Psychometric evaluation of clinician- and caregiver-reported clinical severity assessments for individuals with CDKL5 deficiency disorder.

OBJECTIVE: The CDKL5 Clinical Severity Assessment (CCSA) is a comprehensive, content-validated measurement tool capturing the diverse challenges of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD), a genetically caused developmental epileptic encephalopathy (DEE). The CCSA is divided into clinician-reported (CCSA-Clinician) and caregiver-reported (CCSA-Caregiver) assessments. The aim of this study was to evaluate the factor structure of these measures through confirmatory factor analysis (CFA) and evaluate their validity and reliability. METHODS: Participants were recruited from the International CDKL5 Clinical Research Network to take part in an in-clinic CCSA-Clinician evaluation (n = 148) and/or complete the CCSA-Caregiver questionnaire (n = 198). CFA was used to determine domains, and factor loadings and validity were assessed. For the CCSA-Clinician, inter-rater reliability was assessed by nine CDD experienced clinicians via 14 pre-recorded evaluations. Eight clinicians re-viewed and re-scored the videos after 4 weeks to evaluate intra-rater reliability. The CCSA-Caregiver was completed on a second occasion by 34 caregivers after 2-4 weeks to assess test-retest reliability. RESULTS: CFA resulted in three domains for the CCSA-Clinician (motor and movement, communication, vision) and four domains for the CCSA-Caregiver (seizures, behavior, alertness, feeding), with good item loadings across both measures. Structural statistics, internal consistency, discriminant validity, and reliability were satisfactory for both measures, and scores were consistent between known groups. SIGNIFICANCE: This study provides strong evidence that the CCSA measures are suitable to assess the clinical severity of individuals with CDD, supporting their use in clinical trials. Further evaluation of responsiveness to change in a longitudinal assessment is planned. Use may also be appropriate in similar DEEs but would require validation in those populations.

Parent-reported outcome measures evaluating communication in individuals with rare neurodevelopmental disorders: A systematic review.

BACKGROUND: Communication impairments are a leading concern for parent caregivers of individuals with rare neurodevelopmental disorders (RNDDs). Clinical trials of disease modifying therapies require valid and responsive outcome measures that are relevant to individuals with RNDDs. Identifying and evaluating current psychometric properties for communication measures is a critical step towards the selection and use of appropriate instruments. AIMS: This systematic review offers (1) a description of parent-reported communication measures and (2) evidence for their psychometric properties, in RNDDs. METHODS: The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022334649). MEDLINE (Ovid), Embase, PsychINFO, Web of Science, CINAHL Plus, Cochrane Library, ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry were searched from inception to August 2023. Methodological assessment of quality was completed using the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Parent-reported measures used in observational studies and clinical trials were identified. Data on utility, reliability and validity for RNDDs were extracted. MAIN CONTRIBUTION: Sixteen parent-reported communication measures were used in RNDD research, the Vineland Adaptive Behavior Scales being most commonly used. Validation data in RNDDs were identified for six of these measures. Limitations related to sample size or the scope of psychometric testing. CONCLUSIONS: Many communication measures have been used for RNDDs but there are few data validating their use. Valid and reliable methods of measuring communication in persons with RNDDs is a priority for future high-quality clinical trials. WHAT THIS PAPER ADDS: What is already known on the subject Communication is a critical domain for families with a child with a rare neurodevelopmental disorder (RNDD). Validated outcome measures are essential for accurate evaluation and interpretation of responses to treatments in clinical trials. What this paper adds to existing knowledge We identified 16 parent-reported communication measures that have been used with RNDDs, but only six measures had validation data for at least one RNDD. High quality evidence is accumulating, with all validation studies in this review published between 2020 to 2023. Modifications of existing measures may be required to assess communication for RNDDs. What are the clinical implications of this work? This systematic review catalogues the available psychometric data for communication measures and indicates an ongoing need for new validation studies to ensure they are fit-for-purpose for upcoming clinical trials in RNDDs. This review will inform the selection of communication measures for clinical trials and research studies.

Modification of a parent-report sleep scale for individuals with CDKL5 deficiency disorder: a psychometric study.

