Acceptability of a virtual prostate cancer survivorship care model in rural Australia: A multi-methods, single-centre feasibility pilot.

DESIGN: A multi-methods, single-centre pilot comprising a quasi-experimental pre-/post-test design and an exploratory qualitative study. SETTING: A rural Australian hospital and health service. PARTICIPANTS: Men newly diagnosed with localised prostate cancer who were scheduled to undergo, or had undergone, radical or robotic prostatectomy surgery within the previous 3 months. INTERVENTION: The intervention comprised a 12-week virtual care program delivered via teleconference by a specialist nurse, using a pre-existing connected care platform. The program was tailored to the post-operative recovery journey targeting post-operative care, psychoeducation, problem-solving and goal setting. MAIN OUTCOME MEASURES: Primary outcome: program acceptability. SECONDARY OUTCOMES: quality of life; prostate cancer-related distress; insomnia severity; fatigue severity; measured at baseline (T1); immediately post-intervention (T2); and 12 weeks post-intervention (T3). RESULTS: Seventeen participants completed the program. The program intervention showed very high levels (≥4/5) of acceptability, appropriateness and feasibility. At T1, 47% (n = 8) of men reported clinically significant psychological distress, which had significantly decreased by T3 (p = 0.020). There was a significant improvement in urinary irritative/obstructive symptoms (p = 0.030) and a corresponding decrease in urinary function burden (p = 0.005) from T1 to T3. CONCLUSIONS: This pilot has shown that a tailored nurse-led virtual care program, incorporating post-surgical follow-up and integrated low-intensity psychosocial care, is both acceptable to rural participants and feasible in terms of implementation and impact on patient outcomes.

Effectiveness of educational and psychological survivorship interventions to improve health-related quality of life outcomes for men with prostate cancer on androgen deprivation therapy: a systematic review.

OBJECTIVES: Androgen deprivation therapy (ADT), a common treatment for prostate cancer, has debilitating impacts on physical and psychological quality of life. While some interventions focus on managing the physical side effects of ADT, there is a paucity of interventions that also address psychosocial and educational needs. The objective of this systematic review was to identify psychological and educational survivorship interventions targeting health-related quality of life (HRQoL) outcomes in men on ADT. DESIGN: A systematic review of randomised controlled trials. DATA SOURCES: Web of Science, Cochrane, EBSCO Host, PubMed, SCOPUS from inception (1984) to 28 January 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Psychological and/or educational survivorship interventions targeting HRQoL outcomes for men on ADT; minimum 80% of participants on ADT; used a validated HRQoL outcome measure; published in English in a peer-reviewed journal. DATA EXTRACTION AND SYNTHESIS: Data extraction using pre-specified study criteria was conducted. Heterogeneity of eligible studies precluded a meta-analysis. RESULTS: A total of 3381 publications were identified with eight meeting the criteria. Interventions were either psychological with a cognitive behavioural approach (n=4), or educational with (n=2) or without (n=2) psychoeducational components.Two studies reported a statistically significant improvement using a specific HRQoL measure. Most studies were not adequately powered and/or included small sample sizes limiting the conclusions that can be drawn on effectiveness. The most effective interventions were (i) individually based, (ii) educational with a psychoeducational component, (iii) supplemented with information packages and/or homework and (iv) included personalised needs assessments. CONCLUSION: There is a paucity of literature reporting psychological and educational survivorship interventions targeting HRQoL outcomes for men on ADT. What is urgently needed are person-centred survivorship interventions that are flexible enough to identify and address individual needs, taking into account the impact ADT has on both physical and psychological quality of life. PROSPERO REGISTRATION NUMBER: CRD4202230809.

Heart Rate Variability and Pulse Rate Variability: Do Anatomical Location and Sampling Rate Matter?

