Faculty Bibliography

BACKGROUND:Pediatric MetS prevalence varies due to lack of consensus on evaluative criteria and associated thresholds, with most not recommending a diagnosis <10 years. However, MetS risk components are becoming evident earlier in life and affect races and ethnicities disproportionately. OBJECTIVES:To compare the prevalence of MetS based on existing definitions and elucidate racial- and ethnic-specific characteristics associated with MetS prevalence. METHODS:The baseline and follow-up samples included 900 and 557 children 7-10 years, respectively. Waist circumference, BMI percentile, blood pressure, fasting plasma glucose (FPG), insulin, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were measured. Agreement between MetS definitions was quantified via kappa statistics. MetS and risk factor prevalence and the predictability of metabolic parameters on MetS eight months later was evaluated via logistic regression. McFadden pseudo-R2 was reported as a measure of predictive ability, and the Akaike information criterion evaluated fit of each model. RESULTS:The baseline sample was 55.0% male and 71.6% Hispanic, followed by non-Hispanic White (NHW) (17.3%) and non-Hispanic Black (NHB) (11.1%), with an average age of 9.2 years. MetS prevalence ranged from 7.6% to 21.4%, highest in Hispanic (9.0%-24.0%) and lowest in NHB children (4.0%-14.0%). Highest agreement was between Ford et al. and Cook et al. definitions (K = 0.88) and lowest agreements were consistently with the International Diabetes Federation criteria (K ≤ 0.57). Compared to NHW children, Hispanic children had higher odds for MetS (OR: 1.7; p = 0.03) and waist circumference, HDL-C, and FPG risk factors (p < 0.05), while NHB children had higher odds for the FPG risk factor (p ≤ 0.007) and lower odds for the plasma triglycerides risk factor (p = 0.002), across multiple MetS definitions. In longitudinal analyses, HDL-C was the strongest independent predictor of MetS in Hispanic and NHW children (p < 0.001 and p < 0.01, respectively), while plasma triglycerides was the strongest independent predictor of MetS in NHB children (p < 0.05). CONCLUSIONS:MetS prevalence was high in children ≤10 years, and proposed criteria are susceptible to racial and ethnic bias, diagnosing some populations more than other populations with high cardiovascular risk. Earlier preventative measures should be imposed in clinical settings, accounting for racial and ethnic differences, to mitigate disease onset.

BACKGROUND/AIMS/UNASSIGNED:High follow-up is critical in randomized clinical trials. We developed novel approaches to modify in-person visits and complete follow-up during COVID-19. Since these strategies are broadly applicable to circumstances wherein follow-up is difficult, they may help in contingency planning. The objective of this article is to develop and evaluate new approaches to replace detailed, in-person study visits for two trials focused on preventing diabetic foot complications. METHODS/UNASSIGNED:A quasi-experimental pre-post design compared approaches for follow-up during COVID-19 to approaches pre-COVID-19. Study subjects were outpatients at two Veterans Affairs Medical Centers. Following a research "hold," research resumed in February 2021 for Self-monitoring, Thermometry and Educating Patients for Ulcer Prevention (STEP UP) (n = 241), which focused on preventing recurrent foot ulcers, and in April 2021 for Preventing Amputation by Tailored Risk-based Intervention to Optimize Therapy (PATRIOT) (n = 406), which focused on preventing pre-ulcerative and ulcerative lesions. To complete data collection, we shortened visits, focused on primary and secondary outcomes, and conducted virtual visits when appropriate. For STEP UP, we created a 20-min assessment process that could be administered by phone. Since PATRIOT required plantar photographs to assess foot lesions, we conducted short face-to-face visits. We explored differences and assessed proportion completing visit, visit completion/100 person-months and compared COVID-19 to pre- COVID-19 using unadjusted risk ratios, incidence rate ratios, all with associated 95% confidence intervals (CIs). Finally, we report time-to-visit curves. RESULTS/UNASSIGNED:In both studies, participants whose follow-up concluded pre- COVID-19 seemed older than those whose follow-up concluded during COVID-19 (PATRIOT: 68.0 (67.2, 68.9) versus 65.2 years (61.9, 68.5); STEP UP: 67.5 (66.2, 68.9) versus 65.3 (63.3, 67.3)). For STEP UP, we completed 91 visits pre- COVID-19 (37.8% (31.6%, 44.2%)) and 63 visits during COVID-19 (78.8% (68.2%, 87.1%)). This was over 1309 person-months pre-COVID-19, and over 208.8 person-months during COVID-19; the visit completion rate/100 person-months were: pre-COVID-19 7.0 (5.6, 8.5), COVID-19 30.2 (23.2, 38.6); risk ratio: 2.1 (1.7, 2.5); and incidence rate ratio 4.3 (3.1, 5.9). Similarly, for PATRIOT, we completed 316 visits pre-COVID-19 (77.8% (73.5%, 81.8%)) and 27 assessments during COVID-19 (84.4% (67.2%, 94.7%)). This was over 1192.7 person-months pre-COVID-19 and 39.3 person-months during COVID-19. The visit completion rate/100 person-months in PATRIOT were: pre-COVID-19 2.7 (2.4, 3.0), COVID-19 6.9 (4.5, 10); risk ratio 1.1 (0.9, 1.3); incidence rate ratio 2.6 (1.8, 3.8). For both studies, the follow-up curves began separating at < 2 months. CONCLUSIONS/UNASSIGNED:We achieved higher completion rates during COVID-19 compared to pre-COVID-19 by modifying visits and focusing on primary and secondary outcomes. These strategies prevent excessive missing data, support more valid conclusions, and improve efficiency. They may provide important alternative strategies to achieving higher follow-up in randomized clinical trials.

