Faculty Bibliography

We would like to respond to some concerns raised by Dr. McClellan in his editorial comment¹ on our article that reported the results of a placebo-controlled study of lurasidone for the treatment of children and adolescents with bipolar I depression.².

Host-related immunodeficiency is known to play a role in the development of multiple myeloma (MM) from its precursor conditions (monoclonal gammopathy of undetermined significance, MGUS, smoldering multiple myeloma, SMM). In order to understand the underlying immune changes in this process, we characterized immune patterns from MGUS to SMM to MM. We further sought to identify potential novel immune biomarkers that may predict progression of SMM to MM. We characterized patterns of circulating lymphocytes in 181 patients using multiparametric flow cytometry. We found decreased B- (p = .0003), increased T- (p = .037) and unaltered NK cell proportions from MGUS to SMM to MM. To gain insights into functional variability, we further characterized immunophenotypic lymphocyte subsets, which uncovered differences in CD57 subsets. Specifically, we found that SMM patients who eventually progressed to MM showed decreased proportions of CD57-CD56 + (p = .0061) and CD57-CD16 + (p = .035) lymphocyte subsets. We thus report novel data characterizing the nature of host-related immunodeficiency in the development of MM. We show sequential changes in lymphocyte subsets from MGUS to SMM to MM. We further suggest that CD57 subsets may serve as potential markers of progression from SMM to MM. Our findings support the study of lymphocyte subsets in the search for immune biomarkers. Such markers could provide clinical guidance in managing myeloma precursor disease.

Dietary Na recommendations are expressed as absolute amounts (mg/d) rather than as Na density (mg/kcal). Our objective was to determine whether the strength of the relationship of Na intake with blood pressure (BP) varied with energy intake. The DASH (Dietary Approaches to Stop Hypertension)-Sodium trial was a randomized feeding trial comparing 2 diets (DASH and control) and 3 levels of Na density. Participants with pre- or stage 1 hypertension consumed diets for 30 days in random order; energy intake was controlled to maintain body weight. This secondary analysis of 379 non-Hispanic black and white participants used mixed-effects models to assess the association of Na and energy intakes with BP. The relationships between absolute Na and both systolic and diastolic BP varied with energy intake. BP rose more steeply with increasing Na at lower energy intake than at higher energy intake (Pinteraction<0.001). On the control diet with 2300 mg Na, both systolic and diastolic BP were higher (3.0 mm Hg; 95% confidence interval, 0.2-5.8; and 2.7 mm Hg; 95% confidence interval, 1.0-4.5, respectively) among those with lower energy intake (higher Na density) than among those with higher energy intake (lower Na density). The association of Na with systolic BP was stronger at lower levels of energy intake in both blacks and whites (P<0.001). The association of Na and diastolic BP varied with energy intake only among blacks (P=0.001). Sodium density should be considered as a metric for expressing dietary Na recommendations.

Background/UNASSIGNED:This study was performed to compare patient-reported tolerability and its barriers in single- vs. split-dose 4-L polyethylene glycol (PEG) bowel preparation for colonoscopy in a large multiethnic, safety-net patient population. Methods/UNASSIGNED:A cross-sectional, dual-center study using a multi-language survey was used to collect patient-reported demographic, medical, socioeconomic, and tolerability data from patients undergoing outpatient colonoscopy. Univariate and multivariate analyses were used to identify demographic and clinical factors significantly associated with patient-reported bowel preparation tolerability. Results/UNASSIGNED:A total of 1023 complete surveys were included, of which 342 (33.4%) completed single-dose and 681 (66.6%) split-dose bowel preparation. Thirty-nine percent of the patients were Hispanic, 50% had Medicaid or no insurance, and 34% had limited English proficiency. Patients who underwent split-dose preparation were significantly more likely to report a tolerable preparation, with less severe symptoms, than were patients who underwent single-dose preparation. Multiple logistic regression revealed that male sex and instructions in the preferred language were associated with tolerability of the single-dose preparation, while male sex and concerns about medications were associated with tolerability of the split-dose preparation. Conclusions/UNASSIGNED:In a large multiethnic safety-net population, split-dose bowel preparation was significantly more tolerable and associated with less severe gastrointestinal symptoms than single-dose preparation. The tolerability of split-dose bowel preparation was associated with social barriers, including concerns about interfering with other medications.

