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Transversus Abdominis Plane Block to Ameliorate Postoperative Pain Outcomes After Laparoscopic Surgery: A Meta-Analysis of Randomized Controlled Trials

De Oliveira, Gildasio S. Jr MD, MSCI; Castro-Alves, Lucas Jorge MD; Nader, Autoun MD; Kendall, Mark C. MD; McCarthy, Robert J. PharmD

doi: 10.1213/ANE.0000000000000066
Pain Medicine: Research Report
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BACKGROUND: Transversus abdominis plane (TAP) block has been used as a multimodal strategy to optimize postoperative pain outcomes; however, it remains unclear which type of surgical procedures can benefit from the administration of a TAP block. Several studies have examined the effect of the TAP block on postoperative pain outcomes after laparoscopic surgical procedures and generated conflicting results. Our main objective in the current investigation was to evaluate the effect of TAP block on postoperative analgesia outcomes for laparoscopic surgical procedures.

METHODS: A search was performed to identify randomized controlled trials that evaluated the effects of the TAP block compared with an inactive group (placebo or “no treatment”) on postoperative pain outcomes in laparoscopic surgical procedures. Primary outcomes included early (0–4 hours) and late (24 hours) postoperative pain at rest and on movement and postoperative opioid consumption (up to 24 hours). Meta-analysis was performed using a random-effects model. Publication bias was evaluated by examining the presence of asymmetric funnel plots using Egger regression test. Meta-regression analysis was performed to establish an association between the local anesthetic dose and the evaluated outcomes.

RESULTS: Ten randomized clinical trials with 633 subjects were included in the analysis. The weighted mean difference (99% confidence interval) of the combined effects favored TAP block over control for pain at rest (≤4 hours, −2.41 [−3.6 to −1.16]) and (at 24 hours, −1.33 [−2.19 to −0.48]) (0–10 numerical scale). Postoperative opioid consumption was decreased in the TAP block group compared with control, weighted mean difference (99% confidence interval) of −5.74 (−8.48 to −2.99) mg morphine IV equivalents. Publication bias was not present in any of the analysis. Preoperative TAP block administration resulted in greater effects on early pain and opioid consumption compared with postoperative administration. Meta-regression analysis revealed an association between local anesthetic dose and the TAP block effect on late pain at rest and postoperative opioid consumption. None of the studies reported symptoms of local anesthetic toxicity.

CONCLUSIONS: TAP block is an effective strategy to improve early and late pain at rest and to reduce opioid consumption after laparoscopic surgical procedures. In contrast, the TAP block was not superior compared with control to reduce early and late pain during movement. Preoperative administration of a TAP block seems to result in greater effects on postoperative pain outcomes. We also detected a local anesthetic dose response on late pain and postoperative opioid consumption.

From the Department of Anesthesiology, Northwestern University, Chicago, Illinois.

Accepted for publication November 15, 2013.

Funding: Department of Anesthesiology, Northwestern University, Chicago, IL.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Gildasio S. De Oliveira Jr, MD, MSCI, Department of Anesthesiology, Northwestern University, 241 East Huron St., F5-704, Chicago, IL. Address e-mail to g-jr@northwestern.edu.

The advance in surgical techniques and the development of anesthetics with low side effect profiles have enabled the current rapid growth of outpatient surgical procedures.1,2 Recently, larger procedures such as prostatectomy and gynecological cancer surgeries have been performed laparoscopically allowing a better and faster postoperative recovery to patients.3,4 Nevertheless, postoperative pain seems to remain a very important factor that can deteriorate the overall quality of recovery after laparoscopic procedures.5,6

Transversus abdominis plane (TAP) block has been used as a multimodal strategy to optimize postoperative pain outcomes. However, in recent reviews evaluating the clinical effectiveness of TAP block, the investigators were not able to identify the surgical procedures, dosing, techniques, and timing that provide optimal analgesia after TAP block.7,8 Since then, evidence suggested an effective role for TAP block to minimize postoperative pain in certain procedures such as cesarean deliveries that do not include intrathecal morphine.9 In contrast, it remains to be determined whether TAP block can improve analgesic outcomes after laparoscopic surgical procedures.

