Support-vector classification of low-dose nitrous oxide administration with multi-channel EEG power spectra.

Support-vector machines (SVMs) can potentially improve patient monitoring during nitrous oxide anaesthesia. By elucidating the effects of low-dose nitrous oxide on the power spectra of multi-channel EEG recordings, we quantified the degree to which these effects generalise across participants. In this single-blind, cross-over study, 32-channel EEG was recorded from 12 healthy participants exposed to 0, 20, 30 and 40% end-tidal nitrous oxide. Features of the delta-, theta-, alpha- and beta-band power were used within a 12-fold, participant-wise cross-validation framework to train and test two SVMs: (1) binary SVM classifying EEG during 0 or 40% exposure (chance = 50%); (2) multi-class SVM classifying EEG during 0, 20, 30 or 40% exposure (chance = 25%). Both the binary (accuracy 92%) and the multi-class (accuracy 52%) SVMs classified EEG recordings at rates significantly better than chance (p < 0.001 and p = 0.01, respectively). To determine the relative importance of frequency band features for classification accuracy, we systematically removed features before re-training and re-testing the SVMs. This showed the relative importance of decreased delta power and the frontal region. SVM classification identified that the most important effects of nitrous oxide were found in the delta band in the frontal electrodes that was consistent between participants. Furthermore, support-vector classification of nitrous oxide dosage is a promising method that might be used to improve patient monitoring during nitrous oxide anaesthesia.

Full-face snorkel masks increase the incidence of hypoxaemia and hypercapnia during simulated snorkelling compared to conventional snorkels.

Introduction: Air flow in full-face snorkel masks (FFSMs) should be unidirectional to prevent rebreathing of exhaled air. This study evaluated rebreathing and its consequences when using FFSMs compared to a conventional snorkel. Methods: In a dry environment 20 participants wore three types of snorkel equipment in random order: Subea Easybreath FFSM; QingSong 180-degree panoramic FFSM; and a Beuchat Spy conventional snorkel (with nose clip), in three conditions: rest in a chair; light; and moderate intensity exercise on a cycle ergometer. Peripheral oxygen saturation, partial pressure of carbon dioxide (PCO2) and oxygen (PO2) in the end tidal gas and FFSM eye-pockets, respiratory rate, minute ventilation, were measured continuously. Experiments were discontinued if oxygen saturation dropped below 85%, or if end-tidal CO2 exceeded 7.0 kPa. Results: Experimental runs with the FFSMs had to be discontinued more often after exceeding 7.0 kPa end-tidal CO2 compared to a conventional snorkel e.g., 18/40 (45%) versus 4/20 (20%) during light intensity exercise, and 9/22 (41%) versus 3/16 (19%) during moderate intensity exercise. Thirteen participants exhibited peripheral oxygen saturations below 95% (nine using FFSMs and four using the conventional snorkel) and five fell below 90% (four using FFSMs and one using the conventional snorkel). The PCO2 and PO2 in the eye-pockets of the FFSMs fluctuated and were significantly higher and lower respectively than in inspired gas, which indicated rebreathing in all FFSM wearers. Conclusions: Use of FFSMs may result in rebreathing due to non-unidirectional flow, leading to hypercapnia and hypoxaemia.

Comparing the EMMA capnograph with sidestream capnography and arterial carbon dioxide pressure at 284 kPa.

Introduction: Capnography aids assessment of the adequacy of mechanical patient ventilation. Physical and physiological changes in hyperbaric environments create ventilation challenges which make end-tidal carbon dioxide (ETCO2) measurement particularly important. However, obtaining accurate capnography in hyperbaric environments is widely considered difficult. This study investigated the EMMA capnograph for hyperbaric use. Methods: We compared the EMMA capnograph to sidestream capnography and the gold standard arterial carbon dioxide blood gas analysis in a hyperbaric chamber. In 12 resting subjects breathing air at 284 kPa, we recorded ETCO2 readings simultaneously derived from the EMMA and sidestream capnographs during two series of five breaths (total 24 measurements). An arterial blood gas sample was also taken simultaneously in five participants. Results: Across all measurements there was a difference of about 0.1 kPa between the EMMA and sidestream capnographs indicating a very slight over-estimation of ETCO2 by the EMMA capnograph, but fundamentally good agreement between the two end-tidal measurement methods. Compared to arterial blood gas pressure the non-significant difference was about 0.3 and 0.4 kPa for the EMMA and sidestream capnographs respectively. Conclusions: In this study, the EMMA capnograph performed equally to the sidestream capnograph when compared directly, and both capnography measures gave clinically acceptable estimates of arterial PCO2.

