Post-operative surveillance for somatotroph, lactotroph and non-functional pituitary adenomas after curative resection: a systematic review.

CONTEXT: Pituitary tumors are the third most common brain tumor and yet there is no standardization of the surveillance schedule and assessment modalities after transsphenoidal surgery. EVIDENCE ACQUISITION: OVID, EMBASE and the Cochrane Library databases were systematically screened from database inception to March 5, 2020. Inclusion and exclusion criteria were designed to capture studies examining detection of pituitary adenoma recurrence in patients 18 years of age and older following surgical resection with curative intent. EVIDENCE SYNTHESIS: A total of 7936 abstracts were screened, with 812 articles reviewed in full text and 77 meeting inclusion criteria for data extraction. A pooled analysis demonstrated recurrence rates at 1 year, 5 years and 10 years for non-functioning pituitary adenomas (NFPA; N = 3533 participants) were 1%, 17%, and 33%, for prolactin-secreting adenomas (PSPA; N = 1295) were 6%, 21%, and 28%, and for growth-hormone pituitary adenomas (GHPA; N = 1257) were 3%, 8% and 13%, respectively. Rates of recurrence prior to 1 year were 0% for NFPA, 1-2% for PSPA and 0% for GHPA. The mean time to disease recurrence for NFPA, PSPA and GHPA were 4.25, 2.52 and 4.18 years, respectively. CONCLUSIONS: This comprehensive review of the literature quantified the recurrence rates for commonly observed pituitary adenomas after transsphenoidal surgical resection with curative intent. Our findings suggest that surveillance within 1 year may be of low yield. Further clinical trials and cohort studies investigating cost-effectiveness of surveillance schedules and impact on quality of life of patients under surveillance will provide further insight to optimize follow-up.

Long-term Follow-up of a Randomized Clinical Trial Comparing Endovascular Revascularization Plus Supervised Exercise With Supervised Exercise Only for Intermittent Claudication.

OBJECTIVE: The goal of this study was to assess the long-term effectiveness of combination therapy for intermittent claudication, compared with supervised exercise only. BACKGROUND: Supervised exercise therapy is recommended as first-line treatment for intermittent claudication by recent guidelines. Combining endovascular revascularization plus supervised exercise shows promising results; however, there is a lack of long-term follow-up. METHODS: The ERASE study is a multicenter randomized clinical trial, including patients between May 2010 and February 2013 with intermittent claudication. Interventions were combination of endovascular revascularization plus supervised exercise (n = 106) or supervised exercise only (n = 106). Primary endpoint was the difference in maximum walking distance at long-term follow-up. Secondary endpoints included differences in pain-free walking distance, ankle-brachial index, quality of life, progression to critical limb ischemia, and revascularization procedures during follow-up. This randomized trial report is based on a post hoc analysis of extended follow-up beyond that of the initial trial. Patients were followed up until 31 July 2017. Data were analyzed according to the intention-to-treat principle. RESULTS: Median long-term follow-up was 5.4 years (IQR 4.9-5.7). Treadmill test was completed for 128/212 (60%) patients. Whereas the difference in maximum walking distance significantly favored combination therapy at 1-year follow-up, the difference at 5-year follow-up was no longer significant (53 m; 99% CI-225 to 331; P = 0.62). No difference in pain-free walking distance, ankle-brachial index, and quality of life was found during long-term follow-up. We found that supervised exercise was associated with an increased hazard of a revascularization procedure during follow-up (HR 2.50; 99% CI 1.27-4.90; P < 0.001). The total number of revascularization procedures (including randomized treatment) was lower in the exercise only group compared to that in the combination therapy group (65 vs 149). CONCLUSIONS: Long-term follow up after combination therapy versus supervised exercise only, demonstrated no significant difference in walking distance or quality of life between the treatment groups. Combination therapy resulted in a lower number of revascularization procedures during follow-up but a higher total number of revascularizations including the randomized treatment. TRIAL REGISTRATION: Netherlands Trial Registry Identifier: NTR2249.

Cost-effectiveness of direct surgery versus preoperative octreotide therapy for growth-hormone secreting pituitary adenomas.