Wearable technology and neuroimaging equipment using photoplethysmography (PPG) have become increasingly popularized in recent years. Several investigations deriving pulse rate variability (PRV) from PPG have demonstrated that a slight bias exists compared to concurrent heart rate variability (HRV) estimates. PPG devices commonly sample at ~20-100 Hz, where the minimum sampling frequency to derive valid PRV metrics is unknown. Further, due to different autonomic innervation, it is unknown if PRV metrics are harmonious between the cerebral and peripheral vasculature. Cardiac activity via electrocardiography (ECG) and PPG were obtained concurrently in 54 participants (29 females) in an upright orthostatic position. PPG data were collected at three anatomical locations: left third phalanx, middle cerebral artery, and posterior cerebral artery using a Finapres NOVA device and transcranial Doppler ultrasound. Data were sampled for five minutes at 1000 Hz and downsampled to frequencies ranging from 20 to 500 Hz. HRV (via ECG) and PRV (via PPG) were quantified and compared at 1000 Hz using Bland-Altman plots and coefficient of variation (CoV). A sampling frequency of ~100-200 Hz was required to produce PRV metrics with a bias of less than 2%, while a sampling rate of ~40-50 Hz elicited a bias smaller than 20%. At 1000 Hz, time- and frequency-domain PRV measures were slightly elevated compared to those derived from HRV (mean bias: ~1-8%). In conjunction with previous reports, PRV and HRV were not surrogate biomarkers due to the different nature of the collected waveforms. Nevertheless, PRV estimates displayed greater validity at a lower sampling rate compared to HRV estimates.

Maximizing the Reliability and Precision of Measures of Prefrontal Cortical Oxygenation Using Frequency-Domain Near-Infrared Spectroscopy.

Frequency-domain near-infrared spectroscopy (FD-NIRS) has been used for non-invasive assessment of cortical oxygenation since the late 1990s. However, there is limited research demonstrating clinical validity and general reproducibility. To address this limitation, recording duration for adequate validity and within- and between-day reproducibility of prefrontal cortical oxygenation was evaluated. To assess validity, a reverse analysis of 10-min-long measurements (n = 52) at different recording durations (1-10-min) was quantified via coefficients of variation and Bland-Altman plots. To assess within- and between-day within-subject reproducibility, participants (n = 15) completed 2-min measurements twice a day (morning/afternoon) for five consecutive days. While 1-min recordings demonstrated sufficient validity for the assessment of oxygen saturation (StO2) and total hemoglobin concentration (THb), recordings ≥4 min revealed greater clinical utility for oxy- (HbO) and deoxyhemoglobin (HHb) concentration. Females had lower StO2, THb, HbO, and HHb values than males, but variability was approximately equal between sexes. Intraclass correlation coefficients ranged from 0.50-0.96. The minimal detectable change for StO2 was 1.15% (95% CI: 0.336-1.96%) and 3.12 µM for THb (95% CI: 0.915-5.33 µM) for females and 2.75% (95%CI: 0.807-4.70%) for StO2 and 5.51 µM (95%CI: 1.62-9.42 µM) for THb in males. Overall, FD-NIRS demonstrated good levels of between-day reliability. These findings support the application of FD-NIRS in field-based settings and indicate a recording duration of 1 min allows for valid measures; however, data recordings of ≥4 min are recommended when feasible.

Prostate Cancer Survivorship Essentials for men with prostate cancer on androgen deprivation therapy: protocol for a randomised controlled trial of a tele-based nurse-led survivorship care intervention (PCEssentials Hormone Therapy Study).

INTRODUCTION: Androgen deprivation therapy (ADT) is commonly used to treat men with locally advanced or metastatic prostate cancer. Men receiving ADT experience numerous side effects and frequently report unmet supportive care needs. An essential part of quality cancer care is survivorship care. To date, an optimal effective approach to survivorship care for men with prostate cancer on ADT has not been described. This protocol describes a randomised trial of tele-based nurse-led survivorship that addresses this knowledge gap: (1) determine the effectiveness of a nurse-led survivorship care intervention (PCEssentials), relative to usual care, for improving health-related quality of life (HR-QoL) in men with prostate cancer undergoing ADT and (2) evaluate PCEssentials implementation strategies and outcomes, including cost-effectiveness, compared with usual care. METHODS AND ANALYSIS: This is an effectiveness-implementation hybrid (type 1) trial with participants randomised to one of two arms: (1) minimally enhanced usual care and (2) nurse-led prostate cancer survivorship essentials (PCEssentials) delivered over four tele-based sessions, with a booster session 5 months after session 1. Eligible participants are Australian men with prostate cancer commencing ADT and expected to be on ADT for a minimum of 12 months. Participants are followed up at 3, 6 and 12 months postrecruitment. Primary outcomes are HR-QoL and self-efficacy. Secondary outcomes are psychological distress, insomnia, fatigue and physical activity. A concurrent process evaluation with participants and study stakeholders will be undertaken to determine effectiveness of delivery of PCEssentials. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Metro South Health HREC (HREC/2021/QMS/79429). All participants are required to provide written informed consent. Outcomes of this trial will be published in peer-reviewed journals. The findings will be presented at conferences and meetings, local hospital departments, participating organisations/clinical services, and university seminars, and communicated at community and consumer-led forums. TRIAL REGISTRATION NUMBER: ACTRN12622000025730.

