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A Systematic Review and Meta-Analysis of the Global Burden of Chronic Pain Without Clear Etiology in Low- and Middle-Income Countries: Trends in Heterogeneous Data and a Proposal for New Assessment Methods

Jackson, Tracy MD; Thomas, Sarah BS; Stabile, Victoria BA; Shotwell, Matthew PhD; Han, Xue MPH; McQueen, Kelly MD, MPH

doi: 10.1213/ANE.0000000000001389
Global Health: Systematic Review Article

BACKGROUND: The global burden of chronic pain is projected to be large and growing, in concert with the burden of noncommunicable diseases. This is the first systematic review and meta-analysis of the prevalence of chronic pain without clear etiology in general, elderly, and working populations of low- and middle-income countries (LMICs).

METHODS: We collected and reported data using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, excluding acute pain or pain associated with a concurrent medical condition. One hundred nineteen publications in 28 LMICs were identified for systematic review; the 68 reports that focused on general adult populations (GP), elderly general populations (EGP), or workers (W) were evaluated using mixed-effects regression meta-analysis.

RESULTS: Average chronic pain prevalence is reported as a percentage of the population, with 95% confidence interval for each pain type and population (GP, EGP, and W; NA is equal to not available): unspecified chronic pain (34[26–42], 62[41–81], and NA); low back pain (21[15–27], 28[16–42], and 52[26–77]); headache (42[27–58], 30[19–43], and 51[13–88]); chronic daily headache (5[3–7], 5[1–12], and 10[0–33]); chronic migraine (GP 12[6–19]); chronic tension type headache (GP 8[3–15]); musculoskeletal pain (25[19–33], 44[28–62], and 79[60–94]); joint pain (14[11–18], 34[16–54], and NA); chronic pelvic/prostatitis pain (GP 4[0–14]); temporomandibular disorder (35[4–78], 8[0–24], and NA); abdominal pain (EGP 17[6–32]); fibromyalgia (Combined GP, EGP, W 6[5–7]); and widespread pain (7[1–18], 19[8–32], and NA). Chronic low back pain and musculoskeletal pain were 2.50 (1.21–4.10) and 3.11 (2.13–4.37) times more prevalent among W, relative to a GP. Musculoskeletal, joint, and unspecified pain were 1.74 (1.03–2.69), 2.36 (1.09–4.02), and 1.83 (1.13–2.65) times more prevalent among the EGP, relative to a GP. There was significant heterogeneity among studies for all pain types (I2 > 90%).

CONCLUSIONS: Chronic pain is prevalent in LMICs, and where there was sufficient evidence, generally more prevalent in EGP and W. This meta-analysis reveals the spectrum of chronic pain without clear etiology in LMICs. Steps should be taken to reduce heterogeneity in the assessment of global chronic pain. Possible actions may include standardization of chronic pain definition, widespread adoption of validated questionnaires across cultures, attention to inequitably burdened populations, and inclusion of queries regarding known associations of chronic pain with social and psychological factors that, in combination, increase the global burden of noncommunicable disease and disability.

From the Vanderbilt University, Nashville, Tennessee.

Accepted for publication March 28, 2016.

Funding: None.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

This report was previously presented, in part, at the Lancet Commission on Global Surgery, which was the subject of an article in Abstract Publication in Lancet Special Supplement Volume 385 S10.

Reprints will not be available from the authors.

Address correspondence to Tracy Jackson, MD, Vanderbilt University, 719 Thompson Lane, Suite 22200, One Hundred Oaks, Nashville, TN 37204. Address e-mail to tracy.jackson@vanderbilt.edu.

