Influence of Eat, Sleep, and Console on Infants Pharmacologically Treated for Opioid Withdrawal: A Post Hoc Subgroup Analysis of the ESC-NOW Randomized Clinical Trial.

Importance: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. Objective: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. Design, Setting, and Participants: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. Exposure: Opioid treatment for NOWS and the ESC care approach. Main Outcomes and Measures: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. Results: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). Conclusion and Relevance: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. Trial Registration: ClinicalTrials.gov Identifier: NCT04057820.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal.

BACKGROUND: Although clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach - the Eat, Sleep, Console care approach - is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown. METHODS: In this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks' gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death. RESULTS: A total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups. CONCLUSIONS: As compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.).

Mpox Vaccine Interest Survey Prioritization and Data Flow: Maricopa County, Arizona, July-August 2022.

With increasing mpox cases in Maricopa County, Arizona, the county's health department launched a survey on July 11, 2022, to gather eligibility and contact data and provide clinic information to those interested in JYNNEOS as postexposure prophylaxis (PEP) or expanded postexposure prophylaxis(PEP++). Survey data were matched to case and vaccination data. Overall, 343 of the 513 respondents (66.9%) who reported close contact with an mpox case patient received PEP and 1712 of the 3379 respondents (50.7%) who were unsure of their contact status received PEP++. This outreach intervention connected potential close contacts unknown to MCDPH with PEP or PEP++. (Am J Public Health. 2023;113(5):504-508. https://doi.org/10.2105/AJPH.2023.307224).

Reduction of Rare-Earth Metal Complexes Induced by γ Irradiation.

The utility of γ irradiation for generating unstable, low oxidation state molecular species containing rare-earth metal ions in frozen solution has been examined. The method was evaluated by irradiating Ln(III) precursors (Ln = Sc, Y, and La) in a solid matrix of 2-methyltetrahydrofuran at 77 K with a 700 keV 137Cs source to generate free electrons capable of reducing the Ln(III) species. These experiments yielded EPR and UV-visible spectroscopic data that matched those of the known Ln(II) species [(C5H4SiMe3)3YII]1-, [(C5H4SiMe3)3LaII]1-, and {ScII[N(SiMe3)2]3}1-. Irradiation of the La(III) complex LaIII[N(SiMe3)2]3 by this method gave EPR and UV-visible absorption spectra consistent with {LaII[N(SiMe3)2]3}1-, a species that had previously eluded preparation by chemical reduction. Specifically, the irradiation product exhibited an axial EPR spectrum split into eight lines by the I = 7/2 139La nucleus (g⊥ = 1.98, g|| = 2.06, Aave = 519.1 G). The UV-visible absorption spectrum contains broad bands centered at 390 and 670 nm that are consistent with a La(II) ion in a trigonal ligand environment based on time-dependent density functional theory which qualitatively reproduces the observed spectrum. Additionally, the rate of formation of the [(C5H4SiMe3)3YII]1- species during the irradiation of (C5H4SiMe3)3YIII was monitored by measuring the concentration via UV-visible spectroscopy over time to provide data on the rate at which a molecular species is reduced in a glass via γ irradiation.

Using Automation, Prioritization, and Collaboration to Manage a COVID-19 Case Surge in Maricopa County, Arizona, 2020.

During summer 2020, the Maricopa County Department of Public Health (MCDPH) responded to a surge in COVID-19 cases. We used internet-based platforms to automate case notifications, prioritized investigation of cases more likely to have onward transmission or severe COVID-19 based on available preinvestigation information, and partnered with Arizona State University (ASU) to scale investigation capacity. We assessed the speed of automated case notifications and accuracy of our investigation prioritization criteria. Timeliness of case notification-the median time between receipt of a case report at MCDPH and first case contact-improved from 11 days to <1 day after implementation of automated case notification. We calculated the sensitivity and positive predictive value (PPV) of the investigation prioritization system by applying our high-risk prioritization criteria separately to data available pre- and postinvestigation to determine whether a case met these criteria preinvestigation, postinvestigation, or both. We calculated the sensitivity as the percentage of cases classified postinvestigation as high risk that had also been classified as high risk preinvestigation. We calculated PPV as the percentage of all cases deemed high risk preinvestigation that remained so postinvestigation. During June 30 to July 31, 2020, a total of 55 056 COVID-19 cases with an associated telephone number (94% of 58 570 total cases) were reported. Preinvestigation, 8799 (16%) cases met high-risk criteria. Postinvestigation, 17 037 (31%) cases met high-risk criteria. Sensitivity was 52% and PPV was 98%. Automating case notifications, prioritizing investigations, and collaborating with ASU improved the timeliness of case contact, focused public health resources toward high-priority cases, and increased investigation capacity. Establishing partnerships between health departments and academia might be a helpful strategy for future surge capacity planning.