Individual and area level factors associated with the breast cancer diagnostic-treatment interval in Queensland, Australia.

BACKGROUND: Delays to breast cancer treatment can lead to more aggressive and extensive treatments, increased expenses, increased psychological distress, and poorer survival. We explored the individual and area level factors associated with the interval between diagnosis and first treatment in a population-based cohort in Queensland, Australia. METHODS: Data from 3216 Queensland women aged 20 to 79, diagnosed with invasive breast cancer (ICD-O-3 C50) between March 2010 and June 2013 were analysed. Diagnostic dates were sourced from the Queensland Cancer Registry and treatment dates were collected via self-report. Diagnostics-treatment intervals were modelled using flexible parametric survival methods. RESULTS: The median interval between breast cancer diagnosis and first treatment was 15 days, with an interquartile range of 9-26 days. Longer diagnostic-treatment intervals were associated with a lack of private health coverage, lower pre-diagnostic income, first treatments other than breast conserving surgery, and residence outside a major city. The model explained a modest 13.7% of the variance in the diagnostic-treatment interval [Formula: see text]. Sauerbrei's D was 0.82, demonstrating low to moderate discrimination performance. CONCLUSION: Whilst this study identified several individual- and area-level factors associated with the time between breast cancer diagnosis and first treatment, much of the variation remained unexplained. Increased socioeconomic disadvantage appears to predict longer diagnostic-treatment intervals. Though some of the differences are small, many of the same factors have also been linked to screening and diagnostic delay. Given the potential for accumulation of delay at multiple stages along the diagnostic and treatment pathway, identifying and applying effective strategies address barriers to timely health care faced by socioeconomically disadvantaged women remains a priority.

Adolescent Sport-Related Concussion and the Associated Neurophysiological Changes: A Systematic Review.

BACKGROUND: Sport-related concussion (SRC) has been shown to induce cerebral neurophysiological deficits, quantifiable with electroencephalography (EEG). As the adolescent brain is undergoing rapid neurodevelopment, it is fundamental to understand both the short- and long-term ramifications SRC may have on neuronal functioning. The current systematic review sought to amalgamate the literature regarding both acute/subacute (≤28 days) and chronic (>28 days) effects of SRC in adolescents via EEG and the diagnostic accuracy of this tool. METHODS: The review was registered within the Prospero database (CRD42021275256). Search strategies were created and input into the PubMed database, where three authors completed all screening. Risk of bias assessments were completed using the Scottish Intercollegiate Guideline Network and Methodological Index for Non-Randomized Studies. RESULTS: A total of 128 articles were identified; however, only seven satisfied all inclusion criteria. The studies ranged from 2012 to 2021 and included sample sizes of 21 to 81 participants, albeit only ∼14% of the included athletes were females. The studies displayed low-to-high levels of bias due to the small sample sizes and preliminary nature of most investigations. Although heterogeneous methods, tasks, and analytical techniques were used, 86% of the studies found differences compared with control athletes, in both the symptomatic and asymptomatic phases of SRC. One study used raw EEG data as a diagnostic indicator demonstrating promise; however, more research and standardization are a necessity. CONCLUSIONS: Collectively, the findings highlight the utility of EEG in assessing adolescent SRC; however, future studies should consider important covariates including biological sex, maturation status, and development.

Correction: The burden of chronic diseases among Australian cancer patients: Evidence from a longitudinal exploration, 2007-2017.

[This corrects the article DOI: 10.1371/journal.pone.0228744.].