A systematic review of electroencephalography in acute cerebral hypoxia: clinical and diving implications.

Introduction: Hypoxia can cause central nervous system dysfunction and injury. Hypoxia is a particular risk during rebreather diving. Given its subtle symptom profile and its catastrophic consequences there is a need for reliable hypoxia monitoring. Electroencephalography (EEG) is being investigated as a real time monitor for multiple diving problems related to inspired gas, including hypoxia. Methods: A systematic literature search identified articles investigating the relationship between EEG changes and acute cerebral hypoxia in healthy adults. Quality of clinical evidence was assessed using the Newcastle-Ottawa scale. Results: Eighty-one studies were included for analysis. Only one study investigated divers. Twelve studies described quantitative EEG spectral power differences. Moderate hypoxia tended to result in increased alpha activity. With severe hypoxia, alpha activity decreased whilst delta and theta activities increased. However, since studies that utilised cognitive testing during the hypoxic exposure more frequently reported opposite results it appears cognitive processing might mask hypoxic EEG changes. Other analysis techniques (evoked potentials and electrical equivalents of dipole signals), demonstrated sustained regulation of autonomic responses despite worsening hypoxia. Other studies utilised quantitative EEG analysis techniques, (Bispectral index [BISTM], approximate entropy and Lempel-Ziv complexity). No change was reported in BISTM value, whilst an increase in approximate entropy and Lempel-Ziv complexity occurred with worsening hypoxia. Conclusions: Electroencephalographic frequency patterns change in response to acute cerebral hypoxia. There is paucity of literature on the relationship between quantitative EEG analysis techniques and cerebral hypoxia. Because of the conflicting results in EEG power frequency analysis, future research needs to quantitatively define a hypoxia-EEG response curve, and how it is altered by concurrent cognitive task loading.

Connected consciousness after tracheal intubation in young adults: an international multicentre cohort study.

BACKGROUND: Connected consciousness, assessed by response to command, occurs in at least 5% of general anaesthetic procedures and perhaps more often in young people. Our primary objective was to establish the incidence of connected consciousness after tracheal intubation in young people aged 18-40 yr. The secondary objectives were to assess the nature of these responses, identify relevant risk factors, and determine their relationship to postoperative outcomes. METHODS: This was an international, multicentre prospective cohort study using the isolated forearm technique to assess connected consciousness shortly after tracheal intubation. RESULTS: Of 344 enrolled subjects, 338 completed the study (mean age, 30 [standard deviation, 6.3] yr; 232 [69%] female). Responses after intubation occurred in 37/338 subjects (11%). Females (13%, 31/232) responded more often than males (6%, 6/106). In logistic regression, the risk of responsiveness was increased with female sex (odds ratio [ORadjusted]=2.7; 95% confidence interval [CI], 1.1-7.6; P=0.022) and was decreased with continuous anaesthesia before laryngoscopy (ORadjusted=0.43; 95% CI, 0.20-0.96; P=0.041). Responses were more likely to occur after a command to respond (and not to nonsense, 13 subjects) than after a nonsense statement (and not to command, four subjects, P=0.049). CONCLUSIONS: Connected consciousness occured after intubation in 11% of young adults, with females at increased risk. Continuous exposure to anaesthesia between induction of anaesthesia and tracheal intubation should be considered to reduce the incidence of connected consciousness. Further research is required to understand sex-related differences in the risk of connected consciousness.

