Malnutrition risk, outcomes, and costs among older adults undergoing elective surgical procedures: A retrospective cohort study.

BACKGROUND: We examine here the association between malnutrition risk and adverse health outcomes among older adult patients undergoing elective surgical procedures. METHODS: We conducted a retrospective study using linked clinical and administrative databases. Malnutrition risk was assessed prior to surgery, defined by unintentional weight loss and decreased food intake. We performed a logistic regression analysis of the primary outcome, a composite adverse outcome measure, including death, bleeding, pneumonia, and other surgical complications. We conducted Fine-Gray proportional hazard regression analysis of hospital length of stay (LOS). We performed a generalized linear regression analysis of in-hospital cost data. All regression analyses controlled for frailty, age, sex, surgical category, and comorbidities. RESULTS: Of a total of 3457 older adult elective surgical patients (65-102 years), 310 (9.0%) screened positive for malnutrition risk. In multivariable regression analyses, malnutrition risk was associated with an increased risk of the composite adverse outcome (odds ratio [OR] = 1.74; 95% CI = 1.25-2.39), higher hospitalization costs (relative cost = 1.84; 95% CI = 1.59-2.13), and a decreased risk of discharge from the hospital (hazard ratio = 0.67; 95% CI = 0.59-0.77) compared with those who screened negative. CONCLUSION: Older adult patients with malnutrition risk were at an increased risk of adverse surgical outcomes, had longer LOS in the hospital, and incurred higher costs of care. It is important to screen for malnutrition risk and refer older adults for dietetic consults prior to elective surgery.

Measurement and prognosis of frail patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis.

OBJECTIVES: Our objectives were to review the literature to identify frailty instruments in use for transcatheter aortic valve implantation (TAVI) recipients and synthesise prognostic data from these studies, in order to inform clinical management of frail patients undergoing TAVI. METHODS: We systematically reviewed the literature published in 2006 or later. We included studies of patients with aortic stenosis, diagnosed as frail, who underwent a TAVI procedure that reported mortality or clinical outcomes. We categorised the frailty instruments and reported on the prevalence of frailty in each study. We summarised the frequency of clinical outcomes and pooled outcomes from multiple studies. We explored heterogeneity and performed subgroup analysis, where possible. We also used Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to assess the overall certainty of the estimates. RESULTS: Of 49 included studies, 21 used single-dimension measures to assess frailty, 3 used administrative data-based measures, and 25 used multidimensional measures. Prevalence of frailty ranged from 5.67% to 90.07%. Albumin was the most commonly used single-dimension frailty measure and the Fried or modified Fried phenotype were the most commonly used multidimensional measures. Meta-analyses of studies that used either the Fried or modified Fried phenotype showed a 30-day mortality of 7.86% (95% CI 5.20% to 11.70%) and a 1-year mortality of 26.91% (95% CI 21.50% to 33.11%). The GRADE system suggests very low certainty of the respective estimates. CONCLUSIONS: Frailty instruments varied across studies, leading to a wide range of frailty prevalence estimates for TAVI recipients and substantial heterogeneity. The results provide clinicians, patients and healthcare administrators, with potentially useful information on the prognosis of frail patients undergoing TAVI. This review highlights the need for standardisation of frailty measurement to promote consistency. PROSPERO REGISTRATION NUMBER: CRD42018090597.

Is SABR Cost-Effective in Oligometastatic Cancer? An Economic Analysis of the SABR-COMET Randomized Trial.

