The effect of posture and exercise on blood CO kinetics during the optimized carbon monoxide rebreathing procedure.

An indispensable precondition for the determination of hemoglobin mass (Hbmass) and blood volume by CO rebreathing is complete mixing of CO in the blood. The aim of this study was to demonstrate the kinetics of CO in capillary and venous blood in different body positions and during moderate exercise. Six young subjects (4 male, 2 female) performed three 2-min CO rebreathing tests in seated (SEA) & supine (SUP) positions as well as during moderate exercise (EX) on a bicycle ergometer. Before, during, and until 15 min after CO rebreathing cubital venous and capillary blood samples were collected simultaneously and COHb% was determined. COHb% kinetics were significantly slower in SEA than in SUP or EX. Identical COHb% in capillary and venous blood were reached in SEA after 5.0 ± 2.3 min, in SUP after 3.2 ± 1.3 min and in EX after 1.9 ± 1.2 min (EX vs. SEA p < .01, SUP vs. SEA p < .05). After 7th min, Hbmass did not differ between the resting positions (capillary: SEA 766 ± 217 g, SUP 761 ± 227 g; venous: SEA 759 ± 224 g, SUP 744 ± 207 g). Under exercise, however, a higher Hbmass (p < .05) was determined (capillary: 823 ± 221 g, venous: 804 ± 226 g). In blood, the CO mixing time in the supine position is significantly shorter than in the seated position. By the 6th minute complete mixing is achieved in either position giving similar Hbmass determinations. CO-rebreathing under exercise conditions, however, leads to ∼7% higher Hbmass values.

Iron Status and Homeostasis Across 2 Competitive Seasons in NCAA Division I Collegiate Cross-Country Runners Residing at Low Altitude.

PURPOSE: Inflammatory cytokines including interleukin-6 can upregulate hepcidin and decrease iron absorption. Endurance exercise is associated with transient increases in cytokines, which may alter the risk of iron deficiency (ID). This study examined whether chronic elevations in basal levels of cytokines and hepcidin were associated with ID in highly trained runners. METHODS: Fifty-four collegiate runners (26 males and 28 females) living at ∼1625 m were recruited from an NCAA Division I cross-country team for this prospective cohort study. Over 2 seasons, fasted, preexercise blood draws were performed in the morning 4 times per season and were analyzed for hemoglobin concentration, ferritin, soluble transferrin receptor (sTfR), hepcidin, and 10 cytokines. Stages of ID were defined using ferritin, sTfR, and hemoglobin concentration. During the study, a registered dietician provided all runners with iron supplements using athletic department-created guidelines. RESULTS: Fifty-seven percent of females and 35% of males exhibited stage 2 ID (ferritin <20 ng/mL or sTfR >29.5 nmol/L) at least once. Cytokines, ferritin, and sTfR exhibited changes through the 2 years, but changes in cytokines were not associated with alterations in hepcidin, ferritin, or sTfR. In males and females, lower ferritin was associated with lower hepcidin (both P < .0001). One female exhibited higher hepcidin and lower iron stores compared with other individuals, suggesting a different etiology of ID. CONCLUSION: ID is common in highly trained collegiate runners. In general, the high prevalence of ID in this population is not associated with alterations in basal hepcidin or cytokine levels.

Efficacy and safety of adjunctive padsevonil in adults with drug-resistant focal epilepsy: Results from two double-blind, randomized, placebo-controlled trials.

