A Primer on Artificial Intelligence for Healthcare Administrators.

Healthcare administrators steer their organizations' strategic direction with an emphasis on quality, value and efficiency, aiming to improve patient outcomes and ensure operational sustainability. Artificial intelligence (AI) has become a transformative force in healthcare in the past decade, with Canadian health systems and research institutions investing in AI solutions to address critical healthcare challenges. This primer delivers a fundamental guide to essential AI concepts in healthcare and provides practical guidance to prepare organizations for AI readiness.

Prognostic value of blood pressure in ambulatory heart failure: a meta-analysis and systematic review. Ambulatory blood pressure predicts heart failure prognosis.

Previous primary studies have explored the association between blood pressure (BP) and mortality in ambulatory heart failure (HF) patients reporting varying and contrasting associations. The aim is to determine the pooled BP prognostic value and explore potential reasons for between-study inconsistency. We searched Medline, Cochrane, EMBASE and CINAHL from January 2005 to October 2018 for studies with ≥ 50 events (mortality and/or hospitalization) and included BP in a multivariable model in ambulatory HF patients. We pooled hazard ratios (random effects model) for systolic BP (SBP) or diastolic BP (DBP) effect on mortality and/or hospitalization risk. We used a priori defined sub-group analyses to explore heterogeneity and GRADE approach to assess the certainty of the evidence. Seventy-one eligible articles (239,467 screened) at low to moderate risk of bias included 235,752 participants. Higher SBP was associated with reduced all-cause mortality (HR 0.93, 95%CI 0.91-0.95, I2 = 87.13%, moderate certainty), all-cause hospitalization events (HR 0.91, 95%CI 0.88-0.93, I2 = 44.4%, high certainty) and their composite endpoint (HR 0.93 per 10 mmHg, 95%CI 0.91-0.94, I2 = 86.3%, high certainty). DBP did not demonstrate a statistically significant effect for all outcomes. The association strength was significantly weaker in studies following patients with either LVEF > 40%, higher average SBP (> 130 mmHg), increasing age and diabetes. All other a priori subgroup hypotheses did not explain between study differences. Higher ambulatory SBP is associated with reduced risk of all-cause mortality and hospitalization. Patients with lower BP and reduced LVEF are in a high-risk group of developing adverse events with moderate certainty of evidence.

Resting Heart Rate as an Important Predictor of Mortality and Morbidity in Ambulatory Patients With Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Resting heart rate is a risk factor of adverse heart failure outcomes; however, studies have shown controversial results. This meta-analysis evaluates the association of resting heart rate with mortality and hospitalization and identifies factors influencing its effect. METHODS AND RESULTS: We systematically searched electronic databases in February 2019 for studies published in 2005 or before that evaluated the resting heart rate as a primary predictor or covariate of multivariable models of mortality and/or hospitalization in adult ambulatory patients with heart failure. Random effects inverse variance meta-analyses were performed to calculate pooled hazard ratios. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence quality. Sixty-two studies on 163,445 patients proved eligible. Median population heart rate was 74 bpm (interquartile range 72-76 bpm). A 10-bpm increase was significantly associated with increased risk of all-cause mortality (hazard ratio 1.10, 95% confidence interval 1.08-1.13, high quality). Overall, subgroup analyses related to patient characteristics showed no changes to the effect estimate; however, there was a strongly positive interaction with age showing increasing risk of all-cause mortality per 10 bpm increase in heart rate. CONCLUSIONS: High-quality evidence demonstrates increasing resting heart rate is a significant predictor of all-cause mortality in ambulatory patients with heart failure on optimal medical therapy, with consistent effect across most patient factors and an increased risk trending with older age.

Economic Consequences of Adult Living Kidney Donation: A Systematic Review.