PURPOSE: The phase 2 randomized study SABR-COMET demonstrated that in patients with controlled primary tumors and 1 to 5 oligometastatic lesions, SABR was associated with improved progression-free survival (PFS) compared with standard of care (SoC), but with higher costs and treatment-related toxicities. The aim of this study was to assess the cost-effectiveness of SABR versus SoC in this setting. METHODS AND MATERIALS: A Markov model was constructed to perform a cost-utility analysis from the Canadian health care system perspective. Utility values and transition probabilities were derived from individual-level data from the SABR-COMET trial. One-way, 2-way, and probabilistic sensitivity analyses were performed. Costs were expressed in 2018 CAD. A separate analysis based on US payer's perspective was performed. An incremental cost-effectiveness ratio (ICER) at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was used. RESULTS: In the base case scenario, SABR was cost-effective at an ICER of $37,157 per QALY gained. This finding was most sensitive to the number of metastatic lesions treated with SABR (ICER: $28,066 per QALY for 2, increasing to $64,429 per QALY for 5), difference in chemotherapy use (ICER: $27,173-$53,738 per QALY), and PFS hazard ratio (HR) between strategies (ICER: $31,548-$53,273 per QALY). Probabilistic sensitivity analysis revealed that SABR was cost-effective in 97% of all iterations. Two-way sensitivity analysis demonstrated a nonlinear relationship between the number of lesions and the PFS HR. To maintain cost-effectiveness for each additional metastasis, the HR must decrease by approximately 0.047. The US cost analysis yielded similar results, with an ICER of $54,564 (2018 USD per QALY) for SABR. CONCLUSIONS: SABR is cost-effective for patients with 1 to 5 oligometastatic lesions compared with SoC.

Cost-Effectiveness Analysis of Frailty Assessment in Older Patients Undergoing Coronary Artery Bypass Grafting Surgery.

BACKGROUND: In perioperative settings, frailty assessment has been shown to reduce mortality. This study examined the cost effectiveness of frailty assessment among patients aged 65 with coronary artery disease under consideration for coronary artery bypass grafting surgery. METHODS: A combined decision tree and Markov model was developed to estimate costs and quality-adjusted life years (QALYs) over a 21-year time horizon. Clinical parameters were obtained from published literature. Utilities were derived from the literature and the Canadian Community Health Survey. Costs were obtained from the Ontario fee schedule and published literature. Sensitivity and scenario analyses were conducted to assess the robustness of the results. Expected value of perfect information (EVPI) analysis was conducted to estimate the value of further research. RESULTS: The frailty assessment initiative had a lower average cost than no frailty assessment ($19,567 compared with $20,062). QALYs with frailty assessment were 0.47 years more than with no frailty assessment. Thus, frailty assessment was dominant compared with no frailty assessment. Results were robust to changes in the input parameters. At a willingness to pay (WTP) threshold of $50,000/QALY, there was 100% probability of frailty assessment being cost-effective, and the EVPI per patient was $0. Scenario and sensitivity analysis showed frailty screening remained cost effective when changing the cohort average age, removing health benefits for nonfrail patients, and using subjective judgement to modify effectiveness parameters. CONCLUSIONS: Frailty assessment may be good value for money. However, limited availability of geriatric consultation services, may hinder implementation. Thus, the estimated benefits of frailty screening may not be achievable in practice.

Antithrombotic treatment after coronary artery bypass graft surgery: systematic review and network meta-analysis.

OBJECTIVE: To assess the effects of different oral antithrombotic drugs that prevent saphenous vein graft failure in patients undergoing coronary artery bypass graft surgery. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, Web of Science, CINAHL, and the Cochrane Library from inception to 25 January 2019. ELIGIBILITY CRITERIA: for selecting studies Randomised controlled trials of participants (aged ≥18) who received oral antithrombotic drugs (antiplatelets or anticoagulants) to prevent saphenous vein graft failure after coronary artery bypass graft surgery. MAIN OUTCOME MEASURES: The primary efficacy endpoint was saphenous vein graft failure and the primary safety endpoint was major bleeding. Secondary endpoints were myocardial infarction and death. RESULTS: This review identified 3266 citations, and 21 articles that related to 20 randomised controlled trials were included in the network meta-analysis. These 20 trials comprised 4803 participants and investigated nine different interventions (eight active and one placebo). Moderate certainty evidence supports the use of dual antiplatelet therapy with either aspirin plus ticagrelor (odds ratio 0.50, 95% confidence interval 0.31 to 0.79, number needed to treat 10) or aspirin plus clopidogrel (0.60, 0.42 to 0.86, 19) to reduce saphenous vein graft failure when compared with aspirin monotherapy. The study found no strong evidence of differences in major bleeding, myocardial infarction, and death among different antithrombotic therapies. The possibility of intransitivity could not be ruled out; however, between-trial heterogeneity and incoherence were low in all included analyses. Sensitivity analysis using per graft data did not change the effect estimates. CONCLUSIONS: The results of this network meta-analysis suggest an important absolute benefit of adding ticagrelor or clopidogrel to aspirin to prevent saphenous vein graft failure after coronary artery bypass graft surgery. Dual antiplatelet therapy after surgery should be tailored to the patient by balancing the safety and efficacy profile of the drug intervention against important patient outcomes. STUDY REGISTRATION: PROSPERO registration number CRD42017065678.