OBJECTIVE: To characterize efficacy, safety/tolerability, and pharmacokinetics of padsevonil (PSL) administered concomitantly with ≤3 antiseizure medications (ASMs) for observable focal seizures in adults with drug-resistant epilepsy in two multicenter, randomized, double-blind, placebo-controlled, parallel-group trials. METHODS: The phase 2b dose-finding trial (EP0091/NCT03373383) randomized patients 1:1:1:1:1 to PSL 50/100/200/400 mg or placebo twice daily (b.i.d.). The phase 3 efficacy trial (EP0092/NCT03739840) randomized patients 1:1:1:1 to PSL 100/200/400 mg or placebo b.i.d. Patients with observable (focal aware with motor symptoms, focal impaired awareness, focal to bilateral tonic-clonic) focal seizures for ≥3 years, experiencing them ≥4 times per 28 days including during the 4-week baseline period despite treatment with ≥4 lifetime ASMs including current ASMs, were enrolled. RESULTS: In EP0091 and EP0092, 410 and 231 patients, respectively, were randomized and received at least one dose of trial medication. In patients in EP0091 on PSL 50/100/200/400 mg b.i.d. (n = 80/82/81/81, respectively) versus placebo (n = 81), outcomes included percentage reductions over placebo in observable focal seizure frequency during the 12-week maintenance period: 17.2%, 19.1% (p = 0.128), 19.2% (p = 0.128), 12.4% (p = 0.248); 75% responder rates (p-values for odds ratios): 13.8%, 12.2% (p = 0.192), 11.1% (p = 0.192), 16.0% (p = 0.124) versus 6.2%; 50% responder rates: 33.8% (p = 0.045), 31.7% (p = 0.079), 25.9% (p = 0.338), 32.1% (p = 0.087), versus 21.0%; TEAEs were reported by 82.7% (67/81), 78.3% (65/83), 74.4% (61/82), 90.1% (73/81) versus 78.3% (65/83). In patients in EP0092 on PSL 100/200/400 mg b.i.d. (n = 60/56/56, respectively) versus placebo (n = 54), outcomes included percentage reductions over placebo: -5.6% (p = 0.687), 6.5% (p = 0.687), 6.3% (p = 0.687); 75% responder rates: 15.3% (p = 0.989), 12.5% (p = 0.989), 14.3% (p = 0.989) versus 13.0%; 50% responder rates: 35.6% (p = 0.425), 33.9% (p = 0.625), and 42.9% (p = 0.125) versus 27.8%; TEAEs were reported by 80.0% (48/60), 78.9% (45/57), 83.1% (49/59) versus 67.3% (37/55). SIGNIFICANCE: In both trials, the primary outcomes did not reach statistical significance in any PSL dose group compared with placebo. PSL was generally well tolerated, and no new safety signals were identified.

ActivPAL accuracy in determining metabolic rate during walking, running and cycling.

To evaluate the ActivPAL's (AcP) ability to estimate METs during walking, running and cycling. Twenty physically active participants performed two submaximal exercises using a treadmill and cycle ergometer. The treadmill session involved varying speeds with a fixed grade and varying grade at fixed walking and running speeds. The cycling session involved fixed power, while cadence was varied and fixed cadence, while power was varied. Four AcPs (two AcP3 & two AcP4) were worn. ActivPAL MET estimations were compared to METS determined via indirect calorimetry. The AcP MET estimations between units and models did not differ. The AcP underestimated (-15% to -61%) METs with increasing speed and was unable to detect an increase in metabolic rate with a change in grade for walking and running. The AcP underestimated (-33% to -60%) METs during cycling and was unable to detect increases in metabolic rate when cadence was fixed, while power increased. The AcP can identify when exercise occurs and provides consistent information across units/models. However, the current AcP algorithm does not provide accurate estimates of METs during walking, running and cycling in a controlled laboratory setting, which would suggest limited accuracy in the field.

The importance of lean mass and iron deficiency when comparing hemoglobin mass in male and female athletic groups.

