Faculty Bibliography

OBJECTIVE:We previously found that antibiotic use at <24 months of age was associated with slightly higher body weight at 5 years of age. In this study, we examine associations of early life antibiotic prescriptions with weight outcomes at 108 to 132 months of age ("10 years"). METHODS:We used electronic health record data from 2009 through 2016 from 10 health systems in PCORnet, a national distributed clinical research network. We examined associations of any (vs no) antibiotics at <24 months of age with body mass index z-score (BMI-z) at 10 years adjusted for confounders selected a priori. We further examined dose response (number of antibiotic episodes) and antibiotic spectrum (narrow and broad). RESULTS:Among 56,727 included children, 57% received any antibiotics at <24 months; at 10 years, mean (standard deviation) BMI-z was 0.54 (1.14), and 36% had overweight or obesity. Any versus no antibiotic use at <24 months was associated with a slightly higher BMI-z at 10 years among children without a complex chronic condition (β 0.03; 95% confidence interval [CI] 0.01, 0.05) or with a complex chronic condition (β 0.09; 95% CI 0.03, 0.15). Any versus no antibiotic use was not associated with odds of overweight or obesity at 10 years among children without (odds ratio 1.02; 95% CI 0.97, 1.07) or with a complex chronic condition (odds ratio 1.07; 95% CI 0.96, 1.19). CONCLUSIONS:The small and likely clinically insignificant associations in this study are consistent with our previous 5-year follow-up results, suggesting that, if this relationship is indeed causal, early increases in weight are small but maintained over time.

The intraclass correlation coefficient (ICC) is a classical index of measurement reliability. With the advent of new and complex types of data for which the ICC is not defined, there is a need for new ways to assess reliability. To meet this need, we propose a new distance-based ICC (dbICC), defined in terms of arbitrary distances among observations. We introduce a bias correction to improve the coverage of bootstrap confidence intervals for the dbICC, and demonstrate its efficacy via simulation. We illustrate the proposed method by analyzing the test-retest reliability of brain connectivity matrices derived from a set of repeated functional magnetic resonance imaging scans. The Spearman-Brown formula, which shows how more intensive measurement increases reliability, is extended to encompass the dbICC.

The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease (CKD) recommends a target systolic blood pressure under 120 mmHg based on standardized office blood pressure measurement. Here, we examined the potential implications of this new guideline for blood pressure lowering with antihypertensive medication among adults in the United States with CKD compared to the 2012 KDIGO guideline (target blood pressure 130/80 mmHg or under with albuminuria or 140/90 mmHg or under without albuminuria) and the 2017 American College of Cardiology/American Heart Association (target blood pressure under 130/80 mmHg) guideline. Additionally, we determined implications of the 2021 KDIGO guideline for angiotensin converting enzyme inhibitor (ACEi) or angiotensin II-receptor blocker (ARB) use for those with albuminuria (recommended at systolic blood pressure of 120 mmHg or over) compared to the 2012 KDIGO guideline (recommended at blood pressures over 130/80 mmHg). Data were analyzed from 1,699 adults with CKD (estimated glomerular filtration rate 15-59 ml/min/1.73m² or a urinary albumin-to-creatinine ratio of 30 mg/g or more) in the 2015-2018 National Health and Nutrition Examination Survey and averaged up to three standardized blood pressure measurements. Among adults with CKD, 69.5% were eligible for blood pressure lowering according to the 2021 KDIGO guideline, compared with 49.8% as per 2012 KDIGO or 55.6% as per 2017 American College of Cardiology/American Heart Association guidelines. Among those with albuminuria, 78.2% were eligible for ACEi/ARB use by the 2021 KDIGO guideline compared with 71.0% by the 2012 KDIGO guideline. However, only 39.1% were taking an ACEi/ARB. Thus, our findings highlight opportunities to improve blood pressure management and reduce cardiovascular risk among adults in the United States with CKD.