Does hyperbaric oxygen cause narcosis or hyperexcitability? A quantitative EEG analysis.

Divers breathe higher partial pressures of oxygen at depth than at the surface. The literature and diving community are divided on whether or not oxygen is narcotic. Conversely, hyperbaric oxygen may induce dose-dependent cerebral hyperexcitability. This study evaluated whether hyperbaric oxygen causes similar narcotic effects to nitrogen, and investigated oxygen's hyperexcitability effect. Twelve human participants breathed "normobaric" air and 100% oxygen, and "hyperbaric" 100% oxygen at 142 and 284 kPa, while psychometric performance, electroencephalography (EEG), and task load perception were measured. EEG was analyzed with functional connectivity and temporal complexity algorithms. The spatial functional connectivity, estimated using mutual information, was summarized with the global efficiency network measure. Temporal complexity was calculated with a "default-mode-network (DMN) complexity" algorithm. Hyperbaric oxygen-breathing caused no change in EEG global efficiency or in the psychometric test. However, oxygen caused a significant reduction of DMN complexity and a reduction in task load perception. Hyperbaric oxygen did not cause the same changes in EEG global efficiency seen with hyperbaric air, which likely related to a narcotic effect of nitrogen. Hyperbaric oxygen seemed to disturb the time evolution of EEG patterns that could be taken as evidence of early oxygen-induced cortical hyperexcitability. These findings suggest that hyperbaric oxygen is not narcotic and will help inform divers' decisions on suitable gas mixtures.

Comment on Mankowska et al. Critical Flicker Fusion Frequency: A Narrative Review. Medicina 2021, 57, 1096.

We have read with great interest the review by Mankowska et al. [...].

EEG functional connectivity is sensitive for nitrogen narcosis at 608 kPa.

Divers commonly breathe air, containing nitrogen. Nitrogen under hyperbaric conditions is a narcotic gas. In dives beyond a notional threshold of 30 m depth (405 kPa) this can cause cognitive impairment, culminating in accidents due to poor decision making. Helium is known to have no narcotic effect. This study explored potential approaches to developing an electroencephalogram (EEG) functional connectivity metric to measure narcosis produced by nitrogen at hyperbaric pressures. Twelve human participants (five female) breathed air and heliox (in random order) at 284 and 608 kPa while recording 32-channel EEG and psychometric function. The degree of spatial functional connectivity, estimated using mutual information, was summarized with global efficiency. Air-breathing at 608 kPa (experienced as mild narcosis) caused a 35% increase in global efficiency compared to surface air-breathing (mean increase = 0.17, 95% CI [0.09-0.25], p = 0.001). Air-breathing at 284 kPa trended in a similar direction. Functional connectivity was modestly associated with psychometric impairment (mixed-effects model r2 = 0.60, receiver-operating-characteristic area, 0.67 [0.51-0.84], p = 0.02). Heliox breathing did not cause a significant change in functional connectivity. In conclusion, functional connectivity increased during hyperbaric air-breathing in a dose-dependent manner, but not while heliox-breathing. This suggests sensitivity to nitrogen narcosis specifically.

Arterial blood gas measurements during deep open-water breath-hold dives.

