Western populations are aging rapidly. Current census data suggest that by the year 2050, the number of people aged 65 years or older in the United States will double relative to this decade1; these data are closely mirrored in other jurisdictions such as Canada and Western Europe.2,3 While rapid growth in the older age demographic has major impacts on all areas of medicine, it is especially relevant in the perioperative setting. Advanced age predicts a 2- to 4-fold increase in rates of morbidity and mortality,4,5 and over 50% of people having major surgery are >65 years of age.6,7
Despite the increased relative risk associated with older age, however, most older people survive surgery without experiencing a serious complication (>95% survival and >75% without a major complication).8,9 This suggests that identification of a high-risk stratum within the older surgical population may allow for more targeted application of scarce health care resources to achieve value from perioperative enhanced care pathways and processes. While many risk stratification tools exist to help identify high-risk patients, few have been routinely operationalized in clinical practice.10
Over the past 10 years, frailty has emerged as a robust and clinically relevant entity that is commonly present in older people who experience adverse outcomes after surgery. As a multidimensional geriatric syndrome, the concept of frailty has been translated from geriatric medicine practice across many areas of acute care medicine. Interest in frailty in the perioperative setting has increased exponentially. However, many challenges exist regarding conceptualization of frailty, routine identification, and application of targeted interventions to improve outcomes. The objective of this review is to provide an overview of frailty relevant to perioperative clinicians, including defining frailty, reviewing techniques to operationalize frailty assessment before surgery, exploring pathways that may lead from frailty to adverse postoperative outcomes and discussing established and emerging interventions that may target these pathways to meaningfully improve outcomes for the growing number of older people with frailty who undergo surgery each year.
WHAT IS (OR ISN’T) FRAILTY?
Frailty is a multidimensional syndrome characterized by decreased reserves that leaves an individual vulnerable to adverse outcomes due to decreased tolerance of stressors (physical, physiologic, or psychosocial).11–14 However, conceptualizing the specific features that underly frailty has eluded consensus. In general, experts agree that frailty is a multidimensional construct that includes deficits related to physical performance, nutritional status, mental health, and cognition.14 Consensus has not been reached, however, on how to operationalize measurement of physical performance, nutrition, mental health, or cognition in clinical frailty assessments.
There is consensus, however, regarding what frailty isn’t. First, although related, frailty is distinct from concepts such as disability and comorbidity.11 Next, although investigators have occasionally defined frailty in research settings using single laboratory or diagnostic imaging values (eg, hypoalbuminemia, muscle cross-sectional area [a measure of sarcopenia]), these values on their own cannot allow direct measurement of an individual’s frailty status.14 Furthermore, although deficits will accumulate during the normal aging process, frailty is not directly synonymous with aging, but can instead be used to better identify individuals who are substantially more vulnerable relative to others of the same age.13 Finally, the prevalence of frailty increases exponentially with increased age; however, frailty is not solely a geriatric syndrome. In fact, several studies in perioperative and critical care medicine have found that the presence of frailty at younger ages is associated with a greater relative risk of adverse outcome than frailty present in older individuals.15,16
In the perioperative setting, a useful definition is that frailty is an aggregate expression of risk that results from accumulation of age- and disease-related deficits across multiple domains.17,18 This definition reflects the fact that frailty represents a global risk state (eg, it is not solely a risk factor for single organ complications), that frailty status can be impacted both by processes of aging (such as cellular and tissue breakdown) and disease-specific processes (eg, proinflammatory features of diabetes, or decreased cardiac function in coronary artery disease) and that frailty is a multidimensional entity that cannot be quantified by a single measurement.
Two leading frameworks are currently used to conceptualize frailty (Figure 1).12 The first is the phenotype model,17 where the presence of frailty is thought to be a primarily internal phenomenon occurring at the cellular level, caused by breakdown and dysregulation of energetics that are expressed phenotypically. This phenotype can then be identified through the measurement of gait speed, grip strength, energy levels, weight loss, and falls. The second conceptual framework is the accumulating deficits model.13,19 In this approach, frailty is thought of as a measurement of the biologic (as opposed to chronologic) aging process; instead of counting calendar years, one counts the number of deficits present across multiple domains (≥30 deficits must be assessed).20 The degree of frailty present can then be quantified by dividing the number of deficits present by the number of deficits assessed, which generates a score between 0 (no frailty) and 1 (completely frail). Regardless of the conceptual framework, however, it is crucial to recognize that frailty, although often described as being present or absent, is best used as a graded condition where higher levels of frailty equate to greater vulnerability and risk of adverse outcomes.
