Interventions were often multifaceted (n = 9, 82%), and most studies (n = 8, 73%) achieved positive outcomes in at least some outcomes measured. No studies evaluated clinician- or system-level strategies. Few studies (n = 5, 45%) described how they tailored strategies to disadvantaged groups or how they addressed person-centered care concepts apart from enabling self-management. Future research is needed to develop, implement, evaluate, and scale-up multilevel strategies to enhance equitable, person-centered OA care for disadvantaged groups including women.

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.

Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: A systematic review.

INTRODUCTION: Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is limited in solid organ transplant recipients. The aim of this systematic review was to evaluate the current efficacy and safety data of SGLT2 inhibitors in adult kidney, heart, lung, and liver transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus. METHOD: We searched MEDLINE, MEDLINE Epub, CENTRAL, CDSR, EMBASE, CINAHL, and sources of unpublished literature. All primary interventional and observational studies on SGLT2 inhibitors in transplant recipients were included. Clinical outcomes included mortality, cardiovascular and kidney events, and adverse events such as graft rejection. Surrogate markers including hemoglobin A1c (HbA1c) and weight reduction were also evaluated. RESULTS: Of the 17 studies that were included in this systematic review, there were 15 studies on kidney transplant recipients (n = 2417 patients) and two studies on heart transplant recipients (n = 122 patients). There was only one randomized controlled trial which evaluated 49 kidney transplant patients over 24 weeks. Overall, studies were heterogeneous in study design, sample size, duration of diabetes, time to SGLT2 inhibitor initiation post-transplantation (ranging from 0.88 to 11 years post kidney transplant; five to 5.7 years post heart transplant) and follow-up (ranging from 0.4 to 5.25 years in kidney transplant patients; 0.75 to one year in heart transplant patients). Only one retrospective study evaluated mortality as a part of a composite outcome in kidney transplant patients; however, study limitations restrict generalizability of results. Overall, studies could not confirm clinical cardiovascular and kidney benefits in the transplant population. Findings suggested that SGLT2 inhibitors may improve glycemic control; however, they are associated with urinary tract infection. Diabetic ketoacidosis and acute kidney injury also occurred in these studies, with precipitating factors such as infection and acute heart failure exacerbation. CONCLUSIONS: While SGLT2 inhibitors are promising agents with expanding indications in the non-transplant population, these agents may not be suitable for all solid organ transplant recipients, and close monitoring (e.g. for urinary tract infections) and patient education (e.g. sick day management) are essential if these agents are initiated. Evidence is based on short-term findings and suggests an association with hemoglobin A1c reduction and increased adverse events. Further long-term randomized controlled trials are needed to evaluate the effect of SGLT2 inhibitors on clinically important outcomes, including mortality reduction, in solid organ transplant recipients.

Pharmacy Practice Standards for Outpatient Nephrology Settings.

Patients with kidney disease represent a medically complex group of patients with high medication burdens that could benefit from clinical pharmacy services as part of the interdisciplinary care team to optimize medication use. The "Advancing American Kidney Health" executive order includes new value-based reimbursement models to be tested by the Center for Medicare and Medicaid Innovation beginning January 2021 and January 2022. Advancing American Kidney Health executive order poses opportunities for the inclusion of comprehensive medication management. Following an iterative process integrating input from a diverse expert panel, published standards, clinical practice guidelines, peer review, and stakeholder feedback, our group developed practice standards for pharmacists caring for patients with kidney disease in health care settings. The standards focus on activities that are part of direct patient care and also include activities related to public health and advocacy, population health, leadership and management, and teaching, education and dissemination of knowledge. These standards are intended to be used by a variety of professionals, from pharmacists starting new practices to practice managers looking to add a pharmacist to the clinical team, to create standardization in services provided.

Patterns of Antimicrobial Use in an Outpatient Hemodialysis Unit.

