Publications

2019
Ridout KK, Ridout SJ, Guille C, Mata DA, Akil H, Sen S. Physician-Training Stress and Accelerated Cellular Aging. Biol Psychiatry. 2019.Abstract
BACKGROUND: Stress is a key precipitant for many common diseases, but established biological markers to track stress and guide investigations into mechanisms linking stress and disease are lacking. Cross-sectional studies have identified correlations between stress and telomere attrition, but no large, longitudinal studies examining the impacts of chronic stress on telomere length exist. Residency training for physicians is a well-established stressful experience and can be used as a prospective stress model. METHODS: In a longitudinal cohort study of 250 interns (first-year residents) at 55 United States hospital systems serving during the 2015-2016 academic year, we examined associations between measures of the residency experience and saliva-measured telomere attrition. RESULTS: Telomere length shortened significantly over the course of internship year, from mean ± SD of 6465.1 ± 876.8 base pairs before internship to 6321.5 ± 630.6 base pairs at the end of internship (t = 2.69; p = .008). Stressful early family environments and neuroticism were significantly associated with shorter preinternship telomere length. Longer work hours were associated with greater telomere intern telomere loss over the year (p = .002). Of note, the mean telomere attrition during internship year was six times greater than the typical annual attrition rate identified in a recent meta-analysis. CONCLUSIONS: This work implicates telomere attrition as a biologically measurable consequence of physician training, with the magnitude of attrition associated with workload. Identification of an objective, biological sequela of residency stress may help to facilitate the development of effective interventions. Further, the findings implicate telomere attrition as an objective biomarker to follow the pathologic effects of stress, in general.
Szymaniak JA, Mata DA, Cole AP. Are historical studies relevant in the setting of grade migration?. BJU Int. 2019;123 (3) :375-376.
2018
Lewandrowski K, Keegan A, Makarenko V, Maryamchak E, Mata DA, Palte MJ, Rudolf JW, Safdar N, Schmidt RJ, Stuart L, et al. Development of a Commercial Reference Laboratory Elective Rotation for Residents in Clinical Pathology. Am J Clin Pathol. 2018;150 (6) :485-490.Abstract
Objectives: To develop a curriculum for a commercial reference laboratory clinical pathology training elective. Methods: A 4-day elective at Quest Diagnostics was developed. The elective included 32 sessions composed of interactive didactic sessions and laboratory tours/demonstrations. Ten residents who attended the elective completed a written evaluation and scored each component of the curriculum. Results: Written comments were very positive and demonstrated the goals of the elective were achieved. Laboratory tours and one-on-one sessions with the medical directors were especially well received. Most of the residents stated that the rotation gave them exposure to an area of laboratory medicine that they were not familiar with. Conclusions: The elective provided a resident training experience that was highly regarded and exposed residents to an area of laboratory medicine not encountered in most pathology training programs. Our curriculum could serve as a model for establishing a similar elective in other training programs.
Rotenstein LS, Torre M, Ramos MA, Rosales RC, Guille C, Sen S, Mata DA. Prevalence of Burnout Among Physicians: A Systematic Review. JAMA. 2018;320 (11) :1131-1150.Abstract
Importance: Burnout is a self-reported job-related syndrome increasingly recognized as a critical factor affecting physicians and their patients. An accurate estimate of burnout prevalence among physicians would have important health policy implications, but the overall prevalence is unknown. Objective: To characterize the methods used to assess burnout and provide an estimate of the prevalence of physician burnout. Data Sources and Study Selection: Systematic search of EMBASE, ERIC, MEDLINE/PubMed, psycARTICLES, and psycINFO for studies on the prevalence of burnout in practicing physicians (ie, excluding physicians in training) published before June 1, 2018. Data Extraction and Synthesis: Burnout prevalence and study characteristics were extracted independently by 3 investigators. Although meta-analytic pooling was planned, variation in study designs and burnout ascertainment methods, as well as statistical heterogeneity, made quantitative pooling inappropriate. Therefore, studies were summarized descriptively and assessed qualitatively. Main Outcomes and Measures: Point or period prevalence of burnout assessed by questionnaire. Results: Burnout prevalence data were extracted from 182 studies involving 109 628 individuals in 45 countries