Abstract
Purpose
The purpose of this study was to evaluate associations between postgraduate disciplinary actions (PGDA) by state licensing boards and physician assistant (PA) school documented professionalism violations (DPV) and academic probation.
Methods
This was a retrospective cohort study comprising PA graduates from 2001 to 2011 at 3 institutions (n = 1364) who were evaluated for the main outcome of PGDA and independent variable of DPV and academic probation. Random-effects multiple logistic regression and accelerated failure time parametric survival analysis were used to investigate the association of PGDA with DPV and academic probation.
Results
Postgraduate disciplinary action was statistically significant and positively associated with DPV when unadjusted (odds ratio [OR] = 5.15; 95% CI: 1.62–16.31; P = .01) and when adjusting for age, sex, overall PA program GPA (GPA), and Physician Assistant National Certifying Exam Score (OR = 5.39; 95% CI: 1.54–18.85; P = .01) (fully adjusted). Academic probation increased odds to 8.43 times (95% CI: 2.85–24.92; P < .001) and 9.52 times (95% CI: 2.38–38.01; P < .001) when fully adjusted.
Conclusion
Students with professionalism violation or academic probation while in the PA school had significant higher odds of receiving licensing board disciplinary action compared with those who did not. Academic probation had a greater magnitude of effect and could represent an intersection of professionalism and academic performance.
Introduction
Knowledge and skills of medical professionalism norms and standards are paramount for clinical practice. Professionalism violations in the health care workforce can be detrimental to institutions, colleagues, individual careers, and ultimately patients.1-11 Physician assistants (PAs) are vital members of the health care team,12-16 and professionalism is essential. Physician assistant training is a period in which students receive compressed and intensive instruction. On average, PA educational programs have a length of 27 months,17 and students must acquire knowledge and skills in clinical medicine, interpersonal communication, ethical practice, and professional behavior at a rapid pace. Dealing with lapses in professionalism is a challenging task, often performed in brief time frames during student enrollment. A retrospective cohort study of 1655 PAs who graduated from 1990 through 2015 found that the prevalence of postgraduate disciplinary actions (PGDA) by state PA licensing boards in the cohort was 0.96%.18 Among those with violations, 75% were violations of professional norms.18 According to the National Commission on Certification of Physician Assistants (NCCPA) as of December 31, 2017, there were 123,089 certified PAs.19 Although the prevalence of 0.96% PGDA may seem small, it suggests there may be an estimated 1182 PAs with disciplinary action by state licensing boards.
Physician unprofessional behavior has been linked to adverse patient outcomes, increased malpractice claims, and overall higher cost of care.1,6,10,20-22 In a study of 14,314 physicians licensed in Oklahoma, the prevalence of board actions was approximately 2.8%.23 Case-control studies of medical school graduates have indicated that disciplinary action by a medical board is correlated with unprofessional behavior in medical school, low academic performance, and low Medical College Admission Test scores.24,25 Previous studies have been conducted in the context of case-control studies with few matching criteria for cases and controls, increasing the possibility of biased effect estimates.24,25 Individual characteristics associated with physician discipline have also been identified, such as male.26
Previously, there were no studies that evaluated the association between documented professionalism violations (DPV) or low academic performance during PA education and subsequent PGDA by state PA licensing boards, particularly studies that evaluate retrospective cohort data.
The purpose of this study was to evaluate the association of DPV during PA education and academic probation to PGDA by state PA licensing boards.
Methods
Data Collection
Student data were collected from 3 PA programs, including the University of Florida, Gainesville, Florida, Northeastern University, Boston, Massachusetts, and the University of Utah, Salt Lake City, Utah, for classes graduating between 2001 and 2011. Documented professionalism violation was defined as any documented violation of program policy or professional medical norms within the student record. Violation of professional medical norms included any explicit or implicit violation of the American Medical Association Modernized Code of Medical Ethics.27 In addition, DPV inclusion criteria included alignment with established professionalism domains in the medical education literature (reliability and responsibility; self-improvement and adaptability; relationships with students, faculty, staff, and patients; and upholding medical ethical principles and integrity).28-30 Academic probation was defined as documentation in the student record indicating academic probation. These data were linked with regional professional records and coded to indicate whether students received PGDA from the year of graduation through 2020. Specifically, publicly available board-licensure records were consulted in the state of PA education and states with known work or residence history if available. All institutions provided Institutional Review Board approval for this study.
