Brigham And Women's Hospital Research Articles

Development of an Algorithm to Identify Patients with Physician-Documented Insomnia

We developed an insomnia classification algorithm by interrogating an electronic medical records (EMR) database of 314,292 patients. The patients received care at Massachusetts General Hospital (MGH), Brigham and Women’s Hospital (BWH), or both, between 1992 and 2010. Our algorithm combined structured variables (such as International Classification of Diseases 9th Revision [ICD-9] codes, prescriptions, laboratory observations) and unstructured variables (such as text mentions of sleep and psychiatric disorders in clinical narrative notes). The highest classification performance of our algorithm was achieved when it included a combination of structured variables (billing codes for insomnia, common psychiatric conditions, and joint disorders) and unstructured variables (sleep disorders and psychiatric disorders). Our algorithm had superior performance in identifying insomnia patients compared to billing codes alone (area under the receiver operating characteristic curve [AUROC] = 0.83 vs. 0.55 with 95% confidence intervals [CI] of 0.76–0.90 and 0.51–0.58, respectively). When applied to the 314,292-patient population, our algorithm classified 36,810 of the patients with insomnia, of which less than 17% had a billing code for insomnia. In conclusion, an insomnia classification algorithm that incorporates clinical notes is superior to one based solely on billing codes. Compared to traditional methods, our study demonstrates that a classification algorithm that incorporates physician notes can more accurately, comprehensively, and quickly identify large cohorts of insomnia patients.

The impact of health insurance status on the stage of cervical cancer diagnosis at a tertiary care center in Massachusetts

ObjectiveTo evaluate the impact of insurance status on the stage of cervical cancer diagnosed and treated at a tertiary care center in Massachusetts and review the preceding screening history. MethodsAn IRB approved retrospective cohort study was conducted of patients with a diagnosis of cervical cancer treated at Brigham and Women's Hospital (BWH) between January 2011 and June 2016. Clinical and demographic data was extracted from the longitudinal medical record. Statistical analysis was performed using SAS. Results117 cases of cervical cancer met the inclusion criteria during the study period. Most patients (76%) were diagnosed with stage I disease. On univariate analysis, compared to patients with private insurance, patients with public insurance or no documented insurance presented at older ages, were more likely to be non-white races, and present with advanced stage disease. In an adjusted model, the risk of being diagnosed with advanced stage disease persisted among women with public or no documented insurance, adjusted odds ratio (aOR) 4.13 (1.37–12.45). There was no difference in screening history among women with private vs. public insurance, p = 0.30. ConclusionsDespite access to insurance, patients with public issued insurance had an increased risk of presenting with advanced stage cervical cancer in this cohort. These data suggest that additional barriers to screening and prevention may exist and are important for future investigation.

Residual Convolutional Neural Network for the Determination of IDH Status in Low- and High-Grade Gliomas from MR Imaging.

Purpose: Isocitrate dehydrogenase (IDH) mutations in glioma patients confer longer survival and may guide treatment decision making. We aimed to predict the IDH status of gliomas from MR imaging by applying a residual convolutional neural network to preoperative radiographic data.Experimental Design: Preoperative imaging was acquired for 201 patients from the Hospital of University of Pennsylvania (HUP), 157 patients from Brigham and Women's Hospital (BWH), and 138 patients from The Cancer Imaging Archive (TCIA) and divided into training, validation, and testing sets. We trained a residual convolutional neural network for each MR sequence (FLAIR, T2, T1 precontrast, and T1 postcontrast) and built a predictive model from the outputs. To increase the size of the training set and prevent overfitting, we augmented the training set images by introducing random rotations, translations, flips, shearing, and zooming.Results: With our neural network model, we achieved IDH prediction accuracies of 82.8% (AUC = 0.90), 83.0% (AUC = 0.93), and 85.7% (AUC = 0.94) within training, validation, and testing sets, respectively. When age at diagnosis was incorporated into the model, the training, validation, and testing accuracies increased to 87.3% (AUC = 0.93), 87.6% (AUC = 0.95), and 89.1% (AUC = 0.95), respectively.Conclusions: We developed a deep learning technique to noninvasively predict IDH genotype in grade II-IV glioma using conventional MR imaging using a multi-institutional data set. Clin Cancer Res; 24(5); 1073-81. ©2017 AACR.

