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Background/Objective Neurostimulants may improve or accelerate cognitive and functional recovery after intracerebral hemorrhage (ICH), ischemic stroke (IS), or subarachnoid hemorrhage (SAH), but few studies have described their safety and effectiveness in the intensive care unit (ICU). The objective of this study was to describe amantadine and modafinil administration practices during acute stroke care starting in the ICU and to evaluate safety and effectiveness. Methods Consecutive adult ICU patients treated with amantadine and/or modafinil following acute non-traumatic IS, ICH, or SAH were evaluated. Neurostimulant administration data were extracted from the electronic medication administration record, including medication (amantadine, modafinil, or both), starting dose, time from stroke to initiation, and whether the neurostimulant was continued at hospital discharge. Patients were considered responders if they met two of three criteria within 9 days of neurostimulant initiation: increase in Glasgow coma scale (GCS) score ≥ 3 points from pre-treatment baseline, improved wakefulness or participation documented in caregiver notes, or clinical improvement documented in physical or occupational therapy notes. Potential confounders of the effectiveness assessment and adverse drug effects were also recorded. Results A total of 87 patients were evaluable during the 3.7-year study period, including 41 (47%) with ICH, 29 (33%) with IS, and 17 (20%) with SAH. The initial neurostimulant administered was amantadine in 71 (82%) patients, modafinil in 13 (15%), or both in 3 (3%) patients. Neurostimulants were initiated a median of 7 (4.25, 12.75) days post-stroke (range 1–27 days) for somnolence (77%), not following commands (32%), lack of eye opening (28%), or low GCS (17%). The most common starting dose was 100 mg twice daily for both amantadine (86%) and modafinil (54%). Of the 79 patients included in the effectiveness evaluation, 42 (53%) were considered responders, including 34/62 (55%) receiving amantadine monotherapy and 8/24 (33%) receiving both amantadine and modafinil at the time they met the definition of a responder. No patient receiving modafinil monotherapy was considered a responder. The median time from initiation to response was 3 (2, 5) days. Responders were more frequently discharged home or to acute rehabilitation compared to non-responders (90% vs 62%, p = 0.006). Among survivors, 63/72 (88%) were prescribed a neurostimulant at hospital discharge. The most common potential adverse drug effect was sleep disruption (16%). Conclusions Neurostimulant administration during acute stroke care may improve wakefulness. Future controlled studies with a neurostimulant administration protocol, prospective evaluation, and discretely defined response and safety criteria are needed to confirm these encouraging findings. Electronic supplementary material The online version of this article (10.1007/s12028-020-00986-4) contains supplementary material, which is available to authorized users.

Amantadine and modafinil are neurostimulants that may improve cognitive and functional recovery post-stroke, but the existing study results vary, and no comprehensive review has been published. This systematic review describes amantadine and modafinil administration practices post-stroke, evaluates timing and impact on clinical effectiveness measures, and identifies the incidence of potential adverse drug effects. A librarian-assisted search of the MEDLINE (PubMed) and EMBASE databases identified all English-language publications with “amantadine” or “modafinil” in the title or abstract from inception through February 1, 2020. Publications meeting predefined Patient, Intervention, Comparator, Outcome (PICO) criteria were included: Patients (≥ 18 years of age post-stroke); Intervention (amantadine or modafinil administration); Comparison (pretreatment baseline or control group); Outcomes (cognitive or functional outcome). Amantadine and modafinil administration practices, cognitive and functional outcomes, and incidence of potential adverse drug effects were collected following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance. Quantitative analyses were not performed due to heterogeneity in the clinical effectiveness measures; descriptive data are presented as number (percent) or median (interquartile range). Of 12,620 publications initially identified, 10 amantadine publications (n = 121 patients) and 12 modafinil publications (n = 120 patients) were included. Amantadine was initiated 39 (16, 385) days post-stroke, with most common initial doses of 100 mg once or twice daily (range 100–200 mg/day), and final daily dose of 200 (188, 200) mg/day. Modafinil was initiated 170 (17, 496) days post-stroke, with initial and final daily doses of 100 (100, 350) mg/day and 200 (100, 350) mg/day, respectively. The most common indication was consciousness disorders for amantadine (n = 3/10 publications; 30%) and fatigue for modafinil (n = 5/12; 42%). Forty unique clinical effectiveness measures (1.8 per study) with 141 domains (6.4 per study) were described across all studies. A positive response in at least one clinical effectiveness measure was reported in 70% of amantadine publications and 83% of modafinil publications. Only one publication each for amantadine (10%; n = 5 patients) and modafinil (8%; n = 21 patients) studied acutely hospitalized or ICU patients; both were randomized studies showing improvements in neurocognitive function for amantadine and fatigue for modafinil. Potential adverse drug effects were reported in approximately 50% of publications, most commonly visual hallucinations with amantadine (2% of patients) and dizziness (5% of patients) and dry eyes or mouth (5% of patients). Amantadine and modafinil may improve cognitive and functional recovery post-stroke, but higher-quality data are needed to confirm this conclusion, especially in the acute care setting.