Correction: The cost-effectiveness of controlling cervical cancer using a new 9-valent human papillomavirus vaccine among school-aged girls in Australia.

[This corrects the article DOI: 10.1371/journal.pone.0223658.].

Disease mapping: Geographic differences in population rates of interventional treatment for prostate cancer in Australia.

BACKGROUND: Treatment decisions for men diagnosed with prostate cancer depend on a range of clinical and patient characteristics such as disease stage, age, general health, risk of side effects and access. Associations between treatment patterns and area-level factors such as remoteness and socioeconomic disadvantage have been observed in many countries. OBJECTIVE: To model spatial differences in interventional treatment rates for prostate cancer at high spatial resolution to inform policy and decision-making. METHODS: Hospital separations data for interventional treatments for prostate cancer (radical prostatectomy, low dose rate and high dose rate brachytherapy) for men aged 40 years and over were modelled using spatial models, generalised linear mixed models, maximised excess events tests and k-means statistical clustering. RESULTS: Geographic differences in population rates of interventional treatments were found (p<0.001). Separation rates for radical prostatectomy were lower in remote areas (12.2 per 10 000 person-years compared with 15.0-15.9 in regional and major city areas). Rates for all treatments decreased with increasing socioeconomic disadvantage (radical prostatectomy 19.1 /10 000 person-years in the most advantaged areas compared with 12.9 in the most disadvantaged areas). Three groups of similar areas were identified: those with higher rates of radical prostatectomy, those with higher rates of low dose brachytherapy, and those with low interventional treatment rates but higher rates of excess deaths. The most disadvantaged areas and remote areas tended to be in the latter group. CONCLUSIONS: The geographic differences in treatment rates may partly reflect differences in patients' physical and financial access to treatments. Treatment rates also depend on diagnosis rates and thus reflect variation in investigation rates for prostate cancer and presentation of disease. Spatial variation in interventional treatments may aid identification of areas of under-treatment or over-treatment.

Correction: Cost-effectiveness evaluations of the 9-Valent human papillomavirus (HPV) vaccine: Evidence from a systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0233499.].

The Effect of Hypercapnia on Cortical Metabolic Rate and Mitochondrial Redox Status.

Hypercapnia is commonly used as a vasodilatory stimulus in both basic and clinical research. There have been conflicting reports about whether cerebral metabolic rate of oxygen (CMRO2) is maintained at normal levels during increases of cerebral blood flow (CBF) and oxygen delivery caused by hypercapnia.This study aims to provide insight into how hypercapnia may impact CMRO2 and brain mitochondrial function. We introduce data from mouse cortex collected with a novel multimodality system which combines MRI and near-infrared spectroscopy (NIRS). We quantify CBF, tissue oxygen saturation (StO2), oxidation state of the mitochondrial enzyme cytochrome c oxidase (CCO), and CMRO2.During hypercapnia, CMRO2 did not change while CBF, StO2, and the oxidation state of CCO increased significantly. This paper supports the conclusion that hypercapnia does not change CMRO2. It also introduces the application of a multimodal NIRS-MRI system which enables non-invasive quantification of CMRO2, and other physiological variables, in the cerebral cortex of mouse models.

Treatment intervals and survival for women diagnosed with early breast cancer in Queensland: the Breast Cancer Outcomes Study, a population-based cohort study.