Variables and Covariates
The main outcome variable was PGDA (binary), which was encoded true for PAs who received one or more PGDA. Exploratory analysis examined the use of ordinal levels of PGDA, but there was no appreciable change in outcome after one. The first independent variable of interest was DPV (binary), which was encoded true for PAs who received one or more DPVs during education. The second independent variable of interest was academic probation (binary), which was encoded true for any PA who received one or more instances of academic probation during education. Covariates included program (3-level categorical), age (continuous), sex (binary), overall PA program grade point average (GPA) (continuous), Physician Assistant National Certifying Exam (PANCE) score (continuous), and race (5-level categorical).
Statistical Analysis
We conducted random-effects multiple logistic regression clustered on program to investigate the associations of PGDA with DPV and academic probation, respectively. Models were run with only primary variables of interest and with covariate adjustment. Postestimation diagnostics showed good model fit in all cases. Exploratory analysis examined interactions among categorical variables, but none were found to be significant. All statistical analyses were conducted in R 4.1 and Stata 17.
Sensitivity Analysis
For secondary analysis, we constructed Kaplan-Meier survival curves and performed Cox regression to explore associations between independent variables of interest and time to PGDA. The Cox regression used a shared frailty term for program to cluster random effects. Although estimates were confirmatory of logistic regression, regression diagnostics showed that the proportional hazards (PH) assumption was not fulfilled. To drop the PH assumption, we conducted a tertiary analysis using accelerated failure time parametric survival regression.31,32 Models were initially fit using multiple distributions (exponential, Weibull, log-normal, and log-logistic), and final regression was conducted using an exponential distribution, which had the lowest Bayesian information criterion.33 Regression diagnostics showed good model fit and predictive power.
Missing Data
Missingness for the outcome (PGDA) and 2 independent variables of interest (DPV, academic probation) was 0%. Missingness for covariates varied from 0.4% (sex) to 4% (GPA). Although adjustment for race would have been favorable, its overall missingness was 31.8%. Thus, it was excluded from primary analysis but was used in sensitivity analysis. The original analysis plan called for adjustment by socioeconomic status, but such data were intractable to collect.
Results
Statistical Analysis Results
Among the total cohort of 1,364 graduates from 3 institutions, 1.2% (n = 16) had one or more DPV and 5.4% (n = 74) had documented academic probation. Table 1 summarizes the characteristics and professional data of the cohort.
Table 1.
Characteristics and Professional Data From a Cohort Across 3 PA Programs (2001–2011)*
Characteristic/Professional Data | Program 1 (N = 644) | Program 2 (N = 351) | Program 3 (N = 369) | Total (N = 1364) |
PGDA | ||||
Yes | 5 (0.8%) | 6 (1.7%) | 5 (1.4%) | 16 (1.2%) |
No | 639 (99.2%) | 345 (98.3%) | 364 (98.6%) | 1,348 (98.8%) |
DPV during PA education | ||||
Yes | 35 (5.4%) | 29 (8.3%) | 22 (6.0%) | 86 (6.3%) |
No | 609 (94.6%) | 322 (91.7%) | 347 (94.0%) | 1,278 (93.7%) |
Documented academic probation | ||||
Yes | 26 (4.0%) | 30 (8.5%) | 18 (4.9%) | 74 (5.4%) |
No | 618 (96.0%) | 321 (91.5%) | 351 (95.1%) | 1,290 (94.6%) |
Age | ||||
Mean age | 27.2 ± 5.58 | 27.7 ± 5.61 | 30.9 ± 4.80 | 28.3 ± 5.61 |
Sex | ||||
Male | 160 (24.8%) | 97 (27.6%) | 158 (42.8%) | 415 (30.4%) |
Female | 478 (74.2%) | 254 (72.4%) | 211 (57.2%) | 943 (69.1%) |
Missing | 6 (0.9%) | 0 (0%) | 0 (0%) | 6 (0.4%) |
GPA | 3.47 ± 0.310 | 3.64 ± 0.200 | 3.47 ± 0.279 | 3.52 ± 0.29 |
PANCE score | 536 ± 113 | 535 ± 107 | 511 ± 117 | 529 ± 113 |
Race | ||||
Asian | 20 (3.1%) | <5 | 11 (3.0%) | 33 (2.4%) |
Black or African American | 24 (3.7%) | <5 | <5 | 29 (2.1%) |
Hispanic or Latino | 30 (4.7%) | <5 | 23 (6.2%) | 56 (4.1%) |
White | 476 (73.9%) | 25 (7.1%) | 298 (80.8%) | 799 (58.6%) |
Other | 8 (1.2%) | 0 (0.0%) | 5 (1.4%) | 13 (1.0%) |
Missing | 86 (13.4%) | 319 (90.9%) | 29 (7.9%) | 434 (31.8%) |
N (%) or mean ± standard deviation.