Investigation of a Severe Acute Respiratory Syndrome Coronavirus 2 Delta (B.1.617.2) Variant Outbreak Among Residents of a Skilled Nursing Facility and Vaccine Effectiveness Analysis: Maricopa County, Arizona, June-July 2021.

BACKGROUND: Short-term rehabilitation units present unique infection control challenges because of high turnover and medically complex residents. In June 2021, the Maricopa County Department of Public Health was notified of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta outbreak in a skilled nursing facility short-term rehabilitation unit. We describe the outbreak and assess vaccine effectiveness (VE). METHODS: Facility electronic medical records were reviewed for residents who spent > 1 night on the affected unit between June 10 and July 23, 2021, to collect demographics, SARS-CoV-2 test results, underlying medical conditions, vaccination status, and clinical outcomes. Coronavirus disease 2019 VE estimates using Cox proportional hazards models were calculated. RESULTS: Forty (37%) of 109 short-stay rehabilitation unit residents who met inclusion criteria tested positive for SARS-CoV-2. SARS-CoV-2-positive case-patients were mostly male (58%) and White (78%) with a median age of 65 (range, 27-92) years; 11 (27%) were immunocompromised. Of residents, 39% (10 cases, 32 noncases) received 2 doses and 9% (4 cases, 6 noncases) received 1 dose of messenger RNA (mRNA) vaccine. Among nonimmunocompromised residents, adjusted 2-dose primary-series mRNA VE against symptomatic infection was 80% (95% confidence interval, 15-95). More cases were hospitalized (33%) or died (38%) than noncases (10% hospitalized; 16% died). CONCLUSIONS: In this large SARS-CoV-2 Delta outbreak in a high-turnover short-term rehabilitation unit, a low vaccination rate and medically complex resident population were noted alongside severe outcomes. VE of 2-dose primary-series mRNA vaccine against symptomatic infection was the highest in nonimmunocompromised residents. Health departments can use vaccine coverage data to prioritize facilities for assistance in preventing outbreaks.

A 9.2-GHz clock transition in a Lu(II) molecular spin qubit arising from a 3,467-MHz hyperfine interaction.

Spins in molecules are particularly attractive targets for next-generation quantum technologies, enabling chemically programmable qubits and potential for scale-up via self-assembly. Here we report the observation of one of the largest hyperfine interactions for a molecular system, Aiso = 3,467 ± 50 MHz, as well as a very large associated clock transition. This is achieved through chemical control of the degree of s-orbital mixing into the spin-bearing d orbital associated with a series of spin-½ La(II) and Lu(II) complexes. Increased s-orbital character reduces spin-orbit coupling and enhances the electron-nuclear Fermi contact interaction. Both outcomes are advantageous for quantum applications. The former reduces spin-lattice relaxation, and the latter maximizes the hyperfine interaction, which, in turn, generates a 9-GHz clock transition, leading to an increase in phase memory time from 1.0 ± 0.4 to 12 ± 1 µs for one of the Lu(II) complexes. These findings suggest strategies for the development of molecular quantum technologies, akin to trapped ion systems.

Design and Implementation of a COVID-19 Case Investigation Program: An Academic-Public Health Partnership, Arizona, 2020.

From May through July 2020, Arizona was a global hotspot for new COVID-19 cases. In response to the surge of cases, local public health departments looked for innovative ways to form external partnerships to address their staffing needs. In collaboration with the Maricopa County Department of Public Health, the Arizona State University Student Outbreak Response Team (SORT) created and implemented a virtual call center to conduct public health case investigations for COVID-19. SORT officially launched a dedicated COVID-19 case investigation program after 3 weeks of program design and training. From June 29 through November 8, 2020, SORT recruited and trained 218 case investigators, completed 5000 case patient interviews, and closed 10 000 cases. Our team also developed process improvements to address disparities in case investigation timeliness. A strong infrastructure designed to accommodate remote case investigations, paired with a large workforce, enabled SORT to provide additional surge capacity for the county's high volume of cases. University-driven multidisciplinary case investigator teams working in partnership with state, tribal, and local public health staff members can be an effective tool for supporting a diverse and growing public health workforce. We discuss the essential design factors involved in building a university program to complement local COVID-19 response efforts, including workflows for case management, volunteer case investigator recruitment and training, secure technology platforms for conducting case investigations remotely, and robust data-tracking procedures for maintaining quality control and timely case reporting.

