Treatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs: A Systematic Review.

Importance: Multiple continuous intravenous anesthetic drugs (CIVADs) are available for the treatment of refractory status epilepticus (RSE). There is a paucity of data comparing the different types of CIVADs used for RSE. Objective: To systematically review and compare outcome measures associated with the initial CIVAD choice in RSE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Evidence Review: Data sources included English and non-English articles using Embase, MEDLINE, PubMed, and Web of Science (January 1994-June 2023) as well as manual search. Study selection included peer-reviewed studies of 5 or more patients and at least 1 patient older than 12 years with status epilepticus refractory to a benzodiazepine and at least 1 standard antiseizure medication, treated with continuously infused midazolam, ketamine, propofol, pentobarbital, or thiopental. Independent extraction of articles was performed using prespecified data items. The association between outcome variables and CIVAD was examined with an analysis of variance or χ2 test where appropriate. Binary logistic regressions were used to examine the association between outcome variables and CIVAD with etiology, change in mortality over time, electroencephalography (EEG) monitoring (continuous vs intermittent), and treatment goal (seizure vs burst suppression) included as covariates. Risk of bias was addressed by listing the population and type of each study. Findings: A total of 66 studies with 1637 patients were included. Significant differences among CIVAD groups in short-term failure, hypotension, and CIVAD substitution during treatment were observed. Non-epilepsy-related RSE (vs epilepsy-related RSE) was associated with a higher rate of CIVAD substitution (60 of 120 [50.0%] vs 11 of 43 [25.6%]; odds ratio [OR], 3.11; 95% CI, 1.44-7.11; P = .006) and mortality (98 of 227 [43.2%] vs 7 of 63 [11.1%]; OR, 17.0; 95% CI, 4.71-109.35; P < .001). Seizure suppression was associated with mortality (OR, 7.72; 95% CI, 1.77-39.23; P = .005), but only a small subgroup was available for analysis (seizure suppression: 17 of 22 [77.3%] from 3 publications vs burst suppression: 25 of 98 [25.5%] from 12 publications). CIVAD choice and EEG type were not predictors of mortality. Earlier publication year was associated with mortality, although the observation was no longer statistically significant after adjusting SEs for clustering. Conclusions and Relevance: Epilepsy-related RSE was associated with lower mortality compared with other RSE etiologies. A trend of decreasing mortality over time was observed, which may suggest an effect of advances in neurocritical care. The overall data are heterogeneous, which limits definitive conclusions on the choice of optimal initial CIVAD in RSE treatment.

Prevalence of lipoprotein(a) measurement in patients with or at risk of cardiovascular disease.

INTRODUCTION: Lipoprotein(a) [Lp(a)] is a genetically determined independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease. Despite recommendations from professional societies in the cardiovascular field, the awareness of elevated Lp(a) as a risk factor and screening for Lp(a) are suspected to be low. METHODS: We conducted a retrospective, observational case control study of patient charts from January 1, 2017 to June 19, 2022. The primary aims were 1) to describe the proportion of patients at the healthcare network's primary care and cardiology clinics that met Lp(a) screening criteria and were tested; and 2) to describe the proportion of patients throughout the entire healthcare network that had Lp(a) measured. RESULTS: Of the 2,412,020 patient charts in the health network, only 5,942 (0.25 %) had Lp(a) measured. Of the 84,581 patients in primary care or cardiology clinics who met screening criteria, only 1,311 (1.55 %) had Lp(a) measured. Patients with Lp(a) measured were more likely to be younger, non-Hispanic/Latinx, had a lipid panel measured, a cardiac computed tomography (CT) imaging study, and higher low-density lipoprotein-cholesterol. Patients with ASCVD, heart failure, ischemic heart disease, aortic stenosis, peripheral vascular disease, or a stroke did not feature highly among patients who received Lp(a) testing. Having an abnormal or risk-enhancing Lp(a) level was associated with being female and/or being Black/African American. CONCLUSIONS: Despite increased awareness of Lp(a) and its contribution to cardiovascular disease there exists a paucity of testing. Increased Lp(a) testing can identify patients who have an increased cardiovascular risk underestimated by other metrics.