DPV, documented professionalism violations; GPA, overall PA program grade point average; PA, physician assistant; PANCE, Physician Assistant National Certifying Exam; PGDA, postgraduate disciplinary actions.
Previous DPV and academic probation were both statistically significantly associated with increased odds of PGDA (Table 2). Participants with any previous DPV had 5.15 times greater odds of PGDA than those without previous DPV (95% CI: 1.62–16.31; P = .01) and 5.39 times when adjusting for covariates (fully adjusted) of age, sex, GPA, and PANCE score (95% CI: 1.54–18.85; P = .01). Participants with documented academic probation had increased odds of PGDA with 8.43 times greater odds (95% CI: 2.85–24.92; P < .001) and 9.52 times greater odds (95% CI: 2.38–38.01; P < .001) when fully adjusted.
Table 2.
Results of Logistic Regression (95% Confidence Interval) [P Value]
Outcome | Model 1* | Model 2† |
Any DPV | 5.15 (1.62–16.31) [.01] | 5.39 (1.54–18.85) [.01] |
Academic probation | 8.43 (2.85–24.92) [<.001] | 9.52 (2.38–38.01) [<.001] |
Estimates are in odds ratios (exponentiated log odds).
Adjusted for age, sex, overall PA program grade point average, Physician Assistant National Certifying Exam score.
DPV, documented professionalism violations.
All estimates are higher when adjusting for race (and thereby dropping 434 missing observations). This suggests that participants with unreported race were less likely to have received violations or probation than those who self-reported race. However, no category of race had a statistically significant impact on professional citations in any model.
Sensitivity Analysis Results
Previous DPV and academic probation were both significantly associated with faster average time to PGDA compared with those without DPV or academic probation (Table 3). Participants who receive DPVs had an accelerated time ratio of 0.21 (95% CI: 0.07–0.65; P = .01), which represents 4.8 times faster average time to PGDA than those without previous DPV and 0.20 (95% CI: 0.06–0.69; P = .01) for 5 times faster average time when fully adjusted. Participants with prior academic probation had an accelerated time ratio of 0.13 (95% CI: 0.05–0.37; P < .001), a 7.7 times faster time to PGDA than those who do not. Fully adjusted estimate is 0.11 (95% CI: 0.03–0.43; P < .001) for 9.1 times faster time to PGDA.
Table 3.
Results of Accelerated Failure Time Parametric Survival Analysis, Assessing on Average How Much Faster a Postgraduate Disciplinary Action Is Received by Participants With Previous DPV and Academic Probation Recipients
Outcome | Model 1* | Model 2† |
Any DPV | 0.21 (0.07–0.65) [.01] | 0.2 (0.06–0.69) [.01] |
Academic probation | 0.13 (0.05–0.37) [<.001] | 0.11 (0.03–0.43) [<.001] |
Results of accelerated failure time regression (95% confidence interval) [P value].
Estimates are in time ratios.
Adjusted for age, sex, overall PA program grade point average, Physician Assistant National Certifying Exam score.
DPV, documented professionalism violations.