STUDY OBJECTIVES: Sleep difficulties are common in CDKL5 deficiency disorder (CDD), a developmental and epileptic encephalopathy (DEE). This study evaluated the factor structure of the Disorders of Initiating and Maintaining Sleep (DIMS), Disorders of Excessive Daytime Somnolence (DOES) and Sleep Breathing Disorders (SBD) domains of the Sleep Disturbance Scale for Children (SDSC) for CDD. METHODS: A cross-sectional psychometric study design was used. Data were collected for 125 individuals aged 3 years or older who attended a US Centers of Excellence clinic or registered with the International CDKL5 Disorder Database. RESULTS: The median age was 10.3 years (range 3.2 - 40.7 years) and 105 (84%) were female. Two of the three SBD items related were not observed by most respondents and analysis was restricted to the DIMS and DOES domains. Using all items in the initial confirmatory factor analysis, two items in the DIMS domain and one item in the DOES domain loaded poorly. After deleting these items and repeating the analysis, item loading (0.524-0.814) and internal consistency (DIMS: 0.78, DOES: 0.76) statistics were good. The square of the inter-domain correlation coefficient was 0.17, less than Average Variance Extracted values for both domains and indicating good discriminant validity. The Tucker-Lewis and Comparative Fit indices were slightly lower than the threshold of >0.9 for establishing goodness of fit. CONCLUSIONS: The modified DIMS and DOES domains from the SDSC could be suitable clinical outcome assessments of insomnia and related impairments in CDD and potentially other DEE conditions.

Communication of individuals with CDKL5 deficiency disorder as observed by caregivers: A descriptive qualitative study.

CDKL5 deficiency disorder (CDD) is a genetically caused developmental epileptic encephalopathy that causes severe communication impairments. Communication of individuals with CDD is not well understood in the literature and currently available measures are not well validated in this population. Accurate and sensitive measurement of the communication of individuals with CDD is important for understanding this condition, clinical practice, and upcoming interventional trials. The aim of this descriptive qualitative study was to understand how individuals with CDD communicate, as observed by caregivers. Participants were identified through the International CDKL5 Disorder Database and invited to take part if their child had a pathogenic variant of the CDKL5 gene and they had previously completed the Communication and Symbolic Behavior Checklist (CSBS-DP ITC). The sample comprised caregivers of 23 individuals with CDD, whose ages ranged from 2 to 30 years (median 13 years), 15 were female, and most did not use words. Semistructured interviews were conducted via videoconference and analyzed using a conventional content analysis. Three overarching categories were identified: mode, purpose and meaning, and reciprocal exchanges. These categories described the purposes and mechanism of how some individuals with CDD communicate, including underpinning influential factors. Novel categories included expressing a range of emotions, and reciprocal exchanges (two-way interactions that varied in complexity). Caregivers observed many communication modes for multiple purposes. Understanding how individuals with CDD communicate improves understanding of the condition and will guide research to develop accurate measurement for clinical practice and upcoming medication trials.

The development, content and response process validation of a caregiver-reported severity measure for CDKL5 deficiency disorder.

BACKGROUND: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity. METHODS: We conducted cognitive interviews with 15 parent caregivers of 1-39-year-old children with CDD. Caregivers discussed their understanding and concerns regarding appropriateness of both questions and answer options. Item wording and questionnaire structure were adjusted iteratively to ensure questions were understood as intended. RESULTS: The CCSA was refined during three rounds of cognitive interviews into two measures: (1) the CDD Developmental Questionnaire - Caregiver (CDQ-Caregiver) focused on developmental skills, and (2) the CDD Clinical Severity Assessment - Caregiver (CCSA-Caregiver) focused on symptom severity. Branching logic was used to ensure questions were age and skill appropriate. Initial pilot data (n = 11) suggested no floor effects. CONCLUSIONS: This study modified the caregiver portion of the initial CCSA and provided evidence for its content and response process validity.

Validating the Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC) Beyond Infancy in the CDKL5 Deficiency Disorder.