Arthritis and use of hydroxychloroquine associated with a decreased risk of macrophage activation syndrome among adult patients hospitalized with systemic lupus erythematosus.

Background Macrophage activation syndrome (MAS) is an uncommon but serious complication of systemic lupus erythematosus (SLE). We aimed to identify factors associated with MAS among adult hospitalized SLE patients. Methods Within the Brigham and Women's Hospital (BWH) Lupus Center Registry, we identified adult SLE patients > age 17 who had been hospitalized from 1970 to 2016, with either ferritin > 5000 ng/ml during admission or "macrophage activation syndrome" or "MAS" in discharge summary. We confirmed MAS by physician diagnosis in medical record review. We matched each hospitalized SLE patient with MAS to four SLE patients hospitalized without MAS (by SLE diagnosis date ±1 year). We employed conditional logistic regression models to identify clinical factors associated with MAS among hospitalized SLE patients. Results Among 2094 patients with confirmed SLE, we identified 23 who had a hospitalization with MAS and compared them to 92 hospitalized without MAS. Cases and controls had similar age at SLE diagnosis (29.0 vs. 30.5, p = 0.60), and hospital admission (43.0 vs. 38.3, p = 0.80), proportion female (78% vs. 84%, p = 0.55), and time between SLE diagnosis and hospitalization (1971 vs. 1732 days, p = 0.84). Arthritis (OR 0.04 (95% CI 0.004-0.35)) and hydroxychloroquine use (OR 0.18 (95% CI 0.04-0.72)) on admission were associated with decreased MAS risk. Admission Systemic Lupus Erythematosus Disease Activity Index scores (30 vs. 19, p = 0.002) and lengths of stay (16 days vs. 3 days, p < 0.0001) were much higher among cases. Death during hospitalization was 19% among cases and 3% among controls ( p = 0.03). Conclusions In this case-control study of hospitalized adult SLE patients, arthritis and hydroxychloroquine use at hospital admission were associated with decreased MAS risk. Further studies are needed to validate these factors associated with lowered MAS risk.

Malformations attributed to the process of vascular disruption.

Several malformations have been attributed to the process of vascular disruption. The central hypothesis for this etiology is that blood flow to a structure has been altered after that structure had formed normally. The decreased blood flow leads to hypoxia, endothelial cell damage, hemorrhage, tissue loss, and repair. After recovery, some structures are normal and others show either tissue loss or structural abnormalities, such as syndactyly and constriction rings. The phenotypic features of the 7,020 infants with one or more malformations, who were born to women who had always planned to deliver at Brigham and Women's Hospital (BWH) between, 1972 and 2012, that is, maternal nontransfers, were reviewed. The phenotypes associated with vascular disruption, such as the amniotic band syndrome and terminal transverse limb defects (TTLD), were identified. One hundred and five fetuses and infants had malformations attributed to the process of vascular disruption. Some specific causes of the amniotic band limb deformity were identified. TTLD with associated small digit-like nubbins occurred at three levels: proximal forearm, wrist, and metacarpal-phalangeal joint. Other causes included severe hemoglobinopathies and exposures to misoprostol and to prenatal procedures. Malformations attributed to the process of vascular disruption were a distinctive entity, among the recognized etiologies. The timing of the causative event in the first trimester was established for infants with exposures to either the prostaglandin misoprostol or the prenatal diagnosis procedure chorionic villus sampling. One challenge is to identify the developmental steps in vascular disruption when no causative exposure can be identified.

The MELD-Plus: A generalizable prediction risk score in cirrhosis.