OBJECTIVES: To assess associations between breast cancer-specific survival and timeliness of treatment, based on 2020 Australian guidelines for the treatment of early breast cancer. DESIGN: Population-based cohort study; analysis of linked Queensland Cancer Register, patient medical record, and National Death Index data, supplemented by telephone interviews. SETTING, PARTICIPANTS: Women aged 20-79 years diagnosed with invasive breast cancer during 1 March 2010 - 30 June 2013, followed to 31 December 2020. MAIN OUTCOME MEASURES: Breast cancer-specific survival for women who received or did not receive treatment within the recommended timeframe, overall and for six treatment intervals; optimal cut-points for each treatment interval; characteristics of women for whom treatment was not provided within the recommended timeframe. RESULTS: Of 5426 eligible women, 4762 could be invited for interviews; complete data were available for 3044 women (56% of eligible women, 65% of invited women). Incomplete compliance with guideline interval recommendations was identified for 1375 women (45%); their risk of death from breast cancer during the follow-up period was greater than for those for whom guideline compliance was complete (adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 1.04-1.96). Risk of death was greater for women for whom the diagnosis to surgery interval exceeded 29 days (aHR, 1.76; 95% CI, 1.19-2.59), the surgery to chemotherapy interval exceeded 36 days (aHR, 1.63; 95% CI, 1.13-2.36), or the chemotherapy to radiotherapy interval exceeded 31 days (aHR, 1.83; 95% CI, 1.19-2.80). Treatment intervals longer than recommended were more frequent for women for whom breast cancer was detected by public facility screening (adjusted odds ratio [aOR], 1.58; 95% CI, 1.22-2.04) or by symptoms (aOR, 1.39; 95% CI, 1.09-1.79) than when cancer had been detected in private facilities, and for women without private health insurance (aOR, 1.96; 95% CI, 1.66-2.32) or living outside major cities (aOR, 1.38; 95% CI, 1.18-1.62). CONCLUSIONS: Breast cancer-specific survival was poorer for women for whom the diagnosis to surgery, surgery to chemotherapy, or chemotherapy to radiotherapy intervals exceeded guideline-recommended limits. Our findings support 2020 Australian guideline recommendations regarding timely care.

Temporal Pattern of Cortical Hypoxia in Multiple Sclerosis and Its Significance on Neuropsychological and Clinical Measures of Disability.

OBJECTIVE: Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. It has been hypothesized that hypoxia plays a role in the pathogenesis of MS. This study was undertaken to investigate the reproducibility of non-invasively measured cortical microvascular hemoglobin oxygenation (St O2 ) using frequency domain near-infrared spectroscopy (fdNIRS), investigate its temporal pattern of hypoxia in people with MS (pwMS), and its relationship with neurocognitive function and mood. METHODS: We investigated the reproducibility of fdNIRS measurements. We measured cortical hypoxia in pwMS, and the relationships between St O2 , neurocognitive function, fatigue, and measures of physical disability. Furthermore, we cataloged the temporal pattern of St O2 measured at 1-week intervals for 4 weeks, and at 8 weeks and ~1 year. RESULTS: We show that fdNIRS parameters were highly reproducible in 7 healthy control participants measured over 6 days (p > 0.05). There was low variability between and within subjects. In line with our previous findings, we show that 33% of pwMS (n = 88) have cortical microvascular hypoxia. Over 8 weeks and at ~1 year, St O2 values for normoxic and hypoxic groups did not change significantly. There was no significant association between cognitive function and St O2 . This conclusion should be revisited as only a small proportion of the relapsing-remitting MS group (21%) was cognitively impaired. INTERPRETATION: The fdNIRS parameters have high reproducibility and repeatability, and we have demonstrated that hypoxia in MS is a chronic condition, lasting at least a year. The results show a weak relationship between cognitive functioning and oxygenation, indicating future study is required. ANN NEUROL 2023;94:1067-1079.

The temporal neurovascular coupling response remains intact during sinusoidal hypotensive and hypertensive challenges.

Introduction. Neurovascular coupling (NVC) describes the coupling of neuronal metabolic demand to blood supply, which has shown to be impaired with chronic hypertension, as well as with prolonged hypotension. However, it is unknown the extent the NVC response remains intact during transient hypo- and hyper-tensive challenges.Methods. Fifteen healthy participants (9 females/6 males) completed a visual NVC task ('Where's Waldo?') over two testing sessions, consisting of cyclical 30 s eyes closed and opened portions. The Waldo task was completed at rest (8 min) and concurrently during squat-stand maneuvers (SSMs; 5 min) at 0.05 Hz (10 s squat/stand) and 0.10 Hz (5 s squat-stand). SSMs induce 30-50 mmHg blood pressure oscillations, resulting in cyclical hypo- and hyper-tensive swings within the cerebrovasculature, allowing for the quantification of the NVC response during transient hypo- and hyper-tension. Outcome NVC metrics included baseline, peak, relative increase in cerebral blood velocity (CBv), and area-under-the-curve (AUC30) within the posterior and middle cerebral arteries indexed via transcranial Doppler ultrasound. Within-subject, between-task comparisons were conducted using analysis of variance with effect size calculations.Results. Differences were noted between rest and SSM conditions in both vessels for peak CBv (allp< 0.045) and the relative increase in CBv (allp <0.049) with small-to-large effect sizes. AUC30 metrics were similar between all tasks (allp> 0.090) with negligible-to-small effect sizes.Conclusions. Despite the SSMs eliciting ∼30-50 mmHg blood pressure oscillations, similar levels of activation occurred within the neurovascular unit across all conditions. This demonstrated the signaling of the NVC response remained intact during cyclical blood pressure challenges.