Crystallographic characterization of rare-earth cyano-tri-phenyl-borate complexes and the cyano-borates [NCBPh3]1-, [NCBPh2Me]1-, and [NCBPh2(µ-O)BPh2]1.

The investigation of the coordination chemistry of rare-earth metal complexes with cyanide ligands led to the isolation and crystallographic characterization of the Ln III cyano-tri-phenyl-borate complexes di-chlorido-(cyano-tri-phenyl-borato-κN)tetra-kis-(tetra-hydro-furan-κO)lanthanide(III), [LnCl2(C19H15BN)(C4H8O)4] [lanthanide (Ln) = dysprosium (Dy) and yttrium Y)] from reactions of LnCl3, KCN, and NaBPh4. Attempts to independently synthesize the tetra-ethyl-ammonium salt of (NCBPh3)- from BPh3 and [NEt4][CN] in THF yielded crystals of the phenyl-substituted cyclic borate, tetra-ethyl-aza-nium 2,2,4,6-tetra-phenyl-1,3,5,2λ4,4,6-trioxatriborinan-2-ide, C8H20N+·C24H20B3O3 - or [NEt4][B3(µ-O)3(C6H5)4]. The mechanochemical reaction of BPh3 and [NEt4][CN] without solvent produced crystals of tetra-ethyl-aza-nium cyano-diphenyl-λ4-boranyl di-phenyl-borinate, C8H20N+·C25H20B2NO- or [NEt4][NCBPh2(µ-O)BPh2]. Reaction of BPh3 and KCN in THF in the presence of 2.2.2-cryptand (crypt) led to a crystal of bis-[(2.2.2-cryptand)potassium] 2,2,4,6-tetra-phenyl-1,3,5,2λ4,4,6-trioxatriborinan-2-ide cyano-methyl-diphenyl-borate tetra-hydro-furan disolvate, 2C18H36KN2O6 +·C24H20B3O3 -·C14H13BN-·2C4H8O or [K(crypt)]2[B3(µ-O)3(C6H5)4][NCBPh2Me]·2THF. The [NCBPh2(µ-O)BPh2]1- and (NCBPh2Me)1- anions have not been structurally characterized previously. The structure of 1-Y was refined as a two-component twin with occupancy factors 0.513 (1) and 0.487 (1). In 4, one solvent mol-ecule was disordered and included using multiple components with partial site-occupancy factors.

Associations of Total, Cognitive/Affective, and Somatic Depressive Symptoms and Antidepressant Use With Cardiovascular Disease-Relevant Biomarkers in HIV: Veterans Aging Cohort Study.

OBJECTIVE: We sought to determine the associations of total, cognitive/affective, and somatic depressive symptoms and antidepressant use with biomarkers of processes implicated in cardiovascular disease in HIV (HIV-CVD). METHODS: We examined data from 1546 HIV-positive and 843 HIV-negative veterans. Depressive symptoms were assessed using the Patient Health Questionnaire-9, and past-year antidepressant use was determined from Veterans Affair pharmacy records. Monocyte (soluble CD14 [sCD14]), inflammatory (interleukin-6 [IL-6]), and coagulation (D-dimer) marker levels were determined from previously banked blood specimens. Linear regression models with multiple imputation were run to estimate the associations between depression-related factors and CVD-relevant biomarkers. RESULTS: Among HIV-positive participants, greater somatic depressive symptoms were associated with higher sCD14 (exp[b] = 1.02, 95% confidence interval [CI] = 1.00-1.03) and D-dimer (exp[b] = 1.06, 95% CI = 1.00-1.11) after adjustment for demographics and potential confounders. Further adjustment for antidepressant use and HIV factors slightly attenuated these relationships. Associations were also detected for antidepressant use, as selective serotonin reuptake inhibitor use was related to lower sCD14 (exp[b] = 0.95, 95% CI = 0.91-1.00) and IL-6 (exp[b] = 0.86, 95% CI = 0.76-0.96), and tricyclic antidepressant use was related to higher sCD14 (exp[b] = 1.07, 95% CI = 1.03-1.12) and IL-6 (exp[b] = 1.14, 95% CI = 1.02-1.28). Among HIV-negative participants, total, cognitive/affective, and somatic depressive symptoms were associated with higher IL-6, and tricyclic antidepressant use was related to higher sCD14. CONCLUSIONS: Our novel findings suggest that a) monocyte activation and altered coagulation may represent two pathways through which depression increases HIV-CVD risk and that b) tricyclic antidepressants may elevate and selective serotonin reuptake inhibitors may attenuate HIV-CVD risk by influencing monocyte and inflammatory activation.

