Abstract
Background
Costeffectiveness acceptability curves (CEACs) describe the probability that a new treatment or intervention is costeffective. The net benefit regression framework (NBRF) allows costeffectiveness analysis to be done in a simple regression framework. The objective of the paper is to illustrate how net benefit regression can be used to construct a CEAC.
Methods
One hundred patients referred for ambulatory monitoring with syncope or presyncope were randomized to a onemonth external loop recorder (n = 49) or 48hour Holter monitor (n = 51). The primary endpoint was symptomrhythm correlation during monitoring. Direct costs were calculated based on the 2003 Ontario Health Insurance Plan (OHIP) fee schedule combined with hospital case costing of labour, materials, service and overhead costs for diagnostic testing and related equipment.
Results
In the loop recorder group, 63.27% of patients (31/49) had symptom recurrence and successful activation, compared to 23.53% in the Holter group (12/51). The cost in US dollars for loop recording was $648.50 and $212.92 for Holter monitoring. The incremental costeffectiveness ratio (ICER) of the loop recorder was $1,096 per extra successful diagnosis. The probability that the loop recorder was costeffective compared to the Holter monitor was estimated using net benefit regression and plotted on a CEAC. In a sensitivity analysis, bootstrapping was used to examine the effect of distributional assumptions.
Conclusion
The NBRF is straightforward to use and interpret. The resulting uncertainty surrounding the regression coefficient relates to the CEAC. When the link from the regression's pvalue to the probability of costeffectiveness is tentative, bootstrapping may be used.
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Background
Out patient ambulatory monitoring is often performed in patients with syncope (e.g., fainting or passing out) that present in the primary care setting to diagnose or exclude an arrhythmia, a potentially serious etiology [1–6]. This shortterm monitoring device may take the form of an external loop recorder or a Holter monitor. The purpose of monitoring is to obtain a symptomrhythm correlation during the monitored period (i.e., to have the monitoring device actively record a patient experiencing symptoms). Several studies have reported the diagnostic yield of the two monitoring modalities, suggesting a higher yield from the longer duration of monitoring provided by a loop recorder [3, 7–12]. One recent randomized trial confirmed the higher diagnostic yield [5]. There is a lack of data about the cost of investigation of syncope presenting in the community. Referred and hospitalized patients are known to generate costs estimated between $3,000 and $25,000 dollars [13–19]. After a primary diagnostic trial [5], we sought to establish the cost of investigation of "communityacquired" syncope and to evaluate the costeffectiveness of the two monitoring strategies in a prospective randomized trial [20].
A new health care treatment, intervention or technology is costeffective if (1) the extra cost of (2) an extra unit of effect is less than (3) the decision maker's willingness to pay for it. A costeffectiveness analysis (CEA) can report (1) and (2), representing two of the three pieces of information necessary to determine costeffectiveness. Specifically, an incremental costeffectiveness ratio (ICER) is the ratio of extra cost to extra effect (i.e., ΔC/ΔE). Thus, a CEA generates an estimate of the extra cost for an additional unit of effect, but the merit of the tradeoff is typically a matter of opinion. In other words, the data are generally silent on whether the extra effect is worth the extra cost. For example, a new drug for multiple sclerosis may provide an extra quality adjusted life year (QALY) for £35,000. The new drug is costeffective if the decision maker is willing to pay £35,000 or more for an extra QALY. Thus the verdict of costeffectiveness depends upon the decision maker's willingness to pay (λ), a value not known from the cost and effect data. There is additional uncertainty beyond the fact that λ is unknown. The uncertainty comes from the fact that the sample ICER is a statistical estimate. For example, if the true ICER is £30,000 per QALY, the ICER estimate could be more or less due to sampling variability. In fact, the multiple sclerosis drug with the ICER estimate of £35,000 per QALY could have a true ICER of £30,000 per QALY. It would be a mistake to conclude there is no chance that the drug is costeffective if λ = £31,000, for example.
The costeffectiveness acceptability curve (CEAC) elegantly handles both uncertainty problems. This paper, building on recent work by Fenwick and colleagues [21], illustrates how to use the net benefit regression framework (NBRF) [22] to construct a CEAC. After a brief summary of relevant statistical concepts, this paper uses clinical trial data from a recently published CEA comparing external loop recorders with Holter monitors for ambulatory monitoring of syncope.