The effects of an acute weight stigma exposure on cardiovascular reactivity among women with obesity and hypertension: A randomized trial.

OBJECTIVE: Weight stigma induces cardiovascular health consequences for people with obesity. How stigma affects cardiovascular reactivity in individuals with both obesity and hypertension is not known. METHODS: In a randomized experiment, we assessed the influence of two video exposures, depicting either weight stigmatizing (STIGMA) or non-stigmatizing (NEUTRAL) scenes, on cardiovascular reactivity [resting blood pressure (BP), heart rate (HR), ambulatory BP (ABP), and ambulatory HR (AHR)], among women with obesity and high BP (HBP; n=24) or normal BP (NBP; n=25). Systolic ABP reactivity was the primary outcome. Laboratory BP and HR were measured before/during/following the videos, and ABP and AHR were measured over 19 hours (10 awake hours, 9 sleep hours) upon leaving the laboratory. A repeated measures ANCOVA tested differences in BP and HR changes from baseline in the laboratory and over ambulatory conditions between the two groups after each video, controlling for body mass index, baseline BP and HR. RESULTS: Laboratory SBP/DBP increased 5.5+7.3/2.4+8.8mmHg more in women with HBP than NBP following the STIGMA versus NEUTRAL video (Ps<0.05). For the primary outcome, ABP increased more in HBP than NBP over sleep (SBP/DBP=4.2+20.6/4.7+14.2mmHg; Ps<0.05) following the STIGMA versus NEUTRAL video, as did HR during sleep (7.5+15.7bpm more in HBP than NBP; P<0.05). CONCLUSIONS: Weight stigma increases cardiovascular reactivity among women with obesity and HBP in the laboratory and under ambulatory conditions. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov (Identifier: NCT04161638).

Minimum clinically important difference (MCID) of the personal impact of epilepsy scale (PIES).

INTRODUCTION: The Personal Impact of Epilepsy Scale (PIES) assesses patient functional status in subscales of (1) seizure impact, (2) medication effects, (3) mood & social status, and (4) overall quality of life. This study was designed to determine the Minimal Clinically Important Change (MCID) in PIES subscale and total scores that demonstrate improvement. METHODS: To ascertain the correspondence of PIES score change and clinical status change (improved, same, worse) in each PIES subscale and total score, we used two distinct retrospective anchor-based assessments of clinical status (patient self-assessment and trained rater assessment) across two clinic visits. Mean PIES scores were compared between clinical status groups, controlling for days between visits and initial clinical status. Personal Impact of Epilepsy Scale score change was quantified for each group to determine MCID. A small prospective proof-of-concept study was conducted in a separate subject group. RESULTS: Patient self-report anchor analysis demonstrated lower (better) PIES scores in the "improved" group vs the "worse" group on the mood & social subscale (p < .001) and total score (p = .002), with a similar trend on the seizure subscale (p = 0.056). Clinical rater anchor analysis demonstrated lower PIES scores in the "improved" vs "worse" group in the mood & social subscale (p = .029) and a trend in total score (p = .082). For the "improved" group, the reduction in PIES scores between visits averaged across both anchor analyses was 8.14% for subscales and 8.67% for total score. DISCUSSION/CONCLUSION: Reduction of 8% on a PIES subscale or total score indicates meaningful improvement in patient clinical status, and is designated the MCID for this instrument. Personal Impact of Epilepsy Scale can be useful in day-to-day clinical care and as an outcome metric in clinical research.

A New Force-Activated Separation Device for the Prevention of Peripheral Intravenous Restarts.