International law recognizes pain management as a basic human right; nations are therefore ethically mandated to provide pain treatment as part of their core obligations under the right to health.1 Pain has been described in global literature as a symptom of modifiable disease, injury, or trauma; and when chronic, pain is presumed to reflect a failure of the treatment of the underlying disease process. However, 8 of the top 12 disabling noncommunicable disease (NCD) conditions globally—low back pain (LBP), neck pain, migraine, arthritis, other musculoskeletal (MSK) conditions, depression, anxiety, and drug use disorder—are all either pain conditions or psychological conditions strongly associated with chronic pain and often have no clear initiating event.2 Undifferentiated LBP, most often without specific etiology, is the leading cause of years lost to disability worldwide.3 Support for the scope of this issue comes from analysis of the years lived with disability (YLD) resulting from 289 diseases and injuries from 1990 to 2010 for the Global Burden of Disease (GBD) Study: NCDs account for 78.6% of YLDs worldwide; of the NCDs, MSK disorders contributed to 21.3% of all YLDs, and mental/behavioral disorders accounted for 22.7%.2

The global burden of chronic pain is projected to be large and growing, in parallel to NCD burden. Documentation of the pain burden has not been consistent in the international literature, and little progress has been made toward managing this growing crisis. This, coupled with the reported global reduction in economic productivity and increasing disability of patients with chronic painful conditions, prompted this systemic literature review and meta-analysis. It is intended to define the current state of the literature on chronic pain prevalence in low- and middle-income countries (LMICs), specifically with regard to types of disabling chronic pains that often occur without clear inciting etiologies.

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METHODS

The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for systematic review were used to collect and report data. Peer-reviewed publications were searched in PubMed, Medline, Embase, Scopus, PsycINFO, and the Cochrane Database of Systematic Reviews. The query string template, “pain and (chronic or persistent) and (low income countries or middle income countries or LMIC or Africa or Asia or Central America or Latin America or South America) and (incidence or prevalence)” was formatted as necessary for each database system. LMIC classification was confirmed by cross-referencing with the World Bank list of Countries by Income Level. Low-income economies are defined as those with a Gross National Income per capita, calculated using the World Bank Atlas method, of $1045 or less in 2013; middle-income economies are those with a Gross National Income per capita of >$1045 but <$12,746. All languages were included. Studies of populations <18 years of age, with acute pain, or pain known to be related to surgery, trauma, infection, or underlying disease were excluded. Copies of unpublished or unavailable studies were sought out by direct author communication. Studies not in English were translated via googletranslate.

One thousand two hundred fifty articles were identified by 2 independent reviewers from searches done up to and including December 2013. There was >98% concordancy in results from the reviewers’ searches. After abstract review, 311 were deemed potentially relevant. Two hundred thirteen of these were excluded: 17 had no full text available; 11 were review articles; and 186 were related to acute pain, chronic pain treatment, validation of pain tools, or described pain related to surgery, trauma, infection, or other medical conditions. After reference review of the remaining 97 relevant full texts, 58 additional articles were identified and reviewed; 20 of these were only available as abstracts and 16 were review articles. With the 22 additional relevant texts from references, 119 full text articles were identified (Figure 1). Data describing 441,516 people in 28 LMICs were extracted systematically per protocol described in Table 1.

Table 1

Table 1

Figure 1

Figure 1

Of the 119 articles subjected to systematic review (Supplemental Digital Content, http://links.lww.com/AA/B431), meta-analysis was conducted on only the 68 individual survey studies in general, elderly, and worker populations. Retrospective chart reviews, clinic populations, and other special populations were excluded to improve generalizability of reported results. Pain prevalence meta-analysis was conducted for each type of pain using linear mixed-effects regression on the Freeman-Tukey transformed prevalence estimates with inverse variance weighting.4 A 95% confidence interval (CI) for the average transformed pain prevalence was computed using the Wald method and back transformed to the probability scale. Clopper-Pearson 95% CIs were computed for individual study proportions. Subgroup analysis was used to separately examine the average prevalence of pain among general patients, elderly patients, and workers. We used the transformed estimates and corresponding standard errors, and a Monte-Carlo technique to approximate the sampling distribution of the ratio of 2 prevalence estimates, assuming that the estimates are statistically independent. The corresponding distribution function was used as a pivot to compute an approximate 95% CI for the prevalence ratio.5 This type of meta-analysis assumes that each study represents an independent sample from a subpopulation of heterogeneous LMICs, with additional heterogeneity associated with study design and unspecified study-specific factors. In particular, the average pain prevalence across studies cannot be interpreted as the prevalence of pain in all surveyed LMICs, because many of these studies do not represent a random sample from all such populations. Study heterogeneity was graphically assessed using forest plots of the study-specific pain prevalence, the inconsistency value (denoted I2), which is the percentage of variability among study-specific prevalence estimates that is due to study heterogeneity rather than sampling variability, and Cochran Q test, where P values <0.05 were considered statistically significant. I2 represents the fraction of variability in the study-specific prevalence estimates that cannot be explained by sampling variability. An I2 value near 1 indicates that the prevalence estimates differ among studies to a degree that cannot be explained by chance, had each study used the same methodology, and sampled the same population of respondents. Significant heterogeneity often occurs when studies included for meta-analysis sample different populations, use different measurement instruments, or use other nonstandardized methodology, as might be expected in a survey of LMIC pain studies.