Methods
One hundred patients referred for ambulatory monitoring with syncope or presyncope (hereafter described as syncope) were randomized to a onemonth external loop recorder (n = 49) or 48hour Holter monitor (n = 51). Patients provided written informed consent, and the protocol was approved by the University of Western Ontario Ethics Review Board. The primary endpoint was symptomrhythm correlation during monitoring. Direct costs in Canadian dollars were calculated from the Ministry of Health's perspective based on the 2003 Ontario Health Insurance Plan (OHIP) fee schedule for professional fees and on hospital case costing data for the calculation of labour, materials, service and overhead for diagnostic testing and related equipment. Costs were converted to US Dollars using a conversion rate converted on July 20th, 2005 of ($1 USD = $1.21543 CAD) [20].
Loop recorders were both more costly and more effective than Holter monitors. For the loop recorder, the cost in US dollars was $648.50 and for the Holter monitor $212.92 [20]. The extra cost of $435.58 for the loop recorder was accompanied by a 39.74% increase of success while monitoring (in the loop recorder group 31 of 49 or 63.27% of patients had symptom recurrence and successful activation, compared to 12 of 51 or 23.53% in the Holter group). The ICER estimate was $1096 per additional diagnosis. The CEAC finds purchase here as there is uncertainty about the maximum a decision maker would pay for an additional diagnosis coupled with the statistical variability inherent in trial data. As an alternative to the method illustrated by Fenwick and colleagues [21], we use the NBRF to show how to construct the CEAC.
The CEAC has been advocated for summarizing the results of a CEA because it highlights the relationship between the assessment of costeffectiveness and the unknown λ [23–27]. As originally described, the CEAC originates from a Bayesian context; however, the CEAC can be given a frequentist interpretation. For a given λ, the CEAC is equal to one minus the onesided significance level for testing the null hypothesis that the "new treatment" is not costeffective (i.e., the additional benefits are outweighed by the additional costs) [25, 28]. Under this frequentist framework, the CEAC can be viewed as illustrating a decision rule for rejecting the null hypothesis that the intervention is not costeffective.
Alternatively, the CEAC can be interpreted in a 'Bayesian' fashion [23, 24] as: the probability that an individual, with a set of prior beliefs about the costeffectiveness of the new treatment, now believes the new treatment to be costeffective (i.e., the additional benefits outweigh the additional costs). While a Bayesian approach provides a welljustified interpretation for a CEAC, it presents other dilemmas. For example, there exist many 'Bayesian' CEACs – namely one for every set of prior beliefs – with no criteria for choosing between them. This is important because every CEAC is 'correct' for its given prior. Thus, the calculation of a Bayesian CEAC requires the specification of the prior distribution of the costeffectiveness data before the data were collected. Typically as a reference case scenario, it is common and convenient to use a 'noninformative' prior which allows the data to overwhelm prior beliefs. However, except in the simplest of examples there is no agreement about the definition of a reference prior distribution and many socalled noninformative priors are not noninformative at all (see section 5.5.1 of [29]). When using a 'noninformative' prior with the NBRF (in this case assuming there is no reason to modify the results of the data analysis), the Bayesian mechanics work in the background and formal derivation of the posterior distribution can be avoided. In other words, one can run a net benefit regression and use the resulting parts to illustrate the probability that a new treatment or intervention is costeffective (NB: The pvalue itself does not provide an estimate of the probability of costeffectiveness when there is prior information. This is a fundamental distinction between the interpretation of a pvalue and a posterior probability [30]. For a more comprehensive discussion about the use of genuine prior information in costeffectiveness analyses readers are referred to [31–33]).