Arterial blood gas (ABG) measurements at both maximum depth and at resurfacing prior to breathing have not previously been measured during free dives conducted to extreme depth in cold open-water conditions. An elite free diver was instrumented with a left radial arterial cannula connected to two sampling syringes through a low-volume splitting device. He performed two open-water dives to a depth of 60 m (197', 7 atmospheres absolute pressure) in the constant weight with fins competition format. ABG samples were drawn at 60 m (by a mixed-gas scuba diver) and again on resurfacing before breathing. An immersed surface static apnea, of identical length to the dives and with ABG sampling at identical times, was also performed. Both dives lasted approximately 2 min. Arterial partial pressure of oxygen ([Formula: see text]) increased during descent from an indicative baseline of 15.8 kPa (after hyperventilation and glossopharyngeal insufflation) to 42.8 and 33.3 kPa (dives 1 and 2) and decreased precipitously (to 8.2 and 8.6 kPa) during ascent. Arterial partial pressure of carbon dioxide ([Formula: see text]) also increased from a low indicative baseline of 2.8 kPa to 6.3 and 5.1 kPa on dives 1 and 2; an increase not explained by metabolic production of CO2 alone since [Formula: see text] actually decreased during ascent (to 5.2 and 4.5 kPa). Surface static apnea caused a steady decrease in [Formula: see text] and increase in [Formula: see text] without the inflections provoked by depth changes. Lung compression and expansion provoke significant changes in both [Formula: see text] and [Formula: see text] during rapid descent and ascent on a deep free dive. These changes generally support predictive hypotheses and previous findings in less extreme settings.NEW & NOTEWORTHY Arterial blood gas measurements at both maximum depth and the surface before breathing on the same dive have not previously been obtained during deep breath-hold dives in cold open-water conditions and competition dive format. Such measurements were obtained in two dives to 60 m (197') of 2 min duration. Changes in arterial oxygen and carbon dioxide (an increase during descent, and a decrease during ascent) support previous observations in less extreme dives and environments.

An Electroencephalogram Metric of Temporal Complexity Tracks Psychometric Impairment Caused by Low-dose Nitrous Oxide.

BACKGROUND: Nitrous oxide produces non-γ-aminobutyric acid sedation and psychometric impairment and can be used as scientific model for understanding mechanisms of progressive cognitive disturbances. Temporal complexity of the electroencephalogram may be a sensitive indicator of these effects. This study measured psychometric performance and the temporal complexity of the electroencephalogram in participants breathing low-dose nitrous oxide. METHODS: In random order, 20, 30, and 40% end-tidal nitrous oxide was administered to 12 participants while recording 32-channel electroencephalogram and psychometric function. A novel metric quantifying the spatial distribution of temporal electroencephalogram complexity, comprised of (1) absolute cross-correlation calculated between consecutive 0.25-s time samples; 2) binarizing these cross-correlation matrices using the median of all channels as threshold; (3) using quantitative recurrence analysis, the complexity in temporal changes calculated by the Shannon entropy of the probability distribution of the diagonal line lengths; and (4) overall spatial extent and intensity of brain complexity, was quantified by calculating median temporal complexity of channels whose complexities were above 1 at baseline. This region approximately overlay the brain's default mode network, so this summary statistic was termed "default-mode-network complexity." RESULTS: Nitrous oxide concentration correlated with psychometric impairment (r = 0.50, P < 0.001). Baseline regional electroencephalogram complexity at midline was greater than in lateral temporal channels (1.33 ± 0.14 bits vs. 0.81 ± 0.12 bits, P < 0.001). A dose of 40% N2O decreased midline (mean difference [95% CI], 0.20 bits [0.09 to 0.31], P = 0.002) and prefrontal electroencephalogram complexity (mean difference [95% CI], 0.17 bits [0.08 to 0.27], P = 0.002). The lateral temporal region did not change significantly (mean difference [95% CI], 0.14 bits [-0.03 to 0.30], P = 0.100). Default-mode-network complexity correlated with N2O concentration (r = -0.55, P < 0.001). A default-mode-network complexity mixed-effects model correlated with psychometric impairment (r2 = 0.67; receiver operating characteristic area [95% CI], 0.72 [0.59 to 0.85], P < 0.001). CONCLUSIONS: Temporal complexity decreased most markedly in medial cortical regions during low-dose nitrous oxide exposures, and this change tracked psychometric impairment.

Investigating critical flicker fusion frequency for monitoring gas narcosis in divers.