OBJECTIVES: Current guidelines mandate organ donation to be financially neutral such that it neither rewards nor exploits donors. This systematic review was conducted to assess the magnitude and type of costs incurred by adult living kidney donors and to identify those at risk of financial hardship. METHODS: We searched English-language journal articles and working papers assessing direct and indirect costs incurred by donors on PubMed, MEDLINE, Scopus, the National Institute for Health Research Economic Evaluation Database, Research Papers in Economics, and EconLit in 2005 and thereafter. Estimates of total costs, types of costs, and characteristics of donors who incurred the financial burden were extracted. RESULTS: Sixteen studies were identified involving 6158 donors. Average donor-borne costs ranged from US$900 to US$19 900 (2019 values) over the period from predonation evaluation to the end of the first postoperative year. Less than half of donors sought financial assistance and 80% had financial loss. Out-of-pocket payments for travel and health services were the most reported items where lost income accounted for the largest proportion (23.2%-83.7%) of total costs. New indirect cost items were identified to be insurance difficulty, exercise impairment, and caregiver income loss. Donors from lower-income households and those who traveled long distances reported the greatest financial hardship. CONCLUSIONS: Most kidney donors are undercompensated. Our findings highlight gaps in donor compensation for predonation evaluation, long-distance donations, and lifetime insurance protection. Additional studies outside of North America are needed to gain a global prospective on how to provide for financial neutrality for kidney donors.

Risk factors for diabetic kidney disease in adults with longstanding type 1 diabetes: results from the Canadian Study of Longevity in Diabetes.

Objectives: Diabetic kidney disease (DKD) is an independent predictor of cardiovascular morbidity and mortality in type 1 diabetes (T1D). We aimed to explore clinical and biochemical factors, including the achievement of American Diabetes Association (ADA) recommended targets associated with DKD in people living with T1D for ≥50 years. Methods: This was a post hoc analysis of a cross-sectional study of 75 participants enrolled in the Canadian Study of Longevity in T1D. We explored diabetes-related complications, including neuropathy, retinopathy, cardiovascular disease, and DKD. Study participants were dichotomized based on the achievement of ADA recommended targets as the low-target group (achieving ≤4 targets, n = 31) and high-target group (achieving >4 targets, n = 44). The outcome of interest was DKD defined by estimated glomerular filtration rate (eGFR) values <60/mL/min/1.73 m2 and/or 24-h albumin excretion >30 mg. Multivariable logistic regression models were employed to estimate odds ratios (ORs) for DKD with 95% confidence intervals (CIs). Results: Of the 75 participants with prolonged T1D duration (45% male, mean age 66 years), 25 participants had DKD and 50 did not. There was no statistical difference between the high- and low-target groups in terms of age and body mass index. eGFR was significantly higher and the prevalence of diabetic retinopathy was significantly lower in the high-target group. Older age at diagnosis of T1D and lower frequency component to high-frequency component ratio increased the odds of having DKD. Conclusions: In adults with prolonged T1D duration, older age at diagnosis and lower heart rate variability may be associated with DKD.

Cinacalcet versus standard treatment for chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Chronic kidney disease-mineral and bone disorders (CKD-MBD) have been associated with poor health outcomes, including diminished quality and length of life. Standard management for CKD-MBD includes phosphate restricted diet, vitamin D and phosphate binders. Persistently elevated parathyroid hormone levels may require the addition of cinacalcet hydrochloride (cinacalcet), which sensitizes calcium receptors in the parathyroid gland. PURPOSE: The objective of this systematic review is to compare, in patients with CKD-MBD the effect of cinacalcet versus standard treatment on patient-important outcomes, including parathyroidectomy, fractures, hospitalizations due to cardiovascular events, cardiovascular mortality, all-cause mortality, and intermediate outcomes, in particular Kidney Disease Outcome Quality Initiative targets. METHODS: Data sources included MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Web of Science from 1996 to June 2015. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible trials. We calculated the effect estimates (risk ratios or mean differences) and 95% confidence intervals, as well as statistical measures of variability in results across studies using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate quality of evidence about estimates of effect on an outcome-by-outcome basis for all outcomes. We presented our results with a GRADE summary table. RESULTS: Twenty-four trials including 8311 CKD patients proved eligible. The results left considerable uncertainty regarding the impact of cinacalcet on reducing fractures (relative risk [RR] 0.59, 95% confidence interval [CI] 0.13-2.60; heterogeneity: p = 0.03, I(2)= 78%; very low quality evidence), and indicated that cinacalcet did not reduce hospitalizations due to cardiovascular events (RR 0.93, 95% CI 0.85-1.02, moderate quality of evidence), cardiovascular mortality (RR 0.95, 95% CI 0.84-1.07; heterogeneity p= 0.61, high quality evidence) or all-cause mortality (RR 0.96, 95% CI 0.89-1.04; heterogeneity: p= 0.98, I(2)= 0%; moderate quality evidence). Cinacalcet reduced the need for parathyroidectomy (RR 0.30, 95% CI 0.22-0.42; heterogeneity: p= 0.70, I(2)= 0%; absolute effect 55 fewer per 1000 [95% CI 61 fewer to 45 fewer], high quality of evidence). The most common adverse event associated with cinacalcet therapy was gastrointestinal side effects. Cinacalcet increased nausea (RR 2.16, 95% CI 1.46-3.21, absolute effect 158 more per 1000 [95% CI 82 more to 302 more]) and vomiting (RR 2.15, 95% CI 1.66-2.80, absolute effect 63 more per 1000 [95% CI 109 more to 171 more]). Cinacalcet treatment increased the rate of hypocalcemia (RR 6.0, 95% CI 3.65-9.87; heterogeneity: p= 0.71, I(2)= 0%, absolute effect 20 more per 1000 [95% CI 11 more to 36 more], high quality of evidence). CONCLUSIONS: In the hands of clinicians participating in these studies, cinacalcet decreased the rate of parathyroidectomy but had no influence on mortality. Patients and clinicians can trade of the benefit of fewer parathyroidectomies against the adverse effects.