Clinical impact of disinvestment in hydroxyethyl starch for patients undergoing coronary artery bypass surgery: a retrospective observational study.

PURPOSE: To examine the effect of discontinuing hydroxyethyl starch (HES) solutions on length of hospital stay, transfusion, risk of death, acute kidney injury (AKI), and dialysis. METHODS: We conducted a historical cohort study of linked administrative and clinical databases in patients undergoing coronary artery bypass surgery (CABG) on cardiopulmonary bypass. We used propensity scores to match patients who did not receive HES (after discontinuation) with patients exposed to HES (before discontinuation) and also controlled for albumin exposure. Hospital length of stay (the primary outcome) was analyzed using Fine-Gray proportional hazard regression, with hospital discharge as the outcome and death as a competing risk. Adverse outcomes were compared between matched patients using conditional logistic regression. RESULTS: We compared 1,085 propensity score-matched pairs (n = 2,170) from a pool of 2,757 patients. Discontinuation of HES was associated with shorter length of hospital stay, as evidenced by an increased probability of discharge (hazard ratio, 1.24; 95% confidence interval [CI], 1.14 to 1.35) and a reduced risk of red blood cell transfusion (odds ratio [OR], 0.68; 95% CI, 0.55 to 0.84), plasma transfusion (OR, 0.48; 95% CI, 0.34 to 0.66), and platelet transfusion (OR, 0.62; 95% CI, 0.44 to 0.87). Discontinuation of HES was not associated with in-hospital mortality (OR, 0.74; 95% CI, 0.36 to 1.54), AKI (OR, 0.84; 95% CI, 0.57 to 1.25), or dialysis (OR, 0.83; 95% CI, 0.25 to 2.73). CONCLUSIONS: For patients undergoing CABG on cardiopulmonary bypass, discontinuation of HES was associated with reduced hospital length of stay and reduced blood product transfusion, without measurable change in renal failure, dialysis rate, or in-hospital mortality. Our results should be interpreted with caution, though we found no evidence of harms associated with discontinuing HES. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02329158); registered 31 December, 2014.

Bayesian synthesis using prior information on fracture risk from randomized trials to analyze post-market data.

OBJECTIVE: To conduct a Bayesian evidence synthesis using commonly available statistical procedures to estimate fracture risk for postmenopausal women undergoing hormonal therapy for breast cancer. STUDY DESIGN AND SETTING: Using linked administrative data, we conducted a retrospective cohort study of women aged 66 years or older diagnosed with stage I to III breast cancer in Ontario, Canada, between April 1, 2003, and February 28, 2010. We used data augmentation to perform Bayesian Cox regression of the hazard of a hip, spine, or wrist/forearm fracture, adjusting for age, history of fragility fracture, corticosteroid use, osteoporosis, rheumatoid arthritis, dementia, or diabetes diagnoses. RESULTS: Of 10,259 included in the sample, 3,733 initiated on tamoxifen and 6,526 on an aromatase inhibitor. Posterior probabilities that the hazard ratio (HR) exceeded 1 for aromatase inhibitor compared with tamoxifen were 46% (HR = 0.99, 95% credible interval [CrI] 0.71, 1.25), 35% (HR = 0.94, 95% CrI 0.78, 1.26), and 76% (HR = 1.08, 95% CrI 0.88, 1.32) with an uninformative prior, and 63% (HR = 1.04, 95% CrI 0.83, 1.3), 84% (HR = 1.12, 95% CrI 0.89, 1.4), and 89% (HR = 1.13, 95% CrI 0.93, 1.36) with an informative prior, for hip, spine, and wrist/forearm fractures, respectively. CONCLUSIONS: Prior information resulted in higher posterior probabilities. The strength of evidence for increased risk varied by fracture site.

