ARTICLE
Cost-effectiveness of Competing Strategies for the
Treatment of Pediatric Empyema
Eyal Cohen, MD, MSca,b, Michael Weinstein, MDa,b, David N. Fisman, MD, MPHb,c
aDepartment of Pediatrics andbChild Health Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada;cOntario Central Public Health
Laboratory, Toronto, Ontario, Canada
The authors have indicated they have no financial relationships relevant to this article to disclose.
What’s Known on This Subject
The optimal management of empyema and complicated parapneumonic effusion is controversial. Recent trials and reviews have produced conflicting results, particularly on the relative merits of a CTWF compared with VATS.
What This Study Adds
CTWF is the most cost-effective strategy for treating empyema. VATS would be preferred to CTWF if the differential in length of stay between these 2 strategies were greater than that suggested by published data.
ABSTRACT
BACKGROUND.The optimal management of pediatric empyema is controversial. The purpose of this decision analysis was to assess the relative merits in terms of costs and clinical outcomes associated with competing treatment strategies.
METHODS.A cost-effectiveness analysis was conducted using a Bayesian tree approach. Probability and outcome estimates were derived from the published literature, with preference given to data derived from randomized trials. Costing was based on published estimates from Great Ormond Street Hospital (London, United Kingdom), supplemented by American and Canadian data. Five strategies were evaluated: (1) nonoperative; (2) chest tube insertion; (3) repeated thoracentesis; (4) chest tube insertion with instillation of fibrinolytics; or (5) video-assisted thorascopic surgery. The model was used to project overall costs, survival in life-years, and incremental cost-effectiveness ratios for competing strategies.
RESULTS.In the base-case analysis, chest tube with instillation of fibrinolytics was the least expensive therapy, at $7787 per episode. This strategy was projected to cost less but provide equivalent health benefit when compared with all of the competing strategies except repeated thoracentesis, which had an incremental cost-effectiveness ratio of approximately $6 422 699 per life-year gained relative to chest tube with instillation of fibrinolytics. In univariable and multivariable sensitivity analyses, thorascopic surgery was preferred only when the length of stay associated with chest tube with instillation of fibrinolytics exceeded 10.3 days or when the probability of dying as a result of this strategy exceeded 0.2%, assuming a threshold willingness to pay of $75 000 per life-year gained. Chest tube with instillation of fibrinolytics was preferred in⬎58% of Monte Carlo simulations.
CONCLUSIONS.On the basis of the best available data, chest tube with instillation of fibrinolytics is the most cost-effective strategy for treating pediatric empyema. Video-assisted thorascopic surgery would be preferred to chest tube with instillation of fibrinolytics if the differential in length of stay between these 2 strategies were proven to be greater than that suggested by currently available data.
P
NEUMONIA IS Acommon cause of pediatric hospitalization, andⱕ50% of children hospitalized with pneumonia have an associated parapneumonic effusion.1Most of these effusions resolve spontaneously with treatment ofthe underlying pneumonia. However,⬃5% do not respond to antibiotics, usually because of the development of a “complicated” parapneumonic effusion, characterized by a loculated fibropurulent collection, or empyema. There has been a documented increase in the incidence of pediatric empyemas since the mid-1990s in both the United Kingdom2,3 and the United States,4 possibly because of serotype replacement after the universal introduction of
heptavalent pneumococcal vaccine in infants3,5 or evolving antibiotic resistance patterns.4,6,7
It is generally accepted that empyemas require additional nonmedical management to effect drainage in the form of repeated ultrasound-guided thoracentesis, thoracostomy (chest tube) drainage with or without instillation of intrapleural fibrinolytics, or drainage using video-assisted thorascopic surgery (VATS) or open thoracotomy tech-niques. There is considerable controversy regarding the most appropriate therapy. Current published guidelines recommend insertion of an ultrasound-guided small bore percutaneous chest tube (CT) with instillation of
fibrino-www.pediatrics.org/cgi/doi/10.1542/ peds.2007-1886
doi:10.1542/peds.2007-1886
Key Words
empyema, video-assisted thoracic surgery, chest tubes, decision analysis, cost-effectiveness
Abbreviations
VATS—video-assisted thorascopic surgery CT— chest tube
CTWF— chest tube with instillation of fibrinolytics
ICER—incremental cost-effectiveness ratio tPA—tissue plasminogen activator RCT—randomized, controlled trial WTP—willingness to pay
Accepted for publication Oct 19, 2007 Address correspondence to Eyal Cohen, MD, MSc, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. E-mail: eyal.cohen@sickkids. ca
lytics (CTWF) in any patient with a chest drain inserted for an empyema.8However, proponents of VATS argue
that a surgical approach to the primary management of empyema is associated with shorter hospitalization and a reduced risk of treatment failure.9–11Differences in
inter-pretation of the published literature can be largely at-tributed to an absence of large, adequately powered, randomized, controlled trials to help inform clinicians.
