Faculty Bibliography

BACKGROUND: Diabetic medications are approved by the Food and Drug Administration (FDA) based on efficacy in controlled clinical settings. Real world effectiveness may often vary from the results of clinical trials. We attempted to quantify the "efficacy versus effectiveness" gap at our institution. METHODS: We performed a retrospective analysis of all patients prescribed oral diabetic medications at New York University Langone Medical Center, a large urban tertiary care center, using data extracted from our electronic health record from October 2009 to September 2014. We limited the dataset to include newly diagnosed diabetic patients who were started on monotherapy or a combination pill. We excluded patients who were prescribed insulin or multiple diabetic agents. We used two-tailed Welch's t-tests to compare the initial Hemoglobin A1c (HbA1c), final HbA1c, and total HbA1c reduction to clinical trial data used for FDA approval, with statistical significance defined as p<0.05. RESULTS: Among the 566 of the 2452 patients who met our inclusion criteria, the mean age was 62.9 +/- 12.2 years, the majority of whom were male (51.1%), white (61.1%), non-Hispanic (80.4%), and prescribed metformin monotherapy (70.3%). The mean treatment time for each drug class ranged from 32-39 weeks. The mean initial HbA1c for all groups was 8.95%, the mean final HbA1c was 7.44%, and the mean HbA1c reduction was 0.51%. For almost all drug classes, the initial HbA1c was lower than the initial HbA1c from efficacy trials. For most drug classes, effectiveness was about half of the expected value from efficacy trials. Most patients achieved their goal HbA1c levels [Table]. CONCLUSIONS: In our study population, real world effectiveness did not reflect measures of efficacy from controlled clinical settings. The results highlight the need for clinicians to realize that a medication may not perform as well as it does in a controlled setting and they may need to increase the intensity of treatment more quickly than expected. Also, replicating the results of clinical trials in an actual clinical setting is challenging, both from the perspective of data availability and clinical practice patterns. (Table Presented)

BACKGROUND: Electronic health record (EHR)-based clinical decision support tools (CDS) incorporate individualized data to produce patient-specific recommendations at the point-of-care. However, these tools are often limited in their effectiveness, which may be due to poor consideration of usability. The purpose of this study was to evaluate the utilization of a CDS intervention to increase prescription of Angiotensin Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) for patients with heart failure. METHODS: We performed a retrospective study of hospitalized patients with heart failure from the time of CDS implementation, 7/10/13, through 11/30/15. The CDS that we investigated offers providers an opportunity to prescribe an ACEi or ARB or report a contraindication to therapy for patients with documented heart failure. All patients with an EF < 40% who were not on an ACEi or ARB at time of discharge were included in the study. We identified the number of patients for whom the CDS triggered; of those, we categorized provider response as: dismissed, ordered an ACEi/ARB, or contraindication reported. We then performed manual chart review to identify the CDS reported contraindication and structured chart abstraction with standard guidelines to identify gold standard contraindications. We compared each CDS contraindication to gold standard contraindications to determine their accuracy. RESULTS: Out of the 618 subjects who had an EF < 40% but no ACEi or ARB at the time or discharge, 435/618 (70%) had a triggered CDS. Of these 435 subjects for who a CDS was triggered, 180 (41%) were dismissed, 225 (52%) had a contraindication response and 30 (7%) had a prescription for an ACEi/ARB therapy. Overall the accuracy of the documented CDS was 42% (Table 1). CONCLUSIONS: The CDS that we reviewed was poorly utilized and contraindications documented in the tool poorly correlated with patient clinical status reflected elsewhere in the EHR. These findings identify this CDS as a possible impedance to user workflow. One way to improve CDS tools at the point of care is through thorough usability testing and consideration of physician workflow prior to implementation. (Table Presented)