The main objective of the current investigation was to examine the effect of TAP block on postoperative pain outcomes after laparoscopic surgeries. We also sought to investigate the effect of block timing and local anesthetic dose on the evaluated outcomes.

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METHODS

We performed a quantitative systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.10

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Systematic Search

Published reports of randomized trials evaluating the effects of TAP block on surgical postoperative pain were searched using the National Library of Medicine’s PubMed database, the Cochrane Database of Systematic Reviews, and Google Scholar inclusive of April 21, 2013. Free text and MeSH terms “transversus,” “pain,” “postoperative,” “preoperative,” “analgesia,” and “opioid” were used individually and in all pairwise combinations. No language restriction was used. The search was limited to human subjects aged >18 years. An attempt to identify additional studies not found by the primary search methods was made by reviewing the reference lists from identified studies. No search was performed for unpublished studies. This initial search yielded 115 randomized clinical trials.

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Selection of Included Studies

The study’s inclusion and exclusion criteria were determined before the systematic search. Two authors independently evaluated the abstract and results of the 115 articles obtained by the initial search. Articles that were clearly not relevant based on our inclusion and exclusion criteria were excluded at this phase. Disagreements on inclusion of the articles were resolved by discussion among the evaluators. If an agreement could not be reached, the dispute was resolved with the help of a third investigator. The third investigator was blinded regarding evaluation of the first 2 authors.

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Inclusion and Exclusion Criteria

We included randomized controlled trials that compared perioperative TAP blocks with local anesthetics and an inactive (placebo or “no treatment”) control group in patients undergoing laparoscopic surgical procedures under general anesthesia. Trials that evaluated the effect of the TAP block in patients undergoing a different surgical procedure than laparoscopy were excluded to optimize clinical homogeneity. Studies containing a concurrent use of an alternative multimodal analgesia regimen were excluded if a direct comparison of TAP block and control (sham or no block) could not be established. Included studies had to report at least on pain scores or opioid consumption as postoperative pain outcomes. No minimum sample size was required for inclusion in the meta-analysis.

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Validity Scoring

Two authors independently read the included reports and assessed their methodological validity using a modified Jadad 5-point quality scale.11 The scale evaluates the study for the following: randomization, double-blind evaluation, concealment of study group to evaluator, valid randomization method, and completeness of data at follow-up. Discrepancies in rating of the trials were resolved by discussion among the evaluators. If an agreement could not be reached, the dispute was resolved with the help of a third investigator. Because only randomized trials were included in the analysis, the minimum possible score of an included trial was 1 and the maximum was 5. Trials were not excluded or weighted in the analysis based on quality assessment scores.

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Data Extraction

Two authors independently evaluated the full manuscripts of all included trials and performed data extraction using a data collection form specifically developed for this review.

Discrepancies were resolved by discussion between the investigators. If an agreement could not be reached between the 2 investigators, the decision was made by a third investigator. Data extracted from trials included the local anesthetic type and dose, sample size, number of subjects in treatment groups, follow-up period, type of surgery, early pain scores (≤4 hours) at rest and at movement, late pain scores (24 hours) at rest and at movement, cumulative opioid consumption, time to rescue analgesic administration (minutes), and adverse events. Postoperative opioid consumption was converted to the equivalent dose of IV morphine.12 A visual analog scale or numeric rating scale for pain was converted to a 0 to 10 numeric rating scale.

Data were initially extracted from tables or text. For data not available in tables, the data were abstracted from available figures. Dichotomous data on the presence or absence of adverse effects were extracted and converted to incidence, whereas continuous data were recorded using mean and standard deviation. Data presented only as median and range were converted to means and standard deviation using previously described methodology.13 In studies that involved >1 independent dose group compared with a single control group, the control group was split according to the number of comparisons. When required, the standard deviation for pain scores was estimated using the most extreme values. The most conservative value was used when the same outcome was reported more than once for a determined period.

