A pilot study comparing the DuoFertility(®) monitor with ultrasound in infertile women.

BACKGROUND: The purpose of this study was to assess the accuracy of ovulation detection by the DuoFertility(®) monitor compared with transvaginal ultrasound in infertile women with regular menstrual cycles. METHODS: Eight infertile patients, aged 27-40 years, with a body mass index of 19-29, regular menses, normal ovaries on pelvic ultrasound scan, and normal early follicular luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were recruited from infertility clinics in primary and secondary care for this pilot, prospective, observational study. The patients were asked to use the DuoFertility monitor for the whole cycle, with investigators and patients blind to DuoFertility data. Daily urine LH monitoring commenced on cycle day 8, with daily transvaginal ultrasound following the first positive LH until ovulation was observed. Ovulation was further confirmed by serum progesterone. The main outcome measure was detection of ovulation by the DuoFertility monitor, and correlation between day of ovulation assessed by DuoFertility and ultrasound. RESULTS: DuoFertility identified ovulation as having occurred within one day of that determined via ultrasound in all cycles. The sensitivity of ovulation detection was 100% (95% confidence interval 82-100). The specificity could not be concluded from the data. CONCLUSION: In infertile women with regular cycles, the DuoFertility monitor appears to accurately identify ovulatory cycles and the day of ovulation

Accelerometery as a measure of modifiable physical activity in high-risk elderly preoperative patients: a prospective observational pilot study.

OBJECTIVES: To use wrist-worn accelerometers (Axivity AX3) to establish normative physical activity (PA) and acceptability data for the high-risk elderly preoperative population, to assess whether PA could be modified by a prehabilitation intervention as part of routine care, to assess any correlation between accelerometer-measured PA and self-reported PA and to assess the acceptability of wearing wrist-worn accelerometers in this population. STUDY DESIGN: Prospective, observational, pilot study. SETTING: Single National Health Service Hospital. PARTICIPANTS: Frail patients≥65 years awaiting major surgery referred to a multidisciplinary preoperative clinic at which they received a routine intervention aimed at improving their PA. 35 patients were recruited. Average age 79.9 years (SD=5.6). PRIMARY OUTCOMES: Normative PA data measured as a mean daily Euclidean norm minus one (ENMO) in milli-gravitational units (mg). SECONDARY OUTCOMES: Measure PA levels (mg) following a routine preoperative intervention. Determine correlation between patient-reported PA (measured using the Physical Activity Scale for the Elderly) and accelerometer-measured PA (mg). Assess acceptability of wearing a wrist-worn accelerometer measured using Visual Analogue Scale (VAS) questionnaire and device wear time (hours). RESULTS: Median baseline daily PA was 14.3 mg (IQR 9.75-22.04) with an improvement in PA detected following the intervention (median ENMO post intervention 20.91 mg (IQR 14.83-27.53), p=0.022). There was no significant correlation between accelerometer-measured and self-reported PA (baseline ρ=0.162 (p=0.4), post intervention ρ=-0.144 (p=0.5)). We found high acceptability ratings (median score of 10/10 on VAS, IQR 8-10) and wear-time compliance (163.2 hours (IQR 150-167.5) preintervention and 166.1 hours (IQR 162.5-167) post intervention). CONCLUSIONS: Accelerometery is acceptable to this population and increases in PA levels measured following an unoptimised routine clinical intervention which indicates that health behavioural change interventions may be successful during the preoperative period. Accelerometers may therefore be a useful tool to design and validate interventions for improving PA in this setting. TRIAL REGISTRATION NUMBER: NCT03737903

Inter subject variability and reproducibility of diffusion tensor imaging within and between different imaging sessions.

