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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.

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.

In his letter Curtis (1) raises an important consideration: Because the paraoxonase-1 (PONI) Q192R genotype has long been known to vary across racial/ethnic groups, (2) the gene-environment (G X E) [...]

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, Introduction In the 1991 Persian Gulf War, approximately 700,000 U.S. military personnel and 300,000 people from 41 Coalition countries were deployed to the Kuwaiti Theater of Operations (KTO) for a [...]

Gulf War Illness is associated with toxic exposure to cholinergic disruptive chemicals. The cholinergic system has been shown to mediate the central executive of working memory (WM). The current work proposes that impairment of the cholinergic system in Gulf War Illness patients (GWIPs) leads to behavioral and neural deficits of the central executive of WM. A large sample of GWIPs and matched controls (MCs) underwent functional magnetic resonance imaging during a varied-load working memory task. Compared to MCs, GWIPs showed a greater decline in performance as WM-demand increased. Functional imaging suggested that GWIPs evinced separate processing strategies, deferring prefrontal cortex activity from encoding to retrieval for high demand conditions. Greater activity during high-demand encoding predicted greater WM performance. Behavioral data suggest that WM executive strategies are impaired in GWIPs. Functional data further support this hypothesis and suggest that GWIPs utilize less effective strategies during high-demand WM.

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 SOPAT outpatient clinic for IV access care, laboratory monitoring, and physician follow-up. OPEN ACCESS Academic Editor: David Stuckler, University of Oxford, UNITED KINGDOM Received: May 8, 2015 Accepted: November 6, 2015 Published: December 15,2015 Data Availability Statement: Since the database is composed of electronic medical records data with which statistical identification of individual patients would be difficult to prevent, it can be shared with researchers who meet the criteria for access to confidential data and only with the approval of the UT Southwestern Medical Center's institutional review board (IRB@utsouthwestern.edu). Funding: The authors received no specific funding for this work. Competing Interests: The authors have declared that no competing interests exist. Abbreviations: aHR, adjusted hazard ratio; H-OPAT, healthcare-administered outpatient parenteral antimicrobial therapy; IV, intravenous; OPAT, outpatient parenteral antimicrobial therapy; S-OPAT, self-administered outpatient parenteral antimicrobial therapy. 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 SOPAT 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 SOPAT 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., Introduction A substantial source of hospital costs is the long-term administration of antimicrobial agents to patients with serious or life-threatening infections, such as osteomyelitis, endocarditis, and staphylococcal bacteremia [1-3]. A [...]

Chemical exposures may explain symptoms reported by Gulf War veterans. A group of 249 Gulf War veterans reported symptoms and wartime chemical exposures. Veterans with impaired reasoning and learning were 8.7 times more likely to report wearing flea collars. Veterans with confusion and incoordination were 7.8 times more likely to believe they had been exposed to chemical weapons and 4.3 times more likely to report being in northeastern Saudi Arabia on the same day. Veterans with joint and muscle aches and abnormal sensation were more likely to report exposure to 75% DEET insect repellant. Exposure effects were additive., Objective.--To identify risk factore of factor analysis-derived Gulf War-related syndromes. Design.--A cross-sectional survey. Participants.--A total of 249 Gulf War veterans from the Twenty-fourth Reserve Naval Mobile Construction Battalion. Data Collection.--Participants completed standardized booklets measuring self-reported wartime exposures and present symptoms. Main Outcome Measures.--Associations of factor analysis-derived syndromes with risk factors for chemical interactions that inhibit butyrylcholinesterase and neuropathy target esterase. Results.--Risk of syndrome 1 ("impaired cognition") was greater in veterans who reported wearing flea collate during the war (5 of 20, 25%) than in those who never wore them (7 of 229, 3%; relative risk [RR], 8.7; 95% confidence interval [CI], 3.0-24.7; P Conclusion.--Some Gulf War veterans may have delayed, chronic neurotoxic syndromes from wartime exposure to combinations of chemicals that inhibit butyrylcholinesterase and neuropathy target esterase. JAMA. 1997;277:231-237