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Definition of Relevant Outcome Data

The primary outcomes were early acute postoperative pain scores (visual analog scale or numeric rating scale) at rest and at movement (0–4 hours postoperatively), late acute postoperative pain scores (visual analog scale or numeric rating scale) at rest and at movement (24 hours postoperatively), and cumulative opioid consumption (24 hours) in the postoperative period.

The secondary outcomes were the time to first analgesic administration (minutes); adverse events included postoperative hypotension, nausea, and/or vomiting.

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Meta-Analyses

The weighted mean differences (WMDs) with 99% confidence interval (CI) were determined and reported for continuous data. For dichotomous data (adverse effects), the Peto odds ratio (to account for the potential of 0 counts in the cells for low-frequency outcomes) and 99% CI are reported. For primary outcomes, a significant effect compared with placebo required that the 99% CI for continuous data did not include 0, and for dichotomous secondary data, the 95% CI did not include 1.0. Due to the different surgical procedures, we used a random effect model in an attempt to generalize our findings to studies not included in our meta-analysis.14 Publication bias was evaluated by examining for asymmetric funnel plots using the Egger regression test.15,16 A 1-sided P < 0.05 was considered an indication of an asymmetric funnel plot. A file drawer analysis described by Rosenthal17 was performed in the case of an asymmetric funnel plot. The test estimates the lowest number of additional studies that if they would become available would reduce the combined effect to nonsignificance, assuming the average z value of the combined P values of these missing studies would be 0.

Heterogeneity of the included studies was further evaluated if the I2 statistic was >50%. The I2 statistic is a test of heterogeneity that measures the variability between studies included in a quantitative analysis regarding an evaluated outcome. I2 values range between 0% and 100%, where 0 represents perfect homogeneity among included studies and 100% represents the highest degree of heterogeneity. Further analysis was planned a priori to explore nontrivial heterogeneity of the treatment effect across the included studies, including time of block administration (preoperatively versus postoperatively) and quality of included studies evaluated by the Jadad score. Subgroup analysis was performed to test whether the overall effect of TAP block on evaluated outcomes changed when lower quality studies (Jadad ≤3) were removed from the analysis. The proportion of the total variance explained by the covariates (R2) was calculated by dividing the random-effects pooled estimates of variance (τ2) within studies by the total variance (total τ2). The value obtained was then subtracted from 1. When values were outside the range of 0% to 100%, they were set to the closest value (0% or 100%). A meta-regression analysis was performed to evaluate a possible association between total local anesthetic dose and the effect size on evaluated outcomes. Equipotent doses of ropivacaine were converted to bupivacaine (0.7 mg bupivacaine = 1 mg ropivacaine).18,19 Because we prespecified 5 primary outcomes (2 pain states at 2 times each, plus opioids), we assessed a P value <0.01 as significant to minimize the chance of type I error.

Analysis was performed using Stata version 11 (StataCorp LP, College Station, TX) and Comprehensive Meta-analysis software version 2 (Biostat, Englewood, NJ).

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RESULTS

Of the initially evaluated abstracts, 18 studies initially met the inclusion criteria (Fig. 1). Eight studies were subsequently excluded: 3 did not report on evaluated outcomes,20–22 1 evaluated children,23 1 trial did not provide a direct comparison between TAP blocks and control,24 and 3 reported on surgical procedures other than laparoscopy.25–27 The characteristics of included studies are listed in Table 1. The evaluated trials included data from 633 subjects and were published between 2009 and 2013.28–37 All TAP blocks were performed under ultrasound guidance. The median (interquartile range) number of patients in the included studies receiving TAP block was 34.5 (27–43). The median (interquartile range) of the modified Jadad scale score was 4 (4–5). All 10 studies reported on opioid consumption and/or pain scores. Four studies reported pain scores for both rest and activity.28,30–32