OBJECTIVE:To conduct a dimensional analysis to identify conceptual gaps around shared decision making (SDM) in reproductive health care and to refine the conceptual definition of SDM as related to contraceptive counseling. DATA SOURCES:We identified source data through systematic searches of the CINAHL and PubMed databases. STUDY SELECTION:We included peer-reviewed research and nonresearch articles that addressed contraceptive counseling for pregnancy prevention in the United States. We did not consider date of publication as an inclusion criterion. We included 35 articles in the final review. DATA EXTRACTION:Using dimensional analysis, we extracted data to clarify the definition of SDM as a socially constructed concept that varies by perspective and context. DATA SYNTHESIS:Data synthesis enabled us to compare SDM from patient and provider perspectives and to identify four primary dimensions of SDM that varied by context: Patient Preferences, Relationship, Provider Bias, and Clinical Suitability. CONCLUSION:The four dimensions we identified illustrate the complexity and depth of SDM in contraceptive counseling encounters and broaden the definition of SDM to more than an encounter in which decision making incorporates clinician expertise and patient participation. We identified several assumptions that indicate the need for improved understanding that SDM is not a universal concept across perspectives and contexts. Most researchers in the included articles addressed the Patient Preferences dimension. Fewer considered the patient-provider relationship, the effect of provider bias, and the effect of specific clinical circumstances on SDM. We propose a conceptual map and model that can be used to refine the concepts that inform SDM and guide providers and researchers. Future research is needed to address the remaining gaps.

RATIONALE & OBJECTIVE/UNASSIGNED:Adherence to recommended medical treatment is critical in chronic kidney disease (CKD) to prevent complications and progression to kidney failure. Overall adherence to treatment is low in CKD, and as few as 40% of patients with kidney failure receive any documented CKD-related care. The purpose of this study was to explore the experiences of patients with CKD and their adherence to CKD treatment plans, and the role their health care providers played in supporting their adherence. STUDY DESIGN/UNASSIGNED:One-on-one interviews were conducted in 2019-2020 using a semi-structured interview guide. Participants described experiences with adherence to treatment plans and what they did when experiencing difficulty. SETTING & PARTICIPANTS/UNASSIGNED:Participants were recruited from the Chronic Renal Insufficiency Cohort (CRIC) study. All CRIC participants were older than 21 years with CKD stages 2-4; this sample consisted of participants from the University of Pennsylvania CRIC site. ANALYTICAL APPROACH/UNASSIGNED:Interviews were recorded, transcribed, and coded using conventional content analysis. Data were organized into themes using NVivo 12. RESULTS/UNASSIGNED:. From analysis of factors relevant to treatment planning and adherence, following 4 major themes emerged: patient factors (multiple chronic conditions, motivation, outlook), provider factors (attentiveness, availability/accessibility, communication), treatment planning factors (lack of plan, proactive research, provider-focused treatment goals, and shared decision making), and treatment plan responses (disagreeing with treatment, perceived capability deficit, lack of information, and positive feedback). LIMITATIONS/UNASSIGNED:The sample was drawn from the CRIC study, which may not be representative of the general population with CKD. CONCLUSIONS/UNASSIGNED:These themes align with Behavioral Learning Theory, which includes concepts of internal antecedents (patient factors), external antecedents (provider factors), behavior (treatment planning factors), and consequences (treatment plan responses). In particular, the treatment plan responses point to innovative potential intervention approaches to support treatment adherence in CKD.