Hemoglobin mass (Hbmass) is important for athletes because it helps determine maximal aerobic power. This study examined how lean mass, iron deficiency (ID), and sex influence Hbmass in athletic and nonathletic groups. NCAA Division I student athletes (21 men, 75 women; altitude: 1,625 m) were recruited from six athletic teams; 14 male and 12 female full-time students (non-varsity athletes) served as control subjects. Hbmass, body composition, and iron homeostasis parameters, including ferritin, soluble transferrin receptor (sTfR), hepcidin, erythroferrone, and 10 inflammatory cytokines, were measured two to four times across a competitive/training season. ID was defined as ferritin < 25 ng/mL. Hbmass was more closely related to lean mass (r2 = 0.90) than body mass (r2 = 0.69, P < 0.01). Compared with female subjects, male subjects had 19.9% higher Hbmass relative to body mass (HbmassBM) but only 7.5% higher Hbmass relative to lean mass (HbmassLEAN) (both P < 0.001). Prevalence of ID was higher in female than male subjects (47% vs. 9%, P < 0.01) but did not vary between groups. HbmassLEAN was 5% lower in ID vs. non-ID female subjects; HbmassBM was not different. ID was associated with lower hepcidin, elevated sTfR, and elevated erythroferrone but not with differences in inflammatory cytokines. Hbmass varied significantly between athletic groups and across sex, but the majority of these differences are explained by differences in lean mass. ID was common in female subjects and was associated with lower HbmassLEAN and hepcidin but not with differences in HbmassBM or inflammatory cytokines. Hbmass relative to lean mass seems advantageous when monitoring iron deficiency.NEW & NOTEWORTHY Differences in hemoglobin mass (Hbmass) between groups and across sex are primarily due to differences in lean mass. Iron deficiency (ID) independently decreases Hbmass; this effect is best characterized with Hbmass relative to lean mass. ID is common in females and is associated with lower hepcidin and elevated erythroferrone but not with differences in inflammatory cytokines. Hbmass relative to lean mass accurately quantifies hematological alterations secondary to iron deficiency.

Chronic Exposure to Low-Dose Carbon Monoxide Alters Hemoglobin Mass and V˙O2max.

By blocking the oxygen binding sites on the hemoglobin molecule, chronic low-dose carbon monoxide (CO) administration may produce similar effects to those of exposure to altitude. PURPOSE: This study aimed to determine the effect of chronic low-dose CO application on hemoglobin mass (Hbmass) and V˙O2max. METHODS: For 3 wk, 11 healthy and moderately trained male subjects inhaled a CO bolus five times per day to increase their HbCO concentration by ~5%. Another 11 subjects received a placebo. Hbmass, serum erythropoietin concentration, ferritin, and basic hematological parameters were determined before and weekly during and until 3 wk after the CO inhalation period. V˙O2max tests on a cycle ergometer were performed before and after the CO administration period. RESULTS: In the CO group, Hbmass increased from 919 ± 69 to 962 ± 78 g in week 3 (P < 0.001) and was maintained for the following 3 wk. Reticulocytes (%) and immature reticulocyte fraction significantly increased after 1 wk. Serum erythropoietin concentration tended to increase after 1 wk (P = 0.07) and was suppressed in the postperiod (P < 0.01). Ferritin decreased during the inhalation period (from 106 ± 37 to 72 ± 37 ng·mL, P < 0.001). V˙O2max tended to increase from 4230 ± 280 to 4350 ± 350 mL·min (P < 0.1) immediately after the inhalation period and showed a significant relationship to the change in Hbmass (y = 4.1x - 73.4, r = 0.70, P < 0.001). CONCLUSIONS: Chronic continuous exposure to low-dose CO enhances erythropoietic processes resulting in a 4.8% increase in Hbmass. The individual changes in Hbmass were correlated to the corresponding changes in V˙O2max. Examination of ethical and safety concerns is warranted before the implementation of low-dose CO inhalation in the clinical/athletic setting as a tool for modifying Hbmass.

A Retrospective Analysis of Collegiate Athlete Blood Biomarkers at Moderate Altitude.

