Acute Kidney Injury and Subsequent Kidney Failure With Replacement Therapy Incidence in Older Adults With Advanced CKD: A Cohort Study of US Veterans.

Rationale & Objective: Advanced age is a major risk factor for chronic kidney disease (CKD) development, which has high heterogeneity in disease progression. Acute kidney injury (AKI) hospitalization rates are increasing, especially among older adults. Previous AKI epidemiologic analyses have focused on hospitalized populations, which may bias results toward sicker populations. This study examined the association between AKI and incident kidney failure with replacement therapy (KFRT) while evaluating age as an effect modifier of this relationship. Study Design: Retrospective cohort study. Setting & Participants: 24,133 Veterans at least 65 years old with incident CKD stage 4 from 2011 to 2013. Exposures: AKI, AKI severity, and age. Outcomes: KFRT and death. Analytical Approach: The Fine-Gray competing risk regression was used to model AKI and incident KFRT with death as a competing risk. A Cox regression was used to model AKI severity and death. Results: Despite a nonsignificant age interaction between AKI and KFRT, a clinically relevant combined effect of AKI and age on incident KFRT was observed. Compared with our oldest age group without AKI, those aged 65-74 years with AKI had the highest risk of KFRT (subdistribution HR [sHR], 14.9; 95% CI, 12.7-17.4), whereas those at least 85 years old with AKI had the lowest (sHR, 1.71; 95% CI, 1.22-2.39). Once Veterans underwent KFRT, their risk of death increased by 44%. A 2-fold increased risk of KFRT was observed across all AKI severity stages. However, the risk of death increased with worsening AKI severity. Limitations: Our study lacked generalizability, was restricted to ever use of medications, and used inpatient serum creatinine laboratory results to define AKI and AKI severity. Conclusions: In this national cohort, advanced age was protective against incident KFRT but not death. This is likely explained by the high frequency of deaths observed in this population (51.1%). Nonetheless, AKI and younger age are substantial risk factors for incident KFRT.

Older adults are at risk of acute kidney injury (AKI) and subsequent nonrecovery from AKI, resulting in long-term dialysis. Hospitalized patients have often been used in the past to study AKI. This could lead to biased conclusions when inferring from sicker populations. That is why we created a national cohort of 24,133 Veterans at least 65 years old with incident chronic kidney disease (CKD) stage 4 to examine the relationship between AKI and age and subsequent kidney failure with replacement therapy (KFRT). The data have showed that AKI and younger age are substantial risk factors for incident KFRT. As for older age, it appears to be protective against KFRT but not death. This is likely explained by the high frequency of deaths observed in our cohort.

Increasing Preterm Delivery and Small for Gestational Age Trends in South Carolina during the COVID-19 Pandemic.

Preterm delivery (PTD) complications are a major cause of childhood morbidity and mortality. We aimed to assess trends in PTD and small for gestational age (SGA) and whether trends varied between race-ethnic groups in South Carolina (SC). We utilized 2015-2021 SC vital records linked to hospitalization and emergency department records. PTD was defined as clinically estimated gestation less than (<) 37 weeks (wks.) with subgroup analyses of PTD < 34 wks. and < 28 wks. SGA was defined as infants weighing below the 10th percentile for gestational age. This retrospective study included 338,532 (243,010 before the COVID-19 pandemic and 95,522 during the pandemic) live singleton births of gestational age ≥ 20 wks. born to 260,276 mothers in SC. Generalized estimating equations and a change-point during the first quarter of 2020 helped to assess trends. In unadjusted analyses, pre-pandemic PTD showed an increasing trend that continued during the pandemic (relative risk (RR) = 1.04, 95% CI: 1.02-1.06). PTD < 34 wks. rose during the pandemic (RR = 1.07, 95% CI: 1.02-1.12) with a significant change in the slope. Trends in SGA varied by race and ethnicity, increasing only in Hispanics (RR = 1.02, 95% CI: 1.00-1.04) before the pandemic. Our study reveals an increasing prevalence of PTD and a rise in PTD < 34 wks. during the pandemic, as well as an increasing prevalence of SGA in Hispanics during the study period.

Geographic, Patient, and VA Medical Center Variation in the Receipt and Mode of Primary Care in a National Sample of Veterans with Diabetes during 2020.

