Faculty Bibliography

Background: Many uremic retention solutes are products of gut bacterial metabolism. Protein-binding renders these solutes poorly dialyzable. In a prior study we observed that a single dose of 250 mg of vancomycin, given by mouth, resulted in a significant (40%) decrease in the plasma concentration of indoxyl sulfate and p-cresyl sulfate over a period of one week. In this study we compared the changes in plasma concentration of a panel of protein-bound uremic retention solutes in response to the once-weekly oral administration of 250 mg of vancomycin or placebo over a period of 8 weeks.
Method(s): Eight subjects with chronic, stable ESRD on thrice-weekly hemodialysis via AV fistula in the River Renal Dialysis Unit in Bellevue Hospital, were randomized to two groups, utilizing a single-blinded procedure. Baseline plasma samples were collected prior to the initial dose of vancomycin or placebo and at weeks one, two, three, four, and eight. Uremic retention solutes were measured by MS-HPLC.
Result(s): Six of the eight uremic retention solutes (Table 1) demonstrated a significant decline in concentration over the eight week period of once-weekly vancomycin administration. The magnitude of the decline makes it more likely that gut production was reduced rather than renal excretion increased. Solute concentrations remained unchanged over the same period of placebo administration.
Conclusion(s): The significant decline in the plasma concentrations of multiple uremic retention solutes provides evidence of the importance of the gut microbiome in the generation of these solutes. The reduction in concentrations of indoxyl sulfate, p-cresyl sulfate, and kynurenic acid, recognized as likely uremic toxins, suggests that altering the gut microbiome might provide a valuable therapeutic strategy in the management of ESRD

Background: Clinical decision support (CDS) has been shown to im-prove compliance with evidence-based care but its impact is often diminished due to issues such as poor usability, insufficient integration into workflow, and alert fatigue. Non-interruptive CDS may be less subject to alert fatigue but there has been little assessment of its usability. The purpose of this study was to perform usability testing on interruptive and non-interruptive versions of a CDS. Methods: We conducted a usability study ofa CDS tool that recommended prescribing an angiotensin converting enzyme (ACE) inhibitor for inpatients with heart failure. We developed two versions of the CDS that varied in its format: an interruptive alert, in which the CDS popped-up at the time of order entry, and a non-interruptive alert, which was displayed in a checklist section of the Electronic Health Record (EHR). We recruited inpatient providers to use both versions in a laboratory setting. We randomly assigned providers to first trigger the interruptive or non-interruptive alert. Providers were given a clinical scenario and asked to " think aloud" as they worked through the CDS; we then conducted a brief semi-structured interview about usability. We used a constant comparative analysis informed by the Five Rights of CDS framework to analyze the interviews. Inpatient providers from different disciplines were recruited until thematic saturation was reached. Results: Of 12 providers who participated in usability testing, seven used the interruptive followed by the non-interruptive CDS and five used the non-interruptive CDS initially. We categorized codes into four themes related to the Five Rights of CDS and determined some codes to be general to the CDS while others were specific to the interruptive or non-interruptive version (Table). Providers noted that the interruptive alert was readily noticed but generally impeded workflow. Providers found the non-interruptive CDS to be less annoying but had lower visibility; although they liked the ability to address the non-interruptive CDS at any time, some providers questioned whether it would ultimately be used. Conclusions: Providers expressed annoyance in working with an inter-ruptive CDS. Although the non-interruptive CDS was more appealing, providers admitted that it may not be used unless integrated with workflow. One potential solution was a combination of the two formats: supplementing a non-interruptive alert with an occasional, well-timed interruptive alert if uptake was insufficient