PURPOSE: The objective of this study was to compare the cost-effectiveness of preoperative octreotide therapy followed by surgery versus the standard treatment modality for growth-hormone secreting pituitary adenomas, direct surgery (that is, surgery without preoperative treatment) from a public third-party payer perspective. METHODS: We developed an individual-level state-transition microsimulation model to simulate costs and outcomes associated with preoperative octreotide therapy followed by surgery and direct surgery for patients with growth-hormone secreting pituitary adenomas. Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs [2020 United States (US) Dollars], quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, direct surgery was found to be the dominant strategy as it yielded lower costs and greater health effects (QALYs) compared to preoperative octreotide strategy in the second-order Monte Carlo microsimulation. The ICER was most sensitive to probability of remission following primary therapy and duration of preoperative octreotide therapy. Accounting for joint parameter uncertainty, direct surgery had a higher probability of demonstrating a cost-effective profile compared to preoperative octreotide treatment at 77% compared to 23%, respectively. CONCLUSIONS: Using standard benchmarks for cost-effectiveness in the US ($100,000/QALY), preoperative octreotide therapy followed by surgery may not be cost-effective compared to direct surgery for patients with growth-hormone secreting pituitary adenomas but the result is highly sensitive to initial treatment failure and duration of preoperative treatment.

Public Health and Cost Benefits of Successful Reperfusion After Thrombectomy for Stroke.

Background and Purpose- The benefit that endovascular thrombectomy offers to patients with stroke with large vessel occlusions depends strongly on reperfusion grade as defined by the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Our aim was to determine the lifetime health and cost consequences of the quality of reperfusion for patients, healthcare systems, and society. Methods- A Markov model estimated lifetime quality-adjusted life years (QALY) and lifetime costs of endovascular thrombectomy-treated patients with stroke based on eTICI grades. The analysis was performed over a lifetime horizon in a United States setting, adopting healthcare and societal perspectives. The reference case analysis was conducted for stroke at 65 years of age. National health and cost consequences of improved eTICI 2c/3 reperfusion rates were estimated. Input parameters were based on best available evidence. Results- Lifetime QALYs increased for every grade of improved reperfusion (median QALYs for eTICI 0/1: 2.62; eTICI 2a: 3.46; eTICI 2b: 5.42; eTICI 2c: 5.99; eTICI 3: 6.73). Achieving eTICI 3 over eTICI 2b reperfusion resulted on average in 1.31 incremental QALYs as well as healthcare and societal cost savings of $10 327 and $20 224 per patient. A 10% increase in the eTICI 2c/3 reperfusion rate of all annually endovascular thrombectomy-treated patients with stroke in the United States is estimated to yield additional 3656 QALYs and save $21.0 million and $36.8 million for the healthcare system and society, respectively. Conclusions- Improved reperfusion grants patients with stroke additional QALYs and leads to long-term cost savings. Procedural strategies to achieve complete reperfusion should be assessed for safety and feasibility, even when initial reperfusion seems to be adequate.

Management of Reducible Ventral Hernias: Clinical Outcomes and Cost-effectiveness of Repair at Diagnosis Versus Watchful Waiting.

OBJECTIVE: To compare long-term clinical and economic outcomes associated with 3 management strategies for reducible ventral hernia: repair at diagnosis (open or laparoscopic) and watchful waiting. BACKGROUND: There is variability in ventral hernia management. Recent data suggest watchful waiting is safe; however, long-term clinical and economic outcomes for different management strategies remain unknown. METHODS: We built a state-transition microsimulation model to forecast outcomes for individuals with reducible ventral hernia, simulating a cohort of 1 million individuals for each strategy. We derived cohort characteristics (mean age 58 years, 63% female), hospital costs, and perioperative mortality from the Nationwide Inpatient Sample (2003-2011), and additional probabilities, costs, and utilities from the literature. Outcomes included prevalence of any repair, emergent repair, and recurrence; lifetime costs; quality-adjusted life years (QALYs); and incremental cost-effectiveness ratios. We performed stochastic and probabilistic sensitivity analyses to identify parameter thresholds that affect optimal management, using a willingness-to-pay threshold of $50,000/QALY. RESULTS: With watchful waiting, 39% ultimately required repair (14% emergent) and 24% recurred. Seventy per cent recurred with repair at diagnosis. Laparoscopic repair at diagnosis was cost-effective compared with open repair at diagnosis (incremental cost-effectiveness ratio $27,700/QALY). The choice of operative strategy (open vs laparoscopic) was sensitive to cost and postoperative quality of life. When perioperative mortality exceeded 5.2% or yearly recurrence exceeded 19.2%, watchful waiting became preferred. CONCLUSIONS: Ventral hernia repair at diagnosis is very cost-effective. The choice between open and laparoscopic repair depends on surgical costs and postoperative quality of life. In patients with high risk of perioperative mortality or recurrence, watchful waiting is preferred.