While telemedicine infrastructure was in place within the Veterans Health Administration (VHA) healthcare system before the onset of the COVID-19 pandemic, geographically varying ordinances/closures disrupted vital care for chronic disease patients such as those with type 2 diabetes. We created a national cohort of 1,647,158 non-Hispanic White, non-Hispanic Black, and Hispanic veterans with diabetes including patients with at least one primary care visit and HbA1c lab result between 3.5% and 20% in the fiscal year (FY) 2018 or 2019. For each VAMC, the proportion of telehealth visits in FY 2019 was calculated. Two logistic Bayesian spatial models were employed for in-person primary care or telehealth primary care in the fourth quarter of the FY 2020, with spatial random effects incorporated at the VA medical center (MC) catchment area level. Finally, we computed and mapped the posterior probability of receipt of primary care for an "average" patient within each catchment area. Non-Hispanic Black veterans and Hispanic veterans were less likely to receive in-person primary care but more likely to receive tele-primary care than non-Hispanic white veterans during the study period. Veterans living in the most socially vulnerable areas were more likely to receive telehealth primary care in the fourth quarter of FY 2020 compared to the least socially vulnerable group but were less likely to receive in-person care. In summary, racial minorities and those in the most socially vulnerable areas were less likely to receive in-person primary care but more likely to receive telehealth primary care, potentially indicating a disparity in the impact of the pandemic across these groups.

The Association of Hypertensive Disorders of Pregnancy with Infant Mortality, Preterm Delivery, and Small for Gestational Age.

Gestational hypertension, preeclampsia, eclampsia, and chronic hypertension (CHTN) are associated with adverse infant outcomes and disproportionately affect minoritized race/ethnicity groups. We evaluated the relationships between hypertensive disorders of pregnancy (HDP) and/or CHTN with infant mortality, preterm delivery (PTD), and small for gestational age (SGA) in a statewide cohort with a diverse racial/ethnic population. All live, singleton deliveries in South Carolina (2004-2016) to mothers aged 12-49 were evaluated for adverse outcomes: infant mortality, PTD (20 to less than <37 weeks) and SGA (<10th birthweight-for-gestational-age percentile). Logistic regression models adjusted for sociodemographic, behavioral, and clinical characteristics. In 666,905 deliveries, mothers had superimposed preeclampsia (HDP + CHTN; 1.0%), HDP alone (8.0%), CHTN alone (1.8%), or no hypertension (89.1%). Infant mortality risk was significantly higher in deliveries to women with superimposed preeclampsia, HDP, and CHTN compared with no hypertension (relative risk [RR] = 1.79, 1.39, and 1.48, respectively). After accounting for differing risk by race/ethnicity, deliveries to women with HDP and/or CHTN were more likely to result in PTD (RRs ranged from 3.14 to 5.25) or SGA (RRs ranged from 1.67 to 3.64). As CHTN, HDP and superimposed preeclampsia confer higher risk of adverse outcomes, prevention efforts should involve encouraging and supporting mothers in mitigating modifiable cardiovascular risk factors.

Using implementation science to evaluate a population-wide genomic screening program: Findings from the first 20,000 In Our DNA SC participants.

We use the implementation science framework RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) to describe outcomes of In Our DNA SC, a population-wide genomic screening (PWGS) program. In Our DNA SC involves participation through clinical appointments, community events, or at home collection. Participants provide a saliva sample that is sequenced by Helix, and those with a pathogenic variant or likely pathogenic variant for CDC Tier 1 conditions are offered free genetic counseling. We assessed key outcomes among the first cohort of individuals recruited. Over 14 months, 20,478 participants enrolled, and 14,053 samples were collected. The majority selected at-home sample collection followed by clinical sample collection and collection at community events. Participants were predominately female, White (self-identified), non-Hispanic, and between the ages of 40-49. Participants enrolled through community events were the most racially diverse and the youngest. Half of those enrolled completed the program. We identified 137 individuals with pathogenic or likely pathogenic variants for CDC Tier 1 conditions. The majority (77.4%) agreed to genetic counseling, and of those that agreed, 80.2% completed counseling. Twelve clinics participated, and we conducted 108 collection events. Participants enrolled at home were most likely to return their sample for sequencing. Through this evaluation, we identified facilitators and barriers to implementation of our state-wide PWGS program. Standardized reporting using implementation science frameworks can help generalize strategies and improve the impact of PWGS.

