Prescribing patterns and medications costs in patients on maintenance hemodialysis and peritoneal dialysis.

BACKGROUND AND HYPOTHESIS: Polypharmacy is a significant clinical issue for patients on dialysis but has been incompletely studied. We investigated the prevalence and costs of polypharmacy in a population-based cohort of participants treated with hemodialysis (HD) or peritoneal dialysis (PD). METHODS: We studied adults aged ≥ 20 years in Alberta, Canada receiving maintenance HD or PD as of March 31, 2019. We characterized participants as users of 0-29 drug categories of interest and those aged ≥ 65 as users/non-users of potentially inappropriate medications (PIM). We calculated the number of drug categories, daily pill burden, total annual cost, and annual cost per participant, and compared this to an age- and sex-matched cohort from the general Alberta population. RESULTS: Among 2 248 participants (mean age 63 years; 39% female) on HD (n = 1 781) or PD (n = 467), the median number of prescribed drug categories was 6 [interquartile range (IQR) 4, 8]; median daily pill burden was 8.0 (IQR 4.6, 12.6) pills/day, with 5% prescribed ≥ 21.7 pills/day, and 16.5% prescribed ≥ 15 pills/day. Twelve % were prescribed at least one drug that is contraindicated in kidney failure. The median annual per participant cost was ${\$}$3,831, totaling approximately ${\$}$11.6 million annually for all participants. When restricting to the 1 063 participants aged ≥ 65, the median number of PIM categories was 2 (IQR 1, 2), with a median PIM pill burden of 1.2 pills/day (IQR 0.5, 2.4). Compared to PD participants, HD participants had similar daily pill burden, higher use of PIM, and higher annual per participant cost. Pill burden and associated costs for participants on dialysis were more than 3-fold and 10-fold higher, respectively, compared to the matched participants from the general population. CONCLUSION: Participants on dialysis have markedly higher use of prescription medications and associated costs than the general population. Effective methods to de-prescribe in the dialysis population are needed.

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.

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.

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.

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.

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.

Medications Used Routinely in Primary Care to be Dose-Adjusted or Avoided in People With Chronic Kidney Disease: Results of a Modified Delphi Study.

Background: Chronic kidney disease (CKD) affects up to 18% of those over the age of 65 years. Potentially inappropriate medication prescribing in people with CKD is common. Objectives: Develop a pragmatic list of medications used in primary care that required dose adjustment or avoidance in people with CKD, using a modified Delphi panel approach, followed by a consensus workshop. Methods: We conducted a comprehensive literature search to identify potential medications. A group of 17 experts participated in a 3-round modified Delphi panel to identify medications for inclusion. A subsequent consensus workshop of 8 experts reviewed this list to prioritize medications for the development of point-of-care knowledge translation materials for primary care. Results: After a comprehensive literature review, 59 medications were included for consideration by the Delphi panel, with a further 10 medications added after the initial round. On completion of the 3 Delphi rounds, 66 unique medications remained, 63 requiring dose adjustment and 16 medications requiring avoidance in one or more estimated glomerular filtration rate categories. The consensus workshop prioritized this list further to 24 medications that must be dose-adjusted or avoided, including baclofen, metformin, and digoxin, as well as the newer SGLT2 inhibitor agents. Conclusion and Relevance: We have developed a concise list of 24 medications commonly used in primary care that should be dose-adjusted or avoided in people with CKD to reduce harm. This list incorporates new and frequently prescribed medications and will inform an updated, easy to access source for primary care providers.

Lower opioid and higher adjuvant analgesic use in patients on haemodialysis: A single-centre cross-sectional study.

