Hypertension Canada's 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children.

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

Vancomycin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis.

BACKGROUND: Sustained low-efficiency dialysis (SLED) is a hybrid form of dialysis that is increasingly used in critically ill patients with kidney injury and hemodynamic instability. Antimicrobial dosing for patients receiving SLED is informed by pharmacokinetic studies that describe the drug clearance. Studies available to assist in the dosing of vancomycin in the context of SLED are lacking. OBJECTIVE: The objective of this prospective observational study was to describe the population pharmacokinetics of vancomycin in critically ill patients receiving SLED, and use simulation studies to propose dosing strategies. METHODS: Serial serum samples were obtained from 31 critically ill patients prescribed vancomycin while receiving SLED. Vancomycin concentrations were quantified in plasma using a validated liquid chromatography mass spectrometry/mass spectrometry method. A population pharmacokinetic model was developed, and Monte Carlo simulation was used to determine the probability of target attainment at different doses. RESULTS: From a total of 335 serum samples from 31 patients receiving 52 sessions of SLED therapy, a two-compartment linear model with zero-order input was developed. The mean (standard deviation) clearance of vancomycin on and off SLED was 5.97 (4.04) and 2.40 (1.46) L/h, respectively. Using pharmacodynamic targets for efficacy (area under the concentration-time curve from time zero to 24 h [AUC24]/minimum inhibitory concentration [MIC] ≥ 400) and safety (AUC24 ≥ 700), a loading dose of 2400 mg followed by daily doses of 1600 mg is recommended. Subsequent dosing should be informed by therapeutic drug monitoring of vancomycin levels. CONCLUSIONS: In critically ill patients receiving SLED, vancomycin clearance is highly variable with a narrow therapeutic window. Empiric dosing is proposed but subsequent dosing should be guided by drug levels.

The case for cautious consumption: NSAIDs in chronic kidney disease.

PURPOSE OF REVIEW: Strong epidemiological and pathologic evidence associates NSAIDs with kidney disease, both acute and chronic. Hence, the usage of NSAIDs has decreased in patients with, or at risk for, chronic kidney disease (CKD). Coupled with this has been a rise in use of opioids and other non-NSAID alternatives, which do come with significant, and underrecognized, risk of nonrenal adverse events. We review the literature to understand if this shift is appropriate or deleterious. RECENT FINDINGS: NSAIDs do have a low but tangible risk in causing acute kidney injury, electrolyte imbalances, and increasing blood pressure. However, their role in causing progressive kidney disease is due to long-term usage in high cumulative dosages, and the use of NSAIDs in combination with other agents. Alternatives such as opioids, tramadol, gabapentin and baclofen have weak evidence to support their use and strong evidence to show their harm in patients with CKD. SUMMARY: Tradeoffs are inherent in using active pharmaceuticals, and NSAIDs are no exception. Balancing potential benefits with possible adverse effects around pain management should be a part of every conversation for patients with kidney disease.

Are iso-osmolar, as compared to low-osmolar, contrast media cost-effective in patients undergoing cardiac catheterization? An economic analysis.

PURPOSE: Contrast-induced acute kidney injury is a prominent complication following cardiac catheterization, though the risk has progressively decreased in recent times with appropriate risk stratification and use of safer contrast agents. Despite data supporting further lowering of risk with the iso-osmolar agent, iodixanol, uptake has lagged, perhaps due to increased upfront cost of this agent. We undertook an economic analysis to estimate the cost-effectiveness of a strategy utilizing iodixanol compared to using a low-osmolar contrast agent. METHODS: We created a Markov model to evaluate the two strategies, and included a differential relative risk of contrast-induced acute kidney injury, based on a systematic review of the literature. Downstream clinical events, including need for dialysis and mortality, were modeled using data from existing published literature. A third-party payer perspective was utilized for the analysis and presentation of the primary economic analysis. RESULTS: The strategy of using iodixanol dominated in both the low-risk and high-risk base case analyses. However, the difference was quite small in the low-risk scenario (lifetime cost: C$678,034 vs. C$678,059 and life expectancy: 19.80 vs. 19.72 years). The difference was more marked (life expectancy 15.65 vs. 14.15 years and cost C$680,989 vs. C$682,023) in the high-risk case analysis. This was robust across most of the variables tested in sensitivity analyses. CONCLUSION: The use of iodixanol, compared with low-osmolar contrast agents, for cardiac catheterization, results in a small benefit clinical outcomes, and in a savings in direct healthcare costs. Overall, our analysis supports the use of iodixanol for cardiac catheterization, especially in patients at high risk of acute kidney injury.

Time-Varying Association of Individual BP Components with eGFR in Late-Stage CKD.