INTRODUCTION: Critical flicker fusion frequency (CFFF) has been used in various studies to measure the cognitive effects of gas mixtures at depth, sometimes with conflicting or apparently paradoxical results. This study aimed to evaluate a novel automatic CFFF method and investigate whether CFFF can be used to monitor gas-induced narcosis in divers. METHODS: Three hyperbaric chamber experiments were performed: 1) Automated and manual CFFF measurements during air breathing at 608 kPa (n = 16 subjects); 2) Manual CFFF measurements during air and heliox breathing at sea level (101.3 kPa) and 608 kPa (n = 12); 3) Manual CFFF measurements during oxygen breathing at sea level, 142 and 284 kPa (n = 10). All results were compared to breathing air at sea level. RESULTS: Only breathing oxygen at sea level, and at 284 kPa, caused a significant decrease in CFFF (2.5% and 2.6% respectively compared to breathing air at sea level. None of the other conditions showed a difference with sea level air breathing. CONCLUSIONS: CFFF did not significantly change in our experiments when breathing air at 608 kPa compared to air breathing at sea level pressure using both devices. Based on our results CFFF does not seem to be a sensitive tool for measuring gas narcosis in divers in our laboratory setting.

Pupillometry is not sensitive to gas narcosis in divers breathing hyperbaric air or normobaric nitrous oxide.

INTRODUCTION: Gas narcosis impairs divers when diving deeper. Pupillometry is sensitive to alcohol intoxication and it has been used in anaesthesia to assess nitrous oxide narcosis. It is a potential novel method to quantify narcosis in diving. The aim of this study was to evaluate pupillometry for objective measurement of narcosis during exposure to hyperbaric air or nitrous oxide. METHOD: Pupil size in 16 subjects was recorded directly at surface pressure and during air breathing at 608 kPa (equivalent to 50 metres' seawater depth) in a hyperbaric chamber. Another 12 subjects were exposed to nitrous oxide at end-tidal percentages of 20, 30 and 40% in random order at surface pressure. Pupil size and pupil light reflex were recorded at baseline and at each level of nitrous oxide exposure. RESULTS: Pupil size did not significantly change during exposure to hyperbaric air or nitrous oxide. The pupil light reflex, evaluated using percentage constriction and minimum diameter after exposure to a light stimulus, was affected significantly only during the highest nitrous oxide exposure - an end-tidal level of 40%. CONCLUSION: Pupillometry is insensitive to the narcotic effect of air at 608 kPa in the dry hyperbaric environment and to the effects of low dose nitrous oxide. Pupillometry is not suitable as a monitoring method for gas narcosis in diving.

Deep anaesthesia: The Thailand cave rescue and its implications for management of the unconscious diver underwater.

INTRODUCTION: In 2018 12 children and one adult were anaesthetised before being extricated through over a kilometre of flooded cave in Thailand. Full face dive masks (FFMs) putatively capable of maintaining constant positive airway pressure (CPAP) were employed. Here we describe the anaesthetic intervention and investigate the CPAP capability of the FFM. METHODS: Pressure was measured inside and outside the Interspiro Divator FFM during 10 tidal and 10 vital capacity breaths in divers at the surface and submerged with the mask deployed on open-circuit scuba (10 divers); and a closed-circuit rebreather (five divers). Relative in-mask pressure was calculated as the difference between inside and outside pressures. We also measured the in-mask pressure generated by activation of the second stage regulator purge valve in open-circuit mode. RESULTS: When submerged in open-circuit mode the mean relative in-mask pressure remained positive in normal tidal breathing (inhalation 0.6 kPa [95% CI 0.3-0.9]; exhalation 1.1 [0.8-1.4]) and vital capacity breathing (inhalation 0.8 [0.4-1.1]; exhalation 1.2 [0.9-1.4]). As expected, the relative in-mask pressure was predominantly negative when used on closed-circuit with back mounted counter-lungs due to a negative static lung load. Mean in-mask pressure during purge valve operation was 3.99 kPa (approximately equal to 40 cmH2O) (range: 2.56 to 5.3 kPa). CONCLUSIONS: The CPAP function of the Interspiro Divator FFM works well configured with open-circuit scuba. This may have contributed to the success of the Thailand cave rescue. Caution is required in generalising this success to other diving scenarios.

Adherence to and satisfaction with low-intensity physical activity and supervised moderate-high intensity exercise during chemotherapy for breast cancer.