The NBRF was introduced to facilitate the use of regression tools in economic evaluation [22]. Net benefit regression uses as the dependent variable, net benefit nb_{i}= λ·effect_{i} cost_{i}from personlevel effect (effect_{i}) and cost (cost_{i}) data (as a matter of preference, the analyst may use net health benefits [34] instead of net monetary benefits [35]). When ordinary least squares (OLS) is used to estimate the simple linear regression
nb_{i}= β_{0} + β_{1}TX + ε
where TX is a "new treatment" indicator variable (e.g., TX = 1 if the patient received a loop recorder and TX = 0 if the patient received a Holter monitor), the coefficient estimate of β_{1}, call this b_{1}, equals the difference in mean nb for the loop and Holter groups. It can be shown [22] that when this difference is greater than zero (i.e., when the loop group has greater mean net benefits than the Holter group), then ΔC/ΔE < λ. In other words, if b_{1} > 0, then the loop recorder is costeffective relative to the Holter monitor (or the incremental net benefit is positive). The statistical uncertainty involving the cost and effect data is expressed in the pvalue for b_{1}. The pvalue for b_{1} can be used to make the yaxis of the CEAC [22, 25]; however, caution must be exercised in two regards.
Using the NBRF and a Bayesian perspective, the CEAC illustrates the probability that a "new treatment" is costeffective by graphing the probability that β_{1} > 0 as a function of λ. Most statistical packages have regression programs that report a twosided pvalue, but in this case a onesided probability is indicated. Because the twosided pvalue is twice as much probability as is needed, it is necessary to divide it by two (this converts the twosided pvalue into a onesided pvalue). Figure 1 illustrates this and the importance of checking the sign of b_{1}. When b_{1} < 0, the probability that new treatment is costeffective equals the onesided pvalue, and when b_{1} > 0, the probability that new treatment is costeffective equals one minus the onesided pvalue. Thus when using the pvalue from a regression to make a CEAC, one must check that one is using the onesided pvalue and that one is doing the correct calculation given the sign of b_{1} (i.e., 1/2 pvalue of b_{1} when b_{1} < 0 or 1  1/2 pvalue of b_{1} when b_{1} > 0). Lastly, because the pvalue of a parametric analysis is derived from a distributional assumption, nonparametric methods like bootstrapping may offer better alternatives when distributional concerns arise (e.g., the data do not appear distributed normally or with constant variance).
Results
Each study participant who received a loop recorder incurred costs of $648.50 and 31 of the 49 (63.27%) had symptom recurrence and successful activation. In comparison, the Holter monitors cost $212.92 for each study participant and only 12 of the 51 (23.53%) experienced a successful outcome. The NBRF was implemented by estimating with OLS the regression
nb_{i}= β_{0} + β_{1}LOOP + ε
where LOOP is an indicator variable equaling one if the patient received a loop recorder and zero if the patient received a Holter monitor. Table 1 shows how the net benefit statistic (nb_{i}) was calculated for each person when λ was set to $1000.
Table 2 presents the complete results of five net benefit regressions using λ = $500, $1000, $1500, $2000 and $2500. To illustrate how the CEAC can be computed using net benefit regression, Table 3 lists regression estimates of the LOOP indicator variable for λ = $500 through $3000 (the horizontal axis for the CEAC) as well as the regression and bootstrap estimates of the probability that the loop recorder is costeffective (the vertical axis for the CEAC). For λ < $1000, the estimate of the incremental net benefit is negative (i.e., b_{1} < 0), so the quantity to calculate for the CEAC's vertical axis is simply one half of the twosided pvalue. For λ > $1000, the estimate of the incremental net benefit is positive (i.e., b_{1} > 0), so the quantity to calculate for the CEAC's vertical axis is one minus one half of the twosided pvalue. Figure 2 illustrates the resulting CEAC. Because the pvalue is based on distributional assumptions that may not hold with small sample sizes or nonconstant variance, bootstrapping can be used as a nonparametric alternative to obtain values for the CEAC's vertical axis. For this example, we drew 1000 bootstrapped samples of n = 100 from our original sample. The resulting estimates of the probability that the incremental net benefit is positive are reported in the last column of Table 3.
Discussion
A CEAC indicates a 50% chance of costeffectiveness when λ equals the sample estimate of the ICER [26]. The ICER for the loop recorder was $1,096 per extra successful diagnosis. Table 3 shows that when λ is within $500 of the ICER estimate, the probability of costeffectiveness is quite sensitive. For example, at λ = $500, the probability that loop recorders are costeffective is 0%, but at λ = $1500 it is approximately 88%. Figure 2 illustrates this, as the most dramatic gains in the height of the curve (from 0% to 88%) occur between λ = $500 and $1500. Alternatively, the curve is mostly flat for λ < $ 500 and λ > $1500. While we may never know the real value of λ, if it is assumed to be near the low range of the costs generated by referred and hospitalized patients (e.g., $3000 dollars), there appears to be a good chance that loop recorders are costeffective.