Although not a substitute for definitive clinical trials, a decision analysis can help guide clinicians in determin-ing the optimal choice of therapy for patients through synthesis of the best available data and by explicitly weighing the expected health and economic benefits of competing strategies. Our objective was to compare the projected costs and clinical outcomes associated with 5 competing strategies for the management of pediatric empyema to determine whether short-term increases in costs associated with new technologies are likely to be counterbalanced by diminished length of stay and im-proved clinical outcomes.
METHODS
Decision Analytic Model
We constructed a decision tree (Fig 1) to evaluate the cost-effectiveness of competing strategies for the man-agement of pediatric empyema. We used a Bayesian tree approach to estimate the payoffs of each strategy. The strategies considered were, in order of increasing inva-siveness: (1) nonoperative (antibiotics with or without delayed CT insertion); (2) immediate CT insertion with-out instillation of fibrinolytic agents; (3) repeated thora-centesis; (4) CTWF; or (5) VATS. The model outputs were costs (in US $) and benefits (life expectancy in life-years). Incremental analyses were performed by ranking all 5 of the strategies in order of increasing effectiveness after eliminating strategies that were more costly and less effective than another strategy (simple dominance). We then calculated the incremental cost-effectiveness ratio (ICER) for each strategy, defined as the marginal cost divided by the marginal benefit, com-FIGURE 1
pared with the next most expensive option. When a given strategy had a higher cost but lower ICER than the next most effective strategy, the less effective strategy was eliminated by so-called “weak dominance.” All of the analyses were performed on TreeAge Pro 2006 Suite (TreeAge, Williamstown, MA).
Costs
Base-case unit cost data expressed in US dollars were obtained from published estimates from a large, interna-tionally recognized pediatric institution, Great Ormond Street Hospital (London, United Kingdom),12
supple-mented by recommended rates of reimbursement in Canada or the United States, where available. For sen-sitivity analyses, we also estimated Canadian costs from our hospital and American costs from published facility and physician charges for empyema management,13
us-ing a cost/charge ratio of 0.4,14 supplemented by the
average per-diem Medicare hospital reimbursement for pneumonia and pleurisy in 0- to 17-year-olds,15
physi-cian reimbursement,16and medication costs.17All of the
costs were converted to 2006 dollars using the medical services component of the consumer price index.18All of
the patients receiving fibrinolytics were assumed to re-ceive 6 doses of urokinase, and costing of 1 to 6 doses of
an alternative fibrinolytic agent (tissue plasminogen ac-tivator [tPA]) was incorporated into sensitivity analyses. Costs of parenteral antibiotics were not modeled, be-cause they were assumed to be proportionately related to length of stay and could be captured with liberal estimates of the cost per day in hospital. We also did not incorporate outpatient costs after discharge, such as di-agnostic imaging and oral antibiotics, because these can be assumed to be identical in all arms of the study as per current treatment guidelines.8The cost estimates used in
the analysis are summarized in Table 1.
Outcomes
Mortality estimates were based on available data. A meta-analysis of observational trials only described mor-tality in conservatively treated patients.10In the absence
of reports of empyema-related mortality for other ther-apeutic modalities, we used published data on estimates of attributable mortality from anesthesia (0.005%)19and
lifetime attributable cancer mortality risk from chest computed tomography radiation exposure in a young child (0.100%).20,21 For repeated thoracentesis, we
as-sumed that the procedure was performed on the patient 3 times22without anesthesia and relied on estimates on
the risk of pneumothorax (2.5% per thoracentesis),23 TABLE 1 Base-Case and Plausible Range Estimates for Selected Model Variables
Parameter Base Case, GOSH/HSC/US
Estimates
Plausible Range Ref No(s).
