Pre-discharge prognostic factors of physical function among older adults with hip fracture surgery: a systematic review.

INTRODUCTION: To identify, organize, and assess the evidence level of pre-discharge prognostic factors of physical function beyond discharge after hip fracture surgery. METHODS: We performed a systematic search of four databases (PubMed, Embase, CINAHL, PsycINFO) for longitudinal studies of prognostic factors of physical function at ≥ 1 month among older adults ≥ 50 years old with surgically treated hip fracture, complemented with hand-searching. Two reviewers independently screened papers for inclusion and assessed the quality of all the included papers using the Quality in Prognosis Studies (QUIPS) tool. We assigned the evidence level for each prognostic factor based on consistency in findings and study quality. RESULTS: From 98 papers that met our inclusion criteria, we identified 107 pre-discharge prognostic factors and organized them into the following seven categories: demographic, physical, cognitive, psychosocial, socioeconomic, injury-related, and process of care. Potentially modifiable factors with strong or moderate evidence of an association included total length of stay, physical function at discharge, and grip strength. Factors with strong or moderate evidence of no association included gender, fracture type, and time to surgery. Factors with limited, conflicting, or inconclusive evidence included body-mass index, psychological resilience, depression, and anxiety. CONCLUSIONS: Our findings highlight potentially modifiable prognostic factors that could be targeted and non-modifiable prognostic factors that could be used to identify patients who may benefit from more intensive intervention or to advise patients on their expectations on recovery. Examining the efficacies of existing interventions targeting these prognostic factors would inform future studies and whether any of such interventions could be incorporated into clinical practice.

Chapter 6: assessing applicability of medical test studies in systematic reviews.

Use of medical tests should be guided by research evidence about the accuracy and utility of those tests in clinical care settings. Systematic reviews of the literature about medical tests must address applicability to real-world decision-making. Challenges for reviews include: (1) lack of clarity in key questions about the intended applicability of the review, (2) numerous studies in many populations and settings, (3) publications that provide too little information to assess applicability, (4) secular trends in prevalence and the spectrum of the condition for which the test is done, and (5) changes in the technology of the test itself. We describe principles for crafting reviews that meet these challenges and capture the key elements from the literature necessary to understand applicability.

Impact of the COVID-19 pandemic on a tertiary care public hospital in Singapore: resources and economic costs.

BACKGROUND: The COVID-19 pandemic has prompted hospitals to respond with stringent measures. Accurate estimates of costs and resources used in outbreaks can guide evaluations of responses. We report on the financial expenditure associated with COVID-19, the bed-days used for COVID-19 patients and hospital services displaced due to COVID-19 in a Singapore tertiary hospital. METHODS: We conducted a retrospective cost analysis from January to December 2020 in the largest public hospital in Singapore. Costs were estimated from the hospital perspective. We examined financial expenditures made in direct response to COVID-19; hospital admissions data related to COVID-19 inpatients; and the number of outpatient and emergency department visits, non-emergency surgeries, inpatient days in 2020, compared with preceding years of 2018 and 2019. Bayesian time-series was used to estimate the magnitude of displaced services. RESULTS: USD $41.96 million was incurred in the hospital for COVID-19-related expenses. Facilities set-up and capital assets accounted for 51.6% of the expenditure; patient-care supplies comprised 35.1%. Of the 19,611 inpatients tested for COVID-19 in 2020, 727 (3.7%) had COVID-19. The total inpatient- and intensive care unit (ICU)-days for COVID-19 patients in 2020 were 8009 and 8 days, respectively. A decline in all hospital services was observed from February following a raised disease outbreak alert level; most services quickly resumed when the lockdown was lifted in June. CONCLUSION: COVID-19 led to an increase in healthcare expenses and a displacement in hospital services. Our findings are useful for informing economic evaluations of COVID-19 response and provide some information about the expected costs of future outbreaks.

Serum Cholesterol Levels within the High Normal Range Are Associated with Better Cognitive Performance among Chinese Elderly.