Antithrombotic therapy in patients receiving saphenous vein coronary artery bypass grafts: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: The current evidence for the prevention of saphenous vein graft failure (SVGF) after coronary artery bypass graft (CABG) surgery consists of direct head-to-head comparison of treatments (including placebo) in randomised-controlled trials (RCTs) and observational studies. However, summarising the evidence using traditional pairwise meta-analyses does not allow the inclusion of data from treatments that have not been compared head to head. Exclusion of such comparisons could impact the precision of pooled estimates in a meta-analysis. Hence, to address the challenge of whether aspirin alone or in addition to another antithrombotic agent is a more effective regimen to improve SVG patency, a network meta-analysis (NMA) is necessary. The objectives of this study are to synthesise the available evidence on antithrombotic agents (or their combination) and estimate the treatment effects among direct and indirect treatment comparisons on SVGF and major adverse cardiovascular events, and to generate a treatment ranking according to their efficacy and safety outcomes. METHODS: We will perform a systematic review of RCTs evaluating antithrombotic agents in patients undergoing CABG. A comprehensive English literature search will be conducted using electronic databases and grey literature resources to identify published and unpublished articles. Two individuals will independently and in duplicate screen potential studies, assess the eligibility of potential studies and extract data. Risk of bias and quality of evidence will also be evaluated independently and in duplicate. We will investigate the data to ensure its suitability for NMA, including adequacy of the outcome data and transitivity of treatment effects. We plan to estimate the pooled direct, indirect and the mixed effects for all antithrombotic agents using a NMA. ETHICS AND DISSEMINATION: Due to the nature of the study, there are no ethical concerns nor informed consent required. We anticipate that this NMA will be the first to simultaneously assess the relative effects of multiple antithrombotic agents in patients undergoing CABG. The results of this NMA will inform clinicians, patients and guideline developers the best available evidence on comparative effects benefits of antithrombotic agents after CABG while considering the side effect profile to support future clinical decision-making. We will disseminate the results of our systematic review and NMA through a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017065678.

The Role of Decision Models in Health Care Policy: A Case Study.

BACKGROUND: In 2009, the Centers for Medicare and Medicaid Services (CMS) underwent a National Coverage Determination on computed tomography colonography (CTC) to screen for colorectal cancer. The Cancer Intervention & Surveillance Network developed decision models to inform this decision. The purpose of our study was to investigate the role of models in this decision. METHODS: We performed a descriptive case study. We conducted semistructured telephone interviews with members of the CMS coverage and analysis group (CAG) and Medicare Coverage and Analysis Advisory Committee (MEDCAC) panelists. Informed by previously published literature, we developed a coding scheme to analyze interview transcripts, MEDCAC meeting transcripts, and the final CMS decision memo. RESULTS: Four members of the CAG and 8 MEDCAC panelists were interviewed. The total number of codes across all study documents was 772. We found evidence that decision makers believed in the adequacy of models to inform decision making. In interview transcripts, the code Models Are Adequate to Inform was more frequent than the code Models Are Inadequate to Inform (47 times v. 5). Discussion of model conceptualization dominated the MEDCAC meeting (Model Conceptualization assigned 113 times) and was frequently discussed during interviews (Model Conceptualization assigned 84 times). We also found evidence that the models helped to focus the policy discussion. Across study documents, the codes Focus on Cost, Focus on Clinical-Health Impact, and Focus on Inadequacy of Evidence Base were assigned 99, 98, and 97 times, respectively. CONCLUSIONS: Decision makers involved in the CTC decision believed in the adequacy of models to inform coverage decisions. The model played a role in focusing the CTC coverage policy discussion.