BACKGROUND AND OBJECTIVES: The association of individual BP components with changes in eGFR in patients with late-stage CKD is unknown. The objectives of our study were to examine the associations of systolic BP, diastolic BP, and pulse pressure with continuous temporal changes in eGFR and an eGFR decline ≥30% in late-stage CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study (2010-2015) of patients with CKD in a multidisciplinary CKD clinic with an eGFR≤30. The associations of repeat measures of BP (systolic BP, diastolic BP, and pulse pressure) with eGFR were examined using general linear mixed models. The associations of BP components and eGFR decline ≥30% were examined with time-varying Cox models. RESULTS: In total, 1203 patients were followed for a median of 548 days (interquartile range, 292-913), with an average of 6.7 visits and BP measures per patient. Mean baseline systolic BP, diastolic BP, pulse pressure, and eGFR were 139.2 mmHg, 73.2 mmHg, 64.9 mmHg, and 16.8 ml/min, respectively. Systolic BP and diastolic BP measures over time were statistically significantly associated with changes in eGFR (P<0.001), whereas pulse pressure was not. Patients with extremes of systolic BP (<105 or >170) and high diastolic BP (>90) measures were at a higher risk of GFR decline ≥30% (systolic BP <105: hazard ratio, 1.51; 95% confidence interval, 0.98 to 2.34; systolic BP >170: hazard ratio, 1.62; 95% confidence interval, 1.05 to 2.49; referent systolic BP =121-130; diastolic BP =81-90: hazard ratio, 1.40; 95% confidence interval, 0.99 to 1.86; diastolic BP >90: hazard ratio, 1.83; 95% confidence interval, 1.21 to 2.77; referent diastolic BP =61-70). The findings were consistent after multiple sensitivity analyses. Pulse pressure was not significantly associated with risk of eGFR decline. CONCLUSIONS: In patients referred to a multidisciplinary care clinic with late-stage CKD, only extremes of systolic BP and elevations of diastolic BP were associated with eGFR decline.

Progressively Earlier Initiation of Renal Replacement Therapy for Acute Kidney Injury Is Unwarranted and Potentially Harmful.

BACKGROUND: The optimal timing of renal replacement therapy (RRT) initiation for acute kidney injury (AKI) is unknown. There is debate as to whether starting RRT earlier for AKI is superior to starting it only after 'conventional', life-threatening indications are present. SUMMARY: In recent years, there has been an ongoing trend in clinical practice to initiate RRT for AKI long before indications appear. Observational studies show many patients now begin RRT for AKI in the absence of 'conventional' indications. While this shift may have been prompted by observational studies suggesting improved outcomes with earlier RRT, there was not sufficient justification for a change in clinical practice: many recent, observational studies suggest that early RRT may not beneficial or may be even harmful. Moreover, none of 3 underpowered RCTs reported to date found 'early' RRT initiation beneficial. Lowering the threshold for RRT initiation inevitably leads to more patients receiving unnecessary treatment and this is a matter of concern, considering the fact that complications are potentially fatal and RRT is very costly. While we await definitive studies, calls to shift clinical practice back toward the initiation of RRT for 'conventional', life-threatening indications only, should be heeded. KEY MESSAGES: 'Earlier' initiation of RRT for AKI is already occurring in clinical practice but is not justified on the basis of the studies to date. Lowering the threshold for initiation leads to more patients receiving unnecessary RRT. RRT has potentially fatal complications and is expensive. While we await definitive trials, RRT should be started only after 'conventional', life-threatening indications occur and not earlier.

E-health physical activity interventions and moderate-to-vigorous intensity physical activity levels among working-age women: a systematic review protocol.

BACKGROUND: The rapid pace of modern life requires working-age women to juggle occupational, family, and social demands. Despite the large numbers of working-age women in developed countries and the proven benefits of regular moderate-to-vigorous intensity aerobic physical activity (MVPA) in chronic disease prevention, few women meet current physical activity (PA) recommendations of 150 min of MVPA per week. It is important that appropriate and effective behavioral interventions targeting PA are identified and developed to improve the MVPA levels of working-age women. As women worldwide embrace modern technologies, e-health innovations may provide opportune and convenient methods of implementing programs and strategies to target PA in an effort to improve MVPA levels and cardiometabolic health. Previous reviews on this topic have been limited; none have focused on working-age women from developed countries who exhibit inappropriately low PA levels. It remains unknown as to which e-health interventions are most effective at increasing MVPA levels in this population. The purpose of this systematic review is to examine the effectiveness of e-health interventions in raising MVPA levels among working-age women in developed countries and to examine the effectiveness of these interventions in improving the health of women. METHODS: Eight electronic databases will be searched to identify all prospective cohort and experimental studies examining the impact of e-health interventions for increasing MVPA levels among working-age women (mean age 18-65 years) in developed countries. Gray literature including theses, dissertations, and government reports will also be examined. Study quality will be assessed using a modified Downs and Black checklist, and risk of bias will be assessed within and across all included studies using the Cochrane's risk of bias tool and Grades of Recommendation, Assessment, Development and Evaluation approach. A quantitative synthesis in the form of meta-analyses for measures of MVPA and health outcomes will be conducted where possible. DISCUSSION: This review will determine the effectiveness of e-health interventions in raising MVPA levels in working-age women in developed countries. It will form a contemporary, rigorously developed, and reliable research base for policy makers and stakeholders; and inform and influence the development and implementation of effective e-health interventions designed to increase MVPA levels and improve health outcomes in this population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009534.