Background and aimsAccurate assessment of the risk of mortality following a cirrhosis-related admission can enable health-care providers to identify high-risk patients and modify treatment plans to decrease the risk of mortality.MethodsWe developed a post-discharge mortality prediction model for patients with a cirrhosis-related admission using a population of 314,292 patients who received care either at Massachusetts General Hospital (MGH) or Brigham and Women’s Hospital (BWH) between 1992 and 2010. We extracted 68 variables from the electronic medical records (EMRs), including demographics, laboratory values, diagnosis codes, and medications. We then used a regularized logistic regression to select the most informative variables and created a risk score that comprises the selected variables. To evaluate the potential for generalizability of our score, we applied it on all cirrhosis-related admissions between 2010 and 2015 at an independent EMR data source of more than 18 million patients, pooled from different health-care systems with EMRs. We calculated the areas under the receiver operating characteristic curves (AUROCs) to assess prediction performance.ResultsWe identified 4,781 cirrhosis-related admissions at MGH/BWH hospitals, of which 778 resulted in death within 90 days of discharge. Nine variables were the most effective predictors for 90-day mortality, and these included all MELD-Na’s components, as well as albumin, total cholesterol, white blood cell count, age, and length of stay. Applying our nine-variable risk score (denoted as “MELD-Plus”) resulted in an improvement over MELD and MELD-Na scores in several prediction models. On the MGH/BWH 90-day model, MELD-Plus improved the performance of MELD-Na by 11.4% (0.78 [95% CI, 0.75–0.81] versus 0.70 [95% CI, 0.66–0.73]). In the MGH/BWH approximate 1-year model, MELD-Plus improved the performance of MELD-Na by 8.3% (0.78 [95% CI, 0.76–0.79] versus 0.72 [95% CI, 0.71–0.73]). Performance improvement was similar when the novel MELD-Plus risk score was applied to an independent database; when considering 24,042 cirrhosis-related admissions, MELD-Plus improved the performance of MELD-Na by 16.9% (0.69 [95% CI, 0.69–0.70] versus 0.59 [95% CI, 0.58–0.60]).ConclusionsWe developed a new risk score, MELD-Plus that accurately stratifies the short-term mortality of patients with established cirrhosis, following a hospital admission. Our findings demonstrate that using a small set of easily accessible structured variables can help identify novel predictors of outcomes in cirrhosis patients and improve the performance of widely used traditional risk scores.

Association of anti-cyclic citrullinated protein antibodies, erosions, and rheumatoid factor with disease activity and work productivity: A patient registry study.

To evaluate associations between the presence of anti-cyclic citrullinated protein antibodies (anti-CCP) and rheumatoid factor (RF) and other outcomes, including joint erosions and both clinical and economic endpoints, in patients with rheumatoid arthritis (RA). Data from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS), a prospective registry of adult RA patients with established or recent-onset RA, were analyzed. Logistic regression models were constructed to test associations between anti-CCP/RF seropositivity and erosive disease and the presence of anti-CCP/RF seropositivity plus erosive disease and (1) RA severity; (2) hospitalizations; (3) durable medical equipment (DME) use; and (4) worker productivity (e.g., employment status). Covariates in these models included patient age, gender, race, body mass index (BMI), number of comorbidities, and treatment. Among 1309 registrants, those who were positive (vs. negative) for anti-CCP were 2.72 times more likely to have erosions (OR = 2.72; 95% CI: 1.77-4.18; P < 0.001). Individuals positive (vs. negative) for RF were 36% more likely to have erosions (95% CI: 0.88-2.08; P = 0.162). Patients with anti-CCP seropositivity and erosions were significantly more likely to: (1) have higher disease activity as measured by the Disease Activity Score in 28 joints C-reactive protein (DAS28-CRP ≥ 2.6); (2) be hospitalized; (3) use DME; and (4) be unemployed, disabled, or long-term disabled. For the first time in a "real-world" setting including patients with both recent-onset and chronic RA, this study demonstrated that the combination of anti-CCP seropositivity and erosions were significantly associated with more adverse clinical and health-economic consequences, including a lower probability of low disease activity and higher health resource utilization, despite use of biologic disease-modifying antirheumatic drugs by many patients. This dual presentation may signal a need for more intensive therapies, even when observed in patients with chronic, as well as recent-onset, RA. Trial registration [Brigham and Women's Hospital (BWH) Rheumatoid Arthritis Sequential Study; Registry URL: https://clinicaltrials.gov/ct2/show/NCT01793103; ClinicalTrials.gov Identifier NCT01793103].