Gulf War veterans experiencing Gulf War-related illnesses may have neurologic injuries. Twenty-three affected veterans, 10 healthy veterans who were deployed, and 10 healthy non-deployed veterans in the same battalion, matched for age, sex, and education, underwent tests of neurologic and psychologic functioning. Testers did not know which veterans were health from those with complaints. The affected veterans had more abnormal scores compared with healthy veterans, although their scores generally fell within normal limits. Results are compatible with exposure to nervous-system damaging chemicals., Objective.--To determine whether Gulf War-related illnesses are associated with central or peripheral nervous system dysfunction. Design.--Nested case-control study. Participants.--Twenty-three veterans with factor analysis-derived syndromes (the cases), 10 well veterans deployed to the Gulf War (the deployed controls), and 10 well veterans not deployed to the Gulf War (the nondeployed controls). Method.--With investigators blinded to group identities, participants underwent objective neurophysiological, audiovestibular, neuroradiological, neuropsychologicai, and blood tests. Main Outcome Measures.--Evidence of neurologic dysfunction. Results.--Compared with the 20 controls, the 23 cases had significantly more neuropsychological evidence of brain dysfunction on the Halstead Impairment Index (P=.01), greater interside asymmetry of the wave I to wave III interpeak latency of brain stem auditory evoked potentials (P=.02), greater interocular asymmetry of nystagmic velocity on rotational testing, increased asymmetry of saccadic velocity (P=.04), more prolonged interpeak latency of the lumbar-to-cerebral peaks on posterior tibial somatosensory evoked potentials (on right side, P=.03, and on the left side, P=.005), and diminished nystagmic velocity after caloric stimulation bilaterally (P values range from .02 to .04). Cases (n=5) with syndrome 1 ("impaired cognition") were the most impaired on brain stem auditory evoked potentials (P=.005); those (n=13) with syndrome 2 ("confusion-ataxia") were the most impaired on the Halstead Impairment Index (P=.006), rotational testing (P=.01), asymmetry of saccadic velocity (P=.03), and somatosensory evoked potentials (P[Less than or equal to].01); and those (n=5) with syndrome 3 ("arthro-myo-neuropathy") were the most impaired on caloric stimulation (P[Less than or equal to].01). Conclusions.--The 3 factor-derived syndromes identified among Gulf War veterans appear to represent variants of a generalized injury to the nervous system. JAMA. 1997;277:223-230

Gulf War veterans reporting health problems since the war may have experienced nerve injury. Researchers compared and analyzed symptom reports from 175 Gulf War veterans reporting health problems and 74 veterans reporting no health problems. Analysis revealed that symptoms fell into three primary groups, or syndromes: problems with attention, memory, reasoning, and depression; problems with thinking, disorientation, balance, dizziness, and impotence; problems with joint and muscle pain and weakness and abnormal sensations. Psychological testing revealed no evidence of posttraumatic stress disorder, depression, hypochondria, or malingering., Objective.--To search for syndromes in Persian Gulf War veterans. Participants.--Two hundred forty-nine (41%) of the 606 Gulf War veterans of the Twenty-fourth Reserve Naval Mobile Construction Battalion living in 5 southeastern states participated; 145 (58%) had retired from service, and the rest were still serving in the battalion. Design.--Participants completed a standardized survey booklet measuring the anatomical distributions or characteristics of each symptom, a booklet measuring wartime exposures, and a standard psychological personality assessment inventory. Two-stage factor analysis was used to disentangle ambiguous symptoms and identify syndromes. Main Outcome Measures.--Factor analysis-derived syndromes. Results.--Of 249 participants, 175 (70%) reported having had serious health problems that most attributed to the war, and 74 (30%) reported no serious health problems. Principal factor analysis yielded 6 syndrome factors, explaining 71% of the variance. Dichotomized syndrome indicators identified the syndromes in 63 veterans (25%). Syndromes 1 ("impaired cognition," characterized by problems with attention, memory, and reasoning, as well as insomnia, depression, daytime sleepiness, and headaches), 2 ("confusion-ataxia," characterized by problems with thinking, disorientation, balance disturbances, vertigo, and impotence), and 3 ("arthro-myo-neuropathy," characterized by joint and muscle pains, muscle fatigue, difficulty lifting, and extremity paresthesias) represented strongly clustered symptoms; whereas, syndromes 4 ("phobia-apraxia"), 5 ("fever-adenopathy"), and 6 "Weakness-incontinence") involved weaker clustering and mostly overlapped syndromes 2 and 3. Veterans with syndrome 2 were 12.5 times (95% confidence interval, 3.5-44.8) more likely to be unemployed than those with no health problems. A psychological profile, found in 48.4% of those with the syndromes, differed from posttraumatic stress disorder, depression, somatoform disorder, and malingering. Conclusion.--These findings support the hypothesis that clusters of symptoms of many Gulf War veterans represent discrete factor analysis-derived syndromes that appear to reflect a spectrum of neurologic injury involving the central, peripheral, and autonomic nervous systems. JAMA. 1997;277:215-222