Discussion
Postgraduate disciplinary action by PA licensing boards is statistically significant and positively associated with DPV and academic probation during PA education. Odds of PGDA are 5.15 times higher among those with previous DPV (odds ratio [OR] = 5.15; 95% CI: 1.62–16.31; P = .01), and odds are 5.39 times higher (OR = 5.39; 95% CI: 1.54–18.85; P = .01) when adjusting for age, sex, GPA, and PANCE score. Academic probation during PA education has an even higher magnitude of significance with 8.43 times higher odds of postgraduate disciplinary action (95% CI: 2.85–24.92; P < .001) and 9.52 times higher (95% CI: 2.38–38.01; P < .001) when fully adjusted. This is the first study to evaluate the associations of professionalism violations and academic performance with PA licensing board actions. These associations improve generalizability and strengthen the conclusions of previous studies showing similar associations of professionalism violations and academic performance with state licensing board disciplinary action during physician training. In addition, our findings bring forth academic probation as a significant concern for future behaviors and activities that prompt licensing board actions. Individuals who work in the provision of medical care have an increased level of responsibility that should result in professionalism of the highest standards. Ignoring or underreacting to professionalism concerns during PA education can lead to a multitude of adverse consequences, including poor medical outcomes, legal proceedings, financial implications, and general lack of trust in health care system.
Knowledge and skills around medical professionalism and professional behavior standards are paramount among those needed to prepare students for clinical practice. Identification of factors associated with future disciplinary actions can identify populations at risk and who may benefit most from focused professionalism education and intervention. This study sets the foundation for further evaluation of the association between DPV and academic probation during medical professional education and subsequent PGDA by state licensing boards. While we found no statistically significant impact of race or sex in this study, future research would need to look specifically at racial and gender bias.
Krupat et al34 have reported that disciplined medical students were 5 times more likely to undergo disciplinary review during residency and during clinical practice, 10% of those were sued or sanctioned. Furthermore, Papadakis et al24 have reported that physicians sanctioned or disciplined by their state medical boards had professionalism lapses during medical school at a higher rate than their non disciplined peers.
Strengths
The methodology of this study was strong with a geographically diverse represented sample of PA programs. Use of a retrospective cohort model provided an opportunity to gather a large amount of data at once and perform a robust analysis of multiple antecedents to our outcome measure. This study evaluated both the association of professionalism violations and academic probation with PGDA for PAs rather than just professionalism violations. Moreover, this study covers the review of up to 20 years for some of the cohorts evaluated, offering a long-term perspective for the associations.
Limitations
The limitations of our study include a relatively small sample size from 3 PA programs. Occurrences of postgraduate discipline and state medical board sanctions are rare and could have been missed by searches of public records. In addition, student records were searched at individual programs, and institutional records were hand-explored for probationary data. Professionalism disciplinary actions were also rare, and some could be missed or underreported. Historical definitions of academic probation were not available; thus, variability in the definition of academic probation is possible. Although the duration of this study looked for state medical board actions for a 20-year postgraduate duration, not all graduates were followed up for 20 years. For example, the later graduation cohorts did not have a full 20 years since graduation. The main objective outcome variable, state licensing board action, is a relatively rare event and only wielded in egregious circumstances. Many of the professionalism issues may not have been recorded because of subjective bias. The type of medical board action was not stratified. Early versus late career board actions were not stratified. Those students who were dismissed or failed to graduate were not included in the analysis contributing to the possibility of undercounting the effect of professionalism. There are few prospective studies in professionalism, and mostly, these follow students forward over a short period of time.
Future Work
Further research should examine best practices and effective methods for PA educators to handle professionalism lapses and individuals' responses to attempts of remediation. This study shows the predictive propensity of previous professionalism lapses in postgraduate board actions; however, more research should be targeted at methods for changing future professional behavior. Although we found no statistically significant impact of race or sex in this study, future research will need to examine the issue of racial and gender bias in PA education. Furthermore, future studies to evaluate weaponization of professionalism are warranted.
Conclusions
Documented professionalism violations or academic probation while in the PA school is significantly associated with higher odds of receiving licensing board disciplinary action. While DPV have a high magnitude of effect, academic probation has a greater magnitude of effect. This could represent an intersection of professionalism and academic performance. Meaningful and substantial efforts to identify and address professional behavior violations and academic probation during medical professional training are essential to maintain the integrity and reputation of the PA profession.
ACKNOWLEDGMENTS
This study was funded in part by a grand award from Physician Assistant Education Association, Washington, DC. Funding of the study does not necessarily constitute endorsement of the findings of this research report by Physician Assistant Education Association.