THE PREVALENCE OF FRAILTY BEFORE SURGERY
Risk factors may be considered important for prognostication and care planning for a variety of reasons.21 Typically, one would consider a risk factor to have particular importance if (1) the risk factor is prevalent, (2) the risk factor is strongly predictive of outcome (eg, >50% relative risk increase), and/or (3) if the risk factor is potentially modifiable.22 Below, we discuss the expected prevalence of frailty in surgical patients, while subsequent sections will address the strength of association and possible modifiability of frailty.
In the general (ie, nonsurgical) population, frailty prevalence increases exponentially with age. At age 65 years, prevalence is typically <10%, while above age 85 years, prevalence typically exceeds 50%.23 The prevalence of frailty in surgical populations differs substantially from the general population and is the product of several considerations. First, the prevalence of frailty is highly influenced by the instrument used to assess frailty (as well as the threshold used to define frailty when applying the instrument). For example, the frailty defining diagnosis approach (where the presence of one or more of a set of diagnoses typically associated with adverse aging is used to define frailty24,25) tends to estimate a relatively low prevalence (<10% in elective surgery15), whereas multidimensional clinical frailty assessments (eg, Fried Phenotype [FP], Clinical Frailty Scale [CFS]) tend to estimate a prevalence of 30%–40%.26 The type and urgency of surgery is also an important predictor of prevalence. For example, prevalence of frailty in prostatectomy is much lower than cystectomy,27 as surgically amenable prostate cancer has lower symptom burden than bladder cancer and prostatectomy is typically only considered for individuals with prolonged expected survival. Frailty prevalence also tends to be higher for emergency (versus elective) procedures. For example, a population-based study of major emergency surgery reported an 8-fold higher prevalence of frailty than a similar study of major elective surgery that used the same frailty definition and data source.15,28 Overall, age-stratified prevalence of frailty is higher in surgical populations compared to community-based samples. Using a clinically assessed multidimensional frailty instrument in the elective setting (where average age approximates 70 years), one would expect to identify frailty in approximately 30% of patients presenting for nononcologic surgery,29 with prevalence approaching 50% in cancer surgery.30 In a similarly aged community-based sample, frailty prevalence would approximate 10%–15%.31 Higher prevalence and severity can be expected in emergency settings.
THE IMPACT OF FRAILTY ON PERIOPERATIVE OUTCOMES
Surgery induces substantial physiologic stress even for healthy individuals.32 Therefore, it is not surprising that the presence of frailty before surgery is strongly associated with increased risk of adverse outcomes and higher resource utilization. Across an ever-expanding epidemiologic literature that now includes large studies using administrative data, prospective registries, primary prospective observational studies, and systematic reviews, frailty is consistently associated with at least a 2-fold increase in the risk of major morbidity, mortality, and readmissions.33–35 Furthermore, given the increasing focus on patient-reported outcomes and the importance of functional measures for older surgical patients, it is of primary importance to recognize that frailty doubles the odds of new patient-reported disability,26 impaired quality of life,33,34 and increases the odds of nonhome discharge 5-fold among older people previously living in the community.26,36 In addition, length of stay, costs, and other measures of resource use are consistently higher for older people with frailty, with a 15%–60% increase across a variety of studies.26,36,37
While relative increases in risk, as well as risk estimates adjusted for important confounders (such as surgery type, urgency, indication, etc) are important to clinicians and help to communicate expected outcomes to patients and their families, absolute risk estimates are typically better understood and more meaningful when providing prognostic information before surgery.38,39 Fortunately, the absolute risk of death in the month after surgery is relatively low, even for individuals with frailty (typically <5% after major, elective noncardiac surgery).8 However, 1-year mortality rates are often substantial and may exceed 40% after major elective surgery for cancer (which likely reflects the interplay between surgery, frailty, and the underlying oncologic process).15,30,40 There is also a consistent dose-response relationship, where higher frailty scores (regardless of instrument) are associated with greater risk of death.29,33