Impact of averaging fNIRS regional coherence data when monitoring people with long term post-concussion symptoms.

Significance: Functional near-infrared spectroscopy (fNIRS), with its measure of delta hemoglobin concentration, has shown promise as a monitoring tool for the functional assessment of neurological disorders and brain injury. Analysis of fNIRS data often involves averaging data from several channel pairs in a region. Although this greatly reduces the processing time, it is uncertain how it affects the ability to detect changes post injury. Aim: We aimed to determine how averaging data within regions impacts the ability to differentiate between post-concussion and healthy controls. Approach: We compared interhemispheric coherence data from 16 channel pairs across the left and right dorsolateral prefrontal cortex during a task and a rest period. We compared the statistical power for differentiating groups that was obtained when undertaking no averaging, vs. averaging data from 2, 4, or 8 source detector pairs. Results: Coherence was significantly reduced in the concussion group compared with controls when no averaging was undertaken. Averaging all 8 channel pairs before undertaking the coherence analysis resulted in no group differences. Conclusions: Averaging between fiber pairs may eliminate the ability to detect group differences. It is proposed that even adjacent fiber pairs may have unique information, so averaging must be done with caution when monitoring brain disorders or injury.

Enhanced liver X receptor signalling reduces brain injury and promotes tissue regeneration following experimental intracerebral haemorrhage: roles of microglia/macrophages.

BACKGROUND: Inflammation-exacerbated secondary brain injury and limited tissue regeneration are barriers to favourable prognosis after intracerebral haemorrhage (ICH). As a regulator of inflammation and lipid metabolism, Liver X receptor (LXR) has the potential to alter microglia/macrophage (M/M) phenotype, and assist tissue repair by promoting cholesterol efflux and recycling from phagocytes. To support potential clinical translation, the benefits of enhanced LXR signalling are examined in experimental ICH. METHODS: Collagenase-induced ICH mice were treated with the LXR agonist GW3965 or vehicle. Behavioural tests were conducted at multiple time points. Lesion and haematoma volume, and other brain parameters were assessed using multimodal MRI with T2-weighted, diffusion tensor imaging and dynamic contrast-enhanced MRI sequences. The fixed brain cryosections were stained and confocal microscopy was applied to detect LXR downstream genes, M/M phenotype, lipid/cholesterol-laden phagocytes, oligodendrocyte lineage cells and neural stem cells. Western blot and real-time qPCR were also used. CX3CR1CreER: Rosa26iDTR mice were employed for M/M-depletion experiments. RESULTS: GW3965 treatment reduced lesion volume and white matter injury, and promoted haematoma clearance. Treated mice upregulated LXR downstream genes including ABCA1 and Apolipoprotein E, and had reduced density of M/M that apparently shifted from proinflammatory interleukin-1ß+ to Arginase1+CD206+ regulatory phenotype. Fewer cholesterol crystal or myelin debris-laden phagocytes were observed in GW3965 mice. LXR activation increased the number of Olig2+PDGFRα+ precursors and Olig2+CC1+ mature oligodendrocytes in perihaematomal regions, and elevated SOX2+ or nestin+ neural stem cells in lesion and subventricular zone. MRI results supported better lesion recovery by GW3965, and this was corroborated by return to pre-ICH values of functional rotarod activity. The therapeutic effects of GW3965 were abrogated by M/M depletion in CX3CR1CreER: Rosa26iDTR mice. CONCLUSIONS: LXR agonism using GW3965 reduced brain injury, promoted beneficial properties of M/M and facilitated tissue repair correspondent with enhanced cholesterol recycling.

Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19.