As reflected in the last two columns of Table 3, the probability of costeffectiveness calculated using the pvalue was nearly identical to that calculated using the bootstrapping method. This finding may be related to the fact that the cost data in this trial did not vary by patient within treatment group. All patients receiving a loop recorder had costs of $648.50 and all patients receiving a Holter monitor had costs of $212.92. When both patient level costs and effect data vary, net benefit regression can still be used to construct a CEAC (i.e., the statistical uncertainty involving the cost and effect data is expressed in the pvalue). However, the assumptions necessary to use the pvalue may not hold; for example, the presence of skewness or heteroskedasticity in the data suggests caution when using the pvalue. Indeed, for low values of λ, the almost inevitable nonnormal distribution of costs can challenge the assumptions made in using the pvalue in the regression approach. For this reason, empirical examples of the NBRF typically use bootstrapping to generate CEACs [36–38]. However, as noted by a reviewer, the bootstrap is not necessarily robust, particularly in CEAs when there is also concern about the use of parametric methods because of skewness. In addition to the incremental net benefit (β_{1}), net benefit regression provides an estimate of the mean net benefit of "usual care" (β_{0}), the mean net benefit of "new treatment" (β_{0} + β_{1}) and also regression diagnostic information (e.g., the residual errors and R^{2}). Thus, the NBRF facilitates using regression diagnostics (see the "Regression Diagnostics" section and Figure 6 in [22]) to improve the quality of economic evaluations.
Conclusion
The NBRF provides a way for economic evaluations to use the variety of tools that have been developed for regression. For any value of λ, net benefit regression produces a costeffectiveness estimate, and the CEAC produces a costeffectiveness probability. To allow for the fact that the analyst does not know the decision maker's λ, the horizontal axis of a CEAC varies in the style of a sensitivity analysis, and the statistical uncertainty about costeffectiveness is reflected on the vertical axis. This paper has illustrated how the NBRF can be used to construct a CEAC. When the link from a net benefit regression's pvalue to the probability of costeffectiveness is tentative, bootstrapping provides an alternative.
Abbreviations
 CEACs:

costeffectiveness acceptability curves
 ICER:

incrememtnal costeffectiveness ratio
 NBRF:

net benefit regression framework
 OHIP:

Ontario Health Insurance Plan
 OLS:

ordinary least squares
 QALY:

quality adjusted life year
References
Jonas S, Klein I, Dimant J: Importance of Holter monitoring in patients with periodic cerebral symptoms. Ann Neurol. 1977, 1: 470474. 10.1002/ana.410010511.
Gendelman HE, Linzer M, Gabelman M, Smoller S, Scheuer J: Syncope in a general hospital patient population. Usefulness of the radionuclide brain scan, electroencephalogram, and 24hour Holter monitor. N Y State J Med. 1983, 83: 11611165.
Bass EB, Curtiss EI, Arena VC, Hanusa BH, Cecchetti A, Karpf M, Kapoor WN: The duration of Holter monitoring in patients with syncope. Is 24 hours enough?. Arch Intern Med. 1990, 150: 10731078. 10.1001/archinte.150.5.1073.
Linzer M, Yang EH, Estes NAIII, Wang P, Vorperian VR, Kapoor WN: Diagnosing syncope. Part 1: Value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med. 1997, 126: 989996.
Sivakumaran S, Krahn AD, Klein GJ, Finan J, Yee R, Renner S, Skanes AC: A prospective randomized comparison of loop recorders versus Holter monitors in patients with syncope or presyncope. Am J Med. 2003, 115: 15. 10.1016/S00029343(03)00233X.
Kapoor WN: Evaluation and management of the patient with syncope. JAMA. 1992, 268: 25532560. 10.1001/jama.268.18.2553.
Gibson TC, Heitzman MR: Diagnostic efficacy of 24hour electrocardiographic monitoring for syncope. Am J Cardiol. 1984, 53: 10131017. 10.1016/00029149(84)906283.
Linzer M, Yang EH, Estes NAIII, Wang P, Vorperian VR, Kapoor WN: Diagnosing syncope. Part 2: Unexplained syncope. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med. 1997, 127: 7686.