Culprit vessel versus immediate complete revascularization in patients with ST-segment myocardial infarction-a systematic review.

BACKGROUND: Guidelines suggest percutaneous intervention (PCI) of only the culprit artery in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, recent randomized controlled trials (RCTs) suggest benefit to performing PCI of other stenotic vessels at the same time as culprit vessel PCI. METHODS: We conducted a systematic review with complete case meta-analysis and sensitivity analyses. Data sources included MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and CINAHL from 1946 to March 2014; MEDLINE and EMBASE from March 2014 to March 2015; and scanning of literature for new studies until August 2015. All RCTs comparing multivessel versus culprit-only PCI in patients with STEMI were eligible. The primary outcomes of interest were recurrent myocardial infarction (MI), recurrent revascularization, and mortality. We combined data from trials to estimate the pooled risk ratio (RR) and associated 95% CIs using random-effects models. RESULTS: Five RCTs including 1,606 patients of whom 1,568 had complete data proved eligible. Multivessel revascularization was associated with decreased risk of repeat revascularization (RR 0.36, 95% CI 0.27-0.49, risk difference 9.7% over 2 years) and recurrent nonfatal MI (RR 0.58, 95% CI 0.36-0.93, risk difference 1.8% over 2 years), without increase in mortality (RR 0.82, 95% CI 0.53-1.26) or other adverse events. CONCLUSIONS: Pooled data provide moderate-certainty evidence that performance of multivessel PCI will provide an appreciable reduction in nonfatal MI and high-certainty evidence that it will reduce need for repeat revascularization. Patients are likely to place a high value on these benefits.

Sleep quality and its correlates in patients with chronic kidney disease: a cross-sectional design.

PURPOSE: Since sympathovagal imbalance influences clinical phenomena, such as hypertension, diabetes mellitus, chronic kidney disease (CKD) and sleeping problems, there should be correlations between these conditions. We hypothesized that sleep quality would be correlated with estimated glomerular filtration rate (eGFR), blood pressure and the presence of diabetes. METHODS: We included 303 CKD patients in this study. We employed the Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI) and Short Form 36 Quality of Life Health Survey Questions (SF-36) to screen sleeping disturbances, depression and quality of life, respectively. A chart review was performed for the patients' demographics, diagnoses and certain laboratory parameters--including blood glucose, hemoglobin, albumin, calcium, phosphate, parathyroid hormone and eGFR. Multivariate logistic regression models were employed to estimate odds ratios with 95% confidence intervals. RESULTS: We included 303 patients in this cross-sectional study. A total of 101 patients were on dialysis. In the univariate models, gender, calcium and mental component summary scores (MCS) reached a significant level of 0.1, and those covariates were included in the multivariate analysis. The reduced models included gender and MCS categories. Female gender increases the risk for poor sleep quality. In our report, evidence suggests MCS domain scores are inversely related to the risk for impaired sleep. CONCLUSION: Our results indicated a high burden of sleep disturbances in kidney patients. In addition, female gender and having low MCS scores may influence sleep quality in kidney patients.

