Visual outcomes and their association with grey and white matter microstructure in adults born preterm with very low birth weight.

Individuals born with very low birth weight (VLBW; < 1500 g) have a higher risk of reduced visual function and brain alterations. In a longitudinal cohort study, we assessed differences in visual outcomes and diffusion metrics from diffusion tensor imaging (DTI) at 3 tesla in the visual white matter pathway and primary visual cortex at age 26 in VLBW adults versus controls and explored whether DTI metrics at 26 years was associated with visual outcomes at 32 years. Thirty-three VLBW adults and 50 term-born controls was included in the study. Visual outcomes included best corrected visual acuity, contrast sensitivity, P100 latency, and retinal nerve fibre layer thickness. Mean diffusivity, axial diffusivity, radial diffusivity, and fractional anisotropy was extracted from seven regions of interest in the visual pathway: splenium, genu, and body of corpus callosum, optic radiations, lateral geniculate nucleus, inferior-fronto occipital fasciculus, and primary visual cortex. On average the VLBW group had lower contrast sensitivity, a thicker retinal nerve fibre layer and higher axial diffusivity and radial diffusivity in genu of corpus callosum and higher radial diffusivity in optic radiations than the control group. Higher fractional anisotropy in corpus callosum areas were associated with better visual function in the VLBW group but not the control group.

Visual function in adults born preterm with very low birth weight-A two-country birth cohort study.

PURPOSE: The purpose of the study was to investigate visual function and vision-related general health in adults that were born preterm with very low birth weight (VLBW: birth weight < 1500 g) in their 30s-40s. METHODS: We recruited 137 adults born preterm with VLBW and 158 term-born controls aged 31-43 years from two birth cohorts: the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight in a Lifetime Perspective study (Norway). We used neonatal data and measured refraction, best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, contrast sensitivity, visual fields, intraocular pressure (IOP), self-reported vision-targeted health status with the National Eye Institute Visual Function Questionnaire-25. RESULTS: VLBW adults had a lower BCVA ETDRS score than controls: mean (SD) better eye 86.7 (13.4) versus 90.2 (4.4), p = 0.02; mean (SD) worse eye 82.3 (14.9) versus 87.6 (4.6), p = 0.003. VLBW adults also had lower contrast sensitivity thresholds in several spatial frequencies and scored lower than controls in eight out of the 12 subscales of self-reported vision-targeted health status. Refraction, visual fields and IOP were similar between groups. Two VLBW participants were blind. None had been treated for retinopathy of prematurity. CONCLUSION: We suggest that lower visual function and vision-related health represent life-long consequences of prematurity and VLBW in the studied 31- to 43-year-old cohort. The underlying mechanisms remain to be determined.

Mental health, pain and tiredness in adults born very preterm or with very low birthweight.

AIM: Adults born preterm have increased risk of mental health problems and other neurodevelopmental conditions. We aimed to investigate associations of mental health with pain and tiredness in adults born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) and at term, and whether these associations are influenced by physical activity. METHODS: As part of an EU Horizon 2020 project, individual participant data from six prospective cohort studies were harmonised for 617 VP/VLBW and 1122 term-born participants. Mental health was assessed by the Achenbach System of Empirically Based Assessment Adult Self-Report. Pain and tiredness were harmonised based on specific items from self-reported questionnaires. Associations between mental health and pain or tiredness were explored by linear regression. RESULTS: An increase in the mental health scales internalising, externalising and total problems was associated with increased pain and tiredness in the preterm and term group alike. Results were maintained when adjusting for physical activity. CONCLUSION: The findings indicate that associations between mental health, pain and tiredness in adults are independent of gestation or birthweight. Future research should explore other potential mechanisms that may underlie the increased risk of mental health problems in the preterm population.

Retinal structure and visual pathway function at school age in children born extremely preterm: a population-based study.

BACKGROUND: Children born extremely preterm (gestational age < 28 weeks) show reduced visual function even without any cerebral or ophthalmological neonatal diagnosis. In this study, we aimed to assess the retinal structure with optical coherence tomography (OCT) and visual function with pattern-reversal visual evoked potentials (PR-VEPs) in a geographically defined population-based cohort of school-aged children born extremely preterm. Moreover, we aimed to explore the association between measures of retinal structure and visual pathway function in this cohort. METHODS: All children born extremely preterm from 2006-2011 (n = 65) in Central Norway were invited to participate. Thirty-six children (55%) with a median age of 13 years (range = 10-16) were examined with OCT, OCT-angiography (OCT-A), and PR-VEPs. The foveal avascular zone (FAZ) and circularity, central macular vascular density, and flow were measured on OCT-A images. Central retinal thickness, circumpapillary retinal nerve fibre layer (RNFL) and inner plexiform ganglion cell layer (IPGCL) thickness were measured on OCT images. The N70-P100 peak-to-peak amplitude and N70 and P100 latencies were assessed from PR-VEPs. RESULTS: Participants displayed abnormal retinal structure and P100 latencies (≥ 2 SD) compared to reference populations. Moreover, there was a negative correlation between P100 latency in large checks and RNFL (r = -.54, p = .003) and IPGCL (r = -.41, p = .003) thickness. The FAZ was smaller (p = .003), macular vascular density (p = .006) and flow were higher (p = .004), and RNFL (p = .006) and IPGCL (p = .014) were thinner in participants with ROP (n = 7). CONCLUSION: Children born extremely preterm without preterm brain injury sequelae have signs of persistent immaturity of retinal vasculature and neuroretinal layers. Thinner neuroretinal layers are associated with delayed P100 latency, prompting further exploration of the visual pathway development in preterms.

