The effect of disease misclassification on the ability to detect a gene-environment interaction: implications of the specificity of case definitions for research on Gulf War illness.

BACKGROUND: Since 1997, research on Gulf War illness (GWI) has predominantly used 3 case definitions-the original Research definition, the CDC definition, and modifications of the Kansas definition-but they have not been compared against an objective standard. METHODS: All 3 case definitions were measured in the U.S. Military Health Survey by a computer-assisted telephone interview in a random sample (n = 6,497) of the 1991 deployed U.S. military force. The interview asked whether participants had heard nerve agent alarms during the conflict. A random subsample (n = 1,698) provided DNA for genotyping the PON1 Q192R polymorphism. RESULTS: The CDC and the Modified Kansas definition without exclusions were satisfied by 41.7% and 39.0% of the deployed force, respectively, and were highly overlapping. The Research definition, a subset of the others, was satisfied by 13.6%. The majority of veterans meeting CDC and Modified Kansas endorsed fewer and milder symptoms; whereas, those meeting Research endorsed more symptoms of greater severity. The group meeting Research was more highly enriched with the PON1 192R risk allele than those meeting CDC and Modified Kansas, and Research had twice the power to detect the previously described gene-environment interaction between hearing alarms and RR homozygosity (adjusted relative excess risk due to interaction [aRERI] = 7.69; 95% CI 2.71-19.13) than CDC (aRERI = 2.92; 95% CI 0.96-6.38) or Modified Kansas without exclusions (aRERI = 3.84; 95% CI 1.30-8.52) or with exclusions (aRERI = 3.42; 95% CI 1.20-7.56). The lower power of CDC and Modified Kansas relative to Research was due to greater false-positive disease misclassification from lower diagnostic specificity. CONCLUSIONS: The original Research case definition had greater statistical power to detect a genetic predisposition to GWI. Its greater specificity favors its use in hypothesis-driven research; whereas, the greater sensitivity of the others favor their use in clinical screening for application of future diagnostic biomarkers and clinical care.

Changes in Epidemiology of Acetaminophen Overdoses in an Urban County Hospital After 20 Years.

INTRODUCTION: Acetaminophen (APAP) toxicity is the main cause of acute liver failure in the United States. A prior series (1992-1995) identified 71 hospitalized adults with APAP toxicity through the International Statistical Classification of Disease and Related Health Problems, 9th revision (ICD-9) code at Parkland Hospital, Dallas, TX. METHODS: We used a laboratory database search of serum APAP levels from 2011 to 2015 to identify patients with APAP toxicity in the same hospital. RESULTS: We identified 140 patients hospitalized for APAP toxicity from 27,143 APAP levels obtained; 35 required Intensive Care Unit (ICU) admission, and there were no deaths. APAP toxicity/100,000 admissions was similar between eras. DISCUSSION: APAP toxicity continues unabated after 20 years but with improved overall outcomes.

Evaluation of a Gene-Environment Interaction of PON1 and Low-Level Nerve Agent Exposure with Gulf War Illness: A Prevalence Case-Control Study Drawn from the U.S. Military Health Survey's National Population Sample.