Morris, KL, Widstrom, L, Goodrich, J, Poddar, S, Rueda, M, Holliday, M, San Millian, I, and Byrnes, WC. A retrospective analysis of collegiate athlete blood biomarkers at moderate altitude. J Strength Cond Res 33(11): 2913-2919, 2019-Blood biomarkers are used to assess overall health and determine positive/negative adaptations to training/environmental stimuli. This study aimed to describe the changes in blood biomarkers in collegiate football (FB) (n = 31) and cross-country (XC) (n = 29; 16 women [FXC], 13 men [MXC]) athletes across a competitive season while training and living at a moderate altitude (1,655 m). This study used a database of previously collected hematological (complete blood count and serum ferritin) and muscle damage (lactate dehydrogenase and creatine kinase) blood biomarkers. Data were analyzed both within and between groups using linear mixed-model and variance component analyses, alpha = 0.05. All 3 groups had significant but different patterns of change in the measured biomarkers. Hematological blood biomarkers increased at different time points but remained within the normal reference ranges with greater between-subject vs. within-subject variability, suggesting no significant decrements to oxygen-carrying capacity across the season for FB, MXC, or FXC. Muscle damage biomarkers increased over time and exceeded the normal reference ranges, indicating cell damage pathology. However, it is also possible that the demands of training and competition might alter baseline values in these athletes, although this cannot be confirmed with the current experimental design. The patterns of change in the hematological and muscle damage biomarkers varied by sport discipline, suggesting that the training/competitive environments of these athletes influence these changes. Further studies should assess how much training, altitude, and nutrition influence these changes by using a more comprehensive set of biomarkers and related performance parameters.

Safety and tolerability of adjunctive lacosamide in a pediatric population with focal seizures - An open-label trial.

PURPOSE: To evaluate safety and tolerability of adjunctive lacosamide in children with focal seizures. METHODS: Patients were eligible for this open-label, fixed-titration trial (SP0847; NCT00938431) if aged 1 month-17 years with focal seizures taking 1-3 antiepileptic drugs. Findings from Cohort 1, aged 5-11 years, who received lacosamide ≤8 mg/kg/day, informed dosing for age-based cohorts 2-5, who then received ≤12 mg/kg/day (≤600 mg/day). Oral lacosamide was initiated at 2 mg/kg/day (1 mg/kg bid) and uptitrated by 2 mg/kg/day/week to the maximum cohort-defined dose (maximum trial duration: 13 weeks). Patients who did not achieve the maximum cohort-defined dose were discontinued. RESULTS: Forty-seven patients (aged 6 months-≤17 years) enrolled (≥1 month-<4 years: n = 15; ≥4-<12 years: n = 23; ≥12-≤17 years: n = 9). 24/47 (51.1%) patients completed the trial at the maximum cohort-defined dose and 40/47 (85.1%) continued lacosamide in the extension trial. Treatment-emergent adverse events (TEAEs) were reported by 42/47 (89.4%) patients. The most common TEAEs (≥10% of patients) were vomiting (21.3%), diarrhea (14.9%), somnolence (12.8%), irritability, dizziness, and pyrexia (10.6% each). Twenty (42.6%) patients discontinued due to TEAEs, most commonly vomiting (8.5%), gait disturbance, dizziness, and somnolence (6.4% each). Six (12.8%) patients reported serious TEAEs, most commonly status epilepticus (3/47; 6.4%). CONCLUSION: This fixed-titration trial supports the safety of adjunctive lacosamide in children (aged 6 months-≤17 years) with focal seizures. The TEAE profile was generally consistent with that observed in trials in adults, and no new safety concerns were identified.

Cardiometabolic Effects of a Workplace Cycling Intervention.

BACKGROUND: In laboratory settings, cycling workstations improve cardiometabolic risk factors. Our purpose was to quantify risk factors following a cycling intervention in the workplace. METHODS: Twenty-one office workers who sat at work ≥6 hours per day underwent baseline physiological measurements (resting blood pressure, blood lipid profile, maximum oxygen consumption [V˙O2max], body composition, and 2-h oral glucose tolerance test). Participants were randomly assigned to a 4-week intervention only group (n = 12) or a delayed intervention group (n = 9) that involved a 4-week control condition before beginning the intervention. During the intervention, participants were instructed to use the cycling device a minimum of 15 minutes per hour, which would result in a total use of ≥2 hours per day during the workday. Following the intervention, physiological measurements were repeated. RESULTS: Participants averaged 1.77 (0.48) hours per day of cycling during the intervention with no changes in actigraphy-monitored noncycling physical activity. Four weeks of the workplace intervention increased V˙O2max (2.07 [0.44] to 2.17 [0.44] L·min-1, P < .01); end of V˙O2max test power output (166.3 [42.2] to 176.6 [46.1] W, P < .01); and high-density lipoprotein cholesterol (1.09 [0.17] to 1.17 [0.24] mmol·L-1, P = .04). CONCLUSIONS: A stationary cycling device incorporated into a sedentary workplace for 4 weeks improves some cardiometabolic risk factors with no compensatory decrease in noncycling physical activity.