BACKGROUND: All physicians need to be skilled at diagnosing, treating, and managing depression. We designed an unannounced standard patient (USP) case to assess residents' clinical skills in addressing depression and explored how those skills are associated with residents' general clinical skills in order to design targeted curriculum on depression. METHODS: The USP was a 26 y.o. male presenting as a new patient to a clinic complaining of fatigue and problems sleeping. Goals of the case were to diagnose a common presentation of depression and make a treatment/follow-up plan. The USP was trained to have a positive PHQ 2 &PHQ 9, family history of depression, and be willing to engage in medication and/or therapy if offered. A post-visit checklist was used by the SPs to assess communication, patient education, and assessment skills using behaviorally anchored items rated as not done, partly done, or well done. A systematic chart review was conducted to examine treatment, quality of documentation, and referrals. Case fidelity was checked by audiotape and confirmed by PHQ 9 score in the EHR. Evidence based treatment was defined as prescribing an SSRI and/or providing a psychiatric referral; if neither of those, scheduling follow-up for within 2 weeks. RESULTS: 122 residents saw the USP case from 2009-2015. Mean visit length = 45 min, SD 25 (14 to 183 min). The patient was screened for depression with a PHQ 2 in 93% of visits; 82% also had a PHQ 9. Overall, 77 residents (63%) provided appropriate treatment: 8% prescribed an SRRI, 23% provided a referral, 19% did both, 7% prescribed a sleep aid and <2 week follow-up, and 43% provided a combination of these treatments. 45 residents (37%) did not provide appropriate treatment: 27 (60%) prescribed a sleep aid and follow-up >2 weeks and 18 (40%) provided no treatment/referral and follow-up >2 weeks. There were no differences in exploration of medical history or substance use, but 83% of residents who treated appropriately had a PHQ 9 compared to 62% of residents who did not treat appropriately. 71% also included depression on the problem list compared to 13%of residents who did not treat appropriately. Residents who treated appropriately had significantly better clinical skills assessed by the USP including: overall communication (71% vs. 54%, p = 0.00), information gathering (72% vs. 55%, p = 0.01), relationship development (75% vs. 60%, p = 0.03), patient education (55% vs. 21%, p = 0.00), and patient activation skills (33% vs. 13%, p = 0.01). CONCLUSIONS: Although almost all residents obtained the relevant information, only about 50% of residents diagnosed depression. PHQ 9 appears to be associated with providing more effective treatment, supporting the importance of health system screening protocols. Residents' communication and depression-specific patient education and activation skills seem to be related to how they identify and manage depression, suggesting that interventions to build these skills may lead to higher quality care

BACKGROUND: Entrustable Professional Activities (EPAs) and milestones are expert judgments made based on many formative assessments. Their validity is dependent on the number of assessments but attention is increasingly being paid to having a "fair" sample of observations equally distributed across residents and contexts. OSCEs provide such a consistent, fair sample of behavior assessed under controlled conditions but have mostly used been used to provide granular skills feedback. We explore how faculty judge the "entrustability" of residents based on observing OSCE cases and then how these entrustments relate to OSCE skills performance. METHODS: In an 11-case OSCE for primary care residents (n = 25; PGY1-3), SPs rated skills in communication (information gathering, relationship development, education/counseling), assessment, patient education (case-specific), physical exam, professionalism, treatment plan, patient satisfaction and patient activation. Summary scores were calculated as%items rated well done (vs not or partly done; internal consistency > .72). Faculty observers then judged how much supervision the resident would need in actual practice to handle the case: 1-requires direct supervision, 2-requires indirect supervision, 3-ready for unsupervised practice, or 4- can supervise others. Mean entrustment rating across cases was correlated with clinical skills. RESULTS: Mean entrustment =2.46 (SD .37), falling between requires indirect supervision and ready for unsupervised practice. On average, residents were judged to need direct supervision in .40 cases (SD .65), indirect supervision in 4.76 (SD 2.03), ready for unsupervised practice in 2.92 (SD 1.80), and able to supervise others in 1.07 cases (SD 1.15) with PGY1 residents needing direct and indirect supervision in more cases than PGY2 and 3 (p = .037). Associations between OSCE performance and faculty entrustment ranged from essentially zero (communication sub-domains of information gathering and education/counseling; case-specific patient education; patient satisfaction) to negative (communication sub-domain of relationship development r = -.25, p = .16; professionalism r = -.21, p = .22) to positive (case-specific assessment, r = .35, p = .07; physical exam r = .30, p = .13; treatment plan r = .40, p = .04; patient activation r = .51, p = .008). Associations between skills performance and entrustment ratings varied by case. CONCLUSIONS: OSCEs provide a valuable opportunity for faculty to make entrustment judgments based on observing the same, complete encounter across many trainees. Entrustment judgments appear to be capturing elements of competence related to but different from SP assessments of performance, including especially "bottom line" aspects of practice such as assessment, physical exam, treatment plans and patient activation. Interestingly, we consider patient activation skills to be an "educationally sensitive patient outcome" i because both teachable and associated with patient outcomes and our results support the importance of this skill set