Table 1

Table 1

Figure 1

Figure 1

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Early (0–4 Hours) Pain at Rest

The aggregate effect of the 6 studies (8 comparisons) evaluating the effect of TAP block on early pain at rest favored TAP block over control with a WMD (99% CI) of −2.41 (−3.6 to −1.16)29–32,35,36 (0–10 numerical scale), P < 0.001 (Fig. 2).Two studies provided 2 comparisons, and both were included in the analysis.35,36 There was no evidence of publication bias as given by the test for an asymmetric funnel plot (P = 0.32). Heterogeneity was high (I2 = 89) and could not be explained by time of block administration (perioperatively versus postoperatively). In contrast, subgroup analysis revealed a greater effect on early pain at rest when TAP block was performed preoperatively, WMD (95% CI) of −2.74 (−4.19 to −1.29), compared with postoperatively, WMD (95% CI) of −1.66 (−2.59 to −0.74), P = 0.01. Fourteen percentage of the total variance could be explained by studies with lower quality (Jadad score ≤3). A meta-regression analysis did not identify an association between the total local anesthetic dose administered and an effect on early pain at rest (slope [95% CI] = 0.0003 [−0.01 to 0.01], P = 0.94 compared with slope = 0).

Figure 2

Figure 2

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Early (0–4 Hours) Pain at Movement

The overall effect of 4 studies28,30–32 evaluating the effect of TAP blocks on early pain at movement compared with control did not show a significant benefit of TAP blocks relative to a wide CI, mean difference (99% CI) of −0.52 (−2.00 to 0.95) (0–10 numerical scale), P = 0.35 (Fig. 3). Heterogeneity was high (I2 = 77), and it could not be explained by removal of the only study in which TAP block was performed postoperatively.32

Figure 3

Figure 3

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Late (24 Hours) Pain at Rest

The overall effect of 7 studies (10 comparisons)29–31,33–36 on the effect of TAP block on late pain at rest compared with control favored TAP block, WMD (99% CI) of −1.33 (−2.19 to −0.48) (0–10 numerical scale), P = 0.001 (Fig. 3). The funnel did not demonstrate asymmetry (P = 0.25). Heterogeneity was high (I2 = 94%). Neither the effect size nor the variance was altered at time of block performance (preoperatively versus postoperatively). The overall effect was larger for lower quality studies (2 comparisons),35 WMD (95% CI) of −2.98 (−3.75 to −2.20) compared with higher quality studies (8 comparisons),29–31,33–35 WMD (95% CI) of −0.99 (−1.67 to −0.31), P < 0.001. A meta-regression analysis identified an association between the total local anesthetic dose administered (milligrams of bupivacaine equivalents) and an effect on late pain at rest (slope [95% CI] = −0.017 [−0.022 to −0.013], P < 0.001 compared with slope = 0; Fig. 4). A meta-regression analysis also identified an association between the total local anesthetic volume administered (milliliters) and an effect on late pain at rest (slope [95% CI] = −0.02 [−0.045 to −0.006], P < 0.001 compared with slope = 0).

Figure 4

Figure 4

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Late Pain (24 Hours) at Movement

The overall effect of 3 studies28,30,31 that examined the effect of TAP block on late pain at movement compared with control did not reveal a significant effect in relation to a large CI, WMD (99% CI) of 0.33 (−0.40 to 1.07) (0–10 numerical scale), P = 0.31. Heterogeneity was low (I2 = 0). All the studies evaluated TAP block performed preoperatively.