First Mildly Ill, Nonhospitalized Case of Coronavirus Disease 2019 (COVID-19) Without Viral Transmission in the United States-Maricopa County, Arizona, 2020.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, nonhospitalized COVID-19 case who traveled to China. METHODS: The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive specimens collected on 22 January 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥ 10 minutes within 2 m). Medium-risk contacts wore all US Centers for Disease Control and Prevention-recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. RESULTS: Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥ 1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. CONCLUSIONS: This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.

Human Rabies Postexposure Prophylaxis Knowledge and Retention Among Health Professionals by Using an Online Continuing Education Module: Arizona, 2012 to 2015.

Rabies postexposure prophylaxis (PEP) is administered for rabies prevention after a human exposure to a potentially rabid animal, such as a bite. Previous studies have reported that rabies PEP is often inappropriately administered. Health professional education was proposed as one potential solution to address inappropriate PEP use. We assessed baseline knowledge, knowledge gain, and knowledge retention among health professionals in Arizona of rabies epidemiology and appropriate PEP administration. Maricopa County Department of Public Health created an online rabies PEP continuing education module and measured knowledge before and after module completion using a 10-question test. The same test was administered three times (pretest, posttest, and retention test at ≥3 months). To assess knowledge gain and retention, we compared median scores using nonparametric methods. A total of 302 respondents completed the pretest (median score, 60%) and posttest (median score, 90%; p < .001); 98 respondents completed all three tests with median scores 60% (pretest), 90% (posttest, p < .01), and 80% (retention test and compared with pretest, p < .01). Sixty-nine (70%) respondents improved their pretest to retention test score by a mean of 2.4 points out of a total 10 points (median: 2 points; range: -5 to 7 points). Only 48% of pretest respondents correctly answered that PEP should not be administered immediately to anyone bitten by a healthy dog. However, 81% and 70% answered correctly on the posttest (p < .0001) and retention test (p = .002), respectively. Respondents demonstrated rabies epidemiology and PEP knowledge gain and ≥3-month knowledge retention after completing the online continuing education module.

Prevalence of gabapentin in drug overdose postmortem toxicology testing results.

BACKGROUND: The goal of this study was to establish and compare baseline data on the prevalence of gabapentin identified through postmortem toxicology testing among drug overdose decedents in several geographically diverse states/jurisdictions with differing levels of drug overdose fatality burdens in 2015. METHODS: Death certificates and postmortem toxicology result reports from five U.S. jurisdictions were used to identify residents who died from drug overdoses in year 2015 and to calculate prevalence rates of gabapentin in postmortem toxicology by jurisdiction. RESULTS: On average, 22% of all drug overdose decedents in our study tested positive for gabapentin. The percentage of gabapentin-positive overdose deaths varied significantly among jurisdictions: 4% in Northeast Tennessee, 7% in Maricopa County, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky (p < 0.0001). Among the drug overdose decedents who tested positive for opioids (including heroin), 26% also tested positive for gabapentin, with significant variation among states/jurisdictions (p < 0.0001). There was a significant difference in the gender distribution among drug overdose decedents who tested positive for gabapentin (46% male) vs. those who tested negative for gabapentin (65% male) (p < 0.0001). In Kentucky, gabapentin was listed as a contributing drug on the death certificate in 40% of the overdose deaths with gabapentin-positive toxicology; in North Carolina this percentage was 57%. CONCLUSIONS: Routine gabapentin postmortem testing and linking of death certificate, medical examiner, coroner, toxicology, and prescription history data will provide more reliable information on the extent of gabapentin misuse, diversion, and implications for clinical care.

Evaluation of a Novel Syndromic Surveillance Query for Heat-Related Illness Using Hospital Data From Maricopa County, Arizona, 2015.