Hypertensive Disorders of Pregnancy and Pre-Pregnancy Hypertension with Subsequent Incident Venous Thromboembolic Events.

Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension contribute to maternal morbidity and mortality. We examined the association of HDP and pre-pregnancy hypertension with subsequent venous thromboembolic (VTE) events. The retrospective cohort study included 444,859 women with ≥1 live, singleton birth in South Carolina (2004-2016). Hospital and emergency department visit and death certificate data defined incident VTE, HDP, and pre-pregnancy hypertension. Birth certificate data also defined the exposures. Adjusted Cox proportional hazards methods modeled VTE events risk. Of the cohort, 2.6% of women had pre-pregnancy hypertension, 5.8% had HDP, 2.8% had both pre-pregnancy hypertension and HDP (both conditions), and 88.8% had neither condition. The risk of incident VTE events within one year of delivery was higher in women with HDP (hazard ratio [HR] = 1.62, 95% confidence interval [CI]: 1.15-2.29) and both conditions (HR = 2.32, 95% CI: 1.60-3.35) compared to those with neither condition as was the risk within five years for women with HDP (HR = 1.35, 95% CI: 1.13-1.60) and for women with both conditions (HR = 1.82, 95% CI: 1.50-2.20). One- and five-year risks did not differ in women with pre-pregnancy hypertension compared to women with neither condition. Compared to non-Hispanic White (NHW) women with neither condition, the incident VTE event risk was elevated within five years of delivery for NHW (HR = 1.29, 95% CI: 1.02-1.63; HR = 1.59, 95% CI: 1.16-2.17) and non-Hispanic Black (NHB; HR = 1.51, 95% CI: 1.16-2.96; HR = 2.08, 95% CI: 1.62-2.66) women with HDP and with both conditions, respectively, and for NHB women with pre-pregnancy hypertension (HR = 1.50, 95% CI: 1.09-2.07). VTE event risk was highest in women with HDP, and the event rates were higher in NHB women than in NHW women in the same exposure group.

Circulating Lipoprotein Sphingolipids in Chronic Kidney Disease with and without Diabetes.

Abnormalities of sphingolipid metabolism play an important role in diabetes. We compared sphingolipid levels in plasma and in isolated lipoproteins between healthy control subjects and two groups of patients, one with chronic kidney disease without diabetes (ND-CKD), and the other with type 2 diabetes and macroalbuminuria (D-MA). Ceramides, sphingomyelins, and sphingoid bases and their phosphates in LDL were higher in ND-CKD and in D-MA patients compared to controls. However, ceramides and sphingoid bases in HDL2 and HDL3 were lower in ND-CKD and in D-MA patients than in controls. Sphingomyelins in HDL2 and HDL3 were lower in D-MA patients than in controls but were normal in ND-CKD patients. Compared to controls, lactosylceramides in LDL and VLDL were higher in ND-CKD patients but not in D-MA patients. However, lactosylceramides in HDL2 and HDL3 were lower in both ND-CKD and D-MA patients than in controls. Plasma hexosylceramides in ND-CKD patients were increased and sphingoid bases decreased in both ND-CKD and D-MA patients. However, hexosylceramides in LDL, HDL2, and HDL3 were higher in ND-CKD patients than in controls. In D-MA patients, only C16:0 hexosylceramide in LDL was higher than in controls. The data suggest that sphingolipid measurement in lipoproteins, rather than in whole plasma, is crucial to decipher the role of sphingolipids in kidney disease.

ß2-Adrenergic receptor agonists as a treatment for diabetic kidney disease.

