Research Spotlight

Deshpande, D., J. C. Alffenaar, C. U. Koser, K. Dheda, M. L. Chapagain, N. Simbar, T. Schon, M. G. G. Sturkenboom, H. McIlleron, P. S. Lee, T. Koeuth, S. G. Mpagama, S. Banu, S. Foongladda, O. Ogarkov, S. Pholwat, E. R. Houpt, S. K. Heysell and T. Gumbo (2018). “d-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal.” Clin Infect Dis 67(suppl_3): S308-s316.

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Background: d-cycloserine is used to treat multidrug-resistant tuberculosis. Its efficacy, contribution in combination therapy, and best clinical dose are unclear, also data on the d-cycloserine minimum inhibitory concentration (MIC) distributions is scant. Methods: We performed a systematic search to identify pharmacokinetic and pharmacodynamic studies performed with d-cycloserine. We then performed a combined exposure-effect and dose fractionation study of d-cycloserine in the hollow fiber system model of tuberculosis (HFS-TB). In parallel, we identified d-cycloserine MICs in 415 clinical Mycobacterium tuberculosis (Mtb) isolates from patients. We utilized these results, including intracavitary concentrations, to identify the clinical dose that would be able to achieve or exceed target exposures in 10000 patients using Monte Carlo experiments (MCEs). Results: There were no published d-cycloserine pharmacokinetics/pharmacodynamics studies identified. Therefore, we performed new HFS-TB experiments. Cyloserine killed 6.3 log10 colony-forming units (CFU)/mL extracellular bacilli over 28 days. Efficacy was driven by the percentage of time concentration persisted above MIC (%TMIC), with 1.0 log10 CFU/mL kill achieved by %TMIC = 30% (target exposure). The tentative epidemiological cutoff value with the Sensititre MYCOTB assay was 64 mg/L. In MCEs, 750 mg twice daily achieved target exposure in lung cavities of 92% of patients whereas 500 mg twice daily achieved target exposure in 85% of patients with meningitis. The proposed MCE-derived clinical susceptibility breakpoint at the proposed doses was 64 mg/L. Conclusions: Cycloserine is cidal against Mtb. The susceptibility breakpoint is 64 mg/L. However, the doses likely to achieve the cidality in patients are high, and could be neurotoxic.

Dearani, J. A., T. K. Rosengart, M. B. Marshall, M. J. Mack, D. R. Jones, R. L. Prager and R. J. Cerfolio (2018). “Incorporating Innovation and New Technology into Cardiothoracic Surgery.” Ann Thorac Surg Nov 21. [Epub ahead of print].

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The appropriate implementation of new technology, root cause analysis of “imperfect” outcomes and the continuous reappraisal of postgraduate training are needed to improve the care of tomorrow’s patients. Healthcare delivery remains one of the most expensive sectors in the United States and the application of new and expensive technology that is necessary for the advancement of this complex specialty must be aligned with providing the best care for our patients. There are a several pathways to innovation; one is partnering with industry and the other is the investigational laboratory. Innovation and the funding thereof come from both the public and the private sector. The majority of new trials that are likely to impact cardiothoracic surgery are industry sponsored trials to meet the requirements necessary for regulatory approval. Cost considerations are paramount when considering integration of innovative technology and treatments into a clinical cardiothoracic surgical practice. The value of any new innovation is determined by the quality divided by the cost, and lean initiatives maximize this equation. The importance and implications of conflict of interest (COI) has been a concern for physicians particularly when new technology or procedures are being incorporated into clinical practice and full disclosures by medical professionals and others involved are essential. Our “societies” and “associations” provide a platform for presentation and peer-reviewed discussion of new procedures, innovations, and trials, etc. and provide a venue for the sharing of knowledge on the highest quality patient care through education and research.

Cullinane, D. C., R. S. Jawa, J. J. Como, A. Moore, D. S. Morris, J. Cheriyan, O. D. Guillamondegui, S. R. Goldberg, L. Petrey, G. Schaefer, K. A. Khwaja, S. E. Rowell, R. R. Barbosa, G. A. Bass, G. Kasotakis and B. R. Robinson (2018). “Management of penetrating intra-peritoneal colon injuries: A meta-analysis and practice management guideline from the Eastern Association for the Surgery of Trauma.” J Trauma Acute Care Surg Nov 20. [Epub ahead of print].