CDKL5 deficiency disorder (CDD) results in early-onset epilepsy and lifelong cognitive and motor impairments. With no validated measure for communication in CDD, this study evaluated the psychometric properties of the Communication and Symbolic Behavior Scales-Developmental Profile Infant Toddler Checklist (CSBS-DP ITC). Caregivers (n = 150; affected individuals aged 1-29 years) completed the CSBS-DP ITC. Distribution of scores indicated a floor effect. There was poor divergent validity for the three-factor model but goodness of fit and convergent validity data were satisfactory for the one-factor model. Individuals with poorer overall functional abilities scored lower on the CSBS-DP ITC. Test-retest reliability was excellent. The floor effect could explain the very high reliability, suggesting problems as a sensitive outcome measure in clinical trials for CDD.

Psychometric properties of QI-Disability in CDKL5 Deficiency Disorder: Establishing readiness for clinical trials.

CDKL5 Deficiency Disorder (CDD) is a rare genetic disorder with symptoms of epilepsy, developmental impairments, and other comorbidities. Currently, there are no outcome measures for CDD with comprehensive evidence of validation. This study aimed to evaluate the psychometric properties of the Quality of Life Inventory-Disability (QI-Disability) in CDD. Quality of Life Inventory-Disability was administered to 152 parent caregivers registered with the International CDKL5 Disorder Database (ICDD). Confirmatory factor analysis was conducted and the goodness of fit of the factor structure was assessed. Fixed-effects linear regression models examined the responsiveness of QI-Disability to reported changes in child health. A subset of parent caregivers (n = 56) completed QI-Disability, as well as additional health-related questions, on two occasions separated by four weeks to evaluate test-retest reliability. Test-retest reliability was assessed using intra-class correlations (ICCs) calculated from QI-Disability scores. Based upon adjustments for changes in child health, ICCs were recalculated to estimate responsiveness to change. Confirmatory factor analysis, internal consistency, and divergent validity were mostly satisfactory, except divergent validity was not satisfactory for the Social Interactions and Independence domains. The Physical Health, Social Interactions, Leisure, and Total scores responded to changes in the child's Physical health, and the Negative Emotions and Leisure domains responded to changes in the child's behavior. Unadjusted and adjusted ICC values were above 0.8 for the Positive Emotions, Negative Emotions, Social Interactions, Leisure, Independence domains and Total score, and above 0.6 for the Physical Health domain. Findings suggest that QI-Disability is suitable to assess the quality of life of children and adults with CDD and could be of value for upcoming clinical trials.

Factors influencing the attainment of major motor milestones in CDKL5 deficiency disorder.

This study investigated the influence of factors at birth and in infancy on the likelihood of achieving major motor milestones in CDKL5 Deficiency Disorder (CDD). Data on 350 individuals with a pathogenic CDKL5 variant was sourced from the International CDKL5 Disorder Database. A first model included factors available at birth (e.g., sex, variant group and mosaicism) and the second additionally included factors available during infancy (e.g., age at seizure onset, number of anti-seizure medications used, experience of a honeymoon period and formal therapy). Cox regression was used to model the time to achieve the milestones. The probability of attaining the outcomes at specific ages was estimated by evaluating the time-to-event function at specific covariate values. Independent sitting and walking were achieved by 177/350 and 57/325 children respectively. By seven years of age, 67.1% of females but only 37.3% of males could sit independently. About a quarter each of females and males achieved independent walking by eight and six years, respectively. When observed from birth, female gender, a late truncating variant and mosaicism impacted most positively on the likelihood of independent sitting. When observed from one year, later seizure onset and experiencing a honeymoon period also improved the likelihood of independent sitting. Factors that favoured sitting (except gender) also improved walking. Having a truncating variant between aa178 and aa781 reduced the likelihood of achieving independent sitting and walking. It is possible to utilise factors occurring early in life to inform the likelihood of future motor development in CDD.

Quality of life beyond diagnosis in intellectual disability - Latent profiling.