We have previously shown that the long-acting ß2-adrenergic receptor (ß2-AR) agonist formoterol induced recovery from acute kidney injury in mice. To determine whether formoterol protected against diabetic nephropathy, the most common cause of end-stage kidney disease (ESKD), we used a high-fat diet (HFD), a murine type 2 diabetes model, and streptozotocin, a murine type 1 diabetes model. Following formoterol treatment, there was a marked recovery from and reversal of diabetic nephropathy in HFD mice compared with those treated with vehicle alone at the ultrastructural, histological, and functional levels. Similar results were seen after formoterol treatment in mice receiving streptozotocin. To investigate effects in humans, we performed a competing risk regression analysis with death as a competing risk to examine the association between Veterans with chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), who use ß2-AR agonists, and Veterans with CKD but no COPD, and progression to ESKD in a large national cohort of Veterans with stage 4 CKD between 2011 and 2013. Veterans were followed until 2016 or death. ESKD was defined as the initiation of dialysis and/or receipt of kidney transplant. We found that COPD was associated with a 25.6% reduction in progression from stage 4 CKD to ESKD compared with no COPD after adjusting for age, diabetes, sex, race-ethnicity, comorbidities, and medication use. Sensitivity analysis showed a 33.2% reduction in ESKD in Veterans with COPD taking long-acting formoterol and a 20.8% reduction in ESKD in Veterans taking other ß2-AR agonists compared with those with no COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a treatment for diabetic nephropathy and perhaps other forms of CKD.NEW & NOTEWORTHY Diabetic nephropathy is the most common cause of ESKD. Formoterol, a long-acting ß2-adrenergic receptor (ß2-AR) agonist, reversed diabetic nephropathy in murine models of type 1 and 2 diabetes. In humans, there was an association with protection from progression of CKD in patients with COPD, by means of ß2-AR agonist intake, compared with those without COPD. These data indicate that ß2-AR agonists, especially formoterol, could be a new treatment for diabetic nephropathy and other forms of CKD.

Use of a multi-phased approach to identify and address facilitators and barriers to the implementation of a population-wide genomic screening program.

INTRODUCTION: Population-wide genomic screening for CDC Tier-1 conditions offers the ability to identify the 1-2% of the US population at increased risk for Hereditary Breast and Ovarian Cancer, Lynch Syndrome, and Familial Hypercholesterolemia. Implementation of population-wide screening programs is highly complex, requiring engagement of diverse collaborators and implementation teams. Implementation science offers tools to promote integration of these programs through the identification of determinants of success and strategies to address potential barriers. METHODS: Prior to launching the program, we conducted a pre-implementation survey to assess anticipated barriers and facilitators to reach, effectiveness, adoption, implementation, and maintenance (RE-AIM), among 51 work group members (phase 1). During the first year of program implementation, we completed coding of 40 work group meetings guided by the Consolidated Framework for Implementation Research (CFIR) (phase 2). We matched the top barriers to implementation strategies identified during phase 2 using the CFIR-ERIC (Expert Recommendation for Implementing Change) matching tool. RESULTS: Staffing and workload concerns were listed as the top barrier in the pre-implementation phase of the program. Top barriers during implementation included adaptability (n = 8, 20%), complexity (n = 14, 35%), patient needs and resources (n = 9, 22.5%), compatibility (n = 11, 27.5%), and self-efficacy (n = 9, 22.5%). We identified 16 potential implementation strategies across six ERIC clusters to address these barriers and operationalized these strategies for our specific setting and program needs. CONCLUSION: Our findings provide an example of successful use of the CFIR-ERIC tool to guide implementation of a population-wide genomic screening program.

Applying the R = MC2 implementation science heuristic to assess the impact of readiness on reach and implementation of a population-wide genomic screening program.

Population-wide genomic screening for genes that have high penetrance and clinical actionability enhances the opportunity to identify individuals at risk for developing hereditary conditions. Organizational readiness has been shown to influence the likelihood of successful implementation of complex initiatives such as the integration of population-wide genomic screening in clinical settings. We use the organizational readiness heuristic R = MC2 to better understand three factors that influence readiness for implementation of In Our DNA SC, a population-wide genomic screening program: motivation to implement, general capacity of an organization, and innovation-specific capacities. We then assessed the influence of these readiness factors on implementation outcomes of reach (measured through enrollment rate) and implementation (measured through the number of DNA samples collected). Data were collected pre-implementation and captured during the three-month pilot phase of the In Our DNA SC program. We collected administrative data from the electronic health record and quantitatively captured elements of readiness through surveys distributed to provider champions and clinical administrative champions at the 10 sites implementing the population-wide genomic screening program. We facilitated innovation-specific capacity through training offered at each site, as well as technical assistance through weekly meetings with other implementing sites, and resources available to all staff. Forty percent of provider champions attended training and 80% of administrative champions attended training. An average of 3.7 additional staff were trained at each implementing site. Satisfaction with training positively influenced reach (ß = 0.0121, p = 0.0271) but did not impact implementation. Provider engagement (innovation capabilities) was associated with reach (ß = 0.0020, p = 0.0251) and clinical administrator engagement was associated with sample collection rate (ß = 0.2599, ß = 0.038). Readiness to change is considered one of the most important factors in understanding the potential opportunity for implementation. We found that motivation to adopt a population-wide genomic screening program positively impacted the program's reach. The type of champion influenced discrete outcomes, with provider champions positively impacting reach and administrative champions influencing implementation (assessed through sample collection rate). As genomics continues to be integrated into clinical practice, it will be important to understand the contextual factors that influence readiness for implementation and design support throughout the life-course of implementation to ensure the success of large-scale, complex initiatives.