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BACKGROUND: The management of penetrating colon injuries in civilians has evolved over the last four decades. The objectives of this meta-analysis are to evaluate the current treatment regimens available for penetrating colon injuries and assess the role of anastomosis in damage control surgery to develop a practice management guideline for surgeons. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, a subcommittee of the Practice Management Guidelines section of EAST conducted a systematic review using MEDLINE and EMBASE articles from 1980 through 2017. We developed three relevant problem, intervention, comparison, and outcome (PICO) questions regarding penetrating colon injuries. Outcomes of interest included mortality and infectious abdominal complications. RESULTS: Thirty-seven studies were identified for analysis, of which 16 met criteria for quantitative meta-analysis and included 705 patients considered low-risk in six prospective randomized studies. Seven hundred thirty-eight patients in 10 studies undergoing damage control laparotomy (DCL) and repair or resection and anastomosis (R&A) were included in a separate meta-analysis. Meta-analysis of high-risk patients undergoing repair or R&A was not feasible due to inadequate data. CONCLUSIONS: In adult civilian patients sustaining penetrating colon injury without signs of shock, significant hemorrhage, severe contamination, or delay to surgical intervention, we recommend that colon repair or R&A be performed rather than routine colostomy. In adult high-risk civilian trauma patients sustaining penetrating colon injury, we conditionally recommend that colon repair or R&A be performed rather than routine colostomy. In adult civilian trauma patients sustaining penetrating colon injury who had DCL, we conditionally recommend that routine colostomy not be performed; instead, definitive repair or delayed R&A or anastomosis at initial operation should be performed rather than routine colostomy. LEVEL OF EVIDENCE: Systematic review/meta-analysis, Level III.

Crews, D. C. and D. E. Wesson (2018). “Persistent Bias: A Threat to Diversity among Health Care Leaders.” Clin J Am Soc Nephrol 13(11): 1757-1759.

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Much of the bias experienced by African Americans in United States health care organizations goes beyond the interpersonal, with which most are familiar, to include that which is structural, i.e., interconnected institutions whose linkages to racialized policies and practices are historically rooted and continue to be culturally and/or politically reinforced. One example is the development of candidate pools from which to choose organizational leaders exclusively through use of referrals from existing physician employees and/or existing organizational leaders. In not too distant United States history, African Americans were specifically excluded from health care organizations and, if hired, were excluded from leadership. This very recent history has limited the exposure of African Americans to settings in which their leadership potential can be recognized. Consequently, focusing the leadership search process on referrals from within the organization inadvertently puts African American candidates at a distinct disadvantage and perpetuates a narrative that reinforces the status quo. [Excerpt from text, p. 757; no abstract available.]

Copeland, L. A., J. E. Zeber, L. V. Thibodeaux, R. T. McIntyre, E. M. Stock and A. K. Hochhalter (2018). “Postdischarge Correlates of Health Literacy Among Medicaid Inpatients.” Popul Health Manag 21(6): 493-500.

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Health literacy may represent a target for intervention to improve hospital transitions. This study analyzed the association of health literacy with postdischarge utilization among Medicaid patients treated in an integrated health care system. Discharged inpatients covered by Medicaid (N = 112) participated in this observational study set in a single 600-bed hospital in a private, nonprofit, integrated health care system in the southwestern United States. Participants completed surveys within 15 days of discharge, self-reporting demographics, self-care behaviors, and 2 measures of health literacy (REALM-SF [Short Form of the Rapid Estimate of Adult Literacy in Medicine] and Chew [health literacy screen from Chew et al]). Electronic medical records data were incorporated to determine occurrence of 30-day/90-day postdischarge emergency visits and readmission. Half the respondents (54%) scored at the high-school grade equivalent on REALM-SF, while 46% scored adequate health literacy on the Chew. Forty percent (40%) experienced either emergency care or readmission within 90 days post discharge. Patients who were younger, female, or living with children had relatively better health literacy. Health literacy itself was not associated with readmission or postdischarge emergency care, although African American race was. Although Medicaid patients varied considerably on health literacy, this factor was not associated with adverse health care outcomes. Future work should better identify individuals requiring supportive transition services to reduce problems following hospital discharge.