Research Spotlight

Kodali, S., M. R. Williams, D. Doshi, R. T. Hahn, K. H. Humphries, V. T. Nkomo, D. J. Cohen, P. S. Douglas, M. Mack, K. Xu, L. Svensson, V. H. Thourani, E. M. Tuzcu, N. J. Weissman, M. Leon and A. J. Kirtane (2016). “Sex-Specific Differences at Presentation and Outcomes Among Patients Undergoing Transcatheter Aortic Valve Replacement: A Cohort Study.” Ann Intern Med 164(6): 377-384.

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BACKGROUND: Female sex is associated with poorer outcomes after surgical aortic valve replacement (SAVR). Data on sex-specific differences after transcatheter aortic valve replacement (TAVR) are conflicting. OBJECTIVE: To examine sex-specific differences in patients undergoing TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) trial. DESIGN: Secondary analysis of the randomized and nonrandomized portions of the PARTNER trial. (ClinicalTrials.gov: NCT00530894). SETTING: 25 hospitals in the United States, Canada, and Germany. PATIENTS: High-risk and inoperable patients (1220 women and 1339 men). INTERVENTION: TAVR. MEASUREMENTS: Demographic characteristics, cardiac and noncardiac comorbidities, mortality, stroke, rehospitalization, vascular complications, bleeding complications, and echocardiographic valve parameters. RESULTS: At baseline, women had lower rates of hyperlipidemia, diabetes, smoking, and renal disease but higher Society of Thoracic Surgeons Predicted Risk of Mortality scores (11.9% vs. 11.1%; P < 0.001). After TAVR, women had more vascular complications (17.3% vs. 10.0%; difference, 7.29 percentage points [95% CI, 4.63 to 9.95 percentage points]; P < 0.001) and major bleeding (10.5% vs. 7.7%; difference, 2.8 percentage points [CI, 0.57 to 5.04 percentage points]; P = 0.012) but less frequent moderate and severe paravalvular regurgitation (6.0% vs. 14.3%; difference, -8.3 percentage points [CI, -11.7 to -5.0 percentage points]; P < 0.001). At 30 days, the unadjusted all-cause mortality rate (6.5% vs. 5.9%; difference, 0.6 percentage point [CI, -1.29 to 2.45 percentage points]; P = 0.52) and stroke incidence (3.8% vs. 3.0%; difference, 0.8 percentage point [CI, -0.62 to 2.19 percentage points]; P = 0.28) were similar. At 1 year, all-cause mortality was significantly lower in women than in men (19.0% vs. 25.9%; hazard ratio, 0.72 [CI, 0.61 to 0.85]; P < 0.001). LIMITATION: Secondary analysis that included nonrandomized trial data. CONCLUSION: Despite a higher incidence of vascular and bleeding complications, women having TAVR had lower mortality than men at 1 year. Thus, sex-specific risk in TAVR is the opposite of that in SAVR, for which female sex has been shown to be independently associated with an adverse prognosis. PRIMARY FUNDING SOURCE: Edwards Lifesciences.

Janke-Stedronsky, S. R., D. S. Greenawalt, E. M. Stock, J. Y. Tsan, A. A. MacCarthy, D. J. MacCarthy and L. A. Copeland (2016). “Association of parental status and diagnosis of posttraumatic stress disorder among veterans of Operations Iraqi and Enduring Freedom.” Psychol Trauma 8(1): 72-79.

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Research indicates that concerns about disruption of family relationships during military service may be associated with greater posttraumatic stress symptomatology. The current study sought to extend previous findings by examining the relative odds of a posttraumatic stress disorder (PTSD) diagnosis among Operations Enduring and Iraqi Freedom (OEF/OIF) veterans with dependent children versus veterans without dependent children. Administrative databases were queried to identify 36,334 OEF/OIF veterans with dependent children seeking care in the Veterans Health Administration (VA) during fiscal years 2006-2009. These veterans were matched 1:1 on age, gender, and demobilization date to veterans without dependent children (N = 72,668). In unconditional analyses, OEF/OIF veterans with dependent children versus those without were significantly more likely to incur a PTSD diagnosis (44% vs. 28%). After controlling for demographic variables, mental health utilization, and other serious mental illness, OEF/OIF veterans with dependent children were about 40% more likely to carry a diagnosis of PTSD. The association was stronger for men than for women. It may be of value for clinicians to consider parental status when assessing and treating veterans with PTSD. In-depth study of OEF/OIF veterans is needed to determine whether disruption of family relationships leads to increased psychological stress or parents are more likely than nonparents to seek VA mental health services for PTSD symptoms.

Filardo, G., B. da Graca, D. M. Sass, B. D. Pollock, E. B. Smith and M. A. Martinez (2016). “Trends and comparison of female first authorship in high impact medical journals: observational study (1994-2014).” BMJ 352: i847.

