Publications

Venous thromboembolism occurs in up to one-third of patients with primary brain tumors. Spontaneous intracranial hemorrhage (ICH) is also a frequent occurrence in these patients, but there is limited data on the safety of therapeutic anticoagulation. To determine the rate of ICH in patients treated with enoxaparin, we performed a matched, retrospective cohort study with blinded radiology review for 133 patients with high-grade glioma. After diagnosis of glioma, the cohort that received enoxaparin was 3 times more likely to develop a major ICH than those not treated with anticoagulation (14.7% vs 2.5%; P = .036; hazard ratio [HR], 3.37; 95% confidence interval [CI], 1.02-11.14). When enoxaparin was analyzed as a time-varying covariate, anticoagulation was associated with a >13-fold increased risk of hemorrhage (HR, 13.26; 95% CI, 3.33-52.85; P < .0001). Overall survival was significantly shorter for patients who suffered a major ICH on enoxaparin compared with patients not receiving anticoagulation (3.3 vs 10.2 months; log-rank P = .012). We applied a validated ICH prediction risk score PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke), and observed that all major ICHs on enoxaparin occurred in the setting of a PANWARDS score ≥25, corresponding with a sensitivity of 100% (95% CI, 63% to 100%) and a specificity of 40% (95% CI, 25% to 56%). We conclude that caution is warranted when considering therapeutic anticoagulation in patients with high-grade gliomas given the increased risk of ICH and poor prognosis after a major hemorrhage on anticoagulation. The PANWARDS score may assist clinicians in identifying the patients at greatest risk of suffering a major intracranial hemorrhage with anticoagulation.

OBJECTIVE: To determine whether there were gender differences in likelihood of receiving a first National Institutes of Health (NIH) R01 award among 5445 instructors and assistant professors at Harvard Medical School (HMS).

MATERIALS AND METHODS: Data on R01 award principal investigators were obtained from NIH ExPORTER and linked with faculty data. Using Cox proportional hazard regression, we examined the association of gender with receipt of first R01 award between 2008 and 2015 accounting for demographics, research productivity metrics, and professional characteristics.

RESULTS: Compared to males, females had fewer publications, lower h-index, smaller coauthor networks and were less likely to be assistant professors (p < 0.0001). Four hundred and thirteen of 5445 faculty (7.6%) received their first R01 award during the study period. There was no gender difference in receipt of R01 awards in age-adjusted (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.70-1.08) or multivariable-adjusted models (HR: 1.07, 95% CI: 0.86-1.34). Compared to white males, there was a nonsignificant 10%, 18%, and 30% lower rate of R01 receipt among white, Asian or Pacific Islander, and underrepresented minority females, respectively. These differences were eliminated in the multivariable-adjusted model. Network reach, age, HMS start year, h-index, academic rank, previous K award, terminal degree, and HMS training were all significant predictors of receiving an R01 award.

CONCLUSIONS: A relatively small proportion of HMS junior faculty obtained their first NIH R01 award during the study period. There was no significant gender difference in likelihood of award. However, we are unable to distinguish faculty that never applied from those who applied and were not successful.

OBJECTIVE: We sought to depict the topical, geospatial, and temporal diffusion of the 2015 North American Menopause Society position statement on the nonhormonal management of menopause-associated vasomotor symptoms released on September 21, 2015, and its associated press release from September 23, 2015.

METHODS: Three data sources were used: online news articles, National Public Radio, and Twitter. For topical diffusion, we compared keywords and their frequencies among the position statement, press release, and online news articles. We also created a network figure depicting relationships across key content categories or nodes. For geospatial diffusion within the United States, we compared locations of the 109 National Public Radio (NPR) stations covering the statement to 775 NPR stations not covering the statement. For temporal diffusion, we normalized and segmented Twitter data into periods before and after the press release (September 12, 2015 to September 22, 2015 vs September 23, 2015 to October 3, 2015) and conducted a burst analysis to identify changes in tweets from before to after.

RESULTS: Topical information diffused across sources was similar with the exception of the more scientific terms "vasomotor symptoms" or "vms" versus the more colloquial term "hot flashes." Online news articles indicated media coverage of the statement was mainly concentrated in the United States. NPR station data showed similar proportions of stations airing the story across the four census regions (Northeast, Midwest, south, west; P = 0.649). Release of the statement coincided with bursts in the menopause conversation on Twitter.

CONCLUSIONS: The findings of this study may be useful for directing the development and dissemination of future North American Menopause Society position statements and/or press releases.