Malformations Surveillance: Comparison between Findings at Birth and Age 1 Year.

Malformations surveillance programs among newborn infants are used to determine the prevalence of congenital anomalies. A comparison in the same group of infants between the malformations detected at birth and those detected at 1 year of age will identify errors in the surveillance process and, also, the abnormalities more likely not to be detected at birth, but later in the first year of life. The malformations identified at birth by Brigham and Women's Hospital (BWH) in the years 2000 and 2005 have been compared with the abnormalities detected in the same infants up to age 1 year by the Massachusetts Birth Defects Monitoring Program. The Massachusetts Birth Defects Monitoring Program identified 557 malformed infants in 2000 and 415 in 2005. Of these, 34 (3.5%) of the malformed infants were missed at birth by BWH Surveillance Program. An additional 22 (2.3%) malformed infants had delayed detection, as they were identified later in the first year. The reasons were the fact that: (1) the Surveillance staff reviewed the physicians' recorded findings only on the first day of life; (2) failure of the examining pediatrician to record the presence of a malformation in her/his notes. The most common abnormalities with delayed detection were mild heart defects, such as atrial septal defects. These findings emphasize the importance in a newborn malformations surveillance program of continued follow up in the first days of life, especially in small, premature infants. Birth Defects Research 110:142-147, 2018. © 2017 Wiley Periodicals, Inc.

Evaluating the feasibility of the KDIGO CKD referral recommendations

BackgroundIn 2012, the international nephrology organization Kidney Disease Improving Global Outcomes (KDIGO) released recommendations for nephrology referral for chronic kidney disease (CKD) patients. The feasibility of adhering to these recommendations is unknown.MethodsWe conducted a retrospective analysis of the primary care population at Brigham and Women’s Hospital (BWH). We translated referral recommendations based upon serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria into a set of computable criteria in order to project referral volume if the KDIGO referral recommendations were to be implemented. Using electronic health record data, we evaluated each patient using the computable criteria at the times that the patient made clinic visits in 2013. We then compared the projected referral volume with baseline nephrology clinic volume.ResultsOut of 56,461 primary care patients at BWH, we identified 5593 (9.9%) who had CKD based on albuminuria or estimated GFR. Referring patients identified by the computable criteria would have resulted in 2240 additional referrals to nephrology. In 2013, this would represent a 38.0% (2240/5892) increase in total nephrology patient volume and 67.3% (2240/3326) increase in new referral volume.ConclusionsThis is the first study to examine the projected impact of implementing the 2012 KDIGO referral recommendations. Given the large increase in the number of referrals, this study is suggestive that implementing the KDIGO referral guidelines may not be feasible under current practice models due to a supply-demand mismatch. We need to consider new strategies on how to deliver optimal care to CKD patients using the available workforce in the U.S. health care system.

The Impact of Margins on Outcomes After Wedge Resection for Stage I Non-Small Cell Lung Cancer

The relationship between margin distance and recurrence and survival for stage I non-small cell lung carcinoma (NSCLC) less than or equal to 2 cm is not clear. Patient clinicopathologic data were reviewed from a pooled data set of stage I NSCLC lesions less than or equal to 2 cm resected by wedge resection at Brigham and Women's Hospital (BWH) between 2000 and 2005 and the International Early Lung and Cardiac Action Program (I-ELCAP) between 1999 and 2015. Multivariable models were constructed to evaluate the relationship between margin distance and recurrence and survival, adjusting for patient age, sex, tumor size, and histologic type. Optimal margin distance was determined for recurrence-free and overall survival using maximum χ2 values among survival distributions. Of 182 cases, 138 tumors had margin distance reported (113 BWH and 25 I-ELCAP). The average tumor size was 13.3 mm, and margin distance was 8.3 mm. During a mean follow-up of 49.6 months, there were 33 recurrences and 59 deaths. Increased margin distance was independently associated with lower risk of recurrence (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.83-0.98). Margin distance was also independently associated with longer survival (hazard ratio [HR], 0.94; 95% CI, 0.90-0.98). A margin distance greater than 9 mm was associated with longest recurrence-free survival and a margin distance greater than 11 mm was associated with longest overall survival. Increased margin distance was independently associated with lower risk of recurrence and longer overall survival in patients undergoing wedge resection for NSCLC tumors less than or equal to 2 cm. These findings suggest that with a minimum appropriate margin distance, wedge resection may yield outcomes comparable to those of lobectomy.