BACKGROUND: Patients receiving hemodialysis (HD) are at high risk of infections, including those caused by multidrug-resistant organisms. Given that antimicrobial exposure is a major risk factor for the emergence of these resistant organisms, minimizing inappropriate use is imperative. To optimize use, it is important to understand patterns of antimicrobial prescribing in this setting. OBJECTIVES: To measure antimicrobial use and to describe prescribing patterns among patients receiving outpatient HD. METHODS: A retrospective observational case series study was performed in an outpatient HD unit from February to April 2017. Adults for whom at least 1 antimicrobial was prescribed were included. The primary outcome was total antimicrobial days of therapy (DOT) per 1000 patient-days. Secondary outcomes were the characteristics of the antimicrobial prescriptions, in terms of antimicrobial class, indication, purpose, route, and prescriber group. RESULTS: Antimicrobials were prescribed for 53 (16%) of the 330 patients treated in the HD unit during the study period; the total number of prescriptions was 75. Antimicrobial use was 27.5 DOTs/1000 patient-days. Fluoroquinolones were the most frequently prescribed type of antimicrobial (n = 17, 23%), whereas the second most frequently prescribed were first-generation cephalosporins (n = 16, 21%). The most common indication was skin or soft-tissue infection (n = 14, 19%), followed by bloodstream infection (n = 13, 17%). Of the 75 antimicrobials, 48 (64%) were prescribed for empiric therapy, 19 (25%) for targeted therapy, and 8 (11%) for prophylaxis. Two-thirds of the antimicrobials prescribed (n = 50, 67%) were oral medications, and most (n = 72, 96%) were ordered by hospital prescribers. CONCLUSIONS: Antimicrobial use was common in this study setting, with 1 in 6 HD patients receiving this type of medication. The findings of this study create opportunities to standardize antimicrobial prescribing at the local level for common infections that occur in patients receiving outpatient HD.

CONTEXTE: Les patients sous hémodialyse (HD) présentent un risque élevé d'infections, y compris celles provoquées par des organismes multirésistants. Étant donné que l'exposition aux antimicrobiens est un facteur de risque majeur pour l'émergence de ces organismes résistants, il est impératif de minimiser l'utilisation inappropriée. Pour optimiser l'utilisation, il importe de comprendre les tendances de prescription d'antimicrobiens dans ce contexte. OBJECTIFS: Mesurer l'utilisation des antimicrobiens et décrire les schémas de prescription chez les patients recevant une HD ambulatoire. MÉTHODES: Une étude rétrospective de séries de cas a été réalisée dans une unité d'hémodialyse pour patients externes de février à avril 2017. Les adultes à qui au moins 1 antimicrobien avait été prescrit ont été inclus dans l'étude. Le paramètre d'évaluation principal était le nombre total de jours de traitement antimicrobien (JTA) pour 1000 jours-patients. Les paramètres secondaires étaient les caractéristiques des prescriptions d'antimicrobiens, en termes de classe d'antimicrobiens, d'indication, d'objectif, de voie d'administration et de groupe de prescripteurs. RÉSULTATS: Des antimicrobiens ont été prescrits à 53 (16 %) des 330 patients traités dans l'unité d'HD au cours de la période d'étude, pour un nombre total de prescriptions de 75. L'utilisation d'antimicrobiens était de 27,5 JTA/1000 jours-patients. Les fluoroquinolones étaient le type d'antimicrobien le plus fréquemment prescrit (n = 17, 23 %) et les céphalosporines de première génération (n = 16, 21 %) étaient le deuxième type. Une infection de la peau ou des tissus mous (n = 14, 19 %) était l'indication la plus courante, suivie d'une infection du sang (n = 13, 17 %). Sur les 75 antimicrobiens, 48 (64 %) ont été prescrits pour un traitement empirique, 19 (25 %) pour un traitement ciblé et 8 (11 %) pour une prophylaxie. Les deux tiers des antimicrobiens prescrits (n = 50, 67 %) étaient des médicaments oraux, et la plupart (n = 72, 96 %) ont été prescrits par des prescripteurs hospitaliers. CONCLUSIONS: L'utilisation d'antimicrobiens était courante dans le cadre de cette étude, où 1 patient sous HD sur 6 recevait ce type de médicament. Les résultats de cette étude créent des opportunités de normaliser la prescription d'antimicrobiens au niveau local pour les infections courantes qui surviennent chez les patients recevant une HD ambulatoire.

Development and validation of a constipation treatment toolkit for patients on hemodialysis.