OBJECTIVES: The association between cognitive function and cholesterol levels is poorly understood and inconsistent results exist among the elderly. The purpose of this study is to investigate the association of cholesterol level with cognitive performance among Chinese elderly. DESIGN: A cross-sectional study was implemented in 2012 and data were analyzed using generalized additive models, linear regression models and logistic regression models. SETTING: Community-based setting in eight longevity areas in China. SUBJECTS: A total of 2000 elderly aged 65 years and over (mean 85.8±12.0 years) participated in this study. MEASUREMENTS: Total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) concentration were determined and cognitive impairment was defined as Mini-Mental State Examination (MMSE) score ≤23. RESULTS: There was a significant positive linear association between TC, TG, LDL-C, HDL-C and MMSE score in linear regression models. Each 1 mmol/L increase in TC, TG, LDL-C and HDL-C corresponded to a decreased risk of cognitive impairment in logistic regression models. Compared with the lowest tertile, the highest tertile of TC, LDL-C and HDL-C had a lower risk of cognitive impairment. The adjusted odds ratios and 95% CI were 0.73(0.62-0.84) for TC, 0.81(0.70-0.94) for LDL-C and 0.81(0.70-0.94) for HDL-C. There was no gender difference in the protective effects of high TC and LDL-C levels on cognitive impairment. However, for high HDL-C levels the effect was only observed in women. High TC, LDL-C and HDL-C levels were associated with lower risk of cognitive impairment in the oldest old (aged 80 and older), but not in the younger elderly (aged 65 to 79 years). CONCLUSIONS: These findings suggest that cholesterol levels within the high normal range are associated with better cognitive performance in Chinese elderly, specifically in the oldest old. With further validation, low cholesterol may serve a clinical indicator of risk for cognitive impairment in the elderly.

Physician attitudes about anticoagulation for nonvalvular atrial fibrillation in the elderly.

BACKGROUND: Our goal was to determine whether patient age affects a physician's reported likelihood of using anticoagulant therapy or the intensity of anticoagulant therapy for patients with nonvalvular atrial fibrillation. METHODS: We surveyed a nationwide sample of 1189 randomly selected office-based practitioners in three strata: primary care (geriatrics, internal medicine, family practice, and general practice), cardiology, and neurology. A vignette-based questionnaire was used to measure attitudes and beliefs regarding anticoagulation risks and effectiveness, barriers to anticoagulation in clinical practice, and likelihood of using anticoagulation and target intensity of anticoagulation at three patient ages (55, 65, and 75 years) for four clinical scenarios (chronic non-valvular atrial fibrillation with mild left atrial enlargement, intermittent or paroxysmal atrial fibrillation, recent-onset atrial fibrillation, and atrial fibrillation with recent [3 months] embolic stroke). RESULTS: The overall response rate was 38%. The mean likelihoods of using anticoagulation for the three ages were unequal (P < .0001) for each scenario. Most physicians were "very" or "somewhat" likely to use anticoagulant therapy for a 65-year-old with left atrial enlargement (71%), intermittent or paryoxysmal atrial fibrillation (68%), recent-onset atrial fibrillation (86%), or embolic stroke (96%). Fewer physicians were likely to use anticoagulant therapy for a 75-year-old with left atrial enlargement (63%), intermittent or paroxysmal atrial fibrillation (56%), recent-onset atrial fibrillation (80%), or embolic stroke (93%). Among physicians equally likely to use anticoagulation for 65- and 75-year-old patients, intensity of anticoagulant therapy (target international normalized ratio or prothrombin time ratio) was lower (P < .04) for the 75-year-old. CONCLUSION: Anticoagulant therapy may be less often and less intensively used for elderly patients with nonvalvular atrial fibrillation.

Racial variations in the rates of carotid angiography and endarterectomy in patients with stroke and transient ischemic attack.

BACKGROUND: Carotid endarterectomy is emerging as the treatment of choice for patients with symptomatic carotid artery stenosis at low operative risk. We sought to determine if racial variations in the rate of carotid angiography and endarterectomy exist in the Veteran Affairs health care system among patients who are insulated from the cost of their care. METHODS: From a national database of all hospitalizations at Veterans Affairs medical centers, we identified a cohort of patients with diagnoses of stroke or transient ischemic attack who were likely to be candidates for carotid angiography and endarterectomy. We used logistic regression to determine if the patient's race was associated with receiving carotid angiography and endarterectomy, after adjusting for patient's age, degree of eligibility for Veterans Affairs care, socioeconomic status, comorbidities associated with hospital admission, and geographic region of the hospital. RESULTS: Of the 35 922 veterans in the cohort, 3535 (9.8%) underwent angiography during the study period and 1249 (3.5%) had carotid endarterectomy. Blacks constituted 18.2% of the patients with a history of stroke or transient ischemic attack, 9.8% of the patients having angiography, but only 4.2% of the patients undergoing carotid endarterectomy. Whites constituted 77.1% of the patients with a history of stroke or transient ischemic attack, 86.1% of the patients receiving angiography, and 93.0% of those having carotid endarterectomies. After adjusting for confounding variables, black patients continued to have a significantly lower likelihood than white patients of undergoing angiography (risk ratio = 0.47; 95% confidence interval = 0.42, 0.53) and subsequent endarterectomy (risk ratio = 0.28; 95% confidence interval = 0.20, 0.38). CONCLUSIONS: Socioeconomic status and access to care within a large managed health care system do not fully explain racial differences in the rate of carotid angiography and endarterectomy. Either referral bias for evaluation for carotid endarterectomy or racial differences in the extent and location of cerebrovascular disease are more important explanations for the observed racial variations.