Purpose The relationships between reproductive risk factors, including use of hormone replacement therapy and oral contraceptives and severity of age-related maculopathy (ARM) among postmenopausal women were evaluated. We hypothesized that exposure to endogenous or exogenous estrogens would be associated with a reduced risk of advanced ARM. Design Cross-sectional study. Methods The 394 subjects were postmenopausal women with ARM. Logistic regression analysis was used to compare the effects of several reproductive factors across two groups: 193 subjects with nonadvanced ARM and 201 subjects with advanced ARM. Results Women with ARM who had used postmenopausal estrogen therapy in the past had significantly lower odds of advanced ARM than nonusers, after controlling for other known and potential risk factors (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.30 to 0.98). Older age at menarche was associated with increased odds of advanced ARM (OR = 1.16, 95% CI = 1.00 to 1.35). Conclusions These findings suggest that exposure to exogenous estrogens may have a beneficial effect of reducing the risk of advanced types of ARM in postmenopausal women with ARM. Few therapeutic or preventive measures currently exist for ARM; therefore, these results deserve further evaluation.

The US Department of Transportation (DOT) regulates on-the-job alcohol use by operators of certain categories of commercial transport. For aircraft, trains, and commercial vessels, operators are subject to sanctions for having > or = 0.04 g% blood alcohol concentration (BAC). This study examines the effects of alcohol (between 0.04 and 0.05 g% BAC) on simulated merchant ship handling. A two-group randomized factorial design was used to compare beverage alcohol to placebo while controlling for baseline performance on a previous day. The study was conducted in the Maritime Simulation Center at Maine Maritime Academy, Castine, ME. Participants were 38 volunteer deck officer cadets in their junior or senior year, at least 21 years of age, with previous experience on a bridge simulator. Following a baseline trial on Day 1, on Day 2 participants were randomized to receive alcohol (0.6 g/kg for males and 0.5 g/kg for females) or placebo. After allowing time for absorption, participants completed a bridge simulator task. For baseline and performance trials, participants were randomized to one of four bridge simulator scenarios, each representing passage of a fully loaded container vessel through a channel with commercial traffic. The aggregate scenario score given by blinded maritime educators measured performance. A main effect for alcohol was found indicating that performance was significantly impaired by this low dose of alcohol relative to performance in the placebo condition. These findings are consistent with current federal regulations that limit low-dose alcohol exposure for the operators of commercial transport vehicles. Further research is required to determine effects at lower BACs.