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RESULTS

The countries reporting data are depicted in Figure 2. Definitions of pain and chronicity are compared in Figure 3 and dramatically illustrate the major reason for heterogeneity in the published prevalence data thus far.

Figure 2

Figure 2

Figure 3

Figure 3

Figure 4 is the summary of prevalence estimates from the 68 surveys included in our meta-analysis, characterized by pain type, and stratified by population (with 95% CI). Proportion ratios comparing subgroups are also included. The number of articles reporting prevalence of a specific pain type varied between 4 (temporomandibular disorder [TMD]) and 33 (LBP)(Figure 5). The total number of surveyed subjects varied from 1936 (fibromyalgia) to 80,076 (LBP). For each pain type, there was significant heterogeneity (I2 > 0.9) in prevalence among studies.

Figure 4

Figure 4

Figure 5

Figure 5

The sample prevalence of unspecified chronic pain ranged from 13% to 49.4%. However, even within Brazilian general populations, sample prevalence ranged from 33.5% (12-month point prevalence with self-reported chronicity) to 42% (pain lasting >6 months). A similar heterogeneity is illustrated in Figure 6; a forest plot of LBP prevalence in each subpopulation. All other pain types demonstrated similar heterogeneity: the I2 values and 95% confidence limits ranged from 0.93 to 1.00, indicating that most of the variability among study-specific prevalence estimates is due to study heterogeneity rather than sampling variability.

Figure 6

Figure 6

The pooled prevalence of chronic pain in all combined populations varied between 6% (3–10, chronic daily headache [HA]) and 48% (36–59, MSK pain). In general populations, the chronic pain prevalence varied between 5% (3–7, chronic daily HA) and 42% (27–58, HA). The prevalence of chronic pain among elderly general populations was between 5% (1–12, chronic daily HA) and 62% (41–81, unspecified pain). In workers, chronic pain prevalence varied between 10% (0–33, chronic daily HA) and 79% (60–94, MSK pain).

Chronic LBP and MSK pain were 2.50 (1.21–4.10) and 3.11 (2.13–4.37) times more prevalent among workers, relative to the general population. MSK pain was 1.79 (1.16–2.94) times more prevalent among workers, relative to the elderly. MSK, joint, and unspecified pain were 1.74 (1.03–2.69), 2.36 (1.09–4.02), and 1.83 (1.13–2.65) times more prevalent among the elderly, relative to the general population. There were no statistically significant differences among subgroups for other pain types.

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DISCUSSION

Chronic pain contributes significantly to the GBD. Attempts to capture the global prevalence of chronic pain in LMICs are limited but critically important, because known risk factors for chronic pain (like psychological trauma, interpersonal violence and low socioeconomic status) are higher than in high-income countries (HICs). Especially in areas with limited resources, allocation of treatment for chronic pain and its underlying contributors must be determined based on accurate, standardized data to ensure cost-effective improvement in outcomes, and effectively reduce the GBD attributable to chronic pain.