Complications are common in people with frailty, with rates exceeding 50%.41 Accordingly, a recent systematic review has identified frailty as the strongest risk factor for the development of postoperative morbidity in older patients.41 Delirium is also common in older surgical patients, with rates estimated between 10% and 50% depending on the type and urgency of surgery.42 Frailty is a strong risk factor for developing delirium after major surgery (odds ratio = 4.1),43,44 and its strength of association with delirium incidence was exceeded only by a history of delirium in a recent systematic review.44
While older people place a high value on survival, expected function, and quality of life outcomes may be of even greater importance in the setting of acute illness.45 Unfortunately, these patient-centered and patient-reported outcomes are rarely evaluated in perioperative frailty studies, and an even lower proportion provide clinically meaningful information.34 Where these data do exist, evidence suggests that frailty is a strong predictor of adverse functional outcomes. In a multicenter cohort study of over 700 participants, our group found that 1 in 5 older people with frailty were experiencing a new or meaningfully worsened disability 3 months after major elective noncardiac surgery. We have also found that 15%–50% of older people with frailty who lived independently in the community before surgery were unable to achieve home discharge after elective procedures.26,36 Overall, our prospective data suggest that 29% of people with frailty either die, are institutionalized, or go home with a new disability in the 90 days after major, elective noncardiac surgery.26 These data are consistent with the cardiac literature, where older people with frailty face an approximately 20% absolute increase in the likelihood of dying or having reduced quality of life (compared to people without frailty) a year after surgery.46
Finally, while most studies describing the association of frailty with adverse outcomes focus on major inpatient surgery, it is also important to recognize that frailty predicts adverse outcomes in surgeries typically considered low risk. These include urgent and emergent appendectomy and cholecystectomy procedures, where the relative impact of frailty on mortality is stronger than for laparotomy or bowel resection.28 Furthermore, after ambulatory hernia, breast, thyroid, or parathyroid surgery, frailty is associated with a greater than 3-fold increase in the odds of complications.47
PREOPERATIVE FRAILTY ASSESSMENT
To improve outcomes for older people with frailty, perioperative clinicians must first routinely identify frailty before surgery. However, despite guidelines from specialty societies, national institutions, and multidisciplinary groups that recommend frailty assessment as a best practice,48–50 there is currently little evidence that frailty assessment occurs routinely in preoperative care.51,52 The urgent need to increase the application of routine frailty assessment is further highlighted by recent evidence linking preoperative frailty assessment (and subsequent communication to the perioperative team) with improved postoperative outcomes for older people with frailty.53
Many barriers to preoperative frailty assessment exist.54 These include a lack of clarity on which frailty instrument to choose among the dozens described in the literature, time pressures that preclude the addition of further tests or assessments in an already busy preoperative clinic, the need for specialized assessments or instrument scoring for certain frailty scales, and other considerations. We suggest that the choice of frailty instrument should be informed by considerations of accuracy (ie, how well outcomes are predicted) and feasibility (ie, how practical it is to use in routine preoperative practice). Based on a careful review of the literature, we have identified at least 40 unique frailty instruments or proxy measures that have been used in clinical settings before surgery (Supplemental Digital Content, Appendix A, http://links.lww.com/AA/C985). The best-studied instruments include the FP (based on the frailty phenotype conceptual model17), the CFS (a clinically oriented adaptation of the accumulating deficits Frailty Index [FI]18), the FI (direct application of the accumulating deficits frailty model19), and the Edmonton Frail Scale (EFS; a reduced version of the accumulating deficits FI55) (Table).20,56–58 Other well-studied approaches include the use of a physical performance measure (eg, short physical performance battery59 or 6-minute walk test60) or a modified FI (typically applied to the National Surgical Quality Improvement Program data61); however, these approaches are limited by a lack of multidimensionality. In other words, using an isolated measure of physical performance does not capture aspects of nutrition, cognition, or mental health, while the modified FI lacks adequate deficits (12 vs the recommended ≥30) and is more consistent with a modified comorbidity index.