BACKGROUND:Multiple chronic health conditions have been associated with exposure to the September 11, 2001 World Trade Center (WTC) terrorist attacks (9/11). We assessed whether excess deaths occurred during 2003-2014 among persons directly exposed to 9/11, and examined associations of 9/11-related exposures with mortality risk. MATERIALS AND METHODS/METHODS:Deaths occurring in 2003-2014 among members of the World Trade Center Health Registry, a cohort of rescue/recovery workers and lower Manhattan community members who were exposed to 9/11, were identified via linkage to the National Death Index. Participants' overall levels of 9/11-related exposure were categorized as high, intermediate, or low. We calculated standardized mortality ratios (SMR) using New York City reference rates from 2003 to 2012. Proportional hazards were used to assess associations of 9/11-related exposures with mortality, accounting for age, sex, race/ethnicity and other potential confounders. RESULTS:We identified 877 deaths among 29,280 rescue/recovery workers (3.0%) and 1694 deaths among 39,643 community members (4.3%) during 308,340 and 416,448 person-years of observation, respectively. The SMR for all causes of death was 0.69 [95% confidence interval (CI) 0.65-0.74] for rescue/recovery workers and 0.86 (95% CI 0.82-0.90) for community members. SMRs for diseases of the cardiovascular and respiratory systems were significantly lower than expected in both groups. SMRs for several other causes of death were significantly elevated, including suicide among rescue recovery workers (SMR 1.82, 95% CI 1.35-2.39), and brain malignancies (SMR 2.25, 95% CI 1.48-3.28) and non-Hodgkin's lymphoma (SMR 1.79, 95% CI 1.24-2.50) among community members. Compared to low exposure, both intermediate [adjusted hazard ratio (AHR) 1.36, 95% CI 1.10-1.67] and high (AHR 1.41, 95% CI 1.06-1.88) levels of 9/11-related exposure were significantly associated with all-cause mortality among rescue/recovery workers (p-value for trend 0.01). For community members, intermediate (AHR 1.13, 95% CI 1.01-1.27), but not high (AHR 1.14, 95% CI 0.94-1.39) exposure was significantly associated with all-cause mortality (p-value for trend 0.03). AHRs for associations of overall 9/11-related exposure with heart disease- and cancer-related mortality were similar in magnitude to those for all-cause mortality, but with 95% CIs crossing the null value. CONCLUSIONS:Overall mortality was not elevated. Among specific causes of death that were significantly elevated, suicide among rescue/recovery workers is a plausible long-term consequence of 9/11 exposure, and is potentially preventable. Elevated mortality due to other causes, including non-Hodgkin's lymphoma and brain cancer, and small but statistically significant associations of 9/11-related exposures with all-cause mortality hazard warrant additional surveillance.

EXECUTIVE SUMMARY/UNASSIGNED:While many aspects of patient care have transitioned to digital technology, the patient registration process often is still paper based. Several studies have examined the effects of changes in clinic workflows and appointment scheduling on patient satisfaction, but few have investigated changes from a paper-based to a paperless registration process. The authors measured patient and staff satisfaction before and after implementation of a new, tablet-based registration process at NYU Langone Health's Center for Women's Health in New York City. Mean preimplementation patient satisfaction scores on the six questions related to the registration process (1-5 scale, with 5 being the highest score) ranged from 4.0 to 4.5. Postimplementation satisfaction scores on the nine questions (six premeasure questions and three additional questions related to the tablet-based process) ranged from 4.4 to 4.6, with four of the six premeasures showing statistically significant improvement in patient satisfaction. Staff satisfaction was generally lower (2.8-3.6 preimplementation and 2.8-4 postimplementation), with no statistically significant difference between time frames. Patient satisfaction was relatively high under the paper registration process, and it improved significantly in some respects under the paperless process, while staff satisfaction did not change. The convenience and ease of use of a paperless registration system can help maintain or increase patient and staff satisfaction while introducing new workflows and improving the efficiency of the outpatient registration process. In adopting technology that can lead to changing workflows, organizations should train staff members and support them during the process.