BACKGROUND/UNASSIGNED:Bradycardia and asystole events are common among patients treated with maintenance hemodialysis. However, triggers of these events in patients on maintenance hemodialysis (HD), particularly during the long interdialytic period when these events cluster, are uncertain. METHODS/UNASSIGNED:The Monitoring in Dialysis Study (MiD) enrolled 66 patients on maintenance HD who were implanted with loop recorders and followed for 6 months. We analyzed associations of predialysis laboratory values with clinically significant bradyarrhythmia or asystole (CSBA) during the 12 hours before an HD session. Associations with CSBA were analyzed with mixed-effect models. Adjusted negative binomial mixed-effect regression was used to estimate incidence rate ratios (IRR) for CSBA. We additionally evaluated associations of CSBA at any time during follow-up with time-averaged dialytic and laboratory parameters and associations of peridialytic parameters with occurrence of CSBA from the start of one HD session to the beginning of the next. RESULTS/UNASSIGNED:=0.04). Use of dialysate sodium concentrations ≤135 (versus 140) mEq/L was associated with a reduced risk of CSBA from the start of one session to the beginning of next. CONCLUSIONS/UNASSIGNED:Although a few factors had modest associations with CSBA in some analyses, we did not identify any robust associations of modifiable parameters with CSBA in the MiD Study. Further investigation is needed to understand the high rates of arrhythmia in the hemodialysis population.

BACKGROUND AND OBJECTIVE/UNASSIGNED:With the coronavirus disease 2019 (COVID-19) pandemic, rates of in-hospital antimicrobial use increased due to perceived bacterial and fungal coinfections along with COVID-19. We describe the incidence of these coinfections and antimicrobial use in patients hospitalized with COVID-19 to help guide effective antimicrobial use in this population. SETTING/UNASSIGNED:This study was conducted in 3 tertiary-care referral university teaching hospitals in New York City. METHODS/UNASSIGNED:This multicenter retrospective observational cohort study involved all patients admitted with COVID-19 from January 1, 2020, to February 1, 2021. Variables of interest were extracted from a de-identified data set of all COVID-19 infections across the health system. Population statistics are presented as median with interquartile range (IQR) or proportions with 95% confidence intervals (CIs) as indicated. RESULTS/UNASSIGNED:Among 7,209 of patients admitted with COVID-19, 663 (9.2%) had a positive culture from the respiratory tract or blood sometime during their initial hospital admission. Positive respiratory cultures occurred found in 449 (6.2%) patients, and 20% were collected within 48 hours of admission. Blood culture positivity occurred in 334 patients (4.6%), with 33.5% identified within 48 hours of admission. A higher proportion of patients received antimicrobials in the first wave than in the later pandemic period (82.4% vs 52.0%). Antimicrobials were prescribed to 70.1% of inpatients, with a median of 6 antimicrobial days per patient. Infection-free survival decreased over the course of hospitalization. CONCLUSIONS/UNASSIGNED:We detected a very low incidence of coinfection with COVID-19 at admission. A longer duration of hospitalization was associated with an increased risk of coinfection. Antimicrobial use far exceeded the true incidence and detection of coinfections in these patients.

OBJECTIVE/UNASSIGNED:To characterize factors associated with increased risk of outpatient parenteral antimicrobial therapy (OPAT) complication. DESIGN/UNASSIGNED:Retrospective cohort study. SETTING/UNASSIGNED:Four hospitals within NYU Langone Health (NYULH). PATIENTS/UNASSIGNED:All patients aged ≥18 years with OPAT episodes who were admitted to an acute-care facility at NYULH between January 1, 2017, and December 31, 2020, who had an infectious diseases consultation during admission. RESULTS/UNASSIGNED:< .001). CONCLUSIONS/UNASSIGNED:Discharge to an SARC is strongly associated with increased risks of readmission for OPAT-related complications and CRBSI. Loss to follow-up with the infectious diseases service is strongly associated with increased risk of readmission and CRBSI. CRBSI prevention during SARC admission is a critically needed public health intervention. Further work must be done for patients undergoing OPAT to improve their follow-up retention with the infectious diseases service.