PURPOSE: In this study, we investigated factors associated with program adherence and patient satisfaction with a home-based physical activity program (Onco-Move, N = 77) and a supervised exercise program with a home-based component (OnTrack, N = 76). METHODS: We assessed adherence via self-report (home-based program) and attendance records (supervised program). We used logistic regression analysis to identify sociodemographic, clinical and behavioural variables associated with program adherence. Patient satisfaction was assessed with self-report and is reported descriptively. RESULTS: Fifty-one percent of Onco-Move and 62% of OnTrack participants were adherent to the home-based program, while 59% of OnTrack participants were adherent to the supervised sessions. Higher baseline physical fitness was associated with higher adherence to home-based components. Higher disease stage and having a partner were associated with adherence to OnTrack supervised sessions. Overall satisfaction with the exercise programs was high, but ratings of coaching provided by professionals for the home-based components were low. Patients offered suggestions for improving delivery of the programs. CONCLUSIONS: These findings point to factors relevant to program adherence and suggest ways in which such programs can be improved. Providing additional time and training for health care professionals could improve the quality and hopefully the effectiveness of the interventions. The use of online diaries and smartphone apps may provide additional encouragement to participants. Finally, allowing greater flexibility in the planning and availability of supervised exercise training in order to accommodate the variability in cancer treatment schedules and the (acute) side effects of the treatments could also enhance program adherence. TRIAL REGISTRATION: Netherlands Trial Register, NTR2159. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2159.

Performance of cartridge and granular carbon dioxide absorbents in a closed-circuit diving rebreather.

INTRODUCTION: Scrubbers in closed-circuit rebreather systems remove carbon dioxide (CO2) from the exhaled gas. In an attempt to be more user-friendly and efficient, the ExtendAir® non-granular, pre-formed scrubber cartridge has been developed. The cartridge manufacturer claims twice the absorptive capacity of granular CO2 absorbent, with less variability, lower work of breathing, and reduced exposure to caustic chemicals after a flood. To our knowledge there are no published data that support these claims. METHODS: Cartridge (ExtendAir®) and granular (Sofnolime® 797) scrubbers of equal volume and mass were tested five times in an immersed and mechanically ventilated O2ptima rebreather. Exercise protocols involving staged (90 minutes 6 MET, followed by 2 MET) and continuous (6 MET) activity were simulated. We compared: duration until breakthrough, and variability in duration, to endpoints of 1.0 kPa and 0.5 kPa inspired partial pressure of CO2; inspiratory-expiratory pressure difference in the breathing loop; and pH of eluted water after a 5 minute flood. RESULTS: Mean difference in scrubber endurance was 0-20% in favour of the ExtendAir® cartridge, depending on exercise protocol and chosen CO2 endpoint. There were no meaningful differences in endpoint variability, inspiratory-expiratory pressure in the loop, or pH in the eluted water after a flood. CONCLUSIONS: Cartridge and granular scrubbers were very similar in duration, variability, ventilation pressures, and causticity after a flood. Our findings were not consistent with claims of substantial superiority for the ExtendAir® cartridge.

Recruitment to and pilot results of the PACES randomized trial of physical exercise during adjuvant chemotherapy for colon cancer.

PURPOSE: We report the recruitment rate, reasons for and factors influencing non-participation, and descriptive results of a randomized controlled trial of two different exercise programs for patients with colon cancer undergoing adjuvant chemotherapy. METHODS: Participants were randomized to a low-intensity, home-based program (Onco-Move), a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack), or Usual Care. Non-participants provided reasons for non-participation and were asked to complete a questionnaire assessing behavioral and attitudinal variables. Trial participants completed performance-based and self-reported outcome measures prior to randomization, at the end of chemotherapy, and at the 6-month follow-up. RESULTS: Twenty-three of 63 referred patients agreed to participate in the trial. All 40 non-participants provided reasons for non-participation. Forty-five percent of the non-participants completed the questionnaire. Those who did not want to exercise had higher fatigue scores at baseline and a more negative attitude toward exercise. Compliance to both programs was high and no adverse events occurred. On average, the colon cancer participants were able to maintain or improve their physical fitness levels and maintain or decrease their fatigue levels during chemotherapy and follow-up. CONCLUSIONS: Recruitment of patients with colon cancer to a physical exercise trial during adjuvant chemotherapy proved to be difficult, underscoring the need to develop more effective strategies to increase participation rates. Both home-based and supervised programs are safe and feasible in patients with colon cancer undergoing chemotherapy. Effectiveness needs to be established in a larger trial. TRIAL REGISTRATION: Netherlands Trial Register - NTR2159.