OBJECTIVE: Systemic hypoxia occurs in COVID-19 infection; however, it is unknown if cerebral hypoxia occurs in convalescent individuals. We have evidence from other conditions associated with central nervous system inflammation that hypoxia may occur in the brain. If so, hypoxia could reduce the quality of life and brain function. This study was undertaken to assess if brain hypoxia occurs in individuals after recovery from acute COVID-19 infection and if this hypoxia is associated with neurocognitive impairment and reduced quality of life. METHODS: Using frequency-domain near-infrared spectroscopy (fdNIRS), we measured cerebral tissue oxygen saturation (StO2) (a measure of hypoxia) in participants who had contracted COVID-19 at least 8 weeks prior to the study visit and healthy controls. We also conducted neuropsychological assessments and health-related quality of life assessments, fatigue, and depression. RESULTS: Fifty-six percent of the post-COVID-19 participants self-reported having persistent symptoms (from a list of 18), with the most reported symptom being fatigue and brain fog. There was a gradation in the decrease of oxyhemoglobin between controls, and normoxic and hypoxic post-COVID-19 groups (31.7 ± 8.3 µM, 27.8 ± 7.0 µM and 21.1 ± 7.2 µM, respectively, p = 0.028, p = 0.005, and p = 0.081). We detected that 24% of convalescent individuals' post-COVID-19 infection had reduced StO2 in the brain and that this relates to reduced neurological function and quality of life. INTERPRETATION: We believe that the hypoxia reported here will have health consequences for these individuals, and this is reflected in the correlation of hypoxia with greater symptomology. With the fdNIRS technology, combined with neuropsychological assessment, we may be able to identify individuals at risk of hypoxia-related symptomology and target individuals that are likely to respond to treatments aimed at improving cerebral oxygenation.

The relationship between cytochrome c oxidase, CBF and CMRO2 in mouse cortex: A NIRS-MRI study.

Quantifying relationships between cerebral blood flow (CBF), mitochondrial function (cytochrome c oxidase oxidation state), and metabolic rate of oxygen (CMRO2) could provide useful insight into normal neurovascular coupling, as well as regulation of oxidative metabolism in neurological disorders. This paper uses a multimodal NIRS-MRI method to quantify these parameters in rodent brain and, in so doing, provides novel information on the regulation of oxygen metabolism by stimulating with hypercapnia or variations in oxygenation. Under hypercapnia, although oxygenation, oxidation state, and CBF increased, there was no increase in CMRO2. Also, there was no correlation between CBF and CCO oxidation state. Conversely, changing oxygenation resulted in a strong correlation between the oxidation of CCO and CBF. This proves that the association between CBF and the redox state of CCO is not fixed and depends on the type of perturbation. Having a means to measure CBF and CCO oxidation state simultaneously will help understanding their contribution to intact neurovascular coupling and detecting abnormal cellular oxygen metabolism in many neurological disorders.

Cerebral Hemodynamics and Microvasculature Changes in Relation to White Matter Microstructure After Pediatric Mild Traumatic Brain Injury: An A-CAP Pilot Study.

Advanced neuroimaging techniques show promise as a biomarker for mild traumatic brain injury (mTBI). However, little research has evaluated cerebral hemodynamics or its relation to white matter microstructure post-mTBI in children. This novel pilot study examined differences in cerebral hemodynamics, as measured using functional near-infrared spectroscopy (fNIRS), and its association with diffusion tensor imaging (DTI) metrics in children with mTBI or mild orthopedic injury (OI) to address these gaps. Children 8.00-16.99 years of age with mTBI (n = 9) or OI (n = 6) were recruited in a pediatric emergency department, where acute injury characteristics were assessed. Participants completed DTI twice, post-acutely (2-33 days) and chronically (3 or 6 months), and fNIRS ∼1 month post-injury. Automated deterministic tractography was used to compute DTI metrics. There was reduced absolute phase globally and coherence in the dorsolateral pre-frontal cortex (DLPFC) after mTBI compared to the OI group. Coherence in the DLPFC and absolute phase globally showed distinct associations with fractional anisotropy in interhemispheric white matter pathways. Two fNIRS metrics (coherence and absolute phase) differentiated mTBI from OI in children. Variability in cerebral hemodynamics related to white matter microstructure. The results provide initial evidence that fNIRS may have utility as a clinical biomarker of pediatric mTBI.