New transient ischemic attack and stroke: outpatient management by primary care physicians.

BACKGROUND: Patients with transient ischemic attack (TIA) or stroke frequently first contact their primary care physician rather than seeking care at a hospital emergency department. The purpose of the present study was to identify a group of patients seen by primary care physicians in an office setting for a first-ever TIA or stroke and characterize their evaluation and management. METHODS: Practice audit based on retrospective, structured medical record abstraction from 27 primary care medical practices in 2 geographically separate communities in the eastern United States. RESULTS: Ninety-five patients with a first-ever TIA and 81 with stroke were identified. Seventy-nine percent of those with TIA vs 88% with stroke were evaluated on the day their symptoms occurred (P =.12). Only 6% were admitted to a hospital for evaluation and treatment on the day of the index visit (2% TIA; 10% stroke; P =.03); only an additional 3% were admitted during the subsequent 30 days. Specialists were consulted for 45% of patients. A brain imaging study (computed tomography or magnetic resonance imaging) was ordered on the day of the index visit in 30% (23% TIA, 37% stroke; P =.04), regardless of whether the patient was referred to a specialist. Carotid ultrasound studies were obtained in 28% (40% TIA, 14% stroke; P<.001), electrocardiograms in 19% (18% TIA, 21% stroke; P =.60), and echocardiograms in 16% (19% TIA, 14% stroke; P =.34). Fewer than half of patients with a prior history of atrial fibrillation (n = 24) underwent anticoagulation when evaluated at the index visit. Thirty-two percent of patients (31% TIA, 33% stroke; P =.70) were not hospitalized and had no evaluations performed during the first month after presenting to a primary care physician with a first TIA or stroke. Of these patients, 59% had a change in antiplatelet therapy on the day of the index visit. CONCLUSIONS: Further primary care physician education regarding the importance of promptly and fully evaluating patients with TIA or stroke may be warranted, and barriers to implementation of established secondary stroke prevention strategies need to be carefully explored. Arch Intern Med. 2000;160:2941-2946

Quality of anticoagulation management among patients with atrial fibrillation: results of a review of medical records from 2 communities.

BACKGROUND: Most treatment of patients at risk for stroke is provided in the ambulatory setting. Although many studies have addressed the proportion of eligible patients with atrial fibrillation (AF) receiving warfarin sodium, few have addressed the quality of their anticoagulation management. OBJECTIVE: As a comprehensive assessment of quality, we analyzed the proportion of eligible patients receiving warfarin, the proportion of time their international normalized ratios (INRs) were within the target range, and, when an out-of-target range INR value occurred, the time until the next INR measurement was made. METHODS: Retrospective review of the medical records of 660 patients with AF managed by general internists and family practitioners in Rochester, NY, and the Research Triangle area of North Carolina. RESULTS: Only 34.7% of eligible patients with AF received warfarin. The INR values were out of the target range approximately half the time, and the response to these values was not always timely. For all the measures considered, both Rochester practices with access to an anticoagulation service had higher (albeit not ideal) quality of warfarin management than the remaining practices. CONCLUSIONS: We found significant deficiencies in the practice of warfarin management and suggestive evidence that anticoagulation services can partially ameliorate these deficiencies. More research is needed to describe the quality of anticoagulation management in typical practice and how this management can be improved.

Clinical and radiographic findings that lead to intervention in diabetic patients with foot ulcers. A nationwide survey of primary care physicians.