Composition of Frailty Instruments Commonly Studied in the Perioperative Setting
||Clinical Frailty Scale
||Edmonton Frail Scale
||Weight loss: >10 lbs unintentionally in the previous year
||1. Very fit: People who are robust, very active, and motivated. These people commonly exercise regularly. They are among the fittest of their age
||Cognition: Clock draw test
|Low body mass index
||Grip strength: lowest 20% (by sex and body mass index)
||2. Well: People who have no active disease symptoms but are less fit than category 1. Often, they exercise or are very active occasionally
||General health: Number of hospital admissions in the past year
|Obstructive sleep apnea
||3. Managing well: People whose medical problems are well controlled, but they are rarely active beyond walking.
||Functional independence: Number of activities of daily living requiring assistance
||Slowness: 15-foot walking speed (by sex and height)
||4. Vulnerable: While not dependent on others for daily help, often symptoms limit activities. A common complaint is being “slowed up,” and/or being tired during the day
||Social support: Availability of reliable help
||Low activity: Kilocalories per week (males <383, females <270)
||Medication use: Presence of polypharmacy
||5. Mildly frail: These people often have more evident slowing and need help in high order IADLs. Typically, this impairs shopping and walking outside alone, meal preparation, and housework
|Coronary artery disease
|Peptic ulcer disease
||Medication use: Forgetting to take prescribed medications
|Peripheral vascular disease
||6. Moderately frail: People need help with all outside activities and with keeping house. Inside, they often have problems with stairs and need help with bathing and might need minimal help with dressing
||Nutrition: Unintentional weight loss
||Mood: Feelings of sadness or depression
|Assistance needed dressing
||7. Severely frail: Completely dependent for all personal care from whatever cause (physical or cognitive). Even so, they seem stable and not at high risk of dying (within ~6 mo)
|Assistance needed meals
|Assistance needed shopping
||Continence: Presence of urinary incontinence
||9. Terminally ill: Approaching the end of life. This category applies to people with a life expectancy <6 mo, who are not evidently frail
||Functional performance: Timed up and go test
|Possibly inappropriate medication
AD8-Alzheimer’s Disease in 8 questions questionnaire57
; PHQ-2-Patient Health Questionnaire56
; The Frailty Index is calculated as a number from 0 to 1 by dividing the number of deficits present by the number of deficits measured (ie, 30) as recommended by Searle et al.20
One point is assigned for the presence of each feature of the phenotype, resulting in a score from 0 to 5. Following assessment, an individual is assigned a score on the scale. Zero to 2 points are assigned to each question, creating a score that ranges from 0 to 17.
Abbreviations: CAGE, cut down, annoyed, guilty, eye-opener; IADL, instrumental activities of daily living; PHQ-2, 2 question Personal Health Questionnaire.
Typically, the association of different frailty instruments with outcomes does not differ substantially. For example, systematic reviews generally find that all adequately powered studies find significantly higher rates of mortality in those with frailty than in people without frailty.33,34 The consistent association of any frailty instrument with adverse outcomes can be demonstrated for most relevant outcomes. Unfortunately, the literature provides few studies that directly compare different frailty instruments head to head. Of those that have, authors have not found evidence of significantly different strengths of association between the instruments under study. The consistency of effect sizes found between different frailty instruments and outcomes is somewhat surprising, as different instruments typically identify the presence of preoperative frailty with only moderate agreement (Cohen’s kappa = 0.4–0.6),26,62 with much higher variation in agreement in nonoperative settings (Cohen’s kappa = 0.1–0.8).63,64 In comparing the ability of the CFS to the FP in identifying older individuals who go on to die or develop new disability after elective noncardiac surgery, we found no evidence of a difference in sensitivity, specificity, or odds ratios.26 Similarly, Cooper et al62 found no difference between the FP and FI when predicting prolonged length of stay, complications, or discharge disposition after orthopedic surgery, while Esses et al65 found no difference between the modified FI, risk analysis index, and Ganapathi index in cardiac surgery. However, Wang et al66 did find the CFS to be more strongly associated with length of stay and discharge disposition than the FRAIL Scale in orthopedics.