The authors thank Physician Assistant Education Association (PAEA), the PAEA Grants and Scholarship Review Committee, and the Don Pedersen Research Grants Program for supporting this study.
Footnotes
The authors declare no conflict of interest.
REFERENCES
- 1.Rawson JV, Thompson N, Sostre G, Deitte L. The cost of disruptive and unprofessional behaviors in health care. Acad Radiol. 2013;20(9):1074-1076. [DOI] [PubMed] [Google Scholar]
- 2.Rosenstein AH, O'Daniel M. Disruptive behavior and clinical outcomes: perceptions of nurses and physicians. Am J Nurs. 2005;105(1):54-64. [DOI] [PubMed] [Google Scholar]
- 3.Cochran AMD, Elder WBPD. Effects of disruptive surgeon behavior in the operating room. Am J Surg. 2015;209(1):65-70. doi: 10.1016/j.amjsurg.2014.09.017 [DOI] [PubMed] [Google Scholar]
- 4.Riskin A, Erez A, Foulk TA, et al. The impact of rudeness on medical team performance: a randomized trial. Pediatrics (Evanston). 2015;136(3):487-495. doi: 10.1542/peds.2015-1385 [DOI] [PubMed] [Google Scholar]
- 5.Mazzocco K, Petitti DB, Fong KT, et al. Surgical team behaviors and patient outcomes. Am J Surg. 2009;197(5):678-685. [DOI] [PubMed] [Google Scholar]
- 6.Lagoo J, Berry WR, Miller K, et al. Multisource evaluation of surgeon behavior is associated with malpractice claims. Ann Surg. 2019;270(1):84-90. doi: 10.1097/SLA.0000000000002742 [DOI] [PubMed] [Google Scholar]
- 7.Cooper WO, Guillamondegui O, Hines OJ, et al. Use of unsolicited patient observations to identify surgeons with increased risk for postoperative complications. JAMA Surg. 2017;152(6):522-529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Cooper WO, Hickson GB, Guillamondegui OD, et al. Professionalism of admitting and consulting services and trauma patient outcomes. Ann Surg. 2022;275(5):883-890. doi: 10.1097/SLA.0000000000005416 [DOI] [PubMed] [Google Scholar]
- 9.Ehie O, Muse I, Hill L, Bastien A. Professionalism: microaggression in the healthcare setting. Curr Opin Anaesthesiol. 2021;34(2):131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Cooper WO, Spain DA, Guillamondegui O, et al. Association of coworker reports about unprofessional behavior by surgeons with surgical complications in their patients. JAMA Surg. 2019;154(9):828-834. doi: 10.1001/jamasurg.2019.1738 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Whittemore AD. The impact of professionalism on safe surgical care. J Vasc Surg. 2007;45(2):415-419. [DOI] [PubMed] [Google Scholar]
- 12.Kawar E, DiGiovine B. MICU care delivered by PAs versus residents: do PAs measure up? JAAPA. 2011;24(1):36-41. [DOI] [PubMed] [Google Scholar]
- 13.Kurtzman ET, Barnow BS. A comparison of nurse practitioners, physician assistants, and primary care physicians' patterns of practice and quality of care in health centers. Med Care. 2017;55(6):615-622. [DOI] [PubMed] [Google Scholar]
- 14.van Den Brink G, Hooker R, Van Vught A, Vermeulen H, Laurant M. The cost-effectiveness of physician assistants/associates: a systematic review of international evidence. PLoS One. 2021;16(11):e0259183. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Roy CL, Liang CL, Lund M, et al. Implementation of a physician assistant/hospitalist service in an academic medical center: impact on efficiency and patient outcomes. J Hosp Med. 2008;3(5):361-368. [DOI] [PubMed] [Google Scholar]
- 16.Timmons EJ. The effects of expanded nurse practitioner and physician assistant scope of practice on the cost of Medicaid patient care. Health Policy. 2017;121(2):189-196. [DOI] [PubMed] [Google Scholar]
- 17.Physician Assistant Education Association. By the Numbers: Program Report 32: Data From the 2016 Program Survey. Washington, DC: PAEA; 2017. [Google Scholar]
- 18.Barry C, Honda T, Spackman J, Parente J, Patel D, Coombs J. Professionalism Beyond PA Education: Licensing Board Disciplinary Actions. Washington, DC: PAEA Education Forum; 2019. [Google Scholar]
- 19.The National Commission on Certification of Physician Assistants. 2017 Statistical Profile of Certified Physician Assistants, Annual Report. 2018. https://prodcmsstoragesa.blob.core.windows.net/uploads/files/2017StatisticalProfileofCertifiedPhysicianAssistants%206.27.pdf.