Costs, US $
Hospitalization day (gross costing) 781a/650/1068 700–2000 12, 13, 15
Blood transfusion 500a 200–600 36, 37
CT insertion (surgeon or radiologist/anesthetist/ operating room)
1192a/1100/3118 1000–5000 12–15
Fibrinolytics (6 doses of urokinase) 484a 90–639 12, 34
Fibrinolytics (1–6 doses of tPA) 1400 90–2000 17
Repeated thoracentesis 200a 100–500 22, 38
VATS (surgeon, anesthetist, or operating room) 4121a/2243/5408 4000–6000 12–15
Computer tomography chest scan 864a/850/465 400–1000 12, 16
Length of stay, d
Nonoperative therapy strategy 20.0 8.0–28.0 10
Chest tube strategy 1.28 * LOS CTWF 1.16–1.41 * LOS CTWF 32
CTWF strategy 6.7 6.0–20.0 12, 32
Repeated thoracentesis strategy 22.0 14.4–29.6 22
VATS strategy 6.0 5.8–16.6 10, 12, 13
Outcome probabilities
Bleeding (requiring transfusion) from fibrinolytics
0.02 0.0–0.04 Unpublishedb
Pneumothorax from repeated thoracentesis 0.075 0.025–0.1 22, 23
Death from nonoperative therapy 0.03 0.0–0.1 10
Death from CT therapy 0.00005 0.00005–0.01 19
Death from CTWF therapy 0.00005 0.00005–0.01 19
Death from VATS 0.001 0.00005–0.01 19–21
Death from pneumothorax 0.0005 0.0001–0.01 —
Failure from nonoperative therapy 0.236 0.0–0.67 10
Failure from CT therapy 0.16 0.10–0.24 31, 32
Failure from CTWF therapy 0.09 0.0–0.17 12, 31, 32
Failure from repeated thoracentesis 0.14 0.05–0.30 22
Failure from VATS 0.1 0.0–0.2 12, 13
GOSH indicates Great Ormond Street Hospital; HSC, Hospital for Sick Children; LOS, length of stay. aThese costing estimates were used for base-case estimates.
assuming a mortality of 0.05% in patients who devel-oped a pneumothorax. For all of the sensitivity analyses, we examined mortality rates ⱕ1% for each arm. The base-case costs and probabilities with all of the plausible ranges of variables are presented in Table 2.
Base-Case Analysis
The base case was a previously healthy 5-year-old boy with an ultrasound-confirmed empyema and a normal life expectancy of 72.4 years, based on standard life tables available through Statistics Canada (www.statcan. ca/english/freepub/84-537-XIE/tables.htm). An age of 5 years was chosen, because this is a common median age of presentation of empyema in trials, and male gender was chosen, because the condition is more prevalent in boys.24 Base-case probabilities and outcome estimates
were derived from the published medical literature, with preference given to grouped means or proportions of pooled data derived from randomized, controlled trials (RCTs) comparing therapeutic strategies; in the absence of RCT data, we used estimates from a meta-analysis of observational studies.10 RCTs were found in PubMed
using the search terms “empyema” OR “pleural effu-sion” AND “randomized, controlled trials” and limiting the search to children (0 –18 years). Manual review of the reference lists of identified studies, as well as the reference list of recently published systematic reviews of the pediatric empyema literature,8,10were also examined
to identify other studies. For the repeated thoracentesis arm, trial or pooled data were unavailable, so we used data from the only known published observational study on this therapy in pediatric empyema.22 Liberal
estimates of plausible ranges were derived from the 95% confidence interval of the data presented or the next best data source. For instance, if RCT data were used for the base case, then the widest range of data from either the individual RCTs or from the pooled observational data determined the plausible range.