Erythropoietic effects of low-dose cobalt application.

Cobaltous ions (Co2+ ) stabilize HIFα, increase endogenous erythropoietin (EPO) production, and may, therefore, be used as a performance-enhancing substance. To date, the dosage necessary to stimulate erythropoiesis is unknown. The aim of this study was, therefore, to determine the minimum dosage necessary to increase erythropoietic processes. In a first double-blind placebo-controlled study (n = 5), single oral Co2+ dosages of 5 mg (n = 6) and 10 mg (n = 7) were administered to healthy young men. Cubital venous blood and urine samples were collected before and up to 24 hours after Co2+ administration. In a second study, the same daily Co2+ dosages were administered for five days (placebo: n = 5, 5 mg: n = 9, 10 mg: n = 7). Blood and urine samples were taken the day before administration and at day 3 and day 5. Plasma [EPO] was elevated by 20.5 ± 16.9% at 5 hours after the single 5-mg administration (p < 0.05) and by 52.8 ± 23.5% up to 7 hours following the 10-mg Co2+ administration (p < 0.001). Urine [Co2+ ] transiently increased, with maximum values 3-5 hours after Co2+ ingestion (5 mg: from 0.8 ± 1.1 to 153.6 ± 109.4 ng/mL, 10 mg: from 1.3 ± 1.7 to 338.0 ± 231,5 ng/mL). During the five days of Co2+ application, 5 mg showed a strong tendency to increase [EPO], while the 10-mg application significantly increased [EPO] at day 5 by 27.2 ± 26.4% (p < 0.05) and the immature reticulocyte fraction by 49.9 ± 21.7% (p < 0.01). [Ferritin] was decreased by 12.4 ± 10.4 ng/mL (p < 0.05). An oral Co2+ dosage of 10 mg/day exerts clear erythropoietic effects, and 5 mg/day tended to increase plasma EPO concentration.

Does Metabolic Rate Increase Linearly with Running Speed in all Distance Runners?

Running economy (oxygen uptake or metabolic rate for running at a submaximal speed) is one of the key determinants of distance running performance. Previous studies reported linear relationships between oxygen uptake or metabolic rate and speed, and an invariant cost of transport across speed. We quantified oxygen uptake, metabolic rate, and cost of transport in 10 average and 10 sub-elite runners. We increased treadmill speed by 0.45 m · s -1 from 1.78 m · s -1 (day 1) and 2.01 m · s -1 (day 2) during each subsequent 4-min stage until reaching a speed that elicited a rating of perceived exertion of 15. Average runners' oxygen uptake and metabolic rate vs. speed relationships were best described by linear fits. In contrast, the sub-elite runners' relationships were best described by increasing curvilinear fits. For the sub-elites, oxygen cost of transport and energy cost of transport increased by 12.8% and 9.6%, respectively, from 3.58 to 5.14 m · s -1 . Our results indicate that it is not possible to accurately predict metabolic rates at race pace for sub-elite competitive runners from data collected at moderate submaximal running speeds (2.68-3.58 m · s -1 ). To do so, metabolic rate should be measured at speeds that approach competitive race pace and curvilinear fits should be used for extrapolation to race pace.

The Influence of Oxygen Saturation on the Relationship Between Hemoglobin Mass and VO 2 max.