OBJECTIVE: To compare quality of life (QOL) across diagnoses associated with intellectual disability, construct QOL profiles and evaluate membership by diagnostic group, function and comorbidities. METHOD: Primary caregivers of 526 children with intellectual disability (age 5-18 years) and a diagnosis of cerebral palsy, autism spectrum disorder, Down syndrome, CDKL5 deficiency disorder or Rett syndrome completed the Quality of Life Inventory-Disability (QI-Disability) questionnaire. Latent profile analysis of the QI-Disability domain scores was conducted. RESULTS: The mean (SD) total QOL score was 67.8 (13.4), ranging from 60.3 (14.6) for CDD to 77.5 (11.7) for Down syndrome. Three classes describing domain scores were identified: Class 1 was characterised by higher domain scores overall but poorer negative emotions scores; Class 2 by average to high scores for most domains but low independence scores; and Class 3 was characterised by low positive emotions, social interaction, and leisure and the outdoors scores, and extremely low independence scores. The majority of individuals with autism spectrum disorder and Down syndrome belonged to Class 1 and the majority with CDKL5 deficiency disorder belonged to Class 3. Those with better functional abilities (verbal communication and independent walking were predominately members of Class 1 and those with frequent seizures were more often members of Class 2 and 3. CONCLUSION: The profiles illustrated variation in QOL across a diverse group of children. QOL evaluations illustrate areas where interventions could improve QOL and provide advice to families as to where efforts may be best directed.

Initial Validation and Reliability of the CDKL5 Deficiency Disorder Hand Function Scale (CDD-Hand).

Pathogenic variants in the CDKL5 gene result in CDKL5 deficiency disorder (CDD), which is characterized by early-onset epilepsy, severe developmental delay, and often, cortical visual impairment. Validated clinical outcome measures are needed for future clinical trials to be successful. This study aimed to adapt the Rett Syndrome Hand Function Scale for CDKL5 deficiency disorder and evaluate its feasibility, acceptability, content validity, and reliability. Consultation with a cortical visual impairment experienced specialist and the Consumer Reference Group informed modifications to the instructions of the Rett Syndrome Hand Function Scale for children with CDKL5 deficiency disorder (CDD-Hand). Eighty-six families registered with the International CDKL5 Disorder Database provided video clips of their child's hand function and provided feedback about the measure. Video data were coded by 2 researchers to evaluate intra- and interrater reliability. This study provides initial evidence of validation and reliability. The scale appears to be suitable for a range of ages and functional abilities for CDKL5 deficiency disorder.

Negative impact of insomnia and daytime sleepiness on quality of life in individuals with the cyclin-dependent kinase-like 5 deficiency disorder.

Cyclin-dependent kinase-like 5 (CDKL5) gene pathogenic variants result in CDKL5 deficiency disorder (CDD). Early onset intractable epilepsy and severe developmental delays are prominent symptoms of CDD. Comorbid sleep disturbances are a major concerning symptom for families. We aimed to explore the relationship between insomnia, daytime sleepiness, sleep medications and quality of life in children with CDD. Caregivers of 129 children with CDD in the International CDKL5 Disorder Database completed the Quality-of-Life Inventory-Disability (QI-Disability) questionnaire and "Disorders of Maintaining Sleep" (DIMS) and the "Disorders of Excessive Somnolence" (DOES) items of the Sleep Disturbance Scale for Children. Adjusting for covariates, a unit increase in DOES score was associated with reduced quality of life total (coefficient -3.06, 95% confidence interval [CI] 1.35-7.80), physical health (coefficient -7.20, 95% CI -10.64, -3.76) and negative emotions (coefficient -3.90, 95% CI -7.38, -0.42) scores. Adjusting for covariates, a unit increase in DIMS score was associated with reduced negative emotions (coefficient -6.02, 95% CI -10.18, -2.86). Use of sleep medications had small influences on the effect sizes. This study highlights the importance of sleep problems as a determinant of quality of life in children with CDD, consistent with effects observed for other groups of children with intellectual disability. Excessive daytime sleepiness was particularly associated with detrimental effects on quality of life. Further research in optimal behavioural and pharmaceutical management of sleep problems for this population is required.

Devising a Missing Data Rule for a Quality of Life Questionnaire-A Simulation Study.