Cost-effectiveness of Endovascular Therapy for Acute Ischemic Stroke: A Systematic Review of the Impact of Patient Age.

Purpose To determine the impact of patient age on the cost-effectiveness of endovascular therapy (EVT) in addition to standard care (SC) in large-vessel-occlusion stroke for patients aged 50 to 100 years in the United States. Materials and Methods A decision-analytic Markov model was used to estimate direct and indirect lifetime costs and quality-adjusted life years (QALYs). Age-dependent input parameters were obtained from the literature. Deterministic and probabilistic sensitivity analysis for age at index stroke were used. The willingness-to-pay (WTP) was set to thresholds of $50 000, $100 000, and $150 000 per QALY. The study applied a U.S. setting for health care and societal perspectives. Incremental costs and effectiveness were derived from deterministic and probabilistic sensitivity analysis. Acceptability rates at different WTP thresholds were determined. Results EVT+SC was the dominant strategy in patients aged 50 to 79 years. The highest incremental effectiveness (2.61 QALYs) and cost-savings (health care perspective, $99 555; societal perspective, $146 385) were obtained in 50-year-old patients. In octogenarians (80-89 years), EVT+SC led to incremental QALYs at incremental costs with acceptability rates of more than 85%, more than 99%, and more than 99% at a WTP of $50 000, $100 000, and $150 000 per QALY, respectively. In nonagenarians (90-99 years), acceptability rates at a WTP of $50 000 per QALY dropped but stayed higher than 85% and higher than 95% at thresholds of $100 000 and $150 000 per QALY. Conclusion Using contemporary willingness-to-pay thresholds in the United States, endovascular therapy in addition to standard care reduces lifetime costs for patients up to 79 years of age and is cost-effective for patients aged 80 to 100 years.

To share or not to share? Expected pros and cons of data sharing in radiological research.

The aims of this paper are to illustrate the trend towards data sharing, i.e. the regulated availability of the original patient-level data obtained during a study, and to discuss the expected advantages (pros) and disadvantages (cons) of data sharing in radiological research. Expected pros include the potential for verification of original results with alternative or supplementary analyses (including estimation of reproducibility), advancement of knowledge by providing new results by testing new hypotheses (not explored by the original authors) on pre-existing databases, larger scale analyses based on individual-patient data, enhanced multidisciplinary cooperation, reduced publication of false studies, improved clinical practice, and reduced cost and time for clinical research. Expected cons are outlined as the risk that the original authors could not exploit the entire potential of the data they obtained, possible failures in patients' privacy protection, technical barriers such as the lack of standard formats, and possible data misinterpretation. Finally, open issues regarding data ownership, the role of individual patients, advocacy groups and funding institutions in decision making about sharing of data and images are discussed. KEY POINTS: • Regulated availability of patient-level data of published clinical studies (data-sharing) is expected. • Expected benefits include verification/advancement of knowledge, reduced cost/time of research, clinical improvement. • Potential drawbacks include faults in patients' identity protection and data misinterpretation.

Bosniak Classification for Complex Renal Cysts Reevaluated: A Systematic Review.