WHAT IS KNOWN: Opioids are often used to treat chronic non-cancer pain (CNCP) in patients on haemodialysis. Altered pharmacokinetics in this population increases risk for opioid-related adverse events. Although useful in pain management, there is a lack of opioid prescribing guidance for end-stage kidney disease. OBJECTIVE: To characterize opioid usage for CNCP in an outpatient haemodialysis unit. METHODS: Cross-sectional, single-centre, retrospective cohort study of 272 patients receiving outpatient haemodialysis between 01 June and 31 December 2017. Prevalence of prescription or non-prescription opioids, formulation, indication, dosing, prescriber type and therapeutic effectiveness were evaluated. RESULTS: A total of 27 (10%, aged 58 + 12.1 years, 59% women) patients received opioids for CNCP during the study period. Pain aetiology was diverse; 14 (52%) patients experienced multiple concurrent chronic pain conditions. Hydromorphone (55%) and oxycodone (37%) were the most common prescriptions. A majority (85%) of patients used non-opioid analgesics as adjunct therapy, while half (48%) used benzodiazepines or zopiclone concurrently. Patients who completed a pain scale (n = 10) reported a median pain intensity of 6.8/10 ([IQR], 4.5-7.3). DISCUSSION: Opioid usage was lower than expected despite a higher prevalence of concurrent chronic pain conditions. Though this was within opioid usage guidelines, pain may not be sufficiently controlled. High concomitant use of benzodiazepines and Z-drugs introduces the potential for additive adverse effects. Judicious opioid usage can be facilitated with stewardship to effectively treat pain while avoiding associated harms and manage potential drug-drug interactions with common concomitant medications. WHAT IS NEW AND CONCLUSION: The prevalence of chronic opioid use for non-cancer pain in haemodialysis patients was lower than expected at our centre. Despite following the recommended guidelines, pain management was relatively ineffective, and concomitant use of non-opioid analgesics was widespread. Opioid stewardship is recommended to optimize pain treatment and mitigate drug interaction risks.

A systematic review of direct oral anticoagulant use in chronic kidney disease and dialysis patients with atrial fibrillation.

Background: There is a lack of clear benefit and a potential risk of bleeding with direct oral anticoagulant (DOAC) use in chronic kidney disease (CKD) and dialysis patients with atrial fibrillation. The objective of this study was to evaluate how treatment with DOACs affects stroke and bleeding outcomes compared with warfarin or aspirin. Methods: We conducted a systematic review of randomized controlled trials, cohort studies and case series, and searched electronic databases from 1946 to 2017. Studies evaluating stroke and bleeding outcomes with DOAC use in CKD and dialysis patients were included. Results: From 8008 studies, 10 met the inclusion criteria. For moderate CKD patients (estimated glomerular filtration rate <60 mL/min/1.73 m2), there was no difference in stroke outcomes between dabigatran 110 mg [hazard ratio (HR) 0.78, 95% confidence interval (95% CI) 0.51-1.21], rivaroxaban (HR 0.82-0.84, 95% CI 0.25-2.69) and edoxaban (HR 0.87, 95% CI 0.65-1.18) versus warfarin. Dabigatran (150 mg twice daily) and apixaban reduced risk of stroke or systemic embolism significantly more than warfarin for moderate CKD patients (HR 0.55, 95% CI 0.34-0.89 and HR 0.61, 95% CI 0.39-0.94, respectively). Edoxaban and apixaban were associated with reduced major bleeding events (HR 0.50-0.76) compared with warfarin. Rivaroxaban and dabigatran 110 mg and 150 mg showed no significant difference in major bleeding versus warfarin. In hemodialysis (HD) patients, there was no difference in stroke outcomes between apixaban, dabigatran [relative risk (RR) 1.71, 95% CI 0.97-2.99] or rivaroxaban (RR 1.8, 95% CI 0.89-3.64) versus warfarin. In HD patients, rivaroxaban and dabigatran were associated with an increased major bleeding risk (RR 1.45-1.76), whereas there was no major bleeding difference with apixaban compared to warfarin. Limitations: The heterogeneity of major bleeding and stroke definitions of the 10 included studies. Conclusions: Clinicians should continue to weigh the risk of stroke versus bleeding before prescribing DOACs in the CKD and dialysis population.

