Stage racing at altitude induces hemodilution despite an increase in hemoglobin mass

2014 ◽  
Vol 117 (5) ◽  
pp. 463-472 ◽  
Author(s):  
Laura A. Garvican-Lewis ◽  
Yorck O. Schumacher ◽  
Sally A. Clark ◽  
Ryan Christian ◽  
Paolo Menaspà ◽  
...  

Plasma volume (PV) can be modulated by altitude exposure (decrease) and periods of intense exercise (increase). Cycle racing at altitude combines both stimuli, although presently no data exist to document which is dominant. Hemoglobin mass (Hbmass), hemoglobin concentration ([Hb]), and percent reticulocytes (%Retics) of altitude (ALT; n = 9) and sea-level (SL; n = 9) residents were measured during a 14-day cycling race, held at 1,146–4120 m, as well as during a simulated tour near sea level (SIM; n = 12). Hbmass was assessed before and on days 9 and 14 of racing. Venous blood was collected on days 0, 3, 6, 10, and 14. PV was calculated from Hbmass and [Hb]. A repeated-measures ANOVA was used to assess the impact of racing at altitude over time, within and between groups. [Hb] decreased significantly in all groups over time ( P < 0.0001) with decreases evident on the third day of racing. %Retics increased significantly in SL only ( P < 0.0001), with SL values elevated at day 6 compared with prerace ( P = 0.02), but were suppressed by the end of the race ( P = 0.0002). Hbmass significantly increased in SL after 9 ( P = 0.0001) and 14 ( P = 0.008) days of racing and was lower at the end of the race than midrace ( P = 0.018). PV increased in all groups ( P < 0.0001). Multiday cycle racing at altitude induces hemodilution of a similar magnitude to that observed during SL racing and occurs in nonacclimatized SL residents, despite an altitude-induced increase in Hbmass. Osmotic regulatory mechanisms associated with intense exercise appear to supersede acute enhancement of oxygen delivery at altitude.

2012 ◽  
Vol 7 (1) ◽  
pp. 79-83 ◽  
Author(s):  
Torben Pottgiesser ◽  
Laura A. Garvican ◽  
David T. Martin ◽  
Jesse M. Featonby ◽  
Christopher J. Gore ◽  
...  

Hemoglobin mass (tHb) is considered to be a main factor for sea-level performance after “live high–train low” (LHTL) altitude training, but little research has focused on the persistence of tHb following cessation of altitude exposure. The aim of the case study was to investigate short-term effects of various hematological measures including tHb upon completion of a simulated altitude camp. Five female cyclists spent 26 nights at simulated altitude (LHTL, 16.6 ± 0.4 h/d, 3000 m in an altitude house) where tHb was measured at baseline, at cessation of the camp, and 9 d thereafter. Venous blood measures (hemoglobin concentration, hematocrit, %reticulocytes, serum erythropoietin, ferritin, lactate dehydrogenase, and haptoglobin) were determined at baseline; on day 21 during LHTL; and at days 2, 5, and 9 after LHTL. Hemoglobin mass increased by 5.5% (90% confidence limits [CL] 2.5 to 8.5%, very likely) after the LHTL training camp. At day 9 after simulated LHTL, tHb decreased by 3.0% (90%CL −5.1 to −1.0%, likely). There was a substantial decrease in serum EPO (−34%, 90%CL −50 to −12%) at 2 d after return to sea level and a rise in ferritin (23%, 90%CL 3 to 46%) coupled with a decrease in %reticulocytes (−23%, 90%CL −34 to −9%) between day 5 and 9 after LHTL. Our findings show that following a hypoxic intervention with a beneficial tHb outcome, there may be a high probability of a rapid tHb decrease upon return to normoxic conditions. This highlights a rapid component in red-cell control and may have implications for the appropriate timing of altitude training in relation to competition.


2020 ◽  
pp. 1-6
Author(s):  
Yan Wang ◽  
Zong-hui Dang ◽  
Liang-ying Gan ◽  
Ciren Luobu ◽  
Lei Zhang ◽  
...  