Sleep apnea in patients with chronic kidney disease: a single center experience.

PURPOSE: The primary objective of this cross-sectional study was to test factors associated with sleep apnea in patients with chronic kidney disease (CKD). The prevalence of sleep apnea was also assessed. METHODS: We recruited patients with CKD Stage 3-5 who lived in the St. John's area from September 2012 to December 2012. The Berlin Questionnaire and Short Form 36 Quality of Life Health Survey Questions (SF-36) were administered to all participants. RESULTS: We recruited 303 patients (41% female). A total of 157 (51.8%) patients had a high risk for sleep apnea. Higher body mass index and young age were correlated with sleep apnea. Physical component score of SF-36 (PCS) tested as a continuous variable indicated a significant association with the risk for sleep apnea (OR: 0.97, 95% CI: 0.94-0.99, p = 0.03). The association implies 3% change per one point increase in PCS. We categorized mental component score of SF-36 (MCS) into four quartiles, as the linearity assumption was violated. There was a 61% risk increase for poor sleep in those with an MCS score less than the 75th percentile, when compared to those above the 75th percentile (OR: 0.39, 95% CI: 0.21-0.71, p = 0.002). CONCLUSIONS: Sleep apnea is common in kidney patients. People who have low PCS and MCS scores are more prone to sleep apnea or vice versa. Our results also indicate that high BMI and young age are associated with sleep apnea.

Examining the Impacts of the COVID-19 Pandemic on Iraqi Refugees in Canada.

The COVID-19 pandemic has exacerbated health and social inequities among migrant groups more than others. Higher rates of poverty, unemployment, living in crowded households, and language barriers have placed resettled refugees at a higher risk of facing disparities during the COVID-19 pandemic. To understand how this most vulnerable population has been impacted by the ongoing pandemic, this study reports on the responses of 128 Iraqi refugees in the city of London, Ontario, to a survey on the economic, social, and health-related impacts that they have faced for almost two years since the beginning the pandemic. The analysis of the survey indicated that 90.4% of the study population reported having health concerns during the pandemic while 80.3% expressed facing financial distress. The results also show that 58.4% of respondents experienced some form of social isolation. These all suggest that refugees are faced with several barriers which can have a compounding effect on their resettlement experience. These findings provide resettlement and healthcare providers with some information that may assist in reducing the impact of COVID-19 and other possible health security emergencies on resettled refugees and their communities.

Addressing the health human resources crisis: Strategies for retaining women health care professionals in organizations.

Globally, healthcare systems are contending with a pronounced health human resource crisis marked by elevated rates of burnout, heightened job transitions, and an escalating demand for the limited supply of the existing health workforce. This crisis detrimentally affects the quality of patient care, contributing to long wait times, decreased patient satisfaction, and a heightened frequency of patient safety incidents and medical errors. In response to the heightened demand, healthcare organizations are proactively exploring solutions to retain their workforce. With women comprising over 70% of health human resources, this study seeks to gain insight into the unique experiences of women health professionals on the frontlines of healthcare and develop a conceptual framework aimed at facilitating organizations in effectively supporting the retention and advancement of women in healthcare frontline roles. We used grounded theory in this qualitative study. From January 2023 to May 2023, we conducted individual semi-structured interviews with 27 frontline HCWs working in Canada and representing diverse backgrounds. The data underwent thematic analysis, which involved identifying and comprehending recurring patterns across the information to elucidate emerging themes. Our analysis found that organizational, professional, and personal factors shape women's intentions to leave the frontline workforce. Reevaluating organizational strategies related to workforce, fostering a positive work culture, and building the capacity of management to create supportive work environment can collectively transform the work environment. By creating conditions that enable women to perform effectively and find satisfaction in their professional roles, organizations can enhance their ability to retain valuable talent.

Phosphate is associated with frailty in older patients with chronic kidney disease not on dialysis.