Zimetbaum P, Kim KY, Ho KK, Zebede J, Josephson ME, Goldberger AL: Utility of patientactivated cardiac event recorders in general clinical practice. Am J Cardiol. 1997, 79: 371372. 10.1016/S00029149(96)007667.
Zimetbaum PJ, Kim KY, Josephson ME, Goldberger AL, Cohen DJ: Diagnostic yield and optimal duration of continuousloop event monitoring for the diagnosis of palpitations. A costeffectiveness analysis. Ann Intern Med. 1998, 128: 890895.
Schuchert A, Maas R, Kretzschmar C, Behrens G, Kratzmann I, Meinertz T: Diagnostic yield of external electrocardiographic loop recorders in patients with recurrent syncope and negative tilt table test. Pacing Clin Electrophysiol. 2003, 26: 18371840. 10.1046/j.14609592.2003.t01100277.x.
Kapoor WN, Cha R, Peterson JR, Wieand HS, Karpf M: Prolonged electrocardiographic monitoring in patients with syncope. Importance of frequent or repetitive ventricular ectopy. Am J Med. 1987, 82: 2028. 10.1016/00029343(87)90372X.
Kapoor WN, Karpf M, Maher Y, Miller RA, Levey GS: Syncope of unknown origin. The need for a more costeffective approach to its diagnosis evaluation. JAMA. 1982, 247: 26872691. 10.1001/jama.247.19.2687.
Calkins H, Byrne M, elAtassi R, Kalbfleisch S, Langberg JJ, Morady F: The economic burden of unrecognized vasodepressor syncope. Am J Med. 1993, 95: 473479. 10.1016/00029343(93)90329N.
Fogel RI, Evans JJ, Prystowsky EN: Utility and cost of event recorders in the diagnosis of palpitations, presyncope, and syncope. Am J Cardiol. 1997, 79: 207208. 10.1016/S00029149(96)007175.
Krahn AD, Klein GJ, Yee R, Manda V: The high cost of syncope: cost implications of a new insertable loop recorder in the investigation of recurrent syncope. Am Heart J. 1999, 137: 870877. 10.1016/S00028703(99)704114.
Simpson CS, Krahn AD, Klein GJ, Yee R, Skanes AC, Manda V, Norris C: A cost effective approach to the investigation of syncope: relative merit of different diagnostic strategies. Can J Cardiol. 1999, 15: 579584.
Nyman JA, Krahn AD, Bland PC, Griffiths S, Manda V: The costs of recurrent syncope of unknown origin in elderly patients. Pacing Clin Electrophysiol. 1999, 22: 13861394. 10.1111/j.15408159.1999.tb00633.x.
Krahn AD, Klein GJ, Yee R, Hoch JS, Skanes AC: Cost implications of testing strategy in patients with syncope: randomized assessment of syncope trial. J Am Coll Cardiol. 2003, 42: 495501. 10.1016/S07351097(03)006594.
Rockx MA, Hoch JS, Klein GJ, Yee R, Skanes AC, Gula LJ, Krahn AD: Is ambulatory monitoring for "communityacquired" syncope economically attractive? A costeffectiveness analysis of a randomized trial of external loop recorders versus Holter monitoring. Am Heart J. 2005, 150: 106510.1016/j.ahj.2005.08.003.
Fenwick E, Marshall DA, Levy AR, Nichol G: Using and interpreting costeffectiveness acceptability curves: An example using data from a trial of management strategies for atrial fibrillation. BMC Health Serv Res. 2006, 6: 5210.1186/14726963652.
Hoch JS, Briggs AH, Willan AR: Something old, something new, something borrowed, something blue: a framework for the marriage of health econometrics and costeffectiveness analysis. Health Econ. 2002, 11: 415430. 10.1002/hec.678.
van Hout BA, Al MJ, Gordon GS, Rutten FF: Costs, effects and C/Eratios alongside a clinical trial. Health Econ. 1994, 3: 309319.
Briggs A, Fenn P: Confidence intervals or surfaces? Uncertainty on the costeffectiveness plane. Health Econ. 1998, 7: 723740. 10.1002/(SICI)10991050(199812)7:8<723::AIDHEC392>3.0.CO;2O.