The aim of these studies was to provide reference data on intersubject variability and reproducibility of diffusion tensor imaging. Healthy volunteers underwent imaging on two occasions using the same 3T Siemens Verio magnetic resonance scanner. At each session two identical diffusion tensor sequences were obtained along with standard structural imaging. Fractional anisotropy, apparent diffusion coefficient, axial and radial diffusivity maps were created and regions of interest applied in normalised space. The baseline data from all 26 volunteers were used to calculate the intersubject variability, while within session and between session reproducibility were calculated from all the available data. The reproducibility of measurements were used to calculate the overall and within session 95% prediction interval for zero change. The within and between session reproducibility data were lower than the values for intersubject variability, and were different across the brain. The regional mean (range) coefficient of variation figures for within session reproducibility were 2.1 (0.9-5.5%), 1.2 (0.4-3.9%), 1.2 (0.4-3.8%) and 1.8 (0.4-4.3%) for fractional anisotropy, apparent diffusion coefficient, axial and radial diffusivity, and were lower than between session reproducibility measurements (2.4 (1.1-5.9%), 1.9 (0.7-5.7%), 1.7 (0.7-4.7%) and 2.4 (0.9-5.8%); p<0.001). The calculated overall and within session 95% prediction intervals for zero change were similar. This study provides additional reference data concerning intersubject variability and reproducibility of diffusion tensor imaging conducted within the same imaging session and different imaging sessions. These data can be utilised in interventional studies to quantify change within a single imaging session, or to assess the significance of change in longitudinal studies of brain injury and disease.RCUK, Wellcome, OtherThis is the published version. It was originally published by PLoS in PLoS ONE here: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0065941

Feasibility of individualised severe traumatic brain injury management using an automated assessment of optimal cerebral perfusion pressure: the COGiTATE phase II study protocol.

INTRODUCTION: Individualising therapy is an important challenge for intensive care of patients with severe traumatic brain injury (TBI). Targeting a cerebral perfusion pressure (CPP) tailored to optimise cerebrovascular autoregulation has been suggested as an attractive strategy on the basis of a large body of retrospective observational data. The objective of this study is to prospectively assess the feasibility and safety of such a strategy compared with fixed thresholds which is the current standard of care from international consensus guidelines. METHODS AND ANALYSIS: CPPOpt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) is a prospective, multicentre, non-blinded randomised, controlled trial coordinated from Maastricht University Medical Center, Maastricht (The Netherlands). The other original participating centres are Cambridge University NHS Foundation Trust, Cambridge (UK), and University Hospitals Leuven, Leuven (Belgium). Adult severe TBI patients requiring intracranial pressure monitoring are randomised within the first 24 hours of admission in neurocritical care unit. For the control arm, the CPP target is the Brain Trauma Foundation guidelines target (60-70 mm Hg); for the intervention group an automated CPP target is provided as the CPP at which the patient's cerebrovascular reactivity is best preserved (CPPopt). For a maximum of 5 days, attending clinicians review the CPP target 4-hourly. The main hypothesis of COGiTATE are: (1) in the intervention group the percentage of the monitored time with measured CPP within a range of 5 mm Hg above or below CPPopt will reach 36%; (2) the difference in between groups in daily therapy intensity level score will be lower or equal to 3. ETHICS AND DISSEMINATION: Ethical approval has been obtained for each participating centre. The results will be presented at international scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02982122

Dynamic Changes in White Matter Abnormalities Correlate With Late Improvement and Deterioration Following TBI: A Diffusion Tensor Imaging Study.

OBJECTIVE: Traumatic brain injury (TBI) is not a single insult with monophasic resolution, but a chronic disease, with dynamic processes that remain active for years. We aimed to assess patient trajectories over the entire disease narrative, from ictus to late outcome. METHODS: Twelve patients with moderate-to-severe TBI underwent magnetic resonance imaging in the acute phase (within 1 week of injury) and twice in the chronic phase of injury (median 7 and 21 months), with some undergoing imaging at up to 2 additional time points. Longitudinal imaging changes were assessed using structural volumetry, deterministic tractography, voxel-based diffusion tensor analysis, and region of interest analyses (including corpus callosum, parasagittal white matter, and thalamus). Imaging changes were related to behavior. RESULTS: Changes in structural volumes, fractional anisotropy, and mean diffusivity continued for months to years postictus. Changes in diffusion tensor imaging were driven by increases in both axial and radial diffusivity except for the earliest time point, and were associated with changes in reaction time and performance in a visual memory and learning task (paired associates learning). Dynamic structural changes after TBI can be detected using diffusion tensor imaging and could explain changes in behavior. CONCLUSIONS: These data can provide further insight into early and late pathophysiology, and begin to provide a framework that allows magnetic resonance imaging to be used as an imaging biomarker of therapy response. Knowledge of the temporal pattern of changes in TBI patient populations also provides a contextual framework for assessing imaging changes in individuals at any given time point