BACKGROUND: Consensus on the etiology of 1991 Gulf War illness (GWI) has been limited by lack of objective individual-level environmental exposure information and assumed recall bias. OBJECTIVES: We investigated a prestated hypothesis of the association of GWI with a gene-environment (GxE) interaction of the paraoxonase-1 (PON1) Q192R polymorphism and low-level nerve agent exposure. METHODS: A prevalence sample of 508 GWI cases and 508 nonpaired controls was drawn from the 8,020 participants in the U.S. Military Health Survey, a representative sample survey of military veterans who served during the Gulf War. The PON1 Q192R genotype was measured by real-time polymerase chain reaction (RT-PCR), and the serum Q and R isoenzyme activity levels were measured with PON1-specific substrates. Low-level nerve agent exposure was estimated by survey questions on having heard nerve agent alarms during deployment. RESULTS: The GxE interaction of the Q192R genotype and hearing alarms was strongly associated with GWI on both the multiplicative [prevalence odds ratio (POR) of the interaction=3.41; 95% confidence interval (CI): 1.20, 9.72] and additive (synergy index=4.71; 95% CI: 1.82, 12.19) scales, adjusted for measured confounders. The Q192R genotype and the alarms variable were independent (adjusted POR in the controls=1.18; 95% CI: 0.81, 1.73; p=0.35), and the associations of GWI with the number of R alleles and quartiles of Q isoenzyme were monotonic. The adjusted relative excess risk due to interaction (aRERI) was 7.69 (95% CI: 2.71, 19.13). Substituting Q isoenzyme activity for the genotype in the analyses corroborated the findings. Sensitivity analyses suggested that recall bias had forced the estimate of the GxE interaction toward the null and that unmeasured confounding is unlikely to account for the findings. We found a GxE interaction involving the Q-correlated PON1 diazoxonase activity and a weak possible GxE involving the Khamisiyah plume model, but none involving the PON1 R isoenzyme activity, arylesterase activity, paraoxonase activity, butyrylcholinesterase genotypes or enzyme activity, or pyridostigmine. DISCUSSION: Given gene-environment independence and monotonicity, the unconfounded aRERI>0 supports a mechanistic interaction. Together with the direct evidence of exposure to fallout from bombing of chemical weapon storage facilities and the extensive toxicologic evidence of biochemical protection from organophosphates by the Q isoenzyme, the findings provide strong evidence for an etiologic role of low-level nerve agent in GWI. https://doi.org/10.1289/EHP9009.

Pathophysiology and Molecular Imaging of Diabetic Foot Infections.

Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing in prevalence. In 2017, 9.4% of Americans were diagnosed with diabetes mellitus (DM). The growing pervasiveness and financial implications of diabetic foot infection (DFI) indicate an acute need for improved clinical assessment and treatment. Complex pathophysiology and suboptimal specificity of current non-invasive imaging modalities have made diagnosis and treatment response challenging. Current anatomical and molecular clinical imaging strategies have mainly targeted the host's immune responses rather than the unique metabolism of the invading microorganism. Advances in imaging have the potential to reduce the impact of these problems and improve the assessment of DFI, particularly in distinguishing infection of soft tissue alone from osteomyelitis (OM). This review presents a summary of the known pathophysiology of DFI, the molecular basis of current and emerging diagnostic imaging techniques, and the mechanistic links of these imaging techniques to the pathophysiology of diabetic foot infections.

Results and lessons from a hospital-wide initiative incentivised by delivery system reform to improve infection prevention and sepsis care.

BACKGROUND: An academic safety-net hospital leveraged the federally funded state Delivery System Reform Incentive Payment programme to implement a hospital-wide initiative to reduce healthcare-associated infections (HAIs) and improve sepsis care. METHODS: The study period was from 2013 to 2017. The setting is a 770-bed urban hospital with six intensive care units and a large emergency department. Key interventions implemented were (1) awareness campaign and clinician engagement, (2) implementation of HAI and sepsis bundles, (3) education of clinical personnel using standardised curriculum on bundles, (4) training of key managers, leaders and personnel in quality improvement methods, and (5) electronic medical record-based clinical decision support. Throughout the 5-year period, staff received frequent, clear, visible and consistent messages from leadership regarding the importance of their participation in this initiative, performing hand hygiene and preventing potential regulatory failures. Several process measures including bundle compliance, hand hygiene and culture of safety were monitored. The primary outcomes were rates of central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), surgical site infection (SSI) and sepsis mortality. RESULTS: From 2013 to 2017, the hospital-wide rates of HAI reduced: CLABSI from 1.6 to 0.8 per 1000 catheter-days (Poisson regression estimate: -0.19; 95% CI -0.29 to -0.09; p=0.0002), CAUTI from 4.7 to 1.3 per 1000 catheter-days (-0.34; -0.43 to -0.26; p<0.0001) and SSI after 18 types of procedures from 3.4% to 1.3% (-0.29; -0.34 to -0.24; p<0.0001). Mortality of patients presenting to emergency department with sepsis reduced from 9.4% to 2.9% (-0.42; -0.49 to -0.36; p<0.0001). Adherence to bundles of care and hand hygiene and the hospital culture of patient safety improved. Results were sustained through 2019. CONCLUSION: A hospital-wide initiative incentivised by the Delivery System Reform Incentive Payment programme succeeded in reducing HAI and sepsis mortality over 5 years in a sustainable manner.