Pharmacokinetic Study of Cefazolin in Short Daily Hemodialysis.

BACKGROUND: A number of centers across the world offer short daily hemodialysis (SDHD) treatments. To date, cefazolin pharmacokinetics have not been described in patients undergoing SDHD. OBJECTIVE: The purpose of this study was to investigate the effect of SDHD on the pharmacokinetics of cefazolin. METHODS: This was a prospective, open-label, pharmacokinetic study of cefazolin during SDHD in 10 noninfected patients. Participants received a 1-g intravenous (IV) infusion of cefazolin after SDHD on study day 1 and a second dose after SDHD on study day 2. To determine the concentration of cefazolin, 6 blood samples were drawn at 0, 1, 2, 2.3, 4, and 24 hours after initiation of dialysis on day 2, and 2 dialysate samples were drawn at 1 and 2 hours after initiation of dialysis on day 2. Samples were analyzed using high-performance liquid chromatography, and pharmacokinetic parameters were determined. RESULTS: Median interdialysis clearance was 0.16 L/h (interquartile range [IQR]: 0.11-0.21 L/h), and median intradialysis clearance was 1.95 L/h (IQR: 1.66-2.45 L/h). Median interdialysis half-life was 28.2 hours (IQR: 23.5-59.3 hours) as compared with a median intradialysis half-life of 2.3 hours (IQR: 1.7-2.7 hours). The median percentage removal of cefazolin during dialysis was 41% (IQR: 35%-53%). Conclusion and Relevance: Estimated cefazolin dialysis clearance is similar to previous estimates with conventional thrice-weekly regimens. Current dosing recommendations of 1 g IV post-SDHD achieve total serum drug concentrations greater than 40 mg/L in all patients, which is the total drug concentration required for bactericidal activity against Staphylococcus species.

Cardiologists' and nephrologists' management of atrial fibrillation in hemodialysis patients
.

BACKGROUND: Antithrombotic therapy for stroke prevention in atrial fibrillation (AF) is considered a standard of care, but for hemodialysis (HD) patients the benefits are unclear, and bleeding risks are high. Our study objective was to compare cardiologists' and nephrologists' stroke prevention practices in different patient risk scenarios. MATERIALS AND METHODS: A cross-sectional, online survey was distributed to members of three Canadian physician societies (Nephrology, Cardiovascular, Heart Rhythm), and to cardiologists affiliated with three Canadian Universities. The questionnaire included four AF scenarios in HD patients with varying stroke and bleeding risks. Physicians selected one of six antithrombotic therapy options for each scenario. RESULTS: Cardiologists were 3 times more likely than nephro-logists to choose anticoagulant therapy over both antiplatelet and no drug therapy, regardless of stroke or bleeding risk (p < 0.001). Physicians' drug therapy choices in regards to level of stroke and bleeding risk reflected the expected pattern based on current evidence. CONCLUSION: Cardiologists were more likely to prescribe anticoagulant therapy for AF in the HD population compared to nephrologists, regardless of patient stroke or bleeding risk.

Targeted Deprescribing in an Outpatient Hemodialysis Unit: A Quality Improvement Study to Decrease Polypharmacy.