published between 1991 and 2018. In all, 85.7% (156/182) of studies used a version of the Maslach Burnout Inventory (MBI) to assess burnout. Studies variably reported prevalence estimates of overall burnout or burnout subcomponents: 67.0% (122/182) on overall burnout, 72.0% (131/182) on emotional exhaustion, 68.1% (124/182) on depersonalization, and 63.2% (115/182) on low personal accomplishment. Studies used at least 142 unique definitions for meeting overall burnout or burnout subscale criteria, indicating substantial disagreement in the literature on what constituted burnout. Studies variably defined burnout based on predefined cutoff scores or sample quantiles and used markedly different cutoff definitions. Among studies using instruments based on the MBI, there were at least 47 distinct definitions of overall burnout prevalence and 29, 26, and 26 definitions of emotional exhaustion, depersonalization, and low personal accomplishment prevalence, respectively. Overall burnout prevalence ranged from 0% to 80.5%. Emotional exhaustion, depersonalization, and low personal accomplishment prevalence ranged from 0% to 86.2%, 0% to 89.9%, and 0% to 87.1%, respectively. Because of inconsistencies in definitions of and assessment methods for burnout across studies, associations between burnout and sex, age, geography, time, specialty, and depressive symptoms could not be reliably determined. Conclusions and Relevance: In this systematic review, there was substantial variability in prevalence estimates of burnout among practicing physicians and marked variation in burnout definitions, assessment methods, and study quality. These findings preclude definitive conclusions about the prevalence of burnout and highlight the importance of developing a consensus definition of burnout and of standardizing measurement tools to assess the effects of chronic occupational stress on physicians.
Peluso MJ, Rodman A, Mata DA, Kellett AT, van Schalkwyk S, Rohrbaugh RM. A Comparison of the Expectations and Experiences of Medical Students From High-, Middle-, and Low-Income Countries Participating in Global Health Clinical Electives. Teach Learn Med. 2018;30 (1) :45-56.Abstract
Phenomenon: Global health education (GHE) is expanding to include socioculturally and resource-different settings, with the goal of developing a workforce with members who can promote health equity locally and globally. GHE is also no longer limited to students from high-income countries (HICs). However, it is unknown whether the motivations and experiences of medical students from HICs and from low- and middle-income countries (LMICs) participating in GHE clinical electives through institutional partnerships are similar or different. Such an understanding is needed to design programs that meet the needs of participants and effectively train them in the principles and practice of global health. APPROACH: This was a cross-sectional, mixed-methods survey of LMIC students from partner sites rotating at one U.S. medical school, and U.S. students from one medical school rotating at partner sites, between 2010 and 2015. Variables included demographic characteristics of participants, components of the curriculum at the home institution, and components of the away rotation, including perceptions of its content and impact. Content analysis was used to identify themes in the responses provided to open-ended questions. FINDINGS: In all, 63 of 84 (75%) LMIC and 61 of 152 (40%) U.S. students participated. Recall of predeparture training was low for both LMIC and U.S. students (44% and 55%, respectively). Opportunities to experience different healthcare systems, resource-different settings, and cultural exposure emerged as motivators for both groups. Both groups noted differences in doctor-patient relationships, interactions between colleagues, and use of diagnostic testing. U.S. respondents were more likely to perceive differences in the impact of social determinants of health and ethical issues. Both groups felt that their experience affected their interactions with patients and perspectives on education, but U.S. students were more likely to mention perspectives on healthcare delivery and social determinants of health, whereas LMIC respondents noted impacts on career goals. Insights: These results argue that GHE is not restricted to resource-constrained settings and that students from LMICs have similar reasons for participation as those from HICs. LMIC students also identified a lack of emphasis on GHE topics like social determinants of health during GH electives, which could diminish the effectiveness of these experiences. Both U.S. and LMIC students emphasized the cultural component of their GHE experience but had different perceptions regarding core tenets of GHE, such as the social determinants of health and health equity, during these experiences.