Hemoglobin mass (tHb) is a key determinant of maximal oxygen uptake (VO 2 max). We examined whether oxyhemoglobin desaturation (ΔS a O 2 ) at VO 2 max modifies the relationship between tHb and VO 2 max at moderate altitude (1,625 m). Seventeen female and 16 male competitive, endurance-trained moderate-altitude residents performed two tHb assessments and two graded exercise tests on a cycle ergometer to determine VO 2 max and ΔS a O 2 . In males and females respectively, VO 2 max (ml·kg -1 ·min -1 ) ranged from 62.5-83.0 and 44.5-67.3; tHb (g·kg -1 ) ranged from 12.1-17.5 and 9.1-13.0; and S a O 2 at VO 2 max (%) ranged from 81.7-94.0 and 85.7-95.0. tHb was related to VO 2 max when expressed in absolute terms and after correcting for body mass (r=0.94 and 0.86, respectively); correcting by ΔS a O 2 did not improve these relationships (r=0.93 and 0.83). Additionally, there was a negative relationship between tHb and S a O 2 at VO 2 max (r=-0.57). In conclusion, across a range of endurance athletes at moderate altitude, the relationship between tHb and VO 2 max was found to be similar to that observed at sea level. However, correcting tHb by ΔS a O 2 did not explain additional variability in VO 2 max despite significant variability in ΔS a O 2 ; this raises the possibility that tHb and exercise-induced ΔS a O 2 are not independent in endurance athletes.

Effects of 3 Weeks of Oral Low-Dose Cobalt on Hemoglobin Mass and Aerobic Performance.

Introduction: Cobalt ions (Co2+) stabilize HIFα and increase endogenous erythropoietin (EPO) production creating the possibility that Co2+ supplements (CoSupp) may be used as performance enhancing substances. The aim of this study was to determine the effects of a small oral dosage of CoSupp on hemoglobin mass (Hbmass) and performance with the objective of providing the basis for establishing upper threshold limits of urine [Co2+] to detect CoSupp misuse in sport. Methods: Twenty-four male subjects participated in a double-blind placebo-controlled study. Sixteen received an oral dose of 5 mg of ionized Co2+ per day for 3 weeks, and eight served as controls. Blood and urine samples were taken before the study, during the study and up to 3 weeks after CoSupp. Hbmass was determined by the CO-rebreathing method at regular time intervals, and VO2max was determined before and after the CoSupp administration period. Results: In the Co2+ group, Hbmass increased by 2.0 ± 2.1% (p < 0.001) while all the other analyzed hematological parameters did not show significant interactions of time and treatment. Hemoglobin concentration ([Hb]) and hematocrit (Hct) tended to increase (p = 0.16, p = 0.1) and also [EPO] showed a similar trend (baseline: 9.5 ± 3.0, after 2 weeks: 12.4 ± 5.2 mU/ml). While mean VO2max did not change, there was a trend for a positive relationship between changes in Hbmass and changes in VO2max immediately after CoSupp (r = 0.40, p = 0.11). Urine [Co2+] increased from 0.4 ± 0.3 to 471.4 ± 384.1 ng/ml (p < 0.01) and remained significantly elevated until 2 weeks after cessation. Conclusion: An oral Co2+ dosage of 5 mg/day for 3 weeks effectively increases Hbmass with a tendency to increase hemoglobin concentration ([Hb]) and hematocrit (Hct). Because urine Co2+ concentration remains increased for 2 weeks after cessation, upper limit threshold values for monitoring CoSupp can be established.

Breathing valve resistance alters physiological responses during a graded exercise test.

PURPOSE: To determine the impact of breathing valve resistance on peak aerobic capacity ([Formula: see text]) and running economy (RE) in endurance-trained and recreationally active individuals. METHODS: Ten endurance-trained males (ETM), 10 endurance-trained females (ETF), 10 recreationally active males (RAM), and 10 recreationally active females (RAF) participated in this study. On two separate occasions, subjects performed identical graded exercise treadmill protocols using either a Hans Rudolph 2700 (high resistance) or a Daniels' (low resistance) two-way non-rebreathing valve. Parameters obtained from these protocols included energy expenditure (EE), ventilation ([Formula: see text]), heart rate, respiratory exchange ratio, RE, [Formula: see text], and time to exhaustion (TTE). RESULTS: When using the Daniels' valve, all groups had lower submaximal EE (- 2.4, - 3.4, - 2.7, and - 2.0% for ETM, ETF, RAM, and RAF) and better RE (- 2.7, - 3.5, - 1.9, and - 1.8% for ETM, ETF, RAM and RAF) across all submaximal speeds. Only the ET groups had lower submaximal [Formula: see text] (4.6 and 3.8% for ETM and ETF) when using the Daniels' valve. TTE increased when using the Daniels' valve for all groups (6.0, 10.9, 6.2 and 9.8% for ETM, ETF, RAM and RAF), but [Formula: see text] was unaltered. CONCLUSION: Compared to the Daniels' valve, the Hans Rudolph 2700 valve altered the assessment of RE, submaximal EE, and TTE regardless of fitness level or sex, but did not change [Formula: see text]. Therefore, airflow resistance of a breathing valve must be considered when assessing and comparing EE, RE and TTE in the applied and research settings.