BACKGROUND: Polypharmacy in hemodialysis patients can result in adverse patient outcomes. Deprescribing tools can reduce polypharmacy, yet no method exists for an outpatient hemodialysis population. DESIGN: Quality improvement study. SETTING & PARTICIPANTS: 240 patients in a tertiary-care outpatient hemodialysis unit. QUALITY IMPROVEMENT PLAN: We aimed to: (1) develop a deprescribing tool for target medications with poor evidence for efficacy and safety, (2) determine its effectiveness in decreasing polypharmacy, and (3) monitor patient safety and satisfaction. OUTCOMES: The primary outcome was the proportion of target medications completely deprescribed after 4 weeks. Secondary outcomes were the proportion of target medications completely deprescribed after 6 months, average number of medications per patient before and after deprescription, and proportion of successful deprescriptions for each target medication. MEASUREMENTS: Number of medications deprescribed at 4 weeks and 6 months. Patient safety and satisfaction were monitored using drug-specific monitoring parameters. RESULTS: A deprescribing tool for specific medications was developed and implemented in the hemodialysis unit. 5 medication classes were selected: quinine, diuretics, α1-blockers, proton pump inhibitors, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). All 240 patients in the unit were screened using the deprescribing tool. There were 171 of 240 (71%) patients prescribed at least 1 of the 5 target medications, and after applying the tool, 35 of 40 (88%) eligible patients had the medications deprescribed. There were 31 of 40 (78%) target medications completely deprescribed. 6 months after the study, only 5 of 31 (16%) medications discontinued were represcribed. At the end of the study, 57% of patients were taking fewer medications than at baseline. No adverse events were observed. LIMITATIONS: Single-center study that relied on patient self-reporting of medication use and adherence to our recommendations. CONCLUSIONS: Deprescribing tools can be applied successfully in an outpatient hemodialysis unit to reduce polypharmacy while maintaining patient safety and satisfaction.

Development, validation, and implementation of a medication adherence survey to seek a better understanding of the hemodialysis patient.

BACKGROUND: Factors contributing to non-adherence have become a priority for clinicians, healthcare policy makers, and healthcare payers alike. Patients who are non-adherent to their medication regimen appear to have poor health outcomes, with evidence of both high mortality rates and high morbidity in the form of more frequent emergency room admissions, recurrent exacerbations of disease, and poor overall well-being. The primary objective of this study was to identify and describe patient-identified factors associated with non-adherence in patients maintained on chronic hemodialysis. METHODS: A 23-item questionnaire was developed and validated for use in the hemodialysis population. This questionnaire was administered to patients undergoing chronic hemodialysis in a single center during the period of October to December 2013. RESULTS: A total of 156/183 eligible patients consented. Of these 156 patients, 36 (23%) patients reported being non-adherent. The most common non-adherent behaviors were changing the frequency of taking medications and skipping doses. Patients identified information gaps around medication interactions, the flexibility around drug timings, and how best to manage medications that needed to be taken apart from, with, or without food. CONCLUSIONS: Our study shows that, despite an intensive drug education program, almost one quarter of patients continue to have problems with taking medication and that traditional education around medications is insufficient. We propose that clinicians customize education to the patient-driven gaps in knowledge, in particular focusing on the education needed to empower patients to recognize which aspects of their care they can and should modify and which aspects require further clinician input.

Canadian Society of Nephrology commentary on the KDIGO clinical practice guideline for CKD evaluation and management.

We congratulate the KDIGO (Kidney Disease: Improving Global Outcomes) work group on their comprehensive work in a broad subject area and agreed with many of the recommendations in their clinical practice guideline on the evaluation and management of chronic kidney disease. We concur with the KDIGO definitions and classification of kidney disease and welcome the addition of albuminuria categories at all levels of glomerular filtration rate (GFR), the terminology of G categories rather than stages to describe level of GFR, the division of former stage 3 into new G categories 3a and 3b, and the addition of the underlying diagnosis. We agree with the use of the heat map to illustrate the relative contributions of low GFR and albuminuria to cardiovascular and renal risk, though we thought that the highest risk category was too broad, including as it does people at disparate levels of risk. We add an albuminuria category A4 for nephrotic-range proteinuria and D and T categories for patients on dialysis or with a functioning renal transplant. We recommend target blood pressure of 140/90mm Hg regardless of diabetes or proteinuria, and against the combination of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors. We recommend against routine protein restriction. We concur on individualization of hemoglobin A1c targets. We do not agree with routine restriction of sodium intake to <2g/d, instead suggesting reduction of sodium intake in those with high intake (>3.3g/d). We suggest screening for anemia only when GFR is <30mL/min/1.73m(2). We recognize the absence of evidence on appropriate phosphate targets and methods of achieving them and do not agree with suggestions in this area. In drug dosing, we agree with the recommendation of using absolute clearance (ie, milliliters per minute), calculated from the patient's estimated GFR (which is normalized to 1.73m(2)) and the patient's actual anthropomorphic body surface area. We agree with referral to a nephrologist when GFR is <30mL/min/1.73m(2) (and for many other scenarios), but suggest urine albumin-creatinine ratio > 60mg/mmol or proteinuria with protein excretion > 1g/d as the referral threshold for proteinuria.