Resolving whether inhalation of depleted uranium contributed to Gulf War Illness using high-sensitivity mass spectrometry.

Of the hypothesized causes of Gulf War Illness (GWI), a chronic multi-symptom illness afflicting approximately 25% of military personnel deployed to the 1991 Gulf War, exposure to depleted uranium (DU) munitions has attracted international concern. Past research has not tested the potential association of GWI with inhaled DU nor used isotope mass spectrometry of sufficient sensitivity to rigorously assess prior DU exposure. We applied a standard biokinetic model to predict the urinary concentration and uranium isotopic ratios for a range of inhalation exposures. We then applied sensitive mass spectrometry capable of detecting the predicted urinary DU to 154 individuals of a population-representative sample of U.S. veterans in whom GWI had been determined by standard case definitions and DU inhalation exposures obtained by medical history. We found no difference in the 238U/235U ratio in veterans meeting the standard case definitions of GWI versus control veterans, no differences by levels of DU inhalation exposure, and no 236U associated with DU was detected. These findings show that even the highest likely levels of DU inhalation played no role in the development of GWI, leaving exposure to aerosolized organophosphate compounds (pesticides and sarin nerve agent) as the most likely cause(s) of GWI.

Epidemiology and risk factors for varicella zoster virus reactivation in heart transplant recipients.

Heart transplant (HT) recipients are at higher risk of varicella zoster virus (VZV) reactivation. Risk factors for VZV reactivation are currently not well defined, impeding the ability to design and implement strategies to minimize the burden of this illness in this population. Automated data extraction tools were used to retrieve data from the electronic health record (EHR) of all adult HT recipients at our center between 2010 and 2016. Information from the Organ Procurement and Transplantation Network Standard Analysis and Research Files was merged with the extracted data. Potential cases were manually reviewed and adjudicated using consensus definitions. Cumulative incidence and risk factors for VZV reactivation in HT recipients were assessed by the Kaplan-Meier method and Cox modeling, respectively. In 203 HT recipients, the cumulative incidence of VZV reactivation at 8-years post-transplantation was 26.4% (95% CI: 17.8-38.0). The median time to VZV reactivation was 2.1 years (IQR, 1.5-4.1). Half (14/28) of the cases experienced post-herpetic neuralgia (PHN). Post-transplant CMV infection (HR 9.05 [95% CI: 3.76-21.77) and post-transplant pulse-dose steroids (HR 3.19 [95% CI: 1.05-9.68]) were independently associated with a higher risk of VZV reactivation in multivariable modeling. Identification of risk factors will aid in the development of targeted preventive strategies.

The use of automated data extraction tools to develop a solid organ transplant registry: Proof of concept study of bloodstream infections.