Background As tumor genomes are shaped by their interaction with the immune system, a phenomenon known as immunoediting, it is critical to understand how immunotherapies impact this process. Checkpoint inhibitors directly influence T cells responding to neoantigens, as such, these therapies drastically affect the genomes of surviving tumor clones. Similar to the concept of immune camouflage, where genomes of pathogens evolve in a way to avoid immune detection, we hypothesized that tumor clones surviving checkpoint inhibition therapy harbor mutations more prone to immune avoidance. Methods We analyzed a published cohort of Nivolumab-treated melanoma patients (n=41) for which tumor samples were collected from the same site prior ('Pre' samples) and during ('On' samples) Nivolumab therapy.1 The immunogenic and tolerance potential of mutations from the Pre and On samples were evaluated with the Ancer neoantigen screening platform,2 which includes the EpiMatrix algorithm to identify HLA class I and HLA class II neoepitopes and the JanusMatrix algorithm to evaluate neoepitopes for homology with the self genome. Prior work with JanusMatrix showed that neoantigens highly homologous to self might be inhibitory.3 Results Tumor samples collected during Nivolumab therapy demonstrated increased homology (self-like) scores from their matched pre-therapy samples (paired t test, p=0.0475). While this increase in homology with self was significant across the cohort, the effect was more pronounced in patients exhibiting complete (CR) or partial responses (PR), compared to patients with stable (SD) or progressive disease (PD). An ANOVA analysis confirmed that increase in homology after Nivolumab therapy was significantly greater in CR/PR patients, as opposed to SD or PD patients (p=0.0005). This observation was supported by Receiver Operating Characteristic (ROC) analysis discriminating CR/PR patients from SD/PD patients based on differences in homology with self between Pre and On treatment samples (AUC=0.7484, p=0.0313). A comparative ROC analysis employing baseline patient tumor mutation burden (TMB) yielded non-conclusive results (AUC= 0.5054, p=0.9613). Conclusions Our Ancer analysis highlights that Nivolumab therapy affects the tolerance profile of tumors in a manner that is consistent with the concepts of immunoediting and immune camouflaging. Interestingly, tumors in patients with favorable outcomes demonstrated the greatest increase in selflike neoepitopes. This observation suggests that collecting tumor biopsies shortly after the initiation of checkpoint inhibitor therapy and evaluating their tolerance profile may be employed as a prognostic biomarker. Furthermore, this approach highlights in silico tools may distinguish effector from tolerance inducing neoepitopes, a critical feature for designing novel neoantigen-based precision immunotherapies

More than 20 years have elapsed since the September 11, 2001 (9/11) terrorist attacks on the World Trade Center (WTC), Pentagon and at Shanksville, PA. Many persons continue to suffer a variety of physical and mental health conditions following their exposures to a mixture of incompletely characterized toxicants and psychological stressors at the terrorist attack sites. Primary care and specialized clinicians should ask patients who may have been present at any of the 9/11 sites about their 9/11 exposures, especially patients with cancer, respiratory symptoms, chronic rhinosinusitis, gastroesophageal reflux disease, psychiatric symptoms, and substance use disorders. Clinicians, especially those in the NY metropolitan area, should know how to evaluate, diagnose, and treat patients with conditions that could be associated with exposure to the 9/11 attacks and its aftermath. As such, this issue of Archives contains a series of updates to clinical best practices relevant to medical conditions whose treatment is covered by the WTC Health Program. This first paper in the 14-part series describes the purpose of this series, defines the WTC Health Program and its beneficiaries, and explains how relevant Clinical Practice Guidelines were identified. This paper also reminds readers that because physical and mental health conditions are often intertwined, a coordinated approach to care usually works best and referral to health centers affiliated with the WTC Health Program may be necessary, since all such Centers offer multidisciplinary care.

Dietary sodium (Na) restriction is universally prescribedfor hemodialysis patients to decrease adverse outcomes.1 However, few studies have investigated the impact of Na restriction on volume status and blood pressure (BP), and none in American community-dwelling populations in prospective, randomized controlled trial (RCT). The purpose of this feasibility RCT was to assess the effects of three levels of Na intake (unrestricted [control group; CG], 1.5G, 2.4G) on interdialytic weight gain (IDWG) and BP in patients undergoing hemodialysis. We conducted a three-group, double-blinded, RCT of 42 individuals living with end stage kidney disease in a domiciled feeding study. We examined the effects of 5 days of unrestricted Na in the control group (CG, n=14) and Na restriction to 1.5G (n=11) or 2.4G (n=14) per day on IDWG and BP. Our sample was overwhelmingly African American (85%), male (52.2%), with hypertension as the primary etiology of kidney disease (45%). The mean IDWG on Day 1 was 2.62kg (SD=1.54) and BP was 143/75.44 (SD=29.77/17.74). There were no significant differences in the change in IDWG regardless of group membership, although the trend demonstrated a decrease by Day 5. Decreases in BP were also not statistically significant across the groups, but there were potentially meaningful differences in systolic BP of 7mmHg and 11mmHg in the 1.5G and 2.4G groups respectfully, and diastolic BP in the 2.4G group of 7.31mmHg Our small pilot study suggests that Na restriction can reduce IDWG and systolic and diastolic BP in potentially clinically meaningful amounts. The optimal Na intake prescription and the long-term impact on hemodialysis-specific variables and cardiovascular disease remains unclear. A prospective, longitudinal study, with a sample sufficient to achieve adequate power is needed to gain a better understanding of the interplay between dietary sodium and outcomes.
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