Evaluating time in therapeutic range for hemodialysis patients taking warfarin.

Warfarin is frequently used in the hemodialysis (HD) population for atrial fibrillation (AF) and venous thromboembolism (VTE); however, there is insufficient evidence to support this practice. Given that HD patients have 3 - 10 times the risk for both stroke and bleeding than the general population, anticoagulation in these patients is controversial. Time in therapeutic range (TTR) is accepted as a surrogate outcome of clinical effectiveness and safety of warfarin. The primary objective of this study was to evaluate TTR in an HD population. A 6-year retrospective chart review was performed in 46 HD patients on warfarin (target international normaized ratio (INR)=2-3). One year of patient data was collected, which included weekly INRs, demographics and clinical outcomes. TTR was calculated using the Rosendaal and fraction of INRs in range methods. The mean TTR using the Rosendaal and fraction of INRs in range method was 49.2±14.6% and 44.2±13.5%, respectively. Patients were 3 times more likely to be below target than above it, suggesting they were more often at risk of inadequate efficacy rather than toxicity. There were 9 serious bleeding and 9 thrombotic events; these occurred in patients with a TTR<60%. For the 9 serious bleeding events, the median INR on the day of the event was 2.1 (IQR 1.81-2.75). In conclusion, this HD unit is not meeting the TTR goal established in the literature and patients are often subtherapeutic. Further studies to investigate ways to improve TTR are warranted. Ultimately, a prospective study evaluating the safety and efficacy of warfarin in HD patients is needed.

Cost savings using a protocol approach to manage anemia in a hemodialysis unit.

BACKGROUND: National guidelines recommend using anemia management protocols to guide treatment. The objective of this study was to determine if an anemia management protocol would improve hemoglobin (Hgb) indices in hemodialysis patients and to measure whether the protocol would reduce the use and cost of darbepoetin alfa (DBO) and intravenous (IV) iron in hemodialysis patients. METHODS: An anemia management protocol was created and implemented for hemodialysis patients at our institution. A retrospective observational review of the use of DBO and IV iron as well as changes in Hgb, transferrin saturation and ferritin in 174 patients was conducted 6 months before and after implementation of the anemia protocol. RESULTS: The number of Hgb measurements in the target range increased from 44.3 to 46.0% (p = 0.48) after protocol implementation. The mean weekly dose of DBO was reduced from 34.56 ± 31.12 to 31.11 ± 28.64 µg post-protocol implementation (p = 0.011), which translated to a cost savings of USD 41,649 over 6 months. The mean monthly IV iron dose also decreased from 139.56 ± 98.83 to 97.65 ± 79.05 mg (p < 0.005), a cost savings of USD 18,594 over the same time period. CONCLUSION: The use of an anemia management protocol resulted in the deprescribing of DBO and iron agents while increasing the number of patients in the target Hgb range, which led to significant cost savings in the treatment of anemia.

Should statins be used to prevent cardiovascular disease in patients on hemodialysis?

There now exists current evidence that the initiation of statin therapy in patients on hemodialysis does not provide the same cardiovascular benefit as in non-hemodialysis patients. The KDIGO guidelines suggest not to initiate statin therapy in hemodialysis-dependent CKD patients, but to continue therapy in patients who are already on a statin at the time of hemodialysis initiation. A closer monitoring of myopathy is warranted for hemodialysis patients on a statin therapy.

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.

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.