Background: It is known that hypoxia influences many of the biologic processes involved in erythropoiesis; therefore, the high-altitude hypoxia may affect erythropoietin (EPO) responsiveness in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the impact of altitude on EPO responsiveness in MHD patients. Methods: In this retrospective study, MHD patients from Tibet Autonomous Region People’s Hospital (3,650 m above sea level) and Peking University People’s Hospital (43.5 m above sea level) were recruited between May 2016 and December 2018. Patients were divided into 2 groups according to altitude. Variables including age, sex, dialysis vintage, dialysis modality, duration of EPO use, EPO doses, and laboratory tests were collected and analyzed. EPO responsiveness was measured in terms of the EPO resistance index (ERI). ERI was defined as the weekly weight-adjusted dose of EPO (IU/kg/week) divided by hemoglobin concentration (g/dL). The association between ERI and altitude was estimated using a multivariable linear regression model. Results: Sixty-two patients from Tibet Autonomous Region People’s Hospital (high-altitude [HA] group) and 102 patients from Peking University People’s Hospital (low-altitude [LA] group) were recruited. The ERI for HA group and LA group was 6.9 ± 5.1 IU w−1 kg−1 (g/dL)−1 and 11.5 ± 6.4 IU w−1 kg−1 (g/dL)−1, respectively. After adjusting for covariates by multivariable regression, altitude was independently associated with ERI (R2 = 0.245, p < 0.001). Conclusion: Altitude had an independent negative correlation with ERI. This result supported the hypothesis that altitude-associated hypoxia improved EPO responsiveness in MHD patients.


Author(s):  
Andreas Breenfeldt Andersen ◽  
Thomas Christian Bonne ◽  
Jacob Bejder ◽  
Grace Jung ◽  
Tomas Ganz ◽  
...  

Current markers of iron deficiency (ID) such as ferritin and hemoglobin have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a four-week baseline, a four-week intervention at either sea level or altitude, and a four-week follow-up. Participants (n=39) were randomly assigned to 20 IU·kg bw-1 rHuEPO or placebo injections every second day for three weeks during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P≤0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE (P<0.05) and hepcidin levels (P<0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared to altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P<0.05) and ERFE (P≤0.001) parallel with increases in hematocrit (P<0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2=0.13, P<0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an anti-doping context.


2020 ◽  
Vol 128 (2) ◽  
pp. 390-396 ◽  
Author(s):  
Karleigh E. Bradbury ◽  
Beau R. Yurkevicius ◽  
Katherine M. Mitchell ◽  
Kirsten E. Coffman ◽  
Roy M. Salgado ◽  
...  

Acetazolamide (AZ) is a medication commonly used to prevent acute mountain sickness (AMS) during rapid ascent to high altitude. However, it is unclear whether AZ use impairs exercise performance; previous literature regarding this topic is equivocal. The purpose of this study was to evaluate the impact of AZ on time-trial (TT) performance during a 30-h exposure to hypobaric hypoxia equivalent to 3,500-m altitude. Ten men [sea-level peak oxygen consumption (VO2peak): 50.8 ± 6.5 mL·kg−1·min−1; body fat %: 20.6 ± 5.2%] completed 2 30-h exposures at 3,500 m. In a crossover study design, subjects were given 500 mg/day of either AZ or a placebo. Exercise testing was completed 2 h and 24 h after ascent and consisted of 15-min steady-state treadmill walking at 40%–45% sea-level VO2peak, followed by a 2-mile self-paced treadmill TT. AMS was assessed after ~12 h and 22 h at 3,500 m. The incidence of AMS decreased from 40% with placebo to 0% with AZ. Oxygen saturation was higher ( P < 0.05) in AZ versus placebo trials at the end of the TT after 2 h (85 ± 3% vs. 79 ± 3%) and 24 h (86 ± 3% vs. 81 ± 4%). There was no difference in time to complete 2 miles between AZ and PL after 2 h (20.7 ± 3.2 vs. 22.7 ± 5.0 min, P > 0.05) or 24 h (21.5 ± 3.4 vs. 21.1 ± 2.9 min, P > 0.05) of exposure to altitude. Our results suggest that AZ (500 mg/day) does not negatively impact endurance exercise performance at 3,500 m. NEW & NOTEWORTHY To our knowledge, this is the first study to examine the impact of acetazolamide (500 mg/day) versus placebo on self-paced, peak-effort exercise performance using a short-duration exercise test in a hypobaric hypoxic environment with a repeated-measures design. In the present study, acetazolamide did not impact exercise performance after 2-h or 24-h exposure to 3,500-m simulated altitude.


2020 ◽  
Vol 30 (9) ◽  
pp. 1238-1246
Author(s):  
Gloria C. Lehmann ◽  
Philip T. Levy ◽  
Meghna D. Patel ◽  
Timothy Sekarski ◽  
HongJie Gu ◽  
...  