Anaya Y, Mata DA, Letourneau J, Cakmak H, Cedars MI, Rosen MP. A novel oocyte maturation trigger using 1500 IU of human chorionic gonadotropin plus 450 IU of follicle-stimulating hormone may decrease ovarian hyperstimulation syndrome across all in vitro fertilization stimulation protocols. J Assist Reprod Genet. 2018;35 (2) :297-307.Abstract
PURPOSE: Modification of the trigger used to induce final oocyte maturation in in vitro fertilization (IVF) is a major strategy used to reduce the risk of ovarian hyperstimulation syndrome (OHSS). A novel trigger composed of 1500 IU of human chorionic gonadotropin (hCG) plus 450 IU of follicle-stimulating hormone (FSH) has been developed to reduce OHSS risk. This study compares outcomes of the novel trigger to conventional triggers used in high-risk OHSS patients undergoing IVF. METHODS: In this retrospective cohort study, IVF cycles at high risk for OHSS based on a serum estradiol > 5000 pg/ml on trigger day conducted between January 2008 and February 2016 were evaluated. Oocyte maturation was induced with the novel trigger (1500 IU hCG plus 450 IU FSH) or a conventional trigger [3300 IU hCG, gonadotropin-releasing hormone agonist (GnRHa) alone, or GnRHa plus 1500 IU hCG]. IVF cycle outcomes were compared. Trigger strategies were examined for associations with OHSS development using logistic regression. RESULTS: Among 298 eligible IVF cycles identified, there were no differences in oocyte maturation, fertilization, embryo quality, or pregnancy outcomes among all triggers. After adjusting for serum estradiol level and number of follicles, the novel trigger was associated with lower odds of OHSS symptom development compared to the 3300 IU hCG and GnRHa plus hCG 1500 IU triggers (p = 0.007 and 0.04, respectively). CONCLUSIONS: This study suggests that 1500 IU hCG plus 450 IU FSH may be associated with decreased OHSS symptoms compared to conventional triggers, while producing similar IVF and pregnancy outcomes. More important, this novel trigger may provide a superior alternative in down-regulated cycles and in patients with hypothalamic dysfunction where GnRHa triggers cannot be utilized.
2017
Chu YX, Mitchell RN, Mata DA. Improving undergraduate pathology teaching: medical students' perspective-reply. Hum Pathol. 2017;68 :203-204.
Minhas PS, Enogieru IE, Mitchell RN, Mata DA. Passport to pathology: transforming the medical student pathology elective from a passive educational experience to an exciting, immersive clinical rotation. Hum Pathol. 2017;68 :34-39.
Guille C, Frank E, Zhao Z, Kalmbach DA, Nietert PJ, Mata DA, Sen S. Work-Family Conflict and the Sex Difference in Depression Among Training Physicians. JAMA Intern Med. 2017;177 (12) :1766-1772.Abstract
Importance: Depression is common among training physicians and may disproportionately affect women. The identification of modifiable risk factors is key to reducing this disease burden and its negative impact on patient care and physician career attrition. Objective: To determine the presence and magnitude of a sex difference in depressive symptoms and work-family conflict among training physicians; and if work-family conflict impacts the sex difference in depressive symptoms among training physicians. Design, Setting, and Participants: A prospective longitudinal cohort study of medical internship in the United States during the 2015 to 2016 academic year in which 3121 interns were recruited across all specialties from 44 medical institutions. Main Outcomes and Measures: Prior to and during their internship year, participants reported the degree to which work responsibilities interfered with family life using the Work Family Conflict Scale and depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9). Results: Mean (SD) participant age was 27.5 (2.7) years, and 1571 participants (49.7%) were women. Both men and women experienced a marked increase in depressive symptoms during their internship year, with the increase being statistically significantly greater for women (men: mean increase in PHQ-9, 2.50; 95% CI, 2.26-2.73 vs women: mean increase, 3.20; 95% CI, 2.97-3.43). When work-family conflict was accounted for, the sex disparity in the increase in depressive symptoms decreased by 36%. Conclusions and Relevance: Our study demonstrates that depressive symptoms increase substantially during the internship year for men and women, but that this increase is greater for women. The study also identifies work-family conflict as an important potentially modifiable factor that is associated with elevated depressive symptoms in training physicians. Systemic modifications to alleviate conflict between work and family life may improve physician mental health and reduce the disproportionate depression disease burden for female physicians. Given that depression among physicians is associated with poor patient care and career attrition, efforts to alleviate depression among physicians has the potential to reduce the negative consequences associated with this disease.