Learning Objective #1: Recognize the incidence of posterior circulation stroke after cardiac catheterization Learning Objective #2: Recognize how cognitive biases affect clinical decision making CASE: A 57 year old man with hypertension, type 2 diabetes, depression, coronary artery disease s/p PCI and 4-vessel CABG presented with nausea, vomiting, and syncope. He was found to be in complete heart block and underwent emergent pacemaker placement and cardiac catheterization with stent placement to the left circumflex artery. After catheterization, patient reported lightheadedness and cloudiness when walking. He was transferred to the medicine service with sign-out to follow up with physical therapy given "deconditioning" after his acute illness. PT sessions were limited by his hesitancy to walk beyond a few steps. Four days after downgrade, patient reported left sided visual changes. Physical exam was notable for left homon-ymous hemianopia without somatosensory deficits. A non-contrast head CT revealed a new acute to sub-acute right posterior cerebral artery infarction. He was determined to have had an embolic ischemic stroke secondary to cardiac catheterization. His lightheadedness and cloudiness were believed to be secondary to hemianopia. He was medically managed and discharged to SAR. IMPACT: This case involves a common post-catheterization complication as an unusual presentation described as lightheadedness and cloudiness. We attributed the symptoms to overall deconditioning secondary to diagnostic momentum. Furthermore, visual fields were not accurately assessed in this post-procedure patient. Our personal practice now includes exam maneuvers to evaluate posterior circulation on patients post-cardiac catheterization given the high incidence of these strokes in cardiac patients. DISCUSSION: Post-cardiac catheterization strokes are common, with most occurring within 24 hours of the procedure. Of these, approximately 25% involve the posterior circulation often leading to visual field deficits without gross somatosensory deficits. As a result, neurological deficits may often go unnoticed if visual fields are not accurately assessed. Furthermore, patients may not realize a true visual field deficit as they can compensate with neck rotation; initial descriptors may be vague such as lightheadedness or cloudiness. Our case was further complicated by cognitive biases that influenced our decision making; namely, the case was framed as overall deconditioning. As a result, we anchored to a single diagnosis and did not consider neurological deficit as an explanation for our patient's symptoms. We encourage all medical professionals to be cognizant of variability in presentation of visual field deficits and also be keen to their own cognitive biases

BACKGROUND:Through diet and exercise interventions, community centers offer an opportunity to address health-related issues for some of the oldest, most vulnerable members of our society. OBJECTIVES/OBJECTIVE:The purpose of this investigation is to draw upon nationwide data to better characterize the population served by the congregate meals program and to gather more detailed information on a local level to identify opportunities for service enhancement to improve the health and well-being of older adults. DESIGN/METHODS:We examined community center data from two sources: 2015 National Survey of Older Americans Act and surveys from two New York City community centers. To assess nationwide service delivery, we analyzed participant demographics, functional status defined by activities of daily living, and perceptions of services received. MEASUREMENTS/METHODS:Participants from the two New York City community centers completed a four-day food record. Functional measures included the short physical performance battery, self-reported physical function, grip strength, and the Montreal Cognitive Assessment. RESULTS:Nationwide (n=901), most participants rated the meal quality as good to excellent (91.7%), and would recommend the congregate meals program to a friend (96.0%). Local level data (n=22) were collected for an in-depth understanding of diet, physical activity patterns, body weight, and objective functional status measures. Diets of this small, local convenience sample were higher in fat, cholesterol, and sodium, and lower in calcium, magnesium, and fiber than recommended by current United States Dietary Guidelines. Average time engaged in moderate physical activity was 254 minutes per week (SD=227), exceeding the recommended 150 minutes per week, but just 41% (n=9) and 50% (n=11) of participants engaged in strength or balance exercises, respectively. CONCLUSION/CONCLUSIONS:Research is warranted to test whether improvements in the nutritional quality of food served and access/supports for engaging in strength training within community centers could help older adults achieve diet and physical activity recommendations.