OBJECTIVES: We evaluated a novel syndromic surveillance query, developed by the Council of State and Territorial Epidemiologists (CSTE) Heat Syndrome Workgroup, for identifying heat-related illness cases in near real time, using emergency department and inpatient hospital data from Maricopa County, Arizona, in 2015. METHODS: The Maricopa County Department of Public Health applied 2 queries for heat-related illness to area hospital data transmitted to the National Syndromic Surveillance Program BioSense Platform: the BioSense "heat, excessive" query and the novel CSTE query. We reviewed the line lists generated by each query and used the diagnosis code and chief complaint text fields to find probable cases of heat-related illness. For each query, we calculated positive predictive values (PPVs) for heat-related illness. RESULTS: The CSTE query identified 674 records, of which 591 were categorized as probable heat-related illness, demonstrating a PPV of 88% for heat-related illness. The BioSense query identified 791 patient records, of which 589 were probable heat-related illness, demonstrating a PPV of 74% for heat-related illness. The PPV was substantially higher for the CSTE novel and BioSense queries during the heat season (May 1 to September 30; 92% and 85%, respectively) than during the cooler seasons (55% and 29%, respectively). CONCLUSION: A novel query for heat-related illness that combined diagnosis codes, chief complaint text terms, and exclusion criteria had a high PPV for heat-related illness, particularly during the heat season. Public health departments can use this query to meet local needs; however, use of this novel query to substantially improve public health heat-related illness prevention remains to be seen.

Paneth-cell-disruption-induced necrotizing enterocolitis in mice requires live bacteria and occurs independently of TLR4 signaling.

Necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality in premature infants. Both human surgical specimens and animal models suggest a potential involvement of Paneth cells in NEC pathogenesis. Paneth cells play critical roles in epithelial homeostasis, innate immunity and host-microbial interactions. Yet, the complex interplay between Paneth cell disruption, epithelial barrier dysfunction and microbial-driven inflammation remains unclear in the immature intestine. In this study, mucosal intestinal injury consistent with human NEC was induced in postnatal day 14-16 (P14-P16) mice by disrupting Paneth cells, followed by gavage with Klebsiella pneumonia. Mucosal injury was determined by histology, serum cytokine levels and epithelial barrier dysfunction. Toll-like receptor 4 (TLR4) activation was examined using protein expression, gene expression, and TLR4-/- mice. Finally, the role of bacteria was evaluated using heat-killed bacteria, conditioned media, Bacillus cereus and cecal slurries. We found that live bacteria were required to induce injury; however, TLR4 activation was not required. NEC induced by Paneth cell disruption results in altered localization of tight junction proteins and subsequent loss of barrier function. Prior research has shown a requirement for TLR4 activation to induce NEC-like damage. However, many infants develop NEC in the absence of Gram-negative rod bacteremia, raising the possibility that alternative pathways to intestinal injury exist. In this study, we show a previously unknown mechanism for the development of intestinal injury equivalent to that seen in human NEC and that is not dependent on TLR4 pathways. These data are congruent with the new hypothesis that NEC may be the consequence of several disease processes ending in a final common inflammatory pathway.

Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development.

Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A2-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent "first hit", rendering IUGR intestine susceptible to further injury, infection, or inflammation.

Evaluation of hematologic variables in newborn C57/BL6 mice up to day 35.

BACKGROUND: Hematologic variables are often analyzed in animal analogs during the investigation of complex disease etiologies such as necrotizing enterocolitis. However, reference intervals (RI) can vary depending on animal strain, age, and sampling site. Reference intervals have been published for adult C57BL/6J mice, but not newborn C57BL/6J mice. OBJECTIVES: The purpose of the present study was to determine hematologic RI in newborn C57BL/6J mice up to day 35. METHODS: C57BL/6J mice founders from The Jackson Laboratory were bred at the University of Iowa. Blood samples were obtained via facial vein sampling at postnatal days 0 (p0), p7, p14, p21, p28, or young adulthood (p35). CBCs were determined with the Sysmex XT-2000iV analyzer within 30 minutes of blood collection at a 1:10 dilution. Statistics were determined using nonparametric methods following ASVCP guidelines. RESULTS: Hematologic RI were determined for each of the 6 groups (n = 247, n ≥ 39 per group). Significantly higher values for HGB, RBC, and PLT counts were observed with advancing developmental age. Total WBC counts remained relatively stable during the first 35 days of life. However, WBC differential counts were dominated by neutrophils and lymphocytes in the younger mice, with a trend toward a lymphocytic leukogram on day 35. CONCLUSIONS: These results illustrate the dynamic changes in hematologic variables during murine development after birth. Utilization of age-specific RI is advised when evaluating data derived from experimental perinatal mouse models.

Depression and human immunodeficiency virus infection are risk factors for incident heart failure among veterans: Veterans Aging Cohort Study.

BACKGROUND: Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF. METHODS AND RESULTS: Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99). CONCLUSIONS: Our study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.