The high failure rate (46%) of peripheral intravenous catheters (PIVCs) is well-documented. There is limited research examining the effect of forces/pulls on PIVC complications. New breakaway connectors called force-activated separation devices (FASD) separate when a damaging force is placed on a PIVC. In a randomized, controlled trial, patients were assigned 1:1 to a control group receiving PIVC standard of care (SOC) or SOC with FASD added to the catheter. The primary outcome was total mechanical complications requiring a PIVC restart. Secondary outcomes were delay in therapy, PIVC restarts, and adverse events. Outcomes were compared in an intention-to-treat analysis (N = 302) and per-protocol analysis (N = 287). There were less total mechanical complications in FASD compared with SOC (22 vs 41, respectively; P < .01). The treatment group was a predictor of total delay in therapy (minutes), indicating a greater estimated total delay in therapy in SOC than FASD (B = 69.53; 95% CI, 28.32-110.73; P = .001). There were more adverse events in SOC (127) than FASD (76; P = .001). Results were consistent in the per-protocol analysis. Use of a FASD showed a reduction in total mechanical complications. These results support use of the FASD as a safer and time-saving alternative to current SOC.

Development of a Novel Clinical Decision Support System for Exercise Prescription Among Patients With Multiple Cardiovascular Disease Risk Factors.

Cardiovascular disease (CVD) risk factors cluster in an individual. Exercise is universally recommended to prevent and treat CVD. Yet, clinicians lack guidance on how to design an exercise prescription (ExRx) for patients with multiple CVD risk factors. To address this unmet need, we developed a novel clinical decision support system to prescribe exercise (prioritize personalize prescribe exercise [P3-EX]) for patients with multiple CVD risk factors founded upon the evidenced-based recommendations of the American College of Sports Medicine (ACSM) and American Heart Association. To develop P3-EX, we integrated (1) the ACSM exercise preparticipation health screening recommendations; (2) an adapted American Heart Association Life's Simple 7 cardiovascular health scoring system; (3) adapted ACSM strategies for designing an ExRx for people with multiple CVD risk factors; and (4) the ACSM frequency, intensity, time, and time principle of ExRx. We have tested the clinical utility of P3-EX within a university-based online graduate program in ExRx among students that includes physicians, physical therapists, registered dietitians, exercise physiologists, kinesiologists, fitness industry professionals, and kinesiology educators in higher education. The support system P3-EX has proven to be an easy-to-use, guided, and time-efficient evidence-based approach to ExRx for patients with multiple CVD risk factors that has applicability to other chronic diseases and health conditions. Further evaluation is needed to better establish its feasibility, acceptability, and clinical utility as an ExRx tool.

Venous thromboemboli associated with acute aerobic exercise: A review of case report commonalities.

Venous thromboembolic (VTE) events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in otherwise low-risk healthy athletes following acute bouts of aerobic exercise. PURPOSE: To review case reports and assess the commonalities of athletic individuals with VTE, as well as return-to-play (RTP) recommendations. METHODS: We reviewed 47 reports (20 DVTs, 15 PEs, and 12 DVTs/PEs, 19 women) of trained individuals who were diagnosed with DVT and/or PE following aerobic exercise. We assessed frequency of VTE risk factors, presenting symptoms, and RTP recommendations. RESULTS: The age of women (24.6 ± 7.0 years) was lower (P < .01) than of men (40.6 ± 13.6 years). Of the 19 women, 14 (73.7%) used oral contraceptives. Thirteen cases (27.7%) reported a recent period of prolonged inactivity (>1 hour), and another 12 cases were found to have an antithrombin disorder following testing after diagnosis. The most frequently reported symptoms were muscle pain in 26 of 32 (81.3%) DVT or DVT/PE cases, and dyspnea in 21 of 27 (77.8%) PE or DVT/PE cases. Despite these common symptoms, the estimated time from first report of symptoms to confirmed diagnosis was 56.3 ± 118.7 days and 25 cases (53.2%) were initially misdiagnosed. Twenty-three cases (48.9%) did not report RTP recommendations, and those which did varied widely. CONCLUSIONS: Thirty-two cases (~70%) had at least one of three major risk factors, suggesting that many cases of VTE in athletes may be preventable with better education and awareness. The wide variety of RTP recommendations highlights the need for standardized guidelines in this population.