Assumptions
Pediatric trials that described delayed instillation of fi-brinolytics after insertion of a CT were analyzed as being in the CT alone strategy. Adult studies were excluded, because it is well accepted that experiences with adults cannot be extrapolated to children because of the high mortality and coexistent illness in adults with empy-ema.25 All of the children undergoing VATS were
as-sumed to have a single computed tomography chest scan, because most surgeons request this scan be
per-formed before an operation. Other diagnostic imaging scans were excluded from the model, because there are no evidence-based guidelines that recommend the fre-quency and modality of their use in empyema. All of the patients who failed their primary procedure underwent a salvage procedure. This procedure was either the same or more invasive then the initial therapy. If the salvage procedure was surgical, it was assumed to be VATS. Although some clinicians use an open thoracotomy technique for patients who fail primary therapy, the frequency of this procedure and the costs and effective-ness of this procedure are either unknown or have never been evaluated in a trial. In addition, it was assumed that all of the patients had a maximum of a single salvage procedure. Therefore, if there was no improvement from the salvage procedure, the patient would not require yet another salvage procedure. In the absence of outcome data from trials on salvage procedures, it was also as-sumed that the cost and outcome of a salvage procedure were the same as those of the primary procedure. Thus, if a patient failed VATS and required salvage VATS, it was assumed that the costs were twice the costs of a single VATS, and the outcome (survival) was the inde-pendent product of the outcome of 2 VATS procedures. This is congruent with literature reports of the overall cost of patients needing salvage VATS as approximately double that of patients who underwent primary VATS.9
Outcomes of patients receiving fibrinolytic agents were assumed to be independent of the type of agent used (urokinase or tPA) or the frequency of use (1– 6 times per patient).
Because most children with empyema completely re-cover with no clinically important pulmonary sequelae, such as exercise intolerance,8,26–28it was also assumed that
all of the patients who survived empyema to discharge had a normal quality of life after discharge. In other words, the effectiveness outcome of expected life-years was chosen because it approximates quality-adjusted life-years, the standard metric used in many cost-effectiveness analyses.29
Sensitivity Analyses
We performed a deterministic 1-way sensitivity analysis on all of the variables in our model to determine the effect of varying baseline estimates within clinically plausible ranges on our results. Variables that were sen-sitive to changes in baseline estimates were modeled with a 2-way sensitivity analysis.
In addition, we performed Monte Carlo simulations, in which cohorts of simulated patients underwent
man-TABLE 2 Cost, Survival, and Average Cost-effectiveness of Competing Strategies for the Management of Pediatric Empyema
Strategy Cost, $ Incremental Cost, $
Effectiveness, Survival in y
Incremental Effectiveness
C/E, $ per Life-Year
Incremental Cost-effectiveness, $
CTWF 7787 — 72.43 — 108
CT 9436 1649 72.42 ⫺0.005 130 Dominated
VATS 10 632 2845 72.36 ⫺0.070 147 Dominated
Nonoperative 17 874 10 087 70.03 ⫺2.397 255 Dominated
Repeated thoracentesis 18 580 10 793 72.43 0.002 257 6 422 699
agement of empyema. Such simulations use a random-number generator to create unique, simulated individual patients and move them through a series of chance events over time. A running tally of outcomes, costs, and events is recorded, with the creation of simulated co-horts that can be compared with one another. We per-formed 1000 second-order simulations, with character-istics of patient cohorts and probabilities, outcomes, and costs drawn from plausible distributions. Each second-order simulation was composed of 1000 first-second-order prob-abilistic trials (ie, 1 million trials in total), with parameter values held constant. Probabilities were assumed to fol-low distributions, whereas other parameter distribu-tions were assumed to be triangular and bounded by upper and lower bound parameter estimates. Monte Carlo simulations were used to construct cost-acceptabil-ity curves,30 with the likelihood that a given strategy
would be favored plotted against societal willingness-to-pay for an additional life-year.
RESULTS
Base-Case Estimates
The least costly strategy was CTWF with a cost of $7787 and survival of 72.43 years. At a cost of $18 581, re-peated thoracentesis had a marginal increase in life ex-pectancy of⬍1/100th of a year, resulting in an ICER of $6 422 698 per life-year gained relative to CTWF. All of the other strategies had higher cost and lower survival than CTWF. In particular, VATS was $2835 more costly and less effective by 0.07 years than CTWF. The nonop-erative arm was associated with a 2.4-year decreased survival and was, thus, the only strategy associated with a marked (⬎1/10th of a year) difference in survival. Table 2 summarizes the results of the base case for all of the strategies. No qualitative changes in the relative attractiveness of competing strategies occurred with the use of discounted, rather than undiscounted, estimates of life expectancy or with the use of Canadian or US cost estimates.