Because of the threat of Fetal Alcohol Syndrome, pregnant women have been a primary target for interventions that provide information about the risk associated with drinking during pregnancy. In a general population sample of pregnant women, the relationships between alcohol consumption in pregnant women and exposure to four sources of health messages are investigated. Sources included alcohol beverage container labels, point of sale signs, advertisements, and personal conversations. Results from a five year cross-sectional U.S. national survey and a two year longitudinal study of women of childbearing age (18–40 yrs) indicate that the vast majority of the drinking women (80 percent) decrease their alcohol consumption during pregnancy, with 61 percent of the drinkers abstaining completely. Pregnant women who do drink reported consuming relatively low quantities of alcohol, with only four percent consuming more than three drinks in a single day. Unlike previous research, no differences were found ...

Context Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older individuals in many parts of the world. The relative importance of genes and environment in the etiology of this major public health problem is not well understood. Objective To investigate the impact of genetic and environmental factors. Participants Living twins in the National Academy of Sciences–National Research Council World War II Veteran Twin Registry born between 1917 and 1927. Methods Twins were surveyed for the known presence of macular degeneration. Enrolled twins underwent a standardized examination and fundus photography. Age-related macular degeneration evaluation was completed for 840 elderly male twins, 210 monozygotic and 181 dizygotic complete twin pairs, both concordant and discordant for presence or absence of AMD, and 58 singletons. A bivariate twin model incorporating initial screening ascertainment and age effects was employed to partition variation in liability to AMD and signs of maculopathy into additive genetic, common environment, and unique environment components. Main Outcome Measure Heritability of AMD grade and signs of maculopathy based on clinical examination and fundus photographs. Results Of the 840 twins, 331 had no signs of maculopathy and 241 had early signs, while 162 had intermediate AMD and 106 had advanced AMD. Heritability (additive genetic) estimates were significant for overall AMD grade (0.46) and for intermediate (0.67) and advanced (0.71) AMD. Significant unique environmental proportions of variance were also observed for these AMD variables (0.37, 0.19, and 0.24, respectively). Shared or common environmental contributions were not significant (0.05-0.17). For specific macular drusen and retinal pigment epithelial characteristics, significant genetic (0.26-0.71) and unique environmental (0.28-0.64) proportions of variance were detected. Conclusions Genetic factors play a substantial role in the etiology of AMD and associated macular characteristics, explaining 46% to 71% of the variation in the overall severity of the disease. Environmental factors unique to each twin also contribute to the occurrence of this disease. This quantification of relative genetic and environmental contributions to the development of AMD should guide future research on this important cause of blindness.

Background Individuals with early or intermediate stages of age-related macular degeneration (AMD) make up a large, growing segment of the elderly population. Evidence is sparse regarding modifiable factors that may decrease the risk of progression to the advanced forms of AMD. Objective To advise patients with a high risk for advanced forms of AMD about preventive measures through our evaluation of the relationship between dietary fat intake and the progression of early or intermediate AMD to the advanced stages of the disease associated with visual loss. Design A prospective cohort study with an average follow-up time of 4.6 years. Setting A hospital-based clinical retinal practice specializing in macular degeneration. Patients The 261 participants were aged 60 years and older and had some sign of nonexudative AMD and visual acuity of 20/200 or better in at least 1 eye. Main Outcome Measure Progression to advanced AMD, which was defined as having geographic atrophy or neovascular disease. Results Higher total fat intake increased the risk of progression to the advanced forms of AMD, with a relative risk (RR) of 2.90 (95% confidence interval, 1.15-7.32) for the highest fat-intake quartile relative to the lowest fat-intake quartile, after controlling for other factors ( P trend= .01). Animal fat intake was associated with a 2-fold increased risk of progression(RR, 2.29 for the highest quartile compared with the lowest quartile; 95% confidence interval, 0.91-5.72), although the trend for increasing risk with higher animal fat intake was not significant ( P =.09). Higher vegetable fat intake had a stronger relationship with increased risk of AMD progression with an RR of 3.82 (95% confidence interval, 1.58-9.28) for the highest quartile compared with the lowest quartile ( P trend = .003). Saturated, monounsaturated, polyunsaturated, and transunsaturated fats increased the likelihood of progression (RR, 2.09 and P trend = .08; RR, 2.21 and P trend = .04; RR, 2.28 and P trend = .04; RR, 2.39 and P trend = .008, respectively). Higher fish intake was associated with a lower risk of AMD progression among subjects with lower linoleic acid intake. Processed baked goods, which are higher in some of these fats, increased the rate of AMD progression approximately 2-fold, and nuts were protective. Conclusions Among individuals with the early or intermediate stages of AMD, total and specific types of fat intake, as well as some fat-containing food groups, modified the risk of progression to advanced AMD. Fish intake and nuts reduced risk. Since advanced AMD is associated with visual loss and reduced quality of life, these preventive measures deserve additional research and greater emphasis.