Lothgren M, Zethraeus N: Definition, interpretation and calculation of costeffectiveness acceptability curves. Health Econ. 2000, 9: 623630. 10.1002/10991050(200010)9:7<623::AIDHEC539>3.0.CO;2V.
Fenwick E, Claxton K, Sculpher M: Representing uncertainty: the role of costeffectiveness acceptability curves. Health Econ. 2001, 10: 779787. 10.1002/hec.635.
Fenwick E, O'Brien BJ, Briggs A: Costeffectiveness acceptability curvesfacts, fallacies and frequently asked questions. Health Econ. 2004, 13: 405415. 10.1002/hec.903.
O'Hagan A, Stevens JW, Montmartin J: Inference for the costeffectiveness acceptability curve and costeffectiveness ratio. Pharmacoeconomics. 2000, 17: 339349. 10.2165/0001905320001704000004.
Spiegelhalter DJ, Abrams KR, Myles JP: Statistics in practice (Chichester, England). Bayesian approaches to clinical trials and healthcare evaluation. 2004, Chichester, John Wiley & Sons
Goodman SN: Introduction to Bayesian methods I: measuring the strength of evidence. Clin Trials. 2005, 2: 282290. 10.1191/1740774505cn098oa.
O'Hagan A, Stevens JW: A framework for costeffectiveness analysis from clinical trial data. Health Econ. 2001, 10: 303315. 10.1002/hec.617.
Stevens JW, O'Hagan A: Incorporation of genuine prior information in costeffectiveness analysis of clinical trial data. Int J Technol Assess Health Care. 2002, 18: 782790. 10.1017/S0266462302000594.
Al MJ, van Hout BA: A Bayesian approach to economic analyses of clinical trials: the case of stenting versus balloon angioplasty. Health Econ. 2000, 9: 599609. 10.1002/10991050(200010)9:7<599::AIDHEC530>3.0.CO;2#.
Stinnett AA, Mullahy J: Net health benefits: a new framework for the analysis of uncertainty in costeffectiveness analysis. Med Decis Making. 1998, 18: S68S80.
Tambour M, Zethraeus N, Johannesson M: A note on confidence intervals in costeffectiveness analysis. Int J Technol Assess Health Care. 1998, 14: 467471.
McCrone P, Knapp M, Proudfoot J, Ryden C, Cavanagh K, Shapiro DA, Ilson S, Gray JA, Goldberg D, Mann A, Marks I, Everitt B, Tylee A: Costeffectiveness of computerised cognitivebehavioural therapy for anxiety and depression in primary care: randomised controlled trial. Br J Psychiatry. 2004, 185: 5562. 10.1192/bjp.185.1.55.
Lam DH, McCrone P, Wright K, Kerr N: Costeffectiveness of relapseprevention cognitive therapy for bipolar disorder: 30month study. Br J Psychiatry. 2005, 186: 500506. 10.1192/bjp.186.6.500.
Mahoney EM, Mehta S, Yuan Y, Jackson J, Chen R, Gabriel S, Lamy A, Culler S, Caro J, Yusuf S, Weintraub WS: Longterm costeffectiveness of early and sustained clopidogrel therapy for up to 1 year in patients undergoing percutaneous coronary intervention after presenting with acute coronary syndromes without STsegment elevation. Am Heart J. 2006, 151: 219227. 10.1016/j.ahj.2005.02.044.
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Acknowledgements
The authors would like to thank George J. Klein, Raymond Yee, Allan C. Skanes and Lorne J. Gula for their assistance with the initial patient study. Dr. Hoch gratefully acknowledges funding from a Career Scientist Award from the Ontario Ministry of Health and Long Term Care. The Centre for Research on Inner City Health is sponsored by the Ontario Ministry of Health and LongTerm Care. The opinions, results, and conclusions are those of the authors and no endorsement by the ministry is intended or should be inferred.
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Hoch, J.S., Rockx, M.A. & Krahn, A.D. Using the net benefit regression framework to construct costeffectiveness acceptability curves: an example using data from a trial of external loop recorders versus Holter monitoring for ambulatory monitoring of "community acquired" syncope. BMC Health Serv Res 6, 68 (2006). https://doi.org/10.1186/14726963668
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DOI: https://doi.org/10.1186/14726963668