Ceftazidime-avibactam was used to treat 77 patients with carbapenem-resistant Enterobacteriaceae (CRE) infections at our center. Thirty- and 90-day survival rates were 81% and 69%, respectively; rates were higher than predicted by SAPS II and SOFA scores at the onset of infection. Clinical success was achieved in 55% of patients, but varied by site of infection. Success rates were lowest for pneumonia (36%) and higher for bacteremia (75%) and urinary tract infections (88%). By multivariate analysis, pneumonia (P=0.045) and receipt of renal replacement therapy (RRT;P=0.046) were associated with clinical failure. Microbiologic failures occurred in 32% of patients, and occurred more commonly among patients infected with KPC-3-producing than KPC-2-producing CRE (P=0.002). Pneumonia was an independent predictor of microbiologic failures (P=0.007). Ceftazidime-avibactam resistance emerged in 10% of patients, including 14% infected withKlebsiella pneumoniaeand 32% with microbiologic failures. RRT was an independent predictor for the development of resistance (P=0.009). Resistance was identified exclusively amongK. pneumoniaeharboring variant KPC-3 enzymes. Upon phylogenetic analysis of whole genome sequences, resistant isolates from 87.5% (7/8) of patients clustered within a previously defined sequence type (ST)258, clade II sub-lineage; resistant isolates from one patient clustered independently from other ST258, clade II isolates. In conclusion, our report offers new insights into the utility and limitations of ceftazidime-avibactam across CRE infection types. Immediate priorities are to identify ceftazidime-avibactam dosing and therapeutic regimens that improve upon the poor outcomes among patients with pneumonia, and in those receiving RRT.

BACKGROUND:A substantial proportion of all pheochromocytomas is currently detected during the evaluation of an adrenal incidentaloma. Recently, it has been suggested that biochemical testing to rule out pheochromocytoma is unnecessary in case of an adrenal incidentaloma with an unenhanced attenuation value ≤10 Hounsfield Units (HU) at computed tomography (CT). OBJECTIVES/OBJECTIVE:We aimed to determine the sensitivity of the 10 HU threshold value to exclude a pheochromocytoma. METHODS:Retrospective multicenter study with systematic reassessment of preoperative unenhanced CT scans performed in patients in whom a histopathologically proven pheochromocytoma had been diagnosed. Unenhanced attenuation values were determined independently by two experienced radiologists. Sensitivity of the 10 HU threshold was calculated, and interobserver consistency was assessed using the intraclass correlation coefficient (ICC). RESULTS:214 patients were identified harboring a total number of 222 pheochromocytomas. Maximum tumor diameter was 51 (39-74) mm. The mean attenuation value within the region of interest was 36 ± 10 HU. Only one pheochromocytoma demonstrated an attenuation value ≤10 HU, resulting in a sensitivity of 99.6% (95% CI: 97.5-99.9). ICC was 0.81 (95% CI: 0.75-0.86) with a standard error of measurement of 7.3 HU between observers. CONCLUSION/CONCLUSIONS:The likelihood of a pheochromocytoma with an unenhanced attenuation value ≤10 HU on CT is very low. The interobserver consistency in attenuation measurement is excellent. Our study supports the recommendation that in patients with an adrenal incidentaloma biochemical testing for ruling out pheochromocytoma is only indicated in adrenal tumors with an unenhanced attenuation value >10 HU.

Background: Catheter ablation has become an increasingly common elective therapy for symptomatic atrial fbrillation (AF). Few data are available regarding outcomes of urgent AF ablation performed during AF related hospital admission, and the impact of these procedures on healthcare utilization. Objective: To evaluate patient characteristics, procedural outcomes, and impact on healthcare utilization in patients undergoing urgent AF ablation. Methods: Procedural outcomes of patients undergoing urgent frst-time AF ablation during an AF related hospital admission between 1/2014 and 8/2017 at a single tertiary care medical center were compared to those of 2:1 matched control patients undergoing frst-time elective AF ablation. An inverse probability weighted marginal structural model was constructed and the weighted means of the average hospital days and number of hospital visits in the six-months post ablation were compared. Results: 25 patients (1% of frst-time AF ablations) underwent an urgent procedure. There were no major procedural complications in either group. Incidence of arrhythmia recurrence within one year was similar in urgent and elective patients (20% vs. 18%, respectively, p=0.85). Urgent ablation patients had a greater number of hospital utilization days in the 6-months pre-ablation (mean 8.9+/-4.5 vs 2.6+/-1.1, p<.001) and a similar number of hospital utilization days in the 6-months post-ablation (1.8+/-4.5 vs 0.59+/- 1.07, p=.05) The marginal structural model of the change in number of hospital visits due to being in the urgent ablation group was-0.924 (-1.43 to-0.41; P <0.001). Conclusion: Urgent ablation for treatment resistant, symptomatic AF is feasible and safe with procedural outcomes were similar to those of elective AF ablation. There is and increased rate of healthcare utilization in prior to ablation in the urgent group, and a statistically signifcant reduction in healthcare utilization following urgent AF ablation. Defning the cost-effectiveness of and optimal patient selection for urgent ablation requires further investigation