AbstractBackground:Pre-mature birth impacts left ventricular development, predisposing this population to long-term cardiovascular risk. The aims of this study were to investigate maturational changes in rotational properties from the neonatal period through 1 year of age and to discern the impact of cardiopulmonary complications of pre-maturity on these measures.Methods:Pre-term infants (<29 weeks at birth, n = 117) were prospectively enrolled and followed to 1-year corrected age. Left ventricular basal and apical rotation, twist, and torsion were measured by two-dimensional speckle-tracking echocardiography and analysed at 32 and 36 weeks post-menstrual age and 1-year corrected age. A mixed random effects model with repeated measures analysis was used to compare rotational mechanics over time. Torsion was compared in infants with and without complications of cardiopulmonary diseases of pre-maturity, specifically bronchopulmonary dysplasia, pulmonary hypertension, and patent ductus arteriosus.Results:Torsion decreased from 32 weeks post-menstrual age to 1-year corrected age in all pre-term infants (p < 0.001). The decline from 32 to 36 weeks post-menstrual age was more pronounced in infants with cardiopulmonary complications, but was similar to healthy pre-term infants from 36 weeks post-menstrual age to 1-year corrected age. The decline was due to directional and magnitude changes in apical rotation over time (p < 0.05).Conclusion:This study tracks maturational patterns of rotational mechanics in pre-term infants and reveals torsion declines from the neonatal period through 1 year. Cardiopulmonary diseases of pre-maturity may negatively impact rotational mechanics during the neonatal period, but the myocardium recovers by 1-year corrected age.


2020 ◽  
Vol 9 (11) ◽  
pp. 3687
Author(s):  
Ana F. Pereira-da-Mota ◽  
Jéssica Costa ◽  
Ana Amorim-de-Sousa ◽  
José M. González-Méijome ◽  
António Queirós

This study aimed to evaluate the effects of two months of orthokeratology (OK) treatment in the accommodative response of young adult myopes. Twenty eyes (21.8 ± 1.8 years) were fitted with the Paragon CRT® 100 LENS to treat myopia between −1.00 and −2.00 D. Low- and high-contrast visual acuity (LCDVA and HCDVA), central objective refraction, light disturbance (LD), and objective accommodative response (using the Grand Seiko WAM-5500 open-field autorefractometer coupled with a Badal system) were measured at baseline (BL) before lens wear and after 1, 15, 30, and 60 nights of OK. Refractive error correction was achieved during the first fifty days of OK lens wear, with minimal changes afterwards. LD analysis showed a transient increase followed by a reduction to baseline levels over the first 30 nights of treatment. The accommodative response was lower than expected for all target vergences in all visits (BL: 0.61 D at 1.00 D to 0.96 D at 5.00 D; 60 N: 0.36 D at 1.00 D to 0.79 D at 5.00 D). On average, the accommodative lag decreases over time with OK lens wear. However, these differences were not statistically significant (p > 0.050, repeated-measures ANOVA and Friedman test). This shows that overnight OK treatment does not affect objectively measured the accommodative response of young, low myopic eyes after two months of treatment stabilization.


2020 ◽  
pp. 1-11
Author(s):  
Thijs J. Burger ◽  
Frederike Schirmbeck ◽  
Jentien M. Vermeulen ◽  
Piotr J. Quee ◽  
Mariken B. de Koning ◽  
...  

Abstract Background Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients. Methods In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes (‘normal’, ‘mixed’ and ‘impaired’) in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype. Results Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype. Conclusions Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.


2021 ◽  
Author(s):  
James H Ford II ◽  
Aaron Gilson

Abstract Background: Sustainability capacity (SC), which is an organization’s ability to implement and maintain change, is influenced by internal attributes, environmental contextual influencers, and intervention attributes. Temporal changes in staff SC perceptions, as well as the influence of quality improvement collaborative (QIC) participation, has generally not been explored. This project addresses this gap, measuring staff SC perceptions at four time points (baseline and every 9 months) for clinics participating in an intervention – the Network for the Improvement of Addiction Treatment QIC initiative (called NIATx200).Methods: A mixed linear model repeated measures analysis was applied to matched staff members (n=908, representing 2,329 total cases) across the evaluation timeframe. Three separate statistical models assessed potential predictors of SC perceptions: Time (Models I-III); NIATx200 intervention, staff job function, and tenure (Models II &III); and NIATx200 participation hours and four organizational variables (Model III).Results: For Model I, staff perceptions of total SC increased throughout most of the study (t1,4=-6.74, p<.0001; t2,4=-3.100, p<.036; t3,4=-0.23, p=ns). Model II did not change Model I’s overall Time effect, but combined NIATx200 services (t=-2.23, p=.026), staff job function (t=-3.27, p=.001), and organizational administrators (t=-3.50, p=.001) were also significantly associated with greater perceptions of total SC. Inclusion of additional variables in Model III demonstrated the importance of a higher participation level (t=-3.09, p<.002) and being in a free-standing clinic (t=-2.06, p<.04) on staff perceptions of total SC. Conclusion: Although staff exposure to sustainability principals was minimal in NIATx200, staff perceptions about their organization’s SC significantly differed over time. However, an organization’s participation level in a QIC became the principal predictor of staff SC perceptions, regardless of other factors’ influence. Given these findings, it is possible to develop and introduce specific sustainability content within the structure of a QIC to assess the impact on staff SC perceptions over time and the sustainment of organizational change.Trial Registration: ClinicalTrials.gov, NCT00934141 Registered July 6, 2009. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT00934141


2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 174-174
Author(s):  
Elizabeth Ann Kvale ◽  
Maria J Pisu ◽  
Courtney Williams ◽  
Kelly Kenzik ◽  
Andres Azuero ◽  
...  