An active learning curriculum improves fellows' knowledge and faculty teaching skills.

ObjectivesTraditional didactic lectures are the mainstay of teaching for graduate medical education, although this method may not be the most effective way to transmit information. We created an active learning curriculum for Brigham and Women’s Hospital (BWH) gastroenterology fellows to maximize learning. We evaluated whether this new curriculum improved perceived knowledge acquisition and knowledge base. In addition, our study assessed whether coaching faculty members in specific methods to enhance active learning improved their perceived teaching and presentation skills.MethodsWe compared the Gastroenterology Training Exam (GTE) scores before and after the implementation of this curriculum to assess whether an improved knowledge base was documented. In addition, fellows and faculty members were asked to complete anonymous evaluations regarding their learning and teaching experiences.ResultsFifteen fellows were invited to 12 lectures over a 2-year period. GTE scores improved in the areas of stomach (p<0.001), general gastroenterology (p=0.005), esophagus (p<0.001), and small bowel (p=0.001), and the total score (p=0.001) between pre- and postimplementation of the active learning curriculum. Scores in hepatology, as well as biliary and pancreatic study, showed a trend toward improvement (p>0.05). All fellows believed the lectures were helpful, felt more prepared to take the GTE, and preferred the interactive format to traditional didactic lectures. All lecturers agreed that they acquired new teaching skills, improved teaching and presentation skills, and learned new tools that could help them teach better in the future.ConclusionAn active learning curriculum is preferred by GI fellows and may be helpful for improving transmission of information in any specialty in medical education. Individualized faculty coaching sessions demonstrating new ways to transmit information may be important for an individual faculty member’s teaching excellence.

Frequency and morbidity of temporomandibular joint involvement in adult patients with a history of juvenile idiopathic arthritis

Purpose Most patients with juvenile idiopathic arthritis (JIA) have temporomandibular joint (TMJ) involvement, but little is known about the natural history of TMJ disease as these children enter adulthood. The purpose of this study was to evaluate adults with a history of JIA to document the frequency and severity of TMJ abnormalities and morbidity. The authors hypothesized that most would have persistent TMJ disease as adults. Materials and Methods This cross-sectional study included adults (>19 years of age) with JIA who were managed at Boston Children's Hospital (BCH) as children and at Brigham and Women's Hospital (BWH) as adults. History of a TMJ problem was not considered for enrollment. Patients completed a questionnaire and underwent physical examination and maxillofacial cone-beam computed tomography (CBCT). Additional data were obtained from medical records. Associations between TMJ abnormalities at CBCT and arthritis history, TMJ pain and function, facial asymmetry, malocclusion, and cephalometric analysis were examined. Results Of 129 eligible patients contacted, 21 (42 TMJs) were enrolled. Mean age was 26.0 ± 6.1 years and mean duration of care for JIA at the BCH and BWH was 13.7 ± 6.5 years. TMJ pain was present in 62% of patients (n = 13); 43% (n = 9) had a TMJ functional limitation and 76% (n = 16) had lower facial asymmetry. Abnormalities were found in the TMJs on 55% of CBCT scans, with 79% showing bilateral deformities. There was at least 1 cephalometric measurement of mandibular size or position that was more than 1 standard deviation beyond normal in 81% of patients (n = 17). Only 4 patients (19%) had previously been evaluated for a TMJ problem. Conclusion TMJ abnormalities and related morbidity are common in adult patients with a history of JIA. Therefore, an early screening protocol for TMJ involvement in children with a new diagnosis of JIA would be beneficial and long-term follow-up into adulthood should be routine.