BACKGROUND: We created an electronic health record-based registry using automated data extraction tools to study the epidemiology of bloodstream infections (BSI) in solid organ transplant recipients. The overarching goal was to determine the usefulness of an electronic health record-based registry using data extraction tools for clinical research in solid organ transplantation. METHODS: We performed a retrospective single-center cohort study of adult solid organ transplant recipients from 2010 to 2015. Extraction tools were used to retrieve data from the electronic health record, which was integrated with national data sources. Electronic health records of subjects with positive blood cultures were manually adjudicated using consensus definitions. One-year cumulative incidence, risk factors for BSI acquisition, and 1-year mortality were analyzed by Kaplan-Meier method and Cox modeling, and 30-day mortality with logistic regression. RESULTS: In 917 solid organ transplant recipients the cumulative incidence of BSI was 8.4% (95% confidence interval 6.8-10.4) with central line-associated BSI as the most common source. The proportion of multidrug-resistant isolates increased from 0% in 2010 to 47% in 2015 (p = 0.03). BSI was the strongest risk factor for 1-year mortality (HR=8.44; 4.99-14.27; p<0.001). In 11 of 14 deaths, BSI was the main cause or contributory in patients with non-rapidly fatal underlying conditions. CONCLUSIONS: Our study illustrates the usefulness of an electronic health record-based registry using automated extraction tools for clinical research in the field of solid organ transplantation. A BSI reduces the 1-year survival of solid organ transplant recipients. The most common sources of BSIs in our studies are preventable.

Superiority of Out-of-Office Blood Pressure for Predicting Hypertensive Heart Disease in Non-Hispanic Black Adults.

Black Americans suffer disproportionately from hypertension and hypertensive heart disease. Out-of-office blood pressure (BP) is more predictive for cardiovascular complications than clinic BP; however, the relative abilities of clinic and out-of-office BP to predict left ventricular hypertrophy in black and white adults have not been established. Thus, we aimed to compare associations of out-of-office and clinic BP measurement with left ventricular hypertrophy by cardiac magnetic resonance imaging among non-Hispanic black and white adults. In this cross-sectional study, 1262 black and 927 white participants of the Dallas Heart Study ages 30 to 64 years underwent assessment of standardized clinic and out-of-office (research staff-obtained) BP and left ventricular mass index. In multivariable-adjusted analyses of treated and untreated participants, out-of-office BP was a stronger determinant of left ventricular hypertrophy than clinic BP (odds ratio per 10 mm Hg, 1.48; 95% CI, 1.34-1.64 for out-of-office systolic BP and 1.15 [1.04-1.28] for clinic systolic BP; 1.71 [1.43-2.05] for out-of-office diastolic BP, and 1.03 [0.86-1.24] for clinic diastolic BP). Non-Hispanic black race/ethnicity, treatment status, and lower left ventricular ejection fraction were also independent determinants of hypertrophy. Among treated Blacks, the differential association between out-of-office and clinic BP with hypertrophy was more pronounced than in treated white or untreated participants. In conclusion, protocol-driven supervised out-of-office BP monitoring provides important information that cannot be gleaned from clinic BP assessment alone. Our results underscore the importance of hypertension management programs outside the medical office to prevent hypertensive heart disease, especially in high-risk black adults. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00344903.

Exploring brain mechanisms underlying Gulf War Illness with group ICA based analysis of fMRI resting state networks.

Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW illness (GWI), which is characterized by multiple deficits in cognitive, affective, sensory and nociception domains. In this study we employed resting state fMRI (rsfMRI) to map impairments in brain function in GWI with advanced network analysis. RsfMRI data was obtained from 60 GWI veterans and 30 age-matched military controls. Group independent component analysis (GICA) was conducted to probe the functional connectivity networks in all 90 subjects. GICA revealed impaired functional connectivity (FC) in GWI veterans between a number of brain function networks consistent with their self-reported symptoms. GWI veterans exhibited impaired FC between language networks, and sensory input networks of all modalities as well as motor output networks. GWI veterans also exhibited impaired FC between different sensory perception and motor networks, and between different networks in the sensorimotor domain. These FC impairments provide putative mechanism of central nervous system dysfunction in GWI.

Gulf War illness associated with abnormal auditory P1 event-related potential: Evidence of impaired cholinergic processing replicated in a national sample.