Sensitivity Analyses
Model projections were most sensitive to changes in the anticipated length of stay of CTWF. If the baseline length of stay rose beyond a threshold of 10.3 days, VATS became the preferred option. Similarly, assuming a will-ingness to pay (WTP) of $75 000 per life-year gained, once the probability of mortality from CTWF rose be-yond 0.2%, with all of the other strategies remaining equal, VATS became the preferred option. The predic-tion of CTWF as the preferred strategy was robust to all of the other univariate and bivariate sensitivity analyses. Using a more expensive fibrinolytic agent (tPA) de-creased the threshold value where VATS is preferred to a length of stay of 9.2 days. Given that the cost-per-day base-case estimates were conservative and did not incor-porate the cost of antibiotics, a 2-way sensitivity analysis of cost per day and length of stay of CTWF is described. As shown in Fig 2, increasing the cost per day up to FIGURE 2
Two-way sensitivity analysis of hospital cost per day and length of stay (CTWF). The preferred strategy for any given values along the plausible range is denoted by shading, and the asterisk represents the base-case estimate.
FIGURE 3
$5000 does not change the preferred strategy with base-case assumptions but decreases the threshold length of stay, where VATS becomes the preferred strategy. Pro-jections were insensitive to variation in other model parameters across plausible ranges. There were no changes in model projections when we simulated sur-vival in girls rather than in boys.
Monte Carlo Simulation
In probabilistic sensitivity analyses that incorporated pa-rameter distributions and random chance, CTWF was the preferred strategy in⬎58% of trials, regardless of the societal WTP threshold (Fig 3). The attractiveness of VATS relative to CTWF and other strategies declined with increasing WTP for a life-year, because the cost savings associated with reduced length of stay became less influential. Repeat thoracentesis became a more at-tractive strategy with increasing WTP, but the likelihood that this strategy was preferred was always ⬍10% for WTP thresholds up to $200 000 per life-year gained.
DISCUSSION
The preferred strategy in this decision analysis was CTWF. Repeated thoracentesis would be preferred only if societal willingness to pay was more than $6 000 000 per life-year gain, a ratio that is generally not considered cost-effective in most health care settings. The results were robust and only sensitive to changes in either length of stay of CTWF or mortality of CTWF beyond the best available estimates in the literature. CTWF was the preferred strategy, regardless of societal willingness to pay for health, in probabilistic sensitivity analyses.
There have been 4 RCTs,12,13,31,32 1 meta-analysis of
observational studies,10 and 1 guideline8 published to
date that have compared the therapeutic options pre-sented in this decision analysis. The results of the RCTs are summarized in Table 3. In the 2 trials comparing CT with CTWF, 1 study described a decreased length of stay in patients who received a CTWF compared with a CT with installation of saline,32 whereas another smaller
trial31found no difference in the length of tube insertion
in the 2 groups but an increase in the need for surgical drainage in the placebo group. Our model provides ad-ditional support for the recommendation that intrapleu-ral fibrinolytic agents decrease the costs associated with treatment of empyema.
Of greater controversy has been the debate over the relative benefit of VATS over CTWF. One small RCT (n⫽
18) showed a significantly reduced length of stay and a nonsignificant trend toward lower cost in patients who received VATS,13whereas another larger study (n⫽60)
demonstrated no difference in length of stay and in-creased costs with VATS.12The difference in the results
of the 2 studies can be attributed largely to differences in length of stay in the nonsurgical arms (13.2 vs 6.0 days), possibly because of the use of fibrinolytics as salvage rather than primary therapy in the CT arm of the smaller study. A meta-analysis of observational studies10on this
question reported improvement in mortality (0.0% vs 3.3%), reintervention rate (2.5% vs 23.5%), length of TABLE
stay (10.8 vs 20.0 days), and duration of chest drain insertion (4.4 vs 10.6 days) in operatively treated pa-tients (VATS or thoracotomy) compared with papa-tients treated with fibrinolytic therapy. The frequency of all of these outcomes and the rate of complications with fi-brinolytics are much higher in this meta-analysis than those reported in the aforementioned RCTs. This could be partially attributed to limitations in the meta-analysis resulting from the inclusion of observational and largely retrospective studies with heterogeneous patient popu-lations from disparate parts of the world. For instance, some studies included children with simple effusions, and there are many potential confounders for all of the outcomes presented. Critics of this review have argued that the systematic reviews of this topic should prefer-entially use the best available data from published RCTs as opposed to simply pooling observational studies.33Our
decision analysis incorporated this recommendation to derive base-case estimates from randomized, controlled trials whenever possible, although we did use other data sources for sensitivity analyses. Our projections were robust in the face of variation of model parameters re-lated to costing and failure rates.