OBJECTIVE: To determine which elements of clinical history, physical examination, and diagnostic tests are important to primary care physicians in their management of foot ulcers in diabetic patients. RESEARCH DESIGN AND METHODS: We conducted a national mail survey of 600 primary care physicians to determine which patient characteristics and diagnostic test results were important in their decisions to seek radiographic studies, surgical referrals, and hospitalization for diabetic patients with foot ulcers. RESULTS: The case characteristics most likely to influence physicians to order advanced diagnostic or therapeutic interventions are the presence of osteomyelitis on plain radiographs, the failure of the ulcer to improve with conservative therapy, and the presence of visible bone, crepitus, or necrosis within the ulcer (P < 0.001). Information from the initial clinical history was less likely to influence physicians to order advanced diagnostic or therapeutic interventions (P < 0.001) than was information from the physical examination. CONCLUSIONS: We conclude that 1) the patient's history is relatively unimportant to primary care physicians in their management of diabetic foot ulcers; 2) the failure of conservative management is a major reason that primary care physicians order surgical referral, hospitalization, or radiographic testing for diabetic patients with foot ulcers; and 3) primary care physicians rely heavily on plain X ray of the foot, a test with poor sensitivity and specificity, in deciding whether to order further interventions for their diabetic patients with foot ulcers.

Have randomized controlled trials of neuroprotective drugs been underpowered? An illustration of three statistical principles.

BACKGROUND AND PURPOSE: The results of phase III trials of neuroprotective drugs for acute ischemic stroke have been disappointing. We examine the question of whether these trials may have been underpowered. METHODS: Computer simulations were based on the binomial distribution. RESULTS: We illustrate that even small overestimates of the efficacy of an intervention can lead to a serious reduction in statistical power, that the use of data from phase II studies tends to lead to such overestimation, and that a minimum clinically important difference derived with cost-effectiveness modeling techniques is considerably smaller than might be suggested by intuition. CONCLUSIONS: We recommend placing more emphasis on minimum clinically important differences when planning stroke trials, with these differences being derived from an assessment of the public health impact obtained in conjunction with the use of epidemiological and cost-effectiveness models. Even small benefits, when averaged over a sufficiently large number of cases, will, in total, accrue to a large positive impact on the public health.

Depression and other determinants of values placed on current health state by stroke patients: evidence from the VA Acute Stroke (VASt) study.

BACKGROUND AND PURPOSE: This prospective study examined the determinants of the utility (value) placed on health status among a sample of patients with acute ischemic and intracerebral hemorrhagic stroke. METHODS: Data were from the VA Acute Stroke (VASt) study, a nationwide prospective cohort of 1073 acute stroke patients admitted at any of 9 Department of Veterans Affairs Medical Center sites between April 1, 1995, and March 31, 1997. The primary outcome was the patient's health status utility as measured by the time-tradeoff method. Data were obtained by telephone interviews at 1, 6, and 12 months and by medical record review. General linear mixed modeling was used to assess the effects of social, psychological, and physical factors on patients' valuations of their current health state. The analysis was confined to the 327 patients who were able to provide self-reports at >/=2 time points. RESULTS: Patients' valuations of their health state status over the initial 12 months after stroke were very stable over time, with only a slight improvement at 6 months, followed by a slight decline at 12 months. In adjusted analyses, living alone, being institutionalized, decreased physical function, and depression were independently associated with lower levels of patient health status utility over time. CONCLUSIONS: Stroke patient health status utilities are relatively stable during the initial year after stroke. In addition to physical function, psychological health and social environment are important determinants of patient health status utility. These factors need to be considered when conducting stroke decision analyses if more accurate conclusions are to be drawn regarding preferred patterns of care.

Improving the reliability of stroke subgroup classification using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria.