PURPOSE: We systematically evaluated the Bosniak classification system with malignancy rates of each Bosniak category, and assessed the effectiveness related to surgical treatment and oncologic outcome based on recurrence and/or metastasis. MATERIALS AND METHODS: In a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria, we selected 39 publications for inclusion in this analysis and categorized them into 1) surgical cohorts-all cysts treated surgically and 2) radiological cohorts-cysts with surgical treatment or radiological followup. RESULTS: A total of 3,036 complex renal cysts were categorized into Bosniak II, IIF, III and IV. In surgical and radiological cohorts pooled estimates showed a malignancy prevalence of 0.51 (0.44, 0.58) in Bosniak III and 0.89 (0.83, 0.92) in Bosniak IV cysts, respectively. Stable Bosniak IIF cysts showed a malignancy rate of less than 1% during radiological followup (surveillance). Bosniak IIF cysts, which showed reclassification to the Bosniak III/IV category during radiological followup (12%), showed malignancy in 85%, comparable to Bosniak IV cysts. The estimated surgical number needed to treat to avoid metastatic disease of Bosniak III and IV cysts was 140 and 40, respectively. CONCLUSIONS: The effectiveness of the Bosniak classification system for complex renal cysts was high in categories II, IIF and IV, but low in category III, and 49% of Bosniak III cysts was overtreated because of a benign outcome. This surgical overtreatment combined with the excellent outcome for Bosniak III cysts may suggest that surveillance is a rational alternative to surgery. This will require further study to assess whether surveillance of Bosniak III cysts will prove safe.

Different Imaging Strategies in Patients With Possible Basilar Artery Occlusion: Cost-Effectiveness Analysis.

BACKGROUND AND PURPOSE: This study evaluated the cost-effectiveness of different noninvasive imaging strategies in patients with possible basilar artery occlusion. METHODS: A Markov decision analytic model was used to evaluate long-term outcomes resulting from strategies using computed tomographic angiography (CTA), magnetic resonance imaging, nonenhanced CT, or duplex ultrasound with intravenous (IV) thrombolysis being administered after positive findings. The analysis was performed from the societal perspective based on US recommendations. Input parameters were derived from the literature. Costs were obtained from United States costing sources and published literature. Outcomes were lifetime costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and net monetary benefits, with a willingness-to-pay threshold of $80,000 per QALY. The strategy with the highest net monetary benefit was considered the most cost-effective. Extensive deterministic and probabilistic sensitivity analyses were performed to explore the effect of varying parameter values. RESULTS: In the reference case analysis, CTA dominated all other imaging strategies. CTA yielded 0.02 QALYs more than magnetic resonance imaging and 0.04 QALYs more than duplex ultrasound followed by CTA. At a willingness-to-pay threshold of $80,000 per QALY, CTA yielded the highest net monetary benefits. The probability that CTA is cost-effective was 96% at a willingness-to-pay threshold of $80,000/QALY. Sensitivity analyses showed that duplex ultrasound was cost-effective only for a prior probability of ≤0.02 and that these results were only minimally influenced by duplex ultrasound sensitivity and specificity. Nonenhanced CT and magnetic resonance imaging never became the most cost-effective strategy. CONCLUSIONS: Our results suggest that CTA in patients with possible basilar artery occlusion is cost-effective.

A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users.

We systematically investigated how 11 overlapping meta-analyses on the association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel could yield contradictory outcomes. The results of the meta-analyses differed because more recent meta-analyses included more primary studies and some had not included conference abstracts. Conclusions differed because between-study heterogeneity and publication bias were handled differently across meta-analyses. All meta-analyses on the clinical end point observed significant heterogeneity and several reported evidence for publication bias, but only one out of eight statistically significant meta-analyses concluded that therefore the association was unproven and one other refrained from quantifying a pooled estimate because of heterogeneity. For the end point stent thrombosis, all meta-analyses reported statistically significant associations with CYP2C19 loss-of-function alleles with no statistically significant evidence for heterogeneity, but only three had investigated publication bias and also found evidence for it. One study therefore concluded that there was no evidence for an association, and one other doubted the association because of a high level of heterogeneity. In summary, meta-analyses on the association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel differed widely with regard to assessment and interpretation of heterogeneity and publication bias. The substantial heterogeneity and publication bias implies that personalized antiplatelet management based on genotyping is not supported by the currently available evidence.Genet Med advance online publication 19 June 2014.

The Cost-Effectiveness of Cognitive-Behavioral Group Training for Patients with Unexplained Physical Symptoms.