OBJECTIVE: One promise of nationwide adoption of electronic health records (EHRs) is the availability of data for large-scale clinical research studies. However, because the same patient could be treated at multiple health care institutions, data from only a single site might not contain the complete medical history for that patient, meaning that critical events could be missing. In this study, we evaluate how simple heuristic checks for data "completeness" affect the number of patients in the resulting cohort and introduce potential biases.

MATERIALS AND METHODS: We began with a set of 16 filters that check for the presence of demographics, laboratory tests, and other types of data, and then systematically applied all 216 possible combinations of these filters to the EHR data for 12 million patients at 7 health care systems and a separate payor claims database of 7 million members.

RESULTS: EHR data showed considerable variability in data completeness across sites and high correlation between data types. For example, the fraction of patients with diagnoses increased from 35.0% in all patients to 90.9% in those with at least 1 medication. An unrelated claims dataset independently showed that most filters select members who are older and more likely female and can eliminate large portions of the population whose data are actually complete.

DISCUSSION AND CONCLUSION: As investigators design studies, they need to balance their confidence in the completeness of the data with the effects of placing requirements on the data on the resulting patient cohort.

BACKGROUND: Business literature has demonstrated the importance of networking and connections in career advancement. This is a little-studied area in academic medicine.

OBJECTIVE: To examine predictors of intra-organizational connections, as measured by network reach (the number of first- and second-degree coauthors), and their association with probability of promotion and attrition.

DESIGN: Prospective cohort study between 2008 and 2012.

SETTING: Academic medical center.

PARTICIPANTS: A total of 5787 Harvard Medical School (HMS) faculty with a rank of assistant professor or full-time instructor as of January 1, 2008.

MAIN MEASURES: Using negative binomial models, multivariable-adjusted predictors of continuous network reach were assessed according to rank. Poisson regression was used to compute relative risk (RR) and 95 % confidence intervals (CI) for the association between network reach (in four categories) and two outcomes: promotion or attrition. Models were adjusted for demographic, professional and productivity metrics.

KEY RESULTS: Network reach was positively associated with number of first-, last- and middle-author publications and h-index. Among assistant professors, men and whites had greater network reach than women and underrepresented minorities (p < 0.001). Compared to those in the lowest category of network reach in 2008, instructors in the highest category were three times as likely to have been promoted to assistant professor by 2012 (RR: 3.16, 95 % CI: 2.60, 3.86; p-trend <0.001) after adjustment for covariates. Network reach was positively associated with promotion from assistant to associate professor (RR: 1.82, 95 % CI: 1.32, 2.50; p-trend <0.001). Those in the highest category of network reach in 2008 were 17 % less likely to have left HMS by 2012 (RR: 0.83, 95 % CI 0.70, 0.98) compared to those in the lowest category.

CONCLUSIONS: These results demonstrate that coauthor network metrics can provide useful information for understanding faculty advancement and retention in academic medicine. They can and should be investigated at other institutions.

IMPORTANCE: Inflammation may contribute to pathological associations among obesity, diabetes mellitus, and cardiovascular disease.

OBJECTIVE: To determine whether targeting inflammation using salsalate compared with placebo reduces progression of noncalcified coronary artery plaque.

DESIGN, SETTING, AND PARTICIPANTS: In the Targeting Inflammation Using Salsalate in Cardiovascular Disease (TINSAL-CVD) trial participants were randomly assigned between September 23, 2008, and July 5, 2012, to 30 months of salsalate or placebo in addition to standard, guideline-based therapies. Randomization was computerized and centrally allocated, with patients, health care professionals, and researchers masked to treatment assignment. Participants were overweight and obese statin-using patients with established, stable coronary heart disease.

INTERVENTIONS: Salsalate (3.5 g/d) or placebo orally over 30 months.

MAIN OUTCOMES AND MEASURES: The primary outcome was progression of noncalcified coronary artery plaque assessed by multidetector computed tomographic angiography. Secondary outcomes were other measures of safety and efficacy.

RESULTS: Two hundred fifty-seven participants were randomized to salsalate (n = 129) or placebo (n = 128). Their mean (SD) age was 60.8 (7.0) years, and 94.0% (236 of 251) were male. One hundred ninety participants (89 in the salsalate group and 101 in the placebo group) completed the study. Compared with baseline, there was no increase in noncalcified plaque volume in the placebo-treated patients and no difference in change between the salsalate and placebo groups (mean difference, -1 mm3; 95% CI, -11 to 9 mm3; P = .87). Salsalate treatment decreased total white blood cell, lymphocyte, monocyte, and neutrophil counts and increased adiponectin levels without change in C-reactive protein levels. Fasting glucose, triglycerides, uric acid, and bilirubin levels were decreased in the salsalate group compared with the placebo group, while hemoglobin levels were increased. Urinary albumin levels increased, with tinnitus and atrial arrhythmias more common, in the salsalate group compared with the placebo group.