LEARNING OBJECTIVE #1: Recognize the clinical presentation and physical exam findings of chronic tophaceous gout LEARNING OBJECTIVE #2: Discuss the management and complications of tophaceous gout CASE: A 40 year-old man with no past medical history presented with 8 months of worsening pain and deforming growths in multiple joints. He first noticed intermittent pain and swelling in the heels of both feet 2 years prior to admission, which progressed to constant pain in his feet, knees, hands, and elbows. Starting 8 months ago, distinct nodules formed on the affected joints; these occasionally burst and released a "toothpaste-like" discharge. He increasingly had difficulty walking and using his hands. The patient had not sought any medical care since emigrating from Mexico 8 years ago, due to lack of insurance. On exam, he had diffuse subcutaneous nodules on the feet, ankles, knees, elbows, earlobes, and hands, most concentrated in the joint spaces. They were firm, non-tender, and yellow to white in color. One nodule was draining a chalky white exudate. He had numerous cyst-like lesions on the shaft of the penis, restricting movement of the foreskin. Range of motion was severely impaired in all extremities. He had a uric acid level of 10.4, alkaline phosphatase of 164, and C-reactive protein of 16.5. Rheumatologic serologies were negative. X-rays of the affected joints showed osteopenic bone, with areas of periarticular erosions, joint space narrowing, and subchondral sclerosis with overlying tophi, all consistent with advanced gout. Fluid from the draining tophus revealed large collections of monosodium urate crystals. IMPACT: This case is a reminder that physicians should be prepared to recognize and manage not only acute gout flares, but also advanced presentations of chronic gout. Particularly when working in populations with limited healthcare access, the diagnosis and treatment of gout may be considerably delayed. Perhaps more importantly from an internist's perspective, recognizing and treating the sequelae and comorbidities of gout may reduce morbidity and mortality in these patients. DISCUSSION: In gout patients, the presence of one or more tophi is an indication to begin urate-lowering therapy (ULT), using xanthase-oxidase inhibitors, which decrease production of urate, and uricosuric agents, which increase renal excretion of uric acid. ULT targets a serum urate of <6 mg/dL; in severe cases, a target of <5 mg/dL is often used. If serum urate remains elevated on both agents, the next step is to add pegloticase, a recombinant uricase that converts urate into the renally cleared allantoin. Even with optimal control of hyperuricemia, tophi may persist for years before disappearing. Notably, all gout patients are at increased risk for cardiovascular disease, metabolic syndrome, and renal disease. However, patients with tophi have additional complications of joint and bone destruction, compressive neuropathies, and ulceration and infection of the tophi. The presence of tophi is also an independent predictor of mortality

Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included bla_IMP, bla_NDM, bla_OXA-48, bla_CTX-M, bla_AmpC, and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log₁₀-CFU decrease for all groups that had CAZ-AVI with ATM (8 μg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log₁₀-CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae.