Effect sizes (eg, odds, risk, and hazard ratios) are only one aspect of predictive performance. For binary outcomes (such as death and complications), other measures of predictive performance must also be considered. These include discrimination (how well an instrument assigns a higher risk to people who truly go on to have the bad outcome), calibration (how well the instrument assigns an expected probability of bad outcome that matches with the observed rate of outcomes), and others.67 Most studies do not provide these important measures. In those that do, frailty instruments typically have an area under the curve (a measure of discrimination where 0.5 represents chance and 1.0 represents perfection) of 0.65–0.85, depending on the outcome being predicted. Even fewer studies directly compare the discrimination and calibration of different instruments. However, a recently published study found that the CFS improved the discrimination of preoperative risk stratification models predicting death or new disability, prolonged length of stay, and institutional discharge to a greater extent that the FP or the FI, while also more meaningfully improving calibration than the other 2 comparators.68
While predictive accuracy must be a foundational consideration when choosing an instrument for risk stratification, if a frailty tool is to be used in clinical practice it must also be feasible.69 Limited data are currently available that formally assess the feasibility of frailty instruments. Time is a primary consideration for busy clinicians. Based on available data, the CFS adds less than a minute to a preoperative assessment, while the EFS typically takes 5 minutes, the FP 5–20 minutes, and the FI approximately 10 minutes. A head-to-head comparison found the CFS to be significantly faster than the FP.26 The CFS was also superior to the FP in terms of ease of use and logistical considerations in the same study. Further considerations that may limit the feasibility of certain frailty instruments include the need for space and timing of walk-based tests for the FP and EFS,70 some difficulty in older patients understanding certain questions on the EFS (including people from differing backgrounds71), the need for a reliable and appropriately calibrated hand-held dynamometer for the grip strength portion of the FP,70 and the need to score subdomain questionnaires for the FP (activity questionnaire) and the EFS (clock draw test). Finally, the need to complete questionnaires and performance tests for the FP and EFS may limit their applicability in emergency surgery cases where patients are acutely ill at the time of assessment. For patients unable to actively participate in an assessment, a modification of the EFS (the reported EFS) has been described,72 while a CFS assessment based on chart review and/or proxy history has been shown to be accurate in critically ill patients.73
In summary, perioperative clinicians must consider the specific characteristics of their preoperative assessment clinic and associated processes when selecting a frailty tool to implement because limited evidence supports the predictive superiority of a single instrument. However, available data do suggest that the CFS may provide some degree of improved discrimination and calibration when predicting patient- and system-important outcomes, while feasibility data consistently identify the CFS as a simple and practical instrument when used for preoperative assessment (see the Table for a detailed description of the CFS).
IMPROVING OUTCOMES FOR OLDER SURGICAL PATIENTS WITH FRAILTY
Preoperative frailty assessment provides an opportunity to identify a relatively homogenous and high-risk stratum of the older surgical population; early evidence suggests that the act of assessment and communication of frailty status to the perioperative team could improve outcomes on its own.53 However, we suggest that frailty assessment most likely represents a first step linking risk stratification to perioperative optimization for high risk older surgical patients, a statement that reflects the underlying multidimensional nature of frailty. In fact, evidence from nonsurgical older populations suggests that prognostic accuracy can be improved by differentiating the major underlying contributors to frailty.74 Therefore, once frailty has been identified, contributors to frailty (ie, physical performance, nutrition, cognition, and mental health) can be highlighted using simple, validated screening tests (Figure 2). This should allow preoperative clinicians to link assessment to rational, evidence-based optimization strategies and support future research into optimization of older people with frailty before surgery.
Surgical stress and postoperative immobility can substantially worsen physical performance in older people with frailty. Older people often experience immobilization after surgery, and when confined to bed rest, even healthy older adults lose 1.5 pounds of muscle mass per week.75 This combination of preexisting physical vulnerability, surgical stress, and immobility can result in significant disability due to loss of lower limb function.26 Therefore, identification of physical vulnerability before surgery could help to select individuals who might benefit from interventions to improve physical function, such as exercise prehabilitation.
While many screeners and questionnaires exist to quantify physical performance before surgery, the Duke Activity Status Index (DASI)76 stands out as feasible and accurate tool. In an international multicenter study, the DASI was found to out-perform cardiopulmonary exercise testing when predicting adverse postoperative events77 and outperformed the more time-intensive 6-minute walk test when predicting the occurrence of new disability.78 Therefore, clinicians could consider the DASI as a screener for physical vulnerability among patients with frailty. One issue with the DASI, however, is that it has not been adequately tested in older people with frailty. Therefore, other standard measures of physical performance in older people, such as the timed up and go test, also deserve serious consideration.79
Once identified, such individuals may benefit from exercise prehabilitation, which has been shown to decrease complication rates80,81 and possibly improve functional outcomes.82,83 While generalizable multicenter randomized trials are still required, preliminary data suggest that people with frailty characteristics may benefit most from exercise before surgery,84 and systematic reviews suggest that multimodal (ie, aerobic and strength training) exercise, performed at least 3 times per week,85 for at least 2 weeks before surgery,86 appears to be the most promising design.