PURPOSE: Frailty is common in older patients with chronic kidney disease (CKD) and has been considered an independent risk factor for adverse clinical outcomes in this population. CKD-associated mineral and bone metabolism (CKD-MBD) increases energy expenditure and causes malnutrition and inflammation leading to frailty. We investigated whether CKD-MBD markers and energy metabolism are associated with frailty in patients with advanced CKD on conservative management. METHODS: In this cross-sectional study, we investigated factors associated with frailty in a sample of 75 patients ≥ 65 years, with stage 4 or 5 CKD. Collected data included age, sex, body mass index, physical activity status, educational level, Charlson Comorbidity Index, and laboratory markers. Frailty was evaluated according to Fried's classification. RESULTS: Frailty was observed in 51.3% and pre-frailty in 47.3%. The frail population was significantly older, with a high proportion of females, more inactive, had lower educational levels, spent a long time sitting throughout the day, and had higher phosphate and fibroblast growth factor 21 (FGF-21). In the multivariate logistic analysis age (odds ratio 1.13, p = 0.026) and phosphate (odds ratio 3.38, p = 0.021) remained independently associated with frailty. CONCLUSION: Serum phosphate seems to be a toxin associated with the frailty phenotype in older patients with CKD. Whether strategies to decrease serum phosphate would reduce the risk of frailty in this population deserves further evaluation.

Operations Research to Solve Kidney Allocation Problems: A Systematic Review.

BACKGROUND: Operations research techniques enable health care administrators to optimize resource allocation and to find solutions to staff and patient scheduling problems. We aimed to conduct the first systematic review of the international literature on the use of operations research for allocating deceased-donor kidneys. METHODS: We searched the MEDLINE, EMBASE, and PubMed databases from inception to February 2023. Two reviewers independently screened the title/abstract and subsequently the full text of potentially eligible articles and abstracted the data. Quality assessment of the final set of studies was conducted using Subben's checklist. RESULTS: Of the 302 citations identified, 5 studies were included. These studies covered three themes, including (1) provider-facing decision aids to determine the timing of transplant for single or multiple patients; (2) system-level planning on kidney allocation based on blood type matching rules; and (3) patient-facilitated wait times estimation using incomplete information. Markov models, sequential stochastic assignment models, and queuing models were amongst the most used techniques. Although we found all included studies to meet Subben's criteria, we believe the checklist in its current form lacks items to assess the validity of model inferences. As such, we ended this review with a set of practical recommendations. CONCLUSIONS: Our review demonstrated the utility of operations research techniques in assisting the system, healthcare providers, and patients in the transplantation process. More research is needed to reach a consensus on a model that can be used to support the decision-making of different stakeholders for efficient kidney allocation, with the ultimate goal of reducing the gap between kidney supply and demand and enhancing the population's well-being.

Critical appraisal and comparison of recommendations of clinical practice guidelines for the treatment of schizophrenia in children and adolescents: a methodological survey.

INTRODUCTION: The production of clinical practice guidelines (CPGs) has grown in the past years. Notwithstanding, the quality of these documents and their recommendations for the treatment of schizophrenia in children and adolescents is still unknown. OBJECTIVE: To assess the quality of the guidelines and recommendations for the treatment of schizophrenia in this population. METHODS: CPGs from 2004 to December 2020 were identified through a systematic search on EMBASE, MEDLINE, PsycINFO, PubMed, Epistemonikos, VHL, Global Index Medicus and specific CPG databases. The CPGs' quality was independently assessed by three reviewers using AGREE II and they were considered of high quality if they scored ≥60% in domains 3 and 6. The evidence classification systems were described, the quality of recommendations was assessed in pairs using AGREE-REX and the recommendations were compared. RESULTS: The database search retrieved 3182 results; 2030 were screened and 29 were selected for full-text reading. Four guidelines were selected for extraction. Two CPGs were considered of high quality in the AGREE II assessment. We described the commonly agreed recommendations for each treatment phase. The pharmacological recommendations were described in all treatment phases. Scores of AGREE-REX were lower for psychosocial recommendations. CONCLUSION: There are still few clinical studies and CPGs regarding schizophrenia in children and adolescents. The quality of the documents was overall low, and the quality of the recommendations report has much to improve. There is also a lack of transparency about the quality of the evidence and the strength of the recommendations. PROTOCOL REGISTRATION NUMBER: CRD42020164899.