BACKGROUND AND PURPOSE: We sought to improve the reliability of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of stroke subtype for retrospective use in clinical, health services, and quality of care outcome studies. The TOAST investigators devised a series of 11 definitions to classify patients with ischemic stroke into 5 major etiologic/pathophysiological groupings. Interrater agreement was reported to be substantial in a series of patients who were independently assessed by pairs of physicians. However, the investigators cautioned that disagreements in subtype assignment remain despite the use of these explicit criteria and that trials should include measures to ensure the most uniform diagnosis possible. METHODS: In preparation for a study of outcomes and management practices for patients with ischemic stroke within Department of Veterans Affairs hospitals, 2 neurologists and 2 internists first retrospectively classified a series of 14 randomly selected stroke patients on the basis of the TOAST definitions to provide a baseline assessment of interrater agreement. A 2-phase process was then used to improve the reliability of subtype assignment. In the first phase, a computerized algorithm was developed to assign the TOAST diagnostic category. The reliability of the computerized algorithm was tested with a series of synthetic cases designed to provide data fitting each of the 11 definitions. In the second phase, critical disagreements in the data abstraction process were identified and remaining variability was reduced by the development of standardized procedures for retrieving relevant information from the medical record. RESULTS: The 4 physicians agreed in subtype diagnosis for only 2 of the 14 baseline cases (14%) using all 11 TOAST definitions and for 4 of the 14 cases (29%) when the classifications were collapsed into the 5 major etiologic/pathophysiological groupings (kappa=0.42; 95% CI, 0.32 to 0.53). There was 100% agreement between classifications generated by the computerized algorithm and the intended diagnostic groups for the 11 synthetic cases. The algorithm was then applied to the original 14 cases, and the diagnostic categorization was compared with each of the 4 physicians' baseline assignments. For the 5 collapsed subtypes, the algorithm-based and physician-assigned diagnoses disagreed for 29% to 50% of the cases, reflecting variation in the abstracted data and/or its interpretation. The use of an operations manual designed to guide data abstraction improved the reliability subtype assignment (kappa=0.54; 95% CI, 0.26 to 0.82). Critical disagreements in the abstracted data were identified, and the manual was revised accordingly. Reliability with the use of the 5 collapsed groupings then improved for both interrater (kappa=0.68; 95% CI, 0.44 to 0.91) and intrarater (kappa=0.74; 95% CI, 0.61 to 0.87) agreement. Examining each remaining disagreement revealed that half were due to ambiguities in the medical record and half were related to otherwise unexplained errors in data abstraction. CONCLUSIONS: Ischemic stroke subtype based on published TOAST classification criteria can be reliably assigned with the use of a computerized algorithm with data obtained through standardized medical record abstraction procedures. Some variability in stroke subtype classification will remain because of inconsistencies in the medical record and errors in data abstraction. This residual variability can be addressed by having 2 raters classify each case and then identifying and resolving the reason(s) for the disagreement.

The value of stroke prevention and treatment.

An emerging issue in stroke prevention and stroke treatment is that therapies shown to be effective in clinical trials are not being used or are being used suboptimally. One of many explanations relates to cost, ranging from concerns about inappropriate use of societal resources to more immediate concerns of organizations and individuals about their financial well-being. Assessing the cost impact of a new therapy, and thus the financial incentives faced by decision-makers, is crucial to understanding and influencing real-world treatment decisions. Assessing cost in the context of health benefits is the object of cost-effectiveness analysis. A cost-effectiveness analysis typically compares the new treatment with a less efficacious yet less costly alternative. This article provides a brief overview of the cost implications of stroke and stroke-related treatments. The example of stroke prevention is used to illustrate how to calculate an incremental cost-effectiveness ratio and help clarify what makes a treatment an especially good value. Because stroke is tremendously expensive and because severe strokes are especially expensive, treatments to prevent stroke and to diminish stroke disability are likely to be an excellent value.

Comparison and meta-analysis of randomized trials of endarterectomy for symptomatic carotid artery stenosis.