Links between discrimination and cardiovascular health among socially stigmatized groups: A systematic review.

BACKGROUND: There is a high prevalence of cardiovascular disease across diverse groups in the U.S. population, and increasing research has identified stigma as a potential barrier to cardiovascular disease prevention and treatment. This systematic review examines evidence linking discrimination and cardiovascular health among socially stigmatized groups. STUDY DESIGN: Six databases were systematically reviewed from inception through February 2018 for studies with adult subjects, focusing on cardiovascular health indicators among social groups stigmatized because of their gender, race/ethnicity, age, body weight/obesity, or sexual orientation. The Newcastle-Ottawa Scale was used to evaluate the methodological quality and risk of bias for nonrandomized studies, and the Cochrane Collaboration 7-item domain for randomized controlled and experimental trials. RESULTS: The search identified 84 eligible studies published between 1984 and 2017. Studies retrieved were categorized according to demonstrated links between stigma and cardiovascular disease risk factors including blood pressure (n = 45), heart rate variability (n = 6), blood/saliva cardiovascular biomarkers (n = 18), as well as other indicators of cardiovascular health (n = 15). Based on the findings from included studies, 86% concluded that there was a significant relationship among stigma or discrimination and cardiovascular health indicators among socially stigmatized groups. However, there were varying degrees of evidence supporting these relationships, depending on the type of discrimination and cardiovascular health indicator. The current evidence implies an association between perceived discrimination and cardiovascular health. However, a majority of these studies are cross-sectional (73%) and focus on racial discrimination (79%), while using a wide variety of measurements to assess social discrimination and cardiovascular health. CONCLUSIONS: Future research should include longitudinal and randomized controlled trial designs, with larger and more diverse samples of individuals with stigmatized identities, using consistent measurement approaches to assess social discrimination and its relationship with cardiovascular health.

FURIN variant associations with postexercise hypotension are intensity and race dependent.

FURIN is a proprotein convertase subtilisin/kexin enzyme important in pro-renin receptor processing, and FURIN (furin, paired basic amino acid cleaving enzyme) variants are involved in multiple aspects of blood pressure (BP) regulation. Therefore, we examined associations among FURIN variants and the immediate blood pressure (BP) response to bouts of aerobic exercise, termed postexercise hypotension (PEH). Obese (30.9 ± 3.6 kg  m-2 ) Black- (n = 14) and White- (n = 9) adults 42.0 ± 9.8 year with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous (VIGOROUS) and moderate (MODERATE) intensity cycling and control. Subjects were then attached to an ambulatory BP monitor for 19 h. We performed deep-targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. FURIN genotypes were coded as the number of minor alleles (#MA) and selected for additional statistical analysis based upon Bonferonni or Benjamini-Yekutieli multiple testing corrected P-values under time-adjusted linear models for 19 hourly BP measurements. After VIGOROUS over 19 h, as FURIN #MA increased in rs12917264 (P = 2.4E-04) and rs75493298 (P = 6.4E-04), systolic BP (SBP) decreased 30.4-33.7 mmHg; and in rs12917264 (P = 1.6E-03) and rs75493298 (P = 9.7E-05), diastolic BP (DBP) decreased 17.6-20.3 mmHg among Blacks only. In addition, after MODERATE over 19 h in FURIN rs74037507 (P = 8.0E-04), as #MA increased, SBP increased 20.8 mmHg among Blacks only. Whereas, after MODERATE over the awake hours in FURIN rs1573644 (P = 6.2E-04), as #MA increased, DBP decreased 12.5 mmHg among Whites only. FURIN appears to exhibit intensity and race-dependent associations with PEH that merit further exploration among a larger, ethnically diverse sample of adults with hypertension.