BACKGROUND: In order to generate valid results in RCTs, it is important to collect unbiased data. Behavioral intervention trials are more difficult to blind than pharmacologic trials. In our ongoing behavioral trial, PATRIOT, which aims to prevent foot complications in diabetes through improved self-care, we are intervening both face-to-face as well as remotely. Consequently blinding is more difficult. Here we illustrate the different blinding processes used. METHODS: In the PATRIOT trial, following randomization during the baseline visit, the intervention group receives computer-based education and demonstration on how to use a special foot thermometer. Following that, intervention participants receive a comprehensive intervention that includes regular telephone counseling and tailored mailings. The control group receives health prevention strategies not related to foot care. For this complex intervention, we needed to develop new strategies to maintain blinding at the participant, research assistant (RA), counselor, outcome adjudicator and data analyst levels. We created a "Blinding Tracker" to identify unblinded and blinded staff so that participants pass from unblinded to blinded staff so that only blinded staff collect data. The integrity of the study is maintained by careful monitoring of blinding with any break in blinding being contained. RESULTS: To date, we have enrolled 221 participants. While participants know the arm to which they are randomized, we needed to make sure that the staff collecting data are blinded. Participants are educated throughout the whole study process by the telephone counselors about the importance of blinding using non-scientific descriptions. Though the counselors know their participant's treatment assignment, they do not know their foot photography results and other outcomes. The RA's, who conduct study visits and collect data, are blinded to treatment assignment. To improve efficiency and preserve blinding, we have different RAs for different phases of a participant's progress. Initially, RAs are initially blinded, but by the end of their involvement with a particular subject, when data collection is done, they become unblinded so they can show the educational videos and demonstrate foot thermometer use. However, RA's can also become unblinded prematurely. To date, out of 96 six-month visits, there have been 26 such instances. RAs are subsequently transitioned off a particular subject to be replaced by a blinded RA. We will also control for RA blinding in the analysis. The adjudicators who read the foot photographs to determine outcomes and the statisticians are blinded to treatment assignment. CONCLUSIONS: Novel techniques have been used to achieve and maintain blinding, but it is resource intensive. While conducting complex trials, vigilance and responsiveness are needed. Finally, blinding information should be incorporated in the analysis in order to get the most valid results

BACKGROUND: The Substance Abuse Research and Education Training (SARET) program is funded by the National Institutes of Drug Abuse in 2006 as a novel approach to spark interest in substance abuse research among medical, dental, nursing, and social work graduate students through a Web-based curriculum and research mentorships. This report presents the initial integration of the intervention in a Master of Social Work (MSW) program, the components of the program, and the mixed-methods evaluation of its effect on students' attitudes towards substance abuse research and treatment. METHODS: SARET comprises 2 main components: stipend-supported research mentorships and a Web-based module series, consisting of 6 interactive, multimedia modules addressing core SA research topics, delivered via course curricula and in the research mentorships. An initial evaluation was designed to assess SARET's acceptability and short-term impact on participants' interest in SA research. The components of this Web-based curriculum evaluation include focus group feedback on the relevance of the modules to SW students, number of courses into which the modules were integrated with number of module completions, changes in interest in SA research associated with module completion. RESULTS: The full series of Web-based modules has been integrated across several courses in the social work curriculum, and social work students have become integral participants in the summer mentored research experience. One hundred eighteen students completed at least 1 module and 42 students completed all 6 modules. Neurobiology, Screening, and Epidemiology were the most widely viewed modules. Students reported positive impact on their vision of SA-related clinical care, more positive attitudes about conducting research, and in some cases, change in career. CONCLUSIONS: The SARET program's modules and summer mentored research increased clinical and research interest related to SUDs, as well as interprofessional attitudes among social work students. Participants have shown some early research success. Longer-term follow-up will enable us to continue to assess the effectiveness of the program.