Aims. Under current US Department of Transportation (DOT) regulations, some commercial vehicle operators are subject to sanctions for having ≥ 00. 04 g% blood alcohol concentrations (BACs) on the job. This study investigated the effects of alcohol (between 0.04 and 0.05 g% BAC) on the simulated operation of a commercial ship's power plant. Design. A balanced placebo design was used in which alcohol administration was fully crossed with expectancy that alcohol was administrated. Setting. The study was conducted at the Massachusetts Maritime Academy, Buzzards Bay, MA, USA. Participants. Participants were 18 volunteer engineering students in their senior year, at least 21 years of age, with previous experience on the diesel simulator. Intervention. Following a baseline trial on day 1, on day 2 participants were randomized to expectancy (told alcohol or placebo) and beverage (receive alcohol or placebo). The dosage was 0.6 g/kg for males and 0.5 g/kg for females. In both baseline and performance days, participants were randomized to one of four diesel simulator scenarios, each replicating a system failure in a power plant subsystem (e.g. main propulsion, electrical generating). Measurement. Performance was measured by time required for problem identification and remediation. Findings. A main effect for alcohol administration was found. In the alcohol condition, simulator performance time was almost twice as long (351 sec) as on the placebo condition (186 sec). The expectancy effect was not significant. Conclusion. These findings support the current federal policy on the hazards of this low alcohol level within the context of commercial shipping.

Background Individuals with early or intermediate stages of age-related macular degeneration (AMD) make up a large and growing segment of our elderly population. To advise these high-risk patients regarding preventive measures, we evaluated anthropomorphic, behavioral, and medical factors associated with progression to the advanced stages of AMD associated with visual loss. Methods The design was a prospective cohort study in a hospital-based retinal practice. The 261 participants were 60 years or older, with some sign of nonadvanced AMD and visual acuity of 20/200 or better in at least 1 eye. The average follow-up time was 4.6 years, and the total person-years of follow-up was 1198. Factors associated with rates of progression to advanced AMD were assessed by the Cox proportional hazards model. Outcome Measures Progression to geographic atrophy and neovascular disease. Results Higher body mass index (calculated as weight in kilograms divided by the square of height in meters) increased the risk for progression to the advanced forms of AMD. Relative risk (RR) was 2.35 (95% confidence interval[CI], 1.27-4.34) for a body mass index of at least 30, and 2.32 (95% CI, 1.32-4.07) for a body mass index of 25 to 29, relative to the lowest category ( P = .007 for trend). Higher waist circumference was associated with a 2-fold increased risk for progression (RR for the highest tertile compared with the lowest, 2.04; 95% CI, 1.12-3.72), with a significant trend for increasing risk with a greater waist circumference ( P = .02). Higher waist-hip ratio also increased the risk for progression (RR, 1.84; 95% CI, 1.07-3.15) for the highest tertile compared with lowest ( P = .02 for trend). More physical activity tended to be associated with a reduced rate of progression (25% reduction for 3 times per week vigorous activity vs none, P = .05 to P = .07). Relative risks for smoking ranged from 1.48 to 1.99, but were not statistically significant. Conclusions Results provide new information regarding modifiable factors for individuals with the early or intermediate stages of this disease. Overall and abdominal obesity increased the risk for progression to advanced AMD, and more physical activity tended to decrease risk. These preventive measures deserve additional research and greater emphasis.