OBJECTIVE: Comparison and meta-analysis of randomized trials of carotid endarterectomy for symptomatic stenosis of the extracranial carotid artery. BACKGROUND: Randomized trials (North American Symptomatic Carotid Endarterectomy Trial [NASCET], the European Carotid Surgery Trial [ECST], and the VA Cooperative Study [VACS]) each show that carotid endarterectomy improves outcomes in selected symptomatic patients with high-grade extracranial carotid artery stenosis. Direct comparisons among the studies have not been possible because of differing methodologies, endpoints, and formats of data reporting. DESIGN/METHODS: Data for specified endpoints and corresponding person-years at risk were obtained for each trial. The rates of nonfatal stroke, nonfatal myocardial infarction, or death for surgically or medically treated patients in the perioperative period (30 days) and thereafter were compared (both including and excluding perioperative events) and then combined using meta-analytic techniques. Data from NASCET and ECST were also analyzed for differences in outcomes by sex. RESULTS: Event rate estimates (with 95% confidence intervals [95% CI]) for the first 30 days (events per person-year, primarily nonfatal stroke) for medically treated patients were 0.44 (0.22 to 0.76) for NASCET, 0.15 (0.04 to 0.38) for ECST, and 0.27 (0.03 to 0.96) for VACS. For surgically treated patients, the corresponding rates (per person-year) were 0.78 (0.49 to 1.19), 0.63 (0.41 to 0.94), and 1.27 (0.58 to 2.43). Event rates per year after 30 days were higher for medically treated patients (0.20 [0.16 to 0.25] versus 0.08 [0.05 to 0.11] for NASCET; 0.12 [0.10 to 0.15] versus 0.07 [0.06 to 0.09] for ECST; and 0.15 [0.07 to 0.25] versus 0.07 [0.03 to 0.16] for VACS). There were no significant differences among the trials, with an overall benefit for surgical therapy (risk ratio estimate, RR = 0.67, 95% CI = 0.54 to 0.83). There were no significant sex-based differences between NASCET and ECST and the overall benefit was not significantly different for men and women (RR = 0.58, 95% CI = 0.45 to 0.74 for men; RR = 0.84, 95% CI = 0.57 to 1.25 for women). CONCLUSIONS: Adjusting for primary endpoints and duration of follow-up, carotid endarterectomy has a similar benefit for symptomatic patients across trials and a similar benefit for men and women.

Inaccuracy of the International Classification of Diseases (ICD-9-CM) in identifying the diagnosis of ischemic cerebrovascular disease.

In administrative databases the International Classification of Diseases, Version 9, Clinical Modification (ICD-9-CM) is often used to identify patients with specific diagnoses. However, certain conditions may not be accurately reflected by the ICD-9 codes. We assessed the accuracy of ICD-9 coding for cerebrovascular disease by comparing ICD-9 codes in an administrative database with clinical findings ascertained from medical record abstractions. We selected patients with ICD-9 diagnostic codes of 433 through 436 (in either the primary or secondary positions) from an administrative database of patients hospitalized in five academic medical centers in 1992. Medical records of the selected patients were reviewed by trained medical abstractors, and the patients' clinical conditions during the admission (stroke, TIA, asymptomatic) were recorded, as well as any history of cerebrovascular symptoms. Results of the medical record review were compared with the ICD-9 codes from the administrative database. More than 85% of those patients with the ICD-9 code 433 were asymptomatic for the index admission. More than one-third of these asymptomatic patients did not undergo either cerebral angiography or carotid endarterectomy. For ICD-9 code 434, 85% of patients were classified as having a stroke and for ICD-9 code 435, 77% had TIAs. For code 436, 77% of patients were classified as having strokes. Limiting the identifying ICD-9 code to the primary position increased the likelihood of agreement with the medical record review. The ICD-9 coding scheme may be inaccurate in the classification of patients with ischemic cerebrovascular disease. Its limitations must be recognized in the analyses of administrative databases selected by using ICD-9 codes 433 through 436.

Meta-analysis: the detection of pancreatic malignancy with positron emission tomography.

BACKGROUND: Several factors contribute to the high mortality of pancreatic cancer, including limitations of diagnostic imaging. AIM: To perform a meta-analysis to assess the diagnostic accuracy of Fluro-deoxy-glucose positron emission tomography with computed tomography compared with computed tomography alone. METHODS: Articles were identified through a MEDLINE search and bibliography review. Summary estimates and receiver operating curves were calculated using Meta-Test 0.6. Publication bias and heterogeneity were assessed with a funnel plot and chi-squared test. RESULTS: The summary estimate and 95% confidence interval for sensitivity and specificity were as follows: computed tomography 81% (72-88%) and 66% (53-77%), PET after a positive computed tomography 92% (87-95%) and 68% (51-81%), PET after a negative computed tomography 73% (50-88%) and 86% (75-93%) and PET after an indeterminate computed tomography 100 and 68%. The area under the summary receiver operating curve was 0.82 for computed tomography and 0.94 for PET. There was no heterogeneity or publication bias. CONCLUSIONS: Our results suggest that although adding Fluro-deoxy-glucose positron emission tomography to the diagnostic work-up may enhance the diagnosis of pancreatic malignancy, its usefulness will vary depending upon the pretest probability of the patient, the results of computed tomography and the provider's testing thresholds. Further evaluation using a well-designed prospective study with a cost-effectiveness analysis is needed to clarify the appropriate role of Fluro-deoxy-glucose positron emission tomography.