Physical activity intensity and subjective well-being in healthy adults.

The effect of physical activity intensity on subjective well-being has not been well established. We examined this relationship among 419 healthy adults using objective and subjective physical activity measurements (sample size varied among well-being assessments). For accelerometers, light-intensity physical activity positively associated with psychological well-being (n = 150) and negatively associated with depression (n = 99); moderate intensity negatively associated with pain severity (n = 419) and positively associated with psychological well-being; sedentary behavior negatively associated with psychological well-being and positively associated with depression (ps < .05). These findings were generally consistent with subjective measurements of physical activity (Question 8, Paffenbarger Questionnaire). Higher levels of sedentary behavior are associated with lower subjective well-being.

The Influence of Compression Socks During a Marathon on Exercise-Associated Muscle Damage.

CONTEXT: Compression socks have become increasingly popular with athletes due to perceived enhancement of exercise performance and recovery. However, research examining the efficacy of compression socks to reduce exercise-associated muscle damage has been equivocal, with few direct measurements of markers of muscle damage. OBJECTIVE: To examine the influence of compression socks worn during a marathon on creatine kinase (CK) levels. DESIGN: A randomized controlled trial. SETTING: 2013 Hartford Marathon, Hartford, CT. PARTICIPANTS: Adults (n = 20) randomized to control (CONTROL; n = 10) or compression sock (SOCK; n = 10) groups. MAIN OUTCOME MEASURES: Blood samples were collected 24 hours before, immediately after, and 24 hours following the marathon for the analysis of CK, a marker of muscle damage. RESULTS: Baseline CK levels did not differ between CONTROL (89.3 [41.2] U/L) and SOCK (100.0 [56.2] U/L) (P = .63). Immediately following the marathon (≤1 h), CK increased 273% from baseline (P < .001 for time), with no difference in exercise-induced changes in CK from baseline between CONTROL (+293.9 [278.2] U/L) and SOCK (+233.1 [225.3] U/L; P = .60 for time × group). The day following the marathon (≤24 h), CK further increased 1094% from baseline (P < .001 for time), with no difference in changes in CK from baseline between CONTROL (+ 1191.9 [1194.8] U/L) and SOCK (+889.1 [760.2] U/L; P = .53 for time × group). These similar trends persisted despite controlling for potential covariates such as age, body mass index, and race finishing time (Ps > .29). CONCLUSIONS: Compression socks worn during a marathon do not appear to mitigate objectively measured markers of muscle damage immediately following and 24 hours after a marathon.

The effect of high-dose atorvastatin on neural activity and cognitive function.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has not been used to assess the effects of statins on the brain. We assessed the effect of statins on cognition using standard neuropsychological assessments and brain neural activation with fMRI on two tasks. METHODS: Healthy statin-naïve men and women (48±15 years) were randomized to 80 mg/day atorvastatin (n=66; 27 men) or placebo (n=84; 48 men) for 6 months. Participants completed cognitive testing while on study drug and 2 months after treatment cessation using alternative test and task versions. RESULTS: There were few changes in standard neuropsychological tests with drug treatment (all P>.56). Total and delayed recall from the Hopkins Verbal Learning Test-Revised increased in both groups (P<.05). The Stroop Color-Word score increased (P<.01) and the 18-Point Clock Test decreased in the placebo group (P=.02) after drug cessation. There were, however, small but significant group-time interactions for each fMRI task: participants on placebo had greater activation in the right putamen/dorsal striatum during the maintenance phase of the Sternberg task while on placebo but the effect was reversed after drug washout (P<.001). Participants on atorvastatin had greater activation in the bilateral precuneus during the encoding phase of the Figural Memory task while on-drug but the effect was reversed after drug washout (P<.001). CONCLUSION: Six months of high dose atorvastatin therapy is not associated with measurable changes in neuropsychological test scores, but did evoke transient differences in brain activation patterns. Larger, longer-term clinical trials are necessary to confirm these findings and evaluate their clinical implications.