Malnutrition is prevalent in people with frailty (10%–20%)87,88 as well as in older surgical patients (15%–60%, with higher rates seen in people with gastrointestinal and cancer diagnoses).89,90 Malnutrition can leave older people vulnerable to physical and physiologic stressors, especially in the setting of surgery. Complications, prolonged length of stay, impaired functional recovery, and delirium are associated with malnutrition.89,91,92 Therefore, addressing macro- and micronutrient deficits represents a promising means of optimizing the older person with frailty before surgery.
Similar to screening for physical performance, many tools are available to screen for malnutrition. These include calculation of body mass index, history of unintentional weight loss, or more specific nutritional screeners, such as the Canadian Nutrition Screening Tool (CNST)93 or Mini Nutritional Assessment.94 The CNST is a simple 2 question screener with good sensitivity (92%), specificity (75%), and interrater agreement (kappa = 0.88).93
While large studies of nutritional supplementation before surgery have not been performed in older people with frailty, protein supplementation has been a key component of several successful multimodal prehabilitation programs.80–82,95 For people performing exercise prehabilitation, meeting protein requirements is especially important as these individuals will be attempting to address preexisting deficits while increasing demand through newly increased activity levels. Current perioperative guidelines recommend 1.5 g/kg/d (based on ideal body weight),90 and it may be advisable to address malnutrition before commencing exercise therapy. Identification of iron deficiency anemia and treatment has also been included in prehabilitation programs and could be considered as well.81
Even among older people with frailty, clinically apparent dementia is uncommon.96 However, mild neurocognitive dysfunction is prevalent and could contribute to the development of postoperative delirium and other adverse outcomes. The Mini-Cog test is currently recommended by best practice guidelines from the American College of Surgeons and American Geriatrics Society and can be considered as a cognitive screener before surgery.48
Once identified, the best available evidence suggests that environmental optimization and avoidance of delirium triggers can be used to reduce delirium after surgery.97 The Hospital Elder Life Program98 represents a bundled approach to delirium prevention (orientation, nutrition, mobilization) that is associated with lower delirium rates in surgical patients.99 The role of cognitive prehabilitation, while promising, requires further study.100,101
Anxiety and depression are common in older surgical patients and can relate to underlying psychosocial stressors, the impact of the surgical diagnosis, or other organic causes of depression. Given the high absolute risk of nonhome discharge among older people with frailty, identifying underlying mental health issues and psychosocial stressors could help to pinpoint individuals who will have more complex discharge needs, reduced support for going home, or both. The 2 question Personal Health Questionnaire (PHQ-2) is 86% sensitive and 78% specific for identifying individuals with major depression and could be considered by preoperative clinicians as a screening tool for depression.56 Unfortunately, to date, little interventional data are available to suggest specific strategies to intervene in this regard. However, well-designed multidisciplinary geriatric care pathways that include preadmission discharge planning show promise for decreasing adverse events and resource use among high-risk older patients.102,103
Frailty is a multidimensional syndrome that is prevalent among older surgical patients, is strongly associated with adverse outcomes, can be feasibly assessed and identified before surgery, and represents a potentially modifiable risk factor. Perioperative clinicians should consider routine frailty assessment using accurate and feasible instruments, while also considering the underlying contributors to frailty to identify specific targets for optimization. Future research will be needed to further refine interventions for preoperative optimization, while also addressing knowledge gaps related to intra- and postoperative care.
Name: Daniel I. McIsaac, MD, MPH, FRCPC.
Contribution: This author helped conceiving the paper, identifying key references, writing, critical review and revisions, and approved the final manuscript and is a guarantor.
Name: David B. MacDonald, MD, FRCPC.
Contribution: This author helped in conceiving the paper, identifying key references, writing, critical review, and revisions, and approved the final manuscript.
Name: Sylvie D. Aucoin, MD, MSc, FRCPC.
Contribution: This author helped conceiving the paper, identifying key references, writing, critical review, and revisions, and approved the final manuscript.
This manuscript was handled by: Robert Whittington, MD.
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