Jhun I, Mata DA, Nordio F, Lee M, Schwartz J, Zanobetti A. Ambient Temperature and Sudden Infant Death Syndrome in the United States. Epidemiology. 2017;28 (5) :728-734.Abstract
BACKGROUND: Sudden infant death syndrome (SIDS) is a leading cause of infant mortality in the United States. While thermal stress is implicated in many risk factors for SIDS, the association between ambient temperature and SIDS remains unclear. METHODS: We obtained daily individual-level infant mortality data and outdoor temperature data from 1972 to 2006 for 210 US cities. We applied a time-stratified case-crossover analysis to determine the effect of ambient temperature on the risk of SIDS by season. We stratified the analysis by race, infant age, and climate. RESULTS: There were a total of 60,364 SIDS cases during our study period. A 5.6°C (10°F) higher daily temperature on the same day was associated with an increased SIDS risk of 8.6% (95% confidence interval [CI] = 3.6%, 13.8%) in the summer, compared with a 3.1% decrease (95% CI = -5.0%, -1.3%) in the winter. Summer risks were greater among black infants (18.5%; 95% CI = 9.3%, 28.5%) than white infants (3.6%; 95% CI = -2.3%, 9.9%), and among infants 3-11 months old (16.9%; 95% CI = 8.9%, 25.5%) than infants 0-2 months old (2.7%; 95% CI = -3.5%, 9.2%). The temperature-SIDS association was stronger in climate clusters in the Midwest and surrounding northern regions. CONCLUSIONS: Temperature increases were associated with an elevated risk of SIDS in the summer, particularly among infants who were black, 3 months old and older, and living in the Midwest and surrounding northern regions.
von Rundstedt F-C, Mata DA, Kryvenko ON, Shah AA, Jhun I, Lerner SP. Utility of Clinical Risk Stratification in the Selection of Muscle-Invasive Bladder Cancer Patients for Neoadjuvant Chemotherapy: A Retrospective Cohort Study. Bladder Cancer. 2017;3 (1) :35-44.Abstract
Introduction: Level I evidence supports the use of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer prior to radical cystectomy (RC). On average, 30-40% of patients achieve a complete pathologic response (i.e., stage pT0) after receiving NAC. Some centers risk-stratify patients, suggesting that there may be a higher-risk population that would derive the most benefit from NAC. Recently, a risk-stratification model developed at M.D. Anderson Cancer Center (MDACC) specified criteria for clinical staging and patient selection for NAC. We applied this model to our own RC patient cohort and evaluated our own experience with clinical risk stratification and the effect of NAC on post treatment risk categories. Methods: We retrospectively reviewed the charts of consecutive patients who underwent RC at two institutions between 2004 and 2014 and noted whether or not they received NAC. We determined the clinical stage by reviewing the exam under anesthesia, transurethral resection biopsy (TURBT) pathology, and preoperative imaging. Patients with cT2-T4a node-negative disease were included. Those with sarcomatoid features or adenocarcinoma were excluded. Patients were classified as high risk if they had tumor-associated hydronephrosis, clinical stage≥T3b-T4a disease, variant histology (i.e., micropapillary or small cell), or lymphovascular invasion (LVI), as specified by the MDACC model. Variables were examined for associations with cancer-specific survival (CSS), overall survival (OS), and risk-category reclassification. Results: We identified 166 patients with a median follow-up time of 22.2 months. In all, 117 patients (70.5%) did not receive NAC, 68 (58.1%) of whom we classified as high risk. Among patients not receiving NAC, CSS and OS were significantly decreased in high-risk patients (log-rank test p = 0.01 for both comparisons). The estimated age-adjusted hazard ratios of high-risk classification for cancer-specific and overall death were 3.2 (95% CI: 1.2 to 8.6) and 2.2 (95% CI: 1.1 to 4.4), respectively. On post-RC final pathology, 23 (46.9%) low-risk patients were up-classified to high risk and 17 (25.0%) high-risk patients were down-classified. Complete pathologic responses (pT0) were achieved in 7 (6.0%) patients and partial responses (pT1, pTa, pTis) were achieved in 28 (23.9%) patients. Of the 49 patients who did receive NAC, 43 (87.8%) received cisplatin-based and six (12.2%) received carboplatin-based regimens. Applying the MDACC model, we categorized 41 (83.7%) patients as high risk prior to NAC treatment. On final pathology, 3 (37.5%) low-risk patients were up-classified and 17 (41.5%) high-risk patients were down-classified. Complete pathologic responses (pT0) were seen in 13 (26.5%) patients and partial responses were seen in 10 (20.4%) patients. Although the utilization of NAC was not statistically significantly associated with CSS or OS (log-rank test p > 0.05 for both comparisons), it was associated with a 1.2 times increased odds (95% CI: 0.4 to 2.1) of post-RC reclassification from high to low risk on age-adjusted logistic regression. Conclusions: We found similar results using the clinical risk-stratification model in our cohort and showed that the high-risk category was associated with lower CSS and OS. NAC was associated with a higher probability of risk reclassification from high to low risk.