User Requirements for a Chronic Kidney Disease Clinical Decision Support Tool to Promote Timely Referral

BackgroundTimely referral of patients with CKD has been associated with cost and mortality benefits, but referrals are often done too late in the course of the disease. Clinical decision support (CDS) offers a potential solution, but interventions have failed because they were not designed to support the physician workflow. We sought to identify user requirements for a chronic kidney disease (CKD) CDS system to promote timely referral. MethodsWe interviewed primary care physicians (PCPs) to identify data needs for a CKD CDS system that would encourage timely referral and also gathered information about workflow to assess risk factors for progression of CKD. Interviewees were general internists recruited from a network of 14 primary care clinics affiliated with Brigham and Women's Hospital (BWH). We then performed a qualitative analysis to identify user requirements and system attributes for a CKD CDS system. ResultsOf the 12 participants, 25% were women, the mean age was 53 (range 37–82), mean years in clinical practice was 27 (range 11–58). We identified 21 user requirements. Seven of these user requirements were related to support for the referral process workflow, including access to pertinent information and support for longitudinal co-management. Six user requirements were relevant to PCP management of CKD, including management of risk factors for progression, interpretation of biomarkers of CKD severity, and diagnosis of the cause of CKD. Finally, eight user requirements addressed user-centered design of CDS, including the need for actionable information, links to guidelines and reference materials, and visualization of trends. ConclusionThese 21 user requirements can be used to design an intuitive and usable CDS system with the attributes necessary to promote timely referral.

Two weeks at Harvard, for two European heart failure trainees

Two European Cardiologists cross the Atlantic for a pioneer Visiting Heart Failure Fellowship at Harvard’s Brigham and Women’s Hospital ![Graphic][1] Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, that is expected to become more prevalent as long-term effects of non-communicable cardiovascular risk markers result in manifest disease1,2. There is a compelling need to develop focused training in this field, to produce a generation of dedicated specialists armed with the tools to advance the field of heart failure treatment and improve patient outcomes. The aim of this report is to describe our specialized visiting observer Fellowship at Brigham and Women’s Hospital (BWH) and Harvard Medical School (both in Boston, Massachusetts, USA) and its role in our ongoing journey as HF specialists. We hope to inspire our colleagues at how this opportunity paved the way in changing our approach to HF management. We are two young Italian cardiologists who have been very interested in HF since we were medical students and then as postgraduate trainees. We first met each other in Zurich in January 2014 as participants of the 1st Postgraduate Course in Heart Failure (PCHF) held by University of Zurich and the European Society of Cardiology Heart Failure Association (ESC-HFA)3. The 2-year course was divided into eight Modules, culminating in a Certificate of Advanced Studies in HF 4. Learning about HF was facilitated by didactic teaching, practical training and networking with participants from many different European and other countries. Importantly, PCHF … [1]: /embed/inline-graphic-1.gif

Frequency and Morbidity of Temporomandibular Joint Involvement in Adult Patients With a History of Juvenile Idiopathic Arthritis

Most patients with juvenile idiopathic arthritis (JIA) have temporomandibular joint (TMJ) involvement, but little is known about the natural history of TMJ disease as these children enter adulthood. The purpose of this study was to evaluate adults with a history of JIA to document the frequency and severity of TMJ abnormalities and morbidity. The authors hypothesized that most would have persistent TMJ disease as adults. This cross-sectional study included adults (>19years of age) with JIA who were managed at Boston Children's Hospital (BCH) as children and at Brigham and Women's Hospital (BWH) as adults. History of a TMJ problem was not considered for enrollment. Patients completed a questionnaire and underwent physical examination and maxillofacial cone-beam computed tomography (CBCT). Additional data were obtained from medical records. Associations between TMJ abnormalities at CBCT and arthritis history, TMJ pain and function, facial asymmetry, malocclusion, and cephalometric analysis were examined. Of 129 eligible patients contacted, 21 (42 TMJs) were enrolled. Mean age was 26.0 ± 6.1years and mean duration of care for JIA at the BCH and BWH was 13.7 ± 6.5years. TMJ pain was present in 62% of patients (n= 13); 43% (n= 9) had a TMJ functional limitation and 76% (n= 16) had lower facial asymmetry. Abnormalities were found in the TMJs on 55% of CBCT scans, with 79% showing bilateral deformities. There was at least 1 cephalometric measurement of mandibular size or position that was more than 1 standard deviation beyond normal in 81% of patients (n= 17). Only 4 patients (19%) had previously been evaluated for a TMJ problem. TMJ abnormalities and related morbidity are common in adult patients with a history of JIA. Therefore, an early screening protocol for TMJ involvement in children with a new diagnosis of JIA would be beneficial and long-term follow-up into adulthood should be routine.