The World Mental Health Surveys, completed in 17 countries (7 LMICs) in 2008, reported the prevalence of chronic pain conditions in the previous 12 months to be 37.3% in developed countries and 41.1% in developing countries, even when controlling for comorbid physical disease.6 Elzahaf et al.7 conducted a systematic literature review (without meta-analysis of global pain in LMICs) and reported worldwide mean prevalence of pain lasting >3 months at 30.3%, although 16 of the 19 included articles reported LBP or neck pain only. In their subgroup analysis of LMICs, the prevalence of chronic pain was 33.9% compared with 29.9% in those in higher income countries. Our systematic literature review with meta-analysis is the third and largest in this series and excluded pain known to have a specific etiology such as injury, cancer, or infection; yet, similarly we found 34% (36–42) prevalence of unspecified chronic pain in LMIC general populations alone. The following is a summary of the literature by specific pain types in LMICs compared with existing global data.

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Low Back Pain

Daily chronic LBP has been difficult to assess systematically because most cross-sectional studies globally rely on self-report or point prevalence, and many do not have a minimal number of continuous days per episode defined. Globally, point prevalence has been reported at 18.1% (1.0–58), 12-month prevalence at 38.1% (0.8–82.5), and annual incidence at 1.5% to 36%. Yearly remission rates range from 54% to 90%, while 4% to 80% will have a recurrence.2,8 In a systematic review of 27 studies evaluating LBP prevalence in Africa since 2000 (primarily South Africa and Nigeria), point prevalence was higher: 32% in adults, with 12-month prevalence of 50% and lifetime prevalence of 62%.9

In our review, the overall prevalence of LBP in LMIC general populations was 21% (15–27); yet, the lowest and highest estimates on the prevalence of chronic LBP were both from general populations in Brazil (4.2%–51%), because chronicity varies from “self-defined” to “at least 7 weeks of LBP in the past 3 months” to “pain lasting at least 6 months.” Overall, our results are consistent with the African review: We found overall prevalence of chronic LBP in LMICs at 31% (24–38), with 21% (15–27) in general populations, 28% (16–42) in the elderly, and 52% (26–77) in workers.

LBP is by far the most commonly studied pain type in workers in LMICs. Annual incidence and lifetime point prevalence are often described in addition to prevalence, making the prevalence data difficult to generalize. For example, 12.8% of Tunisian workers reported chronic LBP >3 months duration in the past 12 months, with 57.1% reporting a lifetime episode, and 50.1% reporting some LBP in the past year.10

The psychosocial reasons for higher rates of LBP in workers and the lack of robust correlation with injury, imaging, or ergonomics have been discussed extensively elsewhere, both globally and in HICs.11,12 There are similar trends in multiple studies in LMICs, especially with regard to the multiple additional somatic pain complaints found in workers presenting with LBP.13,14 Given this, the presence of LBP in workers should prompt consideration of a more widespread chronic pain syndrome and its associated psychological distress because treatment for this would be vastly different than for isolated LBP.

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Headache

Much of what is published globally on HA comes from clinic patients or is described as point prevalence without consistent definition of chronicity or associations; this is similar to the inconsistency in reports in LMICs. The global estimate of any HA in the general population is 46%, with chronicity largely undefined.15 Our meta-analysis shows 42% (27–58) prevalence of any HA in general populations and 51% (13–88) in workers.

The prevalence of any HA is predictably higher than the corresponding well-defined chronic forms. Published global literature, primarily from HICs and Asia, report chronic daily HA in 3.4% of the global population, chronic tension-type HA in 3%, and chronic migraine in 0.6% to 1.7%.15 With the exception of an unexplained higher prevalence of chronic migraine (11%, 6–17) in our analysis of LMICs, these data are consistent. HA prevalence in global literature also tends to peak in the third and fourth decade, consistent with our findings that prevalence in the elderly trends lower than in the general population, although this did not reach clinical significance. Like LBP, chronic HA is commonly associated with psychosocial disability and pain in other sites, especially in workers.16 Although not statistically significant, a trend toward a higher prevalence of chronic HA in working LMIC populations merits further investigation in this group.