Likelihood ratios with confidence: sample size estimation for diagnostic test studies.

Confidence intervals are important summary measures that provide useful information from clinical investigations, especially when comparing data from different populations or sites. Studies of a diagnostic test should include both point estimates and confidence intervals for the tests' sensitivity and specificity. Equally important measures of a test's efficiency are likelihood ratios at each test outcome level. We present a method for calculating likelihood ratio confidence intervals for tests that have positive or negative results, tests with non-positive/non-negative results, and tests reported on an ordinal outcome scale. In addition, we demonstrate a sample size estimation procedure for diagnostic test studies based on the desired likelihood ratio confidence interval. The renewed interest in confidence intervals in the medical literature is important, and should be extended to studies analyzing diagnostic tests.

Likelihood ratios for continuous test results--making the clinicians' job easier or harder?

Clinicians' paradigms for considering diagnostic test results require decisions based on the actual test value. However, when the test result is reported on a continuous scale each possible outcome may not result in unique actions. To simplify decision making, clinicians often break down the continuous scale into dichotomous or ordered outcomes. Likelihood ratios, reported with the test outcome, help summarize the impact of diagnostic tests. Although commonly applied to dichotomous outcomes, likelihood ratios can also be applied to ordinal or continuous results. This application allows investigators to consider the effect of clinically simplifying continuous data into dichotomous or ordinal categories. The parameters of a simple logistic regression equation summarize continuous likelihood ratios, evaluate covariates, generate likelihood ratio lines, and help assess the statistical significance of more complex models. Having visually inspected likelihood ratio lines and considered statistical differences, the investigator should choose the test report format that best accounts the realities driving clinical decisions.

Performing cost-effectiveness analysis by integrating randomized trial data with a comprehensive decision model: application to treatment of acute ischemic stroke.

A recent national panel on cost-effectiveness in health and medicine has recommended that cost-effectiveness analysis (CEA) of randomized controlled trials (RCTs) should reflect the effect of treatments on long-term outcomes. Because the follow-up period of RCTs tends to be relatively short, long-term implications of treatments must be assessed using other sources. We used a comprehensive simulation model of the natural history of stroke to estimate long-term outcomes after a hypothetical RCT of an acute stroke treatment. The RCT generates estimates of short-term quality-adjusted survival and cost and also the pattern of disability at the conclusion of follow-up. The simulation model incorporates the effect of disability on long-term outcomes, thus supporting a comprehensive CEA. Treatments that produce relatively modest improvements in the pattern of outcomes after ischemic stroke are likely to be cost-effective. This conclusion was robust to modifying the assumptions underlying the analysis. More effective treatments in the acute phase immediately following stroke would generate significant public health benefits, even if these treatments have a high price and result in relatively small reductions in disability. Simulation-based modeling can provide the critical link between a treatment's short-term effects and its long-term implications and can thus support comprehensive CEA.

Setting the target for a better cervical screening test: characteristics of a cost-effective test for cervical neoplasia screening.

OBJECTIVE: To determine the potential effects on costs and outcomes of changes in sensitivity and specificity with new screening methods for cervical cancer. METHODS: Using a Markov model of the natural history of cervical cancer, we estimated the effects of sensitivity, specificity, and screening frequency on cost-effectiveness. Our estimates of conventional Papanicolaou test sensitivity of 51% and specificity of 97% were obtained from a meta-analysis. We estimated the effect of reducing false-negative rates from 40-90% and increasing false-positive rates by up to 20%, independently and jointly. We varied the marginal cost of improving sensitivity from $0 to $15. RESULTS: When specificity was held constant, increasing sensitivity of the Papanicolaou test increased life expectancy and costs. When sensitivity was held constant, decreasing specificity of the Papanicolaou test increased costs, an effect that was more dramatic at more frequent intervals. Decreased specificity had a substantial effect on cost-effectiveness estimates of improved Papanicolaou test sensitivity. Most of those effects are related to the cost of evaluation and treatment of low-grade lesions. CONCLUSION: Policies or technologies that increased sensitivity of cervical cytologic screening increased overall costs, even if the cost of the technology was identical to that of conventional Papanicolaou smears. These effects appear to be caused by relatively high prevalence of low-grade lesions and are magnified at frequent screening intervals. Efficient cervical cancer screening requires methods with greater ability to detect lesions that are most likely to become cancerous.