Review of Nonformulary Medication Approvals in an Academic Medical Center

The Joint Commission requires hospitals to formally review formulary medications at least annually based on new clinical information. Although review of nonformulary medication (NFM) use is not required, frequent and inappropriate use of NFMs has the potential to increase hospital costs, negatively affect quality of care, and increase medication errors. Limited resources may restrict an institution's ability to review NFM use in addition to the required annual formulary review. NFM use at Brigham and Women's Hospital (BWH) was reviewed to provide insight on how to best direct an NFM review that is both effective and efficient. How an NFM review may negatively affect cost, quality of care, and medication errors is also inferred. All approved NFM requests between 2009 and 2012 from Brigham and Women's Hospital's computerized provider order entry system were extracted and categorized according to the American Hospital Formulary Service (AHFS) Pharmacologic-Therapeutic Classification System. Of the 15,356,016 new medication orders, there were 223,266 NFM approvals for 433 unique NFMs. NFMs were categorized into 91 AHFS, 14 combination, and 4 "Others" classes. Twenty-five AHFS Classes accounted for approximately the top 90% of all NFM approvals, and the top 2 NFMs in each class accounted for a majority of the NFM approvals. Only a few classes of medications and a few medications within each class accounted for most of the NFM use at BWH. Targeting review of the most frequently used NFMs in each class may be a feasible strategy to reviewing NFMs annually that is both effective and efficient in optimizing formulary benefits.

The positive impact of radiologic imaging on high-stage cutaneous squamous cell carcinoma management

There is limited evidence on the utility of radiologic imaging for prognostic staging of cutaneous squamous cell carcinoma (CSCC). Review utilization of radiologic imaging of high-stage CSCCs to evaluate whether imaging impacted management and outcomes. Tumors classified as Brigham and Women's Hospital (BWH) tumor (T) stage T2B or T3 over a 13-year period were reviewed to identify whether imaging was performed and whether results affected treatment. Disease-related outcomes (DRO: local recurrence, nodal metastasis, death from disease) were compared between patients by type of imaging used. 108 high-stage CSCCs in 98 patients were included. Imaging (mostly computed tomography, 79%) was utilized in 45 (46%) patients and management was altered in 16 (33%) patients who underwent imaging. Patients that received no imaging were at higher risk of developing nodal metastases (nonimaging, 30%; imaging, 13%; P=.041) and any DRO (nonimaging, 42%; imaging, 20%; P=.028) compared to the imaging group. Imaging was associated with a lower risk for DRO (subhazard ratio, 0.5; 95% CI 0.2-0.9; P=.046) adjusted for BWH T stage, sex, and location. Single institution retrospective design and changes in technology overtime. Radiologic imaging of high-stage CSCC may influence management and appears to positively impact outcomes. Further prospective studies are needed to establish which patients benefit from imaging.

Breast cancer screening initiation after turning 40years of age within the PROSPR consortium.