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Postoperative Opioid Consumption (up to 24 Hours)

The aggregated effect of 7 studies (9 comparisons)28,30,32–35,37 evaluating the effect of TAP block on postoperative opioid consumption compared with control favored TAP block, WMD (99% CI) of −5.74 (−8.48 to −2.99) mg IV morphine, P < 0.001 (Fig. 5). Two studies provided 2 comparison, and they were included in the analysis.34,35 The funnel plot did not demonstrate asymmetry (P = 0.12). Heterogeneity was high (I2 = 89%).The aggregated effect of studies evaluating TAP block performed preoperatively was substantially greater, WMD (95% CI) of −6.34 (−8.52 to −4.15) compared with the effect of the only study that evaluated TAP block performed postoperatively, WMD (95% CI) of −0.1 (−5.16 to 4.96), P = 0.03. A meta-regression analysis suggested an association between the total local anesthetic dose administered and an effect on postoperative opioid consumption (slope [95% CI] = −0.02 [−0.03 to −0.007], P = 0.003 compared with slope = 0; Fig. 6).

Figure 5

Figure 5

Figure 6

Figure 6

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Time to First Analgesic Administration (Minutes)

The only study evaluating TAP block on time to first analgesic administration demonstrated an effect compared with control, WMD (95% CI) of 27.0 (15.4–38.5) minutes, P < 0.001.28 This was a high-quality study (Jadad = 5) and evaluated TAP block performed preoperatively.

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Safety Analysis

Local Anesthethetic Toxicity

None of the included studies reported on clinical manifestations of local anesthetic toxicity.

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Postoperative Nausea and Vomiting

The aggregated effect of the studies examining TAP block on postoperative nausea and/or vomiting compared with placebo did not reveal a significant effect in relation to a large CI, odds ratio (95% CI) of 1.5 (0.8–2.7).28,30,31,33

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DISCUSSION

The most important finding of the current investigation is the significant effect of TAP block in the reduction of postoperative pain outcomes for laparoscopic surgical procedures. TAP block reduced early pain at rest, late pain at rest, and postoperative opioid consumption. None of the included studies reported on complications due to the performance of TAP block. Taken together, our results suggest that TAP block may be an effective strategy to improve analgesic outcomes in patients undergoing laparoscopic surgical procedures.

Another important finding of the current investigation was the detection of the preoperative time as the likely optimal period for the administration of TAP block. The preoperative administration of TAP block specifically reduced early pain at rest and postoperative opioid consumption compared with postoperative administration of the block. Our results suggest some preventive analgesic properties of TAP block for early pain from laparoscopic procedures as previously reported and disputed by different investigators.18,38–40 In contrast, we did not observe the same beneficial preventive analgesic properties for late pain at rest. It is possible that the larger opioid consumption in the group that had TAP block performed postoperatively compared with the group that had the block performed preoperatively contributed to the lack of observed differences in late pain scores.

We were also able to detect a relationship between the local anesthetic dose and the effect on some of the outcomes. Studies that used higher doses of local anesthetics reported greater opioid-sparing effects and lower pain scores at 24 hours. In contrast, higher doses of local anesthetics did not result in lower pain scores during the early postoperative hours after surgery. It is important to note that higher doses of local anesthetics have been associated with mild neurotoxicity in patients receiving TAP block for cesarean delivery.41 We only included subjects who received TAP block under general anesthesia, and this fact did not allow us to detect mild neurological symptoms possibly associated with higher doses of local anesthetics.

It was interesting to note that despite a significant reduction in postoperative pain outcomes using TAP block, we were unable to find a reduction in opioid-related side effects such as postoperative nausea and vomiting. The large variation of risk profiles and the differences in the number/dosage of prophylactic antiemetic drugs among studies might have contributed to the lack of benefit from TAP block on postoperative nausea and/or vomiting.42–44 Nevertheless, few studies have reported on the beneficial effect of regional anesthesia techniques in more global recovery outcomes.45

Our group has reported on the overall effect of TAP block to improve the quality of postsurgical recovery after laparoscopic surgery.34,35 In contrast, Kane et al.32 did not detect a beneficial effect on the quality of recovery in subjects undergoing laparoscopic hysterectomy. Several methodological differences such as variations of the surgical procedure and the inclusion of obese subjects could have contributed to the lack of ability of Kane et al.32 to demonstrate an effect of TAP block on the quality of recovery. Even more importantly, Kane et al.32 administered TAP block postoperatively that may have limited the overall effect on analgesic outcomes.