CONCLUSIONS AND RELEVANCE: Salsalate when added to current therapies that include a statin does not reduce progression of noncalcified coronary plaque volume assessed by multidetector computed tomographic angiography in statin-using patients with established, stable coronary heart disease. The absence of progression of noncalcified plaque volume in the placebo group may limit interpretation of the trial results.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00624923.

Federated networks of clinical research data repositories are rapidly growing in size from a handful of sites to true national networks with more than 100 hospitals. This study creates a conceptual framework for predicting how various properties of these systems will scale as they continue to expand. Starting with actual data from Harvard's four-site Shared Health Research Information Network (SHRINE), the framework is used to imagine a future 4000 site network, representing the majority of hospitals in the United States. From this it becomes clear that several common assumptions of small networks fail to scale to a national level, such as all sites being online at all times or containing data from the same date range. On the other hand, a large network enables researchers to select subsets of sites that are most appropriate for particular research questions. Developers of federated clinical data networks should be aware of how the properties of these networks change at different scales and design their software accordingly.

Venous thromboembolism occurs frequently in patients with cancer who have brain metastases, but there is limited evidence supporting the safety of therapeutic anticoagulation. To assess the risk for intracranial hemorrhage associated with the administration of therapeutic doses of low-molecular-weight heparin, we performed a matched, retrospective cohort study of 293 patients with cancer with brain metastases (104 with therapeutic enoxaparin and 189 controls). A blinded review of radiographic imaging was performed, and intracranial hemorrhages were categorized as trace, measurable, and significant. There were no differences observed in the cumulative incidence of intracranial hemorrhage at 1 year in the enoxaparin and control cohorts for measurable (19% vs 21%; Gray test, P = .97; hazard ratio, 1.02; 90% confidence interval [CI], 0.66-1.59), significant (21% vs 22%; P = .87), and total (44% vs 37%; P = .13) intracranial hemorrhages. The risk for intracranial hemorrhage was fourfold higher (adjusted hazard ratio, 3.98; 90% CI, 2.41-6.57; P < .001) in patients with melanoma or renal cell carcinoma (N = 60) than lung cancer (N = 153), but the risk was not influenced by the administration of enoxaparin. Overall survival was similar for the enoxaparin and control cohorts (8.4 vs 9.7 months; Log-rank, P = .65). We conclude that intracranial hemorrhage is frequently observed in patients with brain metastases, but that therapeutic anticoagulation does not increase the risk for intracranial hemorrhage.

PURPOSE: To understand the disciplinary contexts in which faculty work, the authors examined demographics, professional characteristics, research productivity, and advancement across seven clinical departments at Harvard Medical School (HMS) and nationally.

METHOD: HMS analyses included faculty from seven clinical departments-anesthesiology, medicine, neurology, pediatrics, psychiatry, radiology, and surgery-in May 2011 (N = 7,304). National analyses included faculty at 141 U.S. medical schools in the same seven departments as of December 31, 2011 (N = 91,414). The authors used chi-square and Wilcoxon Mann-Whitney tests to compare departmental characteristics.

RESULTS: Heterogeneity in demographics, professional characteristics, and advancement across departments was observed in HMS and national data. At HMS, psychiatry had the highest percentage of underrepresented minority faculty at 6.6% (75/1,139). In anesthesiology, 24.2% (128/530) of faculty were Asian, whereas in psychiatry only 7.9% (90/1,139) were (P < .0001). Female faculty were the majority in pediatrics and psychiatry, whereas in surgery 26.3% (172/654) of the faculty were female (P < .0001). At HMS, surgery, radiology, and neurology had the shortest median times to promotion and the highest median number of publications, H-index, and second-degree centrality. Neurology also had the highest percentage of faculty who had been principal investigators on a National Institutes of Health-funded grant.

CONCLUSIONS: There were differences in demographics, professional characteristics, and advancement across clinical departments at HMS and nationally. The context in which faculty work, of which department is a proxy, should be accounted for in research on faculty career outcomes and diversity inclusion in academic medicine.