174 Background: Patient navigation programs in cancer care have historically focused on assisting persons to overcome barriers to accessing care. Evidence is emerging to support the impact of navigation interventions across the cancer continuum. However, navigation programs have varied designs, resulting in a lack of clarity about the optimal approach to delivering services to patients, and a lack of evidence linking program design to outcomes. Methods: A planned retrospective analysis of Medicare administrative claims for a population of older beneficiaries diagnosed with cancer: The main exposure was the number of contacts in person or over the phone with PCCP navigators in the 6 month period starting from the quarter in which patients enrolled in the PCCP. Repeated measures generalized linear models with normal distribution were used to evaluate trends in total cost over time based on: number of contacts, quarters post-enrollment (TIME), and the interaction between number of contacts and TIME. Intra-correlation was controlled for repeated measures. Results: 4,337 patients were included in this analysis. 17.9% had one contact, 17.7% had two, 22.2% had 3-4, 24.2% had 5-10, and 18.0% had more than 10 contacts. African Americans had a greater number of participants with more than 10 navigator contacts, as stage 4 cancers, and initial or end-of-life phase of care. Patients who received more than 3 contacts had significantly higher levels of baseline cost. Models to evaluate total cost over time demonstrate an effect of navigator contact on cost that is associated with number of contacts. This trend is statistically significant at 3-4 contacts or more, and remains significant at 10 or more contacts. Conclusions: Increased navigator contact is associated with increased slope of decline in utilization and cost indicates that navigation programs should be adequately resourced to deliver care that enables navigators to have contact with patients a minimum of 3-4 contacts over a six month period.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11539-11539
Author(s):  
Suzanne George ◽  
Michael C. Heinrich ◽  
John Raymond Zalcberg ◽  
Sebastian Bauer ◽  
Hans Gelderblom ◽  
...  

11539 Background: Ripretinib is a novel switch-control TKI that broadly inhibits KIT and PDGFRA kinase signaling. In INVICTUS (NCT03353753), a randomized, double-blind, placebo (PBO)-controlled trial of ripretinib in ≥4th-line advanced GIST, ripretinib reduced the risk of disease progression or death by 85% vs PBO with a favorable overall safety profile. Common ( > 20%) adverse events (AEs) included, but were not limited to, alopecia and PPES. Exploratory analyses evaluated the impact of alopecia and PPES on quality of life (QoL). Methods: Patients (pts) with advanced GIST previously treated with at least imatinib, sunitinib, and regorafenib were randomized (2:1) to ripretinib 150 mg QD or PBO. AEs were graded using CTCAE v4 and PROs collected using EQ-5D-5L (EQ5D) and EORTC QLQ-C30 (C30). Repeated measures (RM) models assessed the impact of alopecia and PPES on 5 PROs (EQ5D visual analogue scale; and C30 physical functioning, role functioning, and the overall health and overall QoL questions) within the ripretinib arm. Fixed effects were sex, alopecia/PPES, and ECOG scores at baseline. Results: 128/129 randomized pts received treatment (85 ripretinib 150 mg QD; 43 PBO). Alopecia, regardless of causality, occurred in 44 (51.8%) on ripretinib (34 [40.0%] grade 1; 10 [11.8%] grade 2) and 2 (4.7%) on PBO (both grade 1). PPES occurred in 18 (21.2%) on ripretinib (11 [12.9%] grade 1; 7 [8.2%] grade 2); none on PBO. The median times in days to first occurrence and worst severity grade with ripretinib were 57.0 and 62.5 for alopecia; 56.5 and 57.0 for PPES. The RM models showed a slight trend towards improvement in PRO score over time for pts with alopecia; the only association reaching a P-value of < 0.05 was between alopecia and increased overall QoL. None of the associations between PPES and PRO scores reach P < 0.05. All PRO p-values are nominal, and no statistical significance is being claimed. Conclusions: Ripretinib had a favorable overall safety and tolerability profile. When stratified by alopecia and PPES, patient-reported assessments of function, overall health, and overall QoL were maintained over time. For both alopecia and PPES, onset and maximum severity occurred almost simultaneously, indicating that these events generally did not progressively worsen. These results suggest that alopecia and PPES are manageable and do not have a negative effect on function, overall health, and QoL. Clinical trial information: NCT03353753 .


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