It important to note that the studies included in the current meta-analysis compared TAP block with an inactive control group. Future studies comparing TAP block with other effective multimodal analgesic strategies are warranted. Because the performance of TAP block can be time-consuming and it requires a certain degree of expertise, other less invasive multimodal strategies such as perioperative systemic lidocaine, magnesium, and dexamethasone may be valuable alternatives to TAP block.46–48

Our current meta-analysis has substantial differences from previous quantitative systematic reviews.8,9,49 First, to the best of our knowledge, we included a larger number of trials and subjects in our analysis than previous authors.8,9,49 Second, we specifically examined the efficacy of TAP block for laparoscopic procedures rather than the previous analysis that focused on the efficacy of the TAP block for cesarean delivery.8,49 Last, we were able to demonstrate a preoperative timing benefit of TAP block on analgesic outcomes, as well as a linear association between local anesthetic dose and certain outcomes (opioid consumption and late pain at rest).

We detected a beneficial effect of TAP block for early/late pain at rest but not for early/late pain on movement. Pain on movement is often more severe than pain at rest.50 Complete relief of pain on movement is not commonly achieved with local or systemic analgesic techniques but frequently requires the use of more potent neuraxial techniques. Therefore, it was somewhat expected that TAP block would not be an efficient strategy to minimize postoperative pain on movement.

Although we detected a significant reduction in opioid consumption and pain at rest when TAP block was compared with control, the clinical impact of our findings remains to be examined. Recently, patient-centered outcomes such as quality of recovery scores have been used as a valid measurement of clinical impact for other analgesic interventions.51–54 Future studies examining TAP block should incorporate patient-centered outcomes into their designs to provide additional information regarding the clinical impact of TAP block on recovery of surgical patients.

Our investigation should be interpreted within the context of its limitations. Although we limited the type of surgical procedures and anesthesia techniques to minimize heterogeneity, we observed high heterogeneity in our analysis. Some of the variation in the effect size could be explained by different doses of the local anesthetic administered. Because studies have not directly compared the time of block administration, our subgroup analysis (preoperative versus postoperative administration of TAP block) should only be interpreted as observational and as hypothesis-generating for future studies. Only a large randomized trial can confirm or refute our findings. Another limitation of our study is that we did not register the review protocol on a registry database of systematic reviews. Registration of systematic reviews may prevent reporting bias. Nevertheless, our primary outcomes were identical to previous systematic reviews reported by our group on postoperative pain outcomes.55

In summary, we have detected a beneficial effect of TAP block on analgesia outcomes after laparoscopic surgery. The preoperative period seems to be the optimal time for administration of the block. Dose effects of local anesthetics used for TAP block were detected for late pain and opioid consumption outcomes. None of the included studies reported on the systemic effects related to local anesthetic toxicity. TAP block should be considered an effective analgesic technique to ameliorate postoperative pain after laparoscopic surgical procedures.

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DISCLOSURES

Name: Gildasio S. De Oliveira Jr, MD, MSCI.

Contribution: This author contributed for study design, conduct of the study, data analysis, and manuscript preparation.

Attestation: Gildasio De oliveira approved the final manuscript, attests to the integrity of the original data and the analysis reported in this manuscript, and is the archival author.

Name: Lucas Jorge Castro-Alves, MD.

Contribution: This author contributed for study design, conduct of the study, and manuscript preparation.

Name: Autoun Nader, MD.

Contribution: This author contributed for conduct of the study and manuscript preparation.

Attestation: Autoun Nader approved the final manuscript.

Name: Mark C. Kendall, MD.

Contribution: This author contributed for the manuscript preparation.

Attestation: Mark Kendall approved the final manuscript.

Name: Robert J. McCarthy, PharmD.

Contribution: This author contributed for study design, conduct of the study, data analysis, and manuscript preparation.

Attestation: Robert McCarthy approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

This manuscript was handled by: Spencer S. Liu, MD.

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