2016
Milner DA, Meserve EEK, Soong TR, Mata DA. Statistics for Pathologists. 1st ed. New York: Demos Medical Publishing; 2016 pp. 250. Publisher's Version
Mata DA, Ramasamy R, Lipshultz LI. Testosterone Treatment in Older Men. N Engl J Med. 2016;375 (1) :89.
Mata DA, Ramos MA, Sen S. Resident Physicians With Depression or Depressive Symptoms--In Reply. JAMA. 2016;315 (21) :2347-8.
Mata DA, Ramos MA, Kim MM, Guille C, Sen S. In Their Own Words: An Analysis of the Experiences of Medical Interns Participating in a Prospective Cohort Study of Depression. Acad Med. 2016.Abstract
PURPOSE: To compare the subjective experiences of interns with and without symptoms of depression using a mixed-methods approach. METHOD: In 2007-2008, interns from six institutions were screened for depression before and during internship using an online survey that included the Patient Health Questionnaire (PHQ-9). At the end of internship, participants were asked what made the year difficult, easy, and memorable, and how they had changed. Computerized lexical and qualitative thematic analyses were performed to analyze their free-text responses. RESULTS: Sixty-three percent (244/388) of invited interns participated in the original cohort study. Of those, 42% (103/244) answered the open-ended questions for this analysis. Thirty-five percent (36/103) screened positive for clinically significant depression (i.e., PHQ-9 score ≥ 10) during their intern year. Respondents with symptoms of depression were more likely to report problems with cynicism, exhaustion, and stress, while those without them were more likely to mention positive patient care and educational experiences. Respondents with symptoms of depression preferentially described experiences that "broke" their confidence, sense of well-being, and belief in the medical profession, while those who did not described profoundly positive, life-changing experiences regarding interactions with patients and supportive colleagues, through which they grew personally and professionally. CONCLUSIONS: Depression during internship affects not only objective outcomes like medical errors but also how interns value the profession and themselves, with potentially profound consequences for their future career decisions. Residency programs should implement reactive interventions targeting depression and proactive interventions promoting resilience and well-being to address the issues that lead to depression.
Ramos MA, Rotenstein LS, Mata DA. Student-run free clinics: the USA's psychiatry recruitment solution?. Lancet Psychiatry. 2016;3 (4) :321-2.
Degener S, Mata DA, Youssef R, Gödde D, Tandogdu Z, Roth S, von Rundstedt F-C. A review of molecular predictors of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer. Mini Rev Med Chem. 2016.Abstract
Locally advanced, muscle-invasive urothelial carcinoma of the bladder (MIBC) may be definitively treated with either radiotherapy or radical cystectomy (RC) with urinary diversion. Neoadjuvant chemotherapy (NAC) is typically administered prior to treatment with either modality. Receiving NAC prior to RC might confer a survival advantage compared to undergoing RC alone. However, its usefulness has been questioned due to concerns about overtreatment and toxicity. Having the ability to predict whether individual patients would benefit from or be harmed by NAC would be an important tool in precision medicine. Unfortunately, to date no prognostic or predictive molecular markers have been validated for this purpose. In this manuscript, we review the current state of molecular markers in MIBC treatment and outline how recent advances in whole-genome sequencing may soon improve the selection of precisely targeted therapeutics for the benefit of individual patients.