The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

Herein, updated evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in Canadian adults are detailed. For 2014, 3 existing recommendations were modified and 2 new recommendations were added. The following recommendations were modified: (1) the recommended sodium intake threshold was changed from ≤ 1500 mg (3.75 g of salt) to approximately 2000 mg (5 g of salt) per day; (2) a pharmacotherapy treatment initiation systolic blood pressure threshold of ≥ 160 mm Hg was added in very elderly (age ≥ 80 years) patients who do not have diabetes or target organ damage (systolic blood pressure target in this population remains at < 150 mm Hg); and (3) the target population recommended to receive low-dose acetylsalicylic acid therapy for primary prevention was narrowed from all patients with controlled hypertension to only those ≥ 50 years of age. The 2 new recommendations are: (1) advice to be cautious when lowering systolic blood pressure to target levels in patients with established coronary artery disease if diastolic blood pressure is ≤ 60 mm Hg because of concerns that myocardial ischemia might be exacerbated; and (2) the addition of glycated hemoglobin (A1c) in the diagnostic work-up of patients with newly diagnosed hypertension. The rationale for these recommendation changes is discussed. In addition, emerging data on blood pressure targets in stroke patients are discussed; these data did not lead to recommendation changes at this time. The Canadian Hypertension Education Program recommendations will continue to be updated annually.

What is the feasibility of implementing effective sodium reduction strategies to treat hypertension in primary care settings? A systematic review.

OBJECTIVE: To evaluate whether efficacious counseling methods on sodium restriction can be successfully incorporated into primary care models for the management of hypertension. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment to identify randomized controlled trials of dietary counseling for salt intake reduction that reported significant reduction in 24-h urinary sodium and blood pressure levels among adults with untreated hypertension. Data extraction and assessment of reproducibility and feasibility were done in duplicate and any disagreements were resolved by consensus. RESULTS: Six trials were included for assessment of methods as they were efficacious in reducing sodium intake (24-h urinary sodium excretion) by 73 to 93 mmol/day (intervention) vs. 3.2 to 12.5 mmol/day (control). This was paralleled with a reduction in blood pressure (-4 to -27  mmHg) between groups. In four of the six trials, the methods were described in sufficient detail to be reproducible, but in none of these trials were the 'counseling methods' feasible for application in primary care settings. Apart from multiple sessions of counseling, the reported interventions were supplemented with provision of prepared food, community cooking classes, and intensive inpatient training sessions. CONCLUSION: Despite the availability of efficacious counseling methods for the reduction of sodium intake among newly diagnosed hypertensive patients (feasible within a clinical trial setting), none of these methods, in their present form, are suitable for incorporation into existing primary care settings in countries such as Canada, United States, and UK.

Should the arteriovenous fistula be created before starting dialysis?: a decision analytic approach.

BACKGROUND: An arteriovenous fistula (AVF) is considered the vascular access of choice, but uncertainty exists about the optimal time for its creation in pre-dialysis patients. The aim of this study was to determine the optimal vascular access referral strategy for stage 4 (glomerular filtration rate <30 ml/min/1.73 m(2)) chronic kidney disease patients using a decision analytic framework. METHODS: A Markov model was created to compare two strategies: refer all stage 4 chronic kidney disease patients for an AVF versus wait until the patient starts dialysis. Data from published observational studies were used to estimate the probabilities used in the model. A Markov cohort analysis was used to determine the optimal strategy with life expectancy and quality adjusted life expectancy as the outcomes. Sensitivity analyses, including a probabilistic sensitivity analysis, were performed using Monte Carlo simulation. RESULTS: The wait strategy results in a higher life expectancy (66.6 versus 65.9 months) and quality adjusted life expectancy (38.9 versus 38.5 quality adjusted life months) than immediate AVF creation. It was robust across all the parameters except at higher rates of progression and lower rates of ischemic steal syndrome. CONCLUSIONS: Early creation of an AVF, as recommended by most guidelines, may not be the preferred strategy in all pre-dialysis patients. Further research on cost implications and patient preferences for treatment options needs to be done before recommending early AVF creation.