Cost-utility and cost-effectiveness of physical exercise during adjuvant chemotherapy.

INTRODUCTION: A home-based, low-intensity physical activity program (Onco-Move) and a supervised, moderate-to-high intensity, combined resistance and aerobic exercise program (OnTrack) have proven to be effective in maintaining physical fitness and reducing fatigue among breast cancer patients undergoing adjuvant chemotherapy. This study evaluated the cost-utility and cost-effectiveness of Onco-Move and OnTrack. METHODS: A total of 230 patients were randomized to Onco-Move, OnTrack, or usual care (UC). Health outcomes included quality-adjusted life years (QALYs), general and physical fatigue, and physical fitness measured at baseline, end of chemotherapy, and 6-month follow-up. Societal costs included professional and informal health care, work absenteeism, and unpaid productivity costs. Cost data were based on 3-monthly questionnaires, supplemented by medication data obtained from pharmacies. RESULTS: Onco-Move is not likely to be cost-effective due to the relatively high willingness-to-pay necessary to reach reasonable probabilities of cost-effectiveness (QALY, general and physical fatigue). Incremental cost-effectiveness ratios for OnTrack compared to UC were €26,916/QALY, €788/1-point decrease in general fatigue and €1402/1-point decrease in physical fatigue. The probability of OnTrack being cost-effective ranged from 31% at a willingness-to-pay (WTP) of €0-79% at a WTP of €80,000/QALY, 97% at a WTP of €15,000/1-point decrease in general fatigue, and 86% at a WTP of €24,000/1-point decrease in physical fatigue. Both interventions had a low probability of being cost-effective for physical fitness. The probability of cost-effectiveness for both interventions was greater among compliant participants. CONCLUSIONS: Onco-Move is not likely to be cost-effective. Depending on the decision-makers' willingness-to-pay, OnTrack could be considered cost-effective in comparison with UC. Trial registration Clinical trial registration number of the Netherlands Trial Register-NTR2159.

Why do patients choose (not) to participate in an exercise trial during adjuvant chemotherapy for breast cancer?

OBJECTIVE: Only between 25% and 50% of patients invited to participate in clinical trial-based physical exercise programs during cancer treatment agree to do so. The purpose of this study was to identify factors associated significantly with the decision (not) to participate in a randomized controlled trial of physical exercise during adjuvant chemotherapy for breast cancer. METHODS: Based on questionnaire data, we compared trial participants and non-participants on a range of sociodemographic, clinical health-related, practical, behavioral, and attitudinal variables. RESULTS: Two hundred thirty of 524 patients agreed to participate in the trial (44%). The 294 (56%) non-participants indicated that they wanted to exercise on their own or that they did not wish to exercise in the context of a trial. Those who preferred to exercise on their own were relatively similar to trial participants but were more likely to be in the maintenance exercise stage. Those non-participants who did not wish to exercise had a significantly lower level of education, were less likely to be working, reported more fatigue and lower health-related quality of life, had lower sense of self-efficacy, more negative attitudes towards exercise, less social support, and perceived fewer benefits and more barriers to exercising during treatment than trial participants. CONCLUSION: Minimizing practical barriers to participation, providing educational materials on the potential benefits of exercise, and giving adequate professional and social network encouragement may increase the number of patients willing to exercise during treatment and to participate in such studies. Copyright © 2015 John Wiley & Sons, Ltd.