INTRODUCTION: The cause of constipation is multifactorial and common problem for patients on hemodialysis. A lack of strong evidence on suitable treatment strategies means there is an unorganized approach to selecting therapies, which can exacerbate constipation or worsen symptoms. Clinicians and patients would benefit from a content and face validated treatment algorithm for treating constipation. In this study, our objective was to develop and content and face validate a constipation treatment toolkit for patients on hemodialysis, consisting of treatment algorithm, and patient information tools (pamphlet and video). METHODS: Literature searches were performed to develop an initial toolkit using Lynn's method for developing content-valid clinical tools. Content and face validity were evaluated as per Lynn's method for determining content validity; the algorithm was evaluated by Canadian nephrology clinicians, while patient information tools were evaluated by clinicians and patients. Components were rated on a Likert scale for content relevance and on a 5-point scale for face validity. After each round, the content validity index (CVI) score was calculated and revisions were made based on feedback. FINDINGS: A total of 23 clinicians and 15 patients were interviewed across three validation rounds. After three rounds, the treatment algorithm achieved content (overall CVI = 0.93) and face (91% agreement) validity. Our patient information tools achieved content and face validity (pamphlet overall CVI = 0.99, 85.5% agreement; video overall CVI = 0.99, 90.5% agreement). DISCUSSION: A treatment algorithm and patient information toolkit for the treatment of constipation in patients on hemodialysis were content and face validated via expert review. Further research will be needed to ascertain the effectiveness and implementation of this toolkit.

Multidisciplinary Perspectives of Current Approaches and Clinical Gaps in the Management of Hyperphosphatemia.

Population-based studies have shown that most patients with advanced chronic kidney disease (CKD) do not have optimal phosphate levels. Meta-analyses suggest that there is a morbidity and mortality benefit associated with the lowering of serum phosphate levels. However, to date there is no conclusive evidence from randomized controlled trials (RCTs) that lowering serum phosphate levels reduces the risk of morbidity and mortality. However, hyperphosphatemia may pose a risk to patients and treatment should be considered. We therefore sought to conduct a multidisciplinary review to help guide clinical decision-making pending results of ongoing RCTs. Restricting dietary phosphate intake is frequently the first step in the management of hyperphosphatemia. Important considerations when proposing dietary restriction include the patient's socioeconomic status, lifestyle, dietary preferences, comorbidities, and nutritional status. While dietary phosphate restriction may be a valid strategy in certain patients, serum phosphate reductions achieved solely by limiting dietary intake are modest and should be considered in conjunction with other interventions. Conventional dialysis is also typically insufficient; however phosphate removal may be augmented by increased frequency or duration of dialysis, or through enhanced methods such as hemodiafiltration. Phosphate binders have been shown to reduce absorption of dietary phosphate and lower serum phosphate levels. There are several phosphate binders available, and while they all lower phosphate levels to variable degrees, they differ with respect to their pill burden, potential to induce or exacerbate vascular calcification or ectopic calcification, tissue accumulation, safety, and tolerability. The widespread treatment of hyperphosphatemia requires convincing data from RCTs to ascertain whether lowering serum phosphate levels improves patient-important outcomes, as well as the optimal method and degree of phosphate control. In the interim, the decision and approach used to treat hyperphosphatemia should be based on the best available data, as well as patient needs and clinical judgment.

A retrospective study of antithrombotic therapy use in an outpatient haemodialysis unit.

WHAT IS KNOWN AND OBJECTIVE: Patients on haemodialysis (HD) are at increased risk of both bleeding and thrombotic events, due to comorbidities and nature of dialysis treatment. However, there is a lack of research on evidence-based treatment strategies and prescribing patterns for antithrombotic therapies (ATT) in this population. To characterize ATT use and its main indications in an outpatient HD unit. METHODS: A single-centre retrospective chart review was conducted in a Toronto outpatient HD unit (n = 329). Medical histories, number of ATTs and corresponding indications were collected from adult patients prescribed at least one ATT from 1 October 2019 to 31 December 2019, inclusive. RESULTS AND DISCUSSION: Of 329 patients in the unit, a total of 135 (41%) patients were on at least one ATT. Of these 135 patients, 80% were on monotherapy (55% antiplatelet, 25.1% anticoagulant), 12.6% were on dual antiplatelet therapy (DAPT), and 7.4% were on a antiplatelet and anticoagulant combination. Primary indications for ATT in our cohort were coronary artery disease (CAD; 55%), atrial fibrillation (18.5%) and venous thromboembolism (VTE; 17%). Described ATT use was in-line with current clinical guidelines. Monotherapy was primarily used in our HD cohort, whereas few patients were on dual therapy. Low-dose aspirin was the most common antiplatelet prescribed for secondary prevention of cardiovascular events. Warfarin monotherapy was primarily indicated for VTE, and DAPT aspirin/clopidogrel was the most commonly prescribed for CAD. WHAT IS NEW AND CONCLUSION: Our characterization of ATT use in this HD cohort demonstrates that ATT is often prescribed for a number of different CVD reasons. Overlapping and confounding indications for prescribing ATTs, lack of randomized controlled trials and unclear clinical guidelines mean that individualized risk-benefit assessments for ATT use are still needed to provide care for these high-risk patients. More research to address the safety and efficacy of ATTs is warranted to develop more robust evidence-based treatment guidelines for the HD population.