Learning Objective #1: HSP is an uncommon small vasculitis in adults, often occurring after an infectious illness CASE: A 49 year old female presented to the emergency room with a progressive, painful rash in her lower extremities and abdominal pain over the past 10 days. Patient was in her usual state of health until 10 days prior to admission when she began to notice a skin eruption in her lower extremities associated with pain. The rash spread upwards and patient was seen by a dermatologist as an outpatient, where a biopsy was taken. Patient was prescribed a topical steroid without improvement in symptoms. She also developed a generalized intermittent abdominal pain without hematochezia. No recent upper respiratory infections/other infectious symptoms. Upon arrival to the hospital, patient was in stable condition. Exam was notable for diffuse, palpable purpura in her lower extremities and abdomen. Patient's urinalysis was significant for proteinuria and microscopic hematuria. Chemistries demonstrating baseline renal function. Given her significant abdominal pain, patient was started on prednisone for a presumed diagnosis of Henoch-Schonelin Purpura (HSP). Skin biopsy returned showing small vessel leukocytoclastic vasculitis with IgA, C3 deposition. Patient was maintained on oral steroids for 48 hours with significant improvement in her abdominal pain and rash. As her abdominal ceased, patient was transitioned to colchicine and discharged home. IMPACT: Recognition of this uncommon small vasculitis as a disease that also affects adults. HSP is typically self-limited, but glucocorticoid therapy is warranted in patients with significant gastrointestinal or renal involvement. DISCUSSION: HSP, a predominantly pediatric condition, is a small vessel vasculitis characterized by IgA complex deposition the smaller venules, capillaries, and arterioles of various organ systms. HSP typically occurs after an infectious illness, which our patient did not appear to have. The typical tetrad of symptoms include: skin, arthralgias, gastrointestinal symptoms, and renal disease. Palpable purpura occurs in nearly every patient, typically in the lower extremities and the buttocks. Abdominal pain occurs in 65% of cases. Renal disease is common, more often affecting adults than children. Typical manifestation is hematuria. Significant proteinuria and elevated creatinine occur in a minority of patients, with < 1% of cases progressing to ESRD. HSP is usually a benign, self-limited disease. Patients with mild arthralgias and abdominal pain may be treated with acetaminophen. If severe abdominal pain occurs, steroids are the recommended initial therapy, and have been shown to improve abdom-inal pain, but not otherwise improve overall progression of disease. Colchicine can be considered for mild abdominal symptoms. Additional indication for glucocorticoid therapy includes significant renal involvement (proteinuria > 1g/day). If refractory symptoms, cyclophosphamide or mycophenolate there may be considered

OBJECTIVE:In the United States, hepatocellular carcinoma (HCC) is more common among communities with low socioeconomic status (SES), and these groups tend to be diagnosed with later-stage cancers. Sorafenib is the primary treatment for advanced HCC, however its substantial cost raises concern for access to treatment. METHODS:The newly developed Case-Background method was used to estimate odds ratios for the impacts of various sociodemographic factors on sorafenib access in clinically eligible patients. Socioeconomic status was defined as a factor of median income and education level based on ZIP code of residence. RESULTS:There was a strong association between sorafenib prescription and residence in an area of higher SES. While controlling for age, race/ethnicity, and insurance status, high SES residence doubled the odds of sorafenib prescription (OR=2.05, p&lt;.01). CONCLUSIONS:Low socioeconomic status communities appear to have a reduced chance of receiving the only effective treatment for advanced HCC.

BACKGROUND:Hyaluronic acid (HA), an extracellular matrix component, is degraded in response to local tissue injury or stress. In various animal models of lung injury, HA has been shown to play a mechanistic role in modulating inflammation and injury. While HA is present in the lungs of patients with acute respiratory distress syndrome (ARDS), its relationship to patient outcomes is unknown. METHODS:We studied 86 patients with ARDS previously enrolled in the Phase II Randomized Trial of Fish Oil in Patients with Acute Lung Injury (NCT00351533) at five North American medical centers. We examined paired serum and bronchoalveolar lavage fluid (BALF) samples obtained within 48 hours of diagnosis of ARDS. We evaluated the association of HA levels in serum and BALF with local (lung injury score (LIS)) and systemic (sequential organ failure assessment score (SOFA)) measures of organ dysfunction with regression analysis adjusting for age, sex, race, treatment group, and risk factor for ARDS. RESULTS:We found that both day-0 circulating and alveolar levels of HA were associated with worsening LIS (p = 0.04 and p = 0.003, respectively), particularly via associations with degree of hypoxemia (p = 0.02 and p < 0.001, respectively) and set positive end-expiratory pressure (p = 0.01 and p = 0.02, respectively). Circulating HA was associated with SOFA score (p < 0.001), driven by associations with the respiratory (p = 0.02), coagulation (p < 0.001), liver (p = 0.006), and renal (p = 0.01) components. Notably, the alveolar HA levels were associated with the respiratory component of the SOFA score (p = 0.003) but not the composite SOFA score (p = 0.27). CONCLUSIONS:Elevated alveolar levels of HA are associated with LIS while circulating levels are associated with both lung injury and SOFA scores. These findings suggest that HA has a potential role in both local and systemic organ dysfunction in patients with ARDS.