Forecasting migraine with machine learning based on mobile phone diary and wearable data.

INTRODUCTION: Triggers, premonitory symptoms and physiological changes occur in the preictal migraine phase and may be used in models for forecasting attacks. Machine learning is a promising option for such predictive analytics. The objective of this study was to explore the utility of machine learning to forecast migraine attacks based on preictal headache diary entries and simple physiological measurements. METHODS: In a prospective development and usability study 18 patients with migraine completed 388 headache diary entries and self-administered app-based biofeedback sessions wirelessly measuring heart rate, peripheral skin temperature and muscle tension. Several standard machine learning architectures were constructed to forecast headache the subsequent day. Models were scored with area under the receiver operating characteristics curve. RESULTS: Two-hundred-and-ninety-five days were included in the predictive modelling. The top performing model, based on random forest classification, achieved an area under the receiver operating characteristics curve of 0.62 in a hold-out partition of the dataset. DISCUSSION: In this study we demonstrate the utility of using mobile health apps and wearables combined with machine learning to forecast headache. We argue that high-dimensional modelling may greatly improve forecasting and discuss important considerations for future design of forecasting models using machine learning and mobile health data.

Visual function correlates with neurodevelopment in a population cohort of school-aged children born extremely preterm.

AIM: To investigate visual function and neurodevelopment in a geographically defined population cohort of school-aged children born extremely preterm. METHODS: All children born extremely preterm in Central Norway between 2006 and 2011 (n=65) were identified, and 36 (median age, min/max: 13, 10/16) were included. Best-corrected visual acuity (BCVA), contrast sensitivity (four spatial frequencies), parent-reported challenges and neuropsychological testing in learning, executive functions, motor skills, perception, reaction time, working and visual memory, processing speed, and pattern separation were measured. Brain MRI (3T) was acquired and read by a neuroradiologist. RESULTS: Median (min/max) BCVA letter score was 85 (35/91) in the better and 82 (13/89) in the worse eye. ROP participants (n=7) had lower contrast sensitivity in the two highest spatial frequencies (p = 0.024 and p = 0.004). Parent-reported challenges correlated negatively with BCVA (learning: p = 0.014; executive functions: p = 0.002; motor skills: p = 0.000; and perception: p = 0.001), while motor skills correlated negatively with one (p = 0.010) and perception with two (p = 0.003 and p = 0.009) of four spatial frequencies. Neuropsychological tests were reduced relative to norms. None had MRI-verified preterm brain injury. CONCLUSION: Visual function was subnormal and correlated with parent-reported challenges in a small cohort of extremely preterm school-aged children, indicating that visual function may be a marker of neurodevelopmental outcomes.

Visuopathy of prematurity: is retinopathy just the tip of the iceberg?

Research on retinopathy of prematurity (ROP) focuses mainly on the abnormal vascularization patterns that are directly visible for ophthalmologists. However, recent findings indicate that children born prematurely also exhibit changes in the retinal cellular architecture and along the dorsal visual stream, such as structural changes between and within cortical areas. Moreover, perinatal sustained systemic inflammation (SSI) is associated with an increased risk for ROP and the visual deficits that follow. In this paper, we propose that ROP might just be the tip of an iceberg we call visuopathy of prematurity (VOP). The VOP paradigm comprises abnormal vascularization of the retina, alterations in retinal cellular architecture, choroidal degeneration, and abnormalities in the visual pathway, including cortical areas. Furthermore, VOP itself might influence the developmental trajectories of cerebral structures and functions deemed responsible for visual processing, thereby explaining visual deficits among children born preterm.

A Biofeedback App for Migraine: Development and Usability Study.