- 20.Hickson GB, Federspiel CF, Pichert JW, Miller CS, Gauld-Jaeger J, Bost P. Patient complaints and malpractice risk. JAMA. 2002;287(22):2951-2957. [DOI] [PubMed] [Google Scholar]
- 21.Studdert DM, Bismark MM, Mello MM, Singh H, Spittal MJ. Prevalence and characteristics of physicians prone to malpractice claims. N Engl J Med. 2016;374(4):354-362. [DOI] [PubMed] [Google Scholar]
- 22.Murff HJ, France DJ, Blackford J, et al. Relationship between patient complaints and surgical complications. Qual Saf Health Care. 2006;15(1):13-16. doi: 10.1136/qshc.2005.013847 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Khaliq AA, Dimassi H, Huang C-Y, Narine L, Smego RA, Jr. Disciplinary action against physicians: who is likely to get disciplined? Am J Med. 2005;118(7):773-777. [DOI] [PubMed] [Google Scholar]
- 24.Papadakis MA, Hodgson CS, Teherani A, Kohatsu ND. Unprofessional behavior in medical school is associated with subsequent disciplinary action by a state medical board. Acad Med. 2004;79(3):244-249. [DOI] [PubMed] [Google Scholar]
- 25.Papadakis MA, Teherani A, Banach MA, et al. Disciplinary action by medical boards and prior behavior in medical school. N Engl J Med. 2005;353(25):2673-2682. [DOI] [PubMed] [Google Scholar]
- 26.Kohatsu ND, Gould D, Ross LK, Fox PJ. Characteristics associated with physician discipline: a case-control study. Arch Intern Med. 2004;164(6):653-658. doi: 10.1001/archinte.164.6.653 [DOI] [PubMed] [Google Scholar]
- 27.Brotherton S, Kao A, Crigger BJ. Professing the values of medicine: the modernized AMA code of medical ethics. JAMA. 2016;316(10):1041-1042. doi: 10.1001/jama.2016.9752 [DOI] [PubMed] [Google Scholar]
- 28.Papadakis MA, Osborn EHS, Cooke M, Healy K. A strategy for the detection and evaluation of unprofessional behavior in medical students. Acad Med. 1999;74(9):980-990. doi: 10.1097/00001888-199909000-00009 [DOI] [PubMed] [Google Scholar]
- 29.Papadakis MA, Loeser H, Healy K. Early detection and evaluation of professionalism deficiencies in medical students: one school's approach. Acad Med. 2001;76(11):1100-1106. [DOI] [PubMed] [Google Scholar]
- 30.Teherani A, Hodgson CS, Banach M, Papadakis MA. Domains of unprofessional behavior during medical school associated with future disciplinary action by a State Medical Board. Acad Med. 2005;80(10):S17-S20. [DOI] [PubMed] [Google Scholar]
- 31.Pang M, Platt RW, Schuster T, Abrahamowicz M. Flexible extension of the accelerated failure time model to account for nonlinear and time-dependent effects of covariates on the hazard. Stat Methods Med Res. 2021;30(11):2526-2542. doi: 10.1177/09622802211041759 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Wei L-J. The accelerated failure time model: a useful alternative to the Cox regression model in survival analysis. Stat Med. 1992;11(14‐15):1871-1879. [DOI] [PubMed] [Google Scholar]
- 33.George B, Seals S, Aban I. Survival analysis and regression models. J Nucl Cardiol. 2014;21(4):686-694. doi: 10.1007/s12350-014-9908-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Krupat E, Dienstag JL, Padrino SL, et al. Do professionalism lapses in medical school predict problems in residency and clinical practice? Acad Med. 2020;95(6):888-895. [DOI] [PubMed] [Google Scholar]