Objective Functional gastrointestinal disorders account for a large burden of disease in children. Specifically,constipation tends to comprise 25% or more of visits to Pediatric Gastroenterologists. With the publication ofthe ROME IV criteria, the recognition of functional constipation (FC) as a disease process has become morerefined, yet the pharmacotherapy and lifestyle modifications in the management of children with FC haveremained fairly static. Our aim was to conceptualize, design, and validate an evidence-based, personalizedconstipation action plan with pictograms to aid providers, parents, and patients in the management of FC inchildren. Methods We applied a stepwise approach for the validation of a pediatric Constipation Action Plan(CAP) with pictograms to manage FC. After reviewing available clinical practice guidelines and criterion, ourexpert team agreed on these key elements for inclusion: eating, play, belly pain, stool characteristics, negativesensations during defecation, and defecation accidents. In designing a tool for eventual implementation intothe patient-centered medical home model, we emphasized the concepts of transparency, translucency, and recall in judging the development of pictograms using digital survey analytics. Prior to the recall phase, adistraction test was performed using the Short assessment of health literacy-English version (SAHL-E) toassess respondent health literacy levels. The images were considered valid when: 1. The image demonstratedtransparency of at least 85% 2. The translucency score awarded to the image was >=5 3. The imagedemonstrated recall by at least 85% of the participants Readability of the CAP was assessed using thefollowing tools: Flesch Reading Ease score, Gunning Fog, Flesch-Kincaid Grade Level, The Coleman-Liau Index,The SMOG Index, Automated Readability Index, and Linsear Write Formula. Suitability of the CAP wasevaluated using a modified Suitability Assessment of Materials (SAM) instrument. Results The CAP wascompleted (Figure 1). Pictogram validation: 200 respondents (all with normal SAHL-E scores) completed thepictogram survey. All 12 pictograms demonstrated appropriate transparency, translucency and recall forinclusion in the CAP (Table 1). CAP validation: The CAP combined scores for readability were consistent with afourth grade level. 34 pediatricians responded to the SAM; the mean composite % score generated forsuitability was 90.5, consistent with superior material. Conclusion The Constipation Action Plan is a robustclinical action tool complete with validated pictograms, high readability, and high suitability for use in treatingFC in pediatric patients. The inherent flexibility of the CAP allows it to be tailored to meet the needs of anychild with functional constipation. The CAP represents the next step in the evolution of care for FC. Furtherinvestigation will confirm the CAP can increase caregiver confidence in home management, improvehealthcare related quality of life for the patient, and improve clinical outcomes

RATIONALE & OBJECTIVE:Obesity has been related to risk for chronic kidney disease. However, the associations of different measures of midlife obesity with long-term kidney function trajectories and whether they differ by sex and race are unknown. STUDY DESIGN:Observational study. SETTING & PARTICIPANTS:13,496 participants from the Atherosclerosis Risk in Communities (ARIC) Study. PREDICTORS:Midlife obesity status as measured by body mass index (BMI), waist-to-hip ratio, and predicted percent fat at baseline. OUTCOMES:Estimated glomerular filtration rate (eGFR) calculated using serum creatinine level measured at 5 study visits, and incident kidney failure with replacement therapy (KFRT). ANALYTICAL APPROACH:Mixed models with random intercepts and random slopes for eGFR. Cox proportional hazards models for KFRT. RESULTS:per decade for Black women. Obesity indicators were independently associated with risk for KFRT for all sex-race groups except White men. LIMITATIONS:Loss to follow-up during 3 decades of follow-up with 5 eGFR assessments. CONCLUSIONS:Obesity status is a risk factor for future decline in kidney function and development of KFRT in Black and White women, with less consistent associations among men.