Our team previously reported event-related potential (ERP) and hyperarousal patterns from a study of one construction battalion of the U.S. Naval Reserve who served during the 1991 Persian Gulf War. We sought to replicate these findings in a sample that was more representative of the entire Gulf War-era veteran population, including male and female participants from four branches of the military. We collected ERP data from 40 veterans meeting Haley criteria for Gulf War syndromes 1-3 and from 22 matched Gulf War veteran controls while they performed an auditory oddball task. Reports of hyperarousal from the ill veterans were significantly greater than those from the control veterans, and P1 amplitudes in Syndromes 2 and 3 were significantly higher than P1 amplitudes in Syndrome 1, replicating our previous findings. Many of the contributors to the generation of the P1 potential are also involved in the regulation of arousal and are modulated by cholinergic and dopaminergic systems-two systems whose dysfunction has been implicated in Gulf War illness. These differences among the three syndrome groups where their means were on either side of controls is a replication of our previous ERP study and is consistent with previous imaging studies of this population.

Identification of biologically active δ-lactone eicosanoids as paraoxonase substrates.

The mammalian paraoxonases (PONs 1, 2 and 3) are a family of esterases that are highly conserved within and between species. They exhibit antioxidant and anti-inflammatory activities. However, their physiological function(s) and native substrates are uncertain. Previous structure-activity relationship studies demonstrate that PONs have a high specificity for lipophilic lactones, suggesting that such compounds may be representative of native substrates. This report describes the ability of PONs to hydrolyze two bioactive δ-lactones derived from arachidonic acid, 5,6-dihydroxy-eicosatrienoic acid lactone (5,6-DHTL) and cyclo-epoxycyclopentenone (cyclo-EC). Both lactones were very efficiently hydrolyzed by purified PON3. PON1 efficiently hydrolyzed 5,6-DHTL, but with a specific activity about 15-fold lower than PON3. 5,6-DHTL was a poor substrate for PON2. Cyclo-EC was a poor substrate for PON1 and not hydrolyzed by PON2. Studies with the PON inhibitor EDTA and a serine esterase inhibitor indicated that the PONs are the main contributors to hydrolysis of the lactones in human and mouse liver homogenates. Studies with homogenates from PON3 knockout mouse livers indicated that >80% of the 5,6-DHTL and cyclo-EC lactonase activities were attributed to PON3. The findings provide further insight into the structural requirements for PONs substrates and support the hypothesis that PONs, particularly PON1 and PON3, evolved to hydrolyze and regulate a class of lactone lipid mediators derived from polyunsaturated fatty acids.

Estimating the Health and Economic Impacts of Changes in Local Air Quality.

OBJECTIVES: To demonstrate the benefits-mapping software Environmental Benefits Mapping and Analysis Program-Community Edition (BenMAP-CE), which integrates local air quality data with previously published concentration-response and health-economic valuation functions to estimate the health effects of changes in air pollution levels and their economic consequences. METHODS: We illustrate a local health impact assessment of ozone changes in the 10-county nonattainment area of the Dallas-Fort Worth region of Texas, estimating the short-term effects on mortality predicted by 2 scenarios for 3 years (2008, 2011, and 2013): an incremental rollback of the daily 8-hour maximum ozone levels of all area monitors by 10 parts per billion and a rollback-to-a-standard ambient level of 65 parts per billion at only monitors above that level. RESULTS: Estimates of preventable premature deaths attributable to ozone air pollution obtained by the incremental rollback method varied little by year, whereas those obtained by the rollback-to-a-standard method varied by year and were sensitive to the choice of ordinality and the use of preloaded or imported data. CONCLUSIONS: BenMAP-CE allows local and regional public health analysts to generate timely, evidence-based estimates of the health impacts and economic consequences of potential policy options in their communities.

Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study.

BACKGROUND AND AIMS: Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. METHODS: Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. RESULTS: Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12-2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27-2.85). CONCLUSIONS: Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.