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Temporomandibular Disorder

Prevalence of TMD, largely from HIC estimates, is at least 6% to 10%,17 and the associations between it and multiple other somatic complaints and psychological distress are well known.18 There are very little data in LMICs, and what is available largely focuses on those in specialized pain, HA, or dental clinics; our analysis of a small number of highly heterogeneous data found a combined prevalence of 20% (0–57).

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Chronic Pelvic Pain

Chronic prostatitis/pelvic pain varies between 2% and 16% worldwide and is associated with significant psychosexual dysfunction; most of the data come from males in HICs and Asia.19 In a World Health Organization systematic review of women with chronic pelvic pain, only 22.2% of the data came from LMICs. Most data were reported as point prevalence. Rates of dysmenorrhea varied from 16.8% to 81%, dyspareunia 8% to 21.8%, and noncyclical pain 2.1% to 24%.20 Our meta-analysis revealed 4% (0–14) prevalence of chronic pelvic pain in male general populations in LMICs. No data were available for the elderly and only 1 article described a female population of Iranian workers with a dyspareunia rate of 26.7%.

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Musculoskeletal Pain

The Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) has estimated MSK pain prevalence over the past decade in multiple LMICs in Asia, Africa, and Central/South America; overall rates vary from 14% in Vietnam and China to 47% in Peru. Knee pain (7%–41%) and LBP (6%–35%) were the most frequent pain sites.21 This meta-analysis separated MSK pain and joint pain (and LBP), although many of these sites are variably described both together and separately under the umbrella of MSK pain, further confounding the production of homogeneous statistics.

Overall, in LMICs, our data show that isolated chronic joint pain is less prevalent than MSK complaints in general populations (14%, 11–18 vs 25%, 19–33), but both joint pain (34%, 16–54) and MSK pain (44%, 28–62) prevalences significantly increase in the elderly. MSK pain complaints in workers are even higher (79%, 60–94), although most of these data are point prevalence in LMIC surveys.

These differences in both categorization and chronicity significantly hinder prevalence comparisons in the MSK literature globally. When joint pain is described as lasting at least 6 months and interfering with daily activity, only 12.8% of 1 group of elderly Nigerians reported chronic pain22; yet, if pain is defined as occurring in the previous 3 months, without mention of functional impairment, 22% described MSK pain, 60% had joint pain, and 52.7% claimed “general body pains.”23 Of note, the most common community MSK complaints reported in COPCORD literature worldwide are ill-defined aches and pains.21 In fact, at least one-third of symptoms in both general and clinic populations worldwide are medically unexplained, including up to 85% of LBP and HA. Especially in workers and the elderly in LMICs, joint or MSK pain is often described as widespread or undifferentiated and should prompt evaluation of any pain as a possible manifestation of a more widespread pain syndrome with psychosocial contributors.

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Fibromyalgia Syndrome and Widespread Pain

Fibromyalgia and widespread pain are chronic syndromes without clear etiology, both resulting in sensitization of the overlapping pain, sleep, and mood pathways in the central nervous system. An ongoing peripheral insult or an inflammatory process at a localized site can also result in this central nervous sensitization, leading to the development of more widespread chronic pain at multiple sites and the development of mood and sleep disorders.24 There are indications in the literature that central sensitization leading to widespread pain may be more prevalent than previously thought25; patients and providers may not query a patient about pain in other sites when they present with a chief complaint at only a single location. Fibromyalgia and widespread pain currently have global prevalence rates reported in the literature of 4.3% and 13.2%, respectively.21 Our meta-analysis revealed an incidence of 6% (5–7) fibromyalgia and 12% (6–20) widespread pain in LMIC combined populations.