Obstructive azoospermia (OA) is a rare cause of male infertility, with Congenital Bilateral Absence of The Vas Deferens (CBAVD) being a major cause. A wealth of literature has established an irrefutable link between CFTR mutations and CBAVD, with CBAVD affecting almost all men with cystic fibrosis (CF) disease and a significant portion of men that are CFTR mutation carriers. In the past two decades, assisted reproductive technologies have made the prospect of fathering children a viable possibility in this subset of men, using a combination of sperm extraction techniques and intracystoplasmic sperm injection (ICSI). In order to assess techniques for sperm retrieval, as well as reproductive outcomes, a systemic search of the MEDLINE database was conducted for all articles pertaining to management options for CBAVD, and also all reports describing outcomes of these procedures in the CBAVD population. Both epididymal and testicular sperm extraction (TESE) are viable options for men with CBAVD, and though rigorous data are lacking, live birth rates range from 8% to 50% in most small retrospective series and subset analyses. In addition, there does not appear to be significant differences in the rate of live birth or complications and miscarriages between the various techniques, though further investigation into other factors that limit reproductive potential of men with CFTR mutations and CBAVD is warranted.

Most users of electronic cigarettes (e-cigarettes) report initiating use to quit combustible cigarettes. Nevertheless, high levels of dual use (i.e., using both combustible cigarettes and e-cigarettes) occur among adults. Using formative data from in-depth interviews and employing learner verification, we adapted an existing, validated self-help smoking-cessation intervention (Stop Smoking for Good; SSFG) to create a targeted intervention for dual users, If You Vape: A Guide to Quitting Smoking (IYV). In Phase I, in-depth interviews (n = 28) were conducted to assess relevance of the existing SSFG materials (10 booklets, nine pamphlets) and identify new content for the booklets. Next, for Phase II, learner verification interviews (n = 20 dual users) were conducted to assess their appeal and acceptability. Several key themes emerged from the Phase I in-depth interviews. Findings led to the inclusion of e-cigarette-specific strategies used by successful quitters such as gradually reducing nicotine levels, switching from tobacco flavor to alternative flavors, and limiting e-cigarette use to places one would normally smoke (i.e., not expanding use). Suggestions from Phase II learner verification included broadening the visual appeal for a younger, more diverse demographic, expanding tips for quitting smoking via e-cigarettes, and expanding terminology for e-cigarette devices. Beginning with an efficacious self-help intervention, we used a systematic process to develop a version specifically for dual users.

BACKGROUND:COVID-19 continues to disrupt global health and well-being. In April-May 2020, we generated a digital, remote interactive tool to provide health and well-being resources and foster connectivity among community members through a text messaging platform. OBJECTIVE:This study aimed to prospectively investigate the ability of a health system-based digital, remote, interactive tool to provide health and well-being resources to local community participants and to foster connectivity among them during the early phases of COVID-19. METHODS:We performed descriptive and nonparametric longitudinal statistical analyses to describe and compare the participants' mood ratings over time and thematic analysis of their responses to text messages to further assess mood. RESULTS:From among 393 individuals seeking care in an urban emergency department in an academic setting, engaged in a two-way text messaging platform, we recorded 287 mood ratings and 368 qualitative responses. We observed no difference in the initial mood rating by week of enrollment [Kruskal-Wallis chi-square H(5)=1.34; P=.93], and the average mood rating did not change for participants taken together [Friedman chi-square Q(3)=0.32; P=.96]. However, of participants providing mood ratings at baseline, mood improved significantly among participants who reported a low mood rating at baseline [n=25, 14.97%; Q(3)=20.68; P<.001] but remained stable among those who reported a high mood rating at baseline [n=142, 85.03%; Q(3)=2.84; P=.42]. Positive mood elaborations most frequently included words related to sentiments of thankfulness and gratitude, mostly for a sense of connection and communication; in contrast, negative mood elaborations most frequently included words related to anxiety. CONCLUSIONS:Our findings suggest the feasibility of engaging individuals in a digital community with an emergency department facilitation. Specifically, for those who opt to engage in a text messaging platform during COVID-19, it is feasible to assess and respond to mood-related queries with vetted health and well-being resources.