Effect of Therapeutic Drug Monitoring and Cytochrome P450 2C19 Genotyping on Clinical Outcomes of Voriconazole: A Systematic Review.

OBJECTIVES: To examine current knowledge on the clinical utility of therapeutic drug monitoring (TDM) in voriconazole therapy, the impact of CYP2C19 genotype on voriconazole plasma concentrations, and the role of CYP2C19 genotyping in voriconazole therapy. DATA SOURCES: Three literature searches were conducted for original reports on (1) TDM and voriconazole outcomes and (2) voriconazole and CYP2C19 polymorphisms. Searches were conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception to June 2020. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials, cohort studies, and case series with ≥10 patients were included. Only full-text references in English were eligible. DATA SYNTHESIS: A total of 63 studies were reviewed. TDM was recommended because of established concentration and efficacy/toxicity relationships. Voriconazole trough concentrations ≥1.0 mg/L were associated with treatment success; supratherapeutic concentrations were associated with increased neurotoxicity; and hepatotoxicity associations were more prevalent in Asian populations. CYP2C19 polymorphisms significantly affect voriconazole metabolism, but no relationship with efficacy/safety were found. Genotype-guided dosing with TDM was reported to increase chances of achieving therapeutic range. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Genotype-guided dosing with TDM is a potential solution to optimizing voriconazole efficacy while avoiding treatment failures and common toxicities. CONCLUSIONS: Voriconazole plasma concentrations and TDM are treatment outcome predictors, but research is needed to form a consensus target therapeutic range and dosage adjustment guidelines based on plasma concentrations. CYP2C19 polymorphisms are a predictor of voriconazole concentrations and metabolism, but clinical implications are not established. Large-scale, high-methodological-quality trials are required to investigate the role for prospective genotyping and establish CYP2C19-guided voriconazole dosing recommendations.

Direct Oral Anticoagulant Use in Chronic Kidney Disease and Dialysis Patients With Venous Thromboembolism: A Systematic Review of Thrombosis and Bleeding Outcomes.

OBJECTIVE: To evaluate how treatment with DOACs for VTE affects thrombosis and bleeding outcomes compared to warfarin in CKD and dialysis patients. DATA SOURCES: A literature search was conducted for studies evaluating VTE and bleeding outcomes with DOAC use in CKD and dialysis patients. Searches conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials, from inception to September 22, 2020. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials, cohort studies, and case series with ≥10 patients included. DATA SYNTHESIS: From 7286 studies, nine studies met inclusion criteria. There was no significant difference between DOACs (dabigatran, rivaroxaban, apixaban) and warfarin for reducing recurrent VTE and bleeding events in moderate CKD patients. The risk of overall major bleeding increased when the degree of kidney impairment increased. There was no significant difference between apixaban and warfarin for VTE outcomes in dialysis patients. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: There continues to be a controversial debate whether it may be more beneficial to use DOACs versus warfarin in CKD/dialysis patients with venous thromboembolism (VTE). The risk vs benefit of using DOACs in the CKD/ESKD population should continue to be evaluated for each individual patient. CONCLUSION: Apixaban may be used cautiously as an alternative in acute VTE treatment in severe CKD patients. Insufficient evidence is available to suggest the use of dabigatran and rivaroxaban in this patient population. The benefit of using DOACs in this population for VTE treatment should be weighed against the potential bleeding risk in patients with CKD.