Yet, this may be an underestimate of the true prevalence of widespread pain. For instance, TMD, chronic abdominal pain, and chronic pelvic pain are prevalent in at least 7% to 16% of the LMIC populations reviewed here but are not included in the GBD estimates (although they may fall into categories described as “other”). Certainly, as in HICs, they may all, in fact, be somatic features of a common pain syndrome of central sensitization like fibromyalgia or widespread pain but are unrecognized as such because of the lack of standardized assessment tools to query these associations in people with chronic pain. Therefore, any type of chronic pain without clear etiology, at multiple sites, or associated with depression and anxiety may be a manifestation of an underlying central sensitization syndrome. (Jackson et al., Chronic Pain without Clear Etiology in Low- and Middle-Income Countries: A Narrative Review, in press, A&A 2016.) Similarly, effective treatment of localized peripheral or inflammatory pain will be necessary to prevent the development of more widespread, disabling central sensitization syndromes. In either case, the distinction becomes important for appropriately targeted treatment and resource allocation along the spectrum of chronic pain phenotypes.

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Limitations in the Literature: The Problem of Heterogeneity

The included studies come from a variety of LMICs, although there are a disproportionate number of articles from Brazil and China, which are defined as middle-income countries by the World Bank (studies from Hong Kong were excluded). Overall, there are limited data from low-income countries, in particular those in Central America.

One of the major limitations in assessing chronic pain in comparing studies of chronic pain prevalence is the lack of standardized definitions of pain chronicity. It is often unclear whether reported point prevalence refers to any episode of acute pain or is meant to imply a “point” of chronic pain during a given time. Those that do mention chronicity either rely on the subject’s own definition of chronicity or variably define pain as >3 months or >6 months, for example; it is often unclear whether this refers to daily intermittent pain, recurrent episodes of pain, and/or continuous pain. Future assessment of chronic pain must proceed with an expert consensus statement describing standardized definitions for assessment.

The strong reliance on patients’ self-report of symptoms in most surveys is subject to significant recall bias, especially as the length of recall increases.26,27 Variations in language, culture, age, sex, race, and disease state can influence pain evaluations, and cross-culturally standardized assessment tools should be used when possible.28,29

The majority of the articles included in this review are cross-sectional surveys performed in general populations. Cross-sectional surveyors almost uniformly used some method of systematic sampling (ie, querying every third household) in an attempt to minimize selection bias, although this cannot be excluded. Much data from LMICs are limited to relatively small sample sizes compared with the general population census and may introduce some detection bias, despite efforts to select a demographically representative group or region. This is a general limitation of small surveys indicated to reflect the prevalence of any disease state. However, given the reported high prevalence of chronic pain worldwide, these small numbers should still detect the presence of pain in small populations and should be able to guide larger-scale inquiry. Attrition bias, or refusal to participate, was limited in most surveys; the response rate of those queried was, with few exceptions, over 95%.

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CONCLUSIONS

Although more data are needed from Central/South America and Africa, the body of this evidence supports a high prevalence of chronic pain without clear etiology in LMICs, especially in workers and the elderly. Given the increasing global burden of NCDs, the most disabling of which are associated with chronic pain and its psychosocial associations, accurate standardized assessment of chronic pain must be prioritized to result in effective treatments. Recognizing the significant heterogeneity with which chronic pain is currently categorized and reported, it is essential to standardize the definitions and processes. Assessment of unspecified chronic pain going forward must also incorporate standardized, culturally unbiased queries of known psychosocial associations with chronic pain. The possible presence of multiple painful sites should also be specifically queried in future surveys because resource allocation for the treatment of more widespread central sensitization syndromes, or any chronic pain without known etiology, would be vastly different than that of localized pain with a clear underlying cause.

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DISCLOSURES

Name: Tracy Jackson, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Name: Sarah Thomas, BS.

Contribution: This author helped conduct the study and write the manuscript.

Name: Victoria Stabile, BA.

Contribution: This author helped write the manuscript.

Name: Matthew Shotwell, PhD.

Contribution: This author helped analyze the data and write the manuscript.

Name: Xue Han, MPH.

Contribution: This author helped analyze the data.

Name: Kelly McQueen, MD, MPH.

Contribution: This author helped design the study and write the manuscript.

This manuscript was handled by: Hugo Van Aken, MD, PhD, FRCA, FANZCA, and Stephen L. Shafer, MD.

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