Geographic variation in diabetic retinopathy screening within the Veterans Health Administration.

AIMS: Diabetic retinopathy (DR) remains the leading cause of vision impairment among working-age adults in the United States. The Veterans Health Administration (VA) supplemented its DR screening efforts with teleretinal imaging in 2006. Despite its scale and longevity, no national data on the VA's screening program exists since 1998. Our objective was to determine the influence of geography on diabetic retinopathy screening adherence. METHODS: Setting: VA national electronic medical records. STUDY POPULATION: A national cohort of 940,654 veterans with diabetes (defined as two or more diabetes ICD-9 codes (250.xx)) without a history of DR. EXPOSURES: 125 VA Medical Center catchment areas, demographics, comorbidity burden, mean HbA1c levels, medication use and adherence, as well as utilization and access metrics. MAIN OUTCOME MEASURE: Screening for diabetic retinopathy within the VA medical system within a 2-year period. RESULTS: Within a 2-year time frame 74 % of veterans without a history of DR received retinal screenings within the VA system. After adjustment for age, gender, race-ethnic group, service-connected disability, marital status, and the van Walraven Elixhauser comorbidity score, the prevalence of DR screening varied by VA catchment area with values ranging from 27 % to 86 %. These differences persisted after further adjusting for mean HbA1c level, medication use and adherence as well as utilization and access metrics. CONCLUSIONS: The wide variability in DR screening across 125 VA catchment areas indicates the presence of unmeasured determinants of DR screening. These results are relevant to clinical decision making in DR screening resource allocation.

Racial Differences in Vascular Assessment Prior to Amputation in the Veterans Health Administration.

Purpose: It is unclear whether disparities in the care provided before lower extremity amputation (LEA) is driven by differences in receipt of diagnostic work-up versus revascularization attempts. Methods: We performed a national cohort study of Veterans who underwent LEA between March 2010 and February 2020 to assess receipt of vascular assessment with arterial imaging and/or revascularization in the year prior to LEA. Results: Among 19,396 veterans (mean age 66.8 years; 26.6% Black), Black veterans had diagnostic procedures more often than White veterans (47.5% vs. 44.5%) and revascularization as often (25.8% vs. 24.5%). Conclusion: We must identify patient and facility-level factors associated with LEA as disparities do not appear related to differences in attempted revascularization.

The Combined Effect of Delirium and Falls on Length of Stay and Discharge.

INTRODUCTION: Delirium or a fall are associated with many negative outcomes including increased length of stay (LOS) and discharge to a facility; however, this relationship is incompletely understood. METHODS: A cross-sectional study of all hospitalizations in a large, tertiary care hospital evaluated the effect of delirium and a fall on the outcomes of LOS and risk of being discharged to a facility. RESULTS: The study included 29,655 hospital admissions. A total of 3,707 (12.5%) patients screened positive for delirium and 286 (0.96%) had a reported fall. After adjustment for covariates, relative to patients without delirium or a fall, patients with delirium only had a 1.64-fold longer LOS; patients with fall only had a 1.96-fold longer LOS; and patients who had delirium and fall had a 2.84-fold longer LOS. The adjusted odds of discharge to a facility, relative to those without delirium or a fall, was 8.98 times higher in those with delirium and a fall. CONCLUSIONS: Delirium and falls influence LOS and likelihood of being discharged to a facility. The joint impact of falls and delirium on LOS and facility discharge was more than additive. Hospitals should consider the integrated management of delirium and falls.

Anticipating adaptation: tracking the impact of planned and unplanned adaptations during the implementation of a complex population-based genomic screening program.

In 2021, the Medical University of South Carolina (MUSC) launched In Our DNA SC. This large-scale initiative will screen 100,000 individuals in South Carolina for three preventable hereditary conditions that impact approximately two million people in the USA but often go undetected. In anticipation of inevitable changes to the delivery of this complex initiative, we developed an approach to track and assess the impact of evaluate adaptations made during the pilot phase of program implementation. We used a modified version of the Framework for Reporting Adaptations and Modification-Enhanced (FRAME) and Adaptations to code adaptations made during the 3-month pilot phase of In Our DNA SC. Adaptations were documented in real-time using a REDCap database. We used segmented linear regression models to independently test three hypotheses about the impact of adaptations on program reach (rate of enrollment in the program, rate of messages viewed) and implementation (rate of samples collected) 7 days pre- and post-adaptation. Effectiveness was assessed using qualitative observations. Ten adaptations occurred during the pilot phase of program implementation. Most adaptations (60%) were designed to increase the number and type of patient contacted (reach). Adaptations were primarily made based on knowledge and experience (40%) or from quality improvement data (30%). Of the three adaptations designed to increase reach, shortening the recruitment message potential patients received significantly increased the average rate of invitations viewed by 7.3% (p = 0.0106). There was no effect of adaptations on implementation (number of DNA samples collected). Qualitative findings support improvement in effectiveness of the intervention after shortening the consent form and short-term positive impact on uptake of the intervention as measured by team member's participation. Our approach to tracking adaptations of In Our DNA SC allowed our team to quantify the utility of modifications, make decisions about pursuing the adaptation, and understand consequences of the change. Streamlining tools for tracking and responding to adaptations can help monitor the incremental impact of interventions to support continued learning and problem solving for complex interventions being delivered in health systems based on real-time data.

We tracked adaptations to a large-scale population genetic screening program at the Medical University of South Carolina (MUSC) using the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME). We found adaptations during program roll-out that impacted implementation outcomes. Our approach to tracking adaptations for the program allowed us to quantify the utility of modifications, make decision about pursuing changes, and understand consequences of adaptations.

Association of Health Care Utilization and Access to Care With Vascular Assessment Before Major Lower Extremity Amputation Among US Veterans.

Importance: Patient-level characteristics alone do not account for variation in care among US veterans with peripheral artery disease (PAD). Presently, the extent to which health care utilization and regional practice variation are associated with veterans receiving vascular assessment prior to major lower extremity amputation (LEA) is unknown. Objective: To assess whether demographics, comorbidities, distance to primary care, the number of ambulatory clinic visits (primary and medical specialty care), and geographic region are associated with receipt of vascular assessment prior to LEA. Design, Setting, and Participants: This national cohort study used US Department of Veterans Affairs' Corporate Data Warehouse data from March 1, 2010, to February 28, 2020, for veterans aged 18 or older who underwent major LEA and who received care at Veterans Affairs facilities. Exposures: The number of ambulatory clinic visits (primary and medical specialty care) in the year prior to LEA, geographic region of residence, and distance to primary care. Main Outcomes and Measures: The main outcome was receipt of a vascular assessment (vascular imaging study or revascularization procedure) in the year prior to LEA. Results: Among 19 396 veterans, the mean (SD) age was 66.78 (10.20) years and 98.5% were male. In the year prior to LEA, 8.0% had no primary care visits and 30.1% did not have a vascular assessment. Compared with veterans with 4 to 11 primary care clinic visits, those with fewer visits were less likely to receive vascular assessment in the year prior to LEA (1-3 visits: adjusted odds ratio [aOR], 0.90; 95% CI, 0.82-0.99). Compared with veterans who lived less than 13 miles from the closest primary care facility, those who lived 13 miles or more from the facility were less likely to receive vascular assessment (aOR, 0.88; 95% CI, 0.80-0.95). Veterans who resided in the Midwest were most likely to undergo vascular assessment in the year prior to LEA than were those living in other regions. Conclusions and Relevance: In this cohort study, health care utilization, distance to primary care, and geographic region were associated with intensity of PAD treatment before LEA, suggesting that some veterans may be at greater risk of suboptimal PAD care practices. Development of clinical programs, such as remote patient monitoring and management, may represent potential opportunities to improve limb preservation rates and the overall quality of vascular care for veterans.

The Association between Delirium and In-Hospital Falls: A Cross-Sectional Analysis of a Delirium Screening Program.

Methods: A cross-sectional study using delirium screening and falls reports was used to measure the association between delirium and falls. All inpatient data from August, 2018, to January, 2020, at a large academic medical center were analyzed. A multivariable logistic regression of 29,655 hospital admissions was used to understand the association between in-hospital delirium and falls. Results: Analysis revealed a delirium rate of 12.5% (n = 3,707) of all admissions and 286 (0.9%) admissions with falls; of the falls studied, 37.6% of these patients screened positive for delirium during their admission. Relative to those who screened negative for delirium, admissions that screened positive for delirium had a 2.81 increased odds of falling. Conclusions: Delirium and falls are related. This strong association should motivate health systems to look closely at both problems. Falls and delirium can both have immense impacts on the patient and the health system. The powerful association between them provides a window to reduce these additional patient harms. More specifically, a modern delirium screening tool should be used as part of routine risk assessment focused on reducing in-hospital falls.

Primary Care Counseling of Parents Regarding Childhood Screen Media Use.

Parental beliefs and motivation are instrumental in improving childhood digital media use (DMU). Parents (n = 611) completed questionnaires about childhood DMU assessing knowledge, interest in counseling, motivation to change, self-efficacy, and beliefs. Less than a third correctly recognized screen time limits. Twenty-seven percent received childhood DMU information from a doctor, while 46% stated they would like such information. Only 2% had a doctor-recommended DMU plan. Interest in DMU topics, motivation to improve, and management self-efficacy were moderate. Top negative beliefs were addiction to DMU (52%), sleep problems (39%), obesity (33%), social skills (33%), and inappropriate content (32%). Differences between age categories existed for social (48%, P = .01) and language (14%, P = .01) concerns (highest for toddlers), attention concerns (27%, P = .02; highest in preschoolers), and depression (13%, P < .001) and low self-esteem (8%, P = .04; highest in teens). Findings support further development of approaches to address DMU, tailored by age-specific common parental views.

Racial and ethnic disparities in preterm birth: a mediation analysis incorporating mixtures of polybrominated diphenyl ethers.

Background: Racial and ethnic disparities persist in preterm birth (PTB) and gestational age (GA) at delivery in the United States. It remains unclear whether exposure to environmental chemicals contributes to these disparities. Objectives: We applied recent methodologies incorporating environmental mixtures as mediators in causal mediation analysis to examine whether racial and ethnic disparities in GA at delivery and PTB may be partially explained by exposures to polybrominated diphenyl ethers (PBDEs), a class of chemicals used as flame retardants in the United States. Methods: Data from a multiracial/ethnic US cohort of 2008 individuals with low-risk singleton pregnancies were utilized, with plasma PBDE concentrations measured during early pregnancy. We performed mediation analyses incorporating three forms of mediators: (1) reducing all PBDEs to a weighted index, (2) selecting a PBDE congener, or (3) including all congeners simultaneously as multiple mediators, to evaluate whether PBDEs may contribute to the racial and ethnic disparities in PTB and GA at delivery, adjusted for potential confounders. Results: Among the 2008 participants, 552 self-identified as non-Hispanic White, 504 self-identified as non-Hispanic Black, 568 self-identified as Hispanic, and 384 self-identified as Asian/Pacific Islander. The non-Hispanic Black individuals had the highest mean ∑PBDEs, the shortest mean GA at delivery, and the highest rate of PTB. Overall, the difference in GA at delivery comparing non-Hispanic Black to non-Hispanic White women was -0.30 (95% CI: -0.54, -0.05) weeks. This disparity reduced to -0.23 (95% CI: -0.49, 0.02) and -0.18 (95% CI: -0.46, 0.10) weeks if fixing everyone's weighted index of PBDEs to the median and the 25th percentile levels, respectively. The proportion of disparity mediated by the weighted index of PBDEs was 11.8%. No statistically significant mediation was found for PTB, other forms of mediator(s), or other racial and ethnic groups. Conclusion: PBDE mixtures may partially mediate the Black vs. White disparity in GA at delivery. While further validations are needed, lowering the PBDEs at the population level might help reduce this disparity.

Association of Maternal Caffeine Consumption During Pregnancy With Child Growth.

Importance: Greater caffeine consumption in pregnancy is associated with reduced birth size, but potential associations with childhood growth are unclear. Objective: To evaluate the associations of pregnancy caffeine and paraxanthine measures with child growth in a contemporary cohort with low caffeine consumption and a historical cohort with high caffeine consumption. Design, Setting, and Participants: The Environmental Influences on Child Health Outcomes cohort of the National Institute of Child Health and Human Development Fetal Growth Studies (ECHO-FGS; 10 sites, 2009-2013) was a pregnancy cohort with 1 child measurement between ages 4 and 8 years (follow-up in 2017-2019). The Collaborative Perinatal Project (CPP) was a pregnancy cohort (12 sites, 1959-1965) with child follow-up through 8 years (1960-1974). The current secondary analysis was conducted in 2021 and 2022. Exposures: Concentrations of caffeine and its primary metabolite, paraxanthine, were quantified from plasma (ECHO-FGS) and serum (CPP) collected in the first trimester. Cut points for analyses were defined by quartiles in ECHO-FGS and quintiles in CPP. Main Outcomes and Measures: Child z scores for body mass index, weight, and height were evaluated, as well as fat mass index and percentage and obesity risk measured at 1 time between age 4 and 8 years in ECHO-FGS. In a secondary analysis of the CPP cohort, child z scores and obesity risk longitudinally through age 8 years were evaluated. Results: In ECHO-FGS (median caffeine intake <50 mg/d), 788 children (mean [SD] age, 6.8 [1.0] years; 411 boys [52.2%]) of women in the fourth vs first quartile of plasma caffeine concentrations had lower height z scores (ß = -0.21; 95% CI, -0.41 to -0.02), but differences in weight z scores were only observed in the third quartile (ß = -0.27; 95% CI, -0.47 to -0.07). In CPP, beginning at age 4 years, 1622 children (805 boys [49.7%]) of women in the highest caffeine quintile group had lower height z scores than their peers from the lowest group, with the gap widening with each successive year of age (ß = -0.16 [95% CI, -0.31 to -0.01] at 4 years; ß = -0.37 [95% CI, -0.57 to -0.16] at 8 years). There were slight reductions in weight at ages 5 to 8 years for children in the third vs first caffeine quintile (ß = -0.16 to -0.22). Results were consistent for paraxanthine concentrations in both cohorts. Conclusions and Relevance: Intrauterine exposure to increasing levels of caffeine and paraxanthine, even in low amounts, was associated with shorter stature in early childhood. The clinical implication of reductions in height and weight is unclear; however, the reductions were apparent even with levels of caffeine consumption below clinically recommended guidelines of less than 200 mg per day.

Randomised controlled trial evaluating the effects of screening and referral for social determinants of health on Veterans' outcomes: protocol.

INTRODUCTION: Health policy leaders recommend screening and referral (S&R) for unmet social needs (eg, food) in clinical settings, and the American Heart Association recently concluded that the most significant opportunities for reducing cardiovascular disease (CVD) death and disability lie with addressing the social determinants of CVD outcomes. A limited but promising evidence base supports these recommendations, but more rigorous research is needed to guide health care-based S&R efforts. Funded by the Veteran Health Administration (VA), the study described in this paper will assess the efficacy of S&R on Veterans' connections to new resources to address social needs, reduction of unmet needs and health-related outcomes (adherence, utilisation and clinical outcomes). METHODS AND ANALYSIS: We will conduct a 1-year mixed-methods randomised controlled trial at three VA sites, enrolling Veterans with CVD and CVD-risk. 880 Veterans experiencing one or more social needs will be randomised within each site (n=293 per site) to one of three study arms representing referral mechanisms of varying intensity (screening only, screening and provision of resource sheet(s), screening and provision of resource sheet(s) plus social work assistance). For each Veteran, we will examine associations of unmet social needs with health-related outcomes at baseline, and longitudinally compare the impact of each approach on connection to new resources (primary outcome) and follow-up outcomes over a 12-month period. We will additionally conduct qualitative interviews with key stakeholders, including Veterans to identify potential explanatory factors related to the relative success of the interventions. ETHICS AND DISSEMINATION: Ethics approval was obtained from the VA Central Internal Review Board on 13 July 2021 (reference #: 20-07-Amendment No. 02). Findings will be disseminated through reports, lay summaries, policy briefs, academic publications, and conference presentations. TRIAL REGISTRATION NUMBER: NCT04977583.