BACKGROUND: Biofeedback is effective in treating migraines. It is believed to have a beneficial effect on autonomous nervous system activity and render individuals resilient to stressors that may trigger a migraine. However, widespread use of biofeedback is hampered by the need for a trained therapist and specialized equipment. Emerging digital health technology, including smartphones and wearables (mHealth), enables new ways of administering biofeedback. Currently, mHealth interventions for migraine appear feasible, but development processes and usability testing remain insufficient. OBJECTIVE: The objective of this study was to evaluate and improve the feasibility and usability of an mHealth biofeedback treatment app for adults with migraine. METHODS: In a prospective development and usability study, 18 adults with migraine completed a 4-week testing period of self-administered therapist-independent biofeedback treatment consisting of a smartphone app connected to wearable sensors (Cerebri, Nordic Brain Tech AS). The app included biofeedback training, instructions for self-delivery, and a headache diary. Two wearable sensors were used to measure surface electromyographic voltage at the trapezius muscle and peripheral skin temperature and heart rate at the right second fingertip. Participants were instructed to complete a daily headache diary entry and biofeedback session of 10 minutes duration. The testing period was preceded by a preusability expectation interview and succeeded by a postusability experience interview. In addition, an evaluation questionnaire was completed at weeks 2 and 4. Adherence was calculated as the proportion of 10-minute sessions completed within the first 28 days of treatment. Usability and feasibility were analyzed and summarized quantitatively and qualitatively. RESULTS: A total of 391 biofeedback sessions were completed with a median of 25 (IQR 17-28) per participant. The mean adherence rate was 0.76 (SD 0.26). The evaluation questionnaire revealed that functionality and design had the highest scores, whereas engagement and biofeedback were lower. Qualitative preexpectation analysis revealed that participants expected to become better familiar with physical signals and gain more understanding of their migraine attacks and noted that the app should be simple and understandable. Postusability analysis indicated that participants had an overall positive user experience with some suggestions for improvement regarding the design of the wearables and app content. The intervention was safe and tolerable. One case of prespecified adverse events was recorded in which a patient developed a skin rash from the sticky surface electromyography electrodes. CONCLUSIONS: The app underwent a rigorous development process that indicated an overall positive user experience, good usability, and high adherence rate. This study highlights the value of usability testing in the development of mHealth apps.

Interpersonal stress, anxiety and depressive symptoms: Results from a moderated mediation analysis with resilience / Estrés interpersonal, ansiedad y síntomas depresivos: resultados de una mediación moderada con resiliencia

INTRODUCTION AND OBJECTIVES: Interpersonal stress factors contribute to common mental health problems measured as anxiety and depression. Recently, it is emerging that anxiety precedes depression but not the reverse, and markedly increase in response to stress giving way to depression. As such, anxiety itself could be a predictive risk factor, and mediate the associations between stress and depression. While resilience protects against exposure to stress and common mental health problems, it is unclear to what extent different resilience factors are differentially involved in protection against anxiety and depressive symptoms. This study explored complex theoretical associations between interpersonal stress, anxiety and depressive symptoms and resilience factors. MATERIALS AND METHODS: Participants (N = 210 adults) completed the Resilience Scale for Adults (RSA), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Questionnaire (GAD-7) and the Stressful Life Events Questionnaire (SLE) in a cross-sectional survey. Hierarchical linear regressions and moderated-mediation analyses were performed using PROCESS macro. RESULTS: Interpersonal stress explained more variance in depressive than anxiety symptoms. Support was found for the mediating effect of anxiety symptoms in the relationship between interpersonal stress and depressive symptoms. Resilience factors are differentially involved in protection against anxiety and depressive symptoms. CONCLUSION: Exposure to interpersonal stress is not only directly associated with depressive symptoms but also indirectly through high scores on anxiety symptoms. Uneven functioning and differential impact of resilience factors can help us understand the mixed successes in implementing resilience-based interventions for positive mental health and judiciously allocate scarce and finite resources for intervention

INTRODUCCIÓN Y OBJETIVOS: Los factores de estrés interpersonal contribuyen a problemas comunes de salud mental como ansiedad y depresión. Recientemente, se está demostrando que la ansiedad precede a la depresión, pero no al revés, y que aumenta notablemente en respuesta al estrés dando paso a la depresión. Como tal, la ansiedad en sí misma podría ser un factor de riesgo predictivo y mediar las asociaciones entre el estrés y la depresión. Si bien la resiliencia protege contra la exposición al estrés y los problemas comunes de salud mental, no está claro en qué medida los diferentes factores de resiliencia están involucrados de manera específica en la protección contra la ansiedad y los síntomas depresivos. Este estudio exploró asociaciones teóricas complejas entre estrés interpersonal, ansiedad, síntomas depresivos y factores de resiliencia. Instrumentos y MÉTODO: Los participantes (N = 210 adultos) completaron la Escala de Resiliencia para Adultos (RSA), el Cuestionario de Salud del Paciente (PHQ-9), el Cuestionario de Trastorno de Ansiedad Generalizada (GAD-7) y el Cuestionario de Eventos Vitales Estresantes (SLE) en una encuesta transversal. Se realizaron regresiones lineales jerárquicas y análisis de mediación moderada utilizando PROCESS. RESULTADOS: El estrés interpersonal explicó más variaciones en los síntomas depresivos que en los de ansiedad. Se pudo demostrar el efecto mediador de los síntomas de ansiedad en la relación entre el estrés interpersonal y los síntomas depresivos. Los factores de resiliencia intervienen de manera diferencial en la protección contra la ansiedad y los síntomas depresivos. CONCLUSIONES: La exposición al estrés interpersonal no solo se asocia directamente con los síntomas depresivos, sino también indirectamente, a través de puntuaciones altas en los síntomas de ansiedad. El funcionamiento desigual y el impacto diferencial de los factores de resiliencia pueden ayudarnos a comprender los resultados mixtos obtenidos en la implementación de intervenciones basadas en resiliencia para la salud mental positiva, y asignar juiciosamente los recursos escasos y finitos para la intervención