OBJECTIVE: The aim of the study was to evaluate the cost-effectiveness of a cognitive-behavioral group training compared with a wait-list control for patients with unexplained physical symptoms (UPS). METHODS: A probabilistic decision-analytic Markov model was developed with three health states (poor health, average health, and death) based on a cutoff score of the Physical Component Summary of the short-form 36 health survey. To assess the cost-effectiveness in terms of cost per quality-adjusted life-year (QALY), a societal perspective was adopted. The model consisted of cycles of 3 months and a time horizon of 4 years. Data for the model were derived from a randomized controlled trial, in which 162 patients with UPS were randomized either to cognitive-behavioral group training or to the wait-list control. Data were assessed at baseline and after the training of 3 months or after a wait-list period of 3 months. In addition, the training group was followed in an uncontrolled phase and assessed at 3 months and 1 year after the training. RESULTS: After 4 years, the group training was in terms of cost-effectiveness "dominant" compared with the wait-list control; there was a positive effect of 0.06 QALYs and a €828 reduction in costs. The cost-effectiveness improved with a longer time horizon. A threshold of €30,000/QALY was passed after 18 months. The group training was cost saving after 33 months. CONCLUSIONS: Cognitive-behavioral group training is a cost-effective treatment compared with the wait-list control for patients with UPS.

Can magnetic resonance imaging at 3.0-Tesla reliably detect patients with endometriosis? Initial results.

AIM: The aim of this study was to determine whether an optimized 3.0-Tesla magnetic resonance imaging (MRI) protocol is sensitive and specific enough to detect patients with endometriosis. MATERIAL AND METHODS: This was a prospective cohort study with consecutive patients. Forty consecutive patients with clinical suspicion of endometriosis underwent 3.0-Tesla MRI, including a T2-weighted high-resolution fast spin echo sequence (spatial resolution=0.75 ×1.2 ×1.5 mm³) and a 3D T1-weighted high-resolution gradient echo sequence (spatial resolution=0.75 ×1.2 × 2.0 mm³). Two radiologists reviewed the dataset with consensus reading. During laparoscopy, which was used as reference standard, all lesions were characterized according to the revised criteria of the American Fertility Society. Patient-level and region-level sensitivities and specificities and lesion-level sensitivities were calculated. RESULTS: Patient-level sensitivity was 42% for stage I (5/12) and 100% for stages II, III and IV (25/25). Patient-level specificity for all stages was 100% (3/3). The region-level sensitivity and specificity was 63% and 97%, respectively. The sensitivity per lesion was 61% (90% for deep lesions, 48% for superficial lesions and 100% for endometriomata). The detection rate of obliteration of the cul-the-sac was 100% (10/10) with no false positive findings. The interreader agreement was substantial to perfect (kappa=1 per patient, 0.65 per lesion and 0.71 for obliteration of the cul-the-sac). CONCLUSIONS: An optimized 3.0-Tesla MRI protocol is accurate in detecting stage II to stage IV endometriosis.

Clinical examination versus magnetic resonance imaging in the pretreatment staging of cervical carcinoma: systematic review and meta-analysis.

OBJECTIVES: To review the literature on the diagnostic performance of clinical examination and magnetic resonance imaging (MRI) in detecting parametrial invasion and advanced stage disease (FIGO stage ≥ IIB) in patients with cervical carcinoma. METHODS: Reports of studies were searched using the MEDLINE, EMBASE and Cochrane databases. Two observers reported on data relevant for analysis and methodological quality using the QUADAS scoring system. Publication bias was analysed using Deeks funnel plots. Covariates were added to the model to study the influence on the summary results of the technical and methodological aspects of the clinical examination and MRI. RESULTS: In total, 3,254 patients were included. Partial verification bias was often encountered. Pooled sensitivity was 40 % (95 % CI 25-58) for the evaluation of parametrial invasion with clinical examination and 84 % (95 % CI 76-90) with MRI, 53 % (95 % CI 41-66) for the evaluation of advanced disease with clinical examination, and 79 % (95 % CI 64-89) with MRI. Pooled specificities were comparable between clinical examination and MRI. Different technical aspects of MRI influenced the summary results. CONCLUSIONS: MRI is significantly better than clinical examination in ruling out parametrial invasion and advanced disease in patients with cervical carcinoma. KEY POINTS: • MRI has a higher sensitivity than clinical examination for staging cervical carcinoma. • Clinical examination and MRI have comparably high specificity for staging cervical carcinoma. • Quality of clinical examination studies was lower than that of MRI studies. • The use of newer MRI techniques positively influences the summary results. • Anaesthesia during clinical examination positively influences the summary results.