Can Exercise Improve Cognitive Symptoms of Alzheimer's Disease?

OBJECTIVES: To examine the effects of exercise training on cognitive function in individuals at risk of or diagnosed with Alzheimer's disease (AD). DESIGN: Meta-analysis. SETTING: PubMed, Scopus, ClinicalTrials.gov, and ProQuest were searched from inception until August 1, 2017. PARTICIPANTS: Nineteen studies with 23 interventions including 1,145 subjects with a mean age of 77.0 ± 7.5 were included. Most subjects were at risk of AD because they had mild cognitive impairment (64%) or a parent diagnosed with AD (1%), and 35% presented with AD. INTERVENTION: Controlled studies that included an exercise-only intervention and a nondiet, nonexercise control group and reported pre- and post-intervention cognitive function measurements. MEASUREMENTS: Cognitive function before and after the intervention and features of the exercise intervention. RESULTS: Exercise interventions were performed 3.4 ± 1.4 days per week at moderate intensity (3.7 ± 0.6 metabolic equivalents) for 45.2 ± 17.0 minutes per session for 18.6 ± 10.0 weeks and consisted primarily of aerobic exercise (65%). Overall, there was a modest favorable effect of exercise on cognitive function (d+  = 0.47, 95% confidence interval (CI) = 0.26-0.68). Within-group analyses revealed that exercise improved cognitive function (d+w  = 0.20, 95% CI  = 0.11-0.28), whereas cognitive function declined in the control group (d+w  = -0.18, 95% CI  = -0.36 to 0.00). Aerobic exercise had a moderate favorable effect on cognitive function (d+w  = 0.65, 95% CI = 0.35-0.95), but other exercise types did not (d+w  = 0.19, 95% CI = -0.06-0.43). CONCLUSION: Our findings suggest that exercise training may delay the decline in cognitive function that occurs in individuals who are at risk of or have AD, with aerobic exercise possibly having the most favorable effect. Additional randomized controlled clinical trials that include objective measurements of cognitive function are needed to confirm our findings.

Compression Socks Worn During Flight and Hemostatic Balance in Boston Marathon Runners on Oral Contraceptives.

OBJECTIVE: To investigate the effect of oral contraceptive (OC) use and compression socks on hemostatic activation in women flying cross-country to and from a marathon. DESIGN: Prospective study. SETTING: 2015 Boston Marathon. PARTICIPANTS: Women were divided into non-OC using (CONTROL; n = 12), OC-using (OC; n = 15), and OC-using plus compression sock (OC + SOCK; n = 14) groups. INTERVENTION: Women in OC + SOCK wore compression socks during flights to and from the marathon. MAIN OUTCOME MEASURES: Venous blood samples were collected within 24 hours of arriving in Boston (EXPO), immediately after the marathon (RUN), and within 24 hours after a return flight home (Post-Flight) for analysis of thrombin-antithrombin complex (TAT), d-dimer, and tissue plasminogen activator (t-PA). RESULTS: TAT did not increase with exercise (P = 0.48) and was not affected by group (P = 0.08) or the interaction between these 2 factors (P = 0.80). Group, time, and their interaction were significant for d-dimer (all P < 0.05) such that d-dimer increased with acute exercise to a greater extent (Δ d-dimer from expo to postrace = 909.5 ± 1021.9 ng/mL) in the OC + SOCK group relative to OC (Δ d-dimer = 240.0 ± 178.5 ng/mL; P = 0.02) and CONTROL (Δ d-dimer = 230.3 ± 120.3 ng/mL; P = 0.02). There was a significant effect of time, group, and the interaction on t-PA (all P < 0.01) such that t-PA increased with acute exercise to a greater extent (Δ t-PA from expo to postrace = 19.6 ± 10.0 ng/mL) in the CONTROL group relative to OC (Δ t-PA = 4.0 ± 1.8 ng/mL; P < 0.01) and OC + SOCK (Δ t-PA = 3.3 ± 1.2 ng/mL; P < 0.01). CONCLUSIONS: Female runners using OCs did not exhibit disproportionately increased coagulation. The use of compression socks in women on OCs, surprisingly, resulted in a greater increase in d-dimer after exercise.