Mild traumatic brain injury recovery: a growth curve modelling analysis over 2 years

Background: An improved understanding of the trajectory of recovery after mild traumatic brain injury is important to be able to understand individual patient outcomes, for longitudinal patient care and to aid the design of clinical trials. Objective: To explore changes in health, well-being and cognition over the 2 years following mTBI using latent growth curve (LGC) modelling. Methods Sixty-one adults with mTBI presenting to a UK Major Trauma Centre completed comprehensive longitudinal assessment at up to five time points after injury: 2 weeks, 3 months, 6 months, 1 year and 2 years. Results: Persisting problems were seen with neurological symptoms, cognitive issues and poor quality of life measures including 28% reporting incomplete recovery on the Glasgow Outcome Score Extended at 2 years. Harmful drinking, depression, psychological distress, disability, episodic memory and working memory did not improve significantly over the 2 years following injury. For other measures, including the Rivermead Post-Concussion Symptoms and Quality of Life after Brain Injury (QOLIBRI), LGC analysis revealed significant improvement over time with recovery tending to plateau at 3-6 months. Interpretation Significant impairment may persist as late as 2 years after mTBI despite some recovery over time. Longitudinal analyses which make use of all available data indicate that recovery from mTBI occurs over a longer timescale than is commonly believed. These findings point to the need for long-term management of mTBI targeting individuals with persisting impairment.</div

Mild traumatic brain injury recovery: a growth curve modelling analysis over 2 years

Background An improved understanding of the trajectory of recovery after mild traumatic brain injury is important to be able to understand individual patient outcomes, for longitudinal patient care and to aid the design of clinical trials. Objective To explore changes in health, well-being and cognition over the 2 years following mTBI using latent growth curve (LGC) modelling. Methods Sixty-one adults with mTBI presenting to a UK Major Trauma Centre completed comprehensive longitudinal assessment at up to five time points after injury: 2 weeks, 3 months, 6 months, 1 year and 2 years. Results Persisting problems were seen with neurological symptoms, cognitive issues and poor quality of life measures including 28% reporting incomplete recovery on the Glasgow Outcome Score Extended at 2 years. Harmful drinking, depression, psychological distress, disability, episodic memory and working memory did not improve significantly over the 2 years following injury. For other measures, including the Rivermead Post-Concussion Symptoms and Quality of Life after Brain Injury (QOLIBRI), LGC analysis revealed significant improvement over time with recovery tending to plateau at 3–6 months. Interpretation Significant impairment may persist as late as 2 years after mTBI despite some recovery over time. Longitudinal analyses which make use of all available data indicate that recovery from mTBI occurs over a longer timescale than is commonly believed. These findings point to the need for long-term management of mTBI targeting individuals with persisting impairment

Hemodynamic steroid responsiveness is predictive of neurological outcome after traumatic brain injury