Imaging strategies for acute chest pain in the emergency department.

OBJECTIVE: Echocardiography, radionuclide myocardial perfusion imaging (MPI), and coronary CT angiography (CTA) are the three main imaging techniques used in the emergency department for the diagnosis of acute coronary syndrome (ACS). The purpose of this article is to quantitatively examine existing evidence about the diagnostic performance of these imaging tests in this setting. CONCLUSION: Our systematic search of the medical literature showed no significant difference between the modalities for the detection of ACS in the emergency department. There was a slight, positive trend favoring coronary CTA. Given the absence of large differences in diagnostic performance, practical aspects such as local practice, expertise, medical facilities, and individual patient characteristics may be more important.

Cost-effectiveness of postoperative imaging surveillance strategies for nonfunctional pituitary adenomas after resection with curative intent.

OBJECTIVE: The aim of this study was to determine an optimal follow-up imaging surveillance strategy in terms of cost-effectiveness after resection of nonfunctioning pituitary adenomas with curative intent. METHODS: An individual-level state-transition microsimulation model was used to simulate costs and outcomes associated with three postoperative imaging strategies over a lifetime time horizon: 1) annual MRI surveillance, 2) tapered MRI surveillance (annual surveillance for 5 years followed by surveillance every 2 years), and 3) personalized surveillance (annual surveillance for 5 years followed by surveillance every 2 years when MRI shows remnant disease/postoperative changes, and surveillance at 7, 10, and 15 years for disease-free MRI). Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually. Model outcomes included lifetime costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, annual surveillance yielded higher costs and lower health effects (QALYs) compared with the tapered and personalized surveillance strategies (dominated). Personalized surveillance demonstrated an additional 0.1 QALY at additional cost ($1298) compared with tapered surveillance (7.7 QALYs at a cost of $12,862). The ICER was $11,793/QALY. The optimal decision was most sensitive to the probability of postoperative changes on MRI after surgery and MRI cost. Accounting for parameter uncertainty, personalized surveillance had a higher probability of being a cost-effective surveillance option compared with the alternative strategies at 79%. CONCLUSIONS: Using standard cost-effectiveness thresholds in the US ($100,000/QALY), personalized surveillance that accounted for remnant disease or postoperative changes on MRI was cost-effective compared with alternative surveillance strategies.

Burden of atherosclerosis improves the prediction of coronary heart disease but not cerebrovascular events: the Rotterdam Study.

AIMS: Since atherosclerosis is a systemic process, risk prediction would benefit from targeting multiple components of cardiovascular disease simultaneously. To this end, it is useful to examine the predictive value of non-invasive measures of atherosclerosis in various vascular beds for both coronary heart disease (CHD) and cerebrovascular disease. METHODS AND RESULTS: Between September 2003 and February 2006, 2153 asymptomatic participants (69.6±6.6 years) from the Rotterdam Study underwent a multi-detector computed tomography scan. During a median follow-up of 3.5 years, 58 CHD events (myocardial infarction and CHD death) and 52 cerebrovascular events (TIA and stroke) occurred. Participants were classified into low (<5%), intermediate (5-10%), and high (>10%) 5-year risk categories based on a refitted Framingham risk model. The model was extended by coronary, aortic arch, or carotid calcium and reclassification percentages were calculated. For the outcome CHD, the C-statistic improved from 0.693 for the Framingham refitted model to 0.743, 0.740, and 0.749 by addition of coronary, aortic arch, and carotid calcium, respectively. Reclassification was most substantial in the intermediate risk group where addition of coronary calcium reclassified 56% of persons [net reclassification improvement (NRI): 15%; P<0.01)]. Adding aortic arch calcium led to a reclassification of 32% of persons (NRI: 8%; P=0.01) and adding carotid calcium reclassified 51% (NRI: 9%; P=0.02). In contrast, calcification in any of the three vascular beds did not improve cerebrovascular risk prediction. CONCLUSION: Coronary, aortic arch, and carotid artery calcification significantly improved risk prediction of CHD but not of cerebrovascular events.