The Effects of In-Hospital Intravenous Cold Saline in Postcardiac Arrest Patients Treated with Targeted Temperature Management.

BACKGROUND: Recent data suggest that rapid infusion of intravenous (IV) cold saline for Targeted Temperature Management (TTM) after cardiac arrest is associated with higher rates of rearrest, pulmonary edema, and hypoxia, with no difference in neurologic outcomes or survival when administered by Emergency Medical Services. We sought to determine the effects of IV cold saline administration in the hospital setting in postcardiac arrest patients to achieve TTM and its effect on clinical parameters and neurologic outcomes. METHODS AND RESULTS: A cohort of 132 patients who completed TTM after cardiac arrest in a single institution was retrospectively studied. Patients who did not receive cold saline were matched by age, gender, Glasgow coma scale, downtime, and presenting rhythm to patients who received cold saline. Demographics, cardiac rearrest, diuretic use, time to target temperature, and Cerebral Performance Category (CPC) scores were recorded among other variables. Patients who received cold saline achieved target temperature sooner (280 vs. 345 minutes, p = 0.05), had lower lactate levels on day 1 (4.2 ± 3.5 mM vs. 6.0 ± 4.9 mM, p = 0.019) and day 2 (1.3 ± 2.2 mM vs. 2.2 ± 3.2 mM, p = 0.046), increased incidence of pulmonary edema (51.5% vs. 31.8%, p = 0.006), and increased diuretic utilization (63.6% vs. 42.4%, p = 0.014). There was no significant difference in cardiac rearrest, arterial oxygenation, and CPC scores (ps > 0.05). CONCLUSIONS: Infusion of IV cold saline is associated with shorter time to target temperature, increased incidence of pulmonary edema, and diuretic use, with no difference in cardiac rearrest, survival, and neurologic outcomes.

Deep-targeted sequencing of endothelial nitric oxide synthase gene exons uncovers exercise intensity and ethnicity-dependent associations with post-exercise hypotension.

In previous studies, we found an endothelial nitric oxide synthase gene (NOS3) variant rs2070744 associated with the ambulatory blood pressure (BP) response following bouts of moderate and vigorous intensity acute exercise, termed post-exercise hypotension (PEH). In a validation cohort, we sequenced NOS3 exons for associations with PEH Obese (30.9 ± 3.6 kg.m-2) African American (n = 14) [AF] and Caucasian (n = 9) adults 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects were attached to an ambulatory BP monitor for 19 h. We performed deep-targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (#MA) and selected for additional statistical analysis based upon Bonferonni or Benjamini-Yekutieli multiple testing-corrected P-values under time-adjusted linear models for 19 hourly BP measurements for each subject. After vigorous intensity over 19 h, among NOS3 variants passing multiple testing thresholds, as the #MA increased in rs891512 (P = 6.4E-04), rs867225 (P = 6.5E-04), rs743507 (P = 2.6E-06), and rs41483644 (P = 2.4E-04), systolic (SBP) decreased from 17.5 to 33.7 mmHg; and in rs891512 (P = 9.7E-05), rs867225 (P = 2.6E-05), rs41483644 (P = 1.6E-03), rs3730009 (P = 2.6E-04), and rs77325852 (P = 5.6E-04), diastolic BP decreased from 11.1 mmHg to 20.3 mmHg among AF only. In contrast, after moderate intensity over 19 h in NOS3 rs3918164, as the #MA increased, SBP increased by 16.6 mmHg (P = 2.4E-04) among AF only. NOS3 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. NOS3 should be studied further for its effects on PEH in a large, ethnically diverse sample of adults with hypertension to confirm our findings.