OBJECTIVE: The aim of this study was to devise an evidence-based missing data rule for the Quality of Life Inventory-Disability (QI-Disability) questionnaire specifying how many missing items are permissible for domain and total scores to be calculated using simple imputation. We sought a straightforward rule that can be used in both research and clinical monitoring settings. METHOD: A simulation study was conducted involving random selection of missing items from a complete data set of questionnaire responses. This comprised 520 children with intellectual disability from 5 diagnostic groups. We applied a simple imputation scheme, and the simulated distribution of errors induced by imputation was compared with the previously estimated standard error of measurement (SEM) for each domain. RESULTS: Using a stringent criterion, which requires that the 95th percentile of absolute error be less than the SEM, 1 missing item should be permitted for 2 of the 6 QI-Disability subdomain scores to be calculated and 1 missing item per domain for the total score to be calculated. Other, less stringent criteria would allow up to 2 missing items per domain. CONCLUSION: Empirical evidence about the impact of imputing missing questionnaire responses can be gathered using simulation methods applied to a complete data set. We recommend that such evidence be used in devising a rule that specifies how many items can be imputed for a valid score to be calculated.

Content Validation of Clinician-Reported Items for a Severity Measure for CDKL5 Deficiency Disorder.

CDKL5 deficiency disorder (CDD) results in early-onset seizures and severe developmental impairments. A CDD clinical severity assessment (CCSA) was previously developed with clinician and parent-report items to capture information on a range of domains. Consistent with US Food and Drug Administration (FDA) guidelines, content validation is the first step in evaluating the psychometric properties of an outcome measure. The aim of this study was to validate the content of the clinician-reported items in the CCSA (CCSA-Clinician). Eight neurologists leading the USA CDD Center of Excellence clinics were interviewed using the "think aloud" technique to critique 26 clinician-reported items. Common themes were aggregated, and a literature search of related assessments informed item modifications. The clinicians then participated in 2 consensus meetings to review themes and finalize the items. A consensus was achieved for the content of the CCSA-Clinician. Eight of the original items were omitted, 11 items were added, and the remaining 18 items were revised. The final 29 items were classified into 2 domains: functioning and neurologic impairments. This study enabled refinement of the CCSA-Clinician and provided evidence for its content validity. This preliminary validation is essential before field testing and further validation, in order to advance the instrument toward clinical trial readiness.

Enhanced Decision Making and Working Memory During Exercise in the Heat With Crushed Ice Ingestion.

PURPOSE: To examine the effects of precooling via crushed ice ingestion on cognitive function during exercise in the heat. METHODS: Eleven active men ingested either 7 g·kg-1 of crushed ice (ICE) or thermoneutral water (CON) 30 minutes before running 90 minutes on a treadmill at a velocity equivalent to 65% VO2peak in hot and humid conditions (35.0°C [0.5°C], 53.1% [3.9%] relative humidity). Participants completed 3 cognitive tasks to investigate decision making (8-choice reaction time [CRT]), working memory (serial seven [S7]), and executive control (color multisource interference task [cMSIT]) on arrival, after precooling, and after running. RESULTS: Precooling significantly decreased preexercise core (Tcore) and forehead skin temperature in ICE compared with CON, respectively (Tcore 0.8°C [0.4°C], -0.2°C [0.1°C]; Thead -0.5°C [0.4°C], 0.2°C [0.8°C]; P ≤ .05). Postrun, ICE significantly reduced errors compared with CON for CRT (P ≤ .05; d = 0.90; 90% confidence interval, 0.13-1.60) and S7 (P ≤ .05; d = 1.05; 90% confidence interval, 0.26-1.75). Thermal sensation was lower after precooling with ICE (P ≤ .05), but no significant differences were recorded between conditions for cMSIT errors, skin temperature, heart rate, or ratings of perceived exertion or perceived thirst (P > .05). CONCLUSIONS: Precooling via ICE maintained cognitive accuracy in decision making and working memory during exercise in the heat. Thus, ICE may have the potential to improve sporting performance by resisting deleterious effects of exercise in a hot and humid environment on cognitive function.

Physical and perceptual cooling: Improving cognitive function, mood disturbance and time to fatigue in the heat.