GRADE concept paper 2: Concepts for judging certainty on the calibration of prognostic models in a body of validation studies.

BACKGROUND: Prognostic models combine several prognostic factors to provide an estimate of the likelihood (or risk) of future events in individual patients, conditional on their prognostic factor values. A fundamental part of evaluating prognostic models is undertaking studies to determine whether their predictive performance, such as calibration and discrimination, is reproduced across settings. Systematic reviews and meta-analyses of studies evaluating prognostic models' performance are a necessary step for selection of models for clinical practice and for testing the underlying assumption that their use will improve outcomes, including patient's reassurance and optimal future planning. METHODS: In this paper, we highlight key concepts in evaluating the certainty of evidence regarding the calibration of prognostic models. RESULTS AND CONCLUSION: Four concepts are key to evaluating the certainty of evidence on prognostic models' performance regarding calibration. The first concept is that the inference regarding calibration may take one of two forms: deciding whether one is rating certainty that a model's performance is satisfactory or, instead, unsatisfactory, in either case defining the threshold for satisfactory (or unsatisfactory) model performance. Second, inconsistency is the critical GRADE domain to deciding whether we are rating certainty in the model performance being satisfactory or unsatisfactory. Third, depending on whether one is rating certainty in satisfactory or unsatisfactory performance, different patterns of inconsistency of results across studies will inform ratings of certainty of evidence. Fourth, exploring the distribution of point estimates of observed to expected ratio across individual studies, and its determinants, will bear on the need for and direction of future research.

Machine learning for predicting long-term kidney allograft survival: a scoping review.

Supervised machine learning (ML) is a class of algorithms that "learn" from existing input-output pairs, which is gaining popularity in pattern recognition for classification and prediction problems. In this scoping review, we examined the use of supervised ML algorithms for the prediction of long-term allograft survival in kidney transplant recipients. Data sources included PubMed, the Cumulative Index to Nursing and Allied Health Literature, and the Institute for Electrical and Electronics Engineers (IEEE) Xplore libraries from inception to November 2019. We screened titles and abstracts and potentially eligible full-text reports to select studies and subsequently abstracted the data. Eleven studies were identified. Decision trees were the most commonly used method (n = 8), followed by artificial neural networks (ANN) (n = 4) and Bayesian belief networks (n = 2). The area under receiver operating curve (AUC) was the most common measure of discrimination (n = 7), followed by sensitivity (n = 5) and specificity (n = 4). Model calibration examining the reliability in risk prediction was performed using either the Pearson r or the Hosmer-Lemeshow test in four studies. One study showed that logistic regression had comparable performance to ANN, while another study demonstrated that ANN performed better in terms of sensitivity, specificity, and accuracy, as compared with a Cox proportional hazards model. We synthesized the evidence related to the comparison of ML techniques with traditional statistical approaches for prediction of long-term allograft survival in patients with a kidney transplant. The methodological and reporting quality of included studies was poor. Our study also demonstrated mixed results in terms of the predictive potential of the models.

Dialysis Initiation and All-Cause Mortality Among Incident Adult Patients With Advanced CKD: A Meta-analysis With Bias Analysis.