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OBJECTIVE: To examine changes in representation of women among first authors of original research published in high impact general medical journals from 1994 to 2014 and investigate differences between journals. DESIGN: Observational study. STUDY SAMPLE: All original research articles published in Annals of Internal Medicine, Archives of Internal Medicine, The BMJ, JAMA, The Lancet, and the New England Journal of Medicine (NEJM) for one issue every alternate month from February 1994 to June 2014. MAIN EXPOSURES: Time and journal of publication. MAIN OUTCOME MEASURES: Prevalence of female first authorship and its adjusted association with time of publication and journal, assessed using a multivariable logistic regression model that accounted for number of authors, study type and specialty/topic, continent where the study was conducted, and the interactions between journal and time of publication, study type, and continent. Estimates from this model were used to calculate adjusted odds ratios against the mean across the six journals, with 95% confidence intervals and P values to describe the associations of interest. RESULTS: The gender of the first author was determined for 3758 of the 3860 articles considered; 1273 (34%) were women. After adjustment, female first authorship increased significantly from 27% in 1994 to 37% in 2014 (P<0.001). The NEJM seemed to follow a different pattern, with female first authorship decreasing; it also seemed to decline in recent years in The BMJ but started substantially higher (approximately 40%), and The BMJ had the highest total proportion of female first authors. Compared with the mean across all six journals, first authors were significantly less likely to be female in the NEJM (adjusted odds ratio 0.68, 95% confidence interval 0.53 to 0.89) and significantly more likely to be female in The BMJ (1.30, 1.01 to 1.66) over the study period. CONCLUSIONS: The representation of women among first authors of original research in high impact general medical journals was significantly higher in 2014 than 20 years ago, but it has plateaued in recent years and has declined in some journals. These results, along with the significant differences seen between journals, suggest that underrepresentation of research by women in high impact journals is still an important concern. The underlying causes need to be investigated to help to identify practices and strategies to increase women's influence on and contributions to the evidence that will determine future healthcare policies and standards of clinical practice.

Reyner, K., A. C. Heffner and C. H. Karvetski (2016). “Urinary obstruction is an important complicating factor in patients with septic shock due to urinary infection.” Am J Emerg Med 34(4): 694-696.

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OBJECTIVE: Urinary tract infection (UTI) is a common cause of severe sepsis, and anatomic urologic obstruction is a recognized factor for complicated disease. We aimed to identify the incidence of urinary obstruction complicating acute septic shock and determine the characteristics and outcomes of this group. METHODS: Patients prospectively enrolled in a sepsis treatment pathway registry between October 2013 and July 2014 were reviewed for the diagnosis of UTI. Standardized medical record review was performed to confirm sepsis due to UTI and determine clinical variables including the presence of anatomic urinary obstruction. Patients with septic shock due to UTI with obstruction were compared with those without obstruction. The primary outcomes were incidence of urinary obstruction and hospital mortality. RESULTS: Among 1084 registry enrollees, 209 (19.2%) met inclusion criteria for the study. Acute anatomic obstruction was identified in 22 (10.5%) patients. Hospital mortality in patients with obstruction was 27.3% compared with 11.2% in patients without obstruction (absolute difference of 16.1%; P = .03; 95% confidence interval [CI], 1.2%-30.9%). Hospital length of stay among survivors was 12.8 days compared with 8.3 days (absolute difference of 4.5 days; P = .04; 95% CI, 0.2-8.8 days). History of urinary stone disease was independently associated with obstruction (odds ratio, 5.6; 95% CI, 2.2-14.3). CONCLUSIONS: Approximately 1 in 10 patients presenting with septic shock due to a urinary source is complicated by anatomic urinary obstruction. These patients have significantly higher mortality compared with patients without obstruction. Early imaging of patients with septic shock due to suspected urinary source should be considered to identify obstruction requiring emergency intervention.

Vincenti, F., L. Rostaing, J. Grinyo, K. Rice, S. Steinberg, L. Gaite, M. C. Moal, G. A. Mondragon-Ramirez, J. Kothari, M. S. Polinsky, H. U. Meier-Kriesche, S. Munier and C. P. Larsen (2016). “Belatacept and Long-Term Outcomes in Kidney Transplantation.” N Engl J Med 374(4): 333-343.

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BACKGROUND: In previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. METHODS: We randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). RESULTS: A total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all available data were used in the analysis. A 43% reduction in the risk of death or graft loss was observed for both the more-intensive and the less-intensive belatacept regimens as compared with the cyclosporine regimen (hazard ratio with the more-intensive regimen, 0.57; 95% confidence interval [CI], 0.35 to 0.95; P=0.02; hazard ratio with the less-intensive regimen, 0.57; 95% CI, 0.35 to 0.94; P=0.02), with equal contributions from the lower rates of death and graft loss. The mean estimated glomerular filtration rate (eGFR) increased over the 7-year period with both belatacept regimens but declined with the cyclosporine regimen. The cumulative frequencies of serious adverse events at month 84 were similar across treatment groups. CONCLUSIONS: Seven years after transplantation, patient and graft survival and the mean eGFR were significantly higher with belatacept (both the more-intensive regimen and the less-intensive regimen) than with cyclosporine. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00256750.).