This study investigated the effects of menthol swilling and crushed ice ingestion on cognitive function, total mood disturbance (TMD), and time to fatigue (TTF). Twelve male long-distance runners completed three counterbalanced running trials (3 × 30 minutes at 65% VO2peak and a TTF run at 100% VO2peak ) in hot, humid conditions (35.3 ± 0.3°C, 59.2 ± 2.5% relative humidity). Trials consisted of precooling with crushed ice ingestion and mid-cooling by menthol swilling (MIX), precooling with water ingestion and mid-cooling by menthol swilling (MENTH), and control (CON). Swilling with either 25 mL of menthol solution or placebo occurred upon entry to the heat, at 15-minute intervals during the run and prior to the TTF run. Core temperature, forehead skin temperature, tympanic temperature, perceived thermal sensation, and TMD were significantly lower with MIX compared with MENTH and CON (P < .05). Thirst was satiated in MIX compared with CON; however, MENTH did not have a significant effect. After 90 minutes of running and post-TTF run, fewer errors occurred in the executive control task (P < .05), as well as decision-making and working memory (P > .05; d = 0.5-0.79) between MIX and CON; however, MENTH had no effect compared with CON. The TTF run was significantly longer with MENTH (34.38%; P = .02) and MIX (39.06%; P = .001) compared with CON, with no difference between MENTH and MIX (P = .618). The physical reduction in core and internal head temperature seen with crushed ice ingestion may lead to improvements in cognitive function; however, both MENTH and MIX were sufficient for improving exercise performance.

Internal precooling decreases forehead and core temperature but does not alter choice reaction time during steady state exercise in hot, humid conditions.

This study aimed to determine if precooling via crushed ice ingestion reduces forehead skin temperature (Thead) and core temperature (Tcore) during exercise in the heat and whether it has an effect on choice reaction time (CRT). Ten males commenced a 30 min precooling period, ingesting either 7 g kg-1 of crushed ice (ICE) or room temperature water (CON) prior to cycling 60 min at 55% V̇O2peak in hot, humid conditions (35.0 ± 0.3 °C, 50.2 ± 2.1% Relative Humidity). The CRT task was completed upon arrival and after the precooling period in the lab, then at 15 min intervals during exercise in the heat. Precooling reduced Thead and Tcore to a greater degree in ICE (Thead: -0.8 ± 0.31 °C; Tcore: -0.9 ± 0.3 °C) compared with CON (Thead: -0.2 ± 0.3 °C; Tcore: -0.2 ± 0.2 °C) (p ≤ 0.001). Choice reaction time performance improved throughout the cycle for both conditions (p ≤ 0.05). Ice ingestion lowered thermal sensation (p = 0.003) and skin temperature (d = 0.88; Tskin), while heart rate, ratings of perceived exertion and thirst were similar between conditions (p > 0.05). Precooling effectively reduced Thead and Tcore but did not provide additional improvement in CRT during moderate exercise in the heat. Further investigation is required to determine whether the lower central and peripheral temperature after ice ingestion is beneficial for tasks of greater cognitive effort.

The Effects of Crushed Ice Ingestion Prior to Steady State Exercise in the Heat.

This study examined the physiological effects of crushed ice ingestion before steady state exercise in the heat. Ten healthy males with age (23 ± 3 y), height (176.9 ± 8.7 cm), body-mass (73.5 ± 8.0 kg), VO2peak (48.5 ± 3.6 mL∙kg∙min-1) participated in the study. Participants completed 60 min of cycling at 55% of their VO2peak preceded by 30 min of precooling whereby 7 g∙kg-1 of thermoneutral water (CON) or crushed ice (ICE) was ingested. The reduction in Tc at the conclusion of precooling was greater in ICE (-0.9 ± 0.3 °C) compared with CON (-0.2 ± 0.2 °C) (p ≤ .05). Heat storage capacity was greater in ICE compared with CON after precooling (ICE -29.3 ± 4.8 W∙m-2; CON -11.1 ± 7.3 W∙m-2, p < .05). Total heat storage was greater in ICE compared with CON at the end of the steady state cycle (ICE 62.0 ± 12.5 W∙m-2; CON 49.9 ± 13.4 W∙m-2, p < .05). Gross efficiency was higher in ICE compared with CON throughout the steady state cycle (ICE 21.4 ± 1.8%; CON 20.4 ± 1.9%, p < .05). Ice ingestion resulted in a lower thermal sensation at the end of precooling and a lower sweat rate during the initial stages of cycling (p < .05). Sweat loss, respiratory exchange ratio, heart rate and ratings of perceived exertion and thirst were similar between conditions (p > .05). Precooling with crushed ice led to improved gross efficiency while cycling due to an increased heat storage capacity, which was the result of a lower core temperature.