Electrophysiological correlates of semantic memory retrieval in Gulf War Syndrome 2 patients.

Gulf War veterans meeting criteria for Haley Syndrome 2 of Gulf War illness endorse a particular constellation of symptoms that include difficulty with processing information, word-finding, and confusion. To explore the neural basis of their word-finding difficulty, we assessed event-related potentials (ERPs) associated with semantic memory retrieval in 22 veterans classified as Syndrome 2 and 28 veterans who served as controls. We recorded EEGs while subjects judged whether pairs of words that represented object features combined to elicit a retrieval of an object memory or no retrieval. Syndrome 2 subjects' responses were significantly slower, and those participants were less accurate than controls on the retrieval trials, but they performed similarly on the nonretrieval trials. Analysis of the ERPs revealed a difference between retrievals and nonretrievals that has previously been detected around 750ms at the left temporal region was present in both the Syndrome 2 patients and controls. However, the Syndrome 2 patients also showed an ERP difference between retrievals and nonretrievals at the midline parietal region that had a scalp voltage polarity opposite from that recorded at the left temporal area. We hypothesize that the similarities between task performance and ERP patterns in Syndrome 2 veterans and in patients with amnestic mild cognitive impairment reflect disordered thalamic cholinergic neural activity, possibly in the dorsomedial nucleus.

Cognitive Slowing in Gulf War Illness Predicts Executive Network Hyperconnectivity: Study in a Population-Representative Sample.

Cognitive slowing is a prevalent symptom observed in Gulf War Illness (GWI). The present study assessed the extent to which functional connectivity between dorsolateral prefrontal cortex (DLPFC) and other task-relevant brain regions was predictive of GWI-related cognitive slowing. GWI patients (n = 54) and healthy veteran controls (n = 29) were assessed on performance of a processing speed task (the Digit Symbol Substitution Task; DSST) while undergoing functional magnetic resonance imaging (fMRI). GWI patients were slower on the DSST relative to controls. Bilateral DLPFC connectivity with task-relevant nodes was altered in GWI patients compared to healthy controls during DSST performance. Moreover, hyperconnectivity in these networks predicted GWI-related increases in reaction time on the DSST, whereas hypoconnectivity did not. These results suggest that GWI-related cognitive slowing reflects reduced efficiency in cortical networks.

Memory and functional brain differences in a national sample of U.S. veterans with Gulf War Illness.

Roughly 26-32% of U. S. veterans who served in the 1991 Persian Gulf War report suffering from chronic health problems. Memory complaints are regularly reported by ill Gulf War veterans (GWV), but limited data verify their complaints. This study investigated episodic memory and brain function in a nationally representative sample of GWV, using a face-name memory task and functional magnetic resonance imaging during encoding. A syndrome classification system was used to subdivide ill GWV into the three major Gulf War Illness syndrome types, "impaired cognition" (GWV-1), "confusion ataxia" (GWV-2), and "central pain" (GWV-3). Memory and brain function of ill GWV were contrasted to deployed and nondeployed well GWV controls (GWV-C). Ill GWV exhibited impaired memory function relative to GWV-C but the patterns of functional brain differences varied. Brain activation differentiated the GWV-C from the ill GWV. The different syndrome types also differed from one another in several brain regions. Additionally, the current study was the first to observe differences in brain function between deployed and nondeployed GWV-C. These results provide (1) evidence of memory impairment in ill GWV and differentiate the syndrome types at a functional neurobiological level, and (2) the role of deployment in the war on brain function.