Reducing otolaryngology surgical inefficiency via assessment of tray redundancy.

BACKGROUND: Health care costs in Canada continue to rise. As a result of this relentless increase in healthcare spending, ways to increase efficiency and decrease cost are constantly being sought. Surgical treatment is the mainstay of therapy for many conditions in the field of Otolaryngology- Head and Neck Surgery. The evidence suggests that room exists to optimize tray efficiency as a novel means of improving operating room throughput. METHODS: We conducted a review of instruments on surgical trays for 5 commonly performed procedures between July 5th, 2013 and September 20th, 2013 at St Joseph's Hospital. The Instrument Utilization Rate was calculated; we then designed new 'optimized' trays based on which instruments were used at least 20% of the time. We obtained tray building times from Central Processing Department, then calculated an overall mean time per instrument (to pack the freshly washed instruments). We then determined the time that could be saved by using our new optimized trays. RESULTS: In total, 226 instrument trays were observed (Table 1). The average Instrument Utilization Rate was 27.8% (+/- 13.1). Our optimized trays, on average, reduced tray size by 57%. The average time to pack one instrument was 17.7 seconds. CONCLUSIONS: By selectively reducing our trays, we plan to reduce tray content by an average of 57%. It is important to remember that this number looks at only 5 procedures in the Department of Otolaryngology- Head and Neck Surgery. If this was expanded city-wide to the rest of the departments, the improved efficiency could potentially be quite substantial.

A systematic review and methodological evaluation of published cost-effectiveness analyses of aromatase inhibitors versus tamoxifen in early stage breast cancer.

BACKGROUND: A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs). For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs) of five years of aromatase inhibitors (AI) versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS) but not overall survival (OS) and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. METHODS: We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY). We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. RESULTS: We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. CONCLUSION: Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs. Results of these CEA analyses may be suboptimal for guiding policy.

Cost effectiveness of hepatitis C-related interventions targeting substance users and other high-risk groups: a systematic review.

BACKGROUND AND OBJECTIVE: In developed countries, injection drug users have the highest prevalence and incidence of hepatitis C virus (HCV) infection. Clinicians and policy makers have several options for reducing morbidity and mortality related to HCV infection, including preventing new infections, screening high-risk populations, and optimizing uptake and delivery of antiviral therapy. Cost-effectiveness analyses provide an estimate of the value for money associated with adopting healthcare interventions. Our objective was to determine the cost effectiveness of hepatitis C interventions (prevention, screening, treatment) targeting substance users and other groups with a high proportion of substance users. METHODS: We conducted a systematic search of MEDLINE, EMBASE, CINAHL, HealthSTAR and EconLit, and the grey literature. Studies were critically appraised using the Drummond and Jefferson, Neumann et al. and Philips et al. checklists. We developed and applied a quality appraisal instrument specific to cost-effectiveness analyses of HCV interventions. In addition, we summarized cost-effectiveness estimates using a single currency and year ($US, year 2009 values). RESULTS: Twenty-one economic evaluations were included, which addressed prevention (three), screening (ten) and treatment (eight). The quality of the analyses varied greatly. A significant proportion did not incorporate important aspects of HCV natural history, disease costs and antiviral therapy. Incremental cost-effectiveness ratios (ICERs) ranged from dominant (less costly and more effective) to $US603,352 per QALY. However, many ICERs were less than $US100,000 per QALY. Screening and treatment interventions involving pegylated interferon and ribavirin were generally cost effective at the $US100,000 per QALY threshold, with the exception of some subgroups, such as immune compromised patients with genotype 1 infections. CONCLUSIONS: No clear consensus emerged from the studies demonstrating that prevention, screening or treatment provides better value for money as each approach can be economically attractive in certain subgroups. More high-quality economic evaluations of preventing, identifying and treating HCV infection in substance users are needed.