The major limitation in constructing this model is the inconsistent and limited published data available on this topic. Few RCTs have been published, and all are small, with a maximum of 60 patients enrolled. Attempts to synthesize data from observational trials for pediatric empyema are limited by the varying quality of these largely retrospective studies that make the pooling of results problematic.33In addition, most surgical trials are
contemporary, whereas many nonsurgical trials are not, making time an important source of bias in the assess-ment of outcomes.9 There is marked variation in the
timing of interventions for patients in the published literature. It is well recognized that “late” interventions can be associated with prolonged recovery in both med-ical34and surgical7therapies.
Another limitation in this model is the use of length of stay as an important predictor of cost. Although length of stay has some face validity in that it is affected by the course of diseases and treatments, it is also influ-enced by a number of other extraneous factors, such as patient characteristics, physician preferences, and hospi-tal policy. Also, important attributes of suboptimal health states (eg, pain associated with recovery from a procedure) were not captured at all in this model. Length of stay does serve as a proxy for this outcome, because most patients in the hospital for prolonged pe-riods suffer similar pain, as they tend to all have CTs in situ. Also, given that empyema is an acute condition of relatively short duration, it is not anticipated that esti-mates of disuse of health states would have changed the results of the cost-effectiveness analysis. Parental pref-erences are also important to consider but were not modeled, because these were not readily available and were beyond the scope of this decision analysis.
Most of the cost estimates chosen for use in the study were obtained from published data from a major pedi-atric hospital and replicated with North American data. However, the unit costs may not be applicable to all
health settings. For instance, the estimated cost of the fibrinolytic agent used in the United Kingdom (uroki-nase) is different from published costs of other fibrino-lytic agents (eg, tPA). Costing of tPA varies markedly depending on dosing protocol and location, ranging from as low as $90 per child in our institution, where tPA has been used successfully in a single dose,34 to as
high as $1637 per child for a protocol of 6 doses of tPA using American costing estimates.17,18Urokinase is
cur-rently not available in the United States. Although more study is needed, the best available data seems to suggest that the efficacy of tPA and urokinase in pediatric em-pyema is similar.35
Despite the limitations outlined, this decision analysis can guide clinical decision-making and inform the ratio-nal allocation of health resources. In particular, for pro-ponents of VATS, the potential benefits of cost savings from small decreases in length of stay for VATS are offset by the difference in upfront costs and potentially the hypothetical risk associated with exposure to ionizing radiation from a CT scan. Future trials intended to test the hypothesis that VATS is superior over CTWF need to be designed and powered to show more than just a difference in length of stay, but either a difference in length of stay that is substantial enough to justify the additional expenditures and risks associated with this procedure or evidence for substantial advantages in ef-ficacy as determined by improvements in long-term lung function or exercise tolerance with VATS.
Based on commonly accepted cost-effectiveness thresholds and the best available data, CTWF is the most cost-effective strategy for treating pediatric empyema. Currently, in most centers, the “preferred” treatment is realistically driven by local expertise (eg, a surgeon who can perform VATS, or an interventional radiologist who can insert an image-guided flexible percutaneous cath-eter), as well as health care provider and caregiver pref-erences. However, as a guide to the allocation of re-sources, this cost-effectiveness analysis does support the contention that VATS is not superior to CTWF. VATS would be preferred to CTWF only if the differential in length of stay or survival between these 2 strategies was proven to be greater than that suggested by currently available data.
ACKNOWLEDGMENTS
We thank Drs Ahmed Bayoumi and Sanjay Mahant for helpful comments and Drs Yvonne Yau and Karen Thomas for advice on model estimates.
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DOI: 10.1542/peds.2007-1886
2008;121;e1250
Pediatrics
Eyal Cohen, Michael Weinstein and David N. Fisman
Empyema
Cost-effectiveness of Competing Strategies for the Treatment of Pediatric
Services
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DOI: 10.1542/peds.2007-1886
2008;121;e1250
Pediatrics
Eyal Cohen, Michael Weinstein and David N. Fisman
Empyema
Cost-effectiveness of Competing Strategies for the Treatment of Pediatric
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