INTRODUCTION: To determine the impact of physiologic doses of hydrocortisone on neurologic outcome after traumatic brain injury (TBI).METHODS: We conducted a retrospective study in a neurocritical care unit at a university teaching hospital. We included 29 patients with moderate and severe TBI requiring vasoactive drugs to maintain adequate arterial blood pressure who received corticosteroid. Infected patients were excluded. Blood cortisol levels were measured before and 30 and 60 minutes after the administration of a high-dose corticotropin stimulation test (HDST). Patients received hydrocortisone replacement therapy (200-300 mg/day) and vasoactive drugs requirements were noted. Intracranial pressure was managed according to a predefined protocol.RESULTS: A total of 14 out of 29 (48%) of patients were classified as responders to hydrocortisone (stopping vasoactive drugs within 3 days of starting hydrocortisone). The Glasgow Outcome Score (GOS) was used to assess neurologic outcome at 6 months. A favorable outcome (GOS 4 and 5) was observed in 11 out of 14 (79%) of responders and five out of 15 (33%) of nonresponders (p = 0.03). Of the responders, 12 out of 14 (85%) had a baseline cortisol below 414 nmol/L, and five out of 14 (36%) had primary adrenal insufficiency (AI) (primary AI: low baseline cortisol, and poor response to the HDST). Age, severity of injury, and response to hydrocortisone were predictive of outcome in multiple logistic regression analysis.CONCLUSIONS: Adrenal insufficiency is frequent after TBI, and hydrocortisone replacement therapy seems to be associated with a favorable neurologic outcome.</p

Influence of Concomitant Extracranial Injury on Functional and Cognitive Recovery From Mild Versus Moderateto Severe Traumatic Brain Injury.

OBJECTIVE: To determine the effect of extracranial injury (ECI) on 6-month outcome in patients with mild traumatic brain injury (TBI) versus moderate-to-severe TBI. PARTICIPANTS/SETTING: Patients with TBI (n = 135) or isolated orthopedic injury (n = 25) admitted to a UK major trauma center and healthy volunteers (n = 99). DESIGN: Case-control observational study. MAIN MEASURES: Primary outcomes: (a) Glasgow Outcome Scale Extended (GOSE), (b) depression, (c) quality of life (QOL), and (d) cognitive impairment including verbal fluency, episodic memory, short-term recognition memory, working memory, sustained attention, and attentional flexibility. RESULTS: Outcome was influenced by both TBI severity and concomitant ECI. The influence of ECI was restricted to mild TBI; GOSE, QOL, and depression outcomes were significantly poorer following moderate-to-severe TBI than after isolated mild TBI (but not relative to mild TBI plus ECI). Cognitive impairment was driven solely by TBI severity. General health, bodily pain, semantic verbal fluency, spatial recognition memory, working memory span, and attentional flexibility were unaffected by TBI severity and additional ECI. CONCLUSION: The presence of concomitant ECI ought to be considered alongside brain injury severity when characterizing the functional and neurocognitive effects of TBI, with each presenting challenges to recovery.Funding: This work was partially funded by a Medical Research Council (MRC, UK) Program Grant (Acute brain injury: heterogeneity of mechanisms, therapeutic targets and outcome effects [G9439390 ID 65883]), the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), the UK National Institute of Health Research (NIHR) Biomedical Research Centre at Cambridge, the Technology Platform funding provided by the UK Department of Health and an Engineering and Physical Sciences Research Council (EPSRC, UK) Pathways to Impact award. PJH was supported by the NIHR (Research Professorship and Cambridge BRC). JPP received funding from Academy of Finland – Grant #322381, Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland), the Emil Aaltonen Foundation, the Finnish Brain Foundation and the Maire Taponen Foundation. BJS receives funding from the NIHR Brain Injury MedTech Co-operative, Cambridge and the NIHR Cambridge Biomedical Research Centre (Mental Health Theme). DKM was supported by the NIHR through the NIHR Cambridge Biomedical Research Centre grant and a Senior Investigator Award. VFJN was funded by a Health Foundation/Academy of Medical Sciences Clinician Scientist Fellowship. Acknowledgements: The NIHR/Wellcome Trust Cambridge Clinical Research Facility provided nursing support to aid in the patient recruitment and data collection within the Emergency Department

Within and between session variability of diffusion tensor imaging region of interest measurements.

<p>Individual white matter region of interest measurements for within session reproducibility obtained in the first and second imaging sessions in 26 and 22 subjects respectively, and the between session reproducibility for those 22 subjects who underwent imaging at both sessions. Data displayed are standard deviation of measurements for fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial (AD) and radial (RD) diffusivity.</p