Self-Administered Outpatient Antimicrobial Infusion by Uninsured Patients Discharged from a Safety-Net Hospital: A Propensity-Score-Balanced Retrospective Cohort Study.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) is accepted as safe and effective for medically stable patients to complete intravenous (IV) antibiotics in an outpatient setting. Since, however, uninsured patients in the United States generally cannot afford OPAT, safety-net hospitals are often burdened with long hospitalizations purely to infuse antibiotics, occupying beds that could be used for patients requiring more intensive services. OPAT is generally delivered in one of four settings: infusion centers, nursing homes, at home with skilled nursing assistance, or at home with self-administered therapy. The first three-termed healthcare-administered OPAT (H-OPAT)--are most commonly used in the United States by patients with insurance funding. The fourth--self-administered OPAT (S-OPAT)--is relatively uncommon, with the few published studies having been conducted in the United Kingdom. With multidisciplinary planning, we established an S-OPAT clinic in 2009 to shift care of selected uninsured patients safely to self-administration of their IV antibiotics at home. We undertook this study to determine whether the low-income mostly non-English-speaking patients in our S-OPAT program could administer their own IV antimicrobials at home with outcomes as good as, or better than, those receiving H-OPAT. METHODS AND FINDINGS: Parkland Hospital is a safety-net hospital serving Dallas County, Texas. From 1 January 2009 to 14 October 2013, all uninsured patients meeting criteria were enrolled in S-OPAT, while insured patients were discharged to H-OPAT settings. The S-OPAT patients were trained through multilingual instruction to self-administer IV antimicrobials by gravity, tested for competency before discharge, and thereafter followed at designated intervals in the S-OPAT outpatient clinic for IV access care, laboratory monitoring, and physician follow-up. The primary outcome was 30-d all-cause readmission, and the secondary outcome was 1-y all-cause mortality. The study was adequately powered for readmission but not for mortality. Clinical, sociodemographic, and outcome data were collected from the Parkland Hospital electronic medical records and the US census, constituting a historical prospective cohort study. We used multivariable logistic regression to develop a propensity score predicting S-OPAT versus H-OPAT group membership from covariates. We then estimated the effect of S-OPAT versus H-OPAT on the two outcomes using multivariable proportional hazards regression, controlling for selection bias and confounding with the propensity score and covariates. Of the 1,168 patients discharged to receive OPAT, 944 (81%) were managed in the S-OPAT program and 224 (19%) by H-OPAT services. In multivariable proportional hazards regression models controlling for confounding and selection bias, the 30-d readmission rate was 47% lower in the S-OPAT group (adjusted hazard ratio [aHR], 0.53; 95% CI 0.35-0.81; p = 0.003), and the 1-y mortality rate did not differ significantly between the groups (aHR, 0.86; 95% CI 0.37-2.00; p = 0.73). The S-OPAT program shifted a median 26 d of inpatient infusion per patient to the outpatient setting, avoiding 27,666 inpatient days. The main limitation of this observational study-the potential bias from the difference in healthcare funding status of the groups-was addressed by propensity score modeling. CONCLUSIONS: S-OPAT was associated with similar or better clinical outcomes than H-OPAT. S-OPAT may be an acceptable model of treatment for uninsured, medically stable patients to complete extended courses of IV antimicrobials at home.

New-Onset Myocarditis in an Immunocompetent Adult with Acute Metapneumovirus Infection.

Introduction. A number of viruses have been implicated in viral myocarditis; however, there has been no previous report of human metapneumovirus (hMPV) causing this condition. Discovered in 2001, hMPV is typically associated with upper respiratory illness, mainly affecting children. Case Presentation. We report the case of a 25-year-old man with acute systolic heart failure from viral myocarditis secondary to the hMPV. The patient was initially admitted to the general medical ward but developed increasing oxygen requirements resulting in transfer to the cardiac intensive care unit. Cardiac magnetic resonance imaging was used to help confirm the diagnosis. He was treated with intravenous diuretics, and afterload and preload agents, and he was subsequently discharged home after seven days of hospitalization. Discussion. hMPV is typically a respiratory pathogen; however, it was associated with in myocarditis in our patient. Due to the recent ability to detect this virus, we may see more cases of this, particularly during peak months of infection. Conclusion. This is the first case description of myocarditis associated with hMPV infection.