Calculating metabolic energy expenditure across a wide range of exercise intensities: the equation matters.

We compared 10 published equations for calculating energy expenditure from oxygen consumption and carbon dioxide production using data for 10 high-caliber male distance runners over a wide range of running velocities. We found up to a 5.2% difference in calculated metabolic rate between 2 widely used equations. We urge our fellow researchers abandon out-of-date equations with published acknowledgments of errors or inappropriate biochemical/physical assumptions.

Beneficial Effects of Cooling during Constant Power Non-steady State Cycling.

This study compared the effects of cooling on the energetic and associated physiological and perceptual responses to constant power, non-steady state cycling. Twelve males cycled at their lactate threshold power for 60 min or until exhaustion under 3 conditions: wearing a cooling vest and sleeves (COOL), a synthetic shirt embedded with an active particle technology claimed to facilitate evaporative heat loss (EVAP), and a standard synthetic shirt (CON). When adjusted for time, the increase in gastrointestinal temperature from baseline was reduced during COOL and EVAP compared to CON (1.44±0.45 and 1.52±0.43 vs. 1.66±0.45°C, p<0.05). Sweat rate was reduced during COOL compared to EVAP and CON (1 312±331 vs. 1 525±393 and 1 550±548 mL·h-1, p<0.01). Gross efficiency decreased over time across conditions (p<0.01), but COOL attenuated this decrease by 22% compared to CON (p<0.05). The rating of perceived exertion was reduced during COOL and EVAP compared to CON (p<0.01). In conclusion, cooling using a vest and sleeves or wearing an active particle technology shirt reduced the rise in gastrointestinal temperature and rating of perceived exertion compared to a standard synthetic shirt. Cooling using a vest and sleeves also reduced the decrease in gross efficiency and sweat rate compared to wearing the standard synthetic shirt.

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial.

OBJECTIVE: To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). METHODS: Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose. Investigators could adjust the LCM dose to 100-800 mg/day and add up to two antiepileptic drugs to optimize tolerability and seizure reduction. RESULTS: Three hundred twenty-two patients received LCM: 210 patients (65.2%) completed and 112 (34.8%) discontinued, most commonly owing to withdrawal of consent (9.3%). Two hundred fifty-eight patients (80.1%) had ≥1 year of and 216 (67.1%) had ≥2 years of LCM exposure, of whom 179/258 (69.4%) achieved LCM monotherapy lasting for any 12-month period, and 126/216 (58.3%) patients exposed for ≥24 months achieved LCM monotherapy for any 24-month period. Total exposure = 525.5 patient-years. The median modal dose was 500 mg/day. Two hundred ninety-two patients (90.7%) achieved LCM monotherapy at some point during the study. Sixty-five of 87 patients who exited and 193/235 who completed SP902 were exposed for ≥12 months, and 43.1% and 78.2%, respectively, achieved LCM monotherapy for ≥12 months. Median LCM monotherapy duration was 587.0 days (2-791 days); 91.0% of patients reported treatment-emergent adverse events, of which the most common were dizziness (27.3%), headache (17.1%), and nausea (14.3%). Compared with the SP902 study baseline, 74.2% of patients had a ≥50% seizure reduction and 5.6% were seizure-free at 24 months. SIGNIFICANCE: The majority of patients were receiving LCM monotherapy at 0, 12, and 24 months in this OLE. Lacosamide monotherapy (median dose of 500 mg/day) had a safety profile similar to that of adjunctive therapy studies. These results support the use of lacosamide as long-term monotherapy treatment for adults with POS.