von Rundstedt F-C, Mata DA, Kryvenko ON, Roth S, Degener S, Dreger NM, Goedde D, Assaid A, Kamper L, Haage P, et al. Diagnostic Accuracy of Renal Mass Biopsy: An Ex Vivo Study of 100 Nephrectomy Specimens. Int J Surg Pathol. 2016.Abstract
We investigated the diagnostic accuracy of renal mass biopsy in an ex vivo model, as well as compared the agreement of the preoperative radiological diagnosis with the final pathologic diagnosis. Two 18-gauge needle-core and 2 vacuum-needle biopsies were performed ex vivo from the tumors of 100 consecutive patients undergoing radical nephrectomy between 2006 and 2010. The median tumor size was 5.5 cm. There was no significant difference with regard to cylinder length or tissue quality between the sampling methods. At least 1 of 4 needle cores contained diagnostic tissue in 88% of patients. Biopsy specimens identified clear cell (54%), papillary (13%), or chromophobe (5%) renal cell carcinoma; urothelial carcinoma (6%); oncocytoma (5%); liposarcoma (1%); metastatic colorectal carcinoma (1%); squamous cell carcinoma (1%); unclassified renal cell neoplasm (1%); and no tumor sampled (12%). The sensitivity of the biopsy for accurately determining the diagnosis was 88% (95% CI: 79% to 93%). The specificity was 100% (95% CI: 17% to 100%). Biopsy grade correlated strongly with final pathology (83.5% agreement). There was no difference in average tumor size in cases with the same versus higher grade on final pathology (5.87 vs 5.97; P = .87). Appraisal of tumor histology by radiology agreed with the pathologic diagnosis in 68% of cases. Provided that the biopsy samples the tumor tissue in a renal mass, pathologic analysis is of great diagnostic value in respect of grade and tumor type and correlates well with excisional pathology. This constitutes strong ground for increasingly used renal mass biopsy in patients considering active surveillance or ablation therapy.
Kohn TP, Mata DA, Ramasamy R, Lipshultz LI. Effects of Testosterone Replacement Therapy on Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis. Eur Urol. 2016.Abstract
CONTEXT: There is a potential risk that testosterone replacement therapy (TRT) may exacerbate lower urinary tract symptoms (LUTS) among aging men with late-onset hypogonadism (LOH) because of testosterone's growth-promoting effects on the prostate. OBJECTIVE: To compare the change in LUTS severity as assessed using the International Prostate Symptom Score (IPSS) between men receiving TRT versus placebo for the treatment of LOH. EVIDENCE ACQUISITION: Systematic search of MEDLINE, Embase, ClinicalTrials.gov, and The Cochrane Library for randomized controlled trials of TRT for LOH published between January 1992 and September 2015. Studies were eligible for inclusion if they were a randomized control trial, used TRT, and assessed LUTS outcomes using the IPSS. Estimates were pooled using random effects meta-analysis. Differences by study-level characteristics were estimated using meta-regression. EVIDENCE SYNTHESIS: Data were extracted from 14 trials involving 2029 participants. The average age was 64.5 yr and the average follow-up was 34.4 mo. Seven studies used topical, five used injectable, and two used oral testosterone. There was no statistically significant difference in pooled changes in IPSS from baseline to follow up in men treated with TRT compared with those receiving placebo (-0.41 points [95% confidence interval: -0.89 to 0.07; I(2)=0%, p=0.28] vs. 0.12 points [95% confidence interval: -0.32 to 0.55; I(2)=0%, p=0.81], between-group difference p>0.05). No between-group differences were noted in subanalyses that controlled for potential confounders such as type of testosterone, change in testosterone, aging male symptom scale, or prostate-specific antigen levels (p>0.05 for all comparisons). CONCLUSIONS: In this meta-analysis of 14 clinical trials of TRT for LOH, the change in IPSS was similar among men receiving TRT versus placebo, suggesting that TRT treatment does not worsen LUTS among men with LOH. PATIENT SUMMARY: In this analysis of 14 clinical trials, testosterone replacement therapy did not worsen lower urinary tract symptoms among men being treated for late-onset hypogonadism.
Minhas P, Chu YX, Mata DA. Neuropathology: bridging psychiatry and neurology in medical education. Lancet Psychiatry. 2016;3 (2) :98-100.

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