Although United States clinical guidelines differ, the earliest recommended age for average risk breast cancer screening is 40 years. Little is known about factors influencing screening initiation. We conducted a cohort study within the National Cancer Institute-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We identified 3413 women on their 40th birthday in primary care networks at Geisel School of Medicine at Dartmouth(DH) and Brigham and Women's Hospital(BWH) during 2011-2013 with no prior breast imaging or breast cancer. Cumulative incidence curves and Cox modeling were used to determine time from the 40th birthday to first breast cancer screening, cohort exit, or 42nd birthday. We calculated hazards ratios and 95% confidence intervals from multivariable Cox proportional hazards models. Breast cancer screening cumulative incidence by the 42nd birthday was 62.9% (BWH) and 39.8% (DH). Factors associated with screening initiation were: a primary care visit within a year (HR 4.99, 95% CI 4.23-5.89), an increasing number of primary care visits within a year (p for trend <0.0001), ZIP code of residence annual median household income ≤$52,000 (HR 0.79, 95% CI 0.68-0.92), and health insurancetype (Medicaid HR 0.72, 95% CI 0.58-0.88; Medicare HR 0.55, 95% CI 0.39-0.77; uninsured HR 0.37, 95% CI 0.25-0.57). Breast cancer screening uptake after the 40th birthday varies by health system, primary care visits, median household income, and health insurance type, suggesting the need for further exploration. Future research should evaluate screening performance metrics after initiation and consider cumulative benefits and risks associated with breast cancer screening over time.

The role of face transplantation in the self-inflicted gunshot wound

Facial self-inflicted gunshot wounds (SIGSWs) cause a devastating midfacial defect and pose a challenging problem to the reconstructive surgeon. Face transplantation (FT) has the potential for near-normal restoration in otherwise non-reconstructible defects. Two out of 7 FT recipients at Brigham and Women's Hospital (BWH) sustained SIGSWs. In this study, we illustrate the role of FT in the management of SIGSWs through an aesthetic, functional, and psychosocial examination of outcomes. We performed a retrospective analysis of individuals with SIGSWs who were screened at BWH between 2008 and 2015. We then collected data of the injuries, modes of conventional reconstruction (CR), and deficits. For the FT recipients, we critically reviewed the psychosocial screening process and post-transplantation aesthetic, functional, and psychosocial outcomes. A total of six individuals post-SIGSWs were screened for FT. All of them had undergone CR, with five receiving loco-regional flaps and free tissue transfers, and one undergoing serial debridement and primary soft-tissue repair. Following CR, all suffered from residual functional and aesthetic deficits. Two underwent partial FT and one is currently undergoing FT screening. We describe the pre-transplant psychosocial screening process and the aesthetic, functional, and psychosocial outcomes of the SIGSW FT recipients. We examined the facial SIGSW injury, outcomes of CR, and the mechanism of FT to offer a potential solution to the shortcomings of CR. More importantly, we highlight the critical nature of the psychosocial component of the multidisciplinary evaluation given the history of mental illness and suicidal behavior in this subset of patients.

Metastatic Cutaneous Squamous Cell Carcinoma: The Importance of T2 Stratification and Hematologic Malignancy in Prognostication.

While infrequent, nodal metastases in cutaneous squamous cell carcinoma (cSCC) can result in death from disease. Identification of those at risk for metastases is key to improved prognostication and treatment. To review metastatic cSCC at the study institution. Sixteen patients with metastatic cSCC were identified at the New York University Dermatologic Associates and Cancer Associates from 1998 to 2013. Patients were staged with American Joint Committee on Cancer (AJCC) and modified Brigham and Women's Hospital (BWH) criteria and compared to 32 control subjects. Seven of 16 patients were identified as Stage T2 by AJCC criteria and Stage T2b by BWH criteria; two patients were on Stage T1, three patients were on more advanced T stages, and four patients lacked primary tumor data. Five patients had hematologic malignancy, and one patient had a solid-organ transplant. The modified BWH criteria aims to better prognosticate the large group of T2 AJCC tumors, resulting in the majority of mortality. In the experience of the authors, the majority of patients with metastatic disease were on T2, stratifying to stage T2b by BWH criteria, or more advanced T stages. The findings of this study support BWH stratification of T2 tumors and also indicate that hematologic malignancy is a significant comorbidity associated with a poor outcome.