LEARNING OBJECTIVE #1: Discuss the clinical utility and mechanism of action of a widely used novel immunotherapeutic agents. LEARNING OBJECTIVE #2: Highlight the incidence of endocrinopathies associated with Ipilimumab and Nivolumab. CASE: A 70 year old female with metastatic melanoma presented to the emergency department with fatigue and lethargy for one month. She had recently completed 6 cycles of Nivolumab and Ipilimumab and was currently receiving Nivolumab monotherapy. Over the past month she had worsening fatigue associated with nausea and decreased appetite. Lab work one week prior to admission was significant for newly elevated TSH and low T4, and thyroid replacement therapy was initiated. On the day of admission, she had a syncopal episode at home prompting presentation. On arrival, she was hypotensive to 89/57. Lab work was significant for hyponatremia, hypokalemia, and hypochloremia. Due to concern for adrenal insufficiency, she was started on stress dose hydrocortisone. An AM serum cortisol was 1.5 and ACTH level was undetectable. FSH and LH levels were also low. An MRI of the brain was notable for enhancement of the pituitary gland suggestive of hypophysitis, which was likely a side effect of her immunotherapy. IMPACT: Ipilimumab and Nivolumab are novel immunotherapeutic agents used in the treatment of melanoma, with research investigating their use into other malignancies as well. Endocrinopathies are relatively common side effects of these agents, especially when given as combination therapy. Nonspecific complaints, such as fatigue and nausea in our patient, should warrant a thorough investigation for endocrinopathies in patients with treatment exposure to ipilimumab and/or nivolumab. DISCUSSION: Nivolumab and Ipilimumab are novel immunotherapeutic agents that are currently used for metastatic melanoma and squamous lung carcinoma. Nivolumab antagonizes the binding of Programmed Cell Death Ligand 1 to the programmed cell death 1 receptor (PD-1), activation of which would normally promote T-cell apoptosis. Ipilimumab antagonizes the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), preventing down regulation cytotoxic T lymphocytes. Endocrinopathies are relatively common side effects of checkpoint inhibitors and are thought to be result of auto-immune inflammation. They can manifest as primary hyper/hypothyroidism, primary adrenal insufficiency and/or hypophysitis thereby affecting the multiple hormonal systems. A retrospective review from Memorial Sloan Kettering showed an incidence of hypophysitis of 8 and thyroiditis of 6% following treatment with ipilimumab. The incidence of hypophysitis and thyroiditis increased to 9 and 22% respectively in patients who received combination therapy with ipilimumab and nivolumab. Our patient seemingly developed primary hypothyroidism and hypophysitis causing a secondary adrenal insufficiency secondary to her combination therapy. The initiation of levothyroxine therapy likely precipitated her adrenal insufficiency leading to her syncopal event

BACKGROUND: As healthcare increases demands, primary care physicians need evidenced-based, patient-centered care coordination, effective use of information technology, interdisciplinary team functioning and shared decision-making skills more so in underserved areas. In 2008, we documented 20 years of the NYU/Bellevue Primary Care Internal Medicine Residency Program (NYUBPC) on readiness for practice1. In light of the recent primary care changes we assessed our recent training of Primary Care Residents in high quality, person-centered, systems-savvy, team-based care for the underserved. Specifically we aimed to: 1. Assess the NYUBPCP impact on graduate career choices, values and style 2. Elicit reflections that illustrate complexities in educating primary care physicians METHODS: We surveyed 56 graduates of the NYUBPCP from 2007-2014. The 44 question survey included 12 open-ended questions about career path, current practice, preparedness for practice and specifics about how aspects of training provided necessary skills and knowledge. Responses were unidentified. We received 37 responses, (66%). RESULTS: 36 respondents currently provide clinical care, with about 40% of their time spent in a primary care setting (S.D. 32%). On a 4- point scale 85% either agreed or strongly agreed with Primary Care as a career choice. 74% felt prepared for the challenges of a primary care practice, rating clinical experiences with underserved communities, and the psychosocial, clinical epidemiology and health policy focus as essential aspects of training. All but 4 provide care to medically underserved populations. They valued the community of peers and colleagues that the NYUBPCP provided. While 53% rated their clinical site as hectic/chaotic (4 or 5 on a 5 point scale), only 6% reported persistently feeling burnout. 19% reported at least one symptom of burnout. Qualitative analyses revealed overlapping themes in alumni perceptions of how residency influenced current practice, aspects of training that were difficult to implement and expectations for the future directions of primary care. Responses demonstrated a mismatch between the "purity" of primary care practice graduates strove to achieve after residency and the actuality of a practice influenced by external factors (e.g. time pressures, reimbursement issues and metric achievements). Some found it difficult to be involved with research or advocacy while in full-time clinical practice. Graduates believed the future of primary care lies in a team-based approach. CONCLUSIONS: A training program emphasizing rigorous curriculum, committed role modeling, care of the underserved, and strong residency community for support continues to document high rates of retention in primary care. They are well adapted entering physicians with the skills and attitudes necessary to succeed in primary care and become educators of the next generation