RATIONALE & OBJECTIVES: Due to unmeasured confounding, observational studies have limitations when assessing whether dialysis initiation reduces mortality compared with conservative therapy among adults with advanced chronic kidney disease (CKD). We addressed this issue in this meta-analysis. STUDY DESIGN: Meta-analysis with bias analysis for unmeasured confounding. SETTING & STUDY POPULATION: Adults with stage 4 or 5 CKD who had initiated dialysis or conservative treatment. SELECTION CRITERIA FOR STUDIES: Prospective or retrospective cohort studies comparing survival of dialysis versus conservatively managed patients were searched on MEDLINE and Embase from January 2009 to March 20, 2019. DATA EXTRACTION: HRs of all-cause mortality associated with dialysis initiation compared with conservative treatment. ANALYTICAL APPROACH: We pooled HRs using a random-effects model. We estimated the percentage of effect sizes more protective than HRs of 0.80 and severity of unmeasured confounding that could reduce this percentage to only 10%. Subgroup analysis was performed for studies with only older patients (aged ≥ 65 years). RESULTS: 12 studies were included that involved 16,609 dialysis patients and 3,691 conservatively managed patients. A random-effects model suggested that dialysis initiation was associated with a mean mortality HR of 0.47 (95% CI, 0.34-0.64), in which 92% (95% CI, 50%-100%) of the true effects were more protective than HRs of 0.80. To reduce the percentage of HRs < 0.80 to 10%, unmeasured confounder(s) would need to be associated with both dialysis initiation and mortality by relative risks of 4.05 (95% CI, 2.39-4.15), which is equivalent to shifting each study's estimated HR by 2.31-fold (95% CI, 1.51-2.36). Restricting studies to include only older patients did not modify the results. LIMITATIONS: Limited number of studies and evidence on the absence of publication bias. CONCLUSIONS: Our findings suggest that dialysis initiation considerably reduces mortality among adults with advanced CKD. Future bias-adjusted meta-analyses need to assess outcomes beyond mortality.

Developing trustworthy recommendations as part of an urgent response (1-2 weeks): a GRADE concept paper.

OBJECTIVES: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields. STUDY DESIGN AND SETTING: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group. RESULTS: A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan. CONCLUSION: An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest.

Cost-effectiveness of Deceased-donor Renal Transplant Versus Dialysis to Treat End-stage Renal Disease: A Systematic Review.

Deceased-donor renal transplant (DDRT) is an expensive and potentially risky health intervention with the prospect of improved life and lower long-term costs compared with dialysis. Due to the increasing shortage of kidneys and the associated rise of transplantation costs, certain patient groups may not benefit from transplantation in a cost-effective manner compared with dialysis. The objective of this systematic review was to provide a comprehensive synthesis of evidence on the cost-effectiveness of DDRT relative to dialysis to treat adults with end-stage renal disease and patient-, donor-, and system-level factors that may modify the conclusion. A systematic search of articles was conducted on major databases including MEDLINE, Embase, Scopus, EconLit, and the Health Economic Evaluations Database. Eligible articles were restricted to those published in 2001 or thereafter. Two reviewers independently assessed the suitability of studies and excluded studies that focused on recipients with age <18 years old and those of a living-donor or multiorgan transplant. We show that while DDRT is generally a cost-effective treatment relative to dialysis at conventional willingness-to-pay thresholds, a range of drivers including older patient age, comorbidity, and long wait times significantly reduce the benefit of DDRT while escalating healthcare costs. These findings suggest that the performance of DDRT on older patients with comorbidities should be carefully evaluated to avoid adverse results as evidence suggests that it is not cost-effective. Delayed transplantation may reduce the economic benefits of transplant which necessitates targeted policies that aim to shorten wait times. More recent findings have demonstrated that transplantation using high-risk donors may be a cost-effective and promising alternative to dialysis in the face of a lack of organ availability and fiscal constraints. This review highlights key concepts of health economic evaluations and the relevance of cost-effectiveness to inform care and decision-making in renal programs.

Defining ranges for certainty ratings of diagnostic accuracy: a GRADE concept paper.

OBJECTIVE: The objective of the study was to clarify how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) concept of certainty of evidence applies to certainty ratings of test accuracy. STUDY DESIGN AND SETTING: After initial brainstorming with GRADE Working Group members, we iteratively refined and clarified the approaches for defining ranges when assessing the certainty of evidence for test accuracy within a systematic review, health technology assessment, or guideline. RESULTS: Ranges can be defined both for single test accuracy and for comparative accuracy of multiple tests. For systematic reviews and health technology assessments, approaches for defining ranges include some that do not require value judgments regarding downstream health outcomes. Key challenges arise in the context of a guideline that requires ranges for sensitivity and specificity that are set considering possible effects on all critical outcomes. We illustrate possible approaches and provide an example from a systematic review of a direct comparison between two test strategies. CONCLUSIONS: This GRADE concept paper provides a framework for assessing, presenting, and making decisions based on the certainty of evidence for test accuracy. More empirical research is needed to support future GRADE guidance on how to best operationalize the candidate approaches.