Is positive affect associated with survival? A population-based study of elderly persons.

Study results on the association of positive affect with survival are conflicting. This disagreement potentially arises from poor control for health or negative affect and for the various age groups studied. The authors examined if positive affect predicts survival; whether this association is preserved after controlling for negative affect, socioeconomic status, lifestyle, and health; and whether this association varies with age. The study is set within the population-based Rotterdam Study (1997-2007) and included 4,411 participants aged 61 years or older, followed for on average 7.19 (standard deviation = 2.20) years. Positive affect was not consistently associated with survival across all ages. A significant interaction of positive affect with age on survival (P = 0.02) was found. Subsequent age stratification revealed that positive affect independently predicted survival in elderly persons aged <80 years (per affect score, hazard ratio = 0.96, 95% confidence interval: 0.93, 0.99) but not in those aged ≥80 years in fully adjusted models (hazard ratio = 1.00, 95% confidence interval: 0.96, 1.04). In the oldest old, the association was partly explained by differences in baseline health. In conclusion, the results suggest that there may be an association of positive affect with survival in the younger and middle old but not in the oldest old in whom perception of positive affect is more likely to be determined by health.

Evidence-Based Medicine in Otolaryngology, Part XI: Modeling and Analysis to Support Decisions.

OBJECTIVE: To provide a resource to educate clinical decision makers about the analyses and models that can be employed to support data-driven choices. DATA SOURCES: Published studies and literature regarding decision analysis, decision trees, and models used to support clinical decisions. REVIEW METHODS: Decision models provide insights into the evidence and its implications for those who make choices about clinical care and resource allocation. Decision models are designed to further our understanding and allow exploration of the common problems that we face, with parameters derived from the best available evidence. Analysis of these models demonstrates critical insights and uncertainties surrounding key problems via a readily interpretable yet quantitative format. This 11th installment of the Evidence-Based Medicine in Otolaryngology series thus provides a step-by-step introduction to decision models, their typical framework, and favored approaches to inform data-driven practice for patient-level decisions, as well as comparative assessments of proposed health interventions for larger populations. CONCLUSIONS: Information to support decisions may arise from tools such as decision trees, Markov models, microsimulation models, and dynamic transmission models. These data can help guide choices about competing or alternative approaches to health care. IMPLICATIONS FOR PRACTICE: Methods have been developed to support decisions based on data. Understanding the related techniques may help promote an evidence-based approach to clinical management and policy.

Cost-effectiveness of a hybrid emergency room system for severe trauma: a health technology assessment from the perspective of the third-party payer in Japan.

BACKGROUND: Hybrid emergency room (ER) systems, consisting of an angiography-computed tomography (CT) machine in a trauma resuscitation room, are reported to be effective for reducing death from exsanguination in trauma patients. We aimed to investigate the cost-effectiveness of a hybrid ER system in severe trauma patients without severe traumatic brain injury (TBI). METHODS: We conducted a cost-utility analysis comparing the hybrid ER system to the conventional ER system from the perspective of the third-party healthcare payer in Japan. A short-term decision tree and a long-term Markov model using a lifetime time horizon were constructed to estimate quality-adjusted life years (QALYs) and associated lifetime healthcare costs. Short-term mortality and healthcare costs were derived from medical records and claims data in a tertiary care hospital with a hybrid ER. Long-term mortality and utilities were extrapolated from the literature. The willingness-to-pay threshold was set at $47,619 per QALY gained and the discount rate was 2%. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The hybrid ER system was associated with a gain of 1.03 QALYs and an increment of $33,591 lifetime costs compared to the conventional ER system, resulting in an ICER of $32,522 per QALY gained. The ICER was lower than the willingness-to-pay threshold if the odds ratio of 28-day mortality was < 0.66. Probabilistic sensitivity analysis indicated that the hybrid ER system was cost-effective with a 79.3% probability. CONCLUSION: The present study suggested that the hybrid ER system is a likely cost-effective strategy for treating severe trauma patients without severe TBI.

Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands.

BACKGROUND: The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population. METHODS: A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs. RESULTS: EVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs. CONCLUSION: One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs.