Polychlorinated biphenyls and incident coronary heart disease-related outcomes in Great Lakes fish consumers.

BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) has been linked to risk factors for cardiovascular disease such as increased inflammation, accelerated atherosclerosis, diabetes, and sex hormone dysregulation. Furthermore, there is increasing evidence suggesting associations between internal dose of PCBs and cardiovascular outcomes. OBJECTIVES: The purpose of this study is to investigate longitudinal associations of PCBs with coronary heart disease (CHD)-related outcomes in a cohort of Great Lakes sport fish consumers. METHODS: The Great Lakes Sport Fish Consumer cohort was established in the early 1990's. Eight hundred nineteen participants were followed from 1993 to 2017. Serum PCBs were measured in 1994/1995 (baseline), in 2001, and in 2004, while health history questionnaires were administered in 1996, 2003, 2010, and 2017. Cox models were used to prospectively investigate associations of total PCBs and PCB groupings, based on aryl hydrocarbon receptor activity, with incident self-reported physician diagnosis of coronary heart disease (CHD), myocardial infarction (MI), and angina pectoris. RESULTS: A 2-fold increase in phenobarbital-type PCBs was associated with a 72% increase in likelihood of self-reported incident diagnosis of CHD (HR=1.72, 95% CI: 1.06-2.81; p=0.0294). Similar results were observed for total PCBs (HR=1.68, 95% CI: 1.05-2.69; p=0.0306) and mixed methacholine/phenobarbital type (mixed-type) PCBs (HR=1.60, 95% CI: 1.02-2.52; p=0.0427), but not methacholine-type PCBs. PCBs were not strongly associated with risk of MI or angina. CONCLUSIONS: This study presents evidence that exposure to PCBs increases the risk of developing coronary heart disease. Given the large number of risk factors and causal pathways for CHD, future research is required to better understand biological mechanisms of action for PCBs on CHD.

Clinical Outcomes of Persistent Severe Acute Kidney Injury among Patients with Kidney Disease Improving Global Outcomes Stage 2 or 3 Acute Kidney Injury.

INTRODUCTION: The burden of persistent (≥3 days) severe AKI (PS-AKI) is poorly described among inpatients with stage 2-3 AKI in the ward or ICU. Quantification could motivate targeted interventions to decrease duration of AKI in these high-risk patients. METHODS: This retrospective cohort study included adult patients discharged from January 1, 2017, to December 31, 2019, from US hospitals in the PINC AI Healthcare Database. Patients with KDIGO stage 2 or 3 AKI, length of stay ≥3 days, ≥3 serum creatinine measures, and no history of renal transplant, dialysis, or stage 5 chronic kidney disease were included. Patients were classified as PS-AKI (stage 3 AKI lasting ≥3 days or with death in ≤3 days, or stage 2 or 3 AKI with dialysis in ≤3 days) or not PS-AKI (NPS-AKI) (stage 3 AKI for ≤2 days, or stage 2 AKI without dialysis in ≤3 days). Outcomes during index (initial) hospitalization were PS-AKI incidence, ICU use, and in-hospital mortality, and during 30 days post-discharge were readmissions, in-hospital mortality, dialysis, and "new" dialysis (dialysis among patients without dialysis during index hospitalization). For index outcomes, we used a sensitivity definition, PS-AKISens, that excluded patients who met PS-AKI criteria by dialysis/death in ≤3 days of AKI onset. Multivariable-adjusted logistic regression quantified differences between PS-AKI and NPS-AKI, overall, and separately for ICU and non-ICU patients. RESULTS: Among 126,528 inpatients with stage 2 or 3 AKI, PS-AKI developed in 24.4% (30,916), with 39% of PS-AKI occurring in non-ICU patients. With NPS-AKI as the reference group, adjusted odds ratios (aORs) (95% CI) for PS-AKI and for PS-AKISens were 2.15 (2.09-2.21) and 1.28 (1.24-1.32) for ICU use and 4.58 (4.41-4.75) and 1.79 (1.70-1.89) for in-hospital mortality during index hospitalization. For outcomes during 30 days post-discharge, aORs for PS-AKI versus NPS-AKI were 1.07 (1.02-1.11) for readmissions, 1.33 (1.18-1.49) for in-hospital mortality, 15.66 (13.87-17.67) for dialysis, and 6.80 (5.84-7.93) for new dialysis. Despite higher mortality among ICU patients, aORs for outcomes during index and 30 days post-discharge were similar for ICU and non-ICU patients. CONCLUSION: In and out of the ICU, PS-AKI frequently affected inpatients with stage 2 or 3 AKI and was independently associated with worse clinical outcomes during index hospitalization and during 30 days post-discharge. These results suggest that interventions to prevent persistence of severe AKI may reduce adverse clinical outcomes among patients with stage 2 or 3 AKI in or out of the ICU.

Economic evaluation of expanded hemodialysis with the Theranova 400 dialyzer: A post hoc evaluation of a randomized clinical trial in the United States.

INTRODUCTION: The Theranova 400 is a medium cut-off dialyzer that allows for superior clearance of larger middle molecules than traditional high-flux dialyzers. This study evaluates the association of expanded hemodialysis (HDx) using the Theranova dialyzer versus conventional hemodialysis (HD) with a high-flux dialyzer on hospitalization rates and healthcare costs as compared to conventional HD in a post hoc analysis of a randomized controlled trial. METHODS: In a non-concealed, 24-week clinical trial, maintenance HD patients were randomized to receive treatment with either Theranova 400 or a similar size high-flux dialyzer. Hospitalization rate and average length of stay were calculated from trial data. Use of erythropoiesis-stimulating agents and iron were assumed to be equal and therefore excluded from the model. Average cost per inpatient day was obtained from a publicly available published source. Probabilistic sensitivity analyses were conducted to account for variability in model inputs. FINDINGS: There were 86 patients (389 patient-months) in the Theranova group and 85 patients (366 patient-months) in the high-flux HD group. All-cause hospitalization rate was 45% lower with Theranova compared to high-flux HD (IRR = 0.55; p = 0.05). Average annual estimated cost of hospitalization was $6098 lower with Theranova compared to high-flux HD. Compared to high-flux HD, average annual estimated cost associated with Theranova use was $4772 lower per patient. Hospitalization rate and hospital length of stay were the main drivers of cost. CONCLUSIONS: Use of the Theranova dialyzer is associated with lower estimated costs of care among maintenance HD patients, driven by fewer hospitalization events.

Cost-effectiveness of the TherMax blood warmer during continuous renal replacement therapy.

Hypothermia is a common adverse event during continuous renal replacement therapy (CRRT), affecting multiple organ systems and increasing risk of poor health outcomes among patients with acute kidney injury (AKI) undergoing CRRT. TheraMax blood warmers are the next generation of extracorporeal blood warmers which reduce risk of hypothermia during CRRT. The purpose of this study is to elucidate the potential health economic impacts of avoiding CRRT-induced hypothermia by using the novel TherMax blood warming device. This study compares health care costs associated with use of the new TherMax blood warmer unit integrated with the PrisMax system compared to CRRT with a standalone blood warming device to avoid hypothermia in continuous renal replacement therapy (CRRT). An economic model was developed in which relevant health states for each intervention were normothermia, hypothermia, discharge, and death. Clinical inputs and costs were obtained from a combination of retrospective chart review and publicly available summary estimates. The proportion of AKI patients treated with CRRT who became hypothermic (<36°C) during CRRT treatment was 34.5% in the TherMax group compared to 71.9% in the 'standalone warmer' group. Given the 78.7-year average life expectancy in the US and the assumed average patient age at discharge/death of 65.4 years, the total life-years gained by avoiding mortality related to hypothermia was 9.0 in the TherMax group compared to 8.0 in the 'standalone warmer' group. Cost per life-year gained was $8,615 in the TherMax group versus $10,115 in the 'standalone warmer' group for a difference of -$1,501 favoring TherMax. The incremental cost-effectiveness ratio was negative, indicating superior cost-effectiveness for TherMax versus 'standalone warmer'. The TherMax blood warming device used with the PrisMax system is associated with lower risk of hypothermia, which our model indicates leads to lower costs, lower risk of mortality due to hypothermia, and superior cost-effectiveness.

Impact of the Ebola epidemic on clinical outcomes of HIV-infected soldiers and their dependents in Sierra Leone.

The impact of the 2014-2016 Ebola epidemic in West Africa on human immunodeficiency virus (HIV) treatment in Sierra Leone is unknown, especially for groups with higher HIV prevalence such as the military. Using a retrospective study design, clinical outcomes were evaluated prior to and during the epidemic for 264 HIV-infected soldiers of the Republic of Sierra Leone Armed Forces (RSLAF) and their dependents receiving HIV treatment at the primary RSLAF HIV clinic. Medical records were abstracted for baseline clinical data and clinic attendance. Estimated risk of lost to follow-up (LTFU), default, and number of days without antiretroviral therapy (DWA) were calculated using repeated measures general estimating equations adjusted for age and gender. Due to missing data, 262 patients were included in the final analyses. There was higher risk of LTFU throughout the Ebola epidemic in Sierra Leone compared to the pre-Ebola baseline, with the largest increase in LTFU risk occurring at the peak of the epidemic (relative risk: 3.22, 95% CI: 2.22-4.67). There was an increased risk of default and DWA during the Ebola epidemic for soldiers but not for their dependents. The risk of LTFU, default, and DWA stabilized once the epidemic was largely resolved but remained elevated compared to the pre-Ebola baseline. Our findings demonstrate the negative and potentially lasting impact of the Ebola epidemic on HIV care in Sierra Leone and highlight the need to develop strategies to minimize disruptions in HIV care with future disease outbreaks.

The Impact of Low-Level Lead Toxicity on School Performance among Hispanic Subgroups in the Chicago Public Schools.

BACKGROUND: Environmental lead exposure detrimentally affects children's educational performance, even at very low blood lead levels (BLLs). Among children in Chicago Public Schools (CPS), the severity of the effects of BLL on reading and math vary by racial subgroup (White vs. Hispanic vs. non-Hispanic Black). We investigated the impact of BLL on standardized test performance by Hispanic subgroup (Mexican, Puerto Rican, and Other Hispanic). METHODS: We examined 12,319 Hispanic children born in Chicago between 1994 and 1998 who were tested for BLL between birth and 2006 and enrolled in the 3rd grade at a CPS school between 2003 and 2006. We linked the Chicago birth registry, the Chicago Blood Lead Registry, and 3rd grade Illinois Standard Achievement Test (ISAT) scores to examine associations between BLL and school performance. Primary analyses were restricted to children with BLL below 10 µg/dL (0.483 µmol/L). RESULTS: BLLs below 10 µg/dL (0.483 µmol/L) were inversely associated with reading and math scores in all Hispanic subgroups. Adjusted Relative Risks (RRadj) and 95% confidence intervals (CI) for reading and math failure were 1.34 (95% CI = 1.25, 1.63) and 1.53 (95% CI = 1.32, 1.78), respectively, per each additional 5 µg/dL of lead exposure for Hispanic children; RRadj did not differ across subgroups. We estimate that 7.0% (95% CI = 1.8, 11.9) of reading and 13.6% (95% CI = 7.7, 19.2) of math failure among Hispanic children can be attributed to exposure to BLLs of 5-9 µg/dL (0.242 to 0.435 µmol/L) vs. 0-4 µg/dL (0-0.193 µmol/L). The RRadj of math failure for each 5 µg/dL (0.242 µmol/L) increase in BLL was notably (p = 0.074) stronger among black Puerto Rican children (RRadj = 5.14; 95% CI = 1.65-15.94) compared to white Puerto Rican children (RRadj = 1.50; 95% CI = 1.12-2.02). CONCLUSIONS: Early childhood lead exposure is associated with poorer achievement on standardized reading and math tests in the 3rd grade for Mexican, Puerto Rican, and Other Hispanic children enrolled in Chicago Public Schools. While we did not see interactions between BLL and ISAT performance by Hispanic subgroup, the stronger association between BLL and math failure for Black Puerto Rican children is intriguing and warrants further study.